Inhibition In Primary Motor Cortex Research Articles

A global pause generates nonselective response inhibition during selective stopping.

Selective response inhibition may be required when stopping a part of a multicomponent action. A persistent response delay (stopping-interference effect) indicates nonselective response inhibition during selective stopping. This study aimed to elucidate whether nonselective response inhibition is the consequence of a global pause process during attentional capture or specific to a nonselective cancel process during selective stopping. Twenty healthy human participants performed a bimanual anticipatory response inhibition paradigm with selective stop and ignore signals. Frontocentral and sensorimotor beta-bursts were recorded with electroencephalography. Corticomotor excitability and short-interval intracortical inhibition in primary motor cortex were recorded with transcranial magnetic stimulation. Behaviorally, responses in the non-signaled hand were delayed during selective ignore and stop trials. The response delay was largest during selective stop trials and indicated that stopping-interference could not be attributed entirely to attentional capture. A stimulus-nonselective increase in frontocentral beta-bursts occurred during stop and ignore trials. Sensorimotor response inhibition was reflected in maintenance of beta-bursts and short-interval intracortical inhibition relative to disinhibition observed during go trials. Response inhibition signatures were not associated with the magnitude of stopping-interference. Therefore, nonselective response inhibition during selective stopping results primarily from a nonselective pause process but does not entirely account for the stopping-interference effect.

Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n=14; 61 ± 7yrs) or abnormally enlarged (hyperechogenic; n=9; 60 ± 6yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p=.005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Primary motor cortex function and motor skill acquisition: insights from threshold-hunting TMS.

Modulation of GABA-mediated inhibition in primary motor cortex (M1) is important for the induction of training-induced plasticity. The downregulation of inhibition during acquisition may promote cortical reorganization, whereas an upregulation once performance has plateaued may promote consolidation of the newly acquired skill. GABA-related inhibition in human M1 is routinely assessed using the paired-pulse transcranial magnetic stimulation (TMS) paradigm of short-interval intracortical inhibition (SICI). However, modulation of SICI with motor skill learning is not a consistent finding and may be influenced by TMS parameters. The aim of this study was to compare the modulation of SICI by motor skill learning between conventional and adaptive threshold-hunting techniques with an anterior-posterior and posterior-anterior induced current. Sixteen participants (21-33years) trained with their dominant (right) hand on a sequential visual isometric pinch task. Electromyographic recordings were obtained from the right first dorsal interosseous muscle. Corticomotor excitability and SICI were examined before and immediately after 12 blocks of training. Skill increased throughout the training, with performance plateauing before completion. Corticomotor excitability increased after motor training for both current directions. The amount of SICI was greater with anterior-posterior stimulation than posterior-anterior for both conventional and adaptive threshold-hunting techniques. SICI increased after motor training, but only for adaptive threshold-hunting with an anterior-posterior-induced current. The increased GABA-mediated inhibition evident after motor skill learning may promote consolidation of the newly acquired skill. The findings also support the notion that adaptive threshold-hunting SICI using an anterior-posterior current provides an effective assessment in interventional studies.

The Influence of Primary Motor Cortex Inhibition on Upper Limb Impairment and Function in Chronic Stroke: A Multimodal Study

Background. Stroke is a leading cause of adult disability owing largely to motor impairment and loss of function. After stroke, there may be abnormalities in γ-aminobutyric acid (GABA)-mediated inhibitory function within primary motor cortex (M1), which may have implications for residual motor impairment and the potential for functional improvements at the chronic stage. Objective. To quantify GABA neurotransmission and concentration within ipsilesional and contralesional M1 and determine if they relate to upper limb impairment and function at the chronic stage of stroke. Methods. Twelve chronic stroke patients and 16 age-similar controls were recruited for the study. Upper limb impairment and function were assessed with the Fugl-Meyer Upper Extremity Scale and Action Research Arm Test. Threshold tracking paired-pulse transcranial magnetic stimulation protocols were used to examine short- and long-interval intracortical inhibition and late cortical disinhibition. Magnetic resonance spectroscopy was used to evaluate GABA concentration. Results. Short-interval intracortical inhibition was similar between patients and controls (P = .10). Long-interval intracortical inhibition was greater in ipsilesional M1 compared with controls (P < .001). Patients who did not exhibit late cortical disinhibition in ipsilesional M1 were those with greater upper limb impairment and worse function (P = .002 and P = .017). GABA concentration was lower within ipsilesional (P = .009) and contralesional (P = .021) M1 compared with controls, resulting in an elevated excitation-inhibition ratio for patients. Conclusion. These findings indicate that ipsilesional and contralesional M1 GABAergic inhibition are altered in this small cohort of chronic stroke patients. Further study is warranted to determine how M1 inhibitory networks might be targeted to improve motor function.

