Neurophysiological mechanisms of error monitoring in human and non-human primates.

Performance monitoring is an important executive function that allows us to gain insight into our own behaviour. This remarkable ability relies on the frontal cortex, and its impairment is an aspect of many psychiatric diseases. In recent years, recordings from the macaque and human medial frontal cortex have offered a detailed understanding of the neurophysiological substrate that underlies performance monitoring. Here we review the discovery of single-neuron correlates of error monitoring, a key aspect of performance monitoring, in both species. These neurons are the generators of the error-related negativity, which is a non-invasive biomarker that indexes error detection. We evaluate a set of tasks that allows the synergistic elucidation of the mechanisms of cognitive control across the two species, consider differences in brain anatomy and testing conditions across species, and describe the clinical relevance of these findings for understanding psychopathology. Last, we integrate the body of experimental facts into a theoretical framework that offers a new perspective on how error signals are computed in both species and makes novel, testable predictions.

Cortical origin of theta error signals.

A multi-scale approach elucidated the origin of the error-related-negativity (ERN), with its associated theta-rhythm, and the post-error-positivity (Pe) in macaque supplementary eye field (SEF). Using biophysical modeling, synaptic inputs to a subpopulation of layer-3 (L3) and layer-5 (L5) pyramidal cells (PCs) were optimized to reproduce error-related spiking modulation and inter-spike intervals. The intrinsic dynamics of dendrites in L5 but not L3 error PCs generate theta rhythmicity with random phases. Saccades synchronized the phases of the theta-rhythm, which was magnified on errors. Contributions from error PCs to the laminar current source density (CSD) observed in SEF were negligible and could not explain the observed association between error-related spiking modulation in L3 PCs and scalp-EEG. CSD from recorded laminar field potentials in SEF was comprised of multipolar components, with monopoles indicating strong electro-diffusion, dendritic/axonal electrotonic current leakage outside SEF, or violations of the model assumptions. Our results also demonstrate the involvement of secondary cortical regions, in addition to SEF, particularly for the later Pe component. The dipolar component from the observed CSD paralleled the ERN dynamics, while the quadrupolar component paralleled the Pe. These results provide the most advanced explanation to date of the cellular mechanisms generating the ERN.

Neural correlates of goal-directed and non-goal-directed movements.

What are the cortical neural correlates that distinguish goal-directed and non-goal-directed movements? We investigated this question in the monkey frontal eye field (FEF), which is implicated in voluntary control of saccades. Here, we compared FEF activity associated with goal-directed (G) saccades and non-goal-directed (nG) saccades made by the monkey. Although the FEF neurons discharged before these nG saccades, there were three major differences in the neural activity: First, the variability in spike rate across trials decreased only for G saccades. Second, the local field potential beta-band power decreased during G saccades but did not change during nG saccades. Third, the time from saccade direction selection to the saccade onset was significantly longer for G saccades compared with nG saccades. Overall, our results reveal unexpected differences in neural signatures for G versus nG saccades in a brain area that has been implicated selectively in voluntary control. Taken together, these data add critical constraints to the way we think about saccade generation in the brain.

Pop-out search instigates beta-gated feature selectivity enhancement across V4 layers.

Visual search is a workhorse for investigating how attention interacts with processing of sensory information. Attentional selection has been linked to altered cortical sensory responses and feature preferences (i.e., tuning). However, attentional modulation of feature selectivity during search is largely unexplored. Here we map the spatiotemporal profile of feature selectivity during singleton search. Monkeys performed a search where a pop-out feature determined the target of attention. We recorded laminar neural responses from visual area V4. We first identified "feature columns" which showed preference for individual colors. In the unattended condition, feature columns were significantly more selective in superficial relative to middle and deep layers. Attending a stimulus increased selectivity in all layers but not equally. Feature selectivity increased most in the deep layers, leading to higher selectivity in extragranular layers as compared to the middle layer. This attention-induced enhancement was rhythmically gated in phase with the beta-band local field potential. Beta power dominated both extragranular laminar compartments, but current source density analysis pointed to an origin in superficial layers, specifically. While beta-band power was present regardless of attentional state, feature selectivity was only gated by beta in the attended condition. Neither the beta oscillation nor its gating of feature selectivity varied with microsaccade production. Importantly, beta modulation of neural activity predicted response times, suggesting a direct link between attentional gating and behavioral output. Together, these findings suggest beta-range synaptic activation in V4's superficial layers rhythmically gates attentional enhancement of feature tuning in a way that affects the speed of attentional selection.

