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EEG β-bursts observed over the medial frontal cortex are claimed to mediate response inhibition despite their infrequent occurrence. The weak association with stopping behavior is supposed to be a by-product of the low signal-to-noise ratio of EEG recordings. We tested the premise that β-bursts are more common within the cerebral cortex and more directly associated with response inhibition. We sampled simultaneously EEG and intracortical local field potentials (LFP) within the medial frontal cortex (MFC) of two macaque monkeys performing a response inhibition task. Intracortical β-bursts were just as infrequent as those in EEG and did not parallel the likelihood of canceling a planned response. Cortical β-bursts were more prevalent in upper layers but were not synchronized across a cortical column or with EEG β-bursts. These findings contradict claims for a causal contribution of β-bursts during response inhibition, provide important constraints for biophysical and cortical circuit models, and invite further considerations of β-burst function in cognitive control.

Salient objects stand out (pop-out) from their surroundings, grabbing our attention. Whether this phenomenon is a consequence of bottom-up sensory processing or predicated on top-down influence is debated. We show that the neural computation of attentional pop-out is embedded in the earliest cortical sensory response, seemingly void of feedback from higher-level areas. We measured synaptic and spiking activity across cortical columns in mid-level area V4 of monkeys searching for an attention-grabbing stimulus. Indexed by reaction times and behavioral accuracy, attention was captured at variable times. This moment of attentional capture occurred within the earliest feedforward response, both in terms of timing and spatial location. Moreover, the magnitude of the earliest sensory response predicted reaction times. Crucially, errant attentional selection and consequent behavior was associated with errant selection in sensory cortex. Together, these findings demonstrate a dominant role for feedforward activation of sensory cortex for dictating attentional priority and subsequent behavior.In briefWhy do certain objects stand out from their surroundings and seemingly grab our attention? In this study, Westerberg et al. determine that attentional selection for salient objects in our environment is computed in sensory cortex as soon as sensory information arrives.HighlightsEarly sensory responses in V4 predict attentional selection and behavioral responsesErrant attentional selection in sensory cortex precedes errant behaviorTonic modulation of sensory cortex can regulate attentional selection

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 from the mesoscopic activity of cortical columns to the patterns of EEG we measure at the scalp.HighlightsCognitive EEG production was accurately modeled from empirically measured cortical activity in awake macaques.V4 laminar activity plausibly generates the attention-related signal indexed by the EEG.Models demonstrate the importance of biophysical geometry in cognitive EEG production.

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 β-frequency band (15–29 Hz) of electroencephalogram (EEG). Previous studies with human participants performing stop signal (countermanding) tasks have described reduced frequency of transient β-bursts over sensorimotor cortical areas before movement initiation and increased β-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 β-bursts associated with initiation and cancellation of saccades, we found that β-bursts occur too infrequently to account for the observed stopping behavior. We also found β-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 β band functional significance.SIGNIFICANCE STATEMENTThe finding of increased β-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 β-bursts associated with the cancellation of movements, but we found that β-bursts occur too infrequently to account for observed stopping behavior. Unfortunately, this finding raises doubts whether β-bursts can be a causal mechanism of response inhibition, which impacts future applications in devices such as brain-machine interfaces.

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 (Ih), 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 Ih. 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 Ihwas 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 STATEMENTA 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.

What are the neural correlates that distinguish goal-directed (G) from non-goal-directed movements (nG)? We investigated this question in the monkey frontal eye field, which is implicated in voluntary control of saccades. We found that only for G-saccades, the variability in spike rate across trials decreased, the regularity of spike timings within trials increased, the neural activity increased earlier from baseline and had a concurrent reduction of LFP beta band power.

