Short-interval Intracortical Inhibition Research Articles

Effects of prolonged vibration to the flexor carpi radialis muscle on intracortical excitability

Prolonged local vibration (LV) can induce neurophysiological adaptations thought to be related to long-term potentiation or depression. Yet, how changes in intracortical excitability may be involved remains to be further investigated as previous studies reported equivocal results. We therefore investigated the effects of 30 min of LV applied to the right flexor carpi radialis muscle (FCR) on both short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). SICI and ICF were measured through transcranial magnetic stimulation before and immediately after 30 min of FCR LV (vibration condition) or 30 min of rest (control condition). Measurements were performed during a low-intensity contraction (n = 17) or at rest (n = 7). No significant SICI nor ICF modulations were observed, whether measured during isometric contractions or at rest (p = 0.2). Yet, we observed an increase in inter-individual variability for post measurements after LV. In conclusion, while intracortical excitability was not significantly modulated after LV, increased inter-variability observed after LV may suggest the possibility of divergent responses to prolonged LV exposure.

Transcutaneous auricular vagus nerve stimulation modifies cortical excitability in middle-aged and older adults.

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABAAergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.

Acute hypoalgesic, neurophysiological and perceptual responses to low-load blood flow restriction exercise and high-load resistance exercise.

This study compared the acute hypoalgesic and neurophysiological responses to low-load resistance exercise with and without blood flow restriction (BFR), and free-flow, high-load exercise. Participants performed four experimental conditions where they completed baseline measures of pain pressure threshold (PPT), maximum voluntary force (MVF) with peripheral nerve stimulation to determine central and peripheral fatigue. Corticospinal excitability (CSE), corticospinal inhibition and short interval intracortical inhibition (SICI) were estimated with transcranial magnetic stimulation. Participants then performed low-load leg press exercise at 30% of one-repetition maximum (LL); low-load leg press with BFR at 40% (BFR40) or 80% (BFR80) of limb occlusion pressure; or high-load leg press of four sets of 10 repetitions at 70% one-repetition maximum (HL). Measurements were repeated at 5, 45min and 24h post-exercise. There were no differences in CSE or SICI between conditions (all P>0.05); however, corticospinal inhibition was reduced to a greater extent (11%-14%) in all low-load conditions compared to HL (P<0.005). PPTs were 12%-16% greater at 5min post-exercise in BFR40, BFR80 and HL compared to LL (P≤0.016). Neuromuscular fatigue displayed no clear difference in the magnitude or time course between conditions (all P>0.05). In summary, low-load BFR resistance exercise does not induce different acute neurophysiological responses to low-load, free-flow exercise but it does promote a greater degree of hypoalgesia and reduces corticospinal inhibition more than high-load exercise, making it a useful rehabilitation tool. The changes in neurophysiology following exercise were not related to changes in PPT.

Current perspectives on neuromodulation in ALS patients: A systematic review and meta-analysis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.

Reduction in short interval intracortical inhibition from the early stage reflects the pathophysiology in amyotrophic lateral sclerosis: A meta-analysis study.

Cortical hyperexcitability has been identified as a diagnostic and pathogenic biomarker of amyotrophic lateral sclerosis (ALS). Cortical excitability is assessed by transcranial magnetic stimulation (TMS), a non-invasive neurophysiological technique. The TMS biomarkers exhibiting highest sensitivity for cortical hyperexcitability in ALS remain to be elucidated. A meta-analysis was performed to determine the TMS biomarkers exhibiting the highest sensitivity for cortical hyperexcitability in ALS. A systematic literature review was conducted of all relevant studies published in the English language by searching PubMed, MEDLINE, Embase and Scopus electronic databases from 1 January 2006 to 28 February 2023. Inclusion criteria included studies reporting the utility of threshold tracking TMS (serial ascending method) in ALS and controls. In total, more than 2500 participants, incorporating 1530 ALS patients and 1102 controls (healthy, 907; neuromuscular, 195) were assessed with threshold tracking TMS across 25 studies. Significant reduction of mean short interval intracortical inhibition (interstimulus interval 1-7 ms) exhibited the highest standardized mean difference with moderate heterogeneity (-0.994, 95% confidence interval -1.12 to -0.873, p < 0.001; Q = 38.61, p < 0.05; I2  = 40%). The reduction of cortical silent period duration along with an increase in motor evoked potential amplitude and intracortical facilitation also exhibited significant, albeit smaller, standardized mean differences. This large meta-analysis study disclosed that mean short interval intracortical inhibition reduction exhibited the highest sensitivity for cortical hyperexcitability in ALS. Combined findings from this meta-analysis suggest that research strategies aimed at understanding the cause of inhibitory interneuronal circuit dysfunction could enhance understanding of ALS pathogenesis.