Adaptive threshold hunting for the effects of transcranial direct current stimulation on primary motor cortex inhibition.

Primary motor cortex excitability can be modulated by anodal and cathodal transcranial direct current stimulation (tDCS). These neuromodulatory effects may, in part, be dependent on modulation within gamma-aminobutyric acid (GABA)-mediated inhibitory networks. GABAergic function can be quantified non-invasively using adaptive threshold hunting paired-pulse transcranial magnetic stimulation (TMS). The previous studies have used TMS with posterior-anterior (PA) induced current to assess tDCS effects on inhibition. However, TMS with anterior-posterior (AP) induced current in the brain provides a more robust measure of GABA-mediated inhibition. The aim of the present study was to assess the modulation of corticomotor excitability and inhibition after anodal and cathodal tDCS using TMS with PA- and AP-induced current. In 16 young adults (26 ± 1years), we investigated the response to anodal, cathodal, and sham tDCS in a repeated-measures double-blinded crossover design. Adaptive threshold hunting paired-pulse TMS with PA- and AP-induced current was used to examine separate interneuronal populations within M1 and their influence on corticomotor excitability and short- and long-interval inhibition (SICI and LICI) for up to 60min after tDCS. Unexpectedly, cathodal tDCS increased corticomotor excitability assessed with AP (P = 0.047) but not PA stimulation (P = 0.74). SICIAP was reduced after anodal tDCS compared with sham (P = 0.040). Pearson's correlations indicated that SICIAP and LICIAP modulation was associated with corticomotor excitability after anodal (P = 0.027) and cathodal tDCS (P = 0.042). The after-effects of tDCS on corticomotor excitability may depend on the direction of the TMS-induced current used to make assessments, and on modulation within GABA-mediated inhibitory circuits.

Perceptual Surprise Improves Action Stopping by Nonselectively Suppressing Motor Activity via a Neural Mechanism for Motor Inhibition.

Motor inhibition is a cognitive control ability that allows humans to stop actions rapidly even after initiation. Understanding and improving motor inhibition could benefit adaptive behavior in both health and disease. We recently found that presenting surprising, task-unrelated sounds when stopping is necessary improves the likelihood of successful stopping. In the current study, we investigated the neural underpinnings of this effect. Specifically, we tested whether surprise-related stopping improvements are due to a genuine increase in motor inhibition. In Experiment 1, we measured motor inhibition in primary motor cortex of male and female humans by quantifying corticospinal excitability (CSE) via transcranial magnetic stimulation and electromyography during a hybrid surprise-Go/NoGo task. Consistent with prior studies of motor inhibition, successful stopping was accompanied by nonselective suppression of CSE; that is, CSE was suppressed even in task-unrelated motor effectors. Importantly, unexpected sounds significantly increased this motor-system inhibition to a degree that was directly related to behavioral improvements in stopping. In Experiment 2, we then used scalp encephalography to investigate whether unexpected sounds increase motor-inhibition-related activity in the CNS. We used an independent stop-signal localizer task to identify a well characterized frontocentral low-frequency EEG component that indexes motor inhibition. We then investigated the activity of this component in the surprise-Go/NoGo task. Consistent with Experiment 1, this signature of motor inhibition was indeed increased when NoGo signals were followed by unexpected sounds. Together, these experiments provide converging evidence suggesting that unexpected events improve motor inhibition by automatically triggering inhibitory control.SIGNIFICANCE STATEMENT The ability to stop ongoing actions rapidly allows humans to adapt their behavior flexibly and rapidly. Action stopping is important in daily life (e.g., stopping to cross the street when a car approaches) and is severely impaired in many neuropsychiatric disorders. Therefore, finding ways to improve action stopping could aid adaptive behaviors in health and disease. Our current study shows that presenting unexpected sounds in stopping situations facilitates successful stopping. This improvement is specifically due to a surprise-related increase in a neural mechanism for motor inhibition, which rapidly suppresses the excitability of the motor system after unexpected events. These findings suggest a tight interaction between the neural systems for surprise processing and motor inhibition and yield a promising avenue for future research.

Inhibition of the primary motor cortex and the upgoing thumb sign.