The Distractor Positivity Component and the Inhibition of Distracting Stimuli.

There has been a long-lasting debate about whether salient stimuli, such as uniquely colored objects, have the ability to automatically distract us. To resolve this debate, it has been suggested that salient stimuli do attract attention but that they can be suppressed to prevent distraction. Some research supporting this viewpoint has focused on a newly discovered ERP component called the distractor positivity (PD), which is thought to measure an inhibitory attentional process. This collaborative review summarizes previous research relying on this component with a specific emphasis on how the PD has been used to understand the ability to ignore distracting stimuli. In particular, we outline how the PD component has been used to gain theoretical insights about how search strategy and learning can influence distraction. We also review alternative accounts of the cognitive processes indexed by the PD component. Ultimately, we conclude that the PD component is a useful tool for understanding inhibitory processes related to distraction and may prove to be useful in other areas of study related to cognitive control.

Frontal eye fields in macaque monkeys: prefrontal and premotor contributions to visually guided saccades.

Neuronal spiking was sampled from the frontal eye field (FEF) and from the rostral part of area 6 that reaches to the superior limb of the arcuate sulcus, dorsal to the arcuate spur when present (F2vr) in macaque monkeys performing memory-guided saccades and visually guided saccades for visual search. Neuronal spiking modulation in F2vr resembled that in FEF in many but not all respects. A new consensus clustering algorithm of neuronal modulation patterns revealed that F2vr and FEF contain a greater variety of modulation patterns than previously reported. The areas differ in the proportions of visuomotor neuron types, the proportions of neurons discriminating a target from distractors during visual search, and the consistency of modulation patterns across tasks. However, between F2vr and FEF we found no difference in the magnitude of delay period activity, the timing of the peak discharge rate relative to saccades, or the time of search target selection. The observed similarities and differences between the 2 cortical regions contribute to other work establishing the organization of eye fields in the frontal lobe and may help explain why FEF in monkeys is identified within granular prefrontal area 8 but in humans is identified within agranular premotor area 6.

Resolving the mesoscopic missing link: Biophysical modeling of EEG from cortical columns in primates.

Event-related potentials (ERP) are among the most widely measured indices for studying human cognition. While their timing and magnitude provide valuable insights, their usefulness is limited by our understanding of their neural generators at the circuit level. Inverse source localization offers insights into such generators, but their solutions are not unique. To address this problem, scientists have assumed the source space generating such signals comprises a set of discrete equivalent current dipoles, representing the activity of small cortical regions. Based on this notion, theoretical studies have employed forward modeling of scalp potentials to understand how changes in circuit-level dynamics translate into macroscopic ERPs. However, experimental validation is lacking because it requires in vivo measurements of intracranial brain sources. Laminar local field potentials (LFP) offer a mechanism for estimating intracranial current sources. Yet, a theoretical link between LFPs and intracranial brain sources is missing. Here, we present a forward modeling approach for estimating mesoscopic intracranial brain sources from LFPs and predict their contribution to macroscopic ERPs. We evaluate the accuracy of this LFP-based representation of brain sources utilizing synthetic laminar neurophysiological measurements and then demonstrate the power of the approach in vivo to clarify the source of a representative cognitive ERP component. To that end, LFP was measured across the cortical layers of visual area V4 in macaque monkeys performing an attention demanding task. We show that area V4 generates dipoles through layer-specific transsynaptic currents that biophysically recapitulate the ERP component through the detailed forward modeling. The constraints imposed on EEG production by this method also revealed an important dissociation between computational and biophysical contributors. As such, this approach represents an important bridge between laminar microcircuitry, through the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.

Dissociation of Medial Frontal ß-Bursts and Executive Control.