SUMMARYThe balance of speed with accuracy requires error detection and performance adaptation. To date, neural concomitants of these processes have been investigated only with noninvasive measures. To provide the first neurophysiological description, macaque monkeys performed visual search under cued speed accuracy tradeoff (SAT). Monkeys changed SAT emphasis immediately after a cued switch while neuron discharges were sampled in medial frontal cortex area supplementary eye field (SEF). A multiplicity of SEF neurons signaled production of choice errors and timing errors. Modulation of SEF activity after choice errors predicted production of un-rewarded corrective saccades. Modulation of activity after timing errors signaled reward prediction error. Adaptation of performance during SAT of visual search was accomplished through pronounced changes in neural state from before search array presentation until after reward delivery. These results contextualize previous findings using noninvasive measures, complement neurophysiological findings in visuomotor structures, endorse the role of medial frontal cortex as a critic relative to the actor instantiated in visuomotor structures, and extend our understanding of the distributed neural mechanisms of SAT.HIGHLIGHTSMedial frontal cortex enables post-error adjustment during SATChoice and timing errors were signaled by partially overlapping neural poolsMedial frontal cortex can proactively modulate visuomotor processesMedial frontal cortex is to visuomotor circuits as critic to actor

Neurons in macaque frontal eye field contribute to spatial but typically not feature selection during visual search. Using an innovative visual search task, we report a serendipitous discovery that some frontal eye field neurons can develop rapid selectivity for stimulus orientation that is used to guide gaze during a visual search task with pro-saccade and anti-saccade responses. This feature selectivity occurs simultaneously at multiple locations for all objects sharing that feature and coincides with when neurons select the singleton of a search array. This feature selectivity also reveals the distinct, subsequent operation of selecting the endpoint of the saccade in pro-saccade as well as anti-saccade trials. These results demonstrate that target selection preceding saccade preparation is composed of multiple operations. We conjecture that singleton selection indexes the allocation of attention, which can be divided, to conspicuous items. Consequently, endpoint selection indexes the focused allocation of attention to the endpoint of the saccade. These results demonstrate that saccade target selection is not a unitary process.SIGNIFICANCE STATEMENTFrontal eye field is well known to contribute to spatial selection for attention and eye movements. We discovered that some frontal eye field neurons can acquire selectivity for stimulus orientation when it guides visual search. The chronometry of neurons with and without feature selectivity reveal distinct operations accomplishing visual search.

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, and 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. Visually-responsive neurons modulated baseline firing rate and the time course of salience evidence. Unlike FEF, the magnitude of visual responses in SC did not vary across SAT conditions, but the time to locate the target was longer in Accurate as compared to Fast trials. Also unlike FEF, the activity of SC movement neurons when saccades were initiated was equivalent in Fast and Accurate trials. Search errors occurred when visual salience neurons in FEF and SC treated distractors as targets, even in the Accurate condition. Saccade-related neural activity in SC but less FEF varied with saccade peak velocity. These results extend our understanding of the cortical and subcortical contributions to SAT.Significance statementNeurophysiological mechanisms of speed-accuracy tradeoff (SAT) have only recently been investigated. This paper 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.

Frontal eye field (FEF) in macaque monkeys contributes to visual attention, visual-motor transformations and production of eye movements. Traditionally, neurons in FEF have been classified by the magnitude of increased discharge rates following visual stimulus presentation, during a waiting period, and associated with eye movement production. However, considerable heterogeneity remains within the traditional visual, visuomovement and movement categories. Cluster analysis is a data-driven method of identifying self-segregating groups within a dataset. Because many cluster analysis techniques exist and cluster outcomes vary with analysis assumptions, consensus clustering aggregates over multiple cluster analyses, identifying robust groups. To describe more comprehensively the neuronal composition of FEF, we applied a consensus clustering technique for unsupervised categorization of patterns of spike rate modulation measured during a memory-guided saccade task. We report ten functional categories, expanding on the traditional three. Categories were distinguished by latency, magnitude, and sign of visual response, presence of sustained activity, and dynamics, magnitude and sign of saccade-related modulation. Consensus clustering can include other metrics and can be applied to datasets from other brain regions to provides better information guiding microcircuit models of cortical function.SIGNIFICANCE STATEMENTThe contribution of a brain region cannot be understood without knowing the diversity, arrangement, and circuitry of constituent neurons. Traditional descriptions of frontal eye field include visual, visuo-saccadic, and saccadic categories. Here, we employ a novel consensus clustering method to identify more reliably functional categories in neural data. While confirming the traditional categories, consensus clustering distinguishes additional, previously unappreciated diversity in neural activity patterns. Such information is necessary to formulate correct microcircuit models of cortical function.