Modulation of intracortical circuits in primary motor cortex during automatic action tendencies.

Humans display automatic action tendencies toward emotional stimuli, showing faster automatic behavior (i.e., approaching a positive stimulus and avoiding a negative stimulus) than regulated behavior (i.e., avoiding a positive stimulus and approaching a negative stimulus). Previous studies have shown that the primary motor cortex is involved in the processing of automatic actions, with higher motor evoked potential amplitudes during automatic behavior elicited by single-pulse transcranial magnetic stimulation. However, it is unknown how intracortical circuits are involved with automatic action tendencies. Here, we measured short-interval intracortical inhibition and intracortical facilitation within the primary motor cortex by using paired-pulse transcranial magnetic stimulation protocols during a manikin task, which has been widely used to explore approaching and avoiding behavior. Results showed that intracortical facilitation was stronger during automatic behavior than during regulated behavior. Moreover, there was a significant negative correlation between reaction times and intracortical facilitation effect during automatic behavior: individuals with short reaction times had stronger faciliatory activity, as shown by higher intracortical facilitation. By contrast, no significant difference was found for short-interval intracortical inhibition between automatic behavior and regulated behavior. The results indicated that the intracortical facilitation circuit, mediated by excitatory glutamatergic neurons, in the primary motor cortex, plays an important role in mediating automatic action tendencies. This finding further supports the link between emotional perception and the action system.

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD)

BackgroundThis study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). MethodsThe study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. ResultsAcute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. ConclusionsThe moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

Effects of different sonication parameters of theta burst transcranial ultrasound stimulation on human motor cortex

BackgroundTheta burst TUS (tbTUS) can induce increased cortical excitability in human, but how different sonication parameters influence the effects are still unknown. ObjectiveTo examine how a range of sonication parameters, including acoustic intensity, pulse repetition frequency, duty cycle and sonication duration, influence the effects of tbTUS on human motor cortical excitability. Methods14 right-handed healthy subjects underwent 8 sessions with different tbTUS parameters in a randomized, cross-over design on separate days. The original tbTUS protocol was studied in one session and one parameter was changed in each of the seven sessions. To examine changes in cortical excitability induced by tbTUS, we measured the motor-evoked potential (MEP) amplitude, resting motor threshold, short-interval intracortical inhibition and intracortical facilitation, as well as short-interval intracortical facilitation before and up to 90 min after tbTUS. ResultsAll conditions increased MEP amplitudes except the condition with low acoustic intensity of 10 W/cm2. Pulse repetition frequency of 5 Hz produced higher MEP amplitudes compared to pulse repetition frequencies of 2 and 10 Hz. In addition, higher duty cycles (5%, 10%, and 15%) and longer sonication durations (40, 80, and 120 s) were associated with longer duration of increased MEP amplitudes. Resting motor threshold remained stable in all conditions. For paired-pulse TMS measures, tbTUS reduced short-interval intracortical inhibition and enhanced short-interval intracortical facilitation, but had no effect on intracortical facilitation. ConclusionsUltrasound bursts repeated at theta (∼5 Hz) frequency is optimal to produce increased cortical excitability with the range of 2–10 Hz. Furthermore, there was a dose-response effect regarding duty cycle and sonication duration in tbTUS for plasticity induction. The aftereffects of tbTUS were associated with a shift of the inhibition/excitation balance toward less inhibition and more excitation in the motor cortex. These findings can be used to determine the optimal tbTUS parameters in neuroscience research and treatment of neurological and psychiatric disorders.