The neural mechanisms of executive and motor control concern both basic researchers and clinicians. In human studies, preparation and cancellation of movements are accompanied by changes in the ß-frequency band (15-29 Hz) of electroencephalogram (EEG). Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient ß-bursts over sensorimotor cortical areas before movement initiation and increased ß-bursting over medial frontal areas with movement cancellation. This modulation has been interpreted as contributing to the trial-by-trial control of behavior. We performed identical analyses of EEG recorded over the frontal lobe of macaque monkeys (one male, one female) performing a saccade countermanding task. While we replicate the occurrence and modulation of ß-bursts associated with initiation and cancellation of saccades, we found that ß-bursts occur too infrequently to account for the observed stopping behavior. We also found ß-bursts were more common after errors, but their incidence was unrelated to response time (RT) adaptation. These results demonstrate the homology of this EEG signature between humans and macaques but raise questions about the current interpretation of ß band functional significance.SIGNIFICANCE STATEMENT The finding of increased ß-bursting over medial frontal cortex with movement cancellation in humans is difficult to reconcile with the finding of modulation too late to contribute to movement cancellation in medial frontal cortex of macaque monkeys. To obtain comparable measurement scales, we recorded electroencephalogram (EEG) over medial frontal cortex of macaques performing a stop signal (countermanding) task. We replicated the occurrence and modulation of ß-bursts associated with the cancellation of movements, but we found that ß-bursts occur too infrequently to account for observed stopping behavior. Unfortunately, this finding raises doubts whether ß-bursts can be a causal mechanism of response inhibition, which impacts future applications in devices such as brain-machine interfaces.

A Minimal Biophysical Model of Neocortical Pyramidal Cells: Implications for Frontal Cortex Microcircuitry and Field Potential Generation.

Ca2+ spikes initiated in the distal trunk of layer 5 pyramidal cells (PCs) underlie nonlinear dynamic changes in the gain of cellular response, critical for top-down control of cortical processing. Detailed models with many compartments and dozens of ionic channels can account for this Ca2+ spike-dependent gain and associated critical frequency. However, current models do not account for all known Ca2+-dependent features. Previous attempts to include more features have required increasing complexity, limiting their interpretability and utility for studying large population dynamics. We overcome these limitations in a minimal two-compartment biophysical model. In our model, a basal-dendrites/somatic compartment included fast-inactivating Na+ and delayed-rectifier K+ conductances, while an apical-dendrites/trunk compartment included persistent Na+, hyperpolarization-activated cation (I h ), slow-inactivating K+, muscarinic K+, and Ca2+ L-type. The model replicated the Ca2+ spike morphology and its critical frequency plus three other defining features of layer 5 PC synaptic integration: linear frequency-current relationships, back-propagation-activated Ca2+ spike firing, and a shift in the critical frequency by blocking I h Simulating 1000 synchronized layer 5 PCs, we reproduced the current source density patterns evoked by Ca2+ spikes and describe resulting medial-frontal EEG on a male macaque monkey. We reproduced changes in the current source density when I h was blocked. Thus, a two-compartment model with five crucial ionic currents in the apical dendrites reproduces all features of these neurons. We discuss the utility of this minimal model to study the microcircuitry of agranular areas of the frontal lobe involved in cognitive control and responsible for event-related potentials, such as the error-related negativity.SIGNIFICANCE STATEMENT A minimal model of layer 5 pyramidal cells replicates all known features crucial for distal synaptic integration in these neurons. By redistributing voltage-gated and returning transmembrane currents in the model, we establish a theoretical framework for the investigation of cortical microcircuit contribution to intracranial local field potentials and EEG. This tractable model will enable biophysical evaluation of multiscale electrophysiological signatures and computational investigation of cortical processing.

The unknown but knowable relationship between Presaccadic Accumulation of activity and Saccade initiation.

The goal of this short review is to call attention to a yawning gap of knowledge that separates two processes essential for saccade production. On the one hand, knowledge about the saccade generation circuitry within the brainstem is detailed and precise - push-pull interactions between gaze-shifting and gaze-holding processes control the time of saccade initiation, which begins when omnipause neurons are inhibited and brainstem burst neurons are excited. On the other hand, knowledge about the cortical and subcortical premotor circuitry accomplishing saccade initiation has crystalized around the concept of stochastic accumulation - the accumulating activity of saccade neurons reaching a fixed value triggers a saccade. Here is the gap: we do not know how the reaching of a threshold by premotor neurons causes the critical pause and burst of brainstem neurons that initiates saccades. Why this problem matters and how it can be addressed will be discussed. Closing the gap would unify two rich but curiously disconnected empirical and theoretical domains.

Performance Monitoring during Visual Priming.

