Friday, July 24, 2009

Dynamic sensitivity of area V4 neurons during saccade preparation.

Han X, Xian SX, Moore T.
Proc Natl Acad Sci U S A. 2009 Jul 21.

During the preparation of saccadic eye movements, visual attention is confined to the target of intended fixation and there is a corresponding diminution of visual sensitivity at nontarget locations. Neurons within the macaque visual cortex exhibit correlates of these perceptual changes, such as in area V4, where neuronal responses are enhanced during the preparation of saccades to stimuli within the receptive field (RF), and responses are suppressed during the preparation of saccades to other locations. Both the perceptual and neurophysiological effects suggest that the sensitivity of visual cortical neurons to input is dynamic during saccade preparation. We probed the contrast sensitivity of area V4 neurons to nontarget stimuli at varying times during the preparation of saccades to locations outside of the neuron's receptive field. We found that the contrast sensitivity of many neurons is profoundly altered within 50 ms of saccade onset. The luminance or color contrast sensitivity of individual V4 neurons could increase, decrease, or remain unchanged before saccade onset. For luminance contrast sensitivity, decreases in sensitivity were more frequent and larger in magnitude, resulting in an overall decrement in sensitivity across the population. For color contrast, the effects were smaller and more heterogeneous, resulting in little or no overall change in sensitivity across the population. Our results demonstrate the dynamic influence that saccade preparation has on the sensitivity of visual cortical neurons and suggest a basis for the changes in perception known to occur during saccade preparation.

PMID: 19622736

Sunday, July 19, 2009

"Referred visual sensations": rapid perceptual elongation after visual cortical deprivation.

Dilks DD, Baker CI, Liu Y, Kanwisher N.
J Neurosci. 2009 Jul 15;29(28):8960-4.

Visual perceptual distortion (i.e., elongation) has been demonstrated in a single case study after several months of cortical deprivation after a stroke. Here we asked whether similar perceptual elongation can be observed in healthy participants after deprivation and, crucially, how soon after deprivation this elongation occurs. To answer this question, we patched one eye, thus noninvasively and reversibly depriving bottom-up input to the region of primary visual cortex (V1) corresponding to the blind spot (BS) in the unpatched eye, and tested whether and how quickly elongation occurs after the onset of deprivation. Within seconds of eye patching, participants perceived rectangles adjacent to the BS to be elongated toward the BS. We attribute this perceptual elongation to rapid receptive field expansion within the deprived V1 as reported in electrophysiological studies after retinal lesions and refer to it as "referred visual sensations" (RVS). This RVS is too fast to be the result of structural changes in the cortex (e.g., the growth of new connections), instead implicating unmasking of preexisting connections as the underlying neural mechanism. These findings may shed light on other reported perceptual distortions, as well as the phenomena of "filling-in."

PMID: 19605633

Thursday, July 16, 2009

Millisecond-timescale optical control of neural dynamics in the nonhuman primate brain.

Han X, Qian X, Bernstein JG, Zhou HH, Franzesi GT, Stern P, Bronson RT, Graybiel AM, Desimone R, Boyden ES.
Neuron. 2009 Apr 30;62(2):191-8.

To understand how brain states and behaviors are generated by neural circuits, it would be useful to be able to perturb precisely the activity of specific cell types and pathways in the nonhuman primate nervous system. We used lentivirus to target the light-activated cation channel channelrhodopsin-2 (ChR2) specifically to excitatory neurons of the macaque frontal cortex. Using a laser-coupled optical fiber in conjunction with a recording microelectrode, we showed that activation of excitatory neurons resulted in well-timed excitatory and suppressive influences on neocortical neural networks. ChR2 was safely expressed, and could mediate optical neuromodulation, in primate neocortex over many months. These findings highlight a methodology for investigating the causal role of specific cell types in nonhuman primate neural computation, cognition, and behavior, and open up the possibility of a new generation of ultraprecise neurological and psychiatric therapeutics via cell-type-specific optical neural control prosthetics.