Modulation of Motor Cortical Inhibition and Facilitation by Touch Sensation from the Glabrous Skin of the Human Hand.

Touch sensation from the glabrous skin of the hand is essential for precisely controlling dexterous movements, yet the neural mechanisms by which tactile inputs influence motor circuits remain largely unexplored. By pairing air-puff tactile stimulation on the hand's glabrous skin with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), we examined the effects of tactile stimuli from single or multiple fingers on corticospinal excitability and M1's intracortical circuits. Our results showed that when we targeted the hand's first dorsal interosseous (FDI) muscle with TMS, homotopic (index finger) tactile stimulation, regardless of its point (fingertip or base), reduced corticospinal excitability. Conversely, heterotopic (ring finger) tactile stimulation had no such effect. Notably, stimulating all five fingers simultaneously led to a more pronounced decrease in corticospinal excitability than stimulating individual fingers. Furthermore, tactile stimulation significantly increased intracortical facilitation (ICF) and decreased long-interval intracortical inhibition (LICI) but did not affect short-interval intracortical inhibition (SICI). Considering the significant role of the primary somatosensory cortex (S1) in tactile processing, we also examined the effects of downregulating S1 excitability via continuous theta burst stimulation (cTBS) on tactile-motor interactions. Following cTBS, the inhibitory influence of tactile inputs on corticospinal excitability was diminished. Our findings highlight the spatial specificity of tactile inputs in influencing corticospinal excitability. Moreover, we suggest that tactile inputs distinctly modulate M1's excitatory and inhibitory pathways, with S1 being crucial in facilitating tactile-motor integration.

Effects of motor cortical and peripheral axonal hyperexcitability on survival in amyotrophic lateral sclerosis

BackgroundIncreased ‘cortical’ and ‘peripheral’ excitability are reportedly associated with shorter survival in amyotrophic lateral sclerosis (ALS) patients, suggesting that hyperexcitability contributes to motor neuron death. However, whether upper or lower...

The role of dorsal premotor cortex in joint action inhibition

Behavioral interpersonal coordination requires smooth negotiation of actions in time and space (joint action—JA). Inhibitory control may play a role in fine-tuning appropriate coordinative responses. To date, little research has been conducted on motor inhibition during JA and on the modulatory influence that premotor areas might exert on inhibitory control. Here, we used an interactive task in which subjects were required to reach and open a bottle using one hand. The bottle was held and stabilized by a co-actor (JA) or by a mechanical holder (vice clamp, no-JA). We recorded two TMS-based indices of inhibition (short-interval intracortical inhibition—sICI; cortical silent period—cSP) during the reaching phase of the task. These reflect fast intracortical (GABAa-mediated) and slow corticospinal (GABAb-mediated) inhibition. Offline continuous theta burst stimulation (cTBS) was used to interfere with dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and control site (vertex) before the execution of the task. Our results confirm a dissociation between fast and slow inhibition during JA coordination and provide evidence that premotor areas drive only slow inhibitory mechanisms, which in turn may reflect behavioral co-adaptation between trials. Exploratory analyses further suggest that PMd, more than PMv, is the key source of modulatory drive sculpting movements, according to the socio-interactive context.

Distinct neuronal circuits mediate cortical hyperexcitability in amyotrophic lateral sclerosis.

