Dynamic fading memory and expectancy effects in the monkey primary visual cortex.

In order to investigate the involvement of the primary visual cortex (V1) in working memory (WM), parallel, multisite recordings of multi-unit activity were obtained from monkey V1 while the animals performed a delayed match-to-sample (DMS) task. During the delay period, V1 population firing rate vectors maintained a lingering trace of the sample stimulus that could be reactivated by intervening impulse stimuli that enhanced neuronal firing. This fading trace of the sample did not require active engagement of the monkeys in the DMS task and likely reflects the intrinsic dynamics of recurrent cortical networks in lower visual areas. This renders an active, attention-dependent involvement of V1 in the maintenance of WM contents unlikely. By contrast, population responses to the test stimulus depended on the probabilistic contingencies between sample and test stimuli. Responses to tests that matched expectations were reduced which agrees with concepts of predictive coding.

Joint encoding of stimulus and decision in monkey primary visual cortex.

We investigated whether neurons in monkey primary visual cortex (V1) exhibit mixed selectivity for sensory input and behavioral choice. Parallel multisite spiking activity was recorded from area V1 of awake monkeys performing a delayed match-to-sample task. The monkeys had to make a forced choice decision of whether the test stimulus matched the preceding sample stimulus. The population responses evoked by the test stimulus contained information about both the identity of the stimulus and with some delay but before the onset of the motor response the forthcoming choice. The results of subspace identification analysis indicate that stimulus-specific and decision-related information coexists in separate subspaces of the high-dimensional population activity, and latency considerations suggest that the decision-related information is conveyed by top-down projections.

Dynamic signatures of the Eureka effect: an EEG study.

The Eureka effect refers to the common experience of suddenly solving a problem. Here, we study this effect in a pattern recognition paradigm that requires the segmentation of complex scenes and recognition of objects on the basis of Gestalt rules and prior knowledge. In the experiments, both sensory evidence and prior knowledge were manipulated in order to obtain trials that do or do not converge toward a perceptual solution. Subjects had to detect objects in blurred scenes and indicate recognition with manual responses. Neural dynamics were assessed with high-density Electroencephalography (EEG) recordings. The results show significant changes of neural dynamics with respect to spectral distribution, coherence, phase locking, and fractal dimensionality. The Eureka effect was associated with increased coherence of oscillations in the alpha and theta bands over widely distributed regions of the cortical mantle predominantly in the right hemisphere. This increase in coherence was associated with decreased beta power over parietal and central regions and with decreased alpha power over frontal and occipital areas. In addition, there was a right hemisphere-lateralized reduction of fractal dimensionality. We propose that the Eureka effect requires cooperation of cortical regions involved in working memory, creative thinking, and the control of attention.

Recurrent dynamics in the cerebral cortex: Integration of sensory evidence with stored knowledge.

Current concepts of sensory processing in the cerebral cortex emphasize serial extraction and recombination of features in hierarchically structured feed-forward networks in order to capture the relations among the components of perceptual objects. These concepts are implemented in convolutional deep learning networks and have been validated by the astounding similarities between the functional properties of artificial systems and their natural counterparts. However, cortical architectures also display an abundance of recurrent coupling within and between the layers of the processing hierarchy. This massive recurrence gives rise to highly complex dynamics whose putative function is poorly understood. Here a concept is proposed that assigns specific functions to the dynamics of cortical networks and combines, in a unifying approach, the respective advantages of recurrent and feed-forward processing. It is proposed that the priors about regularities of the world are stored in the weight distributions of feed-forward and recurrent connections and that the high-dimensional, dynamic space provided by recurrent interactions is exploited for computations. These comprise the ultrafast matching of sensory evidence with the priors covertly represented in the correlation structure of spontaneous activity and the context-dependent grouping of feature constellations characterizing natural objects. The concept posits that information is encoded not only in the discharge frequency of neurons but also in the precise timing relations among the discharges. Results of experiments designed to test the predictions derived from this concept support the hypothesis that cerebral cortex exploits the high-dimensional recurrent dynamics for computations serving predictive coding.

