Short-interval Cortical Inhibition Research Articles

Neurochemical mechanisms underlying serotonergic modulation of neuroplasticity in humans

BackgroundStudies in animals and humans have shown that cortical neuroplasticity can be modulated by increasing serotonin levels by administering selective serotonin reuptake inhibitors (SSRI). However, little is known about the mechanistic background, especially the contribution of intracortical inhibition and facilitation, which depend on gamma-aminobutyric acid (GABA) and glutamate. ObjectiveWe aimed to explore the relevance of drivers of plasticity (glutamate- and GABA-dependent processes) for the effects of serotonin enhancement on tDCS-induced plasticity in healthy humans. MethodsA crossover, partially double-blinded, randomized, and sham-controlled study was conducted in 21 healthy right-handed individuals. In each of the 7 sessions, plasticity was induced via transcranial direct current stimulation (tDCS). Anodal, cathodal, and sham tDCS were applied to the left motor cortex under SSRI (20 mg/40 mg citalopram) or placebo. Short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) were monitored by paired-pulse transcranial magnetic stimulation for 5–6 h after intervention. ResultsUnder placebo, anodal tDCS-induced LTP-like plasticity decreased SICI and increased ICF. In contrast, cathodal tDCS-elicited LTD-like plasticity induced the opposite effect. Under 20 mg and 40 mg citalopram, anodal tDCS did not affect SICI largely, while ICF was enhanced and prolonged. For cathodal tDCS, citalopram converted the increase of SICI and decrease of ICF into antagonistic effects, and this effect was dosage-dependent since it lasted longer under 40 mg when compared to 20 mg. ConclusionWe speculate that the main effects of acute serotonergic enhancement on tDCS-induced plasticity, the increase and prolongation of LTP-like plasticity effects, involves mainly the glutamatergic system.

Differential modulation of corticomotor excitability in older compared to young adults following a single bout of strength -exercise

Evidence shows corticomotor plasticity diminishes with age. Nevertheless, whether strength-training, a proven intervention that induces corticomotor plasticity in younger adults, also takes effect in older adults, remains untested. This study examined the effect of a single-session of strength-exercise on corticomotor plasticity in older and younger adults. Thirteen older adults (72.3 ± 6.5 years) and eleven younger adults (29.9 ± 6.9 years), novice to strength-exercise, participated. Strength-exercise involved four sets of 6–8 repetitions of a dumbbell biceps curl at 70–75% of their one-repetition maximum (1-RM). Muscle strength, cortical, corticomotor and spinal excitability, before and up to 60-minutes after the strength-exercise session were assessed. We observed significant changes over time (p < 0.05) and an interaction between time and age group (p < 0.05) indicating a decrease in corticomotor excitability (18% p < 0.05) for older adults at 30- and 60-minutes post strength-exercise and an increase (26% and 40%, all p < 0.05) in younger adults at the same time points. Voluntary activation (VA) declined in older adults immediately post and 60-minutes post strength-exercise (36% and 25%, all p < 0.05). Exercise had no effect on the cortical silent period (cSP) in older adults however, in young adults cSP durations were shorter at both 30- and 60- minute time points (17% 30-minute post and 9% 60-minute post, p < 0.05). There were no differences in short-interval cortical inhibition (SICI) or intracortical facilitation (ICF) between groups. Although the corticomotor responses to strength-exercise were different within groups, overall, the neural responses seem to be independent of age.

Differences in motor inhibition in young and older musicians and non-musicians at rest.