Cortical hyperexcitability is an important pathophysiological mechanism in amyotrophic lateral sclerosis (ALS), reflecting a complex interaction of inhibitory and facilitatory interneuronal processes that evolves in the degenerating brain. The advances in physiological techniques have made it possible to interrogate progressive changes in the motor cortex. Specifically, the direction of transcranial magnetic stimulation (TMS) stimulus within the primary motor cortex can be utilised to influence descending corticospinal volleys and to thereby provide information about distinct interneuronal circuits. Cortical motor function and cognition was assessed in 29 ALS patients with results compared to healthy volunteers. Cortical dysfunction was assessed using threshold-tracking TMS to explore alterations in short interval intracortical inhibition (SICI), short interval intracortical facilitation (SICF), the index of excitation (IE), and stimulus response (SR) curves using a figure-of-eight coil with the coil oriented relative to the primary motor cortex in a posterior-anterior (PA), lateral-medial (LM), and anterior-posterior (AP) direction. Mean SICI, between interstimulus interval (ISI) of 1-to-7 ms, was significantly reduced in ALS patients compared to healthy controls when assessed with the coil oriented in PA (P = 0.044) and LM (P = 0.005) but not the AP (P = 0.08) directions. A significant correlation between mean SICI oriented in a PA direction and the total Edinburgh Cognitive and Behavioural ALS Screen score (Rho = 0.389, P = 0.037) was evident. In addition, the mean SICF, between ISI 1-to-5 ms, was significantly increased in ALS patients when recorded with TMS coil oriented in PA (P = 0.035) and LM (P < 0.001) directions. In contrast, SICF recorded with TMS coil oriented in the AP direction was comparable between ALS and controls (P = 0.482). The IE was significantly increased in ALS patients when recorded with the TMS coil oriented in PA (P = 0.041) and LM (P = 0.003) directions. In ALS patients, a significant increase in the SR curve gradient was evident compared to controls when recorded with TMS coil oriented in PA (P < 0.001), LM (P < 0.001) and AP (P = 0.002) directions. The present study has established that dysfunction of distinct interneuronal circuits mediates the development of cortical hyperexcitability in ALS. Specifically, complex interplay between inhibitory circuits and facilitatory interneuronal populations, that are preferentially activated by stimulation in posterior-to-anterior or lateral-to-medial directions, promotes cortical hyperexcitability in ALS. Mechanisms that underlie dysfunction of these specific cortical neuronal circuits will enhance understanding of the pathophysiological processes in ALS, with the potential to uncover focussed therapeutic targets.

Short-term changes in the physiology of the primary motor cortex following head impact exposure during a Canadian football game.

This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations. Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05). Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

The effect of single and dual task training on the intracortical inhibition in healthy young adults

Introduction&#x0D; The evidence for changes in intracortical inhibition when executing two tasks simultaneously (i.e., dual tasking) is ambiguous as decreased (Corp et al., 2014) and increased (Corp et al., 2016) inhibition were reported. One way to bring more light into this question is to tests the effect of a single task training (STT) and a dual task training (DTT) on the short interval intracortical inhibition (SICI) during a single balancing task and two different dual tasks in healthy young adults.&#x0D; Methods&#x0D; Twenty-nine healthy young adults were randomly separated into two groups participating in STT (n = 15) or DTT (n = 14) consisting of 6 training sessions within 3 weeks. Before and after the training, a single task (balancing on a rocker board) was performed at two resistance levels (easy and hard). Additionally to the single task, either a cognitive (2-back number recall) or a motor (balancing a ball on a hand-held tray) dual task was executed simultaneously. During execution of these three tasks, SICI was measured with transcranial magnetic stimulation over the motor cortical area representing the right tibialis anterior.&#x0D; Results&#x0D; Training improvements in balance performance were group and task-specific over time (p = .018). While the STT group improved more in the single balance task (12.3% vs. 6.6% DTT), the DTT group had more sway reductions in the motor dual task condition (13.7% vs. 4.5% STT). Similar statistical outcome (p = .034) was observed for the dual task costs (DTC). There was a tendence for SICI (p = .075), mainly indicating higher increase in SICI for the DTT group in the motor dual task (16.0% vs. 5.8% STT). During the execution of the single balance task, the group-specific adaptations in SICI were less pronounced (13.7% DTT vs. 16.2% STT). When analyzing the SICI dual task difference (Δ) from single to dual task, SICI is altered group and task specific (p = .011). The DTT group could increase the dual task difference in SICI in the dual motor condition (Δ 3.2%), whereas the STT group had a decrease (Δ -9.6%).&#x0D; Discussion/Conclusion&#x0D; The results of this study show that DTT causes gains in balance performance and increases in SICI when the secondary task is also a motor task, but not when the second task is a cognitive one. STT is particularly beneficial in the single task. It is therefore assumed that intracortical inhibition is important during the simultaneous performance of two motor tasks, while intracortical inhibition was not modulated in a group-specific manner by the additional cognitive task.&#x0D; References&#x0D; Corp, D. T., Lum, J. A. G., Tooley, G. A., &amp; Pearce, A. J. (2014). Corticospinal activity during dual tasking: A systematic review and meta-analysis of TMS literature from 1995 to 2013. Neuroscience &amp; Biobehavioral Reviews, 43, 74-87. https://doi.org/10.1016/j.neubiorev.2014.03.017&#x0D; Corp, D. T., Rogers, M. A., Youssef, G. J., &amp; Pearce, A. J. (2016). The effect of dual-task difficulty on the inhibition of the motor cortex. Experimental Brain Research, 234, 443-452. https://doi.org/10.1007/s00221-015-4479-2