PMID: 19409264

The effect of microsaccades on the correlation between neural activity and behavior in middle temporal, ventral intraparietal, and lateral intraparietal areas.

Herrington TM, Masse NY, Hachmeh KJ, Smith JE, Assad JA, Cook EP.
J Neurosci. 2009 May 6;29(18):5793-805.

It is widely reported that the activity of single neurons in visual cortex is correlated with the perceptual decision of the subject. The strength of this correlation has implications for the neuronal populations generating the percepts. Here we asked whether microsaccades, which are small, involuntary eye movements, contribute to the correlation between neural activity and behavior. We analyzed data from three different visual detection experiments, with neural recordings from the middle temporal (MT), lateral intraparietal (LIP), and ventral intraparietal (VIP) areas. All three experiments used random dot motion stimuli, with the animals required to detect a transient or sustained change in the speed or strength of motion. We found that microsaccades suppressed neural activity and inhibited detection of the motion stimulus, contributing to the correlation between neural activity and detection behavior. Microsaccades accounted for as much as 19% of the correlation for area MT, 21% for area LIP, and 17% for VIP. While microsaccades only explain part of the correlation between neural activity and behavior, their effect has implications when considering the neuronal populations underlying perceptual decisions.

PMID: 19420247

Central V4 receptive fields are scaled by the V1 cortical magnification and correspond to a constant-sized sampling of the V1 surface.

Motter BC.
J Neurosci. 2009 May 6;29(18):5749-57.

The mapping of the topographic representation of the visual field onto cortical areas changes throughout the hierarchy of cortical visual areas. The changes are believed to reflect the establishment of modules with different spatial processing emphasis. The receptive fields (RFs) of neurons within these modules, however, may not be governed by the same spatial topographic map parameters. Here it is shown that the RFs of area V4 neurons (centered 1-12 degrees in eccentricity) are based on a circularly symmetric sampling of the primary visual cortical retinotopic map. No eccentricity dependent magnification beyond that observed in V1 is apparent in the V4 neurons. The size and shape of V4 RFs can be explained by a simple, constant sized, two-dimensional Gaussian sample of visual input from the retinotopic map laid out across the surface of V1. Inferences about the spatial scale of interactions within the receptive fields of neurons cannot be based on a visual area's apparent cortical magnification derived from topographic mapping.

PMID: 19420243

Representation of confidence associated with a decision by neurons in the parietal cortex.

Kiani R, Shadlen MN.
Science. 2009 May 8;324(5928):759-64.

The degree of confidence in a decision provides a graded and probabilistic assessment of expected outcome. Although neural mechanisms of perceptual decisions have been studied extensively in primates, little is known about the mechanisms underlying choice certainty. We have shown that the same neurons that represent formation of a decision encode certainty about the decision. Rhesus monkeys made decisions about the direction of moving random dots, spanning a range of difficulties. They were rewarded for correct decisions. On some trials, after viewing the stimulus, the monkeys could opt out of the direction decision for a small but certain reward. Monkeys exercised this option in a manner that revealed their degree of certainty. Neurons in parietal cortex represented formation of the direction decision and the degree of certainty underlying the decision to opt out.

PMID: 19423820

A rodent model for the study of invariant visual object recognition.

Zoccolan D, Oertelt N, DiCarlo JJ, Cox DD.
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8748-53.

The human visual system is able to recognize objects despite tremendous variation in their appearance on the retina resulting from variation in view, size, lighting, etc. This ability--known as "invariant" object recognition--is central to visual perception, yet its computational underpinnings are poorly understood. Traditionally, nonhuman primates have been the animal model-of-choice for investigating the neuronal substrates of invariant recognition, because their visual systems closely mirror our own. Meanwhile, simpler and more accessible animal models such as rodents have been largely overlooked as possible models of higher-level visual functions, because their brains are often assumed to lack advanced visual processing machinery. As a result, little is known about rodents' ability to process complex visual stimuli in the face of real-world image variation. In the present work, we show that rats possess more advanced visual abilities than previously appreciated. Specifically, we trained pigmented rats to perform a visual task that required them to recognize objects despite substantial variation in their appearance, due to changes in size, view, and lighting. Critically, rats were able to spontaneously generalize to previously unseen transformations of learned objects. These results provide the first systematic evidence for invariant object recognition in rats and argue for an increased focus on rodents as models for studying high-level visual processing.