Visual exposure enhances stimulus encoding and persistence in primary cortex.

The brain adapts to the sensory environment. For example, simple sensory exposure can modify the response properties of early sensory neurons. How these changes affect the overall encoding and maintenance of stimulus information across neuronal populations remains unclear. We perform parallel recordings in the primary visual cortex of anesthetized cats and find that brief, repetitive exposure to structured visual stimuli enhances stimulus encoding by decreasing the selectivity and increasing the range of the neuronal responses that persist after stimulus presentation. Low-dimensional projection methods and simple classifiers demonstrate that visual exposure increases the segregation of persistent neuronal population responses into stimulus-specific clusters. These observed refinements preserve the representational details required for stimulus reconstruction and are detectable in postexposure spontaneous activity. Assuming response facilitation and recurrent network interactions as the core mechanisms underlying stimulus persistence, we show that the exposure-driven segregation of stimulus responses can arise through strictly local plasticity mechanisms, also in the absence of firing rate changes. Our findings provide evidence for the existence of an automatic, unguided optimization process that enhances the encoding power of neuronal populations in early visual cortex, thus potentially benefiting simple readouts at higher stages of visual processing.

Relation between gamma oscillations and neuronal plasticity in the visual cortex.

Use-dependent long-term changes of neuronal response properties must be gated to prevent irrelevant activity from inducing inappropriate modifications. Here we test the hypothesis that local network dynamics contribute to such gating. As synaptic modifications depend on temporal contiguity between presynaptic and postsynaptic activity, we examined the effect of synchronized gamma (É£) oscillations on stimulation-dependent modifications of orientation selectivity in adult cat visual cortex. Changes of orientation maps were induced by pairing visual stimulation with electrical activation of the mesencephalic reticular formation. Changes in orientation selectivity were assessed with optical recording of intrinsic signals and multiunit recordings. When conditioning stimuli were associated with strong É£-oscillations, orientation domains matching the orientation of the conditioning grating stimulus became more responsive and expanded, because neurons with preferences differing by less than 30° from the orientation of the conditioning grating shifted their orientation preference toward the conditioned orientation. When conditioning stimuli induced no or only weak É£-oscillations, responsiveness of neurons driven by the conditioning stimulus decreased. These differential effects depended on the power of oscillations in the low É£-band (20 Hz to 48 Hz) and not on differences in discharge rate of cortical neurons, because there was no correlation between the discharge rates during conditioning and the occurrence of changes in orientation preference. Thus, occurrence and polarity of use-dependent long-term changes of cortical response properties appear to depend on the occurrence of É£-oscillations during induction and hence on the degree of temporal coherence of the change-inducing network activity.

Stimulus complexity shapes response correlations in primary visual cortex.

Spike count correlations (SCCs) are ubiquitous in sensory cortices, are characterized by rich structure, and arise from structured internal dynamics. However, most theories of visual perception treat contributions of neurons to the representation of stimuli independently and focus on mean responses. Here, we argue that, in a functional model of visual perception, featuring probabilistic inference over a hierarchy of features, inferences about high-level features modulate inferences about low-level features ultimately introducing structured internal dynamics and patterns in SCCs. Specifically, high-level inferences for complex stimuli establish the local context in which neurons in the primary visual cortex (V1) interpret stimuli. Since the local context differentially affects multiple neurons, this conjecture predicts specific modulations in the fine structure of SCCs as stimulus identity and, more importantly, stimulus complexity varies. We designed experiments with natural and synthetic stimuli to measure the fine structure of SCCs in V1 of awake behaving macaques and assessed their dependence on stimulus identity and stimulus statistics. We show that the fine structure of SCCs is specific to the identity of natural stimuli and changes in SCCs are independent of changes in response mean. Critically, we demonstrate that stimulus specificity of SCCs in V1 can be directly manipulated by altering the amount of high-order structure in synthetic stimuli. Finally, we show that simple phenomenological models of V1 activity cannot account for the observed SCC patterns and conclude that the stimulus dependence of SCCs is a natural consequence of structured internal dynamics in a hierarchical probabilistic model of natural images.