Older adults experience a decline in motor inhibition. These declines have been implicated in instrumental activities of daily living. However, studies have revealed that older musicians have behavioral and neurophysiological enhancements in various motor domains compared to non-musicians. This suggests that music training may delay the decline in motor inhibition with aging. Nevertheless, motor inhibition has not been studied in young or older musicians and non-musicians. Thus, the present study aimed to investigate the neurophysiological differences in motor inhibition in aging musicians and non-musicians. A total of 19 healthy young adult musicians, 16 healthy young non-musicians, 13 healthy older adult musicians, and 16 healthy older adult non-musicians were recruited for the study. Transcranial magnetic stimulation single-pulse (SP) and short interval cortical inhibition (SICI) were performed at rest and then converted into inhibition percentage. We did not observe significant differences between young and older musicians and non-musicians in resting SP MEP. Older adults had lower resting SICI MEP than young adults. Older adults (36%) had a greater percentage of inhibition than young adults (16%). However, when controlling for background EMG activity, musicians had a lower inhibition percentage than non-musicians. The results revealed that, despite the greater use of spinal mechanisms, decreased SICI, and increased inhibition percentage in older adults, motor inhibitory circuitry remains intact and functional in both young and older musicians and non-musicians. Future studies will reveal whether there are differences in motor inhibition during movement in musicians across a person's lifespan.

Cortical inhibition on TMS-EEG: interstimulus interval effect on short-interval paired-pulse.

In mental disorders, paired-pulse (PP) transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings usage is increasing to directly evaluate the cortical inhibition of motor and nonmotor regions. One of the most common measures to assess the inhibition is the short-interval cortical inhibition (SICI), which depends on the interstimulus interval (ISI). This measure has been widely used in the motor cortex. However, the number of studies that evaluate other nonmotor regions, such as the dorsolateral prefrontal cortex (DLPFC), are increasing and there is still little knowledge on how the ISI affects those areas.In this pilot study, six subjects underwent a SICI protocol over the DLPFC using ISI values of 2 and 4ms with the aim of comparing them. TMS-EEG signals for both ISIs were characterized regarding the amplitude and latency of the TMS-evoked potentials (TEP) P60 and N100. Whereas the variation of cortical inhibition between ISIs is almost significant for N100, with higher inhibition for an ISI of 2ms, for TEP P60 the variation was not appreciable. Findings are in accordance with the ones in the state-of-the-art obtained in the motor cortex and suggest that a greater inhibition is likely to be produced with an ISI of 2ms.Clinical relevance- This pilot study indicates that cortical inhibition might be better assessed when DLPFC is stimulated with an ISI of 2ms in the SICI protocol.

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

BackgroundCognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies.MethodsWithin this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV).DiscussionThe study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition.Trial registrationThe clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).

N°384 – Short-interval cortical inhibition (SICI): Effect of target tracking on consistency of responses for 1mV and 200µV test-alone targets

N°384 – Short-interval cortical inhibition (SICI): Effect of target tracking on consistency of responses for 1mV and 200µV test-alone targets

Biomarkers of tic severity in children with Tourette syndrome: Motor cortex inhibition measured with transcranial magnetic stimulation.

To compare transcranial magnetic stimulation (TMS)-derived measures of primary motor cortex (M1) physiology between children with and without Tourette syndrome, and to dimensionally analyze TMS measures with Tourette syndrome-related symptom severity. We used a cross-sectional experimental design. Sixty 8- to 12-year-old children participated (30 with Tourette syndrome: three females, mean age 10 years 10 months, standard deviation [SD] 1 year 3 months; 30 typically developing children: seven females, mean age 10 years 7 months, SD 1 year 3 months). In the group with Tourette syndrome, 15 (one female, mean age 10 years 11 months, SD 1 year 3 months) had comorbid attention-deficit/hyperactivity disorder (ADHD), rated with the Conners, Third Edition and the parent-reported ADHD rating scales. Tic severity was rated with the Yale Global Tic Severity Scale and urge severity with the Individualized Premonitory Urge for Tics Scale. M1 short-interval cortical inhibition (SICI) and intracortical facilitation were compared between diagnostic groups and, within the group with Tourette syndrome, correlated with symptom severity using linear mixed-effects models for repeated measures. Accounting for ADHD, we found no difference in SICI or intracortical facilitation in those with Tourette syndrome versus typically developing children (p > 0.1). In the group with Tourette syndrome, reduced M1 SICI predicted greater total (p=0.012) and global (p=0.002) tic severity. There were no associations with urge severity (p > 0.5). Reduced M1 SICI is robustly associated with increased tic, but not urge, severity. Increased tic severity is associated with reduced motor cortex short-interval cortical inhibition (SICI). Children with Tourette syndrome with increased urge severity also show increased tic severity. However, reduced motor cortex SICI is associated with tic, but not urge, severity.

