High gamma activity distinguishes frontal cognitive control regions from adjacent cortical networks.

Though the lateral frontal cortex is broadly implicated in cognitive control, functional MRI (fMRI) studies suggest fine-grained distinctions within this region. To examine this question electrophysiologically, we placed electrodes on the lateral frontal cortex in patients undergoing awake craniotomy for tumor resection. Patients performed verbal tasks with a manipulation of attentional switching, a canonical control demand. Power in the high gamma range (70-250 Hz) distinguished electrodes based on their location within a high-resolution fMRI network parcellation of the frontal lobe. Electrodes within the canonical fronto-parietal control network showed increased power in the switching condition, a result absent in electrodes within default mode, language and somato-motor networks. High gamma results contrasted with spatially distributed power decreases in the beta range (12-30 Hz). These results confirm the importance of fine-scale functional distinctions within the human frontal lobe, and pave the way for increased precision of functional mapping in tumor surgeries.

ß-Bursts over Frontal Cortex Track the Surprise of Unexpected Events in Auditory, Visual, and Tactile Modalities.

One of the fundamental ways in which the brain regulates and monitors behavior is by making predictions about the sensory environment and adjusting behavior when those expectations are violated. As such, surprise is one of the fundamental computations performed by the human brain. In recent years, it has been well established that one key aspect by which behavior is adjusted during surprise is inhibitory control of the motor system. Moreover, because surprise automatically triggers inhibitory control without much proactive influence, it can provide unique insights into largely reactive control processes. Recent years have seen tremendous interest in burst-like ß frequency events in the human (and nonhuman) local field potential-especially over (p)FC-as a potential signature of inhibitory control. To date, ß-bursts have only been studied in paradigms involving a substantial amount of proactive control (such as the stop-signal task). Here, we used two cross-modal oddball tasks to investigate whether surprise processing is accompanied by increases in scalp-recorded ß-bursts. Indeed, we found that unexpected events in all tested sensory domains (haptic, auditory, visual) were followed by low-latency increases in ß-bursting over frontal cortex. Across experiments, ß-burst rates were positively correlated with estimates of surprise derived from Shannon's information theory, a type of surprise that represents the degree to which a given stimulus violates prior expectations. As such, the current work clearly implicates frontal ß-bursts as a signature of surprise processing. We discuss these findings in the context of common frameworks of inhibitory and cognitive control after unexpected events.

Modeling brain dynamics and gaze behavior: Starting point bias and drift rate relate to frontal midline theta oscillations.

Frontal midline theta oscillatory dynamics have been implicated as an important neural signature of inhibitory control. However, most proactive cognitive control studies rely on behavioral tasks where individual differences are inferred through button presses. We applied computational modeling to further refine our understanding of theta dynamics in a cued anti-saccade task with gaze-contingent eye tracking. Using a drift diffusion model, increased frontal midline theta power during high-conflict, relative to low-conflict, trials predicted a more conservative style of responding through the starting point (bias). During both high- and low-conflict trials, increases in frontal midline theta also predicted improvements in response efficiency (drift rate). Regression analyses provided support for the importance of the starting point bias, which was associated with frontal midline theta over the course of the task above-and-beyond both drift rate and mean reaction time. Our findings provide a more thorough understanding of proactive gaze control by linking trial-by-trial increases of frontal midline theta to a shift in starting point bias facilitating a more neutral style of responding.

Neural responses in macaque prefrontal cortex are linked to strategic exploration.

Humans have been shown to strategically explore. They can identify situations in which gathering information about distant and uncertain options is beneficial for the future. Because primates rely on scarce resources when they forage, they are also thought to strategically explore, but whether they use the same strategies as humans and the neural bases of strategic exploration in monkeys are largely unknown. We designed a sequential choice task to investigate whether monkeys mobilize strategic exploration based on whether information can improve subsequent choice, but also to ask the novel question about whether monkeys adjust their exploratory choices based on the contingency between choice and information, by sometimes providing the counterfactual feedback about the unchosen option. We show that monkeys decreased their reliance on expected value when exploration could be beneficial, but this was not mediated by changes in the effect of uncertainty on choices. We found strategic exploratory signals in anterior and mid-cingulate cortex (ACC/MCC) and dorsolateral prefrontal cortex (dlPFC). This network was most active when a low value option was chosen, which suggests a role in counteracting expected value signals, when exploration away from value should to be considered. Such strategic exploration was abolished when the counterfactual feedback was available. Learning from counterfactual outcome was associated with the recruitment of a different circuit centered on the medial orbitofrontal cortex (OFC), where we showed that monkeys represent chosen and unchosen reward prediction errors. Overall, our study shows how ACC/MCC-dlPFC and OFC circuits together could support exploitation of available information to the fullest and drive behavior towards finding more information through exploration when it is beneficial.