Repetitive performance of single-feature (efficient or pop-out) visual search improves RTs and accuracy. This phenomenon, known as priming of pop-out, has been demonstrated in both humans and macaque monkeys. We investigated the relationship between performance monitoring and priming of pop-out. Neuronal activity in the supplementary eye field (SEF) contributes to performance monitoring and to the generation of performance monitoring signals in the EEG. To determine whether priming depends on performance monitoring, we investigated spiking activity in SEF as well as the concurrent EEG of two monkeys performing a priming of pop-out task. We found that SEF spiking did not modulate with priming. Surprisingly, concurrent EEG did covary with priming. Together, these results suggest that performance monitoring contributes to priming of pop-out. However, this performance monitoring seems not mediated by SEF. This dissociation suggests that EEG indices of performance monitoring arise from multiple, functionally distinct neural generators.

Express saccades during a countermanding task.

Express saccades are unusually short latency, visually guided saccadic eye movements. They are most commonly observed when the fixation spot disappears at a consistent, short interval before a target spot appears at a repeated location. The saccade countermanding task includes no fixation-target gap, variable target presentation times, and the requirement to withhold saccades on some trials. These testing conditions should discourage production of express saccades. However, two macaque monkeys performing the saccade countermanding task produced consistent, multimodal distributions of saccadic latencies. These distributions consisted of a longer mode extending from 200 ms to as much as 600 ms after target presentation and another consistently less than 100 ms after target presentation. Simulations revealed that, by varying express saccade production, monkeys could earn more reward. If express saccades were not rewarded, they were rarely produced. The distinct mechanisms producing express and longer saccade latencies were revealed further by the influence of regularities in the duration of the fixation interval preceding target presentation on saccade latency. Temporal expectancy systematically affected the latencies of regular but not of express saccades. This study highlights that cognitive control can integrate information across trials and strategically elicit intermittent very short latency saccades to acquire more reward.NEW & NOTEWORTHY A serendipitous discovery that macaque monkeys produce express saccades under conditions that should discourage them reveals how cognitive control can adapt behavior to maximize reward.

Neurally constrained modeling of speed-accuracy tradeoff during visual search: gated accumulation of modulated evidence.

Stochastic accumulator models account for response times and errors in perceptual decision making by assuming a noisy accumulation of perceptual evidence to a threshold. Previously, we explained saccade visual search decision making by macaque monkeys with a stochastic multiaccumulator model in which accumulation was driven by a gated feed-forward integration to threshold of spike trains from visually responsive neurons in frontal eye field that signal stimulus salience. This neurally constrained model quantitatively accounted for response times and errors in visual search for a target among varying numbers of distractors and replicated the dynamics of presaccadic movement neurons hypothesized to instantiate evidence accumulation. This modeling framework suggested strategic control over gate or over threshold as two potential mechanisms to accomplish speed-accuracy tradeoff (SAT). Here, we show that our gated accumulator model framework can account for visual search performance under SAT instructions observed in a milestone neurophysiological study of frontal eye field. This framework captured key elements of saccade search performance, through observed modulations of neural input, as well as flexible combinations of gate and threshold parameters necessary to explain differences in SAT strategy across monkeys. However, the trajectories of the model accumulators deviated from the dynamics of most presaccadic movement neurons. These findings demonstrate that traditional theoretical accounts of SAT are incomplete descriptions of the underlying neural adjustments that accomplish SAT, offer a novel mechanistic account of decision-making mechanisms during speed-accuracy tradeoff, and highlight questions regarding the identity of model and neural accumulators. NEW & NOTEWORTHY A gated accumulator model is used to elucidate neurocomputational mechanisms of speed-accuracy tradeoff. Whereas canonical stochastic accumulators adjust strategy only through variation of an accumulation threshold, we demonstrate that strategic adjustments are accomplished by flexible combinations of both modulation of the evidence representation and adaptation of accumulator gate and threshold. The results indicate how model-based cognitive neuroscience can translate between abstract cognitive models of performance and neural mechanisms of speed-accuracy tradeoff.

Neural mechanisms of speed-accuracy tradeoff of visual search: saccade vigor, the origin of targeting errors, and comparison of the superior colliculus and frontal eye field.