Motor Function and Physiology in Youth With Neurofibromatosis Type 1

BackgroundNeurofibromatosis type 1 (NF1) is a genetic neurocutaneous disorder commonly associated with motor and cognitive symptoms that greatly impact quality of life. Transcranial magnetic stimulation (TMS) can quantify motor cortex physiology, reflecting the basis for impaired motor function as well as, possibly, clues for mechanisms of effective treatment. We hypothesized that children with NF1 have impaired motor function and altered motor cortex physiology compared to typically developing (TD) control children and children with attention-deficit/hyperactivity disorder (ADHD). MethodsChildren aged 8-17 years with NF1 (n = 21) were compared to children aged 8-12 years with ADHD (n = 59) and TD controls (n = 88). Motor development was assessed using the Physical and Neurological Examination for Subtle Signs (PANESS) scale. The balance of inhibition and excitation in motor cortex was assessed using the TMS measures short-interval cortical inhibition (SICI) and intracortical facilitation (ICF). Measures were compared by diagnosis and tested using bivariate correlations and regression for association with clinical characteristics. ResultsIn NF1, ADHD severity scores were intermediate between the ADHD and TD cohorts, but total PANESS scores were markedly elevated (worse) compared to both (P < 0.001). Motor cortex ICF (excitatory) was significantly lower in NF1 than in TD and ADHD (P < 0.001), but SICI (inhibitory) did not differ. However, in NF1, better PANESS scores correlated with lower SICI ratios (more inhibition; ρ = 0.62, P = 0.003) and lower ICF ratios (less excitation; ρ = 0.38, P = 0.06). ConclusionsTMS-evoked SICI and ICF may reflect processes underlying abnormal motor function in children with NF1.

Corticospinal and spinal adaptations following lower limb motor skill training: a meta-analysis with best evidence synthesis.

Motor skill training alters the human nervous system; however, lower limb motor tasks have been less researched compared to upper limb tasks. This meta-analysis with best evidence synthesis aimed to determine the cortical and subcortical responses that occur following lower limb motor skill training, and whether these responses are accompanied by improvements in motor performance. Following a literature search that adhered to the PRISMA guidelines, data were extracted and analysed from six studies (n = 172) for the meta-analysis, and 11 studies (n = 257) were assessed for the best evidence synthesis. Pooled data indicated that lower limb motor skill training increased motor performance, with a standardised mean difference (SMD) of 1.09 being observed. However, lower limb motor skill training had no effect on corticospinal excitability (CSE), Hoffmann's reflex (H-reflex) ormuscle compound action potential (MMAX)amplitude. The best evidence synthesis found strong evidence for improved motor performance and reduced short-interval cortical inhibition (SICI) following lower limb motor skill training, with conflicting evidence towards the modulation of CSE. Taken together, this review highlights the need for further investigation on how motor skill training performed with the lower limb musculature canmodulate corticospinal responses. This will also help us to better understand whether these neuronal measures are underpinning mechanisms that support an improvement in motor performance.

Is cortical inhibition in primary motor cortex related to executive control?

