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Recent Articles in BMC Neuroscience

Selivanov VA, Sukhomlin T, Centelles JJ, Lee PW, Cascante M
Integration of enzyme kinetic models and isotopomer distribution analysis for studies of in situ cell operation.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S7.
ABSTRACT : A current trend in neuroscience research is the use of stable isotope tracers in order to address metabolic processes in vivo. The tracers produce a huge number of metabolite forms that differ according to the number and position of labeled isotopes in the carbon skeleton (isotopomers) and such a large variety makes the analysis of isotopomer data highly complex. On the other hand, this multiplicity of forms does provide sufficient information to address cell operation in vivo. By the end of last millennium, a number of tools have been developed for estimation of metabolic flux profile from any possible isotopomer distribution data. However, although well elaborated, these tools were limited to steady state analysis, and the obtained set of fluxes remained disconnected from their biochemical context. In this review we focus on a new numerical analytical approach that integrates kinetic and metabolic flux analysis. The related computational algorithm estimates the dynamic flux based on the time-dependent distribution of all possible isotopomers of metabolic pathway intermediates that are generated from a labeled substrate. The new algorithm connects specific tracer data with enzyme kinetic characteristics, thereby extending the amount of data available for analysis: it uses enzyme kinetic data to estimate the flux profile, and vice versa, for the kinetic analysis it uses in vivo tracer data to reveal the biochemical basis of the estimated metabolic fluxes. [Abstract/Link to Full Text]

Arisi I, Cattaneo A, Rosato V
Parameter estimate of signal transduction pathways.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S6.
ABSTRACT : BACKGROUND : The "inverse" problem is related to the determination of unknown causes on the bases of the observation of their effects. This is the opposite of the corresponding "direct" problem, which relates to the prediction of the effects generated by a complete description of some agencies. The solution of an inverse problem entails the construction of a mathematical model and takes the moves from a number of experimental data. In this respect, inverse problems are often ill-conditioned as the amount of experimental conditions available are often insufficient to unambiguously solve the mathematical model. Several approaches to solving inverse problems are possible, both computational and experimental, some of which are mentioned in this article. In this work, we will describe in details the attempt to solve an inverse problem which arose in the study of an intracellular signaling pathway. RESULTS : Using the Genetic Algorithm to find the sub-optimal solution to the optimization problem, we have estimated a set of unknown parameters describing a kinetic model of a signaling pathway in the neuronal cell. The model is composed of mass action ordinary differential equations, where the kinetic parameters describe protein-protein interactions, protein synthesis and degradation. The algorithm has been implemented on a parallel platform. Several potential solutions of the problem have been computed, each solution being a set of model parameters. A sub-set of parameters has been selected on the basis on their small coefficient of variation across the ensemble of solutions. CONCLUSION : Despite the lack of sufficiently reliable and homogeneous experimental data, the genetic algorithm approach has allowed to estimate the approximate value of a number of model parameters in a kinetic model of a signaling pathway: these parameters have been assessed to be relevant for the reproduction of the available experimental data. [Abstract/Link to Full Text]

Presutti C, Rosati J, Vincenti S, Nasi S
Non coding RNA and brain.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S5.
ABSTRACT : Small non coding RNAs are a group of very different RNA molecules, present in virtually all cells, with a wide spectrum of regulatory functions which include RNA modification and regulation of protein synthesis. They have been isolated and characterized in all organisms and tissues, from Archaeobacteria to mammals. In mammalian brain there are a number of these small molecules, which are involved in neuronal differentiation as well as, possibly, in learning and memory. In this manuscript, we analyze the present knowledge about the function of the most important groups of small non-coding RNA present in brain: small nucleolar RNAs, small cytoplasmic RNAs, and microRNAs. The last ones, in particular, appear to be critical for dictating neuronal cell identity during development and to play an important role in neurite growth, synaptic development and neuronal plasticity. [Abstract/Link to Full Text]

Brachya G, Yanay C, Linial M
Synaptic proteins as multi-sensor devices of neurotransmission.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S4.
ABSTRACT : Neuronal communication is tightly regulated in time and space. Following neuronal activation, an electrical signal triggers neurotransmitter (NT) release at the active zone. The process starts by the signal reaching the synapse followed by a fusion of the synaptic vesicle (SV) and diffusion of the released NT in the synaptic cleft. The NT then binds to the appropriate receptor and induces a membrane potential change at the target cell membrane. The entire process is controlled by a fairly small set of synaptic proteins, collectively called SYCONs. The biochemical features of SYCONs underlie the properties of NT release.SYCONs are characterized by their ability to detect and respond to changes in environmental signals. For example, consider synaptotagmin I (Syt1), a prototype of a protein family with over 20 gene and variants in mammals. Syt1 is a specific example of a multi-sensor device with a large repertoire of discrete states. Several of these states are stimulated by a local concentration of signaling molecules such as Ca2+. The ability of this protein to sense signaling molecules and to adopt multiple biochemical states is shared by other SYCONs such as the synapsins (Syns). Specific biochemical states of Syns determine the accessibility of SV for NT release. Each of these states is defined by a specific alternative spliced variant with a unique profile of phosphorylation modified sites.The plasticity of the synapse is a direct reflection of SYCON's multiple biochemical states. State transitions occurs in a wide range of time scales, and therefore these molecules need to cope with events that last milliseconds (i.e., exocytosis in fast responding synapses) and with events that can carry on for many minutes (i.e., organization of SV pools). We suggest that SYCONs are optimized throughout evolution as multi-sensor devices. A full repertoire of the switches leading to alternation of protein states and a detailed characterization of protein-protein network within the synapse is critical for the development of a dynamic model of synaptic transmission. [Abstract/Link to Full Text]

Carson JH, Blondin N, Korza G
Rules of engagement promote polarity in RNA trafficking.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S3.
ABSTRACT : Many cell biological pathways exhibit overall polarity (net movement of molecules in one direction) even though individual molecular interactions in the pathway are freely reversible. The A2 RNA trafficking pathway exhibits polarity in moving specific RNA molecules from the nucleus to localization sites in the myelin compartment of oligodendrocytes or dendritic spines in neurons. The A2 pathway is mediated by a ubiquitously expressed trans-acting trafficking factor (hnRNP A2) that interacts with a specific 11 nucleotide cis-acting trafficking sequence termed the A2 response element (A2RE) found in several localized RNAs. Five different molecular partners for hnRNP A2 have been identified in the A2 pathway: hnRNP A2 itself, transportin, A2RE RNA, TOG (tumor overexpressed gene) and hnRNP E1, each playing a key role in one particular step of the A2 pathway. Sequential interactions of hnRNP A2 with different molecular partners at each step mediate directed movement of trafficking intermediates along the pathway.Specific "rules of engagement" (both and, either or, only if) govern sequential interactions of hnRNP A2 with each of its molecular partners. Rules of engagement are defined experimentally using three component binding assays to measure differential binding of hnRNP A2 to one partner in the presence of each of the other partners in the pathway. Here we describe rules of engagement for hnRNP A2 binding to each of its molecular partners and discuss how these rules of engagement promote polarity in the A2 RNA trafficking pathway.For molecules with multiple binding partners, specific rules of engagement govern different molecular interactions. Rules of engagement are ultimately determined by structural relationships between binding sites on individual molecules. In the A2 RNA trafficking pathway rules of engagement governing interactions of hnRNP A2 with different binding partners provide the basis for polarity of movement of intermediates along the pathway. [Abstract/Link to Full Text]

Alberghina L, Colangelo AM
The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S2.
ABSTRACT : Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking.Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process.This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease. [Abstract/Link to Full Text]

Le Nov�re N
Model storage, exchange and integration.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S11.
ABSTRACT : The field of Computational Systems Neurobiology is maturing quickly. If one wants it to fulfil its central role in the new Integrative Neurobiology, the reuse of quantitative models needs to be facilitated. The community has to develop standards and guidelines in order to maximise the diffusion of its scientific production, but also to render it more trustworthy. In the recent years, various projects tackled the problems of the syntax and semantics of quantitative models. More recently the international initiative BioModels.net launched three projects: (1) MIRIAM is a standard to curate and annotate models, in order to facilitate their reuse. (2) The Systems Biology Ontology is a set of controlled vocabularies aimed to be used in conjunction with models, in order to characterise their components. (3) BioModels Database is a resource that allows biologists to store, search and retrieve published mathematical models of biological interests. We expect that those resources, together with the use of formal languages such as SBML, will support the fruitful exchange and reuse of quantitative models. [Abstract/Link to Full Text]

Klipp E, Liebermeister W
Mathematical modeling of intracellular signaling pathways.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S10.
ABSTRACT : Dynamic modeling and simulation of signal transduction pathways is an important topic in systems biology and is obtaining growing attention from researchers with experimental or theoretical background. Here we review attempts to analyze and model specific signaling systems. We review the structure of recurrent building blocks of signaling pathways and their integration into more comprehensive models, which enables the understanding of complex cellular processes. The variety of mechanisms found and modeling techniques used are illustrated with models of different signaling pathways. Focusing on the close interplay between experimental investigation of pathways and the mathematical representations of cellular dynamics, we discuss challenges and perspectives that emerge in studies of signaling systems. [Abstract/Link to Full Text]

Levi-Montalcini R, Calissano P
The scientific challenge of the 21st century: from a reductionist to a holistic approach via systems biology.
BMC Neurosci. 2006 Oct 30;7 Suppl 1S1. [Abstract/Link to Full Text]

Pl�mpe T, Ehninger D, Steiner B, Klempin F, Jessberger S, Brandt M, R�mer B, Rodriguez GR, Kronenberg G, Kempermann G
Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation.
BMC Neurosci. 2006;777.
BACKGROUND: In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX) expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. RESULTS: We found that (1) 20% of the DCX population were precursor cells in cell cycle, whereas more than 70% were postmitotic, (2) the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3) positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. CONCLUSION: These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis. [Abstract/Link to Full Text]

Diegelmann S, Nieratschker V, Werner U, Hoppe J, Zars T, Buchner E
The conserved protein kinase-A target motif in synapsin of Drosophila is effectively modified by pre-mRNA editing.
BMC Neurosci. 2006;776.
BACKGROUND: Synapsins are abundant synaptic vesicle associated phosphoproteins that are involved in the fine regulation of neurotransmitter release. The Drosophila member of this protein family contains three conserved domains (A, C, and E) and is expressed in most or all synaptic terminals. Similar to mouse mutants, synapsin knock-out flies show no obvious structural defects but are disturbed in complex behaviour, notably learning and memory. RESULTS: We demonstrate that the N-terminal phosphorylation consensus motif RRxS that is conserved in all synapsins investigated so far, is modified in Drosophila by pre-mRNA editing. In mammals this motif represents the target site P1 of protein kinase A (PKA) and calcium/calmodulin dependent protein kinase I/IV. The result of this editing, by which RRFS is modified to RGFS, can be observed in cDNAs of larvae and adults and in both isolated heads and bodies. It is also seen in several newly collected wild-type strains and thus does not represent an adaptation to laboratory culture conditions. A likely editing site complementary sequence is found in a downstream intron indicating that the synapsin pre-mRNA can form a double-stranded RNA structure that is required for editing by the adenosine deaminase acting on RNA (ADAR) enzyme. A deletion in the Drosophila Adar gene generated by transposon remobilization prevents this modification, proving that the ADAR enzyme is responsible for the pre-mRNA editing described here. We also provide evidence for a likely function of synapsin editing in Drosophila. The N-terminal synapsin undeca-peptide containing the genomic motif (RRFS) represents an excellent substrate for in-vitro phosphorylation by bovine PKA while the edited peptide (RGFS) is not significantly phosphorylated. Thus pre-mRNA editing by ADAR could modulate the function of ubiquitously expressed synapsin in a cell-specific manner during development and adulthood. CONCLUSION: Similar to several other neuronal proteins of Drosophila, synapsin is modified by ADAR-mediated recoding at the pre-mRNA level. This editing likely reduces or abolishes synapsin phosphorylation by PKA. Since synapsin in Drosophila is required for various forms of behavioural plasticity, it will be fascinating to investigate the effect of this recoding on learning and memory. [Abstract/Link to Full Text]

Maekawa F, Komine O, Sato K, Kanamatsu T, Uchimura M, Tanaka K, Ohki-Hamazaki H
Imprinting modulates processing of visual information in the visual wulst of chicks.
BMC Neurosci. 2006;775.
BACKGROUND: Imprinting behavior is one form of learning and memory in precocial birds. With the aim of elucidating of the neural basis for visual imprinting, we focused on visual information processing. RESULTS: A lesion in the visual wulst, which is similar functionally to the mammalian visual cortex, caused anterograde amnesia in visual imprinting behavior. Since the color of an object was one of the important cues for imprinting, we investigated color information processing in the visual wulst. Intrinsic optical signals from the visual wulst were detected in the early posthatch period and the peak regions of responses to red, green, and blue were spatially organized from the caudal to the nasal regions in dark-reared chicks. This spatial representation of color recognition showed plastic changes, and the response pattern along the antero-posterior axis of the visual wulst altered according to the color the chick was imprinted to. CONCLUSION: These results indicate that the thalamofugal pathway is critical for learning the imprinting stimulus and that the visual wulst shows learning-related plasticity and may relay processed visual information to indicate the color of the imprint stimulus to the memory storage region, e.g., the intermediate medial mesopallium. [Abstract/Link to Full Text]

Nilsen J, Chen S, Irwin RW, Iwamoto S, Brinton RD
Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function.
BMC Neurosci. 2006;774.
BACKGROUND: Neurodegeneration in Alzheimer's disease is associated with increased apoptosis and parallels increased levels of amyloid beta, which can induce neuronal apoptosis. Estrogen exposure prior to neurotoxic insult of hippocampal neurons promotes neuronal defence and survival against neurodegenerative insults including amyloid beta. Although all underlying molecular mechanisms of amyloid beta neurotoxicity remain undetermined, mitochondrial dysfunction, including altered calcium homeostasis and Bcl-2 expression, are involved in neurodegenerative vulnerability. RESULTS: In this study, we investigated the mechanism of 17beta-estradiol-induced prevention of amyloid beta-induced apoptosis of rat hippocampal neuronal cultures. Estradiol treatment prior to amyloid beta exposure significantly reduced the number of apoptotic neurons and the associated rise in resting intracellular calcium levels. Amyloid beta exposure provoked down regulation of a key antiapoptotic protein, Bcl-2, and resulted in mitochondrial translocation of Bax, a protein known to promote cell death, and subsequent release of cytochrome c. E2 pretreatment inhibited the amyloid beta-induced decrease in Bcl-2 expression, translocation of Bax to the mitochondria and subsequent release of cytochrome c. Further implicating the mitochondria as a target of estradiol action, in vivo estradiol treatment enhanced the respiratory function of whole brain mitochondria. In addition, estradiol pretreatment protected isolated mitochondria against calcium-induced loss of respiratory function. CONCLUSION: Therefore, we propose that estradiol pretreatment protects against amyloid beta neurotoxicity by limiting mitochondrial dysfunction via activation of antiapoptotic mechanisms. [Abstract/Link to Full Text]