PMID: 19429704

Dissociable Neural Effects of Long-term Stimulus-Reward Pairing in Macaque Visual Cortex.

Frankó E, Seitz AR, Vogels R.
J Cogn Neurosci. 2009 Jul 6

It has been proposed that perceptual learning may occur through a reinforcement process, in which consistently pairing stimuli with reward is sufficient for learning. We tested whether stimulus-reward pairing is sufficient to increase the sensorial representation of a stimulus by recording local field potentials (LFPs) in macaque extrastriate area V4 with chronically implanted electrodes. Two oriented gratings were repeatedly presented; one was paired with a fluid reward, whereas no reward was given at any other time. During the course of conditioning the LFP increased for the rewarded compared to the unrewarded orientation. The time course of the effect of stimulus-reward pairing and its reversal differed between an early and late interval of the LFP response: a fast change in the later part of the neural response that was dissociated from a slower change in the early part of the response. The fast change of the late interval LFP suggests that this late LFP change is related to enhanced attention during the presentation of the rewarded stimulus. The slower time course of the early interval response suggests an effect of sensorial learning. Thus, simple stimulus-reward pairing is sufficient to strengthen stimulus representations in visual cortex and does this by means of two dissociable mechanisms.

PMID: 19580385

Dissociable perceptual effects of visual adaptation.

Müller KM, Schillinger F, Do DH, Leopold DA.
PLoS One. 2009 Jul 10;4(7):e6183.

Neurons in the visual cortex are responsive to the presentation of oriented and curved line segments, which are thought to act as primitives for the visual processing of shapes and objects. Prolonged adaptation to such stimuli gives rise to two related perceptual effects: a slow change in the appearance of the adapting stimulus (perceptual drift), and the distortion of subsequently presented test stimuli (adaptational aftereffects). Here we used a psychophysical nulling technique to dissociate and quantify these two classical observations in order to examine their underlying mechanisms and their relationship to one another. In agreement with previous work, we found that during adaptation horizontal and vertical straight lines serve as attractors for perceived orientation and curvature. However, the rate of perceptual drift for different stimuli was not predictive of the corresponding aftereffect magnitudes, indicating that the two perceptual effects are governed by distinct neural processes. Finally, the rate of perceptual drift for curved line segments did not depend on the spatial scale of the stimulus, suggesting that its mechanisms lie outside strictly retinotopic processing stages. These findings provide new evidence that the visual system relies on statistically salient intrinsic reference stimuli for the processing of visual patterns, and point to perceptual drift as an experimental window for studying the mechanisms of visual perception.

PMID: 19593384

Relating neuronal firing patterns to functional differentiation of cerebral cortex.

Shinomoto S, Kim H, Shimokawa T, Matsuno N, Funahashi S, Shima K, Fujita I, Tamura H, Doi T, Kawano K, Inaba N, Fukushima K, Kurkin S, Kurata K, Taira M, Tsutsui K, Komatsu H, Ogawa T, Koida K, Tanji J, Toyama K.
PLoS Comput Biol. 2009 Jul;5(7):e1000433.

It has been empirically established that the cerebral cortical areas defined by Brodmann one hundred years ago solely on the basis of cellular organization are closely correlated to their function, such as sensation, association, and motion. Cytoarchitectonically distinct cortical areas have different densities and types of neurons. Thus, signaling patterns may also vary among cytoarchitectonically unique cortical areas. To examine how neuronal signaling patterns are related to innate cortical functions, we detected intrinsic features of cortical firing by devising a metric that efficiently isolates non-Poisson irregular characteristics, independent of spike rate fluctuations that are caused extrinsically by ever-changing behavioral conditions. Using the new metric, we analyzed spike trains from over 1,000 neurons in 15 cortical areas sampled by eight independent neurophysiological laboratories. Analysis of firing-pattern dissimilarities across cortical areas revealed a gradient of firing regularity that corresponded closely to the functional category of the cortical area; neuronal spiking patterns are regular in motor areas, random in the visual areas, and bursty in the prefrontal area. Thus, signaling patterns may play an important role in function-specific cerebral cortical computation.

