Inhibition In Cortex Research Articles

Altered motor system function in post-concussion syndrome as assessed via transcranial magnetic stimulation

ObjectiveIt is unclear why specific individuals incur chronic symptoms following a concussion. This exploratory research aims to identify and characterize any neurophysiological differences that may exist in motor cortex function in post-concussion syndrome (PCS). MethodsFifteen adults with PCS and 13 healthy, non-injured adults were tested. All participants completed symptom questionnaires, and transcranial magnetic stimulation (TMS) was used to measure intracortical and transcallosal excitability and inhibition in the dominant motor cortex. ResultsCortical silent period (p = 0.02, g = 0.96) and ipsilateral silent period (p = 0.04, g = 0.78) were shorter in the PCS group compared to the control group which may reflect reduced GABA-mediated inhibition in PCS. Furthermore, increased corticomotor excitability was observed in the left hemisphere but not the right hemisphere. ConclusionsThese data suggest that persistent neurophysiological differences are present in those with PCS. The exact contributing factors to such changes remain to be investigated by future studies. SignificanceThis study provides novel evidence of lasting neurophysiological changes in PCS.

Attention Networks in the Parietooccipital Cortex Modulate Activity of the Human Vestibular Cortex during Attentive Visual Processing.

Previous studies in human subjects reported that the parieto-insular vestibular cortex (PIVC), a core area of the vestibular cortex, is inhibited when visual processing is prioritized. However, it has remained unclear which networks in the brain modulate this inhibition of PIVC. Based on previous results showing that the inhibition of PIVC is strongly influenced by visual attention, we here examined whether attention networks in the parietooccipital cortex modulate the inhibition of PIVC. Using diffusion-weighted and resting-state fMRI in a group of female and male subjects, we found structural and functional connections between PIVC and the posterior parietal cortex (PPC), a major brain region of the cortical attention network. We then temporarily inhibited PPC by repetitive transcranial magnetic stimulation (rTMS) and hypothesized that the modulatory influence of PPC over PIVC would be reduced; and, as a result, PIVC would be less inhibited. Subjects performed a visual attentional tracking task immediately after rTMS, and the inhibition of PIVC during attentive tracking was measured with fMRI. The results showed that the inhibition of PIVC during attentive tracking was less pronounced compared with sham rTMS. We also examined the effects of inhibitory rTMS over the occipital cortex and found that the visual-vestibular posterior insular cortex area was less activated during attentive tracking compared with sham rTMS or rTMS over PPC. Together, these results suggest that attention networks in the parietooccipital cortex modulate activity in core areas of the vestibular cortex during attentive visual processing.SIGNIFICANCE STATEMENT Although multisensory integration is generally considered beneficial, it can become detrimental when cues from different senses are in conflict. The occurrence of such multisensory conflicts can be minimized by inhibiting core cortical areas of the subordinate sensory system (e.g., vestibular), thus reducing potential conflict with ongoing processing of the prevailing sensory (e.g., visual) cues. However, it has remained unclear which networks in the brain modulate the magnitude of inhibition of the subordinate sensory system. Here, by investigating the inhibition of the vestibular sensory system when visual processing is prioritized, we show that attention networks in the parietooccipital cortex modulate the magnitude of inhibition of the vestibular cortex.

Analysis of difference in activation or inhibition of cerebral cortex during induction of and emergence from general anesthesia: functional near-infrared spectroscopy

Objective To investigate the brain mechanism of anesthesia-related loss of consciousness and awakening though measuring activation or inhibition of cerebral cortex during induction of and emergence from general anesthesia using functional near-infrared spectroscopy. Methods Twenty-two American Society of Anesthesiologists physical status Ⅰor Ⅱ patients of both sexes, aged 40-80 yr, undergoing thoracoscopic partial lung resection, were selected. The functional near-infrared spectroscopy was used to determine the level of oxyhemoglobin in cerebral cortex before and after anesthesia induction and before and after emergence from anesthesia, and a positive number was considered as activation and a negative number as inhibition. Results Compared with the baseline before anesthesia induction, the level of oxyhemoglobin in the premotor cortex was significantly decreased (P 0.05). Conclusion Frontopolar area is activated, and premotor cortex is inhibited during induction of general anesthesia, indicating that induction of anesthesia may first affect the integrated function of management and execution of the brain, and the motor regulation ability is weakened. Individual difference in brain areas activated during emergence from anesthesia is larger, and activated and inhibited brain regions are not found. Key words: Anesthesia, general; Cerebral cortex; Spectroscopy, near-infrared

Longitudinal assessment of 1H-MRS (GABA and Glx) and TMS measures of cortical inhibition and facilitation in the sensorimotor cortex.