Recent research using paired-pulse transcranial magnetic stimulation (TMS) has shown that the speed with which people can stop an action is linked to GABAergic inhibitory activity in the motor system. Specifically, a significant proportion of the variance in stop signal reaction time (SSRT; a widely used measure of inhibitory control) is accounted for by short-interval cortical inhibition (SICI). It is still unclear whether this relationship reflects a broader link between GABAergic processes and executive functions, or a specific link between GABAergic processes and motor stopping ability. The current study sought to replicate the correlation between SSRT and SICI while investigating whether this association generalises to other measures of inhibitory control and working memory, and to long-interval cortical inhibition (LICI). Participants completed a battery of inhibition (Stop-Signal, Stroop, Flanker) and working memory (n-back, Digit Span, and Operation Span) tasks. We replicated the correlation between SICI and SSRT but found no other correlations between behavioural measures of executive control and the two cortical measures of inhibition. These findings indicate that the relationship between SSRT and SICI is specific to a particular property of response inhibition and likely reflects the function of local inhibitory networks mediated by GABAA.

Acute Effects of High-Intensity Aerobic Exercise on Motor Cortical Excitability and Inhibition in Sedentary Adults.

Transcranial magnetic stimulation studies have demonstrated increased cortical facilitation and reduced inhibition following aerobic exercise, even when examining motor regions separate to the exercised muscle group. These changes in brain physiology following exercise may create favorable conditions for adaptive plasticity and motor learning. One candidate mechanism behind these benefits is the increase in brain-derived neurotropic factor (BDNF) observed following exercise, which can be quantified from a venous blood draw. The aim of this study was to investigate changes in motor cortex excitability and inhibition of the upper limb, and circulating BDNF, following high-intensity interval training (HIIT) on a stationary bicycle. Nineteen sedentary adults participated in a randomized crossover design study involving a single bout of high-intensity interval cycling for 20 min or seated rest. Venous blood samples were collected, and transcranial magnetic stimulation (TMS) was used to stimulate the extensor carpi radialis (ECR), where motor evoked potentials (MEP) were recorded pre- and post-condition. Following exercise, there was a significant increase (29.1%, p < 0.001) in corticospinal excitability measured at 120% of resting motor threshold (RMT) and a reduction in short-interval cortical inhibition (SICI quantified as 86.2% increase in the SICI ratio, p = 0.002). There was a non-significant (p = 0.125) 23.6% increase in BDNF levels. Collectively, these results reflect a net reduction in gamma aminobutyric acid (GABA)ergic synaptic transmission and increased glutamatergic facilitation, resulting in increased corticospinal excitability. This study supports the notion that acute high-intensity exercise provides a potent stimulus for inducing cortical neuroplasticity, which may support enhanced motor learning.

Short latency afferent inhibition: comparison between threshold-tracking and conventional amplitude recording methods.

Short-latency afferent inhibition (SAI), which is conventionally measured as a reduction in motor evoked potential amplitude (A-SAI), is of clinical interest as a potential biomarker for cognitive impairment. Since threshold-tracking has some advantages for clinical studies of short-interval cortical inhibition, we have compared A-SAI with a threshold-tracking alternative method (T-SAI). In the T-SAI method, inhibition was calculated by tracking the required TMS intensity for the targeted MEP amplitude (200 uV) both for the test (TMS only) and paired (TMS and peripheral stimulation) stimuli. A-SAI and T-SAI were recorded from 31 healthy subjects using ten stimuli at each of 12 inter-stimulus intervals, once in the morning and again in the afternoon. There were no differences between morning and afternoon recordings. When A-SAI was normalized by log conversion it was closely related to T-SAI. Between subjects, variability was similar for the two techniques, but within-subject variability was significantly smaller for normalized A-SAI. Conventional amplitude measurements appear more sensitive for detecting changes within-subjects, such as in interventional studies, but threshold-tracking may be as sensitive as detecting abnormal SAI in a patient.

Cortical Inhibition and Plasticity in Major Depressive Disorder.