Balancing the speed-accuracy tradeoff (SAT) is necessary for successful behavior. Using a visual search task with interleaved cues emphasizing speed or accuracy, we recently reported diverse contributions of frontal eye field (FEF) neurons instantiating salience evidence and response preparation. Here, we report replication of visual search SAT performance in two macaque monkeys, new information about variation of saccade dynamics with SAT, extension of the neurophysiological investigation to describe processes in the superior colliculus (SC), and a description of the origin of search errors in this task. Saccade vigor varied idiosyncratically across SAT conditions and monkeys but tended to decrease with response time. As observed in the FEF, speed-accuracy tradeoff was accomplished through several distinct adjustments in the superior colliculus. In "Accurate" relative to "Fast" trials, visually responsive neurons in SC as in FEF had lower baseline firing rates and later target selection. The magnitude of these adjustments in SC was indistinguishable from that in FEF. Search errors occurred when visual salience neurons in the FEF and the SC treated distractors as targets, even in the Accurate condition. Unlike FEF, the magnitude of visual responses in the SC did not vary across SAT conditions. Also unlike FEF, the activity of SC movement neurons when saccades were initiated was equivalent in Fast and Accurate trials. Saccade-related neural activity in SC, but not FEF, varied with saccade peak velocity. These results extend our understanding of the cortical and subcortical contributions to SAT. NEW & NOTEWORTHY Neurophysiological mechanisms of speed-accuracy tradeoff (SAT) have only recently been investigated. This article reports the first replication of SAT performance in nonhuman primates, the first report of variation of saccade dynamics with SAT, the first description of superior colliculus contributions to SAT, and the first description of the origin of errors during SAT. These results inform and constrain new models of distributed decision making.

Response times from ensembles of accumulators.

Decision-making is explained by psychologists through stochastic accumulator models and by neurophysiologists through the activity of neurons believed to instantiate these models. We investigated an overlooked scaling problem: How does a response time (RT) that can be explained by a single model accumulator arise from numerous, redundant accumulator neurons, each of which individually appears to explain the variability of RT? We explored this scaling problem by developing a unique ensemble model of RT, called e pluribus unum, which embodies the well-known dictum "out of many, one." We used the e pluribus unum model to analyze the RTs produced by ensembles of redundant, idiosyncratic stochastic accumulators under various termination mechanisms and accumulation rate correlations in computer simulations of ensembles of varying size. We found that predicted RT distributions are largely invariant to ensemble size if the accumulators share at least modestly correlated accumulation rates and RT is not governed by the most extreme accumulators. Under these regimes the termination times of individual accumulators was predictive of ensemble RT. We also found that the threshold measured on individual accumulators, corresponding to the firing rate of neurons measured at RT, can be invariant with RT but is equivalent to the specified model threshold only when the rate correlation is very high.

Disrupted Saccadic Corollary Discharge in Schizophrenia.

Disruptions in corollary discharge (CD), motor signals that send information to sensory areas and allow for prediction of sensory states, are argued to underlie the perceived loss of agency in schizophrenia. Behavioral and neurophysiological evidence for CD in primates comes largely from the saccadic double-step task, which requires participants to make two visually triggered saccadic eye movements in brief succession. Healthy individuals use CD to anticipate the change in eye position resulting from the first saccade when preparing the second saccade. In the current study with human participants, schizophrenia patients and healthy controls of both sexes performed a modified double-step task. Most trials required a saccade to a single visual target (T1). On a subset of trials, a second target (T2) was flashed shortly following T1. Subjects were instructed to look directly at T2. Healthy individuals also use CD to make rapid, corrective responses following erroneous saccades to T1. To assess CD in schizophrenia, we examined the following on error trials: (1) frequency and latency of corrective saccades, and (2) mislocalization of the corrective (second) saccade in the direction predicted by a failure to use CD to account for the first eye movement. Consistent with disrupted CD, patients made fewer and slower error corrections. Importantly, the corrective saccade vector angle was biased in a manner consistent with disrupted CD. These results provide novel and clear evidence for dysfunctional CD in the oculomotor system in patients with schizophrenia. Based on neurophysiology work, these disturbances might have their basis in medial thalamus dysfunction. SIGNIFICANCE STATEMENT: According to the World Health Organization, acute schizophrenia carries more disability weight than any other disease, but its etiology remains unknown. One promising theory of schizophrenia highlights alterations in a sense of self, in which self-generated thoughts or actions are attributed externally. Disruptions in corollary discharge (CD), motor signals sent to sensory areas that allow for the prediction of impending sensations, are proposed to underlie these symptoms. Direct physiological evidence, however, is limited. In nonhuman primates, inactivation of mediodorsal thalamic neurons disrupts CD associated with eye movements. Using the same task, we show similar impairments in schizophrenia patients, consistent with disrupted CD. These findings allow us to link clinical phenomenology to primate neurophysiology and interpret findings within a biological framework.