Hummel FC, Voller B, Celnik P, Floel A, Giraux P, Gerloff C, Cohen LG
Effects of brain polarization on reaction times and pinch force in chronic stroke.
BMC Neurosci. 2006;773.
BACKGROUND: Previous studies showed that anodal transcranial DC stimulation (tDCS) applied to the primary motor cortex of the affected hemisphere (M1affected hemisphere) after subcortical stroke transiently improves performance of complex tasks that mimic activities of daily living (ADL). It is not known if relatively simpler motor tasks are similarly affected. Here we tested the effects of tDCS on pinch force (PF) and simple reaction time (RT) tasks in patients with chronic stroke in a double-blind cross-over Sham-controlled experimental design. RESULTS: Anodal tDCS shortened reaction times and improved pinch force in the paretic hand relative to Sham stimulation, an effect present in patients with higher impairment. CONCLUSION: tDCS of M1affected hemisphere can modulate performance of motor tasks simpler than those previously studied, a finding that could potentially benefit patients with relatively higher impairment levels. [Abstract/Link to Full Text]

Duret F, Shumikhina S, Molotchnikoff S
Neuron participation in a synchrony-encoding assembly.
BMC Neurosci. 2006;772.
BACKGROUND: Synchronization of action potentials between neurons is considered to be an encoding process that allows the grouping of various and multiple features of an image leading to a coherent perception. How this coding neuronal assembly is configured is debated. We have previously shown that the magnitude of synchronization between excited neurons is stimulus-dependent. In the present investigation we compare the levels of synchronization between synchronizing individual neurons and the synchronizing pool of cells to which they belong. RESULTS: Even though neurons belonged to their respective pools, some cells synchronized for all presented stimuli while others were rather selective and only a few stimulating conditions produced a significant synchronization. In addition the experiments show that one synchronizing pair rarely replicates the level of synchrony between corresponding groups of units. But when synchronizing clusters of neurons increase in number, the correlation (measured as a coefficient of determination) between unit synchronization and the synchronization between the entire pools of cells to which individual neurons belong improves. CONCLUSION: These results prompt the hypothesis that random or spontaneous synchronization becomes progressively less important, whereas coincident spikes related to encoding properties of targets gain significance because a particular configuration of an image biases the excitatory inputs in favor of connections driven by the applied features of the stimulus. [Abstract/Link to Full Text]

Bigini P, Gardoni F, Barbera S, Cagnotto A, Fumagalli E, Longhi A, Corsi MM, Di Luca M, Mennini T
Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice.
BMC Neurosci. 2006;771.
BACKGROUND: The localisation of AMPA and NMDA receptor subunits was studied in a model of degeneration of cervical spinal motoneurons, the wobbler mouse. Cervical regions from early or late symptomatic wobbler mice (4 or 12 weeks of age) were compared to lumbar tracts (unaffected) and to those of healthy mice. RESULTS: No differences were found in the distribution of AMPA and NMDA receptor subunits at both ages. Western blots analysis showed a trend of reduction in AMPA and NMDA receptor subunits, mainly GluR1 and NR2A, exclusively in the cervical region of late symptomatic mice in the triton-insoluble post-synaptic fraction but not whole homogenates. Colocalisation experiments evidenced the expression of GluR1 and NR2A receptors in activated astrocytes from the cervical spinal cord of wobbler mice, GluR2 did not colocalise with GFAP positive cells. No differences were found in the expression of AMPA and NMDA receptor subunits in the lumbar tract of wobbler mice, where neither motoneuron loss nor reactive gliosis occurs. CONCLUSION: In late symptomatic wobbler mice altered levels of GluR1 and NR2A receptor subunits may be a consequence of motoneuron loss rather than an early feature of motoneuron vulnerability. [Abstract/Link to Full Text]

Baldissera FG, Cavallari P, Esposti R
Synchrony of hand-foot coupled movements: is it attained by mutual feedback entrainment or by independent linkage of each limb to a common rhythm generator?
BMC Neurosci. 2006;770.
BACKGROUND: Synchrony of coupled oscillations of ipsilateral hand and foot may be achieved by controlling the interlimb phase difference through a crossed kinaesthetic feedback between the two limbs, or by an independent linkage of each limb cycle to a common clock signal. These alternative models may be experimentally challenged by comparing the behaviour of the two limbs when they oscillate following an external time giver, either alone or coupled together. RESULTS: Ten subjects oscillated their right hand and foot both alone and coupled (iso- or antidirectionally), paced by a metronome. Wrist and ankle angular position and Electromyograms (EMG) from the respective flexor and extensor muscles were recorded. Three phase delays were measured: i) the clk-mov delay, between the clock (metronome beat) and the oscillation peak; ii) the neur (neural) delay, between the clock and the motoneurone excitatory input, as inferred from the EMG onset; and iii) the mech (mechanical) delay between the EMG onset and the corresponding point of the limb oscillation. During uncoupled oscillations (0.4 Hz to 3.0 Hz), the mech delay increased from -7 degrees to -111 degrees (hand) and from -4 degrees to -83 degrees (foot). In contrast, the clk-mov delay remained constant and close to zero in either limb since a progressive advance of the motoneurone activation on the pacing beat (neur advance) compensated for the increasing mech delay. Adding an inertial load to either extremity induced a frequency dependent increase of the limb mechanical delay that could not be completely compensated by the increase of the neural phase advance, resulting in a frequency dependent increment of clk-mov delay of the hampered limb. When limb oscillations were iso- or antidirectionally coupled, either in the loaded or unloaded condition, the three delays did not significantly change with respect to values measured when limbs were moved separately. CONCLUSION: The absence of any significant effect of limb coupling on the measured delays suggests that during hand-foot oscillations, both iso- and antidirectionally coupled, each limb is synchronised to the common rhythm generator by a "private" position control, with no need for a crossed feedback interaction between limbs. [Abstract/Link to Full Text]

Fern� J, Skrede S, Vik-Mo AO, H�vik B, Steen VM
Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: marked differences between various antipsychotic drugs.
BMC Neurosci. 2006;769.
BACKGROUND: The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP) transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1) in four CNS-relevant human cell lines. RESULTS: There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines) displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. CONCLUSION: Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs. [Abstract/Link to Full Text]

Simoneau M, Mercier P, Blouin J, Allard P, Teasdale N
Altered sensory-weighting mechanisms is observed in adolescents with idiopathic scoliosis.
BMC Neurosci. 2006;768.
BACKGROUND: Scoliosis is the most common type of spinal deformity. In North American children, adolescent idiopathic scoliosis (AIS) makes up about 90% of all cases of scoliosis. While its prevalence is about 2% to 3% in children aged between 10 to 16 years, girls are more at risk than boys for severe progression with a ratio of 3.6 to 1. The aim of the present study was to test the hypothesis that idiopathic scoliosis interferes with the mechanisms responsible for sensory-reweighting during balance control. METHODS: Eight scoliosis patients (seven female and one male; mean age: 16.4 years) and nine healthy adolescents (average age 16.5 years) participated in the experiment. Visual and ankle proprioceptive information was perturbed (eyes closed and/or tendon vibration) suddenly and then returned to normal (eyes open and/or no tendon vibration). An AMTI force platform was used to compute centre of pressure root mean squared velocity and sway density curve. RESULTS: For the control condition (eyes open and no tendon vibration), adolescent idiopathic scoliosis patients had a greater centre of pressure root mean squared velocity (variability) than control participants. Reintegration of ankle proprioception, when vision was either available or removed, led to an increased centre of pressure velocity variability for the adolescent idiopathic scoliosis patients whereas the control participants reduced their centre of pressure velocity variability. Moreover, in the absence of vision, adolescent idiopathic scoliosis exhibited an increased centre of pressure velocity variability when ankle proprioception was returned to normal (i.e. tendon vibration stopped). The analysis of the sway density plot suggests that adolescent idiopathic scoliosis patients, during sensory reintegration, do not scale appropriately their balance control commands. CONCLUSION: Altogether, the present results demonstrate that idiopathic scoliosis adolescents have difficulty in reweighting sensory inputs following a brief period of sensory deprivation. [Abstract/Link to Full Text]

Blum S, Runyan JD, Dash PK
Inhibition of prefrontal protein synthesis following recall does not disrupt memory for trace fear conditioning.
BMC Neurosci. 2006;767.
BACKGROUND: The extent of similarity between consolidation and reconsolidation is not yet fully understood. One of the differences noted is that not every brain region involved in consolidation exhibits reconsolidation. In trace fear conditioning, the hippocampus and the medial prefrontal cortex (mPFC) are required for consolidation of long-term memory. We have previously demonstrated that trace fear memory is susceptible to infusion of the protein synthesis inhibitor anisomycin into the hippocampus following recall. In the present study, we examine whether protein synthesis inhibition in the mPFC following recall similarly results in the observation of reconsolidation of trace fear memory. RESULTS: Targeted intra-mPFC infusions of anisomycin or vehicle were performed immediately following recall of trace fear memory at 24 hours, or at 30 days, following training in a one-day or a two-day protocol. The present study demonstrates three key findings: 1) trace fear memory does not undergo protein synthesis dependent reconsolidation in the PFC, regardless of the intensity of the training, and 2) regardless of whether the memory is recent or remote, and 3) intra-mPFC inhibition of protein synthesis immediately following training impaired remote (30 days) memory. CONCLUSION: These results suggest that not all structures that participate in memory storage are involved in reconsolidation. Alternatively, certain types of memory-related information may reconsolidate, while other components of memory may not. [Abstract/Link to Full Text]

Schlamp CL, Li Y, Dietz JA, Janssen KT, Nickells RW
Progressive ganglion cell loss and optic nerve degeneration in DBA/2J mice is variable and asymmetric.
BMC Neurosci. 2006;766.
BACKGROUND: Glaucoma is a chronic neurodegenerative disease of the retina, characterized by the degeneration of axons in the optic nerve and retinal ganglion cell apoptosis. DBA/2J inbred mice develop chronic hereditary glaucoma and are an important model system to study the molecular mechanisms underlying this disease and novel therapeutic interventions designed to attenuate the loss of retinal ganglion cells. Although the genetics of this disease in these mice are well characterized, the etiology of its progression, particularly with respect to retinal degeneration, is not. We have used two separate labeling techniques, post-mortem DiI labeling of axons and ganglion cell-specific expression of the betaGeo reporter gene, to evaluate the time course of optic nerve degeneration and ganglion cell loss, respectively, in aging mice. RESULTS: Optic nerve degeneration, characterized by axon loss and gliosis is first apparent in mice between 8 and 9 months of age. Degeneration appears to follow a retrograde course with axons dying from their proximal ends toward the globe. Although nerve damage is typically bilateral, the progression of disease is asymmetric between the eyes of individual mice. Some nerves also exhibit focal preservation of tracts of axons generally in the nasal peripheral region. Ganglion cell loss, as a function of the loss of betaGeo expression, is evident in some mice between 8 and 10 months of age and is prevalent in the majority of mice older than 10.5 months. Most eyes display a uniform loss of ganglion cells throughout the retina, but many younger mice exhibit focal loss of cells in sectors extending from the optic nerve head to the retinal periphery. Similar to what we observe in the optic nerves, ganglion cell loss is often asymmetric between the eyes of the same animal. CONCLUSION: A comparison of the data collected from the two cohorts of mice used for this study suggests that the initial site of damage in this disease is to the axons in the optic nerve, followed by the subsequent death of the ganglion cell soma. [Abstract/Link to Full Text]

Skogen M, Roth J, Yerkes S, Parekh-Olmedo H, Kmiec E
Short G-rich oligonucleotides as a potential therapeutic for Huntington's Disease.
BMC Neurosci. 2006;765.
BACKGROUND: Huntington's Disease (HD) is an inherited autosomal dominant genetic disorder in which neuronal tissue degenerates. The pathogenesis of the disease appears to center on the development of protein aggregates that arise initially from the misfolding of the mutant HD protein. Mutant huntingtin (Htt) is produced by HD genes that contain an increased number of glutamine codons within the first exon and this expansion leads to the production of a protein that misfolds. Recent studies suggest that mutant Htt can nucleate protein aggregation and interfere with a multitude of normal cellular functions. RESULTS: As such, efforts to find a therapy for HD have focused on agents that disrupt or block the mutant Htt aggregation pathway. Here, we report that short guanosine monotonic oligonucleotides capable of adopting a G-quartet structure, are effective inhibitors of aggregation. By utilizing a biochemical/immunoblotting assay as an initial screen, we identified a 20-mer, all G-oligonucleotide (HDG) as an active molecule. Subsequent testing in a cell-based assay revealed that HDG was an effective inhibitor of aggregation of a fusion protein, comprised of a mutant Htt fragment and green fluorescent protein (eGFP). Taken together, our results suggest that a monotonic G-oligonucleotide, capable of adopting a G-quartet conformation is an effective inhibitor of aggregation. This oligonucleotide can also enable cell survival in PC12 cells overexpressing a mutant Htt fragment fusion gene. CONCLUSION: Single-stranded DNA oligonucleotides capable of forming stable G-quartets can inhibit aggregation of the mutant Htt fragment protein. This activity maybe an important part of the pathogenecity of Huntington's Disease. Our results reveal a new class of agents that could be developed as a therapeutic approach for Huntington's Disease. [Abstract/Link to Full Text]