PMID: 19593378

Wednesday, July 8, 2009

Decoding reveals the contents of visual working memory in early visual areas

Harrison SA, Tong F.
Nature. 2009 Apr 2;458(7238):632-5.

Visual working memory provides an essential link between perception and higher cognitive functions, allowing for the active maintenance of information about stimuli no longer in view. Research suggests that sustained activity in higher-order prefrontal, parietal, inferotemporal and lateral occipital areas supports visual maintenance, and may account for the limited capacity of working memory to hold up to 3-4 items. Because higher-order areas lack the visual selectivity of early sensory areas, it has remained unclear how observers can remember specific visual features, such as the precise orientation of a grating, with minimal decay in performance over delays of many seconds. One proposal is that sensory areas serve to maintain fine-tuned feature information, but early visual areas show little to no sustained activity over prolonged delays. Here we show that orientations held in working memory can be decoded from activity patterns in the human visual cortex, even when overall levels of activity are low. Using functional magnetic resonance imaging and pattern classification methods, we found that activity patterns in visual areas V1-V4 could predict which of two oriented gratings was held in memory with mean accuracy levels upwards of 80%, even in participants whose activity fell to baseline levels after a prolonged delay. These orientation-selective activity patterns were sustained throughout the delay period, evident in individual visual areas, and similar to the responses evoked by unattended, task-irrelevant gratings. Our results demonstrate that early visual areas can retain specific information about visual features held in working memory, over periods of many seconds when no physical stimulus is present.

PMID: 19225460

Comparing face patch systems in macaques and humans.

Tsao DY, Moeller S, Freiwald WA.
Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19514-9

Face recognition is of central importance for primate social behavior. In both humans and macaques, the visual analysis of faces is supported by a set of specialized face areas. The precise organization of these areas and the correspondence between individual macaque and human face-selective areas are debated. Here, we examined the organization of face-selective regions across the temporal lobe in a large number of macaque and human subjects. Macaques showed 6 regions of face-selective cortex arranged in a stereotypical pattern along the temporal lobe. Human subjects showed, in addition to 3 reported face areas (the occipital, fusiform, and superior temporal sulcus face areas), a face-selective area located anterior to the fusiform face area, in the anterior collateral sulcus. These results suggest a closer anatomical correspondence between macaque and human face-processing systems than previously realized.

PMID: 19033466

Linearly additive shape and color signals in monkey inferotemporal cortex

McMahon DB, Olson CR.
J Neurophysiol. 2009 Apr;101(4):1867-75.

How does the brain represent a red circle? One possibility is that there is a specialized and possibly time-consuming process whereby the attributes of shape and color, carried by separate populations of neurons in low-order visual cortex, are bound together into a unitary neural representation. Another possibility is that neurons in high-order visual cortex are selective, by virtue of their bottom-up input from low-order visual areas, for particular conjunctions of shape and color. A third possibility is that they simply sum shape and color signals linearly. We tested these ideas by measuring the responses of inferotemporal cortex neurons to sets of stimuli in which two attributes-shape and color-varied independently. We find that a few neurons exhibit conjunction selectivity but that in most neurons the influences of shape and color sum linearly. Contrary to the idea of conjunction coding, few neurons respond selectively to a particular combination of shape and color. Contrary to the idea that binding requires time, conjunction signals, when present, occur as early as feature signals. We argue that neither conjunction selectivity nor a specialized feature binding process is necessary for the effective representation of shape-color combinations.

PMID: 19144745

Visually driven activation in macaque areas V2 and V3 without input from the primary visual cortex.