The role of left temporo-parietal and inferior frontal cortex in comprehending syntactically complex sentences: A brain stimulation study.

BACKGROUND AND OBJECTIVES: Syntactic competence relies on a left-lateralized network converging on hubs in inferior-frontal and posterior-temporal cortices. We address the question whether anodal transcranial direct current stimulation (a-tDCS) over these hubs can modulate comprehension of sentences, whose syntactic complexity systematically varied along the factors embedding depths and canonicity. Semantic content and length of the sentences were kept identical and forced choice picture matching was required after the full sentence had been presented. METHODS: We used a single-blind, within-subject, sham-controlled design, applying a-tDCS targeting left posterior tempo-parietal (TP) and left inferior frontal cortex (FC). Stimulation sites were determined by individual neuro-navigation. 20 participants were included of whom 19 entered the analysis. Results were analysed using (generalized) mixed models. In a pilot-experiment in another group of 20 participants we validated the manipulation of syntactic complexity by the two factors embedding depth and argument-order. RESULTS: Reaction times increased and accuracy decreased with higher embedding depth and non-canonical argument order in both experiments. Notably a-tDCS over TP enhanced sentence-to-picture matching, while FC-stimulation showed no consistent effect. Moreover, the analysis disclosed a session effect, indicating improvements of task performance especially regarding speed. CONCLUSIONS: We conclude that the posterior 'hub' of the neuronal network affording syntactic analysis represents a 'bottleneck', likely due to working-memory capacity and the challenges of mapping semantic to syntactic information allowing for role assignment. While this does not challenge the role of left inferior-frontal cortex for syntax processing and novel-grammar learning, the application of highly established syntactic rules during sentence comprehension may be considered optimized, thus not augmentable by a-tDCS in the uncompromised network. SIGNIFICANCE STATEMENT: Anodal transcranial direct current stimulation (a-tDCS) over left temporo-parietal cortex enhances comprehension of complex sentences in uncompromised young speakers. Since a-tDCS over left frontal cortex did not elicit any change, the 'bottleneck' for the understanding of complex sentences seems to be the posterior, temporo-parietal rather than the anterior inferior-frontal 'hub' of language processing. Regarding the attested role of inferior-frontal cortex in syntax processing, we suggest that its function is optimized in competent young speakers, preventing further enhancement by (facilitatory) tDCS. Results shed light on the functional anatomy of syntax processing during sentence comprehension; moreover, they open perspectives for research in the lesioned language network of people with syntactic deficits due to aphasia.

The neural mechanism of non-phase-locked EEG activity in task switching.

Flexible switching between different tasks is an important cognitive ability for humans and it is often studied using the task-switching paradigm. Although the neural mechanisms of task switching have been extensively explored in previous studies using event-related potentials techniques, the activity and process mechanisms of non-phase-locked electroencephalography (EEG) have rarely been revealed. For this reason, this paper discusses the processing of non-phase-locked EEG oscillations in task switching based on frequency-band delineation. First, the roles of each frequency band in local brain regions were summarized. In particular, during the proactive control process (the cue-stimulus interval), delta, theta, and alpha oscillations played more roles in the switch condition while beta played more roles in repeat task. In the reactive control process (post-target), delta, alpha, and beta are all related to sensorimotor function. Then, utilizing the functional connectivity (FC) method, delta connections in the frontotemporal regions and theta connections located in the parietal-to-occipital sites are involved in the preparatory period before task switching, while alpha connections located in the sensorimotor areas and beta connections located in the frontal-parietal cortex are involved in response inhibition. Finally, cross-frequency coupling (CFC) play an important role in working memory among different band oscillation. The present study shows that in addition to the processing mechanisms specific to each frequency band, there are some shared and interactive neural mechanism in task switching by using different analysis techniques.