The purpose of the present study was to investigate the long-term stability of water-referenced GABA and Glx neurometabolite concentrations in the sensorimotor cortex using MRS and to assess the long-term stability of GABA- and glutamate-related intracortical excitability using transcranial magnetic stimulation (TMS). Healthy individuals underwent two sessions of MRS and TMS at a 3-month interval. A MEGA-PRESS sequence was used at 3T to acquire MRS signals in the sensorimotor cortex. Metabolites were quantified by basis spectra fitting and metabolite concentrations were derived using unsuppressed water reference scans accounting for relaxation and partial volume effects. TMS was performed using published standards. After performing stability and reliability analyses for MRS and TMS, reliable change indexes were computed for all measures with a statistically significant test-retest correlation. No significant effect of time was found for GABA, Glx and TMS measures. There was an excellent ICC and a strong correlation across time for GABA and Glx. Analysis of TMS measure stability revealed an excellent ICC for rMT CSP and %MSO and a fair ICC for 2ms SICI. There was no significant correlation between MRS and TMS measures at any time point. This study shows that MRS-GABA and MRS-Glx of the sensorimotor cortex have good stability over a 3-month period, with variability across time comparable to that reported in other brain areas. While resting motor threshold, %MSO and CSP were found to be stable and reliable, other TMS measures had greater variability and lesser reliability.

Temporal Dynamics of Corticocortical Inhibition in Human Visual Cortex: A TMS Study

Paired-pulse transcranial magnetic stimulation (ppTMS) has been used extensively to probe local facilitatory and inhibitory function in motor cortex. We previously developed a reliable ppTMS method to investigate these functions in visual cortex and found reduced thresholds for net intracortical inhibition compared to motor cortex. The current study used this method to investigate the temporal dynamics of local facilitatory and inhibitory networks in visual cortex in 28 healthy subjects. We measured the size of the visual disturbance (phosphene) evoked by stimulating visual cortex with a fixed intensity, supra-threshold test stimulus (TS) when that TS was preceded by a sub-threshold conditioning stimulus (CS). We manipulated the inter-stimulus interval (ISI) and assessed how the size of the phosphene elicited by the fixed-intensity TS changed as a function of interval for two different CS intensities (45% and 75% of phosphene threshold). At 45% of threshold, the CS produced uniform suppression of the phosphene elicited by the TS across ISIs ranging from 2 to 200 ms. At 75% of threshold, the CS did not have a significant effect on phosphene size across the 2–15 ms intervals. Intervals of 50–200 ms exhibited statistically significant suppression of phosphenes, however, suppression was not uniform with some subjects demonstrating no change or facilitation. This study demonstrates that the temporal dynamics of local inhibitory and facilitatory networks are different across motor and visual cortex and that optimal parameters to index local inhibitory and facilitatory influences in motor cortex are not necessarily optimal for visual cortex. We refer to the observed inhibition as visual cortex inhibition (VCI) to distinguish it from the phenomenon reported in motor cortex.

Inhibition of the left medial prefrontal cortex (mPFC) prolongs the social defeat-induced anxiogenesis in mice: Attenuation by NMDA receptor blockade in the right mPFC

