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2015
Jaffe-Dax, S, Raviv O, Jacoby N, Loewenstein Y, Ahissar M.  2015.  A Computational Model of Implicit Memory Captures Dyslexics' Perceptual Deficits. The Journal of Neuroscience. 35:12116–12126. AbstractPDF
Dyslexics are diagnosed for their poor reading skills, yet they characteristically also suffer from poor verbal memory and often from poor auditory skills. To date, this combined profile has been accounted for in broad cognitive terms. Here we hypothesize that the perceptual deficits associated with dyslexia can be understood computationally as a deficit in integrating prior information with noisy observations. To test this hypothesis we analyzed the performance of human participants in an auditory discrimination task using a two-parameter computational model. One parameter captures the internal noise in representing the current event, and the other captures the impact of recently acquired prior information. Our findings show that dyslexics' perceptual deficit can be accounted for by inadequate adjustment of these components; namely, low weighting of their implicit memory of past trials relative to their internal noise. Underweighting the stimulus statistics decreased dyslexics' ability to compensate for noisy observations. ERP measurements (P2 component) while participants watched a silent movie indicated that dyslexics' perceptual deficiency may stem from poor automatic integration of stimulus statistics. This study provides the first description of a specific computational deficit associated with dyslexia. SIGNIFICANCE STATEMENT This study presents the first attempt to specify the mechanisms underlying dyslexics' perceptual difficulties computationally by applying a specific model, inspired by the Bayesian framework. This model dissociates between the contribution of sensory noise and that of the prior statistics in an auditory perceptual decision task. We show that dyslexics cannot compensate for their perceptual noise by incorporating prior information. By contrast, adequately reading controls' usage of previous information is often close to optimal. We used ERP measurements to assess the neuronal stage of this deficit. We found that unlike their peers, dyslexics' ERP responses are not sensitive to the relations between the current observation and the prior observation, indicating that they cannot establish a reliable prior.
Loewenstein, Y, Yanover U, Rumpel S.  2015.  Predicting the Dynamics of Network Connectivity in the Neocortex. The Journal of Neuroscience. 35(36):12535–12544. AbstractPDF
Dynamic remodeling of connectivity is a fundamental feature of neocortical circuits. Unraveling the principles underlying these dynamics is essential for the understanding of how neuronal circuits give rise to computations. Moreover, as complete descriptions of the wiring diagram in cortical tissues are becoming available, deciphering the dynamic elements in these diagrams is crucial for relating them to cortical function. Here, we used chronic in vivo two-photon imaging to longitudinally follow a few thousand dendritic spines in the mouse auditory cortex to study the determinants of these spines' lifetimes. We applied nonlinear regression to quantify the independent contribution of spine age and several morphological parameters to the prediction of the future survival of a spine. We show that spine age, size, and geometry are parameters that can provide independent contributions to the prediction of the longevity of a synaptic connection. In addition, we use this framework to emulate a serial sectioning electron microscopy experiment and demonstrate how incorporation of morphological information of dendritic spines from a single time-point allows estimation of future connectivity states. The distinction between predictable and nonpredictable connectivity changes may be used in the future to identify the specific adaptations of neuronal circuits to environmental changes. The full dataset is publicly available for further analysis. SIGNIFICANCE STATEMENT The neural architecture in the neocortex exhibits constant remodeling. The functional consequences of these modifications are poorly understood, in particular because the determinants of these changes are largely unknown. Here, we aimed to identify those modifications that are predictable from current network state. To that goal, we repeatedly imaged thousands of dendritic spines in the auditory cortex of mice to assess the morphology and lifetimes of synaptic connections. We developed models based on morphological features of dendritic spines that allow predicting future turnover of synaptic connections. The dynamic models presented in this paper provide a quantitative framework for adding putative temporal dynamics to the static description of a neuronal circuit from single time-point connectomics experiments.
Mohan H, et al.  2015.  Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex. Cerebral Cortex. Abstract
The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on "full" human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of "full" human neuron morphologies and present direct evidence that human neurons are not "scaled-up" versions of rodent or macaque neurons, but have unique structural and functional properties.
