The pathobiology of psychomotor slowing in psychosis: altered cortical excitability and connectivity.

Psychomotor slowing is a frequent symptom of schizophrenia. Short-interval intracortical inhibition assessed by transcranial magnetic stimulation demonstrated inhibitory dysfunction in schizophrenia. The inhibitory deficit results from additional noise during information processing in the motor system in psychosis. Here, we tested whether cortical inhibitory dysfunction was linked to psychomotor slowing and motor network alterations. In this cross-sectional study, we included 60 patients with schizophrenia and psychomotor slowing determined by the Salpêtrière Retardation Rating Scale, 23 patients without slowing and 40 healthy control participants. We acquired single and double-pulse transcranial magnetic stimulation effects from the left primary motor cortex, resting-state functional connectivity and diffusion imaging on the same day. Groups were compared on resting motor threshold, amplitude of the motor evoked potentials, as well as short-interval intracortical inhibition. Regression analyses calculated the association between motor evoked potential amplitudes or cortical inhibition with seed-based resting-state functional connectivity from the left primary motor cortex and fractional anisotropy at whole brain level and within major motor tracts. In patients with schizophrenia and psychomotor slowing, we observed lower amplitudes of motor evoked potentials, while the short-interval intracortical inhibition/motor evoked potentials amplitude ratio was higher than in healthy controls, suggesting lower cortical inhibition in these patients. Patients without slowing also had lower amplitudes of motor evoked potentials. Across the combined patient sample, cortical inhibition deficits were linked to more motor coordination impairments. In patients with schizophrenia and psychomotor slowing, lower amplitudes of motor evoked potentials were associated with lower fractional anisotropy in motor tracts. Moreover, resting-state functional connectivity between the primary motor cortex, the anterior cingulate cortex and the cerebellum increased with stronger cortical inhibition. In contrast, in healthy controls and patients without slowing, stronger cortical inhibition was linked to lower resting-state functional connectivity between the left primary motor cortex and premotor or parietal cortices. Psychomotor slowing in psychosis is linked to less cortical inhibition and aberrant functional connectivity of the primary motor cortex. Higher neural noise in the motor system may drive psychomotor slowing and thus may become a treatment target.

The phase of tACS-entrained pre-SMA beta oscillations modulates motor inhibition.

Inhibitory control has been linked to beta oscillations in the fronto-basal ganglia network. Here we aim to investigate the functional role of the phase of this oscillatory beta rhythm for successful motor inhibition. We applied 20 Hz transcranial alternating current stimulation (tACS) to the pre-supplementary motor area (pre-SMA) while presenting stop signals at 4 (Experiment 1) and 8 (Experiment 2) equidistant phases of the tACS entrained beta oscillations. Participants showed better inhibitory performance when stop signals were presented at the trough of the beta oscillation whereas their inhibitory control performance decreased with stop signals being presented at the oscillatory beta peak. These results are consistent with the communication through coherence theory, in which postsynaptic effects are thought to be greater when an input arrives at an optimal phase within the oscillatory cycle of the target neuronal population. The current study provides mechanistic insights into the neural communication principles underlying successful motor inhibition and may have implications for phase-specific interventions aimed at treating inhibitory control disorders such as PD or OCD.

Two fundamentally different mechanisms by which unconscious information impairs behavioral performance: Evidence from fMRI and computational modeling.

It is increasingly clear that unconscious information impairs the performance of the corresponding action when the instruction to act is delayed. However, whether this impairment occurs at the response level or at the perceptual level remains controversial. This study used fMRI and a computational model with a pre-post design to address this elusive issue. The fMRI results showed that when the unconscious information containing strong stimulus-response associations was irrelevant to subsequent stimuli, the precuneus in the parietal lobe, which is thought to be involved in sensorimotor processing, was activated. In contrast, when the unconscious information was relevant to subsequent stimuli, regardless of the strength of the stimulus-response associations, some regions in the occipital and temporal cortices, which are thought to be involved in visual perceptual processing, were activated. In addition, the percent signal change in the regions of interest associated with motor inhibition was modulated by compatibility in the irrelevant but not in the relevant stimuli conditions. Modeling of behavioral data further supported that the irrelevant and relevant stimuli conditions involved fundamentally different mechanisms. Our finding reconciles the debate about the mechanism by which unconscious information impairs action performance and has important implications for understanding of unconscious cognition.