Reward-Related Suppression of Neural Activity in Macaque Visual Area V4.

In order for organisms to survive, they need to detect rewarding stimuli, for example, food or a mate, in a complex environment with many competing stimuli. These rewarding stimuli should be detected even if they are nonsalient or irrelevant to the current goal. The value-driven theory of attentional selection proposes that this detection takes place through reward-associated stimuli automatically engaging attentional mechanisms. But how this is achieved in the brain is not very well understood. Here, we investigate the effect of differential reward on the multiunit activity in visual area V4 of monkeys performing a perceptual judgment task. Surprisingly, instead of finding reward-related increases in neural responses to the perceptual target, we observed a large suppression at the onset of the reward indicating cues. Therefore, while previous research showed that reward increases neural activity, here we report a decrease. More suppression was caused by cues associated with higher reward than with lower reward, although neither cue was informative about the perceptually correct choice. This finding of reward-associated neural suppression further highlights normalization as a general cortical mechanism and is consistent with predictions of the value-driven attention theory.

Acute ketamine dysregulates task-related gamma-band oscillations in thalamo-cortical circuits in schizophrenia.

Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1-90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63-80 Hz) in occipital regions and upregulated low frequency (5-28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.

Neuronal oscillations: unavoidable and useful?

Neuronal systems have a high propensity to engage in oscillatory activity because both the properties of individual neurons and canonical circuit motifs favour rhythmic activity. In addition, coupled oscillators can engage in a large variety of dynamical regimes, ranging from synchronization with different phase offsets to chaotic behaviour. Which regime prevails depends on differences between preferred oscillation frequencies, coupling strength and coupling delays. The ability of delay coupled oscillator networks to generate a rich repertoire of temporally structured activation sequences is exploited by central pattern generator networks for the control of movements. However, it is less clear whether temporal patterning of neuronal discharges also plays a role in cognitive processes. Here, it will be argued that the temporal patterning of neuronal discharges emerging from delay coupled oscillator networks plays a pivotal role in all instances in which selective relations have to be established between the responses of distributed assemblies of neurons. Examples are the dynamic formation of functional networks, the selective routing of activity in densely interconnected networks, the attention-dependent selection of sensory signals, the fast and context-dependent binding of responses for further joint processing in pattern recognition and the formation of associations by learning. Special consideration is given to arguments that challenge a functional role of oscillations and synchrony in cognition because of the volatile nature of these phenomena and recent evidence will be reviewed suggesting that this volatility is functionally advantageous.

Endogenously generated gamma-band oscillations in early visual cortex: A neurofeedback study.

Human subjects were trained with neurofeedback (NFB) to enhance the power of narrow-band gamma oscillations in circumscribed regions of early visual cortex. To select the region and the oscillation frequency for NFB training, gamma oscillations were induced with locally presented drifting gratings. The source and frequency of these induced oscillations were determined using beamforming methods. During NFB training the power of narrow band gamma oscillations was continuously extracted from this source with online beamforming and converted into the pitch of a tone signal. We found that seven out of ten subjects were able to selectively increase the amplitude of gamma oscillations in the absence of visual stimulation. One subject however failed completely and two subjects succeeded to manipulate the feedback signal by contraction of muscles. In all subjects the attempts to enhance visual gamma oscillations were associated with an increase of beta oscillations over precentral/frontal regions. Only successful subjects exhibited an additional marked increase of theta oscillations over precentral/prefrontal and temporal regions whereas unsuccessful subjects showed an increase of alpha band oscillations over occipital regions. We argue that spatially confined networks in early visual cortex can be entrained to engage in narrow band gamma oscillations not only by visual stimuli but also by top down signals. We interpret the concomitant increase in beta oscillations as indication for an engagement of the fronto-parietal attention network and the increase of theta oscillations as a correlate of imagery. Our finding support the application of NFB in disease conditions associated with impaired gamma synchronization.

Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event-related fields.

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ-patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole-head MEG-approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ-patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source-localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event-related fields (ERFs) to standard sounds were intact in ScZ-patients. However, the ScZ-group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ-patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082-5093, 2017. © 2017 Wiley Periodicals, Inc.

Functional Connectivity Patterns of Visual Cortex Reflect its Anatomical Organization.

The brain is continuously active, even without external input or task demands. This so-called resting-state activity exhibits a highly specific spatio-temporal organization. However, how exactly these activity patterns map onto the anatomical and functional architecture of the brain is still unclear. We addressed this question in the human visual cortex. We determined the representation of the visual field in visual cortical areas of 44 subjects using fMRI and examined resting-state correlations between these areas along the visual hierarchy, their dorsal and ventral segments, and between subregions representing foveal versus peripheral parts of the visual field. We found that retinotopically corresponding regions, particularly those representing peripheral visual fields, exhibit strong correlations. V1 displayed strong internal correlations between its dorsal and ventral segments and the highest correlation with LGN compared with other visual areas. In contrast, V2 and V3 showed weaker correlations with LGN and stronger between-area correlations, as well as with V4 and hMT+. Interhemispheric correlations between homologous areas were especially strong. These correlation patterns were robust over time and only marginally altered under task conditions. These results indicate that resting-state fMRI activity closely reflects the anatomical organization of the visual cortex both with respect to retinotopy and hierarchy.

Smaller Primary Visual Cortex Is Associated with Stronger, but Less Precise Mental Imagery.

Despite mental imagery's ubiquitous role in human perception, cognition and behavior, one standout question remains unanswered: Why does imagery vary so much from one individual to the next? Here, we used a behavioral paradigm that measures the functional impact of a mental image on subsequent conscious perception and related these measures to the anatomy of the early visual cortex estimated by fMRI retinotopic mapping. We observed a negative relationship between primary visual cortex (V1) surface area and sensory imagery strength, but found positive relationships between V1 and imagery precision (spatial location and orientation). Hence, individuals with a smaller V1 tended to have stronger, but less precise imagery. In addition, subjective vividness of imagery was positively related to prefrontal cortex volume, but unrelated to V1 anatomy. Our findings present the first evidence for the importance of the V1 layout in shaping the strength of human imagination.

Neural Anatomy of Primary Visual Cortex Limits Visual Working Memory.

Despite the immense processing power of the human brain, working memory storage is severely limited, and the neuroanatomical basis of these limitations has remained elusive. Here, we show that the stable storage limits of visual working memory for over 9 s are bound by the precise gray matter volume of primary visual cortex (V1), defined by fMRI retinotopic mapping. Individuals with a bigger V1 tended to have greater visual working memory storage. This relationship was present independently for both surface size and thickness of V1 but absent in V2, V3 and for non-visual working memory measures. Additional whole-brain analyses confirmed the specificity of the relationship to V1. Our findings indicate that the size of primary visual cortex plays a critical role in limiting what we can hold in mind, acting like a gatekeeper in constraining the richness of working mental function.

Expecting to See a Letter: Alpha Oscillations as Carriers of Top-Down Sensory Predictions.