Deschamps, I, Agmon G, Loewenstein Y, Grodzinsky Y.  2015.  The processing of polar quantifiers, and numerosity perception. Cognition. 143:115-128. AbstractPDF
We investigated the course of language processing in the context of a verification task that required numerical estimation and comparison. Participants listened to sentences with complex quantifiers that contrasted in Polarity, a logical property (e.g., more-than-half, less-than-half), and then performed speeded verification on visual scenarios that displayed a proportion between 2 discrete quantities. We varied systematically not only the sentences, but also the visual materials, in order to study their effect on the verification process. Next, we used the same visual scenarios with analogous non-verbal probes that featured arithmetical inequality symbols (<, >). This manipulation enabled us to measure not only Polarity effects, but also, to compare the effect of different probe types (linguistic, non-linguistic) on processing. Like many previous studies, our results demonstrate that perceptual difficulty affects error rate and reaction time in keeping with Weber’s Law. Interestingly, these performance parameters are also affected by the Polarity of the quantifiers used, despite the fact that sentences had the exact same meaning, sentence structure, number of words, syllables, and temporal structure. Moreover, an analogous contrast between the non-linguistic probes (<, >) had no effect on performance. Finally, we observed no interaction between performance parameters governed by Weber’s Law and those affected by Polarity. We consider 4 possible accounts of the results (syntactic, semantic, pragmatic, frequency-based), and discuss their relative merit.
Marc, D, Hagai B.  2015.  Striatal cholinergic interneurons and cortico-striatal synaptic plasticity in health and disease. Movement Disorder. 3(no 8):1014-1025. Abstract
Basal ganglia disorders such as Parkinson's disease, dystonia, and Huntington's disease are characterized by a dysregulation of the basal ganglia neuromodulators (dopamine, acetylcholine, and others), which impacts cortico-striatal transmission. Basal ganglia disorders are often associated with an imbalance between the midbrain dopaminergic and striatal cholinergic systems. In contrast to the extensive research and literature on the consequences of a malfunction of midbrain dopaminergic signaling on the plasticity of the cortico-striatal synapse, very little is known about the role of striatal cholinergic interneurons in normal and pathological control of cortico-striatal transmission. In this review, we address the functional role of striatal cholinergic interneurons, also known as tonically active neurons and attempt to understand how the alteration of their functional properties in basal ganglia disorders leads to abnormal cortico-striatal synaptic plasticity. Specifically, we suggest that striatal cholinergic interneurons provide a permissive signal, which enables long-term changes in the efficacy of the cortico-striatal synapse. We further discuss how modifications in the striatal cholinergic activity pattern alter or prohibit plastic changes of the cortico-striatal synapse. Long-term cortico-striatal synaptic plasticity is the cellular substrate of procedural learning and adaptive control behavior. Hence, abnormal changes in this plasticity may underlie the inability of patients with basal ganglia disorders to adjust their behavior to situational demands. Normalization of the cholinergic modulation of cortico-striatal synaptic plasticity may be considered as a critical feature in future treatments of basal ganglia disorders.
Shteingart, H, Loewenstein Y.  2015.  The Effect of Sample Size and Cognitive Strategy on Probability Estimation Bias. Decison. 2(2):107-117. AbstractPDF
Probability estimation is an essential cognitive function in perception, motor control, and decision making. Many studies have shown that when making decisions in a stochastic operant conditioning task, people and animals behave as if they underesti- mate the probability of rare events. It is commonly assumed that this behavior is a natural consequence of estimating a probability from a small sample, also known as sampling bias. The objective of this article is to challenge this common lore. We show that, in fact, probabilities estimated from a small sample can lead to behaviors that will be interpreted as underestimating or as overestimating the probability of rare events, depending on the cognitive strategy used. Moreover, this sampling bias hypothesis makes an implausible prediction that minute differences in the values of the sample size or the underlying probability will determine whether rare events will be underweighted or overweighed. We discuss the implications of this sensitivity for the design and interpretation of experiments. Finally, we propose an alternative sequential learning model with a resetting of initial conditions for probability estimation and show that this model predicts the experimentally observed robust underweighting of rare events.