Excitatory/inhibitory motor balance reflects individual differences during joint action coordination.

Joint action (JA) is a continuous process of motor co-regulation based on the integration of contextual (top-down) and kinematic (bottom-up) cues from partners. The fine equilibrium between excitation and inhibition in sensorimotor circuits is, thus, central to such a dynamic process of action selection and execution. In a bimanual task adapted to become a unimanual JA task, the participant held a bottle (JA), while a confederate had to reach and unscrew either that bottle or another stabilized by a mechanical clamp (No_JA). Prior knowledge was manipulated in each trial such that the participant knew (K) or not (No_K) the target bottle in advance. Online transcranial magnetic stimulation (TMS) was administered at action-relevant landmarks to explore corticospinal excitability (CSE) and inhibition (cortical silent period [cSP]). CSE was modulated early on before the action started if prior information was available. In contrast, cSP modulation emerged later during the reaching action, regardless of prior information. These two indexes could thus reflect the concurrent elaboration of contextual priors (top-down) and the online sampling of partner's kinematic cues (bottom-up). Furthermore, participants selected either one of two possible behavioural strategies, preferring early or late force exertion on the bottle. One translates into a reduced risk of motor coordination failure and the other into reduced metabolic expenditure. Each strategy was characterised by a specific excitatory/inhibitory profile. In conclusion, the study of excitatory/inhibitory balance paves the way for the neurophysiological determination of individual differences in the combination of top-down and bottom-up processing during JA coordination.

Attentional spatial cueing of the stop-signal affects the ability to suppress behavioural responses.

The ability to adapt to the environment is linked to the possibility of inhibiting inappropriate behaviours, and this ability can be enhanced by attention. Despite this premise, the scientific literature that assesses how attention can influence inhibition is still limited. This study contributes to this topic by evaluating whether spatial and moving attentional cueing can influence inhibitory control. We employed a task in which subjects viewed a vertical bar on the screen that, from a central position, moved either left or right where two circles were positioned. Subjects were asked to respond by pressing a key when the motion of the bar was interrupted close to the circle (go signal). In about 40% of the trials, following the go signal and after a variable delay, a visual target appeared in either one of the circles, requiring response inhibition (stop signal). In most of the trials the stop signal appeared on the same side as the go signal (valid condition), while in the others, it appeared on the opposite side (invalid condition). We found that spatial and moving cueing facilitates inhibitory control in the valid condition. This facilitation was observed especially for stop signals that appeared within 250ms of the presentation of the go signal, thus suggesting an involvement of exogenous attentional orienting. This work demonstrates that spatial and moving cueing can influence inhibitory control, providing a contribution to the investigation of the relationship between spatial attention and inhibitory control.

Impulsivity and inhibitory control in deficit and non-deficit schizophrenia.

BACKGROUND: There is conflicting evidence on impulsivity and its potential relationship with inhibitory control in schizophrenia. This study therefore aimed to identify differences in impulsivity and cognitive and motor inhibition between patients with deficit (DS) and non-deficit (NDS) schizophrenia and healthy controls (HC). We also explored the relationships between impulsivity and different dimensions of inhibitory control in all studied groups. METHODS: The sample comprised 28 DS patients, 45 NDS patients, and 39 age-matched HC. A neuropsychological battery was used. RESULTS: DS patients scored lower in venturesomeness, while those with NDS scored higher in impulsiveness compared to HC. In addition, both groups of patients scored higher on measures of cognitive and motor inhibition, including those relatively independent of information processing speed (although the results were slightly different after adjusting for IQ and/or years of education). Correlations between impulsivity and cognitive inhibition emerged in DS patients, while links between impulsivity and motor inhibition were observed in HC. CONCLUSIONS: Our results suggest the presence of deficits in experimentally assessed inhibitory control in schizophrenia patients, with predominant impulsivity in the NDS population. In addition, impulsivity may affect the cognitive control of inhibition in deficit schizophrenia. Nevertheless, due to the preliminary nature of these findings, they require further empirical verification in future research.