Preparatory attention to visual features primarily relies on non-sensory representation.

Prior knowledge of behaviorally relevant information promotes preparatory attention before the appearance of stimuli. A key question is how our brain represents the attended information during preparation. A sensory template hypothesis assumes that preparatory signals evoke neural activity patterns that resembled the perception of the attended stimuli, whereas a non-sensory, abstract template hypothesis assumes that preparatory signals reflect the abstraction of attended stimuli. To test these hypotheses, we used fMRI and multivariate analysis to characterize neural activity patterns when human participants were prepared to attend a feature and then select it from a compound stimulus. In an fMRI experiment using basic visual feature (motion direction), we observed reliable decoding of the to-be-attended feature from the preparatory activity in both visual and frontoparietal areas. However, while the neural patterns constructed by a single feature from a baseline task generalized to the activity patterns during stimulus selection, they could not generalize to the activity patterns during preparation. Our findings thus suggest that neural signals during attentional preparation are predominantly non-sensory in nature that may reflect an abstraction of the attended feature. Such a representation could provide efficient and stable guidance of attention.

Right inferior frontal gyrus damage is associated with impaired initiation of inhibitory control, but not its implementation.

Inhibitory control is one of the most important control functions in the human brain. Much of our understanding of its neural basis comes from seminal work showing that lesions to the right inferior frontal gyrus (rIFG) increase stop-signal reaction time (SSRT), a latent variable that expresses the speed of inhibitory control. However, recent work has identified substantial limitations of the SSRT method. Notably, SSRT is confounded by trigger failures: stop-signal trials in which inhibitory control was never initiated. Such trials inflate SSRT, but are typically indicative of attentional, rather than inhibitory deficits. Here, we used hierarchical Bayesian modeling to identify stop-signal trigger failures in human rIFG lesion patients, non-rIFG lesion patients, and healthy comparisons. Furthermore, we measured scalp-EEG to detect ß-bursts, a neurophysiological index of inhibitory control. rIFG lesion patients showed a more than fivefold increase in trigger failure trials and did not exhibit the typical increase of stop-related frontal ß-bursts. However, on trials in which such ß-bursts did occur, rIFG patients showed the typical subsequent upregulation of ß over sensorimotor areas, indicating that their ability to implement inhibitory control, once triggered, remains intact. These findings suggest that the role of rIFG in inhibitory control has to be fundamentally reinterpreted.

Brain Activity Associated with the Planning Process during the Long-Time Learning of the Tower of Hanoi (ToH) Task: A Pilot Study.

Planning and decision-making are critical managerial functions involving the brain's executive functions. However, little is known about the effect of cerebral activity during long-time learning while planning and decision-making. This study investigated the impact of planning and decision-making processes in long-time learning, focusing on a cerebral activity before and after learning. The methodology of this study involves the Tower of Hanoi (ToH) to investigate executive functions related to the learning process. Generally, ToH is used to measure baseline performance, learning rate, offline learning (following overnight retention), and transfer. However, this study performs experiments on long-time learning effects for ToH solving. The participants were involved in learning the task over seven weeks. Learning progress was evaluated based on improvement in performance and correlations with the learning curve. All participants showed a significant improvement in planning and decision-making over seven weeks of time duration. Brain activation results from fMRI showed a statistically significant decrease in the activation degree in the dorsolateral prefrontal cortex, parietal lobe, inferior frontal gyrus, and premotor cortex between before and after learning. Our pilot study showed that updating information and shifting issue rules were found in the frontal lobe. Through monitoring performance, we can describe the effect of long-time learning initiated at the frontal lobe and then convert it to a task execution function by analyzing the frontal lobe maps. This process can be observed by comparing the learning curve and the fMRI maps. It was also clear that the degree of activation tends to decrease with the number of tasks, such as through the mid-phase and the end-phase of training. The elucidation of this structure is closely related to decision-making in human behavior, where brain dynamics differ between "thinking and behavior" during complex thinking in the early stages of training and instantaneous "thinking and behavior" after sufficient training. Since this is related to human learning, elucidating these mechanisms will allow the construction of a brain function map model that can be used universally for all training tasks.