Ramirez de Noriega Fernando, Renana E, Odeya M, Lavi A, Eduard L, Hagai B, Zvi I.  2015.  Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Deisease. Stereotactic Functional Neurosurgry. 18(93(2)):114-121. Abstract
Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent medication was reduced on average by 67% (range 15-88). Patients were poorly compliant with PD diaries, and these did not yield useful information. The minor deterioration in quality-of-life scores (Parkinson's Disease Questionnaire-39, Quality of Life Enjoyment and Satisfaction Questionnaire) with CC stimulation were not statistically significant. Two measures of depression (Hamilton Rating Scale D17, Quick Inventory of Depressive Symptomatology - Self-Report) showed a nonsignificant lower score (less depression) with CC stimulation, but a third (Beck Depression Inventory) showed equivalence. Cognitive testing (Mini Mental State Examination) and emotional processing (Montreal Affective Voices) were equivalent for CC and CV. Conclusion: CC STN DBS is safe. For equivalent motor efficacy, no significant difference could be identified between CC and CV stimulation for nonmotor evaluations in PD patients 2 years after surgery.
Santi, A, Friederici A, Makuuchi M, Grodzinsky Y.  2015.  An fMRI study dissociating distance measures computed by Broca's area in movement processing: clause boundary vs. identity.. Frontiers in Psychology. Abstract
http://journal.frontiersin.org/article/10.3389/fpsyg.2015.00654/abstract
Applebaum, M, Kalcheim C.  2015.  Mechanisms of myogenic specification and patterning. In: Vertebrate myogenesis, Stem cells and precursors. Series “Results and Problems in Cell Differentiation”. 56:77-98
Deschamps, I, Agmon G, Loewenstein Y, Grodzinsky Y.  2015.  The Processing of Polar Quantifiers, and Numerosity Perception. Cognition. 143:115-128.deschamps_et_al_cog_2015.pdf
Elyada, YM, Mizrahi A.  2015.  Becoming a mother — circuit plasticity underlying maternal behavior. Current Opinion in Neurobiology. 35:49-56.
Rothschild, G, Mizrahi A.  2015.  Global Order and Local Disorder in Brain Maps. Annual Review of Neuroscience. 38:null.
Cohen, L, Mizrahi A.  2015.  Plasticity during Motherhood: Changes in Excitatory and Inhibitory Layer 2/3 Neurons in Auditory Cortex. The Journal of Neuroscience. 35:1806-1815. Abstract
Maternal behavior can be triggered by auditory and olfactory cues originating from the newborn. Here we report how the transition to motherhood affects excitatory and inhibitory neurons in layer 2/3 (L2/3) of the mouse primary auditory cortex. We used in vivo two-photon targeted cell-attached recording to compare the response properties of parvalbumin-expressing neurons (PVNs) and pyramidal glutamatergic neurons (PyrNs). The transition to motherhood shifts the average best frequency of PVNs to higher frequency by a full octave, with no significant effect on average best frequency of PyrNs. The presence of pup odors significantly reduced the spontaneous and evoked activity of PVN. This reduction of feedforward inhibition coincides with a complimentary increase in spontaneous and evoked activity of PyrNs. The selective shift of PVN frequency tuning should render pup odor-induced disinhibition more effective for high-frequency stimuli, such as ultrasonic vocalizations. Indeed, pup odors increased neuronal responses of PyrNs to pup ultrasonic vocalizations. We conclude that plasticity in the mothers is mediated, at least in part, via modulation of the feedforward inhibition circuitry in the auditory cortex.
2014
David, A, Hagai B, Stanley F.  2014.  Redundant dopaminergic activity may enable compensatory axonal sprouting in Parkinson disease.. Neurology. 82(12):1093-8. Abstract
Neurodegenerative diseases become clinically apparent only after a substantial population of neurons is lost. This raises the possibility of compensatory mechanisms in the early phase of these diseases. The importance of understanding these mechanisms cannot be underestimated because it may guide future disease-modifying strategies. Because the anatomy and physiology of the nigrostriatal dopaminergic pathways have been well described, the study of Parkinson disease can offer insight into these early compensatory mechanisms. Collateral axonal sprouting of dopaminergic terminals into the denervated striatum is the most studied compensatory mechanism in animal (almost exclusively rodent) models of Parkinson disease and is correlated with behavioral recovery after partial lesions. This sprouting, however, does not respect the normal anatomy of the original nigrostriatal pathways and leads to aberrant neuronal networks. We suggest here that the unique physiologic property of the dopaminergic innervation of the striatum, namely redundancy of information encoding, is crucial to the efficacy of compensatory axonal sprouting in the presence of aberrant anatomical connections. Redundant information encoding results from the similarity of representation of salient and rewarding events by many dopaminergic neurons, from the wide axonal field of a single dopaminergic neuron in the striatum, and from the nonspecific spatial effect of dopamine on striatal neurons (volume conductance). Finally, we discuss the relevance of these findings in animal models to human patients with Parkinson disease.