BackgroundThe upgoing thumb sign has been frequently observed in patients with minor strokes and transient ischemic attacks as an indicator of brain involvement. We assessed the effect of primary motor cortex (M1) inhibition in the development of the upgoing thumb sign.MethodsUsed repetitive Transcranial Magnetic Stimulation (rTMS, 1 Hz frequency for 15 min, 1s ISI, 900 pulses) at 60% of resting motor threshold to inhibit the right or left primary motor cortex of 10 healthy individuals. Participants were examined before and after rTMS by a neurologist who was blind to the site of motor cortex inhibition.Results10 neurological intact participants (5 women/5 men) were recruited for this study. 2 cases were excluded due to pre-existing possible thumb signs. After the inhibition of the primary motor cortex, in 6 subjects out of 8, we observed a thumb sign contralateral to the site of primary motor cortex inhibition. In one subject an ipsilateral thumbs sign was noted. In another case, we did not find an upgoing thumb sign.ConclusionThe upgoing thumb sign is a subtle neurological finding that may be related to the primary motor cortex or corticospinal pathways involvements.

GABA and primary motor cortex inhibition in young and older adults: a multimodal reliability study.

The effects of healthy aging on γ-aminobutyric acid (GABA) within primary motor cortex (M1) remain poorly understood. Studies have reported contrasting results, potentially due to limitations with the common assessment technique. The aim of the present study was to investigate the effect of healthy aging on M1 GABA concentration and neurotransmission using a multimodal approach. Fifteen young and sixteen older adults participated in this study. Magnetic resonance spectroscopy (MRS) was used to measure M1 GABA concentration. Single-pulse and threshold-tracking paired-pulse transcranial magnetic stimulation (TMS) protocols were used to examine cortical silent period duration, short- and long-interval intracortical inhibition (SICI and LICI), and late cortical disinhibition (LCD). The reliability of TMS measures was examined with intraclass correlation coefficient analyses. SICI at 1 ms was reduced in older adults (15.13 ± 2.59%) compared with young (25.66 ± 1.44%; P = 0.002). However, there was no age-related effect for cortical silent period duration, SICI at 3 ms, LICI, or LCD (all P > 0.66). The intersession reliability of threshold-tracking measures was good to excellent for both young (range 0.75-0.96) and older adults (range 0.88-0.93). Our findings indicate that extrasynaptic inhibition may be reduced with advancing age, whereas GABA concentration and synaptic inhibition are maintained. Furthermore, MRS and threshold-tracking TMS provide valid and reliable assessment of M1 GABA concentration and neurotransmission, respectively, in young and older adults.NEW & NOTEWORTHY γ-Aminobutyric acid (GABA) in primary motor cortex was assessed in young and older adults using magnetic resonance spectroscopy and threshold-tracking paired-pulse transcranial magnetic stimulation. Older adults exhibited reduced extrasynaptic inhibition (short-interval intracortical inhibition at 1 ms) compared with young, whereas GABA concentration and synaptic inhibition were similar between age groups. We demonstrate that magnetic resonance spectroscopy and threshold-tracking provide valid and reliable assessments of primary motor cortex GABA concentration and neurotransmission, respectively.

Acute aerobic exercise modulates primary motor cortex inhibition.

Aerobic exercise can enhance neuroplasticity although presently the neural mechanisms underpinning these benefits remain unclear. One possible mechanism is through effects on primary motor cortex (M1) function via down-regulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The aim of the present study was to examine how corticomotor excitability (CME) and M1 intracortical inhibition are modulated in response to a single bout of moderate intensity aerobic exercise. Ten healthy right-handed adults were participants. Single- and paired-pulse transcranial magnetic stimulation was applied over left M1 to obtain motor-evoked potentials in the right flexor pollicis brevis. We examined CME, cortical silent period (SP) duration, short- and long-interval intracortical inhibition (SICI, LICI), and late cortical disinhibition (LCD), before and after acute aerobic exercise (exercise session) or an equivalent duration without exercise (control session). Aerobic exercise was performed on a cycle ergometer for 30min at a workload equivalent to 60% of maximal cardiorespiratory fitness (VO2 peak; heart rate reserve=75±3%, perceived exertion=13.5±0.7). LICI was reduced at 10 (52±17%, P=0.03) and 20min (27±8%, P=0.03) post-exercise compared to baseline (13±4%). No significant changes in CME, SP duration, SICI or LCD were observed. The present study shows that GABAB-mediated intracortical inhibition may be down-regulated after acute aerobic exercise. The potential effects this may have on M1 plasticity remain to be determined.

Threshold tracking primary motor cortex inhibition: the influence of current direction.

Paired-pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior-posterior (AP) stimulation preferentially activates late indirect- (I-) waves that are most susceptible to paired-pulse TMS. Threshold tracking TMS can assess intracortical inhibition; however, previous studies have only used a current direction that preferentially recruits early I-waves [posterior-anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I-waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21-50years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I-wave recruitment calculated as the onset latency difference between PA-LM and AP-LM. Short- and long-interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100-260ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I-wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP-induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA.

