Primary Cortical Areas Research Articles

Mechanisms of Saccadic Suppression in Primate Cortical Area V4.

Psychophysical studies have shown that subjects are often unaware of visual stimuli presented around the time of an eye movement. This saccadic suppression is thought to be a mechanism for maintaining perceptual stability. The brain might accomplish saccadic suppression by reducing the gain of visual responses to specific stimuli or by simply suppressing firing uniformly for all stimuli. Moreover, the suppression might be identical across the visual field or concentrated at specific points. To evaluate these possibilities, we recorded from individual neurons in cortical area V4 of nonhuman primates trained to execute saccadic eye movements. We found that both modes of suppression were evident in the visual responses of these neurons and that the two modes showed different spatial and temporal profiles: while gain changes started earlier and were more widely distributed across visual space, nonspecific suppression was found more often in the peripheral visual field, after the completion of the saccade. Peripheral suppression was also associated with increased noise correlations and stronger local field potential oscillations in the α frequency band. This pattern of results suggests that saccadic suppression shares some of the circuitry responsible for allocating voluntary attention. We explore our surroundings by looking at things, but each eye movement that we make causes an abrupt shift of the visual input. Why doesn't the world look like a film recorded on a shaky camera? The answer in part is a brain mechanism called saccadic suppression, which reduces the responses of visual neurons around the time of each eye movement. Here we reveal several new properties of the underlying mechanisms. First, the suppression operates differently in the central and peripheral visual fields. Second, it appears to be controlled by oscillations in the local field potentials at frequencies traditionally associated with attention. These results suggest that saccadic suppression shares the brain circuits responsible for actively ignoring irrelevant stimuli.

7. Thalamic mechanisms in the generation and modulation of the cortical slow oscillation in mice

It is well established that thalamus plays a crucial role in the generation of the synchronous slow oscillation in the cortex during non-REM sleep. The slow/delta power (0.2–4 Hz) is the main measured factor of the quality of sleep. However, the contribution of different thalamic nuclei to the inception of the slow wave activities and its synchronization is not known. We hypothesized that the first-order (specific) thalamic nuclei provide a control of slow waves in primary cortical areas, while higher-order (non-specific) thalamic nuclei may synchronize the slow-wave activities across wide cortical regions. We analyzed local field potentials and spiking activities from different cortical and thalamic areas of anesthetized mice while a thalamic nucleus was inactivated by the GABA-agonist muscimol. Extracellular multiunit recordings in first-order (VPM, VL) and higher-order (PO, CL) thalamic nuclei show dramatically decreased spiking activity and strongly reduced burst firing after inactivation. We conclude that the injection of muscimol strongly reduced the spiking activity and does not potentiate the generation of low-threshold spike mediated bursts. Inactivation of specific thalamic nuclei with muscimol decreased the slow/delta power in the corresponding primary cortical area. The inactivation of a non-specific nucleus with muscimol significantly reduced the delta power in all investigated cortical. Our experiments demonstrate that the thalamus is required for the fine tuning of the cortical slow oscillation. Supported by CIHR and NSERC.

Adolescence is associated with genomically patterned consolidation of the hubs of the human brain connectome

How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.

Emergent Spatial Patterns of Excitatory and Inhibitory Synaptic Strengths Drive Somatotopic Representational Discontinuities and their Plasticity in a Computational Model of Primary Sensory Cortical Area 3b.

Mechanisms underlying the emergence and plasticity of representational discontinuities in the mammalian primary somatosensory cortical representation of the hand are investigated in a computational model. The model consists of an input lattice organized as a three-digit hand forward-connected to a lattice of cortical columns each of which contains a paired excitatory and inhibitory cell. Excitatory and inhibitory synaptic plasticity of feedforward and lateral connection weights is implemented as a simple covariance rule and competitive normalization. Receptive field properties are computed independently for excitatory and inhibitory cells and compared within and across columns. Within digit representational zones intracolumnar excitatory and inhibitory receptive field extents are concentric, single-digit, small, and unimodal. Exclusively in representational boundary-adjacent zones, intracolumnar excitatory and inhibitory receptive field properties diverge: excitatory cell receptive fields are single-digit, small, and unimodal; and the paired inhibitory cell receptive fields are bimodal, double-digit, and large. In simulated syndactyly (webbed fingers), boundary-adjacent intracolumnar receptive field properties reorganize to within-representation type; divergent properties are reacquired following syndactyly release. This study generates testable hypotheses for assessment of cortical laminar-dependent receptive field properties and plasticity within and between cortical representational zones. For computational studies, present results suggest that concurrent excitatory and inhibitory plasticity may underlie novel emergent properties.