Moustafa, AA, Bar-Gad I, Korngreen A, Bergman H.  2014.  Basal ganglia: physiological, behavioral and computational studies. Front Syst. Neurosci.. Abstract
The basal ganglia has received much attention over the last two decades, as it has been implicated in many neurological and psychiatric disorders, including Parkinson's disease (PD), Attention Deficit Hyperactivity Disorder (ADHD), Tourette's syndrome, and dystonia. Most of current basal ganglia research—in both animals and humans—attempts to understand the neural and biochemical substrates of basic motor and learning processes, and how these are affected in human patients as well as animal models of brain disorders, particularly PD. The current volume contains research articles and reviews describing basic, pre-clinical and clinical neuroscience research of the basal ganglia written by researchers of the basal ganglia and attendees of the 11th Triennial Meeting of the International Basal Ganglia Society (IBAGS) that was held on March 3–7th, 2013 at the Princess Hotel, Eilat, Israel. Specifically, articles in this volume include research reports on the biochemistry, computational theory, anatomy, and physiology of single neurons and functional circuitry of the basal ganglia networks. Below, we provide a summary of articles published in the volume. We divided the articles into 4 sections: animal studies, human studies, computational modeling, and reviews.
Mizrahi, A, Shalev A, Nelken I.  2014.  Single neuron and population coding of natural sounds in auditory cortex. Current Opinion in Neurobiology. 24:103-110. Abstract
The auditory system drives behavior using information extracted from sounds. Early in the auditory hierarchy, circuits are highly specialized for detecting basic sound features. However, already at the level of the auditory cortex the functional organization of the circuits and the underlying coding principles become different. Here, we review some recent progress in our understanding of single neuron and population coding in primary auditory cortex, focusing on natural sounds. We discuss possible mechanisms explaining why single neuron responses to simple sounds cannot predict responses to natural stimuli. We describe recent work suggesting that structural features like local subnetworks rather than smoothly mapped tonotopy are essential components of population coding. Finally, we suggest a synthesis of how single neurons and subnetworks may be involved in coding natural sounds.
Yeatman, JD, Wandell BA, Mezer AA.  2014.  Lifespan maturation and degeneration of human brain white matter. Nature Communications. 5 Abstract
Properties of human brain tissue change across the lifespan. Here we model these changes in the living human brain by combining quantitative magnetic resonance imaging (MRI) measurements of R1 (1/T1) with diffusion MRI and tractography (N=102, ages 7–85). The amount of R1 change during development differs between white-matter fascicles, but in each fascicle the rate of development and decline are mirror-symmetric; the rate of R1 development as the brain approaches maturity predicts the rate of R1 degeneration in aging. Quantitative measurements of macromolecule tissue volume (MTV) confirm that R1 is an accurate index of the growth of new brain tissue. In contrast to R1, diffusion development follows an asymmetric time-course with rapid childhood changes but a slow rate of decline in old age. Together, the time-courses of R1 and diffusion changes demonstrate that multiple biological processes drive changes in white-matter tissue properties over the lifespan.
Livneh, Y, Adam Y, Mizrahi A.  2014.  Odor Processing by Adult-Born Neurons. Neuron. :-. Abstract
The adult mammalian brain is continuously supplied with adult-born neurons in the olfactory bulb (OB) and hippocampus, where they are thought to be important for circuit coding and plasticity. However, direct evidence for the actual involvement of these neurons in neural processing is still lacking. We recorded the spiking activity of adult-born periglomerular neurons in the mouse OB in
Moshitch, D, Nelken I.  2014.  The Representation of Interaural Time Differences in High-Frequency Auditory Cortex.. Cerebral cortex. Abstract
Early representations of auditory features often involve neuronal populations whose tuning is substantially wider than behavioral discrimination thresholds. Although behavioral discrimination performance can be sometimes achieved by single neurons when using the appropriate part of their (wide) tuning curves, neurons that encode the resulting high-acuity representations have rarely been described. Here we demonstrate the existence of neurons with extremely narrow tuning for interaural time differences (ITDs), a major physical cue for the azimuth of sound sources. The tuning width of ITD-tuned brainstem neurons is mostly determined by the properties of their acoustic input, and may be 10-100 times wider than behavioral thresholds. In contrast, we show that tuning widths of some neurons in the primary auditory cortex in the cat high-frequency auditory cortex (measured using transposed stimulus) can be very sharp and approach behavioral thresholds. Furthermore, while best ITDs of brainstem neurons often lie outside the range of naturally encountered ITDs (the ethological range), the range of best ITDs of the narrowly tuned cortical neurons corresponds well to the ethological range. Thus, our results suggest that the auditory cortex contains a high-resolution representation of ITDs that explicitly decodes the widely tuned brainstem representations.
Goshen, I.  2014.  The optogenetic revolution in memory research.. Trends in neurosciences. 37(9):511-22. Abstract
Over the past 5 years, the incorporation of optogenetics into the study of memory has resulted in a tremendous leap in this field, initiating a revolution in our understanding of the networks underlying cognitive processes. This review will present recent breakthroughs in which optogenetics was applied to illuminate, both literally and figuratively, memory research, and describe the technical approach, together with the opportunities it offers. Specifically, a large body of literature has been generated, setting the foundation for deciphering the spatiotemporal organization of hippocampal-based memory processing and its underlying mechanisms, as well as the contribution of cortical and amygdalar regions to cognition.
Gudes, S, Barkai O, Caspi Y, Katz B, Lev S, Binshtok AM.  2014.  The Role of Slow and Persistent TTX-resistant Sodium Currents in Acute Tumor Necrosis Factor α - Mediated Increase in Nociceptors Excitability.. Journal of Neurophysiology. :jn.00652.2014. Abstract
Tetrodotoxin (TTX)-resistant sodium channels are key players in determining the input-output properties of peripheral nociceptive neurons. Changes in gating kinetics or in expression of these channels by proinflammatory mediators are likely to cause the hyperexcitability of nociceptivors and pain hypersensitivity observed during inflammation. Proinflammatory mediator, tumor necrosis factor α (TNFα), is secreted during inflammation and is associated with the early onset, as well as long lasting, inflammation-mediated increase in excitability of peripheral nociceptive neurons. Here we studied the underlying mechanisms of the rapid component of TNFα-mediated nociceptive hyperexcitability and acute pain hypersensitivity. We showed that TNFα leads to rapid onset, cyclooxygenase-independent pain hypersensitivity in adult rats. Furthermore, TNFα rapidly and substantially increases nociceptive excitability in-vitro, by decreasing action potential threshold, increasing neuronal gain and decreasing accommodation. We extended on previous studies entailing p38 MAPK-dependent, increase in TTX-resistant sodium currents by showing that TNFα via p38 MAPK, leads to increased availability of TTX-r sodium channels by partial relief of voltage dependence of their slow inactivation, thereby contributing to increase in neuronal gain. Moreover, we showed that TNFα also in a p38 MAPK-dependent manner, increases persistent TTX-r current by shifting the voltage dependence of activation to a hyperpolarized direction, thus producing an increase in inward current at functionally critical subthreshold voltages. Our results suggest that rapid modulation of the gating of TTX-r sodium channels plays a major role in TNFα's-mediated nociceptive hyperexcitability during acute inflammation and may lead to development of effective treatments for inflammatory pain, without modulating the inflammation-induced healing processes.
Blumberg, A, Sailaja B S, Kundaje A, Levin L, Dadon S, Shmorak S, Shaulian E, Meshorer E, Mishmar D.  2014.  Transcription factors bind negatively selected sites within human mtDNA genes.. Genome biology and evolution. 6(10):2634-46. Abstract
Transcription of mitochondrial DNA (mtDNA)-encoded genes is thought to be regulated by a handful of dedicated transcription factors (TFs), suggesting that mtDNA genes are separately regulated from the nucleus. However, several TFs, with known nuclear activities, were found to bind mtDNA and regulate mitochondrial transcription. Additionally, mtDNA transcriptional regulatory elements, which were proved important in vitro, were harbored by a deletion that normally segregated among healthy individuals. Hence, mtDNA transcriptional regulation is more complex than once thought. Here, by analyzing ENCODE chromatin immunoprecipitation sequencing (ChIP-seq) data, we identified strong binding sites of three bona fide nuclear TFs (c-Jun, Jun-D, and CEBPb) within human mtDNA protein-coding genes. We validated the binding of two TFs by ChIP-quantitative polymerase chain reaction (c-Jun and Jun-D) and showed their mitochondrial localization by electron microscopy and subcellular fractionation. As a step toward investigating the functionality of these TF-binding sites (TFBS), we assessed signatures of selection. By analyzing 9,868 human mtDNA sequences encompassing all major global populations, we recorded genetic variants in tips and nodes of mtDNA phylogeny within the TFBS. We next calculated the effects of variants on binding motif prediction scores. Finally, the mtDNA variation pattern in predicted TFBS, occurring within ChIP-seq negative-binding sites, was compared with ChIP-seq positive-TFBS (CPR). Motifs within CPRs of c-Jun, Jun-D, and CEBPb harbored either only tip variants or their nodal variants retained high motif prediction scores. This reflects negative selection within mtDNA CPRs, thus supporting their functionality. Hence, human mtDNA-coding sequences may have dual roles, namely coding for genes yet possibly also possessing regulatory potential.