Widera D, Mikenberg I, Elvers M, Kaltschmidt C, Kaltschmidt B
Tumor necrosis factor alpha triggers proliferation of adult neural stem cells via IKK/NF-kappaB signaling.
BMC Neurosci. 2006;764.
BACKGROUND: Brain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-alpha) is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs) have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation. RESULTS: Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs) that results in increased proliferation. Moreover, we demonstrate IKK-alpha/beta-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU) incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-kappaB) as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-kappaB super-repressor IkappaB-AA1. Pharmacological blockade of IkappaB ubiquitin ligase activity led to comparable decreases in NF-kappaB activity and proliferation. In addition, IKK-beta gene product knock-down via siRNA led to diminished NF-kappaB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFbeta-activated kinase 1 (TAK-1) is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial for future regenerative and anti-tumor medicine. CONCLUSION: TNF-mediated activation of IKK-beta resulted in activation of NF-kappaB and was followed by up-regulation of the bona-fide target gene cyclin D1. Activation of the canonical NF-kappaB pathway resulted in strongly increased proliferation of NSCs. [Abstract/Link to Full Text]

Airey DC, Wu F, Guan M, Collins CE
Geometric morphometrics defines shape differences in the cortical area map of C57BL/6J and DBA/2J inbred mice.
BMC Neurosci. 2006;763.
BACKGROUND: We previously described planar areal differences in adult mouse visual, somatosensory, and neocortex that collectively discriminated C57BL/6J and DBA/2J inbred strain identity. Here we use a novel application of established methods of two-dimensional geometric morphometrics to examine shape differences in the cortical area maps of these inbred strains. RESULTS: We used Procrustes superimposition to align a reliable set of landmarks in the plane of the cortical sheet from tangential sections stained for the cytochrome oxidase enzyme. Procrustes superimposition translates landmark configurations to a common origin, scales them to a common size, and rotates them to minimize an estimate of error. Remaining variation represents shape differences. We compared the variation in shape between C57BL/6J and DBA/2J relative to that within each strain using a permutation test of Goodall's F statistic. Significant differences in shape in the posterior medial barrel subfield (PMBSF), as well as differences in shape across primary sensory areas, characterize the cortical area maps of these common inbred, isogenic strains. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, in both size and shape. These differences suggest polymorphism in genetic factors underlying cortical specification, even between common isogenic strains. Comparing cortical phenotypes between normally varying inbred mice or between genetically modified mice can identify genetic contributions to cortical specification. Geometric morphometric analysis of shape represents an additional quantitative tool for the study of cortical development, regardless of whether it is studied from phenotype to gene or gene to phenotype. [Abstract/Link to Full Text]

Zeng W, Gillis T, Hakky M, Djouss� L, Myers RH, MacDonald ME, Gusella JF
Genetic analysis of the GRIK2 modifier effect in Huntington's disease.
BMC Neurosci. 2006;762.
BACKGROUND: In Huntington's disease (HD), age at neurological onset is inversely correlated with the length of the CAG trinucleotide repeat mutation, but can be modified by genetic factors beyond the HD gene. Association of a relatively infrequent 16 TAA allele of a trinucleotide repeat polymorphism in the GRIK2 3'UTR with earlier than expected age at neurological onset has been suggested to reflect linkage disequilibrium with a functional polymorphism in GRIK2 or an adjacent gene. RESULTS: We have tested this hypothesis by sequencing all GRIK2 exons, the exon-flanking sequences and 3'UTR in several individuals who were crucial to demonstrating the modifier effect, as they showed much earlier age at neurological onset than would be expected from the length of their HD CAG mutation. Though ten known SNPs were detected, no sequence variants were found in coding or adjacent sequence that could explain the modifier effect by linkage disequilibrium with the 16 TAA allele. Haplotype analysis using microsatellites, known SNPs and new variants discovered in the 3'UTR argues against a common ancestral origin for the 16 TAA repeat alleles in these individuals. CONCLUSION: These data suggest that the modifier effect is actually due to the TAA repeat itself, possibly via a functional consequence on the GRIK2 mRNA. [Abstract/Link to Full Text]

Kopanitsa MV, Afinowi NO, Grant SG
Recording long-term potentiation of synaptic transmission by three-dimensional multi-electrode arrays.
BMC Neurosci. 2006;761.
BACKGROUND: Multi-electrode arrays (MEAs) have become popular tools for recording spontaneous and evoked electrical activity of excitable tissues. The majority of previous studies of synaptic transmission in brain slices employed MEAs with planar electrodes that had limited ability to detect signals coming from deeper, healthier layers of the slice. To overcome this limitation, we used three-dimensional (3D) MEAs with tip-shaped electrodes to probe plasticity of field excitatory synaptic potentials (fEPSPs) in the CA1 area of hippocampal slices of 129S5/SvEvBrd and C57BL/6J-TyrC-Brd mice. RESULTS: Using 3D MEAs, we were able to record larger fEPSPs compared to signals measured by planar MEAs. Several stimulation protocols were used to induce long-term potentiation (LTP) of synaptic responses in the CA1 area recorded following excitation of Sch�ffer collateral/commissural fibres. Either two trains of high frequency tetanic stimulation or three trains of theta-burst stimulation caused a persistent, pathway specific enhancement of fEPSPs that remained significantly elevated for at least 60 min. A third LTP induction protocol that comprised 150 pulses delivered at 5 Hz, evoked moderate LTP if excitation strength was increased to 1.5x of the baseline stimulus. In all cases, we observed a clear spatial plasticity gradient with maximum LTP levels detected in proximal apical dendrites of pyramidal neurones. No significant differences in the manifestation of LTP were observed between 129S5/SvEvBrd and C57BL/6J-TyrC-Brd mice with the three protocols used. All forms of plasticity were sensitive to inhibition of N-methyl-D-aspartate (NMDA) receptors. CONCLUSION: Principal features of LTP (magnitude, pathway specificity, NMDA receptor dependence) recorded in the hippocampal slices using MEAs were very similar to those seen in conventional glass electrode experiments. Advantages of using MEAs are the ability to record from different regions of the slice and the ease of conducting several experiments on a multiplexed platform which could be useful for efficient screening of novel transgenic mice. [Abstract/Link to Full Text]

Bangert M, J�rgens U, H�usler U, Altenm�ller E
Classical conditioned responses to absent tones.
BMC Neurosci. 2006;760.
BACKGROUND: Recent evidence for a tight coupling of sensorimotor processes in trained musicians led to the question of whether this coupling extends to preattentively mediated reflexes; particularly, whether a classically conditioned response in one of the domains (auditory) is generalized to another (tactile/motor) on the basis of a prior association in a second-order Pavlovian paradigm. An eyeblink conditioning procedure was performed in 17 pianists, serving as a model for overlearned audiomotor integration, and 14 non-musicians. Results: During the training session, subjects were conditioned to respond to auditory stimuli (piano tones). During a subsequent testing session, when subjects performed keystrokes on a silent piano, pianists showed significantly higher blink rates than non-musicians. CONCLUSION: These findings suggest a tight coupling of the auditory and motor domains in musicians, pointing towards training-dependent mechanisms of strong cross-modal sensorimotor associations even on sub-cognitive processing levels. [Abstract/Link to Full Text]

Linnemann C, Schmeh I, Thier P, Schwarz C
Transient change in GABA(A) receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration.
BMC Neurosci. 2006;759.
BACKGROUND: Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration. RESULTS: We observed a specific reduction in gamma2 subunit gene expression, while alpha1-5, beta1-2, gamma1,3 and delta subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the gamma2 down-regulation was present only after the onset of degeneration at p14. The difference in gamma2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice. CONCLUSION: In conclusion, the down-regulation of gamma2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life. [Abstract/Link to Full Text]

Tuday EC, Olree KS, Horch KW
Differential activation of nerve fibers with magnetic stimulation in humans.
BMC Neurosci. 2006;758.
BACKGROUND: Earlier observations in our lab had indicated that large, time-varying magnetic fields could elicit action potentials that travel in only one direction in at least some of the myelinated axons in peripheral nerves. The objective of this study was to collect quantitative evidence for magnetically induced unidirectional action potentials in peripheral nerves of human subjects. A magnetic coil was maneuvered to a location on the upper arm where physical effects consistent with the creation of unidirectional action potentials were observed.Electromyographic (EMG) and somatosensory evoked potential (SEP) recordings were then made from a total of 20 subjects during stimulation with the magnetic coil. RESULTS: The relative amplitudes of the EMG and SEP signals changed oppositely when the current direction in the magnetic coil was reversed. This effect was consistent with current direction in the coil relative to the arm for all subjects. CONCLUSION: A differential evocation of motor and sensory fibers was demonstrated and indicates that it may be possible to induce unidirectional action potentials in myelinated peripheral nerve fibers with magnetic stimulation. [Abstract/Link to Full Text]

Wiswede D, R�sseler J, Hasselbach S, M�nte TF
Memory recall in arousing situations - an emotional von Restorff effect?
BMC Neurosci. 2006;757.
BACKGROUND: Previous research has demonstrated a relationship between memory recall and P300 amplitude in list learning tasks, but the variables mediating this P300-recall relationship are not well understood. In the present study, subjects were required to recall items from lists consisting of 12 words, which were presented in front of pictures taken from the IAPS collection. One word per list is made distinct either by font color or by a highly arousing background IAPS picture. This isolation procedure was first used by von Restorff. Brain potentials were recorded during list presentation. RESULTS: Recall performance was enhanced for color but not for emotional isolates. Event-related brain potentials (ERP) showed a more positive P300-component for recalled non-isolated words and color-isolated words, compared to the respective non-remembered words, but not for words isolated by arousing background. CONCLUSION: Our findings indicate that it is crucial to take emotional mediator variables into account, when using the P300 to predict later recall. Highly arousing environments might force the cognitive system to interrupt rehearsal processes in working memory, which might benefit transfer into other, more stable memory systems. The impact of attention-capturing properties of arousing background stimuli is also discussed. [Abstract/Link to Full Text]

Recent Articles in BMC Neurology

Kashyap RS, Kainthla RP, Satpute RM, Agarwal NP, Chandak NH, Purohit HJ, Taori GM, Daginawala HF
Differential diagnosis of tuberculous meningitis from partially-treated pyogenic meningitis by cell ELISA.
BMC Neurol. 2004 Oct 22;4(1):16.
BACKGROUND: Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM. METHODS: We developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients. RESULTS: The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM. CONCLUSION: When induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond. [Abstract/Link to Full Text]

Chan Carusone S, Smieja M, Molloy W, Goldsmith CH, Mahony J, Chernesky M, Gnarpe J, Standish T, Smith S, Loeb M
Lack of association between vascular dementia and Chlamydia pneumoniae infection: a case-control study.
BMC Neurol. 2004 Oct 12;4(1):15.
BACKGROUND: Chronic inflammation appears to play a role in the pathogenesis of vascular dementia. Given the association between Chlamydia pneumoniae and stroke, the possibility exists that previous exposure to C. pneumoniae may play a role in vascular dementia. The objective of this study was to determine if there was an association between serological evidence of C. pneumoniae infection or inflammatory markers with vascular dementia. METHODS: 28 case-patients with vascular dementia at a geriatric clinic and 24 caregiver-controls were tested for C. pneumoniae IgG and IgA antibodies. The association between vascular dementia and C. pneumoniae titres as well as inflammatory markers was estimated by using both conditional logistic regression and stratified logistic regression. RESULTS: When matched cases were compared to controls, there was no significant difference in elevated C. pneumoniae specific IgG antibodies (titre >or= 1:32), odds ratio [OR] 1.3 (95% confidence intervals [CI] 0.3 to 6.0), p = 0.71, or in elevated C. pneumoniae specific IgA antibodies (titre >or= 1:16), OR 2.0 (95%CI 0.5 to 8.0), p = 0.33 indicative of past or persistent C. pneumoniae infection. Similarly, no difference in high IgG or IgA antibody levels (IgG titre >or= 1:512 or IgA titre >or= 1:64) between the two groups, indicative of recent C. pneumoniae infection, was found, OR 0.4 (95%CI 0.1 to 2.1), p = 0.27. For C-reactive protein (CRP), the mean difference between 18 matched pairs (case - control) was - 3.33 mg/L. There was no significant difference between cases and controls when comparing log transformed values, OR 0.03 (95%CI 0.00 to 2.89), p = 0.13 or comparing CRP values above or below the median, OR 0.8 (95%CI 0.2 to 3.4), p = 0.71. For fibrinogen, the mean difference between pairs (case - control) was -0.07 g/L. There was no statistical difference between cases and controls when comparing log transformed values, OR 0.6 (95%CI 0.0 to 31.2), p = 0.79 or between fibrinogen values above and below the median, OR = 0.5 (95%CI 0.1 to 2.0), p = 0.50. CONCLUSION: We found no evidence for a significant association between C. pneumoniae infection, inflammatory markers such as CRP and fibrinogen, and vascular dementia. [Abstract/Link to Full Text]

Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N
Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome.
BMC Neurol. 2004 Oct 4;4(1):14.
BACKGROUND: Fatigue is a crucial sensation that triggers rest, yet its underlying neuronal mechanisms remain unclear. Intense long-term fatigue is a symptom of chronic fatigue syndrome, which is used as a model to study the mechanisms underlying fatigue. METHODS: Using magnetic resonance imaging, we conducted voxel-based morphometry of 16 patients and 49 age-matched healthy control subjects. RESULTS: We found that patients with chronic fatigue syndrome had reduced gray-matter volume in the bilateral prefrontal cortex. Within these areas, the volume reduction in the right prefrontal cortex paralleled the severity of the fatigue of the subjects. CONCLUSION: These results are consistent with previous reports of an abnormal distribution of acetyl-L-carnitine uptake, which is one of the biochemical markers of chronic fatigue syndrome, in the prefrontal cortex. Thus, the prefrontal cortex might be an important element of the neural system that regulates sensations of fatigue. [Abstract/Link to Full Text]

van de Vusse AC, Stomp-van den Berg SG, Kessels AH, Weber WE
Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379].
BMC Neurol. 2004 Sep 29;413.
BACKGROUND: Complex Regional Pain Syndrome type one (CRPS I) or formerly Reflex Sympathetic Dystrophy (RSD) is a disabling syndrome, in which a painful limb is accompanied by varying symptoms. Neuropathic pain is a prominent feature of CRPS I, and is often refractory to treatment. Since gabapentin is an anticonvulsant with a proven analgesic effect in various neuropathic pain syndromes, we sought to study the efficacy of the anticonvulsant gabapentin as treatment for pain in patients with CRPS I. METHODS: We did a randomized double blind placebo controlled crossover study with two three-weeks treatment periods with gabapentin and placebo separated by a two-weeks washout period. Patients started at random with gabapentin or placebo, which was administered in identical capsules three times daily. We included 58 patients with CRPS type 1. RESULTS: Patients reported significant pain relief in favor of gabapentin in the first period. Therapy effect in the second period was less; finally resulting in no significant effect combining results of both periods. The CRPS patients had sensory deficits at baseline. We found that this sensory deficit was significantly reversed in gabapentin users in comparison to placebo users. CONCLUSIONS: Gabapentin had a mild effect on pain in CRPS I. It significantly reduced the sensory deficit in the affected limb. A subpopulation of CRPS patients may benefit from gabapentin. [Abstract/Link to Full Text]