What Does the Frontopolar Cortex Contribute to Goal-Directed Cognition and Action?

Understanding the unique functions of different subregions of primate prefrontal cortex has been a longstanding goal in cognitive neuroscience. Yet, the anatomy and function of one of its largest subregions (the frontopolar cortex) remain enigmatic and underspecified. Our Society for Neuroscience minisymposium Primate Frontopolar Cortex: From Circuits to Complex Behaviors will comprise a range of new anatomic and functional approaches that have helped to clarify the basic circuit anatomy of the frontal pole, its functional involvement during performance of cognitively demanding behavioral paradigms in monkeys and humans, and its clinical potential as a target for noninvasive brain stimulation in patients with brain disorders. This review consolidates knowledge about the anatomy and connectivity of frontopolar cortex and provides an integrative summary of its function in primates. We aim to answer the question: what, if anything, does frontopolar cortex contribute to goal-directed cognition and action?

A Neurosurgical Functional Dissection of the Middle Precentral Gyrus during Speech Production.

Classical models have traditionally focused on the left posterior inferior frontal gyrus (Broca's area) as a key region for motor planning of speech production. However, converging evidence suggests that it is not critical for either speech motor planning or execution. Alternative cortical areas supporting high-level speech motor planning have yet to be defined. In this review, we focus on the precentral gyrus, whose role in speech production is often thought to be limited to lower-level articulatory muscle control. In particular, we highlight neurosurgical investigations that have shed light on a cortical region anatomically located near the midpoint of the precentral gyrus, hence called the middle precentral gyrus (midPrCG). The midPrCG is functionally located between dorsal hand and ventral orofacial cortical representations and exhibits unique sensorimotor and multisensory functions relevant for speech processing. This includes motor control of the larynx, auditory processing, as well as a role in reading and writing. Furthermore, direct electrical stimulation of midPrCG can evoke complex movements, such as vocalization, and selective injury can cause deficits in verbal fluency, such as pure apraxia of speech. Based on these findings, we propose that midPrCG is essential to phonological-motoric aspects of speech production, especially syllabic-level speech sequencing, a role traditionally ascribed to Broca's area. The midPrCG is a cortical brain area that should be included in contemporary models of speech production with a unique role in speech motor planning and execution.

Functional architecture of executive control and associated event-related potentials in macaques.

The medial frontal cortex (MFC) enables executive control by monitoring relevant information and using it to adapt behavior. In macaques performing a saccade countermanding (stop-signal) task, we simultaneously recorded electrical potentials over MFC and neural spiking across all layers of the supplementary eye field (SEF). We report the laminar organization of neurons enabling executive control by monitoring the conflict between incompatible responses, the timing of events, and sustaining goal maintenance. These neurons were a mix of narrow-spiking and broad-spiking found in all layers, but those predicting the duration of control and sustaining the task goal until the release of operant control were more commonly narrow-spiking neurons confined to layers 2 and 3 (L2/3). We complement these results with evidence for a monkey homolog of the N2/P3 event-related potential (ERP) complex associated with response inhibition. N2 polarization varied with error-likelihood and P3 polarization varied with the duration of expected control. The amplitude of the N2 and P3 were predicted by the spike rate of different classes of neurons located in L2/3 but not L5/6. These findings reveal features of the cortical microcircuitry supporting executive control and producing associated ERPs.

Cognition and the single neuron: How cell types construct the dynamic computations of frontal cortex.

Frontal cortex is thought to underlie many advanced cognitive capacities, from self-control to long term planning. Reflecting these diverse demands, frontal neural activity is notoriously idiosyncratic, with tuning properties that are correlated with endless numbers of behavioral and task features. This menagerie of tuning has made it difficult to extract organizing principles that govern frontal neural activity. Here, we contrast two successful yet seemingly incompatible approaches that have begun to address this challenge. Inspired by the indecipherability of single-neuron tuning, the first approach casts frontal computations as dynamical trajectories traversed by arbitrary mixtures of neurons. The second approach, by contrast, attempts to explain the functional diversity of frontal activity with the biological diversity of cortical cell-types. Motivated by the recent discovery of functional clusters in frontal neurons, we propose a consilience between these population and cell-type-specific approaches to neural computations, advancing the conjecture that evolutionarily inherited cell-type constraints create the scaffold within which frontal population dynamics must operate.