Temperament Traits in Pediatric Obsessive-Compulsive Disorder in Relation to Tourette Syndrome and Attention-Deficit Hyperactivity Disorder.

INTRODUCTION: Pediatric obsessive-compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS) are often concurrent. This study explores the temperament profile of complex OCD phenotypes. METHODS: A clinical registry recorded demographic data, psychiatric diagnoses, and temperament traits, including novelty seeking (exploratory behaviors), harm avoidance (fear of uncertainty), reward dependence (sentimentality), and persistence (perseverance). Temperament data were accrued from the Junior Temperament and Character Inventory (JTCI). Participants were divided into (1) OCD only; (2) OCD+ADHD or TS; and (3) OCD+ADHD+TS to compare temperament. RESULTS: Participants include 126 youths with OCD (61.9% male, 88.9% white) between the ages 6 and 18 years (12.7 ± 3.1). Among the three groups, the complex neurodevelopmental disorder group OCD+ADHD+TS expresses the highest novelty seeking and lowest persistence. Harm avoidance is increased in all groups compared to reference controls, irrespective of concurrent ADHD or TS. For the OCD+ADHD+TS group, contamination and washing symptoms have higher novelty seeking (p < 0.01), while counting and ordering have lower novelty seeking (p < 0.05). Harm avoidance is increased with aggressive, somatic, and checking symptoms in OCD only (p < 0.01), while persistence is increased with repeating and counting symptoms in the comorbid groups (OCD+ADHD or TS, OCD+ADHD+TS). DISCUSSION/CONCLUSION: The complex subtype, OCD+ADHD+TS, is associated with high novelty seeking and low persistence, while high harm avoidance is linked to pediatric OCD irrespective of ADHD or TS co-occurrence. In sum, pediatric OCD with ADHD and TS confers a unique temperament profile, further refining complex phenotypes of pediatric OCD for future research.

Impulsivity in adolescent girls diagnosed with trichotillomania: an evaluation of clinical and neuropsychological characteristics.

The aim of this study is to compare the clinical and neuropsychological features of impulsivity in adolescent girls with trichotillomania (TTM) and healthy controls, and to assess the relationships between the severity of TTM and the impulsivity/concomitant symptoms of anxiety and depression. The study sample consisted of 43 adolescent girls who were 12 to 18 years old. The Kiddie-Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version DSM-5 (K-SADS-PL) was administered to the adolescents and their parents. All of the participants completed a sociodemographic data form, the Revised Children's Anxiety and Depression Scale-Child Version (RCADS-CV), the Barratt Impulsiveness Scale-Brief (BIS-Brief), and the Massachusetts General Hospital Hairpulling Scale (MGH-HPS). The Eriksen Flanker task, the Stop Signal Reaction Time (SSRT) task, the Go/No-Go task, and the Balloon Analog Risk Task (BART) were used to assess behavioral impulsivity. The adolescents with TTM reported higher levels of impulsivity and anxiety/depression symptoms than the healthy controls, and they also performed worse on the behavioral tasks. While there were no relationships between clinical and behavioral impulsivity and TTM severity, social anxiety symptoms were the most important predictor of the severity of TTM. It seems important to better understand the role of impulsivity in the onset and persistence of TTM symptoms in adolescents.

Related neural networks underlie suppression of emotion, memory, motor processes as identified by data-driven analysis.