Improved subjective sleep quality after three months of balance learning in older adults

Introduction&#x0D; Around half of adults over the age of 60 experience sleep problems (Reid et al., 2006). The most common treatments for sleep disorders like insomnia are pharmacotherapy and cognitive behavioural therapy. Unfortunately, pharmacotherapy often leads to increased mortality and fall rates in older adults, whereas cognitive behavioural therapy is expensive and difficult to access (Patel et al., 2018). Hence, there is an urgent need for new effective and affordable treatments with reduced negative side effects. An important role for the initiation and maintenance of sleep is attributed to gamma-aminobutyric acid (GABA)-mediated inhibition (Saper et al., 2005). On one hand, it has been shown that GABA-mediated inhibition as well as GABA concentrations are lower in older compared to younger adults (Cuypers et al., 2018). On the other hand, balance training was shown to increase GABA-mediated inhibition in young (Taube et al., 2020) and older adults (Kuhn et al., 2023). Therefore, balance learning seems to be a promising treatment for older adults suffering from sleep problems. Furthermore, balance learning was shown to enhance functional connectivity (Ueta et al., 2022). In particular, functional connectivity in the sensorimotor cortex has been associated with better subjective sleep quality (Jiang et al., 2023). Therefore, we hypothesized that balance learning in older adults improves subjective sleep quality through an increase in GABA-mediated inhibition and sensorimotor network functional connectivity.&#x0D; Methods&#x0D; Forty healthy volunteers aged 64-81 years were randomly assigned to either follow a three-month balance learning intervention (minimum of 30 training sessions) or to continue with their daily routines. Thirty-six participants (18 in intervention group, 18 in control group) completed pre and post measurements and were included in the analysis. Before and after the three-month period, subjective sleep quality, balance performance, and neurophysiological and neuroimaging parameters were assessed. The Pittsburgh Sleep Quality Questionnaire (PSQI) was employed to evaluate subjective sleep quality in the preceding four weeks. Balance performance was assessed by determining the sway area in cm2 during a twenty second balance task on the most difficult wobble board level the participant still succeeded at. Short- interval intracortical inhibition (SICI), a measure of the activity of inhibitory interneurons in the motor cortex, was measured using transcranial magnetic stimulations while the participants were balancing on the same wobble board as during the balance performance assessment, and during an afternoon nap. Furthermore, resting-state functional connectivity was assessed with functional magnetic resonance imaging. The PSQI total scores were not normally distributed and therefore square root- transformed prior to the statistical analysis. Differences between post measurements were analysed using analysis of covariance (ANCOVA) with pre values as a covariate. Post-hoc t-tests were applied to determine the direction of change. Correlations between improvements in balance performance and sleep quality and neurochemical and neurophysiological measures were calculated using Spearman correlation analysis.