A Model of Binocular Motion Integration in MT Neurons.

Primate cortical area MT plays a central role in visual motion perception, but models of this area have largely overlooked the binocular integration of motion signals. Recent electrophysiological studies tested binocular integration in MT and found surprisingly that MT neurons lose their hallmark "pattern motion" selectivity when stimuli are presented dichoptically and that many neurons are selective for motion-in-depth (MID). By unifying these novel observations with insights from monocular, frontoparallel motion studies concurrently in a binocular MT motion model, we generated clear, testable predictions about the circuitry and mechanisms underlying visual motion processing. We built binocular models in which signals from left- and right-eye streams could be integrated at various stages from V1 to MT, attempting to create the simplest plausible circuits that accounted for the physiological range of pattern motion selectivity, that explained changes across this range for dichoptic stimulus presentation, and that spanned the spectrum of MID selectivity observed in MT. Our successful models predict that motion-opponent suppression is the key mechanism to account for the striking loss of pattern motion sensitivity with dichoptic plaids, that opponent suppression precedes binocular integration, and that opponent suppression will be stronger in inputs to pattern cells than to component cells. We also found an unexpected connection between circuits for pattern motion selectivity and MID selectivity, suggesting that these two separately studied phenomena could be related. These results also hold in models that include binocular disparity computations, providing a platform for future exploration of binocular response properties in MT. The neural pathways underlying our sense of visual motion are among the most studied and well-understood parts of the primate cerebral cortex. Nevertheless, our understanding is incomplete because electrophysiological research has focused mainly on motion in the 2D frontoparallel plane, even though real-world motion often occurs in three dimensions, involving a change in distance from the viewer. Recent studies have revealed a specialization for sensing 3D motion in area MT, the cortical area most tightly linked to the processing and perception of visual motion. Our study provides the first model to explain how 3D motion sensitivity can arise in MT neurons and predicts how essential features of 2D motion integration may relate to 3D motion processing.

Primary motor and sensory cortical areas communicate via spatiotemporally coordinated networks at multiple frequencies

Skilled movements rely on sensory information to shape optimal motor responses, for which the sensory and motor cortical areas are critical. How these areas interact to mediate sensorimotor integration is largely unknown. Here, we measure intercortical coherence between the orofacial motor (MIo) and somatosensory (SIo) areas of cortex as monkeys learn to generate tongue-protrusive force. We report that coherence between MIo and SIo is reciprocal and that neuroplastic changes in coherence gradually emerge over a few days. These functional networks of coherent spiking and local field potentials exhibit frequency-specific spatiotemporal properties. During force generation, theta coherence (2-6 Hz) is prominent and exhibited by numerous paired signals; before or after force generation, coherence is evident in alpha (6-13 Hz), beta (15-30 Hz), and gamma (30-50 Hz) bands, but the functional networks are smaller and weaker. Unlike coherence in the higher frequency bands, the distribution of the phase at peak theta coherence is bimodal with peaks near 0° and ±180°, suggesting that communication between somatosensory and motor areas is coordinated temporally by the phase of theta coherence. Time-sensitive sensorimotor integration and plasticity may rely on coherence of local and large-scale functional networks for cortical processes to operate at multiple temporal and spatial scales.

Basal Forebrain Cholinergic-Auditory Cortical Network: Primary Versus Nonprimary Auditory Cortical Areas.

Acetylcholine (ACh) release in the cortex is critical for learning, memory, attention, and plasticity. Here, we explore the cholinergic and noncholinergic projections from the basal forebrain (BF) to the auditory cortex using classical retrograde and monosynaptic viral tracers deposited in electrophysiologically identified regions of the auditory cortex. Cholinergic input to both primary (A1) and nonprimary auditory cortical (belt) areas originates in a restricted area in the caudal BF within the globus pallidus (GP) and in the dorsal part of the substantia innominata (SId). On the other hand, we found significant differences in the proportions of cholinergic and noncholinergic projection neurons to primary and nonprimary auditory areas. Inputs to A1 projecting cholinergic neurons were restricted to the GP, caudate-putamen, and the medial part of the medial geniculate body, including the posterior intralaminar thalamic group. In addition to these areas, afferents to belt-projecting cholinergic neurons originated from broader areas, including the ventral secondary auditory cortex, insular cortex, secondary somatosensory cortex, and the central amygdaloid nucleus. These findings support a specific BF projection pattern to auditory cortical areas. Additionally, these findings point to potential functional differences in how ACh release may be regulated in the A1 and auditory belt areas.

