Common and unique neurophysiological signatures for the stopping and revising of actions reveal the temporal dynamics of inhibitory control.

Inhibitory control is a crucial cognitive-control ability for behavioral flexibility that has been extensively investigated through action-stopping tasks. Multiple neurophysiological features have been proposed to represent 'signatures' of inhibitory control during action-stopping, though the processes signified by these signatures are still controversially discussed. The present study aimed to disentangle these processes by comparing simple stopping situations with those in which additional action revisions were needed. Three experiments in female and male humans were performed to characterize the neurophysiological dynamics involved in action-stopping and - changing, with hypotheses derived from recently developed two-stage 'pause-then-cancel' models of inhibitory control. Both stopping and revising an action triggered an early broad 'pause'-process, marked by frontal EEG ß-bursts and non-selective suppression of corticospinal excitability. However, partial-EMG responses showed that motor activity was only partially inhibited by this 'pause', and that this activity can be further modulated during action-revision. In line with two-stage models of inhibitory control, subsequent frontocentral EEG activity after this initial 'pause' selectively scaled depending on the required action revisions, with more activity observed for more complex revisions. This demonstrates the presence of a selective, effector-specific 'retune' phase as the second process involved in action-stopping and -revision. Together, these findings show that inhibitory control is implemented over an extended period of time and in at least two phases. We are further able to align the most commonly proposed neurophysiological signatures to these phases and show that they are differentially modulated by the complexity of action-revision.

Biophysical Modeling of Frontocentral ERP Generation Links Circuit-Level Mechanisms of Action-Stopping to a Behavioral Race Model.

Human frontocentral event-related potentials (FC-ERPs) are ubiquitous neural correlates of cognition and control, but their generating multiscale mechanisms remain mostly unknown. We used the Human Neocortical Neurosolver's biophysical model of a canonical neocortical circuit under exogenous thalamic and cortical drive to simulate the cell and circuit mechanisms underpinning the P2, N2, and P3 features of the FC-ERP observed after Stop-Signals in the Stop-Signal task (SST; N = 234 humans, 137 female). We demonstrate that a sequence of simulated external thalamocortical and corticocortical drives can produce the FC-ERP, similar to what has been shown for primary sensory cortices. We used this model of the FC-ERP to examine likely circuit-mechanisms underlying FC-ERP features that distinguish between successful and failed action-stopping. We also tested their adherence to the predictions of the horse-race model of the SST, with specific hypotheses motivated by theoretical links between the P3 and Stop process. These simulations revealed that a difference in P3 onset between successful and failed Stops is most likely due to a later arrival of thalamocortical drive in failed Stops, rather than, for example, a difference in the effective strength of the input. In contrast, the same model predicted that early thalamocortical drives underpinning the P2 and N2 differed in both strength and timing across stopping accuracy conditions. Overall, this model generates novel testable predictions of the thalamocortical dynamics underlying FC-ERP generation during action-stopping. Moreover, it provides a detailed cellular and circuit-level interpretation that supports links between these macroscale signatures and predictions of the behavioral race model.

The human subthalamic nucleus transiently inhibits active attentional processes.

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson's disease, where modulating the STN via deep brain stimulation (DBS) can release excess inhibition of thalamocortical motor circuits. However, the STN is also anatomically connected to other thalamocortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity and that STN-DBS may cause changes to this inhibition. Here we tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, n = 12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady state visual evoked potential (SSVEP), a well established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behaviour), we avoided possible confounds resulting from STN's motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least 1 week apart (n = 21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60 Hz) activity in the STN. Trial-to-trial modelling further showed that this STN activity statistically mediated the sounds' suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side effects of STN-DBS treatment, especially on attentional processes. Finally, our newly established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than peri-surgical recordings.

Examining motor evidence for the pause-then-cancel model of action-stopping: Insights from motor system physiology.