Schmid MC, Panagiotaropoulos T, Augath MA, Logothetis NK, Smirnakis SM.
PLoS One. 2009;4(5):e5527. Epub 2009 May 13.Click here to read

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by approximately 70%, on average, compared to pre-lesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight.

PMID: 19436733

What response properties do individual neurons need to underlie position and clutter "invariant" object recognition?

Li N, Cox DD, Zoccolan D, Dicarlo JJ.
J Neurophysiol. 2009 Jul;102(1):360-76.

Primates can easily identify visual objects over large changes in retinal position-a property commonly referred to as position "invariance." This ability is widely assumed to depend on neurons in inferior temporal cortex (IT) that can respond selectively to isolated visual objects over similarly large ranges of retinal position. However, in the real world, objects rarely appear in isolation, and the interplay between position invariance and the representation of multiple objects (i.e., clutter) remains unresolved. At the heart of this issue is the intuition that the representations of nearby objects can interfere with one another and that the large receptive fields needed for position invariance can exacerbate this problem by increasing the range over which interference acts. Indeed, most IT neurons' responses are strongly affected by the presence of clutter. While external mechanisms (such as attention) are often invoked as a way out of the problem, we show (using recorded neuronal data and simulations) that the intrinsic properties of IT population responses, by themselves, can support object recognition in the face of limited clutter. Furthermore, we carried out extensive simulations of hypothetical neuronal populations to identify the essential individual-neuron ingredients of a good population representation. These simulations show that the crucial neuronal property to support recognition in clutter is not preservation of response magnitude, but preservation of each neuron's rank-order object preference under identity-preserving image transformations (e.g., clutter). Because IT neuronal responses often exhibit that response property, while neurons in earlier visual areas (e.g., V1) do not, we suggest that preserving the rank-order object preference regardless of clutter, rather than the response magnitude, more precisely describes the goal of individual neurons at the top of the ventral visual stream.

PMID: 19439676

Cortical Connections to Area TE in Monkey: Hybrid Modular and Distributed Organization

Borra E, Ichinohe N, Sato T, Tanifuji M, Rockland KS.
Cereb Cortex. 2009 May 23

To investigate the fine anatomical organization of cortical inputs to visual association area TE, 2-3 small injections of retrograde tracers were made in macaque monkeys. Injections were made as a terminal procedure, after optical imaging and electrophysiological recording, and targeted to patches physiologically identified as object-selective. Retrogradely labeled neurons occurred in several unimodal visual areas, the superior temporal sulcus, intraparietal sulcus (IPS), and prefrontal cortex (PFC), consistent with previous studies. Despite the small injection size (<0.5 mm wide), the projection foci in visual areas, but not in IPS or PFC, were spatially widespread (4-6 mm in extent), and predominantly consisted of neurons labeled by only one of the injections. This can be seen as a quasi-modular organization. In addition, within each projection focus, there were scattered neurons projecting to one of the other injections, together with some double-labeled (DL) neurons, in a more distributed pattern. Finally, projection foci included smaller "hotspots," consisting of intermixed neurons, single-labeled by the different injections, and DL neurons. DL neurons are likely the result of axons having extended, spatially separated terminal arbors, as demonstrated by anterograde experiments. These results suggest a complex, hybrid connectivity architecture, with both modular and distributed components.

PMID: 19443621

Beyond Poisson: increased spike-time regularity across primate parietal cortex

Maimon G, Assad JA.
Neuron. 2009 May 14;62(3):426-40

Cortical areas differ in their patterns of connectivity, cellular composition, and functional architecture. Spike trains, on the other hand, are commonly assumed to follow similarly irregular dynamics across neocortex. We examined spike-time statistics in four parietal areas using a method that accounts for nonstationarities in firing rate. We found that, whereas neurons in visual areas fire irregularly, many cells in association and motor-like parietal regions show increasingly regular spike trains by comparison. Regularity was evident both in the shape of interspike interval distributions and in spike-count variability across trials. Thus, Poisson-like randomness is not a universal feature of neocortex. Rather, many parietal cells have reduced trial-to-trial variability in spike counts that could provide for more reliable firing-rate signals. These results suggest that spiking dynamics may play different roles in different cortical areas and should not be assumed to arise from fundamentally irreducible noise sources.