BackgroundMajor depressive disorder (MDD) is a severe psychiatric disorder that is associated with various cognitive impairments, including learning and memory deficits. As synaptic plasticity is considered an important mechanism underlying learning and memory, deficits in cortical plasticity might play a role in the pathophysiology of patients with MDD. We used Transcranial Magnetic Stimulation (TMS) to assess inhibitory neurotransmission and cortical plasticity in the motor cortex of MDD patients and controls.MethodsWe measured the cortical silent period (CSP) and short interval cortical inhibition (SICI), as well as intermittent theta-burst stimulation (iTBS), in 9 drug-free MDD inpatients and 18 controls.ResultsThe overall response to the CSP, SICI, and iTBS paradigms was not significantly different between the patient and control groups. iTBS induction resulted in significant potentiation after 20 mins in the control group (t(17) = −2.8, p = 0.01), whereas no potentiation was observed in patients.ConclusionsPotentiation of MEP amplitudes was not observed within the MDD group. No evidence was found for medium-to-large effect size differences in CSP and SICI measures in severely depressed drug-free patients, suggesting that reduced cortical inhibition is unlikely to be a robust correlate of the pathophysiological mechanism in MDD. However, these findings should be interpreted with caution due to the high inter-subject variability and the small sample size.SignificanceThese findings advance our understanding of neurophysiological functioning in drug-free severely depressed inpatients.

Corticospinal and intracortical excitability is modulated in the knee extensors after acute strength training

ABSTRACT The corticospinal responses to high-intensity and low-intensity strength-training of the upper limb are modulated in an intensity-dependent manner. Whether an intensity-dependent threshold occurs following acute strength training of the knee extensors (KE) remains unclear. We assessed the corticospinal responses following high-intensity (85% of maximal strength) or low-intensity (30% of maximal strength) KE strength-training with measures taken during an isometric KE task at baseline, post-5, 30 and 60-min. Twenty-eight volunteers (23 ± 3 years) were randomized to high-intensity (n = 11), low-intensity (n = 10) or to a control group (n = 7). Corticospinal responses were evoked with transcranial magnetic stimulation at intracortical and corticospinal levels. High- or low-intensity KE strength-training had no effect on maximum voluntary contraction force post-exercise (P > 0.05). High-intensity training increased corticospinal excitability (range 130–180%) from 5 to 60 min post-exercise compared to low-intensity training (17–30% increase). Large effect sizes (ES) showed that short-interval cortical inhibition (SICI) was reduced only for the high-intensity training group from 5–60 min post-exercise (24–44% decrease) compared to low-intensity (ES ranges 1–1.3). These findings show a training-intensity threshold is required to adjust CSE and SICI following strength training in the lower limb.

Short interval cortical inhibition – literature review of methodology aspects and recommendations

Short interval cortical inhibition – literature review of methodology aspects and recommendations

Associations between Task-Related Modulation of Motor-Evoked Potentials and EEG Event-Related Desynchronization in Children with ADHD.

Children with attention-deficit/hyperactivity disorder (ADHD) have previously shown a decreased magnitude of event-related desynchronization (ERD) during a finger-tapping task, with a large between-group effect. Because the neurobiology underlying several transcranial magnetic stimulation (TMS) measures have been studied in multiple contexts, we compared ERD and 3 TMS measures (resting motor threshold [RMT], short-interval cortical inhibition [SICI], and task-related up-modulation [TRUM]) within 14 participants with ADHD (ages 8-12years) and 17 control children. The typically developing (TD) group showed a correlation between greater RMT and greater magnitude of alpha (10-13Hz, here) ERD, and there was no diagnostic interaction effect, consistent with a rudimentary model of greater needed energy input to stimulate movement. Similarly, inhibition measured by SICI was also greater in the TD group when the magnitude of movement-related ERD was higher; there was a miniscule diagnostic interaction effect. Finally, TRUM during a response-inhibition task showed an unanticipated pattern: in TD children, the greater TMS task modulation (TRUM) was associated with a smaller magnitude of ERD during finger-tapping. The ADHD group showed the opposite direction of association: Greater TRUM was associated with larger magnitude of ERD. Prior EEG results have demonstrated specific alterations of task-related modulation of cortical physiology, and the current results provide a fulcrum for multimodal study.