Soleimani A, Moayyeri A, Akhondzadeh S, Sadatsafavi M, Tavakoli Shalmani H, Soltanzadeh A
Frequency of myasthenic crisis in relation to thymectomy in generalized myasthenia gravis: a 17-year experience.
BMC Neurol. 2004 Sep 11;412.
BACKGROUND: Myasthenic crisis is the most serious life-threatening event in generalized myasthenia gravis (MG) patients. The objective of this study was to assess the long-term impact of thymectomy on rate and severity of these attacks in Iranian patients. METHODS: We reviewed the clinical records from 272 myasthenic patients diagnosed and treated in our neurology clinic during 1985 to 2002. Fifty-three patients were excluded because of unconfirmed diagnosis, ocular form of MG, contraindication to surgery, concomitant diseases and loss to follow-up. The Osserman classification was used to assess the initial severity of the disease. Frequency and severity of the attacks were compared between two groups with appropriate statistical tests according to the nature of variables. Multivariate logistic regression analysis was used to assess the predictors of myasthenic crisis in the group of patients without thymoma. RESULTS: 110 patients were in thymectomy group and the other 109 patients were on medical therapy. These two groups had no significant differences with respect to age at onset, gender, Osserman score in baseline and follow up period. 62 patients (28.3% of all 219 patients) had reported 89 attacks of myasthenic crisis. 20 patients of 62 (32%) were in thymectomy group and 42 (68%) were in the other group. There was significant difference between the two groups in number of patients with crisis (P = 0.001; odds ratio = 2.8 with 95% CI of 1.5 to 5.2). In addition, these attacks were more severe in group of non-thymectomized patients as the duration of ICU admission was longer and they needed more ventilatory support during their attacks. Regression model showed thymectomy and lower age at onset as two predictors of decrement in myasthenic crisis rate in non-thymomatous MG patients. CONCLUSIONS: It is suggested that frequency and severity of myasthenic attacks as important endpoints in evaluation of MG patients. Thymectomy seems to have a preventive role on rate and severity of these attacks. [Abstract/Link to Full Text]

Sadeghi S, Ghavanini M, Ashraf A, Jafari P
Effects of age and leg length upon central loop of the gastrocnemius-soleus H-reflex latency.
BMC Neurol. 2004 Sep 3;411.
BACKGROUND: central loop of the gastrocnemius-soleus H-reflex latency (Tc) that looks promising in the diagnosis of S1 radiculopathy; has been investigated in a few studies and only two of them have focused on the constitutional factors affecting it. Although leg length has been shown to contribute to the Tc, the role of age is controversial. More confusing, none of the previously performed studies have used strict criteria to rule out subclinical neuropathy, so the results could be misleading. This study has been performed to determine the influence of leg length and age on Tc among a carefully selected group of healthy volunteers. METHODS: after screening forty six volunteers by taking history, physical examination and a brief electrophysiologic study; forty of them were selected to enroll into the study. Tc was obtained in all the study subjects and leg length and age were recorded for correlational analyses. RESULTS: this group was consisted of 26 males (65%) and 14 females (35%) with the age range of 19-65 years (Mean +/- SD: 37 +/- 10.7) and leg length range of 29.5-43 centimeters (36.4 +/- 3.4).Mean +/- SD for Tc was 6.78 +/- 0.3. We found a significant correlation between Tc and leg length (p value= 0.003, r = 0.49 and confidence interval 95% = 0.59-0.88), no significant correlation was found between age and Tc (p value= 0.48, r = 0.11), also we obtained the regression equation as: Tc = 0.04L + 5.28 CONCLUSIONS: in contrast to leg length, age was not correlated with Tc. Future studies are required to delineate other contributing factors to Tc. [Abstract/Link to Full Text]

Krymchantowski AV, Bigal ME
Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine.
BMC Neurol. 2004 Jun 28;410.
BACKGROUND: Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID) have also demonstrated efficacy in treating migraine attacks. There is evidence that the combination of a triptan and a NSAID decreases migraine recurrence in clinical practice. The primary aim of this randomized open label study was to assess the recurrence rates in migraine sufferers acutely treated with rizatriptan (RI) alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, RO) vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO). We were also interested in comparing the efficacy rates within these three groups. METHODS: We assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10 men, ages 18 to 65 years, mean 37 years). Patients with IHS migraine were randomized to one out of 3 groups, where they had to treat 6 consecutive moderate or severe attacks in counterbalanced order. In group 1, patients treated the first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA, followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI + TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4 hours, as well as recurrence and side effects were compared. RESULTS: A total of 33 patients finished the study, treating 184 attacks. The pain-free rates at 1 hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS). Pain-free rates at 2 h were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI + RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA). At 4 h, pain-free rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons). The combination of RI + RO was superior to RI and to RI + TA in regard of the absence of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h) was observed in 50% of patients treated with RI, in 15,4% of those treated with RI + RO, and in 7,7% of those treated with RI + TA. CONCLUSIONS: Despite the methodological limitations of this study, the combination of RI and RO revealed a higher response rate at 2 hours. Recurrence was also clearly decreased with both combinations in relation to the use of RI alone. Controlled studies are necessary to provide additional evidence. [Abstract/Link to Full Text]

Togha M, Bakhtavar K
Factors associated with in-hospital mortality following intracerebral hemorrhage: a three-year study in Tehran, Iran.
BMC Neurol. 2004 Jun 14;49.
BACKGROUND: Primary intracerebral hemorrhage (ICH) is one of the common vascular insults with a relatively high rate of mortality. The aim of the current study was to determine the mortality rate and to evaluate the influence of various factors on the mortality of patients with intracerebral hemorrhage (ICH). Demographic characteristics along with clinical features and neuroimaging information on 122 patients with primary ICH admitted to Sina Hospital between 1999-2002 were assessed by multivariate analysis. RESULTS: Of 122 patients diagnosed with intracerebral hemorrhage, 70 were men and 52 were women. Sixty-nine percent of subjects were between 60 to 80 years of age. A history of hypertension was the primary cause in 67.2% of participants and it was found more frequent compared to other cardiovascular risk factors such as a history of ischemic heart disease (17.2%), diabetes mellitus (18%) and cigarette smoking (13.1%).The overall mortality rate among ICH patients admitted to the hospital was 46.7%. About one third of the deaths occurred within the first two days after brain injury. Factor independently associated with in-hospital mortality were Glasgow Coma Scale (GCS) score (</= 8), diabetes mellitus disease, volume of hematoma and and intraventricular hematoma. CONCLUSION: Higher rate of mortality were observed during the first two weeks of hospitalization following ICH. Neuroimaging features along with GCS score can help the clinicians in developing their prognosis. [Abstract/Link to Full Text]

Ruiz-Pe�a JL, Pi�ero P, Sellers G, Argente J, Casado A, Foronda J, Ucl�s A, Izquierdo G
Magnetic resonance spectroscopy of normal appearing white matter in early relapsing-remitting multiple sclerosis: correlations between disability and spectroscopy.
BMC Neurol. 2004 Jun 10;48.
BACKGROUND: What currently appears to be irreversible axonal loss in normal appearing white matter, measured by proton magnetic resonance spectroscopy is of great interest in the study of Multiple Sclerosis. Our aim is to determine the axonal damage in normal appearing white matter measured by magnetic resonance spectroscopy and to correlate this with the functional disability measured by Multiple Sclerosis Functional Composite scale, Neurological Rating Scale, Ambulation Index scale, and Expanded Disability Scale Score. METHODS: Thirty one patients (9 male and 22 female) with relapsing remitting Multiple Sclerosis and a Kurtzke Expanded Disability Scale Score of 0-5.5 were recruited from four hospitals in Andalusia, Spain and included in the study. Magnetic resonance spectroscopy scans and neurological disability assessments were performed the same day. RESULTS: A statistically significant correlation was found (r = -0.38 p < 0.05) between disability (measured by Expanded Disability Scale Score) and N-Acetyl Aspartate (NAA/Cr ratio) levels in normal appearing white matter in these patients. No correlation was found between the NAA/Cr ratio and disability measured by any of the other disability assessment scales. CONCLUSIONS: There is correlation between disability (measured by Expanded Disability Scale Score) and the NAA/Cr ratio in normal appearing white matter. The lack of correlation between the NAA/Cr ratio and the Multiple Sclerosis Functional Composite score indicates that the Multiple Sclerosis Functional Composite is not able to measure irreversible disability and would be more useful as a marker in stages where axonal damage is not a predominant factor. [Abstract/Link to Full Text]

Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, Hill WD, Feuerstein G, Hess DC
Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats.
BMC Neurol. 2004 Apr 26;47.
BACKGROUND: Minocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally. The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens. METHODS: Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation. Pharmacokinetic studies and hemodynamic monitoring were performed on minocycline-treated rats. RESULTS: Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO. At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% and the 3 mg/kg dose significantly reduced infarct size by 34%. With a 6 hour time window there was a non-significant trend in infarct reduction. There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours. Minocycline did not significantly affect hemodynamic and physiological variables. A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg dose. CONCLUSIONS: The neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4-5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke. [Abstract/Link to Full Text]

Unger ER, Nisenbaum R, Moldofsky H, Cesta A, Sammut C, Reyes M, Reeves WC
Sleep assessment in a population-based study of chronic fatigue syndrome.
BMC Neurol. 2004 Apr 19;46.
BACKGROUND: Chronic fatigue syndrome (CFS) is a disabling condition that affects approximately 800,000 adult Americans. The pathophysiology remains unknown and there are no diagnostic markers or characteristic physical signs or laboratory abnormalities. Most CFS patients complain of unrefreshing sleep and many of the postulated etiologies of CFS affect sleep. Conversely, many sleep disorders present similarly to CFS. Few studies characterizing sleep in unselected CFS subjects have been published and none have been performed in cases identified from population-based studies. METHODS: The study included 339 subjects (mean age 45.8 years, 77% female, 94.1% white) identified through telephone screen in a previously described population-based study of CFS in Wichita, Kansas. They completed questionnaires to assess fatigue and wellness and 2 self-administered sleep questionnaires. Scores for five of the six sleep factors (insomnia/hypersomnia, non-restorative sleep, excessive daytime somnolence, sleep apnea, and restlessness) in the Centre for Sleep and Chronobiology's Sleep Assessment Questionnaire (SAQ) were dichotomized based on threshold. The Epworth Sleepiness Scale score was used as a continuous variable. RESULTS: 81.4% of subjects had an abnormality in at least one SAQ sleep factor. Subjects with sleep factor abnormalities had significantly lower wellness scores but statistically unchanged fatigue severity scores compared to those without SAQ abnormality. CFS subjects had significantly increased risk of abnormal scores in the non-restorative (adjusted odds ratio [OR] = 28.1; 95% confidence interval [CI]= 7.4-107.0) and restlessness (OR = 16.0; 95% CI = 4.2-61.6) SAQ factors compared to non-fatigued, but not for factors of sleep apnea or excessive daytime somnolence. This is consistent with studies finding that, while fatigued, CFS subjects are not sleepy. A strong correlation (0.78) of Epworth score was found only for the excessive daytime somnolence factor. CONCLUSIONS: SAQ factors describe sleep abnormalities associated with CFS and provide more information than the Epworth score. Validation of these promising results will require formal polysomnographic sleep studies. [Abstract/Link to Full Text]

Krymchantowski AV
Acute treatment of migraine. Breaking the paradigm of monotherapy.
BMC Neurol. 2004 Jan 28;44.
BACKGROUND: Migraine is a highly prevalent disorder. The disability provoked by its attacks results in suffering as well as considerable economic and social losses. The objective of migraine acute treatment is to restore the patient to normal function as quickly and consistently as possible. There are numerous drugs available for this purpose and despite recent advances in the understanding of the mechanisms and different biological systems involved in migraine attacks, with the development of specific 5-HT agonists known as triptans, current options for acute migraine still stand below the ideal. DISCUSSION: Monotherapeutic approaches are the rule but up to one third of all patients discontinue their medications due to lack of efficacy, headache recurrence, cost and/or side effects. In addition, a rationale has been suggested for the development of polytherapeutic approaches, simultaneously aiming at some of the biological systems involved. This paper reviews the fundamentals for this changing approach as well as the evidence of its better efficacy. CONCLUSION: As a conclusion, most of the patients with a past history of not responding (no pain-free at 2 hours and/or no sustained pain-free at 24 hours) in at least 5 previous attacks should undergo a combination therapy suiting to their individual profile, which must include analgesics or non-steroidal anti-inflammatory agents plus a triptan or a gastro kinetic drug. The three-drug regimen may also be considered. In addition, changing the right moment to take it and the choice for formulations other than oral has also to be determined individually and clearly posted to the patient. [Abstract/Link to Full Text]

Kwak YT
"Closing-in" phenomenon in Alzheimer's disease and subcortical vascular dementia.
BMC Neurol. 2004 Jan 26;43.
BACKGROUND: The 'closing-in' phenomenon is defined as a tendency to close in on a model while copying it. This is one of several constructional apraxia observed in dementia, particularly in Alzheimer's disease (AD). The aim of this study was to investigate the usefulness of it in the differential diagnosis of AD and subcortical vascular dementia (SVD) and to clarify the factors associated with it. METHODS: We operationally defined and classified it into three types, namely overlap, adherent, and near type. We analyzed the incidence of it in patients with AD (n = 98) and SVD (n = 48). RESULTS: AD patients exhibited a significantly higher occurrence of it as compared to SVD patients. Among the different types of it, the overlap and adherent types occurred almost exclusively in AD patients. A discriminant analysis in AD subjects revealed that the scores obtained from the MMSE, CDR, Barthel index, and the Rey-Osterrieth complex figure test were correlated significantly with the occurrence of it. There was no statistical difference between the Q-EEG parameters of patients that exhibited the closing-in phenomenon and those that did not. CONCLUSIONS: This study suggests that the closing-in phenomenon is phase- and AD-specific and might be a useful tool for the differential diagnosis of AD and SVD. [Abstract/Link to Full Text]