Stopping initiated actions is fundamental to adaptive behavior. Longstanding, single-process accounts of action-stopping have been challenged by recent, two-process, 'pause-then-cancel' models. These models propose that action-stopping involves two inhibitory processes: 1) a fast Pause process, which broadly suppresses the motor system as the result of detecting any salient event, and 2) a slower Cancel process, which involves motor suppression specific to the cancelled action. A purported signature of the Pause process is global suppression, or the reduced corticospinal excitability (CSE) of task-unrelated effectors early on in action-stopping. However, unlike the Pause process, few (if any) motor system signatures of a Cancel process have been identified. Here, we used single- and paired-pulse TMS methods to comprehensively measure the local physiological excitation and inhibition of both responding and task-unrelated motor effector systems during action-stopping. Specifically, we measured CSE, short-interval intracortical inhibition (SICI), and the duration of the cortical silent period (CSP). Consistent with key predictions from the pause-then-cancel model, CSE measurements at the responding effector indicated that additional suppression was necessary to counteract Go-related increases in CSE during-action-stopping, particularly at later timepoints. Increases in SICI on Stop-signal trials did not differ across responding and non-responding effectors, or across timepoints. This suggests SICI as a potential source of global suppression. Increases in CSP duration on Stop-signal trials were more prominent at later timepoints. SICI and CSP duration therefore appeared most consistent with the Pause and Cancel processes, respectively. Our study provides further evidence from motor system physiology that multiple inhibitory processes influence action-stopping.

Biophysical modeling of frontocentral ERP generation links circuit-level mechanisms of action-stopping to a behavioral race model.

Human frontocentral event-related potentials (FC-ERPs) are ubiquitous neural correlates of cognition and control, but their generating multiscale mechanisms remain mostly unknown. We used the Human Neocortical Neurosolver(HNN)'s biophysical model of a canonical neocortical circuit under exogenous thalamic and cortical drive to simulate the cell and circuit mechanisms underpinning the P2, N2, and P3 features of the FC-ERP observed after Stop-Signals in the Stop-Signal task (SST). We demonstrate that a sequence of simulated external thalamocortical and cortico-cortical drives can produce the FC-ERP, similar to what has been shown for primary sensory cortices. We used this model of the FC-ERP to examine likely circuit-mechanisms underlying FC-ERP features that distinguish between successful and failed action-stopping. We also tested their adherence to the predictions of the horse-race model of the SST, with specific hypotheses motivated by theoretical links between the P3 and Stop process. These simulations revealed that a difference in P3 onset between successful and failed Stops is most likely due to a later arrival of thalamocortical drive in failed Stops, rather than, for example, a difference in effective strength of the input. In contrast, the same model predicted that early thalamocortical drives underpinning the P2 and N2 differed in both strength and timing across stopping accuracy conditions. Overall, this model generates novel testable predictions of the thalamocortical dynamics underlying FC-ERP generation during action-stopping. Moreover, it provides a detailed cellular and circuit-level interpretation that supports links between these macroscale signatures and predictions of the behavioral race model.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status.

BACKGROUND: Widely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on disorder sub-type (BDI vs II), depressed mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task. RESULTS: Results suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power during the task compared to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, depressed mood, or antipsychotic medication use. CONCLUSIONS: This work suggests that BD sub-type, depressed mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

Early Action Error Processing Is Due to Domain-General Surprise, Whereas Later Processing Is Error Specific.

The ability to adapt behavior after erroneous actions is one of the key aspects of cognitive control. Error commission typically causes people to slow down their subsequent actions [post-error slowing (PES)]. Recent work has challenged the notion that PES reflects adaptive, controlled processing and instead suggests that it is a side effect of the surprising nature of errors. Indeed, human neuroimaging suggests that the brain networks involved in processing errors overlap with those processing error-unrelated surprise, calling into question whether there is a specific system for error processing in the brain at all. In the current study, we used EEG decoding and a novel behavioral paradigm to test whether there are indeed unique, error-specific processes that contribute to PES beyond domain-general surprise. Across two experiments in male and female humans (N = 76), we found that both errors and error-unrelated surprise were followed by slower responses when response-stimulus intervals were short. Furthermore, the early neural processes following error-specific and domain-general surprise showed significant cross-decoding. However, at longer intervals, which provided additional processing time, only errors were still followed by post-trial slowing. Furthermore, this error-specific PES effect was reflected in sustained neural activity that could be decoded from that associated with domain-general surprise, with the strongest contributions found at lateral frontal, occipital, and sensorimotor scalp sites. These findings suggest that errors and surprise initially share common processes, but that after additional processing time, unique, genuinely error-specific processes take over and contribute to behavioral adaptation.SIGNIFICANCE STATEMENT Humans typically slow their actions after errors (PES). Some suggest that PES is a side effect of the unexpected, surprising nature of errors, challenging the notion of a genuine error processing system in the human brain. Here, we used multivariate EEG decoding to identify behavioral and neural processes uniquely related to error processing. Action slowing occurred following both action errors and error-unrelated surprise when time to prepare the next response was short. However, when there was more time to react, only errors were followed by slowing, further reflected in sustained neural activity. This suggests that errors and surprise initially share common processing, but that after additional time, error-specific, adaptive processes take over.