BACKGROUND: Goal-directed behavior benefits from self-regulation of cognitive and affective processes, such as emotional reactivity, memory retrieval, and prepotent motor response. Dysfunction in self-regulation is a common characteristic of many psychiatric disorders, such as PTSD and ADHD. This study sought to determine whether common intrinsic connectivity networks (ICNs; e.g. default mode network) are involved in the regulation of emotion, motor, and memory processes, and if a data-driven approach using independent component analysis (ICA) would successfully identify such ICNs that contribute to inhibitory regulation. METHODS: Eighteen participants underwent neuroimaging while completing an emotion regulation (ER) task, a memory suppression (Think/No-Think; TNT) task, and a motor inhibition (Stop Signal; SS) task. ICA (CONN; MATLAB) was conducted on the neuroimaging data from each task and corresponding components were selected across tasks based on interrelated patterns of activation. Subsequently, ICNs were correlated with behavioral performance variables from each task. RESULTS: ICA indicated a common medial prefrontal network, striatal network, and frontoparietal executive control network, as well as downregulation in task-specific ROIs. CONCLUSIONS: These results illustrate that common ICNs were exhibited across three distinct inhibitory regulation tasks, as successfully identified through a data-driven approach (ICA).

Suppression of Motor Sequence Learning and Execution Through Anodal Cerebellar Transcranial Electrical Stimulation.

Cerebellum (CB) and primary motor cortex (M1) have been associated with motor learning, with different putative roles. Modulation of task performance through application of transcranial direct current stimulation (TDCS) to brain structures provides causal evidence for their engagement in the task. Studies evaluating and comparing TDCS to these structures have provided conflicting results, however, likely due to varying paradigms and stimulation parameters. Here we applied TDCS to CB and M1 within the same experimental design, to enable direct comparison of their roles in motor sequence learning. We examined the effects of anodal TDCS during motor sequence learning in 60 healthy participants, randomly allocated to CB-TDCS, M1-TDCS, or Sham stimulation groups during a serial reaction time task. Key to the design was an equal number of repeated and random sequences. Reaction times (RTs) to implicitly learned and random sequences were compared between groups using ANOVAs and post hoc t-tests. A speed-accuracy trade-off was excluded by analogous analysis of accuracy scores. An interaction was observed between whether responses were to learned or random sequences and the stimulation group. Post hoc analyses revealed a preferential slowing of RTs to implicitly learned sequences in the group receiving CB-TDCS. Our findings provide evidence that CB function can be modulated through transcranial application of a weak electrical current, that the CB and M1 cortex perform separable functions in the task, and that the CB plays a specific role in motor sequence learning during implicit motor sequence learning.

High-definition transcranial direct current stimulation over right dorsolateral prefrontal cortex differentially modulates inhibitory mechanisms for speech vs. limb movement.

Evidence suggests that planning and execution of speech and limb movement are subserved by common neural substrates. However, less is known about whether they are supported by a common inhibitory mechanism. P3 event-related potentials (ERPs) is a neural signature of motor inhibition, which are found to be generated by several brain regions including the right dorsolateral prefrontal cortex (rDLPFC). However, the relative contribution of rDLPFC to the P3 response associated with speech versus limb inhibition remains elusive. We investigated the contribution of rDLPFC to the P3 underlying speech versus limb movement inhibition. Twenty-one neurotypical adults received both cathodal and sham high-definition transcranial direct current stimulation (HD-tDCS) over rDLPFC. ERPs were subsequently recorded while subjects were performing speech and limb Go/No-Go tasks. Cathodal HD-tDCS decreased accuracy for speech versus limb No-Go. Both speech and limb No-Go elicited a similar topographical distribution of P3, with significantly larger amplitudes for speech versus limb at a frontocentral location following cathodal HD-tDCS. Moreover, results showed stronger activation in cingulate cortex and rDLPFC for speech versus limb No-Go following cathodal HD-tDCS. These results indicate (1) P3 is an ERP marker of amodal inhibitory mechanisms that support both speech and limb inhibition, (2) larger P3 for speech versus limb No-Go following cathodal HD-tDCS may reflect the recruitment of additional neural resources-particularly within rDLPFC and cingulate cortex-as compensatory mechanisms to counteract the temporary stimulation-induced decline in speech inhibitory process. These findings have translational implications for neurological conditions that concurrently affect speech and limb movement.