Chemical inhibition and nitrergic stimulation of the left and right medial prefrontal cortex (L and RmPFC), respectively, provoke anxiety in mice. Moreover, LmPFC inhibition immediately followed by a single social defeat stress (SDS) led to anxiogenesis in mice exposed to the elevated plus maze (EPM) 24 h later. Given that glutamate NMDA (N-methyl-D-aspartate) receptors are densely present in the mPFC, we investigated (i) the time course of LmPFC inhibition + SDS-induced anxiogenesis and (ii) the effects of intra-RmPFC injection of AP-7 (a NMDA receptor antagonist) on this long-lasting anxiety. Male Swiss mice received intra-LmPFC injection of CoCl2 (1 mM) and 10 min later were subjected to a single SDS episode and then (i) exposed to the EPM 2, 5, or 10 days later or (ii) 2 days later, received intra-RmPFC injection of AP-7 (0.05 nmol) and were exposed to the EPM to observe the percentage of open arm entries and time (%OE; %OT) and frequency of closed arm entries (CE). Dorsal but not ventral LmPFC inhibition + SDS reduced open arm exploration 2, 5, and 10 days later relative to that of saline-treated or non-defeated mice. Moreover, this effect is not due to locomotor impairment as assessed using the general activity. Intra-RmPFC AP-7 injection 2 days after LmPFC inhibition + SDS prevented this type of anxiogenesis. These results suggest that the integrity of the LmPFC is important for mice to properly cope with SDS, and that NMDA receptor blockade in the RmPFC facilitates resilience to SDS-induced anxiogenesis in mice.

Spatial Clustering of Inhibition in Mouse Primary Visual Cortex

Whether mouse visual cortex contains orderly feature maps is debated. The overlapping pattern of geniculocortical inputs with M2 muscarinic acetylcholine receptor-rich patches in layer 1 (L1) suggests a non-random architecture. Here, we found that L1 inputs from the lateral posterior thalamus (LP) avoid patches and target interpatches. Channelrhodopsin-2-assisted mapping of excitatory postsynaptic currents (EPSCs) in L2/3 shows that the relative excitation of parvalbumin-expressing interneurons (PVs) and pyramidal neurons (PNs) by dLGN, LP, and cortical feedback is distinct and depends on whether the neurons reside in clusters aligned with patches or interpatches. Paired recordings from PVs and PNs show that unitary inhibitory postsynaptic currents (uIPSCs) are larger in interpatches than in patches. The spatial clustering of inhibition is matched by dense clustering of PV terminals in interpatches. The results show that the excitation/inhibition balance across V1 is organized into patch and interpatch subnetworks, which receive distinct long-range inputs and are specialized for the processing of distinct spatiotemporal features.

Responding to Sensorimotor Suggestions: From Endothelial Nitric Oxide to the Functional Equivalence Between Imagery and Perception

The reduced cerebellar gray matter (GM) volume observed in highly hypnotizable individuals (highs) is likely due to the excessive release of endothelial nitric oxide in the brain and could account for their behavioral (postural and visuomotor control) and physiological (paradoxical pain control after cerebellar anodal stimulation) characteristics. Reduced cerebellar GM can induce low inhibition of the cerebral cortex, thus stronger functional equivalence (FE) between imagery and perception and greater proneness to respond to sensorimotor suggestions. In fact, stronger FE suggested in highs by behavioral studies has been confirmed by topological data analysis of EEG signals recorded during sensorimotor and imagery tasks. The authors’ hypothesis cannot be applied to obstructive suggestions likely sustained by mechanisms related to socio-cognitive factors, i.e., oxytocin availability.

Short-interval intracortical inhibition in human primary motor cortex: A multi-locus transcranial magnetic stimulation study

Short-interval intracortical inhibition (SICI) has been studied with paired-pulse transcranial magnetic stimulation (TMS) by administering two pulses at a millisecond-scale interstimulus interval (ISI) to a single cortical target. It has, however, been difficult to study the interaction of nearby cortical targets with paired-pulse TMS. To overcome this limitation, we have developed a multi-locus TMS (mTMS) device, which allows controlling the stimulus location electronically. Here, we applied mTMS to study SICI in primary motor cortex with paired pulses targeted to adjacent locations, aiming to quantify the extent of the cortical region producing SICI in the location of a test stimulus. We varied the location and timing of the conditioning stimulus with respect to a test stimulus targeted to the cortical hotspot of the abductor pollicis brevis (APB) in order to study their effects on motor evoked potentials. We further applied a two-coil protocol with the conditioning stimulus given by an oval coil only to the surroundings of the APB hotspot, to which a subsequent test stimulus was administered with a figure-of-eight coil. The strongest SICI occurred at ISIs below 1 ms and at ISIs around 2.5 ms. These ISIs increased when the conditioning stimulus receded from the APB hotspot. Our two-coil paired-pulse TMS study suggests that SICI at ISIs of 0.5 and 2.5 ms originate from different mechanisms or neuronal elements.