Effects of an Exhaustive Exercise on Motor Skill Learning and on the Excitability of Primary Motor Cortex and Supplementary Motor Area.

We examined, on 28 healthy adult subjects, the possible correlations of an exhaustive exercise, and the consequent high blood lactate levels, on immediate (explicit) and delayed (implicit) motor execution of sequential finger movements (cognitive task). Moreover, we determined with transcranial magnetic stimulation whether changes in motor performance are associated with variations in excitability of primary motor area (M1) and supplementary motor area (SMA). We observed that, after an acute exhaustive exercise, the large increase of blood lactate is associated with a significant worsening of both explicit and implicit sequential visuomotor task paradigms, without gender differences. We also found that, at the end of the exhaustive exercise, there is a change of excitability in both M1 and SMA. In particular, the excitability of M1 was increased whereas that of SMA decreased and, also in this case, without gender differences. These results support the idea that an increase of blood lactate after an exhaustive exercise appears to have a protective effect at level of primary cortical areas (as M1), although at the expense of efficiency of adjacent cortical regions (as SMA).

Two distinct types of remapping in primate cortical area V4

Visual neurons typically receive information from a limited portion of the retina, and such receptive fields are a key organizing principle for much of visual cortex. At the same time, there is strong evidence that receptive fields transiently shift around the time of saccades. The nature of the shift is controversial: Previous studies have found shifts consistent with a role for perceptual constancy; other studies suggest a role in the allocation of spatial attention. Here we present evidence that both the previously documented functions exist in individual neurons in primate cortical area V4. Remapping associated with perceptual constancy occurs for saccades in all directions, while attentional shifts mainly occur for neurons with receptive fields in the same hemifield as the saccade end point. The latter are relatively sluggish and can be observed even during saccade planning. Overall these results suggest a complex interplay of visual and extraretinal influences during the execution of saccades.

Mismatch negativity and neural adaptation: Two sides of the same coin. Response: Commentary: Visual mismatch negativity: a predictive coding view.

Mismatch negativity and neural adaptation: Two sides of the same coin. Response: Commentary: Visual mismatch negativity: a predictive coding view.

Local Slow Waves in Superficial Layers of Primary Cortical Areas during REM Sleep

Sleep is traditionally constituted of two global behavioral states, non-rapid eye movement (NREM) and rapid eye movement (REM), characterized by quiescence and reduced responsiveness to sensory stimuli [1]. NREM sleep is distinguished by slow waves and spindles throughout the cerebral cortex and REM sleep by an "activated," low-voltage fast electroencephalogram (EEG) paradoxically similar to that of wake, accompanied by rapid eye movements and muscle atonia. However, recent evidence has shown that cortical activity patterns during wake and NREM sleep are not as global as previously thought. Local slow waves can appear in various cortical regions in both awake humans [2] and rodents [3-5]. Intracranial recordings in humans [6] and rodents [4, 7] have shown that NREM sleep slow waves most often involve only a subset of brain regions that varies from wave to wave rather than occurring near synchronously across all cortical areas. Moreover, some cortical areas can transiently "wake up" [8] in an otherwise sleeping brain. Yet until now, cortical activity during REM sleep was thought to be homogenously wake-like. We show here, using local laminar recordings in freely moving mice, that slow waves occur regularly during REM sleep, but only in primary sensory and motor areas and mostly in layer 4, the main target of relay thalamic inputs, and layer 3. This finding may help explain why, during REM sleep, we remain disconnected from the environment even though the bulk of the cortex shows wake-like, paradoxical activation.

Audiovisual Association Learning in the Absence of Primary Visual Cortex.