Smith CJ, Emsley HC, Gavin CM, Georgiou RF, Vail A, Barberan EM, del Zoppo GJ, Hallenbeck JM, Rothwell NJ, Hopkins SJ, Tyrrell PJ
Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome.
BMC Neurol. 2004 Jan 15;42.
BACKGROUND: Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome. METHODS: Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume. RESULTS: Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures. CONCLUSIONS: These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome. [Abstract/Link to Full Text]

Jain S, Namboodri KK, Kumari S, Prabhakar S
Loss of circadian rhythm of blood pressure following acute stroke.
BMC Neurol. 2004 Jan 6;41.
BACKGROUND: Epidemiology of acute stroke in developing countries differs from that in the developed world, for example, the age at stroke, risk factors, subtypes of stroke and prognosis. Hypertension remains a dominant risk factor and prognostic indicator in patients with stroke in all communities. The risk of stroke is directly related to elevations of blood pressure. A number of clinical studies have shown that the control of hypertension leads to a reduction in the incidence of stroke in a community. However there is still considerable controversy surrounds the changes in blood pressure in various subtypes of strokes and problem of management of elevated BP after stroke. We studied the circadian rhythm of blood pressure in patients following acute stroke. METHODS: To study the circadian rhythm of blood pressure, fifty consecutive patients with an acute stroke who were admitted to medical emergency within 120 hours of onset were included in the study. After a detailed history and clinical examination, a continuous blood pressure monitor (Spacelab 90207) was attached on the side ipsilateral to intracranial lesion (unaffected arm). The blood pressure was recorded for 24 hours at 15 minutes interval during daytime (6.00 am-6.00 pm) and 20 minutes interval overnight (6 pm to 6 am). RESULTS: Risk factors for stroke in 50 patients included hypertension in 31(62%), diabetes mellitus in 4 (8%), smoking in 13 (26%) and previous history of transient ischemic attack in 7 (14%) patients. Mean systolic pressure and diastolic pressure at admission were higher in patients with hemorrhagic stroke -29 patients (177 +/- 24 mmHg and 105 +/- 19 mmHg respectively) compared to patients with ischemic strokes-21 patients (150 +/- 36 mm Hg and 89 +/- 18 mm Hg respectively, p value <0.01 in both comparisons). The normal diurnal variation in blood pressure (night time dipping of more than 10%) was abolished in 44 (88%) of patients. Out of 44 nondippers, 29 patients showed reverse dipping i.e. rise of BP during night time compared to day time levels. None of the risk factors, clinical or laboratory variables, type of stroke or blood pressure changes differed significantly between these two groups. CONCLUSIONS: Therefore, we showed a pathologically reduced or abolished circadian BP variation after stroke. Absence of normal dipping results in a higher 24 hour blood pressure load and may have more target organ damage than those with normal diurnal variation of blood pressure. [Abstract/Link to Full Text]

Campbell C, Jacob P
Deflazacort for the treatment of Duchenne Dystrophy: a systematic review.
BMC Neurol. 2003 Sep 8;37.
BACKGROUND: To complete a systematic review and meta-analysis based on the clinical question: Is Deflazacort (DFZ), a prednisolone derivative, an effective therapy for improving strength, with acceptable side effects, in children with Duchenne Dystrophy (DD)? METHODS: MEDLINE, EMBASE, Current Contents, Dissertation Abstracts, Health Star, PsychINFO and Cochrane, were searched using the following inclusion criteria: 1) A randomized controlled trial comparing DFZ with placebo or another therapy; 2) Male participants age 2-18 years with DD; 3) Outcomes of (a) any form of strength or functional testing, or (b) any form of side effect. RESULTS: Fifteen studies of potential relevance were identified, with five meeting the inclusion criteria. These five studies included 291 children and were published in English language journals between 1994 and 2000. Two studies compared DFZ versus placebo, two studies compared DFZ with prednisone and one study had both placebo and prednisone comparisions. Two large trials were identified that have not been published in article format. Due to the heterogeneity in outcome measures and the inconsistent reporting of summary statistics a meta-analytic approach could not be taken. CONCLUSIONS: Examining individual studies it appears that DFZ improves strength and functional outcomes compared to placebo, but it remains unclear if it has a benefit over prednisone on similar outcomes. Two trials found that DFZ causes less weight gain than prednisone. [Abstract/Link to Full Text]

Wirdefeldt K, Burgess CE, Westerberg L, Payami H, Schalling M
A linkage study of candidate loci in familial Parkinson's Disease.
BMC Neurol. 2003 Jul 26;36.
BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Most cases are sporadic, however familial cases do exist. We examined 12 families with familial Parkinson's disease ascertained at the Movement Disorder clinic at the Oregon Health Sciences University for genetic linkage to a number of candidate loci. These loci have been implicated in familial Parkinson's disease or in syndromes with a clinical presentation that overlaps with parkinsonism, as well as potentially in the pathogenesis of the disease. METHODS: The examined loci were PARK3, Parkin, DRD (dopa-responsive dystonia), FET1 (familial essential tremor), BDNF (brain-derived neurotrophic factor), GDNF (glial cell line-derived neurotrophic factor), Ret, DAT1 (the dopamine transporter), Nurr1 and Synphilin-1. Linkage to the alpha-synuclein gene and the Frontotemporal dementia with parkinsonism locus on chromosome 17 had previously been excluded in the families included in this study. Using Fastlink, Genehunter and Simwalk both parametric and model-free non-parametric linkage analyses were performed. RESULTS: In the multipoint parametric linkage analysis lod scores were below -2 for all loci except FET1 and Synphilin-1 under an autosomal dominant model with incomplete penetrance. Using non-parametric linkage analysis there was no evidence for linkage, although linkage could not be excluded. A few families showed positive parametric and non-parametric lod scores indicating possible genetic heterogeneity between families, although these scores did not reach any degree of statistical significance. CONCLUSIONS: We conclude that in these families there was no evidence for linkage to any of the loci tested, although we were unable to exclude linkage with both parametric and non-parametric methods. [Abstract/Link to Full Text]

Lucas M, Costa AF, Garc�a-Moreno JM, Solano F, Gamero MA, Izquierdo G
Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene.
BMC Neurol. 2003 Jul 23;35.
BACKGROUND: Cerebral cavernous malformations (CCM) present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members. METHODS: We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old) sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives. RESULTS: The phenotypes of cerebral cavernous malformations (CCMs) in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA. CONCLUSIONS: Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling. [Abstract/Link to Full Text]

Meschia JF, Brott TG, Brown RD, Crook RJ, Frankel M, Hardy J, Merino JG, Rich SS, Silliman S, Worrall BB
The Ischemic Stroke Genetics Study (ISGS) Protocol.
BMC Neurol. 2003 Jul 8;34.
BACKGROUND: The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype. METHODS/DESIGN: The Ischemic Stroke Genetic Study is a prospective, multicenter genetic association study in adults with recent first-ever ischemic stroke confirmed with computed tomography or magnetic resonance imaging. Patients are evaluated at academic medical centers in the United States and compared with sex- and age-matched controls. Stroke subtypes are determined by central blinded adjudication using standardized, validated mechanistic and syndromic classification systems. The panel of genes to be tested for polymorphisms includes beta-fibrinogen and platelet glycoprotein Ia, Iba, and IIb/IIIa. Immortalized cell lines are created to allow for time- and cost-efficient testing of additional candidate genes in the future. DISCUSSION: The study is designed to minimize survival bias and to allow for exploring associations between specific polymorphisms and individual subtypes of ischemic stroke. The data set will also permit the study of genetic determinants of stroke outcome. Having cell lines will permit testing of future candidate risk factor genes. [Abstract/Link to Full Text]

Ho NC, Sandusky S, Madike V, Francomano CA, Dalakas MC
Clinico-pathogenetic findings and management of chondrodystrophic myotonia (Schwartz-Jampel syndrome): a case report.
BMC Neurol. 2003 Jul 2;33.
BACKGROUND: Chondrodystrophic myotonia or Schwartz-Jampel syndrome is a rare genetic disorder characterized by myotonia and skeletal dysplasia. It may be progressive in nature. Recently, the gene responsible for Schwartz-Jampel syndrome has been found and the defective protein it encodes leads to abnormal cartilage development and anomalous neuromuscular activity. CASE PRESENTATION: We report the clinical findings and the management of an 8-year-old boy with this disorder. The molecular findings confirm that the patient is a compound heterozygote with a different splicing mutation in each Perlecan allele. This resulted in a significant reduction in the production of the encoded normal protein. CONCLUSION: We discuss the multi-disciplinary management of Schwartz-Jampel syndrome that will facilitate optimal care and timely intervention of patients with this disorder. [Abstract/Link to Full Text]

Eftekhar B, Gheini M, Ghodsi M, Ketabchi E
Vestibular schwannoma with contralateral facial pain - case report.
BMC Neurol. 2003 Mar 21;32.
BACKGROUND: Vestibular schwannoma (acoustic neuroma) most commonly presents with ipsilateral disturbances of acoustic, vestibular, trigeminal and facial nerves. Presentation of vestibular schwannoma with contralateral facial pain is quite uncommon. CASE PRESENTATION: Among 156 cases of operated vestibular schwannoma, we found one case with unusual presentation of contralateral hemifacial pain. CONCLUSION: The presentation of contralateral facial pain in the vestibular schwannoma is rare. It seems that displacement and distortion of the brainstem and compression of the contralateral trigeminal nerve in Meckel's cave by the large mass lesion may lead to this atypical presentation. The best practice in these patients is removal of the tumour, although persistent contralateral pain after operation has been reported. [Abstract/Link to Full Text]

Goebel A, Moore A, Weatherall R, Roewer N, Schedel R, Sprotte G
Intravenous immunoglobulin in the treatment of primary trigeminal neuralgia refractory to carbamazepine: a study protocol [ISRCTN33042138].
BMC Neurol. 2003 Jan 30;3(1):1.
BACKGROUND: We have recently reported successful treatment of patients with chronic pain syndromes using human pooled intravenous immunoglobulin (IVIG) in a prospective, open-label cohort study. A randomised, placebo controlled, double blinded study is needed to confirm these results. We chose to study patients with carbamazepine resistant primary Trigeminal Neuralgia (rpTN), as these had responded particularly well to IVIG.A protocol involving the use of IVIG in rpTN is complex for three reasons: 1. The effect of IVIG does not follow simple dose-response rules; 2. The response pattern of patients to IVIG was variable and ranged between no effect at all and pain free remission between two weeks and >1 year; 3. TN is characterized by extremely severe pain, for which operative intervention is (if temporarily) helpful in most patients. DESIGN: A placebo controlled, parallel, add-on model was developed and the primary outcome variable defined as the length of time during which patients remain in the study. Study groups are compared using Kaplan-Maier survival analysis. Patients record their response to treatment ("severe, moderate, slight, no pain"). The study coordinator monitors pain diaries. Severe or moderate pain of three days duration will result in termination of the study for that patient. CONCLUSIONS: This study design utilizes a method of survival analysis and is novel in chronic pain research. It allows for both early departure from the study and voluntary crossover upon non-response. It may be applicable to the analysis of IVIG efficacy in other chronic pain syndromes. [Abstract/Link to Full Text]

Greenberg SA
P-ANCA vasculitic neuropathy with 12-year latency between onset of neuropathy and systemic symptoms.
BMC Neurol. 2002 Oct 31;2(1):10.
BACKGROUND: The differential diagnosis of chronic progressive multifocal asymmetric neuropathies is challenging. Vasculitic neuropathies, multifocal forms of chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathies, and asymmetric lower motor neuron disorders are important considerations. CASE PRESENTATION: We report a patient with an unusually long 12-year course of nonsystemic vasculitic neuropathy prior to the development of systemic manifestations. CONCLUSION: We discuss some of the difficulties involved in the diagnosis of chronic progressive multifocal asymmetric neuropathies. [Abstract/Link to Full Text]

Huang C, Wahlund LO, Svensson L, Winblad B, Julin P
Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment.
BMC Neurol. 2002 Sep 12;29.
BACKGROUND: Mild cognitive impairment (MCI) was recently described as a heterogeneous group with a variety of clinical outcomes and high risk to develop Alzheimer's disease (AD). Regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) was used to study the heterogeneity of MCI and to look for predictors of future development of AD. METHODS: rCBF was investigated in 54 MCI subjects using Tc-99m hexamethylpropyleneamine oxime (HMPAO). An automated analysis software (BRASS) was applied to analyze the relative blood flow (cerebellar ratios) of 24 cortical regions. After the baseline examination, the subjects were followed clinically for an average of two years. 17 subjects progressed to Alzheimer's disease (PMCI) and 37 subjects remained stable (SMCI). The baseline SPECT ratio values were compared between PMCI and SMCI. Receiver operating characteristic (ROC) analysis was applied for the discrimination of the two subgroups at baseline. RESULTS: The conversion rate of MCI to AD was 13.7% per year. PMCI had a significantly decreased rCBF in the left posterior cingulate cortex, as compared to SMCI. Left posterior cingulate rCBF ratios were entered into a logistic regression model for ROC curve calculation. The area under the ROC curve was 74%-76%, which indicates an acceptable discrimination between PMCI and SMCI at baseline. CONCLUSION: A reduced relative blood flow of the posterior cingulate gyrus could be found at least two years before the patients met the clinical diagnostic criteria of AD. [Abstract/Link to Full Text]