&#x0D; Results&#x0D; ANCOVA revealed a significant effect of group on balance performance (p = 0.025). Post-hoc tests showed a significant improvement in performance after balance learning, indicated by a mean decrease of sway area by 33% (p = 0.002), while there was no significant change in the control group (p = 0.365). Furthermore, increases in balance performance were significantly associated with increases in SICI during execution of a balance task (r = -0.54, p = 0.02). ANCOVA revealed a significant effect of group on PSQI total score (p = 0.04). Post-hoc tests showed a significant decrease in the balance group by 23% (p = 0.015), indicating better subjective sleep quality after balance learning, while there was no significant change in the control group (p = 0.72). Improved subjective sleep quality in the balance group showed a trend towards an association with increased SICI while participants were falling asleep (r = -0.59, p = 0.07). Furthermore, there was a significant effect of group on functional connectivity (p = 0.005). In the balance group, functional connectivity increased by 40% (p = 0.003), while there were no significant changes in the control group (p = 0.32; p = 0.34). Correlation analysis at the population level revealed significant correlations between SICI during a balance task and balance performance (r = -0.4, p = 0.02), between SICI while balancing and functional connectivity (r = 0.38, p = 0.04), and between functional connectivity and balance performance (r = -0.5, p = 0.006).&#x0D; Discussion/Conclusion&#x0D; After three months of balance learning, older adults did not only show an improved balance performance but also significant improvements in their subjective sleep quality. Moreover, functional connectivity was significantly enhanced after balance learning and was positively associated with changes in SICI during execution of a balance task. These findings may be explained by the idea that functional connectivity plays a crucial role in the functional use of GABA, modulating inhibition across brain regions. Furthermore, the concept of task-specificity of intracortical inhibition is endorsed by the finding that specifically participants who showed an increase in GABAergic inhibition while falling asleep improved their subjective sleep quality. In conclusion, balance learning did improve subjective sleep quality and changes in functional connectivity and GABAergic inhibition might be (part of) the underlying mechanisms driving this change.&#x0D; References&#x0D; Cuypers, K., Maes, C., &amp; Swinnen, S. P. (2018). Aging and GABA. Aging, 10(6), 1186-1187. https://doi.org/10.18632/aging.101480&#x0D; Jiang, C., Cai, S., &amp; Zhang, L. (2023). Functional connectivity of white matter and its association with sleep quality. Nature and Science of Sleep, 15, 287-300. https://doi.org/10.2147/NSS.S406120&#x0D; Kuhn, Y.-A., Bugnon, M., Egger, S., Lehmann, N., Taubert, M., &amp; Taube, W. (2023). Age-related decline in GABAergic intracortical inhibition can be counteracted by long-term learning of balance skills [Manuscript submitted for publication]. Neurosciences and Movement Science, University of Fribourg.&#x0D; Patel, D., Steinberg, J., &amp; Patel, P. (2018). Insomnia in the elderly: A review. Journal of Clinical Sleep Medicine, 14(6), 1017-1024. https://doi.org/10.5664/jcsm.7172&#x0D; Reid, K. J., Martinovich, Z., Finkel, S., Statsinger, J., Golden, R., Harter, K., &amp; Zee, P. C. (2006). Sleep: A marker of physical and mental health in the elderly. The American Journal of Geriatric Psychiatry, 14(10), 860-866. https://doi.org/10.1097/01.JGP.0000206164.56404.ba&#x0D; Saper, C. B., Scammell, T. E., &amp; Lu, J. (2005). Hypothalamic regulation of sleep and circadian rhythms. Nature, 437(7063), 1257-1263. https://doi.org/10.1038/nature04284&#x0D; Taube, W., Gollhofer, A., &amp; Lauber, B. (2020). Training-, muscle- and task-specific up- and downregulation of cortical inhibitory processes. European Journal of Neuroscience, 51(6), 1428-1440. https://doi.org/10.1111/ejn.14538&#x0D; Ueta, K., Mizuguchi, N., Sugiyama, T., Isaka, T., &amp; Otomo, S. (2022). The Motor Engram of Functional Connectivity Generated by Acute Whole-Body Dynamic Balance Training. Medicine and Science in Sports and Exercise, 54(4), 598-608. https://doi.org/10.1249/MSS.0000000000002829