Learning audiovisual associations is mediated by the primary cortical areas; however, recent animal studies suggest that such learning can take place even in the absence of the primary visual cortex. Other studies have demonstrated the involvement of extra-geniculate pathways and especially the superior colliculus (SC) in audiovisual association learning. Here, we investigated such learning in a rare human patient with complete loss of the bilateral striate cortex. We carried out an implicit audiovisual association learning task with two different colors of red and purple (the latter color known to minimally activate the extra-genicular pathway). Interestingly, the patient learned the association between an auditory cue and a visual stimulus only when the unseen visual stimulus was red, but not when it was purple. The current study presents the first evidence showing the possibility of audiovisual association learning in humans with lesioned striate cortex. Furthermore, in line with animal studies, it supports an important role for the SC in audiovisual associative learning.

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention.

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation.

Implication of basal forebrain neurons in arousal through different projecting pathways to sensory primary cortical areas in the rat

Implication of basal forebrain neurons in arousal through different projecting pathways to sensory primary cortical areas in the rat

Lateral Inhibition as the organizer of the bottom-up attentional modulation in the primary visual cortex

Lateral inhibition is known to occur at all levels of processing of visual information: from retinal ganglion cells, through principal cells in LGN to primary cortical areas [1]. The role of this connectivity module is to contrast lateral variation within the simultaneously processed upstream information. Our work is based on local field potential (LFP) multichannel signal data [2] recorded from the cats visual cortices activated by attentional tasks: voluntary (top-down) and stimulus driven (bottom-up). These experiments showed that enhanced beta signals (16-24 Hz) serve as a carrier for distributing attentional activation across the visual system. By measuring the correlation strengths between spontaneous LFP signals in different cortical recording sites it was also found that beta activation maps were organized in a mosaic-like pattern within the visual cortex during bottom-up task, whereas top-down task resulted in spatially homogeneous cortical beta excitation. It was hypothesized that the reason for these different cortical activation patterns was due to lateral inhibition raised by salient visual stimulus during bottom-up task [2]. This work aims to verify a role played by lateral inhibition in producing specific spatial activation patterns found in top-down and bottom-up experimental paradigms by means of computational modelling. We have constructed a model of neuronal network comprised of single compartment excitatory and inhibitory cells activated according to extended Hodgkin-Huxley dynamics. The network consists of 16 domains representing cortical patches [3], where the neuronal connections keep the anatomical weights, proportions and local structure according to experimental data: neurons are more likely to form synapses with neighboring cells within one domain. Additionally, the domains are more likely to be interconnected with adjacent than with distant ones. LFPs are modelled as a sum of synaptic currents taking into account their distances from a point of measurement. The modelled neurons receive two kinds of Poisson inputs, which represent the feed-forward input from the thalamus and feed-back activation from higher order cortical regions. The reinforcement of the latter causes widespread increase in beta band power of LFP and represents diffuse, top-down attentional modulating signal. The input from the thalamus arriving to one or more domains represents bottom-up attentional activation of excitatory and inhibitory neurons evoked by salient visual stimulus. The cortical domains activated by this salient input exert additional lateral inhibition on neighboring domains. Our model shows that the spatial heterogeneity of cortical activation resulting in local decrease of correlation in bottom-up task and homogeneity in top-down task, can be mediated by feed-forward lateral inhibitory influences at the cortical level. The higher cross-correlation variance observed experimentally during bottom-up than in top-down attentional paradigm is also observed in the model. This modelling study, confirmed that mechanism of lateral inhibition may be sufficient in explaining spatial differences in organization of beta activities in visual cortical areas observed during bottom-up and top-down attentional paradigms. The network was modelled by means of PyNEST package.

Bilateral low frequency rTMS of the primary motor cortex may not be a suitable treatment for levodopa-induced dyskinesias in late stage Parkinson's disease

BackgroundIn late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS), delivered at the primary motor cortex (MC) or the supplementary motor area (SMA), may reduce levodopa-induced dyskinesias (LID), either in a single or a multiple session stimulation protocol. In our current clinical research, we examined whether single or multiple (accelerated) sham-controlled bilateral LF rTMS session(s) applied to the primary motor cortices are able to reduce levodopa-induced dyskinesias in patients with advanced Parkinson's disease. MethodsDuring a levodopa challenge test, we first investigated the effect of a single sham-controlled session of LF rTMS (1 Hz) to both left and right primary motor cortical areas on dyskinesias and motor function in nine late-stage Parkinson patients. In a second study, patients were assigned to a five day sham-controlled bilateral motor cortex cross-over accelerated LF rTMS protocol and effects on dyskinesias, motor and executive function and emotional status were assessed. ResultsWe found no significant clinical change in levodopa-induced dyskinesias and motor function with either stimulation protocol. ConclusionsOne or multiple bilateral LF rTMS session(s) applied to the primary motor cortex were unable to reduce levodopa-induced dyskinesias in late-stage Parkinson patients.