Visual Selective Attention P300 Source in Frontal-Parietal Lobe: ERP and fMRI Study.

Visual selective attention can be achieved into bottom-up and top-down attention. Different selective attention tasks involve different attention control ways. The pop-out task requires more bottom-up attention, whereas the search task involves more top-down attention. P300, which is the positive potential generated by the brain in the latency of 300 ~ 600 ms after stimulus, reflects the processing of attention. There is no consensus on the P300 source. The aim of present study is to study the source of P300 elicited by different visual selective attention. We collected thirteen participants' P300 elicited by pop-out and search tasks with event-related potentials (ERP). We collected twenty-six participants' activation brain regions in pop-out and search tasks with functional magnetic resonance imaging (fMRI). And we analyzed the sources of P300 using the ERP and fMRI integration with high temporal resolution and high spatial resolution. ERP results indicated that the pop-out task induced larger P300 than the search task. P300 induced by the two tasks distributed at frontal and parietal lobes, with P300 induced by the pop-out task mainly at the parietal lobe and that induced by the search task mainly at the frontal lobe. Further ERP and fMRI integration analysis showed that neural difference sources of P300 were the right precentral gyrus, left superior frontal gyrus (medial orbital), left middle temporal gyrus, left rolandic operculum, right postcentral gyrus, and left angular gyrus. Our study suggests that the frontal and parietal lobes contribute to the P300 component of visual selective attention.

A causal role of anterior prefrontal-putamen circuit for response inhibition revealed by transcranial ultrasound stimulation in humans.

Stopping an inappropriate response requires the involvement of the prefrontal-subthalamic hyperdirect pathway. However, how the prefrontal-striatal indirect pathway contributes to stopping is poorly understood. In this study, transcranial ultrasound stimulation is used to perform interventions in a task-related region in the striatum. Functional magnetic resonance imaging (MRI) reveals activation in the right anterior part of the putamen during response inhibition, and ultrasound stimulation to the anterior putamen, as well as the subthalamic nucleus, results in significant impairments in stopping performance. Diffusion imaging further reveals prominent structural connections between the anterior putamen and the right anterior part of the inferior frontal cortex (IFC), and ultrasound stimulation to the anterior IFC also shows significant impaired stopping performance. These results demonstrate that the right anterior putamen and right anterior IFC causally contribute to stopping and suggest that the anterior IFC-anterior putamen circuit in the indirect pathway serves as an essential route for stopping.

Processing of embedded response plans is modulated by an interplay of frontoparietal theta and beta activity.

Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive, despite theoretical frameworks, such as the theory of event coding, describing the involved cognitive processes. In a sample of n = 40 healthy participants, we combine time-frequency decomposition and various beamforming methods to examine the neurophysiological dynamics of such action plans, with special emphasis on the interplay of theta and beta frequency activity during the processing of these plans. We show that the integration and rule-guided reactivation of embedded response plans is modulated by a complex interplay of theta and beta activity. Pretrial beta-band activity (BBA) is related to different functional neuroanatomical structures that are activated in a consecutive fashion. Enhanced preparatory activity is positively associated with higher binding-related BBA in the precuneus/parietal areas, indicating that activity in the precuneus/parietal cortex facilitates the execution of an embedded action sequence. Increased preparation subsequently leads to reduced working memory retrieval demands. A cascading pattern of interactions between pretrial and within-trial activity indicates the importance of preparatory brain activity. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.NEW & NOTEWORTHY Even simple actions like opening a door require integration/binding and flexible reactivation of different motor elements. Yet, the neural mechanisms underlying the processing of such "embedded response plans" are largely elusive. The study shows that there are multiple roles of beta and theta oscillations associated with different functional neuroanatomical structures during the integration and reactivation of motor elements during actions.

Cortical feedback loops bind distributed representations of working memory.