High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures of the motor affordance while working memory load was varied. We observed a typical motor affordance signature when working memory load was low; however, it was abolished when load was high. Further, there was increased intracortical inhibition in primary motor cortex under high working memory load. This suggests that being in a state of high cognitive load "sets" the motor system to be imperturbable to distracting motor influences. This makes a novel link between working memory load and the balance of excitatory/inhibitory activity in the motor cortex and potentially has implications for disorders of impulsivity.

Are ipsilateral motor evoked potentials subject to intracortical inhibition?

Paired-pulse transcranial magnetic stimulation (TMS) can be used to examine intracortical inhibition in primary motor cortex (M1), termed short-interval intracortical inhibition (SICI). To our knowledge, SICI has only been demonstrated in contralateral motor evoked potentials (MEPs). Ipsilateral MEPs (iMEPs) are assumed to reflect excitability of an uncrossed oligosynaptic pathway, and can sometimes be evoked in proximal upper-limb muscles using high-intensity TMS. We examined whether iMEPs in the biceps brachii (BB) would be suppressed by subthreshold conditioning, therefore demonstrating SICI of iMEPs. TMS was delivered to the dominant M1 to evoke conditioned (C) and nonconditioned (NC) iMEPs in the nondominant BB of healthy participants during weak bilateral elbow flexion. The conditioning stimulus intensities tested were 85%, 100%, and 115% of active motor threshold (AMT), at 2 ms and 4 ms interstimulus intervals (ISI). The iMEP ratio (C/NC) was calculated for each condition to assess the amount of inhibition. Inhibition of iMEPs was present at 2 ms ISI with 100% and 115% AMT (bothP< 0.03), mediated by a reduction in persistence and size (allP< 0.05). To our knowledge, this is the first demonstration of SICI of iMEPs. This technique may be useful as a tool to better understand the role of ipsilateral M1 during functional motor tasks.

P 147. Impaired modulation of intracortical inhibition during Go–Stop task in schizophrenia

Background Impaired inhibition has been reported in patients with schizophrenia in a variety of cognitive and motor tasks. Recent transcranial magnetic stimulation studies performed during rest show reduced cortical inhibition in primary motor cortex (M1) at rest in schizophrenia patients, supporting the hypothesis of impaired GABA-ergic inhibition as an underlying mechanism. However, cortical excitability and intracortical inhibition in M1 are highly task-dependent, for example, inhibiting a planned motor response leads to reduced excitability and enhanced intracortical inhibition. Studies on task-dependent cortical excitability and inhibition are lacking in schizophrenia. The aim of this study was therefore to investigate cortical excitability and intracortical inhibition during voluntary motor inhibition in patients with schizophrenia. Methods 25 stabilized patients with schizophrenia (DSMIV) and a group of 23 age-comparable healthy volunteers were included. We used a modified version of the Go–Stop task to study voluntary motor inhibition. This task consisted of moving the index finger in response to Go and Stop signals. In 30% of trials the subject received a visual cue to inhibit the prepared finger lift. Paired-pulse transcranial magnetic stimulation (TMS) was used to measure M1 excitability and short-latency intracortical inhibition (SICI%) during three phases of the task: (i) early without movement preparation (Early); (ii) late with preparation of finger lift (Late prep ); and (iii) late with inhibition of finger lift (Late inhib ). Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle. Results Patients and control subjects performed equally on the voluntary inhibition task, with similar stop signal reaction times (mean SSRT controls 189 ± 21 ms and patients 186 ± 31 ms, P = 0.6). TMS at rest revealed similar resting and active motor thresholds in patients and controls (P > 0.9). The cortical silent period was shorter in the patients but did not differ significantly (mean controls 162 ± 30 ms and patients 147 ± 61 ms, P = 0.36). During the Go–Stop task, cortical excitability was similar in patients and controls with a task-dependent modulation of MEPs (mean RMS MEPs: Early = 477 μV, Late prep = 854 μV, and Late inhib = 531 μV; effect of Phase, P F = 4.5, P = 0.02) with posthoc comparisons revealing a significant reduction in the Late inhib phase in patients compared to controls ( P = 0.02). In patients the SICI% during Late inhib correlated negatively with SSRT ( R = − 0.72, P inhib had longer SSRT. Conclusions To our knowledge this is the first study on task-dependent modulation of cortical excitability and intracortical inhibition in patients with schizophrenia. We show that patients with schizophrenia have reduced SICI during voluntary inhibition of a prepared finger lift. Surprisingly, there were no differences found in task performance or in MEP amplitudes during the task. These findings show that schizophrenia patients are capable of inhibiting motor tasks despite having reduced intracortical inhibition. This suggests the use of compensatory mechanisms in voluntary motor inhibition in stabilized schizophrenia patients.