How does Go/No-Go training lead to food devaluation? Separating the effects of motor inhibition and response valence.

Palatable, unhealthy food stimuli can be devalued via Go/No-Go (GNG) training that consistently pairs such stimuli with motor inhibition. However, it remains unclear whether this devaluation is caused via learned associations with motor inhibition or via inferential learning based on the valence of emitted motor responses. The present research disentangles the effects of motor assignment and response valence in GNG training through task instructions. In two studies, chocolate stimuli were consistently paired with motor inhibition ("no-go") or with motor excitation ("go"). Task instructions indicated that no-go responses were negatively valenced ("do not take") and that go responses were positively valenced ("take"), or identified no-go responses as positively valenced ("keep") and go as negatively valenced ("throw away"). The results show an effect of response valence on chocolate evaluations, but no effect of motor assignment: Chocolate stimuli were consistently devalued following pairings with a negatively valenced response, regardless of whether this response entailed motor inhibition or excitation. These findings align best with an inferential account of GNG training, suggesting that devaluation effects critically depend on inferential processes regarding motor response valence. GNG training procedures may, therefore, be optimised by disambiguating the valence of go and no-go motor responses prior to training.

The Role of State and Trait Self-Control on the Sustained Attention to Response Task.

OBJECTIVE: This study aimed to assess the plausibility of self-control depletion, or ego-depletion, as the underlying cognitive resource responsible for performance decrements on the sustained attention to response task. BACKGROUND: Researchers suggested that self-control is a limited cognitive resource used to complete a myriad of processes, including sustained attention. Past research showed that trait self-control affects some sustained attention tasks. However, little research has investigated the effect of self-control as a limited cognitive resource that varies over time (i.e., as a state-dependent variable). METHODS: This experiment investigated the effect of self-control (trait and state) on a sustained motor-inhibition task (e.g., sustained attention to response task; SART). State self-control was manipulated using a between-subjects design-participants in the experimental condition completed a task designed to deplete state self-control prior to performing the SART while the control condition completed a modified version that did not deplete self-control. RESULTS: Trait self-control predicted performance on the SART, but the depletion task (state self-control) had no detectable effect. CONCLUSION: Given the evidence, it is unlikely that state self-control plays a causal role in performance decrements in the SART, but there appears to be some association between performance on the SART and trait self-control. APPLICATION: Trait self-control ought to be considered in future work for personnel selection in real-world tasks that the SART models such as long-distance driving, air traffic control, and TSA operations.

Common and Unique Inhibitory Control Signatures of Action-Stopping and Attentional Capture Suggest That Actions Are Stopped in Two Stages.