PMID: 19447097

Can monkeys choose optimally when faced with noisy stimuli and unequal rewards?

Samuel Feng, Philip Holmes, Alan Rorie, William T. Newsome
PLoS Computational Biology 5(2):e1000284doi:10.1371/journal.pcbi.1000284

We review the leaky competing accumulator model for two-alternative forced-choice decisions with cued responses, and propose extensions to account for the influence of unequal rewards. Assuming that stimulus information is integrated until the cue to respond arrives and that firing rates of stimulus-selective neurons remain well within physiological bounds, the model reduces to an Ornstein-Uhlenbeck (OU) process that yields explicit expressions for the psychometric function that describes accuracy. From these we compute strategies that optimize the rewards expected over blocks of trials administered with mixed difficulty and reward contingencies. The psychometric function is characterized by two parameters: its midpoint slope, which quantifies a subject’s ability to extract signal from noise, and its shift, which measures the bias applied to account for unequal rewards. We fit these to data from two monkeys performing the moving dots task with mixed coherences and reward schedules. We find that their behaviors averaged over multiple sessions are close to optimal, with shifts erring in the direction of smaller penalties. We propose two methods for biasing the OU process to produce such shifts.

Estimates of the contribution of single neurons to perception depend on timescale and noise correlation

Cohen MR, Newsome WT.
J Neurosci. 2009 May 20;29(20):6635-48

The sensitivity of a population of neurons, and therefore the amount of sensory information available to an animal, is limited by the sensitivity of single neurons in the population and by noise correlation between neurons. For decades, therefore, neurophysiologists have devised increasingly clever and rigorous ways to measure these critical variables (Parker and Newsome, 1998). Previous studies examining the relationship between the responses of single middle temporal (MT) neurons and direction-discrimination performance uncovered an apparent paradox. Sensitivity measurements from single neurons suggested that small numbers of neurons may account for a monkey's psychophysical performance (Britten et al., 1992), but trial-to-trial variability in activity of single MT neurons are only weakly correlated with the monkey's behavior, suggesting that the monkey's decision must be based on the responses of many neurons (Britten et al., 1996). We suggest that the resolution to this paradox lies (1) in the long stimulus duration used in the original studies, which led to an overestimate of neural sensitivity relative to psychophysical sensitivity, and (2) mistaken assumptions (because no data were available) about the level of noise correlation in MT columns with opposite preferred directions. We therefore made new physiological and psychophysical measurements in a reaction time version of the direction-discrimination task that matches neural measurements to the actual decision time of the animals. These new data, considered together with our recent data on noise correlation in MT (Cohen and Newsome, 2008), provide a substantially improved account of psychometric performance in the direction-discrimination task.

PMID: 19458234

Sunday, July 5, 2009

Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats

Machado AG, Baker KB, Schuster D, Butler RS, Rezai A.
Brain Res. 2009 Jul 14;1280:107-16.
Science Direct

Novel neurorehabilitative strategies are needed to improve motor outcomes following stroke. Based on the disynaptic excitatory projections of the dentatothalamocortical pathway to the motor cortex as well as to anterior and posterior cortical areas, we hypothesize that chronic electrical stimulation of the contralesional dentate (lateral cerebellar) nucleus output can enhance motor recovery after ischemia via augmentation of perilesional cortical excitability. Seventy-five Wistar rats were pre-trained in the Montoya staircase task and subsequently underwent left cerebral ischemia with the 3-vessel occlusion model. All survivors underwent stereotactic right lateral cerebellar nucleus (LCN) implantation of bipolar electrodes. Rats were then randomized to 4 groups: LCN stimulation at 10 pps, 20 pps, 50 pps or sham stimulation, which was delivered for a period of 6 weeks. Performance on the Montoya staircase task was re-assessed over the last 4 weeks of the stimulation period. On the right (contralesional) side, motor performance of the groups undergoing sham, 10 pps, 20 pps and 50 pps stimulation was, respectively, 2.5+/-2.7; 2.1+/-2.5; 6.0+/-3.9 (p<0.01) and 4.5+/-3.5 pellets. There was no difference on the left (ipsilesional) side motor performance among the sham or stimulation groups, varying from 15.9+/-6.7 to 17.2+/-2.1 pellets. We conclude that contralesional chronic electrical stimulation of the lateral cerebellar nucleus at 20 pps but not at 10 or 50 pps improves motor recovery in rats following ischemic strokes. This effect is likely to be mediated by increased perilesional cortical excitability via chronic activation of the dentatothalamocortical pathway.