Inhibition of lexical representations after violated semantic predictions.

There is a consensus that humans predict upcoming words during sentence processing. Prediction makes language comprehension fast and efficient if this anticipatory processing is accurate. However, often times, predictions are not correct. There is a lack of research investigating the cognitive operations at play when predictions are violated. According to several proposals, such violations lead to an inhibition of the predicted word to facilitate the integration of the unexpected word. Across four experiments, we have tested whether predicted words are indeed inhibited when listeners encounter unexpected stimuli, and whether the linguistic status (word or sound) and semantic congruency of a word (plausible or implausible) influences this purported inhibitory process. Using a Cross-Modal Lexical Priming paradigm, we showed that when predictions are violated, the activation of the predicted word is inhibited, resulting in increased reaction times. These inhibitory effects appear to be language specific, in that they are only observed after unexpected words, as opposed to non-linguistic sounds (tones). However, contrary to a long-held assumption in the field of sentence processing, inhibitory effects are not modulated by the semantic congruency of the unexpected word (i.e., whether the unexpected word is plausible within the sentence context). Indeed, in the current study, any linguistic information that violated listeners' semantic prediction resulted in the inhibition of the predicted word. Thus, the current findings are more compatible with a view in which unexpected linguistic events that are meaningful engage inhibitory processes with the specific purpose of inhibiting the predicted, though out-of-date, word.

Measuring the nonselective effects of motor inhibition using isometric force recordings.

Inhibition is a key cognitive control mechanism humans use to enable goal-directed behavior. When rapidly exerted, inhibitory control has broad, nonselective motor effects, typically demonstrated using corticospinal excitability measurements (CSE) elicited by transcranial magnetic stimulation (TMS). For example, during rapid action-stopping, CSE is suppressed at both stopped and task-unrelated muscles. While such TMS-based CSE measurements have provided crucial insights into the fronto-basal ganglia circuitry underlying inhibitory control, they have several downsides. TMS is contraindicated in many populations (e.g., epilepsy or deep-brain stimulation patients), has limited temporal resolution, produces distracting auditory and haptic stimulation, is difficult to combine with other imaging methods, and necessitates expensive, immobile equipment. Here, we attempted to measure the nonselective motor effects of inhibitory control using a method unaffected by these shortcomings. Thirty male and female human participants exerted isometric force on a high-precision handheld force transducer while performing a foot-response stop-signal task. Indeed, when foot movements were successfully stopped, force output at the task-irrelevant hand was suppressed as well. Moreover, this nonselective reduction of isometric force was highly correlated with stop-signal performance and showed frequency dynamics similar to established inhibitory signatures typically found in neural and muscle recordings. Together, these findings demonstrate that isometric force recordings can reliably capture the nonselective effects of motor inhibition, opening the door to many applications that are hard or impossible to realize with TMS.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status.

Background : Widely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on BD sub-type (BDI vs II), mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task. Results : Results suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power compared during the task to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, mood, or antipsychotic medication use. Conclusions : his work suggests that BD sub-type, mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

Evoked mid-frontal activity predicts cognitive dysfunction in Parkinson's disease.

BACKGROUND: Cognitive dysfunction is a major feature of Parkinson's disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that mid-frontal delta/theta rhythms predict cognitive dysfunction in PD. METHOD: We recruited 100 patients with PD and 49 demographically similar control participants who completed a series of cognitive control tasks, including the Simon, oddball and interval-timing tasks. We focused on cue-evoked delta (1-4 Hz) and theta (4-7 Hz) rhythms from a single mid-frontal EEG electrode (cranial vertex (Cz)) in patients with PD who were either cognitively normal, with mild-cognitive impairments (Parkinson's disease with mild-cognitive impairment) or had dementia (Parkinson's disease dementia). RESULTS: We found that PD-related cognitive dysfunction was associated with increased response latencies and decreased mid-frontal delta power across all tasks. Within patients with PD, the first principal component of evoked electroencephalography features from a single electrode (Cz) strongly correlated with clinical metrics such as the Montreal Cognitive Assessment score (r=0.34) and with National Institutes of Health Toolbox Executive Function score (r=0.46). CONCLUSIONS: These data demonstrate that cue-evoked mid-frontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.

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.

Lingering Neural Representations of Past Task Features Adversely Affect Future Behavior.