The ability to stop an already initiated action is paramount to adaptive behavior. Much scientific debate in the field of human action-stopping currently focuses on two interrelated questions. (1) Which cognitive and neural processes uniquely underpin the implementation of inhibitory control when actions are stopped after explicit stop signals, and which processes are instead commonly evoked by all salient signals, even those that do not require stopping? (2) Why do purported (neuro)physiological signatures of inhibition occur at two different latencies after stop signals? Here, we address both questions via two preregistered experiments that combined measurements of corticospinal excitability, EMG, and whole-scalp EEG. Adult human subjects performed a stop signal task that also contained "ignore" signals: equally salient signals that did not require stopping but rather completion of the Go response. We found that both stop- and ignore signals produced equal amounts of early-latency inhibition of corticospinal excitability and EMG, which took place ∼150 ms following either signal. Multivariate pattern analysis of the whole-scalp EEG data further corroborated that this early processing stage was shared between stop- and ignore signals, as neural activity following the two signals could not be decoded from each other until a later time period. In this later period, unique activity related to stop signals emerged at frontocentral scalp sites, reflecting an increased stop signal P3. These findings suggest a two-step model of action-stopping, according to which an initial, universal inhibitory response to the saliency of the stop signal is followed by a slower process that is unique to outright stopping.SIGNIFICANCE STATEMENT Humans often have to stop their ongoing actions when indicated by environmental stimuli (stop signals). Successful action-stopping requires both the ability to detect these salient stop signals and to subsequently inhibit ongoing motor programs. Because of this tight entanglement of attentional control and motor inhibition, identifying unique neurophysiological signatures of action-stopping is difficult. Indeed, we report that recently proposed early-latency signatures of motor inhibition during action-stopping are also found after salient signals that do not require stopping. However, using multivariate pattern analysis of scalp-recorded neural data, we also identified subsequent neural activity that uniquely distinguished action-stopping from saliency detection. These results suggest that actions are stopped in two stages: the first common to all salient events and the second unique to action-stopping.

Neuromodulation in Beta-Band Power Between Movement Execution and Inhibition in the Human Hippocampus.

INTRODUCTION: The hippocampus is thought to be involved in movement, but its precise role in movement execution and inhibition has not been well studied. Previous work with direct neural recordings has found beta-band (13-30 Hz) modulation in both movement execution and inhibition throughout the motor system, but the role of beta-band modulation in the hippocampus during movement inhibition is not well understood. Here, we perform a Go/No-Go reaching task in ten patients with medically refractory epilepsy to study human hippocampal beta-power changes during movement. MATERIALS AND METHODS: Ten epilepsy patients (5 female; ages 21-46) were implanted with intracranial depth electrodes for seizure monitoring and localization. Local field potentials were sampled at 2000 Hz during a Go/No-Go movement task. Comparison of beta-band power between Go and No-Go conditions was conducted using Wilcoxon signed-rank hypothesis testing for each patient. Sub-analyses were conducted to assess differences in the anterior vs posterior contacts, ipsilateral vs contralateral contacts, and male vs female beta-power values. RESULTS: Eight out of ten patients showed significant beta-power decreases during the Go movement response (p < 0.05) compared to baseline. Eight out of ten patients also showed significant beta-power increases in the No-Go condition, occurring in the absence of movement. No significant differences were noted between ipsilateral vs contralateral contacts nor in anterior vs posterior hippocampal contacts. Female participants had a higher task success rate than males and had significantly greater beta-power increases in the No-Go condition (p < 0.001). CONCLUSION: These findings indicate that increases in hippocampal beta power are associated with movement inhibition. To the best of our knowledge, this study is the first to report this phenomenon in the human hippocampus. The beta band may represent a state-change signal involved in motor processing. Future focus on the beta band in understanding human motor and impulse control will be vital.

ß-Bursts Reveal the Trial-to-Trial Dynamics of Movement Initiation and Cancellation.