Repetitive magnetic stimuli over the motor cortex impair long-term consolidation of a balance task by suppressing up-regulation of intracortical inhibition

Introduction&#x0D; Recent findings have demonstrated that low-frequency repetitive magnetic stimulations (rTMS) over the primary motor cortex (M1) impaired short-term consolidation of a balance task, underscoring the causal connection between M1 and the consolidation of balancing skills (Egger et al., 2023). However, the underlying neural mechanisms induced by rTMS and whether these adaptations endure over an extended period, encompassing multiple acquisition sessions, remain insufficiently elucidated (Censor &amp; Cohen, 2011). So far, its is widely acknowledged that GABAergic processes play an important role for consolidation (Sanes &amp; Donoghue, 2000), at the same time, are affected by learning balance skills (Mouthon &amp; Taube, 2019; Taube et al., 2020). Therefore, the present study aimed to investigate the impact of rTMS on GABA-mediated short-interval intracortical inhibition (SICI) and to explore the role of M1 in the long-term consolidation of a balance task (i.e., across multiple acquisition sessions).&#x0D; Methods&#x0D; Thirty-one volunteers underwent six balance acquisition sessions on a rocker-board, each followed by either rTMS or sham rTMS based on group affiliation. During the first and last training session, SICI was measured twice; before the balance acquisition and after the application of rTMS or sham-rTMS to investigate potential short- and long-term adaptations in intracortical inhibition. Adaptations were assessed during the execution of the learned balance task and in a non-learning postural control task (i.e., stable upright stance).&#x0D; Results&#x0D; Regardless of group affiliation, all participants achieved comparable improvements within the balance acquisition sessions. However, consolidation varied between groups. In particular, between the third and the fourth acquisition session, as Tukey corrected post-hoc tests showed a significant decline in performance for the rTMS group (p = 0.006). Both short- (p = 0.014) and long-term (p = 0.038) adaptations in SICI were affected by rTMS: while the sham rTMS group upregulated SICI, rTMS led to reduced levels of inhibition. No neurophysiological effects were observed in the non-learning control task (upright stance).&#x0D; Discussion/Conclusion&#x0D; The interfering effect of rTMS on balance consolidation and on upregulation of SICI indicates that increased intracortical inhibition is an important mechanism to protect and engrave newly acquired motor memory. Importantly, adaptations in SICI were only apparent during the execution of the learned task.&#x0D; References&#x0D; Censor, N., &amp; Cohen, L. G. (2011). Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory. The Journal of Physiology, 589(1), 21-28. https://doi.org/10.1113/jphysiol.2010.198077&#x0D; Egger, S., Wälchli, M., Rüeger, E., &amp; Taube, W. (2023). Short-term balance consolidation relies on the primary motor cortex: A rTMS study. Scientific Reports, 13, Article 5169. https://doi.org/10.1038/s41598-023-32065-x&#x0D; Mouthon, A., &amp; Taube, W. (2019). Intracortical inhibition increases during postural task execution in response to balance training. Neuroscience, 401, 35-42. https://doi.org/10.1016/j.neuroscience.2019.01.007&#x0D; Sanes, J. N., &amp; Donoghue, J. P. (2000). Plasticity and primary motor cortex. Annual Review of Neuroscience, 23, 393-415. https://doi.org/10.1146/annurev.neuro.23.1.393&#x0D; Taube, W., Gollhofer, A., &amp; Lauber, B. (2020). Training-, muscle- and task-specific up- and downregulation of cortical inhibitory processes. The European Journal of Neuroscience, 51(6), 1428-1440. https://doi.org/10.1111/ejn.14538