Matsumura T, Goto K, Yamanaka G, Lee JH, Zhang C, Hayashi YK, Arahata K
Chromosome 4q;10q translocations; comparison with different ethnic populations and FSHD patients.
BMC Neurol. 2002 Aug 20;27.
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by the weakness of facial, shoulder-girdle and upper arm muscles. Most patients with FSHD have fewer numbers of tandem repeated 3.3-kb KpnI units on chromosome 4q35. Chromosome 10q26 contains highly homologous KpnI repeats, and inter-chromosomal translocation has been reported. METHODS: To clarify the influence on the deletion of the repeats, we surveyed three different ethnic populations and FSHD patients using the BglII/BlnI dosage test. RESULTS: The frequency of translocation in 153 Japanese, 124 Korean, 114 Chinese healthy individuals and 56 Japanese 4q35-FSHD patients were 27.5%, 29.8%, 19.3%, and 32.1%, respectively. The ratio of '4 on 10' (trisomy and quatrosomy of chromosome 4) was higher than that of '10 on 4' (nullsomy and monosomy of chromosome 4) in all populations. CONCLUSIONS: The inter-chromosomal exchange was frequently observed in all four populations we examined, and no significant difference was observed between healthy and diseased groups. [Abstract/Link to Full Text]

Niino M, Kikuchi S, Fukazawa T, Miyagishi R, Yabe I, Tashiro K
An examination of the Apo-1/Fas promoter Mva I polymorphism in Japanese patients with multiple sclerosis.
BMC Neurol. 2002 Aug 21;28.
BACKGROUND: The Apo-1/Fas (CD95) molecule is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor (TNF) receptor family. Both Fas and Fas ligand (FasL) are expressed in activated mature T cells, and prolonged cell activation induces susceptibility to Fas-mediated apoptosis. The Apo-1/Fas gene is located in a chromosomal region that shows linkage in multiple sclerosis (MS) genome screens, and studies indicate that there is aberrant expression of the Apo-1/Fas molecule in MS. METHODS: Mva I polymorphism on the Apo-1/Fas promoter gene was detected by PCR-RFLP from the DNA of 114 Japanese patients with conventional MS and 121 healthy controls. We investigated the association of the Mva I polymorphism in Japanese MS patients using a case-control association study design. RESULTS: We found no evidence that the polymorphism contributes to susceptibility to MS. Furthermore, there was no association between Apo-1/Fas gene polymorphisms and clinical course (relapsing-remitting course or secondary-progressive course). No significant association was observed between Apo-1/Fas gene polymorphisms and the age at disease onset. CONCLUSIONS: Overall, our findings suggest that Apo-1/Fas promoter gene polymorphisms are not conclusively related to susceptibility to MS or the clinical characteristics of Japanese patients with MS. [Abstract/Link to Full Text]

Caro J, Ward A, Ishak K, Migliaccio-Walle K, Getsios D, Papadopoulos G, Torfs K
To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?
BMC Neurol. 2002 Aug 19;26.
BACKGROUND: Patients with Alzheimer's disease experience a progressive loss of cognitive function, and the ability to independently perform activities of daily life. Sometimes a dependent stage is reached quite early in the disease, when caregivers decide that the patients can no longer be left alone safely. This is an important aspect of Alzheimer's for patients, their families, and also health care providers. Understanding the relationship between a patient's current cognitive status and their need for care may assist clinicians when recommending an appropriate management plan. In this study, we investigated the relationship of cognitive function to dependence on caregivers before the patients reach a severe stage of the disease. METHODS: Data were obtained on 1,289 patients with mild-to-moderate Alzheimer's disease studied in two randomised clinical trials of galantamine (ReminylcircledR;). Cognition was assessed using the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-cog) and Mini-Mental State Examination (MMSE). Patients were considered dependent if they required >12 hours of supervision each day or had high care needs. The Disability Assessment for Dementia (DAD) scale was also used as a measure of dependence. Disability was predicted directly using MMSE and ADAS-cog and compared to predictions from converted scores. RESULTS: The odds ratio of dependence was significantly higher amongst the patients with worse cognitive impairment, adjusting for age, gender and antipsychotic medication use. For example, a 4-point difference in ADAS-cog score was associated with an increase of 17% (95% CI 11-23) in the adjusted odds for >12 hours of supervision, and of 35% (95% CI 28-43) for dependence. Disability predicted directly using actual ADAS-cog and scores converted from MMSE values had close agreement using the models developed. CONCLUSION: In patients with mild-to-moderate Alzheimer's disease, even relatively small degrees of poorer cognitive function increased the risk of losing the ability to live independently. [Abstract/Link to Full Text]

Burns JM, Login IS
Confounding factors in diagnosing brain death: a case report.
BMC Neurol. 2002 Jun 26;25.
BACKGROUND: Brain death is strictly defined medically and legally. This diagnosis depends on three cardinal neurological features: coma, absent brainstem reflexes, and apnea. The diagnosis can only be made, however, in the absence of intoxication, hypothermia, or certain medical illnesses. CASE PRESENTATION: A patient with severe hypoxic-ischemic brain injury met the three cardinal neurological features of brain death but concurrent profound hypothyroidism precluded the diagnosis. Our clinical and ethical decisions were further challenged by another facet of this complex case. Although her brain damage indicated a hopeless prognosis, we could not discontinue care based on futility because the only known surrogate was mentally retarded and unable to participate in medical planning. CONCLUSION: The presence of certain medical conditions prohibits a diagnosis of brain death, which is a medicolegal diagnosis of death, not a prediction or forecast of future outcome. While prognostication is important in deciding to withdraw care, it is not a component in diagnosing brain death. [Abstract/Link to Full Text]

Moore DF, Altarescu G, Herscovitch P, Schiffmann R
Enzyme replacement reverses abnormal cerebrovascular responses in Fabry disease.
BMC Neurol. 2002 Jun 18;24.
BACKGROUND: Fabry disease is a lysosomal X-linked enzyme deficiency of alpha-galactosidase A associated with an increased mortality and morbidity due to renal failure, cardiac disease and early onset stroke. METHODS: We examined the functional blood flow response of the brain after visual stimulation (reversing checkerboard pattern), and cerebral vasoreactivity following acetazolamide (15 mg/kg) with [15O]H2O and positron emission tomography (PET) in Fabry disease. Twenty-six hemizygous patients (age range 19-47 years) were enrolled in a randomized double-blind placebo-controlled 6-month trial of enzyme replacement therapy administered by intravenous infusion every two weeks. Regional cerebral blood flow (rCBF) was measured with PET at the beginning and end of the trial. RESULTS: Fabry patients had a significantly greater increase in rCBF following visual stimulation and acetazolamide challenge compared to controls. Visual reactivity was normal. The time for recovery of the cerebral vasculature following acetazolamide was prolonged in Fabry patients compared to controls. The abnormal rCBF response induced by visual stimulation and acetazolamide decreased significantly following enzyme replacement therapy, as did the prolonged recovery of the cerebral vasculature. CONCLUSIONS: Enzyme replacement therapy reverses the exaggerated cerebrovascular response in Fabry disease. [Abstract/Link to Full Text]

Agthong S, Wiwanitkit V
Encephalomeningocele cases over 10 years in Thailand: a case series.
BMC Neurol. 2002 May 13;23.
BACKGROUND: Encephalomeningocele, especially in the frontoethmoidal region, is a form of neural tube defect which affects patients in Southeast Asia more commonly than in Western countries. Its underlying cause is not known but teratogenic environmental agents are suspected. However, nutritional deficiency, as in spina bifida, cannot be excluded. METHODS: This study reports 21 cases of meningocele (without brain tissue in the lesion) and encephalomeningocele (with brain tissue) that were admitted to our hospital for surgical corrections in the period of ten years, from 1990 to 1999. Clinicopathological findings, as well as occupations of family members and prenatal exposures to infectious agents or chemicals were reviewed and analyzed. RESULTS: The most commonly involved area was the frontoethmoidal region, found in 20 cases. The combined pattern between nasoethmoidal and nasoorbital defects was found most frequently (11 from 21 cases) and had more associated abnormalities. Encephalomeningocele had more related abnormalities than meningocele with proportions of 0.6 and 0.3, respectively. CONCLUSIONS: Here, we confirmed that genetic defects are not likely to be the single primary cause of this malformation. However, we could not draw any conclusions on etiologic agents. We suggest that case control studies and further investigation on the role of nutritional deficiencies, especially folic acid, in the pathogenesis of encephalomeningocele are necessary to clarify the underlying mechanisms. [Abstract/Link to Full Text]

Recent Articles in Journal of Neuroinflammation

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Recent Articles in Journal of Vision

Bours RJ, Stuur S, Lankheet MJ
Tuning for temporal interval in human apparent motion detection.
J Vis. 2007;7(1):2.
Detection of apparent motion in random dot patterns requires correlation across time and space. It has been difficult to study the temporal requirements for the correlation step because motion detection also depends on temporal filtering preceding correlation and on integration at the next levels. To specifically study tuning for temporal interval in the correlation step, we performed an experiment in which prefiltering and postintegration were held constant and in which we used a motion stimulus containing coherent motion for a single interval value only. The stimulus consisted of a sparse random dot pattern in which each dot was presented in two frames only, separated by a specified interval. On each frame, half of the dots were refreshed and the other half was a displaced reincarnation of the pattern generated one or several frames earlier. Motion energy statistics in such a stimulus do not vary from frame to frame, and the directional bias in spatiotemporal correlations is similar for different interval settings. We measured coherence thresholds for left-right direction discrimination by varying motion coherence levels in a Quest staircase procedure, as a function of both step size and interval. Results show that highest sensitivity was found for an interval of 17-42 ms, irrespective of viewing distance. The falloff at longer intervals was much sharper than previously described. Tuning for temporal interval was largely, but not completely, independent of step size. The optimal temporal interval slightly decreased with increasing step size. Similarly, the optimal step size decreased with increasing temporal interval. [Abstract/Link to Full Text]

Ho YX, Maloney LT, Landy MS
The effect of viewpoint on perceived visual roughness.
J Vis. 2007;7(1):1.
In previous work, we examined how the apparent roughness of a textured surface changed with direction of illumination. We found that observers exhibited systematic failures of roughness constancy across illumination conditions for triangular-faceted surfaces where physical roughness was defined as the variance of facet heights. These failures could be due, in part, to cues in the scene that confound changes in surface roughness with changes in illumination. These cues include the following: (1) the proportion of the surface in shadow, (2) mean luminance of the nonshadowed portion, (3) the standard deviation of the luminance of the nonshadowed portion, and (4) texture contrast. If the visual system relied on such "pseudocues" to roughness, then it would systematically misestimate surface roughness with changes in illumination much as our observers did despite the availability of depth cues such as binocular disparity. Here, we investigate observers' judgments of roughness when illumination direction and surface orientation are fixed and the observers' viewpoint with respect to the surface changes. We find a similar pattern of results. Observers exhibited patterned failures of roughness constancy with change in viewpoint, and an appreciable part of their failures could be accounted for by the same pseudocues. While the human visual system exhibits some degree of roughness constancy, our results lead to the conclusion that it does not always select the correct cues for a given visual task. [Abstract/Link to Full Text]

Rauschecker AM, Solomon SG, Glennerster A
Stereo and motion parallax cues in human 3D vision: can they vanish without a trace?
J Vis. 2006;6(12):1471-85.
In an immersive virtual reality environment, subjects fail to notice when a scene expands or contracts around them, despite correct and consistent information from binocular stereopsis and motion parallax, resulting in gross failures of size constancy (A. Glennerster, L. Tcheang, S. J. Gilson, A. W. Fitzgibbon, & A. J. Parker, 2006). We determined whether the integration of stereopsis/motion parallax cues with texture-based cues could be modified through feedback. Subjects compared the size of two objects, each visible when the room was of a different size. As the subject walked, the room expanded or contracted, although subjects failed to notice any change. Subjects were given feedback about the accuracy of their size judgments, where the "correct" size setting was defined either by texture-based cues or (in a separate experiment) by stereo/motion parallax cues. Because of feedback, observers were able to adjust responses such that fewer errors were made. For texture-based feedback, the pattern of responses was consistent with observers weighting texture cues more heavily. However, for stereo/motion parallax feedback, performance in many conditions became worse such that, paradoxically, biases moved away from the point reinforced by the feedback. This can be explained by assuming that subjects remap the relationship between stereo/motion parallax cues and perceived size or that they develop strategies to change their criterion for a size match on different trials. In either case, subjects appear not to have direct access to stereo/motion parallax cues. [Abstract/Link to Full Text]

Makovski T, Shim WM, Jiang YV
Interference from filled delays on visual change detection.
J Vis. 2006;6(12):1459-70.
Failure to detect changes to salient visual input across a brief interval has popularized the use of change detection, a paradigm that plays important roles in recent studies of visual perception, short-term memory, and consciousness. Much research has focused on the nature of visual representation for the pre- and postchange displays, yet little is known about how visual change detection is interfered with by events inserted between the pre- and postchange displays. To address this question, we tested change detection of colors, spatial locations, and natural scenes, when the interval between changes was (1) blank, (2) filled with a visual scene, or (3) filled with an auditory word. Participants were asked to either ignore the filled visual or auditory event or attend to it by categorizing it as animate or inanimate. Results showed that the ability to detect visual changes was dramatically impaired by attending to a secondary task during the delay. This interference was significant for auditory as well as for visual interfering events and was invariant to the complexity of the prechange displays. Passive listening produced no interference, whereas passive viewing produced small but significant interference. We conclude that visual change detection relies significantly on central, amodal attention. [Abstract/Link to Full Text]

Curran W, Clifford CW, Benton CP
New binary direction aftereffect does not add up.
J Vis. 2006;6(12):1451-8.
Neural adaptation and inhibition are pervasive characteristics of the primate brain and are probably understood better within the context of visual processing than with any other sensory modality. These processes are thought to underlie illusions in which one motion affects the perceived direction of another, such as the direction aftereffect (DAE) and direction repulsion. The DAE describes how, following prolonged viewing of motion in one direction, the direction of a subsequently viewed test pattern is misperceived. In the case of direction repulsion, the direction difference between two transparently moving surfaces is overestimated. Explanations of the DAE appeal to neural adaptation, whereas direction repulsion is accounted for through lateral inhibition. Here, we report on a new illusion, the binary DAE (bDAE), in which superimposed slow and fast dots moving in the same direction are perceived to move in different directions following adaptation to a mixed-speed stimulus. This new phenomenon is essentially a combination of the DAE and direction repulsion. Interestingly, the magnitude of the bDAE is greater than would be expected simply through a linear combination of the DAE and direction repulsion, suggesting that the mechanisms underlying these two phenomena interact in a nonlinear fashion. [Abstract/Link to Full Text]

Jovancevic J, Sullivan B, Hayhoe M
Control of attention and gaze in complex environments.
J Vis. 2006;6(12):1431-50.
In natural behavior, fixation patterns are tightly linked to the ongoing task. However, a critical problem for task-driven systems is dealing with unexpected stimuli. We studied the effect of unexpected potential collisions with pedestrians on the distribution of gaze of subjects walking in a virtual environment. Pedestrians on a collision course with the subject were surprisingly ineffective in evoking fixations, especially when subjects were additionally occupied with another task, suggesting that potential collisions do not automatically attract attention. However, prior fixations on pedestrians did increase collision detection performance. Additionally, the detection of potential collisions led to a short-term change in the strategy of looking at subsequent pedestrians. The overall pattern of results is consistent with the hypothesis that subjects typically rely on mechanisms that are initiated top-down to detect unexpected events such as potential collisions. For this to be effective, subjects must learn an appropriate schedule for initiating search through experience with the probabilities of environmental events. [Abstract/Link to Full Text]

Kanai R, Paffen CL, Hogendoorn H, Verstraten FA
Time dilation in dynamic visual display.
J Vis. 2006;6(12):1421-30.
How does the brain estimate time? This old question has led to many biological and psychological models of time perception (R. A. Block, 1989; P. Fraisse, 1963; J. Gibbon, 1977; D. L. I. Zakay, 1989). Because time cannot be directly measured at a given moment, it has been proposed that the brain estimates time based on the number of changes in an event (S. W. Brown, 1995; P. Fraisse, 1963; W. D. Poynter, 1989). Consistent with this idea, dynamic visual stimuli are known to lengthen perceived time (J. F. Brown, 1931; S. Goldstone & W. T. Lhamon, 1974; W. T. Lhamon & S. Goldstone, 1974, C. O. Z. Roelofs & W. P. C. Zeeman, 1951). However, the kind of information that constitutes the basis for time perception remains unresolved. Here, we show that the temporal frequency of a stimulus serves as the "clock" for perceived duration. Other aspects of changes, such as speed or coherence, were found to be inconsequential. Time dilation saturated at a temporal frequency of 4-8 Hz. These results suggest that the clock governing perceived time has its basis at early processing stages. The possible links between models of time perception and neurophysiological functions of early visual areas are discussed. [Abstract/Link to Full Text]

Kuai SG, Yu C
Constant contour integration in peripheral vision for stimuli with good Gestalt properties.
J Vis. 2006;6(12):1412-20.
The visual system integrates discrete but aligned local stimuli to form percept of global contours. Previous experiments using "snake" contours showed that contour integration was mainly present in foveal vision but absent or greatly weakened in peripheral vision. In this study, we demonstrated that, for contour stimuli such as circles and ellipses, which bore good Gestalt properties, contour integration for shape detection and discrimination was nearly constant from the fovea to up to 35 degrees visual periphery! Contour integration was impaired by local orientation and position jitters of contour elements, indicating that the same local contour linking mechanisms revealed with snake contour stimuli also played critical roles in integration of our good Gestalt stimuli. Contour integration was also unaffected by global position jittering up to 20% of the contour size and by dramatic shape jittering, which excluded non-contour integration processes such as detection of various local cues and template matching as alternative mechanisms for uncompromised peripheral perception of good Gestalt stimuli. Peripheral contour integration also presented an interesting upper-lower visual field symmetry after asymmetries of contrast sensitivity and shape discrimination were discounted. The constant peripheral performance might benefit from easy detection of good Gestalt stimuli, which popped out from background noise, from a boost of local contour linking by top-down influences and/or from multielement contour linking by long-range interactions. [Abstract/Link to Full Text]

Carlson TA, Hogendoorn H, Verstraten FA
The speed of visual attention: what time is it?
J Vis. 2006;6(12):1406-11.
The time course of visual attention has been studied using a number of experimental designs. Here, we present a refined version of a technique first used by Wundt more than a century ago and demonstrate it as an effective method to measure the speed of visual attention. The method generates precise and robust data quickly and is flexible enough to be adapted into a variety of established paradigms. In the experiment, participants view an array of moving clocks and report the time on a target clock, which was indicated by a peripheral or central cue. We found latencies of around 140 ms when the target was cued peripherally and latencies of around 240 ms when the target was cued centrally. These values are in good agreement with previous literature and support the validity of the technique as a way to measure the speed of visual attention. [Abstract/Link to Full Text]

Howe PD, Thompson PG, Anstis SM, Sagreiya H, Livingstone MS
Explaining the footsteps, belly dancer, Wenceslas, and kickback illusions.
J Vis. 2006;6(12):1396-405.
The footsteps illusion (FI) demonstrates that an object's background can have a profound effect on the object's perceived speed. This illusion consists of a yellow bar and a blue bar that move over a black-and-white, striped background. Although the bars move at a constant rate, they appear to repeatedly accelerate and decelerate in antiphase with each other. Previously, this illusion has been explained in terms of the variations in contrast at the leading and trailing edges of the bars that occur as the bars traverse the striped background. Here, we show that this explanation is inadequate and instead propose that for each bar, the bar's leading edge, trailing edge, lateral edges, and the surrounding background edges all contribute to the bar's perceived speed and that the degree to which each edge contributes to the motion percept is determined by that edge's contrast. We show that this theory can explain all the data on the FI as well as the belly dancer and Wenceslas illusions. We conclude by presenting a new illusion, the kickback illusion, which, although geometrically similar to the FI, is mediated by a different mechanism, namely, reverse phi motion. [Abstract/Link to Full Text]

Kanai R, Wu DA, Verstraten FA, Shimojo S
Discrete color filling beyond luminance gaps along perceptual surfaces.
J Vis. 2006;6(12):1380-95.
Perceived color at a point in space is not determined simply by the color directly stimulating the corresponding retinal position. Surface color is informed by flanking edge signals, which also serve to inhibit the intrusion of signals from neighboring surfaces. Spatially continuous local interactions among color and luminance signals have been implicated in a propagation process often referred to as filling-in. Here, we report a phenomenon of discrete color filling whereby color jumps over luminance gaps filling into disconnected regions of the stimulus. This color filling is found to be blocked at boundaries defined by texture. The color filling is also highly specific to the elements belonging to a common perceptual surface, even when multiple surfaces are transparently overlaid. Our results indicate that color filling can be governed by a host of visual cues outside the realm of first-order color and brightness, via their impact on perceptual surface segmentation and segregation. [Abstract/Link to Full Text]

Levi DM, Tripathy SP
Is the ability to identify deviations in multiple trajectories compromised by amblyopia?
J Vis. 2006;6(12):1367-79.
Amblyopia results in a severe loss of positional information and in the ability to accurately enumerate objects (V. Sharma, D. M. Levi, & S. A. Klein, 2000). In this study, we asked whether amblyopia also disrupts the ability to track a near-threshold change in the trajectory of a single target amongst multiple similar potential targets. In the first experiment, we examined the precision for detecting a deviation in the linear motion trajectory of a dot by measuring deviation thresholds as a function of the number of moving trajectories (T). As in normal observers, we found that in both eyes of amblyopes, threshold increases steeply as T increases from 1 to 4. Surprisingly, for T = 1-4, thresholds were essentially identical in both eyes of the amblyopes and were similar to those of normal observers. In a second experiment, we measured the precision for detecting a deviation in the orientation of a static, bilinear "trajectory" by again measuring deviation thresholds (i.e., angle discrimination) as a function of the number of oriented line "trajectories" (T). Relative to the nonamblyopic eye, amblyopes show a marked threshold elevation for a static target when T = 1. However, thresholds increased with T with approximately the same slope as in their preferred eye and in the eyes of the normal controls. We conclude that while amblyopia disrupts static angle discrimination, amblyopic dynamic deviation detection thresholds are normal or very nearly so. [Abstract/Link to Full Text]

Dal Martello MF, Maloney LT
Where are kin recognition signals in the human face?
J Vis. 2006;6(12):1356-66.
We report two experiments that aimed to determine where in the face the cues that signal kinship fall. In both experiments, participants were shown 30 pairs of photographs of children's faces. Half of the pairs portrayed siblings and half did not. The 220 participants were asked to judge whether each pair of photographs portrayed siblings. We measured the effect on kin recognition performance of masks that covered the upper half or the lower half of the face (Experiment 1) and the eye region or the mouth region (Experiment 2). In Experiment 1, we found that the signal detection estimate of performance d' decreased only 5.3% (ns) when the lower face was masked but by more than 65% when the upper face was masked. We tested whether the combination of kinship information from the two halves of the face can be treated as optimal combination of independent cues and found that it could be. In Experiment 2, we found that masking the eye region led to only a 20% reduction (ns) in performance whereas masking the mouth region led to a nonsignificant increase in performance. We also found that the eye region contains only slightly more information about kinship than the upper half of the face outside of the eye region. [Abstract/Link to Full Text]

Read JC, Cumming BG
Does depth perception require vertical-disparity detectors?
J Vis. 2006;6(12):1323-55.
Stereo depth perception depends on the fact that objects project to different positions in the two eyes. Because our eyes are offset horizontally, these retinal disparities are mainly horizontal, and horizontal disparity suffices to give an impression of depth. However, depending on eye position, there may also be small vertical disparities. These are significant because, given both vertical and horizontal disparities, the brain can deduce eye position from purely retinal information and, hence, derive the position of objects in space. However, we show here that, to achieve this, the brain need measure only the magnitude of vertical disparity; for physically possible stimuli, the sign then follows from the stereo geometry. The magnitude of vertical disparity--and hence eye position--can be deduced from the response of purely horizontal-disparity sensors because vertical disparity moves corresponding features off the receptive fields, reducing the effective binocular correlation. As proof, we demonstrate an algorithm that can accurately reconstruct gaze and vergence angles from the population activity of pure horizontal-disparity sensors and show that it is subject to the induced effect. Given that disparities experienced during natural viewing are overwhelmingly horizontal and that eye position measures require only horizontal-disparity sensors, this work raises two questions: Does the brain in fact contain sensors tuned to nonzero vertical disparities, and if so, why? [Abstract/Link to Full Text]

J�kel F, Wichmann FA
Spatial four-alternative forced-choice method is the preferred psychophysical method for na�ve observers.
J Vis. 2006;6(11):1307-22.
H. R. Blackwell (1952) investigated the influence of different psychophysical methods and procedures on detection thresholds. He found that the temporal two-interval forced-choice method (2-IFC) combined with feedback, blocked constant stimulus presentation with few different stimulus intensities, and highly trained observers resulted in the "best" threshold estimates. This recommendation is in current practice in many psychophysical laboratories and has entered the psychophysicists' "folk wisdom" of how to run proper psychophysical experiments. However, Blackwell's recommendations explicitly require experienced observers, whereas many psychophysical studies, particularly with children or within a clinical setting, are performed with na�ve observers. In a series of psychophysical experiments, we find a striking and consistent discrepancy between na�ve observers' behavior and that reported for experienced observers by Blackwell: Na�ve observers show the "best" threshold estimates for the spatial four-alternative forced-choice method (4-AFC) and the worst for the commonly employed temporal 2-IFC. We repeated our study with a highly experienced psychophysical observer, and he replicated Blackwell's findings exactly, thus suggesting that it is indeed the difference in psychophysical experience that causes the discrepancy between our findings and those of Blackwell. In addition, we explore the efficiency of different methods and show 4-AFC to be more than 3.5 times more efficient than 2-IFC under realistic conditions. While we have found that 4-AFC consistently gives lower thresholds than 2-IFC in detection tasks, we have found the opposite for discrimination tasks. This discrepancy suggests that there are large extrasensory influences on thresholds--sensory memory for IFC methods and spatial attention for spatial forced-choice methods--that are critical but, alas, not part of theoretical approaches to psychophysics such as signal detection theory. [Abstract/Link to Full Text]

Liu T, Heeger DJ, Carrasco M
Neural correlates of the visual vertical meridian asymmetry.
J Vis. 2006;6(11):1294-306.
Human visual performance is better below than above fixation along the vertical meridian-a phenomenon we refer to as vertical meridian asymmetry (VMA). Here, we used fMRI to investigate the neural correlates of the VMA. We presented stimuli of two possible sizes and spatial frequencies on the horizontal and vertical meridians and analyzed the fMRI data in subregions of early visual cortex (V1/V2) that corresponded retinotopically to the stimulus locations. Asymmetries in both the spatial extent and amplitude of the fMRI measurements correlated with the behavioral VMA. These results demonstrate that the VMA has a neural basis at the earliest stages of cortical visual processing and imply that visual performance is limited by the pooled sensory responses of large populations of neurons in the visual cortex. [Abstract/Link to Full Text]

Lappe M, Kuhlmann S, Oerke B, Kaiser M
The fate of object features during perisaccadic mislocalization.
J Vis. 2006;6(11):1282-93.
Visual objects flashed before a saccade appear compressed toward the saccade target. Simultaneously flashed objects merge perceptually into one. To better understand cortical interactions in perisaccadic processing, we study the perception of features of mislocalized objects. We report four new findings: First, when multiple objects of different colors are compressed onto a single position, their color attributes remain distinguishable. Second, color attributes of objects compressed onto the same position compete for access to visual awareness. Third, objects presaccadically mislocalized onto a static background of identical color and luminance appear visible on top of that background. Object shape can be determined. Fourth, objects flashed during a saccade become invisible when a larger object is present at the mislocalized position. Thus, perisaccadic mislocalization affects the position of objects but retains other object features. Mislocalization must either occur in parallel to color and shape processing or at late stages of the visual pathway. [Abstract/Link to Full Text]

Brainard DH, Long�re P, Delahunt PB, Freeman WT, Kraft JM, Xiao B
Bayesian model of human color constancy.
J Vis. 2006;6(11):1267-81.
Vision is difficult because images are ambiguous about the structure of the world. For object color, the ambiguity arises because the same object reflects a different spectrum to the eye under different illuminations. Human vision typically does a good job of resolving this ambiguity-an ability known as color constancy. The past 20 years have seen an explosion of work on color constancy, with advances in both experimental methods and computational algorithms. Here, we connect these two lines of research by developing a quantitative model of human color constancy. The model includes an explicit link between psychophysical data and illuminant estimates obtained via a Bayesian algorithm. The model is fit to the data through a parameterization of the prior distribution of illuminant spectral properties. The fit to the data is good, and the derived prior provides a succinct description of human performance. [Abstract/Link to Full Text]