Motor cortex modulation and reward in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder, the most prevalent developmental disorder in childhood, is a biologically heterogenous condition characterized by impaired attention and impulse control as well as motoric hyperactivity and anomalous motor skill development. Neuropsychological testing often demonstrates impairments in motivation and reward-related decision making in attention-deficit/hyperactivity disorder, believed to indicate dysfunction of the dopamine reward pathway. Development of reliable, non-invasive, easily obtained and quantitative biomarkers correlating with the presence and severity of clinical symptoms and impaired domains of function could aid in identifying meaningful attention-deficit/hyperactivity disorder subgroups and targeting appropriate treatments. To this end, 55 (37 male) 8–12-year-old children with attention-deficit/hyperactivity disorder and 50 (32 male) age-matched, typically-developing controls were enrolled in a transcranial magnetic stimulation protocol—used previously to quantify cortical disinhibition in both attention-deficit/hyperactivity disorder and Parkinson’s Disease—with a child-friendly reward motivation task. The primary outcomes were reward task-induced changes in short interval cortical inhibition and up-modulation of motor evoked potential amplitudes, evaluated using mixed model, repeated measure regression. Our results show that both reward cues and reward receipt reduce short-interval cortical inhibition, and that baseline differences by diagnosis (less inhibition in attention-deficit/hyperactivity disorder) were no longer present when reward was cued or received. Similarly, both reward cues and reward receipt up-modulated motor evoked potential amplitudes, but, differentiating the two groups, this Task-Related-Up-Modulation was decreased in children with attention-deficit/hyperactivity disorder. Furthermore, more severe hyperactive/impulsive symptoms correlated significantly with less up-modulation with success in obtaining reward. These results suggest that in children with attention-deficit/hyperactivity disorder, short interval cortical inhibition may reflect baseline deficiencies as well as processes that normalize performance under rewarded conditions. Task-Related-Up-Modulation may reflect general hypo-responsiveness in attention-deficit/hyperactivity disorder to both reward cue and, especially in more hyperactive/impulsive children, to successful reward receipt. These findings support transcranial magnetic stimulation evoked cortical inhibition and task-induced excitability as biomarkers of clinically relevant domains of dysfunction in childhood attention-deficit/hyperactivity disorder.

Relationship between GABA levels and task-dependent cortical excitability in children with attention-deficit/hyperactivity disorder

ObjectiveCompared to typically developing (TD) peers, children with attention deficit hyperactivity disorder (ADHD) manifest reduced short interval cortical inhibition (SICI) in the dominant motor cortex measured with transcranial magnetic stimulation (TMS). This multimodal study investigates the inhibitory neurophysiology and neurochemistry by evaluating the relationship between SICI and γ-amino butyric acid (GABA+) levels, measured with magnetic resonance spectroscopy (MRS). MethodsAcross two sites, 37 children with ADHD and 45 TD children, ages 8–12 years, participated. Single and paired pulse TMS to left motor cortex quantified SICI during REST and at times of action selection (GO) and inhibition (STOP) during a modified Slater-Hammel stop signal reaction task. MRS quantified GABA+ levels in the left sensorimotor cortex. Relationships between SICI and GABA+, as well as stopping efficiency and clinical symptoms, were analyzed with correlations and repeated-measure, mixed-models. ResultsIn both groups, higher GABA+ levels correlated with less SICI. In TD children only, higher GABA+ levels correlated with larger TMS motor evoked potentials (MEPs) at REST. In GO and STOP trials, higher GABA+ was associated with smaller MEP amplitudes, for both groups. Overall, GABA+ levels did not differ between groups or correlate with ADHD clinical symptoms. ConclusionsIn children with higher motor cortex GABA+, motor cortex is less responsive to inhibitory TMS (SICI). Comparing the relationships between MRS-GABA+ levels and responses to TMS at REST vs. GO/STOP trials suggests differences in inhibitory neurophysiology and neurotransmitters in children with ADHD. These differences are more prominent at rest than during response inhibition task engagement. SignificanceEvaluating relationships between GABA+ and SICI may provide a biomarker useful for understanding behavioral diagnoses.