Abstract TMP35: Short Interval Intracortical Inhibition is Associated With Leg Motor Function in Chronic Stroke

Objective: Stroke disrupts inhibitory and excitatory networks in the brain. To develop better therapies, we need to understand the role of inhibitory and excitatory systems. Paired-pulse transcranial magnetic stimulation (ppTMS) allows for evaluation of these inhibitory and excitatory systems. Our objective was to explore the relationship between Short Interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) ppTMS measures for tibialis anterior (TA) and measures of lower limb motor function in chronic stroke. Methods: Lower limb motor function was evaluated with Fugl-Meyer for Lower Limb (FM), gait speed (max and preferred), Timed-up-and-go (TUG), Functional Gait Assessment (FGA) and Gait Assessment and Intervention Tool (GAIT). SICI was collected with interstimulus interval of 2ms and ICF with 10ms. The conditioning stimulus was 90% and test stimulus was 120% of active motor threshold. Motor evoked potentials (MEPs) were collected for both paretic or non-paretic TAs while volitionally activated to 20% of maximum effort. SICI and ICF were calculated as percent of test stimulus (TS) amplitude. Analysis included descriptive statistics and linear models controlling for age, months post-stroke, and gender. TUG test time was log-transformed. Results: Study participants (n=34) were 66±8 years old, 4.9±4 years after stroke and 76% male. Mean±SD FM was 25.1±3.7 and preferred gait speed was 0.52±0.30 m/s. Relative to TS amplitude, SICI was 107±27% and ICF was 175±71% for paretic leg and, for non-paretic leg, SICI was 108±42% and ICF was 159±66%. For paretic leg after controlling for ICF, a 10% lower SICI was associated with the following: 0.89 point better FM (95% CI: 0.37-1.42), 14% better TUG (95% CI: 3-23%), 0.08 m/s faster max speed (95% CI: 0.02-0.14), and 0.05 m/s faster preferred walking speed (95% CI: 0.01-0.10). For non-paretic limb, a 10% lower SICI was associated with a 0.43 point better FGA (95% CI: 0.11-0.76) while a 10% lower ICF was associated with a 0.73 point better GAIT (95% CI: 0.37-1.10). Conclusion: Greater inhibition with paired pulse of both paretic and non-paretic limbs was predictive better motor abilities. These findings are related to previous work and warrant future investigations.

Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study.

The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function. A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery. Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles ( P < 0.001), lower resting motor threshold (-10.5% of the stimulator output, 95% CI: -16.8 to -4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (-1.1, 95% CI: -1.7 to -0.5, P = 0.001, Cohen d = 0.915). Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.

Beta rebound reduces subsequent movement preparation time by modulating of GABAA inhibition.

Post-movement beta synchronization is an increase of beta power relative to baseline, which commonly used to represent the status quo of the motor system. However, its functional role to the subsequent voluntary motor output and potential electrophysiological significance remain largely unknown. Here, we examined the reaction time of a Go/No-Go task of index finger tapping which performed at the phases of power baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds (ballistic/self-paced) in 13 healthy subjects. We found a correlation between the post-movement beta synchronization and reaction time that larger post-movement beta synchronization prolonged the reaction time during Go trials. To probe the electrophysiological significance of post-movement beta synchronization, we assessed intracortical inhibitory measures probably involving GABAB (long-interval intracortical inhibition) and GABAA (short-interval intracortical inhibition) receptors in beta baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds. We found that short-interval intracortical inhibition but not long-interval intracortical inhibition increased in post-movement beta synchronization peak compared with that in the power baseline, and was negatively correlated with the change of post-movement beta synchronization peak value. These novel findings indicate that the post-movement beta synchronization is related to forward model updating, with high beta rebound predicting longer time for the preparation of subsequent movement by inhibitory neural pathways of GABAA.

Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial

BackgroundTranscranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI).MethodsThis study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase.DiscussionThe study’s findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment.Trial registrationChinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.