During goal-directed behavior, humans purportedly form and retrieve so-called event files, conjunctive representations that link context-specific information about stimuli, their associated actions, and the expected action outcomes. The automatic formation, and later retrieval, of such conjunctive representations can substantially facilitate efficient action selection. However, recent behavioral work suggests that these event files may also adversely affect future behavior, especially when action requirements have changed between successive instances of the same task context (e.g., during task switching). Here, we directly tested this hypothesis with a recently developed method for measuring the strength of the neural representations of context-specific stimulus-action conjunctions (i.e., event files). Thirty-five male and female adult humans performed a task switching paradigm while undergoing EEG recordings. Replicating previous behavioral work, we found that changes in action requirements between two spaced repetitions of the same task incurred a significant reaction time cost. By combining multivariate pattern analysis and representational similarity analysis of the EEG recordings with linear mixed-effects modeling of trial-to-trial behavior, we then found that the magnitude of this behavioral cost was directly proportional to the strength of the conjunctive representation formed during the most recent previous exposure to the same task, that is, the most recent event file. This confirms that the formation of conjunctive representations of specific task contexts, stimuli, and actions in the brain can indeed adversely affect future behavior. Moreover, these findings demonstrate the potential of neural decoding of complex task set representations toward the prediction of behavior beyond the current trial.SIGNIFICANCE STATEMENT Understanding how the human brain organizes individual components of complex tasks is paramount for understanding higher-order cognition. During complex tasks, the brain forms conjunctive representations that link individual task features (contexts, stimuli, actions), which aids future performance of the same task. However, this can have adverse effects when the required sequence of actions within a task changes. We decoded conjunctive representations from electroencephalographic recordings during a task that included frequent changes to the rules determining the response. Indeed, stronger initial conjunctive representations predicted significant future response-time costs when task contexts repeated with changed response requirements. Showing that the formation of conjunctive task representations can have negative future effects generates novel insights into complex behavior and cognition, including task switching, planning, and problem solving.

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.

Two types of motor inhibition after action errors in humans.

Adaptive behavior requires the ability to appropriately react to action errors. Post-error slowing of response times (PES) is one of the most reliable phenomena in human behavior. It has been proposed that PES is partially achieved through inhibition of the motor system. However, there is no direct evidence for this link - or indeed, that the motor system is physiologically inhibited after errors altogether. Here, we used transcranial magnetic stimulation and electromyography to measure cortico-spinal excitability (CSE) across four experiments using a Simon task, in which female and male human participants sometimes committed errors. Errors were followed by reduced CSE at two different time points and in two different modes. Shortly after error commission (250ms) CSE was broadly suppressed - i.e., even task-unrelated motor effectors were inhibited. During the preparation of the subsequent response, CSE was specifically reduced at task-relevant effectors only. This latter effect was directly related to PES, with stronger CSE suppression accompanying greater PES. This suggests that PES is achieved through increased inhibitory control during post-error responses. To provide converging evidence, we then re-analyzed an openly-available EEG dataset that contained both Simon- and Stop-signal tasks using independent component analysis. We found that the same neural source component that indexed action-cancellation in the stop-signal task also showed clear PES-related activity during post-error responses in the Simon task. Together, these findings provide evidence that post-error adaptation is partially achieved through motor inhibition. Moreover, inhibition is engaged in two modes (first non-selective, then selective), aligning with recent multi-stage theories of error processing.SIGNIFICANCE STATEMENTIt is a common observation that humans implement a higher degree of caution when repeating an action during which they just committed a mistake. In the laboratory, such increased 'caution' is reflected in post-error slowing of response latencies. Many competing theories exist regarding the precise neural mechanisms underlying post-error slowing. Using transcranial magnetic stimulation, we show that after error commission, the human cortico-motor system is momentarily inhibited, both immediately after an error and during the preparation of the next action. Moreover, motor inhibition during the latter time period is directly predictive of post-error slowing. This shows that inhibitory control is a key mechanism humans engage to regulate their own behavior in the aftermath of error commission.

A causal role for the human subthalamic nucleus in non-selective cortico-motor inhibition.