Optogenetic inhibition of the medial prefrontal cortex reduces methamphetamine-primed reinstatement in male and female rats.

Preclinical findings suggest sex-differences exist in drug-seeking behavior following methamphetamine (METH) self-administration. The medial prefrontal cortex (mPFC), is thought to contribute to the reinstatement of drug-seeking in males. Glutamatergic neurons project from the prelimbic portion of the mPFC to various brain regions modulating activity including the nucleus accumbens; thus the prelimbic region of the mPFC is thought to contribute to drug-seeking behaviors. Although studied in males, little research has investigated the role of the mPFC in females. The purpose of this study was to investigate if the prelimbic portion of the mPFC plays a role in METH-seeking behavior in both male and female rats. Animals were allowed to self-administer METH, and underwent extinction and two reinstatement sessions. Reinstatement sessions were counterbalanced such that optogenetic inhibition targeting the prelimbic cortex of the mPFC occurred only during one reinstatement session. Results revealed an increase in METH consumption during self-administration in male and female animals. During extinction, lever-pressing behavior decreased as training progressed. Under sham conditions, female rats exhibited significantly higher drug-seeking behavior during reinstatement. However, when optogenetic inhibition was applied, both male and female animals significantly decreased drug-seeking. In both males and females, the prelimbic portion of the mPFC plays an important role in drug-seeking behavior as related to METH-seeking.

The Current and Future Potential of Transcranial Magnetic Stimulation With Electroencephalography in Psychiatry.

The search for biological targets in psychiatric disorders is essential to better understand illness mechanisms and also to monitor and predict response to currently available therapeutic interventions. To this end, the combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) has emerged as a powerful clinical research tool. TMS-EEG allows cortical properties, such as excitability, inhibition, oscillatory activity, and connectivity, to be directly probed within a specific region of the cortex. This review will summarize the state of the current literature on TMS-EEG and its potential to uncover biological targets in psychiatric illnesses, with a focus on major depressive disorder, bipolar disorder, and schizophrenia. Collectively, the reviewed studies suggest that alterations ingamma-aminobutyric acid-mediated inhibition and gamma oscillations in the dorsolateral prefrontal cortex and neighboring frontal regions are potential shared biomarkers in psychiatry, highlighting the potential of TMS-EEG to help identify translational biomarkers.

Slower Binocular Rivalry in the Autistic Brain.

Autism has traditionally been regarded as a disorder of the social brain. Recent reports of differences in visual perception have challenged this notion, but little evidence for altered visual processing in the autistic brain exists. We have previously observed slower behaviorally reported rates of a basic visual phenomenon, binocular rivalry, in autism [1, 2]. During rivalry, two images-one presented to each eye-vie for awareness, alternating back and forth in perception. This competition is modeled to rely, in part, on the balance of excitation and inhibition in visual cortex [3-8], which may be altered in autism [2, 9-14]. Yet direct neural evidence for this potential marker of excitation/inhibition (E/I) balance in autism is lacking. Here, we report a striking alteration in the neural dynamics of binocular rivalry in individuals with autism. Participants viewed true and simulated frequency-tagged binocular rivalry displays while steady-state visually evoked potentials (SSVEPs) were measured over occipital cortex using electroencephalography (EEG). First, we replicate our prior behavioral findings of slower rivalry and reduced perceptual suppression in individuals with autism compared with controls. Second, we provide direct neural evidence for slower rivalry in autism compared with controls, which strongly predicted individuals' behavioral switch rates. Finally, using neural data alone, we were able to predict autism symptom severity (ADOS) and correctly classify individuals' diagnostic status (autistic versus control; 87% accuracy). These findings clearly implicate atypical visual processing in the neurobiology of autism. Down the road, this paradigm may serve as a non-verbal marker of autism for developmental and cross-species research.

What is the effect of bodily illusions on corticomotoneuronal excitability? A systematic review.