Tactile orientation perception: an ideal observer analysis of human psychophysical performance in relation to macaque area 3b receptive fields.

The ability to resolve the orientation of edges is crucial to daily tactile and sensorimotor function, yet the means by which edge perception occurs is not well understood. Primate cortical area 3b neurons have diverse receptive field (RF) spatial structures that may participate in edge orientation perception. We evaluated five candidate RF models for macaque area 3b neurons, previously recorded while an oriented bar contacted the monkey's fingertip. We used a Bayesian classifier to assign each neuron a best-fit RF structure. We generated predictions for human performance by implementing an ideal observer that optimally decoded stimulus-evoked spike counts in the model neurons. The ideal observer predicted a saturating reduction in bar orientation discrimination threshold with increasing bar length. We tested 24 humans on an automated, precision-controlled bar orientation discrimination task and observed performance consistent with that predicted. We next queried the ideal observer to discover the RF structure and number of cortical neurons that best matched each participant's performance. Human perception was matched with a median of 24 model neurons firing throughout a 1-s period. The 10 lowest-performing participants were fit with RFs lacking inhibitory sidebands, whereas 12 of the 14 higher-performing participants were fit with RFs containing inhibitory sidebands. Participants whose discrimination improved as bar length increased to 10 mm were fit with longer RFs; those who performed well on the 2-mm bar, with narrower RFs. These results suggest plausible RF features and computational strategies underlying tactile spatial perception and may have implications for perceptual learning.

Non-invasive brain stimulation for Parkinson's disease: Current concepts and outlook 2015.

In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of non-invasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. Published studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS, including increasing stimulation intensity and novel stimulation parameters, derive their rationale from studies of brain physiology. These novel parameters simulate normal firing patterns or act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control. There may also be diagnostic potential of TMS in characterizing individual traits for personalized medicine.

Nicotinic alteration of functional thalamocortical topography.

The thalamocortical pathways form highly topographic connections from the primary sensory thalamic nuclei to the primary cortical areas. The synaptic properties of these thalamocortical connections are modifiable by activation from various neuromodulators, such as acetylcholine. Cholinergic activation can alter functional properties in both the developing and the mature nervous system. Moreover, environmental factors, such as nicotine, can activate these receptors, although the circuit-level alterations resulting from such nicotinic activation of sensory neural circuits remain largely unexplored. Therefore, we examined alterations to the functional topography of thalamocortical circuits in the developing sensory pathways of the mouse. Photostimulation by uncaging of glutamate was used to map these functional thalamocortical alterations in response to nicotinic receptor activation. As a result, we found that activation of forebrain nicotinic acetylcholine receptors results in an expansion and enhancement of functional thalamocortical topographies as assessed in brain slice preparations using laser-scanning photostimulation by uncaging of glutamate. These physiological changes were correlated with the neuroanatomical expression of nicotinic acetylcholine receptor subtypes (α7 and β2). These circuit-level alterations may provide a neural substrate underlying the plastic development and reshaping of thalamocortical circuitry in response to nicotinic receptor activation.

Neuronal Representation of 3-D Space in the Primary Visual Cortex and Control of Eye Movements.

The aim of this article is to consider the correlations between the structure of the primary visual cortical area V1 and control of coordinated movements of the two eyes. Using the anatomical data available, a schematic map of 3-D space representation in the layer IV of area V1 containing only monocular cells has been constructed. The analysis of this map revealed that binocular neurons of V1, which are formed by convergence of monocular cells, should encode the absolute disparity. Participation of monocular and binocular neurons of V1 in the control of convergence, divergence, and version eye movements is discussed. It is proposed that synchronous contraction of corresponding extraocular muscles of both eyes for vergence might be ensured by duplicated transmission of information from the central part of retina to visual cortex of both hemispheres.