Neural control of visual search by frontal eye field: chronometry of neural events and race model processes.

We investigated the chronometry of neural processes in frontal eye fields of macaques performing double-step saccade visual search in which a conspicuous target changes location in the array on a random fraction of trials. Durations of computational processes producing a saccade to original and final target locations (GO1 and GO2, respectively) are derived from response times (RT) on different types of trials. In these data, GO2 tended to be faster than GO1, demonstrating that inhibition of the initial saccade did not delay production of the compensated saccade. Here, we measured the dynamics of visual, visuomovement, and movement neuron activity in relation to these processes by examining trials when neurons instantiated either process. First, we verified that saccades were initiated when the discharge rate of movement neurons reached a threshold that was invariant across RT and trial type. Second, the time when visual and visuomovement neurons selected the target and when movement neuron activity began to accumulate were not significantly different across trial type. Third, the interval from the beginning of accumulation to threshold of movement-related activity was significantly shorter when instantiating the GO2 relative to the GO1 process. Differences observed between monkeys are discussed. Fourth, random variation of RT was accounted for to some extent by random variation in both the onset and duration of selective activity of each neuron type but mostly by variation of movement neuron accumulation duration. These findings offer new insights into the sources of control of target selection and saccade production in dynamic environments.

Microcircuitry of agranular frontal cortex: testing the generality of the canonical cortical microcircuit.

We investigated whether a frontal area that lacks granular layer IV, supplementary eye field, exhibits features of laminar circuitry similar to those observed in primary sensory areas. We report, for the first time, visually evoked local field potentials (LFPs) and spiking activity recorded simultaneously across all layers of agranular frontal cortex using linear electrode arrays. We calculated current source density from the LFPs and compared the laminar organization of evolving sinks to those reported in sensory areas. Simultaneous, transient synaptic current sinks appeared first in layers III and V followed by more prolonged current sinks in layers I/II and VI. We also found no variation of single- or multi-unit visual response latency across layers, and putative pyramidal neurons and interneurons displayed similar response latencies. Many units exhibited pronounced discharge suppression that was strongest in superficial relative to deep layers. Maximum discharge suppression also occurred later in superficial than in deep layers. These results are discussed in the context of the canonical cortical microcircuit model originally formulated to describe early sensory cortex. The data indicate that agranular cortex resembles sensory areas in certain respects, but the cortical microcircuit is modified in nontrivial ways.

Microcircuitry of agranular frontal cortex: contrasting laminar connectivity between occipital and frontal areas.

Neocortex is striking in its laminar architecture. Tracer studies have uncovered anatomical connectivity among laminae, but the functional connectivity between laminar compartments is still largely unknown. Such functional connectivity can be discerned through spontaneous neural correlations during rest. Previous work demonstrated a robust pattern of mesoscopic resting-state connectivity in macaque primary visual cortex (V1) through interlaminar cross-frequency coupling. Here we investigated whether this pattern generalizes to other cortical areas by comparing resting-state laminar connectivity between V1 and the supplementary eye field (SEF), a frontal area lacking a granular layer 4 (L4). Local field potentials (LFPs) were recorded with linear microelectrode arrays from all laminae of granular V1 and agranular SEF while monkeys rested in darkness. We found substantial differences in the relationship between the amplitude of gamma-band (>30 Hz) LFP and the phase of alpha-band (7-14 Hz) LFP between these areas. In V1, gamma amplitudes in L2/3 and L5 were coupled with alpha-band LFP phase in L5, as previously described. In contrast, in SEF phase-amplitude coupling was prominent within L3 and much weaker across layers. These results suggest that laminar interactions in agranular SEF are unlike those in granular V1. Thus the intrinsic functional connectivity of the cortical microcircuit does not seem to generalize across cortical areas.