BackgroundThis systematic review aimed to summarise and critically appraise the evidence for the effect of bodily illusions on corticomotoneuronal excitability.MethodsFive databases were searched, with two independent reviewers completing study inclusion, risk of bias, transcranial magnetic stimulation (TMS) reporting quality, and data extraction. Included studies evaluated the effect of an illusion that altered perception of the body (and/or its movement) on excitability of motor circuitry in healthy, adult, human participants. Studies were required to: use TMS to measure excitability and/or inhibition; report quantitative outcomes (e.g., motor evoked potentials); compare the illusion to a control or active comparison condition; evaluate that an illusion had occurred (e.g., measured illusion strength/presence).ResultsOf 2,257 studies identified, 11 studies (14 experiments) were included, evaluating kinaesthetic illusions (n = 5), a rubber hand illusion (RHI) paradigm (n = 5), and a missing limb illusion (n = 1). Kinaesthetic illusions (induced via vision/tendon vibration) increased corticomotoneuronal excitability. Conflicting effects were found for traditional, visuotactile RHIs of a static hand. However, embodying a hand and then observing it move (“self-action”) resulted in decreased corticomotoneuronal excitability and increased silent period duration (a measure of Gamma-Aminobutynic acid [GABA]B-mediated intracortical inhibition in motor cortex), with the opposite occurring (increased excitability, decreased inhibition) when the fake hand was not embodied prior to observing movement (“other-action”). Visuomotor illusions manipulating agency had conflicting results, but in the lower risk study, illusory agency over movement resulted in a relative decrease in corticomotoneuronal excitability. Last, an illusion of a missing limb reduced corticomotoneuronal excitability.ConclusionWhile evidence for the effect of bodily illusions on corticomotoneuronal excitability was limited (only 14 experiments) and had a high risk of bias, kinaesthetic illusions and illusions of embodying a hand (and seeing it move), had consistent effects. Future investigations into the role of embodiment and the illusion strength on corticomotoneuronal excitability and inhibition are warranted.

Lack of evidence for interhemispheric inhibition in the lower face primary motor cortex

ObjectiveTo investigate interhemispheric inhibition (IHI) between the facial primary motor cortices (fM1s). MethodsIHI was investigated in 10 healthy subjects using paired-pulse TMS in the depressor anguli oris (DAO), upper trapezius (UT) and first dorsal interosseous (FDI) muscles. Conditioning stimuli (CS) of 90–130% resting motor threshold (RMT) preceded test motor evoked potentials (MEPs) by 7 interstimulus intervals (ISIs) ranging 4–12 ms. In the DAO, we also examined IHI at 1–2 ms ISIs. ResultsIHI was detected in the UT (CS 130% RMT; ISI 8 ms; p = 0.02) and FDI (CS 120% and 130% RMT, at 8–10 ms ISIs; p = 0.004), but not in DAO at any ISI, instead, there was facilitation at 1–4 ms ISIs and 110–130% RMT CS. In the DAO, conditioned responses at 1–4 ms ISIs were significantly larger than both test MEPs and the response induced by the CS alone. ConclusionIn the DAO there was no evidence of IHI even though this was clear in hand and axial muscles. Control experiments excluded a transcallosal origin of the facilitation observed at the shortest intervals. SignificanceData suggest that integrated bilateral control of facial muscles occurs mainly at the level of brainstem circuits engaged by corticobulbar output from fM1.

Inhibitory neuronal changes following a mixed diffuse-focal model of traumatic brain injury.

Traumatic brain injury (TBI) can result in excitation: inhibition imbalance, as well as a range of chronic neurological deficits. However, how TBI affects different interneurons, and how this relates to behavioral abnormalities, remains poorly understood. This study examined the effects of a mixed diffuse-focal model of TBI, the lateral fluid percussion injury (LFPI), on interneurons, 8 weeks post-TBI in rats. Brains were labeled with antibodies against calbindin, parvalbumin, calretinin, neuropeptide Y, and somatostatin, and the number of interneurons were assessed in the cortex and hippocampus following LFPI. LFPI caused a reduction in the numbers of interneurons mediating both perisomatic and dendritic inhibition in the somatosensory cortex. In hippocampus, there were heterogenous changes in the number of interneurons while motor cortex, showed no obvious loss in any of the subsets of interneurons after TBI. In parallel to the investigations of changes in the number of interneurons, we also investigated the long-term behavioral consequences of LFPI. Behaviorally, rats given an LFPI displayed transient reduction in performance in motor tasks and were significantly impaired in reversal learning in the water maze task post-TBI. We also report here progressive neurodegeneration in cortex and hippocampus indicated by Fluoro-Jade C in the different brain areas examined after injury. Our findings suggest differential vulnerability of inhibitory neurons to LFPI in the different brain areas examined after injury. These data will aid in evaluation of new treatments for TBI and help target specific neuronal subtypes as a function of injury time and type.