Predictions strongly influence perception. However, the neurophysiological processes that implement predictions remain underexplored. It has been proposed that high- and low-frequency neuronal oscillations act as carriers of sensory evidence and top-down predictions, respectively (von Stein and Sarnthein 2000; Bastos et al. 2012). However, evidence for the latter hypothesis remains scarce. In particular, it remains to be shown whether slow prestimulus alpha oscillations in task-relevant brain regions are stronger in the presence of predictions, whether they influence early categorization processes, and whether this interplay indeed boosts perception. Here, we directly address these questions by manipulating subjects' prior expectations about the identity of visually presented letters while collecting magnetoencephalographic recordings. We find that predictions lead to increased prestimulus alpha oscillations in a multisensory network representing grapheme/phoneme associations. Furthermore, alpha power interacts with stimulus degradation and top-down expectations to predict visibility ratings, and correlates with the amplitude of early sensory components (P1/N1m complex), suggesting a role in the selective amplification of predicted information. Our results thus indicate that low-frequency alpha oscillations can serve as a mechanism to carry and test sensory predictions about letters.

V1 surface size predicts GABA concentration in medial occipital cortex.

A number of recent studies have established a link between behavior and the anatomy of the primary visual cortex (V1). However, one often-raised criticism has been that these studies provide little insight into the mechanisms of the observed relationships. As inhibitory neural interactions have been postulated as an important mechanism for those behaviors related to V1 anatomy, we measured the concentration of inhibitory gamma-amino butyric acid (GABA) in the medial occipital cortex where V1 is located using magnetic resonance spectroscopy (MRS) and estimated the surface area of V1 using fMRI retinotopic mapping. We found a significant positive relationship between GABA concentration and V1 surface area. This relationship was present irrespective of whether the MRS voxel had a fixed size across participants or was proportionally sized to each individual's V1 surface area. Hence, individuals with a larger V1 had a higher GABA concentration in the medial occipital cortex. By tying together V1 size and GABA concentration, our findings point towards individual differences in the level of neural inhibition that might partially mediate the relationships between behavior and V1 neuroanatomy. In addition, they illustrate how stable microscopic properties of neural activity and function are reflected in macro-measures of V1 structure.

Surface area of early visual cortex predicts individual speed of traveling waves during binocular rivalry.

Binocular rivalry ensues when different images are presented to the 2 eyes with conscious perception alternating between the possible interpretations. For large rivalry displays, perceptual transitions are initiated at one location and spread to other parts of the visual field, a phenomenon termed "traveling wave." Previous studies investigated the underlying neural mechanisms of the traveling wave and surmised that primary visual cortex might play an important role. We used magnetic resonance imaging and behavioral measures in humans to explore how interindividual differences in observers' subjective experience of the wave are related to anatomical characteristics of cortical regions. We measured wave speed in participants and confirmed the long-term stability of the individual values. Retinotopic mapping was employed to delineate borders of visual areas V1-V3 in order to determine surface area and cortical thickness in those regions. Only the surface areas of V1 and V2, but not V3 showed a correlation with wave speed. For individuals with larger V1/V2 area, the traveling wave needed longer to spread across the same distance in visual space. Our results highlight the role of early visual areas in mediating binocular rivalry and suggest possible mechanisms for the correlation between surface area and the traveling waves.

The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study.

Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval stages of a visual WM task with 3 levels of memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched controls. The amount of information patients could store in WM was reduced at all memory load levels. During encoding, activation in left ventrolateral prefrontal cortex (VLPFC) and extrastriate visual cortex, which in controls positively correlated with the amount of stored information, was reduced in patients. Additionally, patients showed disturbed functional connectivity between prefrontal and visual areas. During retrieval, right inferior VLPFC hyperactivation was correlated with hypoactivation of left VLPFC in patients during encoding. Visual WM encoding is disturbed by a failure to adequately engage a visual-prefrontal network critical for the transfer of perceptual information into WM. Prefrontal hyperactivation appears to be a secondary consequence of this primary deficit. Isolating the component processes of WM can lead to more specific neurophysiological markers for translational efforts seeking to improve the treatment of cognitive dysfunction in schizophrenia.

Source-reconstruction of event-related fields reveals hyperfunction and hypofunction of cortical circuits in antipsychotic-naive, first-episode schizophrenia patients during Mooney face processing.

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n = 14) and healthy control participants (n = 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250 components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A'). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission.