Differences In Intracortical Inhibition Research Articles

Individual differences in intracortical inhibition predict action control when facing emotional stimuli.

Efficient inhibitory control in the context of prepotent actions is vital. However, such action inhibition may be profoundly influenced by affective states. Interestingly, research indicates that action control can be either impaired or improved by emotional stimuli. Thus, a great deal of confusion surrounds our knowledge of the complex dynamics subtending emotions and action control. Here, we aimed to investigate whether negative stimuli, even when non-consciously presented and task-irrelevant, can affect action control relative to neutral stimuli. Additionally, we tested whether individual differences in intracortical excitability may predict action control capabilities. To address these issues, we asked participants to complete a modified version of the Stop Signal Task (SST) in which fearful or neutral stimuli were subliminally presented before the go signals as primes. Moreover, we assessed participants' resting-state corticospinal excitability, short intracortical inhibition (SICI), and intracortical facilitation (ICF). Results demonstrated better action control capabilities when fearful stimuli were subliminally presented and interindividual SICI predicted stronger action inhibition capabilities. Taken together, these results shed new light on the intricate dynamics between action, consciousness, and motor control, suggesting that intracortical measures can be used as potential biomarkers of reduced motor inhibition in research and clinical settings.

Cortical silent period reflects individual differences in action stopping performance

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.

Excitability, Inhibition, and Neurotransmitter Levels in the Motor Cortex of Symptomatic and Asymptomatic Individuals Following Mild Traumatic Brain Injury.

Purpose: The purpose of this study was to determine the level of excitability and inhibition, as well as the concentrations of excitatory and inhibitory neurotransmitters, in the motor cortex of individuals with acute and chronic symptoms from mTBI.Methods: Fifty-three individuals were assigned to one of four groups: (i) without history of mTBI (Control), (ii) within 72-h of diagnosis of mTBI (Acute), (iii) with history of mTBI and no remaining symptoms (Chronic Asymptomatic), and (iv) with chronic symptoms from mTBI, lasting at least 3 months post-injury (Chronic Symptomatic). Measures of corticospinal excitability and inhibition were obtained using transcranial magnetic stimulation (TMS). On the same day, measures of glutamate and GABA concentrations were obtained from the primary motor cortex (M1) using proton magnetic resonance spectroscopy.Results: MEP amplitude and area were both significantly lower in the Chronic Symptomatic group compared to the Control and Chronic Asymptomatic groups (p ≤ 0.05). Intracortical inhibition was not significantly different among groups (p = 0.14). The concentration of glutamate in M1 was similar between groups (p = 0.93) while there was a trend for a lower concentration of GABA in the Chronic Symptomatic group compared to the Acute group (p = 0.06).Conclusions: Individuals with chronic mTBI symptoms appear to have lower corticospinal excitability compared with acutely-injured individuals and asymptomatic controls, but the absence of differences in intracortical inhibition, and concentrations of excitatory and inhibitory neurotransmitters in M1 suggests that neurotransmitter changes in the human brain post-mTBI do not follow the pattern typically seen in the animal literature.

Individual differences in intracortical inhibition predict motor-inhibitory performance.

Studies in which single- and paired-pulse TMS was applied during motor task performance have shed considerable light on the functional relevance of popular TMS-derived neurophysiological biomarkers such as short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI). While it has become well established that corticospinal excitability and intracortical inhibition are modulated during the enactment and cancellation of actions, it has remained unclear as to whether interindividual differences in these neurophysiological markers were associated with an individual's actual ability to restrain and cancel actions. In this study, we found that individual differences in both SICI and LICI were positively associated with relevant performance metrics on the go/no-go task and stop-signal task. Specifically, we found that individuals with greater resting SICI and LICI were faster to respond on go trials of the go/no-go task and were also more accurate at inhibiting their manual responses on both go/no-go and stop-signal tasks. These results are in support of findings from our earlier study and also provide new evidence for a general relationship between individual differences in resting-state GABAergic intracortical inhibitory functioning and motor inhibition.

Individual differences in intracortical inhibition during behavioural inhibition

The time required to abort an initiated response can be measured as the Stop Signal Reaction Time (SSRT). We determined whether GABAergic activity in the primary motor cortex (M1), measured using paired-pulse Transcranial Magnetic Stimulation (TMS) was related to SSRT. GABAergic activity in M1 was assessed by measuring Short-Interval Intracortical Inhibition (SICI). In two experiments, participants (males and females) completed the Stop Signal Task while we measured SICI from the first dorsal interosseous muscle. In Experiment 1, SICI was measured at fixed time points after Stop signal onset on Stop trials (50ms, 100ms, 150ms, 200ms), and at corresponding time points for Go trials. In Experiment 2 SICI was measured at fixed time points before the end of the SSRT interval (125ms, 75ms, 25ms) on Stop trials, and at corresponding time points for Go trials. In each experiment, 30 participants were classified as fast stoppers or slow stoppers based on a median split of their SSRTs. Fast stoppers had more SICI than slow stoppers, both when executing a response (Go trials) and when inhibiting a response (Stop trials). Indeed, the correlation between mean SICI and SSRT on successful Stop trials was 0.81. Experiment 2 showed that for fast stoppers (relative to baseline) there was reduced SICI on Go trials and recovery of SICI on Stop trials. Slow stoppers however, showed reduced SICI on Stop and Go trials relative to baseline. Our results show that individuals who are faster at stopping not only show more GABAergic activity in M1, but can more effectively control M1 GABAergic activity to inhibit motor cortical excitability when stopping a response and disinhibit excitability when executing a response.

64. Differences in intracortical inhibition of tongue motor representations between persistent adult developmental stutterers and normal speakers

The causes of developmental stuttering are not known, but increasing evidence shows differences in the motor system of persistent adult developmental stutterers (PADS) in comparison to normal speakers (NS). Right handed males PADS and matched NS (considering age, sex, handedness, smoking habits and musical expertise) were evaluated by using transcranial magnetic stimulation on their tongue primary motor cortex. We assessed resting and active motor thresholds, silent period threshold (SPT), and silent period duration (SPD, stimulating at 130% of SPT) in both hemispheres. Preliminary results suggest the presence of higher SPT for the PADS group with respect to NS. Moreover, SPD were increased in the left hemisphere of PADS with respect to NS. This result suggests a particular intracortical balance in the tongue motor cortex of PADS compared to NS. More specifically, while the higher SPT in PADS could suggest a lower intracortical inhibition, the longer SPD in the left hemisphere of PADS points up to a greater inhibition in these brain regions, thus compensated by the presence of lower inhibition in the right hemisphere of the same group. This data, in line with previous evidence in stuttering research, could be useful for rehabilitative purposes.

Impairment of Procedural Learning and Motor Intracortical Inhibition in Neurofibromatosis Type 1 Patients

BackgroundCognitive difficulties are the most common neurological complications in neurofibromatosis type 1 (NF1) patients. Recent animal models proposed increased GABA-mediated inhibition as one underlying mechanism directly affecting the induction of long-term potentiation (LTP) and learning. In most adult NF1 patients, apparent cognitive and attentional deficits, tumors affecting the nervous system and other confounding factors for neuroscientific studies are difficult to control for. Here we used a highly specific group of adult NF1 patients without cognitive or nervous system impairments. Such selected NF1 patients allowed us to address the following open questions: Is the learning process of acquiring a challenging motor skill impaired in NF1 patients? And is such an impairment in relation to differences in intracortical inhibition? MethodsWe used an established non-invasive, double-pulse transcranial magnetic stimulation (dp-TMS) paradigm to assess practice-related modulation of intracortical inhibition, possibly mediated by gamma-minobutyric acid (GABA)ergic-neurotransmission. This was done during an extended learning paradigm in a group of NF1 patients without any neuropsychological deficits, functioning normally in daily life and compared them to healthy age-matched controls. FindingsNF1 patients experienced substantial decline in motor skill acquisition (F=9.2, p=0.008) over five-consecutives training days mediated through a selective reduction in the early acquisition (online) and the consolidation (offline) phase. Furthermore, there was a consistent decrease in task-related intracortical inhibition as a function of the magnitude of learning (T=2.8, p=0.014), especially evident after the early acquisition phase. InterpretationsCollectively, the present results provide evidence that learning of a motor skill is impaired even in clinically intact NF1 patients based, at least partially, on a GABAergic-cortical dysfunctioning as suggested in previous animal work.

P 216. Impairment of triad conditioned facilitation in amyotrophic lateral sclerosis

Triad conditioned facilitation induced by transcranial magnetic stimulation (TMS) in healthy individuals has been proposed to reflect the intrinsic 40 Hz piper rhythm of the motor cortex. However, it is unclear if triad conditioned facilitation is influenced by degeneration of the motor cortex. Amyotrophic lateral sclerosis (ALS) is characterized among others by degeneration of the motor cortex. We therefore hypothesized that triad conditioned facilitation may be impaired in ALS patients. Moreover, we hypothesized that this triad conditioning paradigm may be helpful to differentiate ALS from cervical myelopathy, an important differential diagnosis. In 10 patients with ALS and 9 patients with cervical myelopathy serving as disease control, we compared single pulse conditioned intracortical inhibition (ICI), intracortical facilitation (ICF) and also triad conditioned facilitation at various interstimulus intervals (ISI) between 3 ms and 50 ms. There were no differences in ICI and ICF between both groups. Both groups also showed similar triad conditioned facilitation at 10 ms ISI. Patients with cervical myelopathy showed normal triad conditioned facilitation at 25 ms ISI comparable to healthy subjects. In contrast ALS patients showed no triad conditioned facilitation at 25 ms. The absence of triad conditioned facilitation at 25 ms ISI in ALS patients may represent changes of the intrinsic rhythm of the motor cortex probably caused by cortical degeneration. Triad conditioned TMS may be a valuable tool to differentiate ALS patients from patients with cervical myelopathy.

Difference in intracortical inhibition of the motor cortex between cortical myoclonus and focal hand dystonia

Objective The short interval intracortical inhibition (SICI) of the motor cortex (M1) is reduced in both cortical myoclonus and focal hand dystonia. This reduction has been attributed to the dysfunction of GABAergic system within the motor cortex. However, the precise mechanisms underlying the reduction may not be entirely identical in these two disorders, being due to primary pathological involvement in M1 or secondary to functional changes outside M1. The aim of this study was to elucidate possible differences in intracortical inhibition between these two disorders. Methods Subjects were 11 patients with benign myoclonus epilepsy, 7 with focal hand dystonia, and 11 normal volunteers. We studied SICI using anterior–posterior (AP) directed and posterior–anterior (PA) directed induced currents in the brain. Results In both disorders, SICI with PA-directed currents was reduced as reported previously. In contrast, SICI studied with AP currents was normal in patients with focal hand dystonia, but reduced in patients with cortical myoclonus. Conclusions The difference between the two disorders might reflect the underlying pathological difference. In cortical myoclonus, the inhibitory interneurons of the motor cortex are affected, whereas the same interneurons are intact in dystonia. The difference in SICI induced by AP and PA directed currents in dystonia may be explained by the following possibilities: the difference in composition of I-waves contributing to EMG generation and the difference in modulation of the interneuronal activity by voluntary contraction. These changes may be secondary to dysregulation of the motor cortex by the basal ganglia or related cortices in dystonia. Significance The SICI using AP directed currents together with the conventional SICI using PA directed currents was able to demonstrate some difference in the intrinsic circuits of M1 between myoclonus and focal hand dystonia. SICI using AP directed currents can provide additional information about the motor cortical excitability changes over those obtained by the previously reported methods.

Progressive suppression of intracortical inhibition during graded isometric contraction of a hand muscle is not influenced by hand preference

GABAergic intracortical inhibition (ICI) in human motor cortex (M1) assists fractionated activation of muscles, and it has been suggested that hemispheric differences in ICI may contribute to hand preference. Previous studies of this issue have all been conducted at rest, with conflicting results. Testing during voluntary activation may reveal functionally relevant differences. In normal subjects, we assessed (1) operation of ICI circuits during selective activation of an intrinsic hand muscle at different forces, and (2) whether this differs between right and left hemispheres. Surface EMG was recorded bilaterally from abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles in eleven right-handed subjects. A circular coil applied paired transcranial magnetic stimulation (TMS) with posteriorly directed current in the brain. Conditioning intensity was 0.8 x active threshold and interstimulus interval was 3 ms. TMS was applied to right or left M1 while subjects were at rest or performing isometric thumb abduction at different forces (0.5, 1, 2, 3, 5 and 10 N) with the contralateral hand. Conditioning TMS was less effective at suppressing the muscle evoked potential in APB during 2-10 N thumb abduction (P < 0.0001) versus rest, but not with lower target forces (0.5, 1 N). Conditioning TMS was less effective for FDI and ADM only during 10 N thumb abduction. We conclude that differential modulation of ICI in M1 during selective muscle activation is a function of target isometric force level. At low forces (<5% MVC), ICI is not modulated for the corticospinal neurons controlling the active or inactive muscles. There is a progressive reduction of ICI effects on corticospinal neurons at higher forces, which is largely restricted to corticospinal neurons controlling the muscle targeted for activation over the range of forces tested (up to approximately 25% MVC). The pattern of ICI modulation with selective voluntary muscle contraction was similar in left and right hemispheres during this relatively simple static task. If hemispheric differences in operation of M1 ICI circuits contribute to hand preference, a more challenging finger movement protocol may be needed to demonstrate this asymmetry.