Modulation of the Disturbed Motor Network in Dystonia by Multisession Suppression of Premotor Cortex

Daily sessions of therapeutic transcranial brain stimulation are thought to prolong or amplify the effect of a single intervention. Here we show in patients with focal hand dystonia that additional, new effects build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. In a sham-controlled study, real or sham continuous theta burst stimulation (cTBS) was given once daily for five consecutive days to dorsolateral premotor cortex (PMd). Five days of real, but not sham, premotor cTBS improved intracortical inhibition in primary motor cortex (M1) to a similar extent on day 1 and day 5. However 5 days of cTBS were required to restore the abnormal PMd-M1 interactions observed on day 1. Similarly, excessive M1 plasticity seen at baseline was also significantly reduced by five days of real premotor cTBS. There was only a marginal benefit on writing. The results show that additional, new effects, at sites distant from the point of stimulation, build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. The results indicate that it may take many days of therapeutic intervention to rebalance activity in a complex network.

GABA-Ergic Dysfunction in Succinic Semialdehyde Dehydrogenase Deficiency

Investigators at the Clinical Epilepsy and Neurorehabilitation Sections, NIH, Bethesda, MD; Albert Ludwigs University, Freiberg, Germany; and Children's National Medical Center, Washington, DC used transcranial magnetic stimulation (TMS) to quantify the excitation and inhibition in primary motor cortex in 8 patients (mean age 15.4 years) with succinic semialdehyde dehydrogenase (SSADH) deficiency.

GABA B -ergic motor cortex dysfunction in SSADH deficiency

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder of GABA degradation leading to elevations in brain GABA and γ-hydroxybutyric acid (GHB). The effect of chronically elevated GABA and GHB on cortical excitability is unknown. We hypothesized that use-dependent downregulation of GABA receptor expression would promote cortical disinhibition rather than inhibition, predominantly via presynaptic GABAergic mechanisms. We quantified the magnitude of excitation and inhibition in primary motor cortex (M1) in patients with SSADH deficiency, their parents (obligate heterozygotes), age-matched healthy young controls, and healthy adults using single and paired pulse transcranial magnetic stimulation (TMS). Long interval intracortical inhibition was significantly reduced and the cortical silent period was significantly shortened in patients with SSADH deficiency compared to heterozygous parents and control groups. Since long interval intracortical inhibition and cortical silent period are thought to reflect GABA(B) receptor-mediated inhibitory circuits, our results point to a particularly GABA(B)-ergic motor cortex dysfunction in patients with SSADH deficiency. This human phenotype is consistent with the proposed mechanism of use-dependent downregulation of postsynaptic GABA(B) receptors in SSADH deficiency animal models. Additionally, the results suggest autoinhibition of GABAergic neurons. This first demonstration of altered GABA(B)-ergic function in patients with SSADH deficiency may help to explain clinical features of the disease, and suggest pathophysiologic mechanisms in other neurotransmitter-related disorders.

Proactive and selective response control may be associated with increased GABA-ergic mediated inhibition in primary motor cortex

Proactive and selective response control may be associated with increased GABA-ergic mediated inhibition in primary motor cortex

Early adaptations in somatosensory cortex after focal ischemic injury to motor cortex

In response to a lesion, intact regions of cortex in both hemispheres undergo adaptive changes in network function. For example, changes in excitability and intracortical inhibition in primary motor cortex (M1) were reported after lesioning contralateral or ipsilateral brain regions. Close interactions exist between M1 and primary somatosensory cortex (S1) within one hemisphere. Therefore, we hypothesized that lasting modifications would occur in S1 excitability after lesioning ipsilateral M1. Imaging of intrinsic optical signals (IOS, at 570 nm) was used to investigate the evolution of the somatosensory cortical response evoked by contralateral median nerve stimulation during the first hour after a photothrombotic lesion to M1 (caudal motor cortex) of the rat (n=10). Control rats (n=6) received no lesion. Perfusion was monitored by Laser speckle imaging and the extent of the resulting lesion was determined histologically. Control animals did not show evidence for reduced perfusion, infarction, or changes in IOS. M1 infarction led to a significant increase in evoked response amplitude, duration, and area of activation, and a shortening of latencies. These parameters reached a plateau around 50 min after ischemia. These results indicate S1 hyperexcitability after M1 injury. Whether these adaptations contribute to functional deficits or play a role in recovery, remains to be determined.