Brooks KR, Stone LS
Spatial scale of stereomotion speed processing.
J Vis. 2006;6(11):1257-66.
To examine the spatial scale of the mechanisms supporting the perception of motion in depth defined by binocular cues, we measured stereomotion speed discrimination thresholds as a function of stimulus size using a two-interval speed comparison task. Stimuli were either random dot stereogram (RDS) bars featuring both the changing disparity (CD) and the interocular velocity difference (IOVD) cues to motion in depth or dynamic random dot stereogram (DRDS) bars featuring the CD cue alone. Monocular speed discrimination performance was also assessed, using half-images of the RDS stimulus. In addition, subjects' stereoacuity for stationary versions of the binocular stimuli was measured. Stimuli ranged in vertical extent from 1.25 to 40 min. Sensitivity to speed differences was strongly related to stimulus height for DRDS stimuli. Performance decreased rapidly as stimulus size was reduced, becoming nearly random for heights below 5 min. However, for RDS stimuli, speed discrimination performance declined with reductions in stimulus size at a far slower rate, providing superior performance at every stimulus size used. Monocular performance was superior still for the majority of subjects, yet showed a similar rate of decline to binocular RDS stimuli. We conclude that the spatial resolution of the CD mechanism and its static disparity inputs is, on average, nearly nine times more coarse than the IOVD system and its monocular motion inputs. Static stereoacuity controls show that this finding cannot be explained by differences in the disparity signals available in our RDS and DRDS stimuli. [Abstract/Link to Full Text]

Brascamp JW, van Ee R, Noest AJ, Jacobs RH, van den Berg AV
The time course of binocular rivalry reveals a fundamental role of noise.
J Vis. 2006;6(11):1244-56.
When our two eyes view incongruent images, we experience binocular rivalry: An ongoing cycle of dominance periods of either image and transition periods when both are visible. Two key forces underlying this process are adaptation of and inhibition between the images' neural representations. Models based on these factors meet the constraints posed by data on dominance periods, but these are not very stringent. We extensively studied contrast dependence of dominance and transition durations and that of the occurrence of return transitions: Occasions when an eye loses and regains dominance without intervening dominance of the other eye. We found that dominance durations and the incidence of return transitions depend similarly on contrast; transition durations show a different dependence. Regarding dominance durations, we show that the widely accepted rule known as Levelt's second proposition is only valid in a limited contrast range; outside this range, the opposite of the proposition is true. Our data refute current models, based solely on adaptation and inhibition, as these cannot explain the long and reversible transitions that we find. These features indicate that noise is a crucial force in rivalry, frequently dominating the deterministic forces. [Abstract/Link to Full Text]

Meese TS, Georgeson MA, Baker DH
Binocular contrast vision at and above threshold.
J Vis. 2006;6(11):1224-43.
A fundamental problem for any visual system with binocular overlap is the combination of information from the two eyes. Electrophysiology shows that binocular integration of luminance contrast occurs early in visual cortex, but a specific systems architecture has not been established for human vision. Here, we address this by performing binocular summation and monocular, binocular, and dichoptic masking experiments for horizontal 1 cycle per degree test and masking gratings. These data reject three previously published proposals, each of which predict too little binocular summation and insufficient dichoptic facilitation. However, a simple development of one of the rejected models (the twin summation model) and a completely new model (the two-stage model) provide very good fits to the data. Two features common to both models are gently accelerating (almost linear) contrast transduction prior to binocular summation and suppressive ocular interactions that contribute to contrast gain control. With all model parameters fixed, both models correctly predict (1) systematic variation in psychometric slopes, (2) dichoptic contrast matching, and (3) high levels of binocular summation for various levels of binocular pedestal contrast. A review of evidence from elsewhere leads us to favor the two-stage model. [Abstract/Link to Full Text]

Brooks KR, Stone LS
Stereomotion suppression and the perception of speed: accuracy and precision as a function of 3D trajectory.
J Vis. 2006;6(11):1214-23.
The precision and accuracy of speed discrimination performance for stereomotion stimuli were assessed for several receding 3D trajectories confined to the horizontal meridian. It has previously been demonstrated in a variety of tasks that detection thresholds are substantially higher when subjects observe a stereomotion stimulus than when simply viewing one of its component monocular half-images--a phenomenon known as stereomotion suppression (C. W. Tyler, 1971). Using monocularly visible motion in depth targets, we found mean speed discrimination thresholds to be higher for stereomotion, compared with monocular lateral speed discrimination thresholds for equivalent stimuli, demonstrating a disadvantage for binocular viewing in the case of speed discrimination as well. Furthermore, speed discrimination thresholds for motion in depth were not systematically affected by trajectory angle; hence, the disadvantage of binocular viewing persists even when there are concurrent changes in binocular visual direction. Lastly, there was a tendency for oblique trajectories of stereomotion to be perceived as faster than equally rapid motion receding directly away from the subject along the midline. Our data, in addition to earlier stereomotion suppression observations, are consistent with a stereomotion system that takes a noisy, weighted difference of the stimulus velocities in the two eyes to compute motion in depth. [Abstract/Link to Full Text]

Stockman A, Langend�rfer M, Smithson HE, Sharpe LT
Human cone light adaptation: from behavioral measurements to molecular mechanisms.
J Vis. 2006;6(11):1194-213.
The ability of the cone visual system to regulate its sensitivity from twilight to bright sunlight is an extraordinary feat of biology. Here, we investigate the changes in visual processing that accompany cone light adaptation over a 5 log10 unit intensity range by combining measures of temporal sensitivity made in one eye with measures of the temporal delay between the two eyes in different states of adaptation. This combination of techniques, which provides more complete information than has been available before, leads to a simple model of steady-state light adaptation. At high light levels, visual sensitivity is maintained mainly by photopigment bleaching. At low-to-moderate light levels, it is maintained by trading unwanted sensitivity for speed and by an additional process that paradoxically increases the overall sensitivity as the light level rises. Each stage of the model can be linked to molecular mechanisms within the photoreceptor: The speeding up can be linked to faster rates of decay of activated molecules; the paradoxical sensitivity increases can be linked to faster rates of molecular resynthesis and to changes in channel sensitivity; and the sensitivity decreases can be linked to bleaching. Together, these mechanisms act to maintain the cone visual system in an optimal operating range and to protect it from overload. [Abstract/Link to Full Text]

Navalpakkam V, Itti L
Top-down attention selection is fine grained.
J Vis. 2006;6(11):1180-93.
Although much is known about the sources and modulatory effects of top-down attentional signals, the information capacity of these signals is less known. Here, we investigate the granularity of top-down attentional signals. Previous theories in psychophysics have provided conflicting evidence on whether top-down guidance is coarse grained (i.e., one gain control term per feature dimension) or fine grained (i.e., multiple gain control terms per dimension). We resolve the conflict by designing new experiments that disentangle top-down from bottom-up contributions, thereby avoiding confounds existing in previous studies. The results of our eye-tracking experiments show that subjects can selectively saccade to items belonging to the relevant feature interval compared with irrelevant intervals within a dimension. This suggests that top-down signals can specify not only the relevant feature dimension but also the relevant feature interval within a dimension. We conclude that top-down signals are fine grained and can specify multiple gain control terms per dimension. [Abstract/Link to Full Text]

van Dam LC, van Ee R
Retinal image shifts, but not eye movements per se, cause alternations in awareness during binocular rivalry.
J Vis. 2006;6(11):1172-9.
Particularly promising studies on visual awareness exploit a generally used perceptual bistability phenomenon, "binocular rivalry"--in which the two eyes' images alternately dominate--because it can dissociate the visual input from the perceptual output. To successfully study awareness, it is crucial to know the extent to which eye movements alter the input. Although there is convincing evidence that perceptual alternations can occur without eye movements, the literature on their exact role is mixed. Moreover, recent work has demonstrated that eye movements, first, correlate positively with perceptual alternations in binocular rivalry, and second, often accompany covert attention shifts (that were previously thought to be purely mental). Here, we asked whether eye movements cause perceptual alternations, and if so, whether it is either the execution of the eye movement or the resulting retinal image change that causes the alternation. Subjects viewed repetitive line patterns, enabling a distinction of saccades that did produce foveal image changes from those that did not. Subjects reported binocular rivalry alternations. We found that, although a saccade is not essential to initiate percept changes, the foveal image change resulting from a (micro)saccade is a deciding factor for percept dominance. We conclude that the foveal image must change to have a saccade cause a change in awareness. This sheds new light on the interaction between spatial attention shifts and perceptual alternations. [Abstract/Link to Full Text]

Pan F, Swanson WH
A cortical pooling model of spatial summation for perimetric stimuli.
J Vis. 2006;6(11):1159-71.
Contemporary models of perimetric sensitivity assume probability summation of retinal ganglion cell sensitivities, ignoring cortical processing. To assess the role of cortical processing in perimetric spatial summation, we used a common form of multiple-mechanism spatial vision model in which the stimulus is sampled by receptive fields analogous to those of simple cells in primary visual cortex. Psychophysical threshold was computed by probability summation across the receptive fields. When the receptive fields were nonoriented (like ganglion cells), the spatial summation function had a large nonmonotonic transitional region that was inconsistent with perimetric spatial summation data. When the receptive fields were orientation tuned (like cortical cells), the model was able to give good fits to perimetric spatial summation data. The predictions of the model were evaluated with a masking study, in which noise masks either enlarged the critical area or changed the shape of the spatial summation functions. We conclude that cortical pooling by multiple spatial mechanisms can account for perimetric spatial summation, whereas probability summation across ganglion cells cannot. [Abstract/Link to Full Text]

Einh�user W, Rutishauser U, Frady EP, Nadler S, K�nig P, Koch C
The relation of phase noise and luminance contrast to overt attention in complex visual stimuli.
J Vis. 2006;6(11):1148-58.
Models of attention are typically based on difference maps in low-level features but neglect higher order stimulus structure. To what extent does higher order statistics affect human attention in natural stimuli? We recorded eye movements while observers viewed unmodified and modified images of natural scenes. Modifications included contrast modulations (resulting in changes to first- and second-order statistics), as well as the addition of noise to the Fourier phase (resulting in changes to higher order statistics). We have the following findings: (1) Subjects' interpretation of a stimulus as a "natural" depiction of an outdoor scene depends on higher order statistics in a highly nonlinear, categorical fashion. (2) Confirming previous findings, contrast is elevated at fixated locations for a variety of stimulus categories. In addition, we find that the size of this elevation depends on higher order statistics and reduces with increasing phase noise. (3) Global modulations of contrast bias eye position toward high contrasts, consistent with a linear effect of contrast on fixation probability. This bias is independent of phase noise. (4) Small patches of locally decreased contrast repel eye position less than large patches of the same aggregate area, irrespective of phase noise. Our findings provide evidence that deviations from surrounding statistics, rather than contrast per se, underlie the well-established relation of contrast to fixation. [Abstract/Link to Full Text]

Vladusich T, Lucassen MP, Cornelissen FW
Edge integration and the perception of brightness and darkness.
J Vis. 2006;6(10):1126-47.
How do induced brightness and darkness signals from local and remote surfaces interact to determine the final achromatic color percept of a target surface? An emerging theory of achromatic color perception posits that brightness and darkness percepts are computed by weighting and summing the induction signals generated at edges in a scene. This theory also characterizes how neighboring edges interact to modulate the gain of brightness and darkness signals induced from one another. Here we assess evidence for this edge integration theory by means of computational modeling and a psychophysical experiment. We quantitatively show how local and remote edge induction signals in disk-ring displays give rise to either contrast or assimilation effects. Spatial integration of same-polarity edge signals supports a contrast effect, whereas integration of opposite-polarity signals supports an assimilation effect, particularly when the remote induction signal is much stronger than the local induction signal. The results confirm a key prediction of edge integration theory, namely, that strong assimilation effects can lead subjects to ignore the polarity of local edge information when setting achromatic color matches. The conditions necessary for strong assimilation effects are also associated with greater difficulty in setting matches, suggesting that caution is required when interpreting matching data in terms of gain control. We describe several avenues for further study of contrast, assimilation, and gain control. [Abstract/Link to Full Text]

Tyler CW, Chen CC
Spatial summation of face information.
J Vis. 2006;6(10):1117-25.
Do all parts of the face contribute equally to face detection or are some parts more detectable than others? To evaluate this issue, we studied detection of the presence of normalized frontal-face images within aperture windows of varying extent. We performed a face summation study using two-alternative forced-choice psychophysics. The face stimuli were scaled to equal eye-to-chin distance, centered on the bridge of the nose, and windowed by fourth-power Gaussian envelopes of various sizes. The faces were intermixed with control stimuli consisting inverted faces to test for configuration effects, split-half inverted faces to perturb the symmetry, and phase-scrambled versions of the faces with equal Fourier energy. Face detectability improved rapidly at first, then at a progressively shallower rate for larger window sizes, in a similar fashion for the three face-based stimulus types. The spectrally equated noise stimuli were less detectable than the face stimuli for all except the smallest apertures. The results were fit with a model incorporating global face-specific and local nonspecific spatial integration mechanisms. Detection of the noise images was consistent with local detection mechanisms accessed through a wide-field attention mechanism. The data for face detection implied detection mechanisms that integrated linearly up to some small size, integrated more slowly up to an intermediate size, and failed to gain any improvement for information beyond some larger size. This performance supports the concept of a specialized face configuration mechanism operating at detection threshold, similar in extent among the observers. [Abstract/Link to Full Text]

Schultz S, Doerschner K, Maloney LT
Color constancy and hue scaling.
J Vis. 2006;6(10):1102-16.
In this study, we used a hue scaling technique to examine human color constancy performance in simulated three-dimensional scenes. These scenes contained objects of various shapes and materials and a matte test patch at the center of the scene. Hue scaling settings were made for test patches under five different illuminations. Results show that subjects had nearly stable hue scalings for a given test surface across different illuminants. In a control experiment, only the test surfaces that belonged to one illumination condition were presented, blocked in front of a black background. Surprisingly, the hue scalings of the subjects in the blocked control experiment were not simply determined by the color codes of the test surface. Rather, they depended on the sequence of previously presented test stimuli. In contrast, subjects' hue scalings in a second control experiment (with order of presentations randomized) were completely determined by the color codes of the test surface. Our results show that hue scaling is a useful technique to investigate color constancy in a more phenomenological sense. Furthermore, the results from the blocked control experiment underline the important role of slow chromatic adaptation for color constancy. [Abstract/Link to Full Text]