The neurophysiological basis of motor control is of substantial interest to basic researchers and clinicians alike. Motor processes are accompanied by prominent field potential changes in the ß-frequency band (15-29 Hz): in trial-averages, movement initiation is accompanied by ß-band desynchronization over sensorimotor areas, whereas movement cancellation is accompanied by ß-power increases over (pre)frontal areas. However, averaging misrepresents the true nature of the ß-signal. Unaveraged ß-band activity is characterized by short-lasting, burst-like events, rather than by steady modulations. Therefore, averaging-based quantifications may miss important brain-behavior relationships. To investigate how ß-bursts relate to movement in male and female humans (N = 234), we investigated scalp-recorded ß-band activity during the stop-signal task, which operationalizes both movement initiation and cancellation. Both processes were indexed by systematic spatiotemporal changes in ß-burst rates. Before movement initiation, ß-bursting was prominent at bilateral sensorimotor sites. These burst-rates predicted reaction time (a relationship that was absent in trial-average data), suggesting that sensorimotor ß-bursting signifies an inhibited motor system, which has to be overcome to initiate movements. Indeed, during movement initiation, sensorimotor burst-rates steadily decreased, lateralizing just before movement execution. In contrast, successful movement cancellation was signified by increased phasic ß-bursting over fronto-central sites. Such ß-bursts were followed by short-latency increases of bilateral sensorimotor ß-burst rates, suggesting that motor inhibition can be rapidly re-instantiated by frontal areas when movements have to be rapidly cancelled. Together, these findings suggest that ß-bursting is a fundamental signature of the motor system, used by both sensorimotor and frontal areas involved in the trial-by-trial control of behavior.SIGNIFICANCE STATEMENT Movement-related ß-frequency (15-29 Hz) changes are among the most prominent features of neural recordings across species, scales, and methods. However, standard averaging-based methods obscure the true dynamics of ß-band activity, which is dominated by short-lived, burst-like events. Here, we demonstrate that both movement-initiation and cancellation in humans are characterized by unique trial-to-trial patterns of ß-bursting. Movement initiation is characterized by steady reductions of ß-bursting over bilateral sensorimotor sites. In contrast, during rapid movement cancellation, ß-bursts first emerge over fronto-central sites typically associated with motor control, after which sensorimotor ß-bursting re-initiates. These findings suggest a fundamentally novel, non-invasive measure of the neural interaction underlying movement-initiation and -cancellation, opening new avenues for the study of motor control in health and disease.

Paired-pulse TMS and scalp EEG reveal systematic relationship between inhibitory GABAa signaling in M1 and fronto-central cortical activity during action stopping.

By stopping actions even after their initiation, humans can flexibly adapt ongoing behavior to changing circumstances. The neural processes underlying the inhibition of movement during action stopping are still controversial. In the 90s, a fronto-central event-related potential (ERP) was discovered in the human EEG response to stop signals in the classic stop-signal task, alongside a proposal that this "stop-signal P3" reflects an inhibitory process. Indeed, both amplitude and onset of the stop-signal P3 relate to overt behavior and movement-related EEG activity in ways predicted by the dominant models of action-stopping. However, neither EEG nor behavior allow direct inferences about the presence or absence of neurophysiological inhibition of the motor cortex, making it impossible to definitively relate the stop-signal P3 to inhibition. Here, we therefore present a multimethod investigation of the relationship between the stop-signal P3 and GABAergic signaling in primary motor cortex, as indexed by paired-pulse transcranial magnetic stimulation (TMS). In detail, we measured short-interval intracortical inhibition (SICI), a marker of inhibitory GABAa activity in M1, in a group of 41 human participants who also performed the stop-signal task while undergoing EEG recordings. In line with the P3-inhibition hypothesis, we found that subjects with stronger inhibitory GABA activity in M1 also showed both faster onsets and larger amplitudes of the stop-signal P3. This provides direct evidence linking the properties of this ERP to a true physiological index of motor system inhibition. We discuss these findings in the context of recent theoretical developments and empirical findings regarding the neural implementation of motor inhibition.NEW & NOTEWORTHY The neural mechanisms underlying rapid action stopping in humans are subject to intense debate, in part because recordings of neural signals purportedly reflecting inhibitory motor control are hard to directly relate to the true, physiological inhibition of motor cortex. For the first time, the current study combines EEG and transcranial magnetic stimulation (TMS) methods to demonstrate a direct correspondence between fronto-central control-related EEG activity following signals to cancel an action and the physiological inhibition of primary motor cortex.

Inhibitory Control of Adjacent Finger Movements while Performing a Modified Version of the Halstead Finger Tapping Test: Effects of Age, Education and Sex.