P2-11-03. TMS over the contralateral primary visual cortex induces cortico-cortical inhibition in the primary motor cortex

P2-11-03. TMS over the contralateral primary visual cortex induces cortico-cortical inhibition in the primary motor cortex

P2-11-02. Inter-individual variability in response to motor cortex inhibition

P2-11-02. Inter-individual variability in response to motor cortex inhibition

Effect of paired-pulse stimulus parameters on the two phases of short interval intracortical inhibition in the quadriceps muscle group.

Short interval intracortical inhibition (SICI) is commonly used to assess inhibition in the motor cortex and is known to be affected by the paired-pulse stimulus parameters (i.e., interstimulus interval [ISI], conditioning stimulus intensity [CSI] and test stimulus intensity [TSI]) used during testing. While the effects of stimulus parameters are well-studied in the upper-extremity, evidence in the lower-extremity is lacking. To comprehensively examine the effects of alterations in paired-pulse stimulus parameters on the two phases of SICI in the quadriceps muscle group. Seventeen adults (8 males, 9 females) volunteered to participate in this study. SICI was examined over a range of CSIs (70-90% active motor threshold [AMT]), TSIs (100-140% AMT), and ISIs (1.0-3.0 ms) using both EMG and torque responses elicited by transcranial magnetic stimulation (TMS). The results indicated that SICI at 1.0 ms ISI was best revealed with a CSI of 70% and TSI ≥110% AMT, whereas SICI at 2.5 ms ISI was best revealed with a CSI of 80-90% and a TSI of ≥130% AMT. Unlike upper-extremity muscles, evaluating SICI with a CSI of 70% AMT and an ISI of 1.0 ms produced the greatest inhibition for all TSIs. In general, inhibitory effects were contaminated by facilitatory effects when using a TSI of 100% AMT. The amount of inhibition was dependent on the stimulation parameters used during testing. A CSI of 70% AMT, ISI of 1.0 ms, and TSI of ≥110% AMT appear to be optimal for measuring SICI in the quadriceps muscle; however, other parameters can be used if careful consideration is given to the described interaction between the parameters.

GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness.

Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.

Motor cortex inhibition and modulation in children with ADHD.

Compared to typically developing (TD) peers, children with attention-deficit/hyperactivity disorder (ADHD) consistently demonstrate impaired transcranial magnetic stimulation (TMS)-evoked short interval cortical inhibition (SICI) of motor evoked potentials (MEPs) in resting motor cortex (M1). To determine whether perturbed M1 physiology also reflects clinically relevant behavioral dysfunction, we evaluated M1 physiology during a cognitive control task taxing motor response selection/inhibition. In this case-control study, behavioral ratings, motor skill (assessed using standardized examination), and left M1 physiology were evaluated in 131 right-handed, 8- to 12-year-old children (66 ADHD: mean 10.5 years, 43 male; 65 TD: mean 10.6 years, 42 male). The primary outcomes were MEP amplitudes and SICI, evaluated during rest and during a modified "racecar" Slater-Hammel stop signal reaction task, with TMS pulses administered 150 ms prior to the target go action and after the dynamic stop cue. Go responses were significantly slower (p = 0.01) and more variable (p = 0.002) in ADHD. Children with ADHD showed less M1 SICI at rest (p = 0.02) and during go (p = 0.03) and stop trials (p = 0.02). Rest M1 excitability increased during response inhibition task engagement (p < 0.0001). This Task-Related Up-Modulation (TRUM) was less robust across and within groups, with diminished task upmodulation associated with significantly more severe ADHD behavioral ratings and slower stop signal reaction times. Children with ADHD show anomalous motor cortex physiology, with deficient SICI across behavioral states and less TRUM from rest to action selection. Associations of these physiologic measures with ADHD symptoms and cognitive control measures support further investigation into biological mechanisms.