SummaryAvoiding distraction by salient irrelevant stimuli is critical to accomplishing daily tasks. Regions of prefrontal cortex control attention by enhancing the representation of task-relevant information in sensory cortex, which can be measured directly in modulation of both single neurons and averaging of the scalp-recorded electroencephalogram [1,2]. However, when irrelevant information is particularly conspicuous, it may distract attention and interfere with the selection of behaviorally relevant information. Many studies have shown that that distraction can be minimized via top-down control [3–5], but the cognitive and neural mechanisms giving rise to this control over distraction remain uncertain and vigorously debated [6–8]. Bridging neurophysiology to electrophysiology, we simultaneously recorded neurons in prefrontal cortex and event-related potentials (ERPs) over extrastriate visual cortex to track the processing of salient distractors during a visual search task. Critically, we observed robust suppression of salient distractor representations in both cortical areas, with suppression arising in prefrontal cortex before being manifest in the ERP signal over extrastriate cortex. Furthermore, only prefrontal neurons that participated in selecting the task-relevant target also showed suppression of the task-irrelevant distractor. This suggests a common prefrontal mechanism for target selection and distractor suppression, with input from prefrontal cortex being responsible for both selecting task-relevant and suppressing task-irrelevant information in sensory cortex. Taken together, our results resolve a long-standing debate over the mechanisms that prevent distraction, and provide the first evidence directly linking suppressed neural firing in prefrontal cortex with surface ERP measures of distractor suppression.

Cortical circuit mechanisms in medial frontal cortex enabling executive control are unknown. Hence, in monkeys performing a saccade countermanding task to earn larger or smaller fluid rewards, we sampled spiking and synaptic activity simultaneously across all layers of the supplementary eye field (SEF), an agranular cortical area contributing to performance monitoring in nonhuman primate and human studies. Laminar-specific synaptic currents with associated spike rate facilitation and suppression represented error production, reward gain or loss feedback, and reward delivery. The latency, polarity and magnitude of current and spike rate modulation were not predicted by the canonical cortical microcircuit. Pronounced synaptic currents in layer 2/3, which are modulated by loss magnitude, will contribute to the error-related negativity (ERN) and feedback-related negativity (FRN). These unprecedented findings reveal critical features of the cortical microcircuitry supporting performance monitoring and demonstrate that SEF can contribute to the error- and feedback-related negativity.

Perceptual decision-making, studied using two-alternative forced-choice tasks, is explained by sequential sampling models of evidence accumulation, which correspond to the dynamics of neurons in sensorimotor structures of the brain1 2. Response inhibition, studied using stop-signal (countermanding) tasks, is explained by a race model of the initiation or canceling of a response, which correspond to the dynamics of neurons in sensorimotor structures3 4. Neither standard model accounts for performance of the other task. Sequential sampling models incorporate response initiation as an uninterrupted non-decision time parameter independent of task-related variables. The countermanding race model does not account for the choice process. Here we show with new behavioral, neural and computational results that perceptual decision making of varying difficulty can be countermanded with invariant efficiency, that single prefrontal neurons instantiate both evidence accumulation and response inhibition, and that an interactive race between two GO and one STOP stochastic accumulator fits countermanding choice behavior. Thus, perceptual decision-making and response control, previously regarded as distinct mechanisms, are actually aspects of more flexible behavior supported by a common neural and computational mechanism. The identification of this aspect of decision-making with response production clarifies the component processes of decision-making.