OBJECTIVE: Selective motor inhibition is known to decline with age. The purpose of this study was to determine the frequency of failures at inhibitory control of adjacent finger movements while performing a repetitive finger tapping task in young, middle-aged and older adults. Potential education and sex effects were also evaluated. METHODS: Kinematic recordings of adjacent finger movements were obtained on 107 healthy adults (ages 20-80) while they performed a modified version of the Halstead Finger Tapping Test (HTFF). Study participants were instructed to inhibit all finger movements while tapping with the index finger. RESULTS: Inability to inhibit adjacent finger movements while performing the task was infrequent in young adults (2.9% of individuals between 20 and 39 years of age) but increased with age (23.3% between the ages of 40 and 59; 31.0% between ages 60 and 80). Females and males did not differ in their inability to inhibit adjacent finger movements, but individuals with a college education showed a lower frequency of failure to inhibit adjacent finger movements (10.3%) compared to those with a high school education (28.6%). These findings were statistically significant only for the dominant hand. CONCLUSION: Selective motor inhibition failures are most common in the dominant hand and occur primarily in older healthy adults while performing the modified version of the HFTT. Monitoring selective motor inhibition failures may have diagnostic significance.

Long-term limb immobilization modulates inhibition-related electrophysiological brain activity.

The effect of long-term immobilization on the motor system has been described during motor preparation, imagination or execution, when the movement has to be performed. But, what happens when the movement has to be suppressed? Does long-term limb immobilization modulate physiological responses underlying motor inhibition? Event-related potentials (ERPs) were recorded in healthy participants performing a Go/Nogo task, either with both hands free to respond (T1/T4: before/after the immobilization) or when left-hand movements were prevented by a cast (T2: as soon as the cast was positioned; T3: after one week of immobilization). In the right (control) side, N140, N2, and P3 components showed the expected greater amplitude in Nogo than in Go trials, irrespective of the timepoint. On the contrary, in the left (manipulated) side, each component of the ERP responses to Nogo trials showed specific differences across timepoints, suggesting that the inhibition-related EEG activity is significantly reduced by the presence of the cast and the duration of the immobilization. Furthermore, inhibition-related theta band activity to Nogo stimuli decreased at post-immobilization blocked session (T3-blocked). Altogether these findings can be interpreted as a consequence of the plastic changes induced by the immobilization, as also demonstrated by the cast-related corticospinal excitability modulation (investigated by using TMS) and by the decreased beta band in response to Go and Nogo trials. Thus, only if we are free to move, then inhibitory responses are fully implemented. After one week of immobilization, the amount of inhibition necessary to block the movement is lower and, consequently, inhibitory-related responses are reduced.

Non-selective inhibition of the motor system following unexpected and expected infrequent events.

Motor inhibition is a key control mechanism that allows humans to rapidly adapt their actions in response to environmental events. One of the hallmark signatures of rapidly exerted, reactive motor inhibition is the non-selective suppression of cortico-spinal excitability (CSE): unexpected sensory stimuli lead to a suppression of CSE across the entire motor system, even in muscles that are inactive. Theories suggest that this reflects a fast, automatic, and broad engagement of inhibitory control, which facilitates behavioral adaptations to unexpected changes in the sensory environment. However, it is an open question whether such non-selective CSE suppression is truly due to the unexpected nature of the sensory event, or whether it is sufficient for an event to be merely infrequent (but not unexpected). Here, we report data from two experiments in which human subjects experienced both unexpected and expected infrequent events during a two-alternative forced-choice reaction time task while CSE was measured from a task-unrelated muscle. We found that expected infrequent events can indeed produce non-selective CSE suppression-but only when they occur during movement initiation. In contrast, unexpected infrequent events produce non-selective CSE suppression relative to frequent, expected events even in the absence of movement initiation. Moreover, CSE suppression due to unexpected events occurs at shorter latencies compared to expected infrequent events. These findings demonstrate that unexpectedness and stimulus infrequency have qualitatively different suppressive effects on the motor system. They also have key implications for studies that seek to disentangle neural and psychological processes related to motor inhibition and stimulus detection.