PMID: 19445910

Neural activity in the visual thalamus reflects perceptual suppression

Wilke M, Mueller KM, Leopold DA
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9465-70

To examine the role of the visual thalamus in perception, we recorded neural activity in the lateral geniculate nucleus (LGN) and pulvinar of 2 macaque monkeys during a visual illusion that induced the intermittent perceptual suppression of a bright luminance patch. Neural responses were sorted on the basis of the trial-to-trial visibility of the stimulus, as reported by the animals. We found that neurons in the dorsal and ventral pulvinar, but not the LGN, showed changes in spiking rate according to stimulus visibility. Passive viewing control sessions showed such modulation to be independent of the monkeys' active report. Perceptual suppression was also accompanied by a marked drop in low-frequency power (9-30 Hz) of the local field potential (LFP) throughout the visual thalamus, but this modulation was not observed during passive viewing. Our findings demonstrate that visual responses of pulvinar neurons reflect the perceptual awareness of a stimulus, while those of LGN neurons do not.

PMID: 19458249

Essential role for a long-term depression mechanism in ocular dominance plasticity.

Yoon BJ, Smith GB, Heynen AJ, Neve RL, Bear MF.
Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9860-5. Epub 2009 May 22

The classic example of experience-dependent cortical plasticity is the ocular dominance (OD) shift in visual cortex after monocular deprivation (MD). The experimental model of homosynaptic long-term depression (LTD) was originally introduced to study the mechanisms that could account for deprivation-induced loss of visual responsiveness. One established LTD mechanism is a loss of sensitivity to the neurotransmitter glutamate caused by internalization of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Although it has been shown that MD similarly causes a loss of AMPARs from visual cortical synapses, the contribution of this change to the OD shift has not been established. Using an herpes simplex virus (HSV) vector, we expressed in visual cortical neurons a peptide (G2CT) designed to block AMPAR internalization by hindering the association of the C-terminal tail of the AMPAR GluR2 subunit with the AP2 clathrin adaptor complex. We found that G2CT expression interferes with NMDA receptor (NMDAR)-dependent AMPAR endocytosis and LTD, without affecting baseline synaptic transmission. When expressed in vivo, G2CT completely blocked the OD shift and depression of deprived-eye responses after MD without affecting baseline visual responsiveness or experience-dependent response potentiation in layer 4 of visual cortex. These data suggest that AMPAR internalization is essential for the loss of synaptic strength caused by sensory deprivation in visual cortex.

PMID: 19470483

High-frequency, long-range coupling between prefrontal and visual cortex during attention.

Gregoriou GG, Gotts SJ, Zhou H, Desimone R.
Science. 2009 May 29;324(5931):1207-10

Electrical recordings in humans and monkeys show attentional enhancement of evoked responses and gamma synchrony in ventral stream cortical areas. Does this synchrony result from intrinsic activity in visual cortex or from inputs from other structures? Using paired recordings in the frontal eye field (FEF) and area V4, we found that attention to a stimulus in their joint receptive field leads to enhanced oscillatory coupling between the two areas, particularly at gamma frequencies. This coupling appeared to be initiated by FEF and was time-shifted by about 8 to 13 milliseconds across a range of frequencies. Considering the expected conduction and synaptic delays between the areas, this time-shifted coupling at gamma frequencies may optimize the postsynaptic impact of spikes from one area upon the other, improving cross-area communication with attention.

PMID: 19478185