Chaisanguanthum, KS, Joshua M, Medina JF, Bialek W, Lisberger SG.  2014.  The Neural Code for Motor Control in the Cerebellum and Oculomotor Brainstem.. eNeuro. 1(1) Abstract
A single extra spike makes a difference. Here, the size of the eye velocity in the initiation of smooth eye movements in the right panel depends on whether a cerebellar Purkinje cell discharges 3 (red), 4 (green), 5 (blue), or 6 (black) spikes in the 40-ms window indicated by the gray shading in the rasters on the left. Spike trains are rich in information that can be extracted to guide behaviors at millisecond time resolution or across longer time intervals. In sensory systems, the information usually is defined with respect to the stimulus. Especially in motor systems, however, it is equally critical to understand how spike trains predict behavior. Thus, our goal was to compare systematically spike trains in the oculomotor system with eye movement behavior on single movements. We analyzed the discharge of Purkinje cells in the floccular complex of the cerebellum, floccular target neurons in the brainstem, other vestibular neurons, and abducens neurons. We find that an extra spike in a brief analysis window predicts a substantial fraction of the trial-by-trial variation in the initiation of smooth pursuit eye movements. For Purkinje cells, a single extra spike in a 40 ms analysis window predicts, on average, 0.5 SDs of the variation in behavior. An optimal linear estimator predicts behavioral variation slightly better than do spike counts in brief windows. Simulations reveal that the ability of single spikes to predict a fraction of behavior also emerges from model spike trains that have the same statistics as the real spike trains, as long as they are driven by shared sensory inputs. We think that the shared sensory estimates in their inputs create correlations in neural spiking across time and across each population. As a result, one or a small number of spikes in a brief time interval can predict a substantial fraction of behavioral variation.
Nelken, I, Bizley J, Shamma SA, Wang X.  2014.  Auditory cortical processing in real-world listening: the auditory system going real.. J Neurosci. 34(46):15135-8. Abstract
The auditory sense of humans transforms intrinsically senseless pressure waveforms into spectacularly rich perceptual phenomena: the music of Bach or the Beatles, the poetry of Li Bai or Omar Khayyam, or more prosaically the sense of the world filled with objects emitting sounds that is so important for those of us lucky enough to have hearing. Whereas the early representations of sounds in the auditory system are based on their physical structure, higher auditory centers are thought to represent sounds in terms of their perceptual attributes. In this symposium, we will illustrate the current research into this process, using four case studies. We will illustrate how the spectral and temporal properties of sounds are used to bind together, segregate, categorize, and interpret sound patterns on their way to acquire meaning, with important lessons to other sensory systems as well.
Main, KL, Pestilli F, Mezer A, Yeatman J, Martin R, Phipps S, Wandell B.  2014.  Speed discrimination predicts word but not pseudo-word reading rate in adults and children.. Brain and language. 138:27-37. Abstract
Visual processing in the magnocellular pathway is a reputed influence on word recognition and reading performance. However, the mechanisms behind this relationship are still unclear. To explore this concept, we measured reading rate, speed-discrimination, and contrast detection thresholds in adults and children with a wide range of reading abilities. We found that speed discrimination thresholds are higher in children than in adults and are correlated with age. Speed discrimination thresholds are also correlated with reading rates but only for real words, not pseudo-words. Conversely, we found no correlations between contrast detection thresholds and the reading rates. We also found no correlations between speed discrimination or contrast detection and WASI subtest scores. These findings indicate that familiarity is a factor in magnocellular operations that may influence reading rate. We suggest this effect supports the idea that the magnocellular pathway contributes to word reading through an analysis of letter position.