Common cortico-basal ganglia models of motor control suggest a key role for the subthalamic nucleus (STN) in motor inhibition.1-3 In particular, when already-initiated actions have to be suddenly stopped, the STN is purportedly recruited via a hyperdirect pathway to net inhibit the cortico-motor system in a broad, non-selective fashion.4 Indeed, the suppression of cortico-spinal excitability (CSE) during rapid action stopping extends beyond the stopped muscle and affects even task-irrelevant motor representations.5,6 Although such non-selective CSE suppression has long been attributed to the broad inhibitory influence of STN on the motor system, causal evidence for this association is hitherto lacking. Here, 20 Parkinson's disease patients treated with STN deep-brain stimulation (DBS) and 20 matched healthy controls performed a verbal stop-signal task while CSE was measured from a task-unrelated hand muscle. DBS allowed a causal manipulation of STN, while CSE was measured using transcranial magnetic stimulation (TMS) over primary motor cortex and concurrent electromyography. In patients OFF-DBS and controls, the CSE of the hand was non-selectively suppressed when the verbal response was successfully stopped. Crucially, this effect disappeared when STN was disrupted via DBS in the patient group. Using this unique combination of DBS and TMS during human behavior, the current study provides first causal evidence that STN is likely involved in non-selectively suppressing the physiological excitability of the cortico-motor system during action stopping. This confirms a core prediction of long-held cortico-basal ganglia circuit models of movement. The absence of cortico-motor inhibition during STN-DBS may also provide potential insights into the common side effects of STN-DBS, such as increased impulsivity.7-11.

Novelty-induced frontal-STN networks in Parkinson's disease.

Novelty detection is a primitive subcomponent of cognitive control that can be deficient in Parkinson's disease (PD) patients. Here, we studied the corticostriatal mechanisms underlying novelty-response deficits. In participants with PD, we recorded from cortical circuits with scalp-based electroencephalography (EEG) and from subcortical circuits using intraoperative neurophysiology during surgeries for implantation of deep brain stimulation (DBS) electrodes. We report three major results. First, novel auditory stimuli triggered midfrontal low-frequency rhythms; of these, 1-4 Hz "delta" rhythms were linked to novelty-associated slowing, whereas 4-7 Hz "theta" rhythms were specifically attenuated in PD. Second, 32% of subthalamic nucleus (STN) neurons were response-modulated; nearly all (94%) of these were also modulated by novel stimuli. Third, response-modulated STN neurons were coherent with midfrontal 1-4 Hz activity. These findings link scalp-based measurements of neural activity with neuronal activity in the STN. Our results provide insight into midfrontal cognitive control mechanisms and how purported hyperdirect frontobasal ganglia circuits evaluate new information.

Action errors impair active working memory maintenance.

The ability to detect and correct action errors is paramount to safe and efficient behavior. Its underlying processes are subject of intense scientific debate. The recent adaptive orienting theory of error processing (AOT) proposes that errors trigger a cascade of processes that purportedly begins with a broad suppression of active motoric and-crucially-cognitive processes. While the motoric effects of errors are well established, an empirical test of their purported suppressive effects on active cognitive processes is still missing. Here, we provide data from seven experiments that clearly demonstrate such effects. Participants maintained information in working memory (WM) and performed different response conflict tasks during the delay period. Motor error commission during the delay period consistently reduced accuracy on the WM probe, demonstrating an error-related impairment of WM maintenance. We discuss the broad theoretical and practical implications of this finding, both for the AOT and beyond. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cortico-subcortical ß burst dynamics underlying movement cancellation in humans.

Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, which include the subthalamic nucleus (STN), motor thalamus, and sensorimotor cortex (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the ß frequency (15-29 Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site recordings from SMC and either STN or motor thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical ß-bursts were increased on successful stop-trials. STN bursts in particular were followed within 50 ms by increased ß-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from SMC, thalamus, and STN) confirmed that ß-bursts in STN temporally precede thalamic ß-bursts. This highly unique set of recordings provides empirical evidence for the role of ß-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.

Neurocognitive development of novelty and error monitoring in children and adolescents.

The abilities to monitor one's actions and novel information in the environment are crucial for behavioural and cognitive control. This study investigated the development of error and novelty monitoring and their electrophysiological correlates by using a combined flanker with novelty-oddball task in children (7-12 years) and adolescents (14-18 years). Potential moderating influences of prenatal perturbation of steroid hormones on these performance monitoring processes were explored by comparing individuals who were prenatally exposed and who were not prenatally exposed to synthetic glucocorticoids (sGC). Generally, adolescents performed more accurately and faster than children. However, behavioural adaptations to error or novelty, as reflected in post-error or post-novelty slowing, showed different developmental patterns. Whereas post-novelty slowing could be observed in children and adolescents, error-related slowing was absent in children and was marginally significant in adolescents. Furthermore, the amplitude of error-related negativity was larger in adolescents, whereas the amplitude of novelty-related N2 was larger in children. These age differences suggest that processes involving top-down processing of task-relevant information (for instance, error monitoring) mature later than processes implicating bottom-up processing of salient novel stimuli (for instance, novelty monitoring). Prenatal exposure to sGC did not directly affect performance monitoring but initial findings suggest that it might alter brain-behaviour relation, especially for novelty monitoring.