Determining the Intracortical Responses After a Single Session of Aerobic Exercise in Young Healthy Individuals: A Systematic Review and Best Evidence Synthesis.

Alibazi, RJ, Pearce, AJ, Rostami, M, Frazer, AK, Brownstein, C, and Kidgell, DJ. Determining the intracortical responses after a single session of aerobic exercise in young healthy individuals: a systematic review and best evidence synthesis. J Strength Cond Res 35(2): 562-575, 2021-A single bout of aerobic exercise (AE) may induce changes in the excitability of the intracortical circuits of the primary motor cortex (M1). Similar to noninvasive brain stimulation techniques, such as transcranial direct current stimulation, AE could be used as a priming technique to facilitate motor learning. This review examined the effect of AE on modulating intracortical excitability and inhibition in human subjects. A systematic review, according to PRISMA guidelines, identified studies by database searching, hand searching, and citation tracking between inception and the last week of February 2020. Methodological quality of included studies was determined using the Downs and Black quality index and Cochrane Collaboration of risk of bias tool. Data were synthesized and analyzed using best-evidence synthesis. There was strong evidence for AE not to change corticospinal excitability and conflicting evidence for increasing intracortical facilitation and reducing silent period and long-interval cortical inhibition. Aerobic exercise did reduce short-interval cortical inhibition, which suggests AE modulates the excitability of the short-latency inhibitory circuits within the M1; however, given the small number of included studies, it remains unclear how AE affects all circuits. In light of the above, AE may have important implications during periods of rehabilitation, whereby priming AE could be used to facilitate motor learning.

Motor cortex facilitation: a marker of attention deficit hyperactivity disorder co-occurrence in autism spectrum disorder

The neural correlates distinguishing youth with Autism Spectrum Disorder (ASD-) and ASD with co-occurring Attention Deficit Hyperactivity Disorder (ASD+) are poorly understood despite significant phenotypic and prognostic differences. Paired-pulse transcranial magnetic stimulation (TMS) measures, including intracortical facilitation (ICF), short interval cortical inhibition (SICI), and cortical silent period (CSP) were measured in an age matched cohort of youth with ASD- (n = 20), ASD + (n = 29), and controls (TDC) (n = 24). ASD− and ASD+ groups did not differ by IQ or social functioning; however, ASD+ had significantly higher inattention and hyperactivity ratings. ICF (higher ratio indicates greater facilitation) in ASD+ (Mean 1.0, SD 0.19) was less than ASD− (Mean 1.3, SD 0.36) or TDC (Mean 1.2, SD 0.24) (F2,68 = 6.5, p = 0.003; post-hoc tests, ASD+ vs either TDC or ASD−, p ≤ 0.05). No differences were found between groups for SICI or age corrected active/resting motor threshold (AMT/RMT). Across all ASD youth (ASD− and ASD+), ICF was inversely correlated with worse inattention (Conners-3 Inattention (r = −0.41; p < 0.01) and ADHDRS-IV Inattention percentile (r = −0.422, p < 0.01) scores. ICF remains intact in ASD− but is impaired in ASD+. Lack of ICF is associated with inattention and executive function across ASD. Taken with the present findings, ADHD may have a distinct electrophysiological “signature” in ASD youth. ICF may constitute an emerging biomarker to study the physiology of ADHD in ASD, which may align with disease prognosis or treatment response.