Working memory-the brain's ability to internalize information and use it flexibly to guide behaviour-is an essential component of cognition. Although activity related to working memory has been observed in several brain regions1-3, how neural populations actually represent working memory4-7 and the mechanisms by which this activity is maintained8-12 remain unclear13-15. Here we describe the neural implementation of visual working memory in mice alternating between a delayed non-match-to-sample task and a simple discrimination task that does not require working memory but has identical stimulus, movement and reward statistics. Transient optogenetic inactivations revealed that distributed areas of the neocortex were required selectively for the maintenance of working memory. Population activity in visual area AM and premotor area M2 during the delay period was dominated by orderly low-dimensional dynamics16,17 that were, however, independent of working memory. Instead, working memory representations were embedded in high-dimensional population activity, present in both cortical areas, persisted throughout the inter-stimulus delay period, and predicted behavioural responses during the working memory task. To test whether the distributed nature of working memory was dependent on reciprocal interactions between cortical regions18-20, we silenced one cortical area (AM or M2) while recording the feedback it received from the other. Transient inactivation of either area led to the selective disruption of inter-areal communication of working memory. Therefore, reciprocally interconnected cortical areas maintain bound high-dimensional representations of working memory.

Self-regulation and frontal EEG alpha activity during infancy and early childhood: A multilevel meta-analysis.

Integrating behavioral and neurophysiological measures has created new and advanced ways to understand the development of self-regulation. Electroencephalography (EEG) has been used to examine how self-regulatory processes are related to frontal alpha power during infancy and early childhood. However, findings across previous studies have been inconsistent. To address this issue, the current meta-analysis synthesized all prior literature examining associations between individual differences in self-regulation and frontal EEG alpha power (baseline and/or task). In total, 23 studies consisting of 1275 participants between 1 month and 6 years of age were included, which yielded 149 effect sizes. Findings of the three-level meta-analytic model demonstrated a non-significant overall association between self-regulation and frontal alpha power. Yet, significant moderating effects were found for self-regulation construct (emotion regulation, effortful control, executive function), self-regulation measurement (behavioral task, computer assessment, lab observation, questionnaire), and children's mean age. Self-regulation was only significantly correlated with frontal alpha power when studies focused on the executive functioning construct. Moreover, the use of behavioral tasks or questionnaires and a higher mean age of the children resulted in small but significant effect size estimates. Higher frontal alpha power values were related to higher order top-down mechanisms of self-regulation, indicating that these mechanisms might become stronger when the frontal cortex is sufficiently developed. The findings of the current meta-analysis highlight the importance of longitudinal analyses and multimethod approaches in future work to reach a more comprehensive understanding of the role of frontal EEG alpha activity in the etiology of individual differences in early self-regulation. RESEARCH HIGHLIGHTS: The first meta-analysis of individual differences in self-regulation and frontal EEG alpha power during infancy and early childhood demonstrated a non-significant overall association. Moderation analyses revealed that variations in frontal alpha power were significantly associated with executive function, but not with effortful control and emotion regulation. Frontal alpha power was related to variations in self-regulation when measured by behavioral tasks and questionnaires, but not via computer assessments and lab observations. The association between individual differences in self-regulation and frontal alpha power becomes significantly stronger with age.

The rostral medial frontal cortex is crucial for engagement in consummatory behavior.

The medial frontal cortex (MFC) in rodents emits rhythmic activity that is entrained to the animal's licking cycle during consumption and encodes the value of consumed fluids. These signals are especially prominent in the rostral half of the MFC. This region is located above an orbitofrontal region where mu-opioid receptors regulate intake and reversible inactivation reduces behavioral measures associated with the incentive value and palatability of liquid sucrose. Here, we examined the effects of reversible inactivation and stimulation of mu-opioid receptors in rostral MFC on behavior in an incentive contrast licking task. Adult male rats licked to receive access to liquid sucrose, which alternated between high (16%) and low (4%) values over 30 s periods. Bilateral infusion of muscimol reduced the total number of licks over the 30 min test sessions, the time spent actively consuming sucrose, and the ratio of licks for the higher and lower value fluids. Inactivation did not alter licking frequency or variability or microstructural measures such as the duration of licking bouts that are classically associated with the palatability of a liquid reward. Infusions of [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO; 1 µg/µL) at the same sites had inconsistent behavioral effects across different subjects. Our findings suggest that the rostral MFC has a distinct role in the control of consummatory behavior and contributes to persistent consumption and not to the expression of palatability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Covariations between pupil diameter and supplementary eye field activity suggest a role in cognitive effort implementation.

In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF.