Examining motor evoked potential amplitude and short-interval intracortical inhibition on the up-going and down-going phases of a transcranial alternating current stimulation (tacs) imposed alpha oscillation.

Many brain regions exhibit rhythmical activity thought to reflect the summed behaviour of large populations of neurons. The endogenous alpha rhythm has been associated with phase-dependent modulation of corticospinal excitability. However, whether exogenous alpha rhythm, induced using transcranial alternating current stimulation (tACS) also has a phase-dependent effect on corticospinal excitability remains unknown. Here, we triggered transcranial magnetic stimuli (TMS) on the up- or down-going phase of a tACS-imposed alpha oscillation and measured motor evoked potential (MEP) amplitude and short-interval intracortical inhibition (SICI). There was no significant difference in MEP amplitude or SICI when TMS was triggered on the up- or down-going phase of the tACS-imposed alpha oscillation. The current study provides no evidence of differences in corticospinal excitability or GABAergic inhibition when targeting the up-going (peak) and down-going (trough) phase of the tACS-imposed oscillation.

The Role of Alpha Power in the Suppression of Anticipated Distractors During Verbal Working Memory.

As working memory (WM) is limited in capacity, it is important to direct neural resources towards processing task-relevant information while ignoring distractors. Neural oscillations in the alpha frequency band (8-12 Hz) have been suggested to play a role in the inhibition of task-irrelevant information during WM, although results are mixed, possibly due to differences in the type of WM task employed. Here, we examined the role of alpha power in suppression of anticipated distractors of varying strength using a modified Sternberg task where the encoding and retention periods were temporally separated. We recorded EEG while 20 young adults completed the task and found: (1) slower reaction times in strong distractor trials compared to weak distractor trials; (2) increased alpha power in posterior regions from baseline prior to presentation of a distractor regardless of condition; and (3) no differences in alpha power between strong and weak distractor conditions. Our results suggest that parieto-occipital alpha power is increased prior to a distractor. However, we could not find evidence that alpha power is further modulated by distractor strength.

Intermittent single-joint fatiguing exercise reduces TMS-EEG measures of cortical inhibition.

Fatiguing intermittent single-joint exercise causes an increase in corticospinal excitability and a decrease in intracortical inhibition when measured with peripherally recorded motor evoked potentials (MEPs) after transcranial magnetic stimulation (TMS). Combined TMS and electroencephalography (TMS-EEG) allows for more direct recording of cortical responses through the TMS-evoked potential (TEP). The aim of this study was to investigate the changes in the excitatory and inhibitory components of the TEP during fatiguing single-joint exercise. Twenty-three young (22 ± 2 yr) healthy subjects performed intermittent 30-s maximum voluntary contractions of the right first dorsal interosseous muscle, followed by a 30-s relaxation period repeated for a total of 15 min. Six single-pulse TMSs and one peripheral nerve stimulation (PNS) to evoke maximal M wave (Mmax) were applied during each relaxation period. A total of 90 TMS pulses and 5 PNSs were applied before and after fatiguing exercise to record MEP and TEP. The amplitude of the MEP (normalized to Mmax) increased during fatiguing exercise ( P < 0.001). There were no changes in local and global P30, N45, and P180 of TEPs during the development of intermittent single-joint exercise-induced fatigue. Global analysis, however, revealed a decrease in N100 peak of the TEP during fatiguing exercise compared with before fatiguing exercise ( P = 0.02). The decrease in N100 suggests a fatigue-related decrease in global intracortical GABAB-mediated inhibition. The increase in corticospinal excitability typically observed during single-joint fatiguing exercise may be mediated by a global decrease in intracortical inhibition. NEW & NOTEWORTHY Fatiguing intermittent single-joint exercise causes an increase in corticospinal excitability and a decrease in intracortical inhibition when measured with transcranial magnetic stimulation (TMS)-evoked potentials from the muscle. The present study provides new and direct cortical evidence, using TMS-EEG to demonstrate that during single-joint fatiguing exercise there is a global decrease in intracortical GABAB-mediated inhibition.

Transcranial Magnetic Stimulation-EEG Biomarkers of Poststroke Upper-Limb Motor Function.

BACKGROUND: Motor evoked potentials obtained with transcranial magnetic stimulation (TMS) can provide valuable information to inform stroke neurophysiology and recovery but are difficult to obtain in all stroke survivors due to high stimulation thresholds. OBJECTIVE: To determine whether transcranial magnetic stimulation evoked potentials (TEPs) evoked using a lower stimulus intensity, below that necessary for recording motor evoked potentials, could serve as a marker of poststroke upper-limb motor function and were different compared to healthy adults. METHODS: Eight chronic stroke survivors (66 ± 21 years) and 15 healthy adults (53 ± 10 years) performed a motor function task using a customized grip-lift manipulandum. TMS was applied to the lesioned motor cortex, with TEPs recorded using simultaneous high-definition electroencephalography (EEG). RESULTS: Stroke participants demonstrated greater hold ratio with the manipulandum. Cluster-based statistics revealed larger P30 amplitude in stroke participants, with significant clusters over frontal (P = .016) and parietal-occipital electrodes (P = .023). There was a negative correlation between the N45 peak amplitude and hold ratio in stroke participants (r = -.83, P = .02), but not controls. CONCLUSIONS: TEPs can be recorded using lower stimulus intensities in chronic stroke. The global P30 TEP response differed between stroke participants and healthy controls, with results suggesting that the TEP can be used as a biomarker of upper-limb behavior.

Simulation of electromyographic recordings following transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a technique that enables noninvasive manipulation of neural activity and holds promise in both clinical and basic research settings. The effect of TMS on the motor cortex is often measured by electromyography (EMG) recordings from a small hand muscle. However, the details of how TMS generates responses measured with EMG are not completely understood. We aim to develop a biophysically detailed computational model to study the potential mechanisms underlying the generation of EMG signals following TMS. Our model comprises a feed-forward network of cortical layer 2/3 cells, which drive morphologically detailed layer 5 corticomotoneuronal cells, which in turn project to a pool of motoneurons. EMG signals are modeled as the sum of motor unit action potentials. EMG recordings from the first dorsal interosseous muscle were performed in four subjects and compared with simulated EMG signals. Our model successfully reproduces several characteristics of the experimental data. The simulated EMG signals match experimental EMG recordings in shape and size, and change with stimulus intensity and contraction level as in experimental recordings. They exhibit cortical silent periods that are close to the biological values and reveal an interesting dependence on inhibitory synaptic transmission properties. Our model predicts several characteristics of the firing patterns of neurons along the entire pathway from cortical layer 2/3 cells down to spinal motoneurons and should be considered as a viable tool for explaining and analyzing EMG signals following TMS. NEW & NOTEWORTHY A biophysically detailed model of EMG signal generation following transcranial magnetic stimulation (TMS) is proposed. Simulated EMG signals match experimental EMG recordings in shape and amplitude. Motor-evoked potential and cortical silent period properties match experimental data. The model is a viable tool to analyze, explain, and predict EMG signals following TMS.

Neuroplasticity and network connectivity of the motor cortex following stroke: A transcranial direct current stimulation study.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that has potential for clinical utility in neurorehabilitation. However, recent evidence indicates that the responses to tDCS are highly variable. This study investigated whether electroencephalographic (EEG) measures of functional connectivity of the target network were associated with the response to ipsilesional anodal tDCS in stroke survivors. Ten chronic stroke patients attended two experimental sessions in a randomized cross-over trial and received anodal or sham tDCS. Single-pulse transcranial magnetic stimulation was used to quantify change in corticospinal excitability following tDCS. At the beginning of each session, functional connectivity was estimated using the debiased-weighted phase lag index from EEG recordings at rest. Magnetic resonance imaging identified lesion location and lesion volume. Partial least squares regression identified models of connectivity which maximally accounted for variance in anodal tDCS responses. Stronger connectivity of a network with a seed approximating the stimulated ipsilesional motor cortex, and clusters of electrodes approximating the ipsilesional parietal cortex and contralesional frontotemporal cortex in the alpha band (8-13 Hz) was strongly associated with a greater increase of corticospinal excitability following anodal tDCS. This association was not observed following sham stimulation. Addition of a structural measure(s) of injury (lesion volume) provided an improved model fit for connectivity between the seed electrode and ipsilesional parietal cortex, but not the contralesional frontotemporal cortex. TDCS has potential to greatly assist stroke rehabilitation and functional connectivity appears a robust and specific biomarker of response which may assist clinical translation of this therapy.

Resting state functional connectivity measures correlate with the response to anodal transcranial direct current stimulation.

Responses to non-invasive brain stimulation are highly variable between subjects. Resting state functional connectivity was investigated as a marker of plasticity induced by anodal transcranial direct current stimulation (tDCS). Twenty-six healthy adults (15 male, 26.4 ± 6.5 years) were tested. Experiment 1 investigated whether functional connectivity could predict modulation of corticospinal excitability following anodal tDCS. Experiment 2 determined test-retest reliability of connectivity measures. Three minutes of electroencephalography was recorded and connectivity was quantified with the debiased weighted phase lag index. Anodal (1 mA, 20 min) or sham tDCS was applied to the left primary motor cortex (M1), with a change in motor evoked potential amplitude recorded from the right first dorsal interosseous used as a marker of tDCS response. Connectivity in the high beta frequency (20-30 Hz) between an electrode approximating the left M1 (C3) and electrodes overlying the left parietal cortex was a strong predictor of tDCS response (cross-validated R2  = 0.69). Similar relationships were observed for alpha (8-13 Hz; R2  = 0.64), theta (4-7 Hz; R2  = 0.53), and low beta (14-19 Hz; R2  = 0.58) frequencies, however, test-retest reliability of connectivity measures was strongest for the high beta frequency model (ICC = 0.65; good reliability). Further investigation of the high beta model found that greater connectivity between C3 and a cluster of electrodes approximately overlying the left parietal cortex was associated with stronger responses to anodal (rho = 0.61, P = 0.03), but not sham tDCS (rho = 0.43, P = 0.14). Functional connectivity is a strong predictor of the neuroplastic response to tDCS and may be one important characteristic to assist targeted tDCS application.

Combined transcranial alternating current stimulation and continuous theta burst stimulation: a novel approach for neuroplasticity induction.

Non-invasive brain stimulation can induce functionally relevant plasticity in the human cortex, making it potentially useful as a therapeutic tool. However, the induced changes are highly variable between individuals, potentially limiting research and clinical utility. One factor that might contribute to this variability is the level of cortical inhibition at the time of stimulation. The alpha rhythm (~ 8-13 Hz) recorded with electroencephalography (EEG) is thought to reflect pulsatile cortical inhibition; therefore, targeting non-invasive brain stimulation to particular phases of the alpha rhythm may provide an approach to enhance plasticity induction. Transcranial alternating current stimulation (tACS) has been shown to entrain cortical oscillations in a frequency-specific manner. We investigated whether the neuroplastic response to continuous theta burst stimulation (cTBS) was enhanced by timing bursts of stimuli to the peak or the trough of a tACS-imposed alpha rhythm. While motor evoked potentials (MEPs) were unaffected when cTBS was applied in-phase with the peak of the tACS-imposed oscillation, MEP depression was enhanced when cTBS was applied in-phase with the trough. This enhanced MEP depression was dependent on the individual peak frequency of the endogenous alpha rhythm recorded with EEG prior to stimulation, and was strongest in those participants classified as non-responders to standard cTBS. These findings suggest that tACS may be used in combination with cTBS to enhance the plasticity response. Furthermore, the peak frequency of endogenous alpha, as measured with EEG, may be used as a simple marker to pre-select those individuals likely to benefit from this approach.

Resistant Against De-depression: LTD-Like Plasticity in the Human Motor Cortex Induced by Spaced cTBS.

The long-term depression (LTD)-like changes in human primary motor cortex (M1) excitability induced by continuous theta burst stimulation (cTBS) are subject to reversal (i.e., de-depression) following behavioral engagement of M1, limiting its therapeutic potential under behaviorally relevant conditions. Experiments in animals suggest that the repeated, spaced application of stimulation trains may consolidate synaptic plasticity, making it resistant to reversal by physiological activity. Although there is evidence that repeated cTBS prolongs LTD-like M1 neuroplasticity in humans, whether these effects are resistant to de-depression has not been tested. We investigated whether the neuroplastic effects of paired cTBS trains were resistant to de-depression by a sustained, submaximal voluntary contraction of the hand muscles. In the absence of cTBS, voluntary contraction had no effect on motor evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. While the LTD-like MEP depression induced by a single cTBS was abolished by subsequent voluntary contraction, paired cTBS induced MEP depression that was resistant to reversal. This MEP depression was also resistant to reversal when an experimental de-depression protocol was used instead of a voluntary contraction. Our findings suggest that repeated cTBS applications consolidate LTD-like M1 neuroplasticity, which may have important implications for the clinical application of cTBS.

Task-related changes in intracortical inhibition assessed with paired- and triple-pulse transcranial magnetic stimulation.

Recent research has demonstrated a task-related modulation of postsynaptic intracortical inhibition within primary motor cortex for tasks requiring isolated (abduction) or synergistic (precision grip) muscle activation. The current study sought to investigate task-related changes in pre- and postsynaptic intracortical inhibition in motor cortex. In 13 young adults (22.5 ± 3.5 yr), paired-pulse transcranial magnetic stimulation (TMS) was used to measure short (SICI)- and long-interval intracortical inhibition (LICI) (i.e., postsynaptic motor cortex inhibition) in first dorsal interosseous muscle, and triple-pulse TMS was used to investigate changes in SICI-LICI interactions (i.e., presynaptic motor cortex inhibition). These measurements were obtained at rest and during muscle activation involving isolated abduction of the index finger and during a precision grip using the index finger and thumb. SICI was reduced during abduction and precision grip compared with rest, with greater reductions during precision grip. The modulation of LICI during muscle activation depended on the interstimulus interval (ISI; 100 and 150 ms) but was not different between abduction and precision grip. For triple-pulse TMS, SICI was reduced in the presence of LICI at both ISIs in resting muscle (reflecting presynaptic motor cortex inhibition) but was only modulated at the 150-ms ISI during index finger abduction. Results suggest that synergistic contractions are accompanied by greater reductions in postsynaptic motor cortex inhibition than isolated contractions, but the contribution of presynaptic mechanisms to this disinhibition is limited. Furthermore, timing-dependent variations in LICI provide additional evidence that measurements using different ISIs may not represent activation of the same cortical process.

An investigation of cortical neuroplasticity following stroke in adults: is there evidence for a critical window for rehabilitation?

BACKGROUND: Evidence in animal stroke models suggests that neuroplasticity takes place maximally in a specific time window after an ischaemic lesion, which may coincide with the optimal time to intervene with rehabilitation. The aim of this study is to investigate neurophysiological evidence for a "critical window" of enhanced neuroplasticity in patients following ischaemic stroke, and establish its duration. We will also investigate changes in cortical inhibition following stroke, and the influence this has on functional recovery. METHODS/DESIGN: We will recruit participants recently admitted to the Stroke Unit of major metropolitan hospitals who have had a stroke and can provide informed consent. Participants will be excluded if they have any contraindications to Transcranial Magnetic Stimulation. We will compare neurophysiological outcomes in an age-matched healthy control group. We conservatively hypothesise a 5% increase in neuroplasticity at the optimal timing following stroke, compared to control participants, and require 43 patients following stroke to detect a significant difference with 80% power. The primary outcome is the change in the motor evoked potential (MEP) amplitude in a hand muscle, after the administration of a plasticity-inducing paradigm to the affected hemisphere. Secondary outcomes include measures of cortical excitability, intracortical inhibition and arm function. DISCUSSION: The data from this trial will clarify whether there is a critical window for neuroplastic change in the brain following stroke. If so, intensive rehabilitation during this period could be more effective, reducing long-term disability and the cost burden of stroke.

Cognitive abilities in preterm and term-born adolescents.

OBJECTIVE: To investigate the influence of a range of prenatal and postnatal factors on cognitive development in preterm and term-born adolescents. STUDY DESIGN: Woodcock-Johnson III Tests of Cognitive Abilities were used to assess general intellectual ability and 6 broad cognitive abilities in 145 young adolescents aged approximately 12.5 years and born 25-41 weeks gestational age (GA). To study potential links between neurophysiologic and cognitive outcomes, corticomotor excitability was measured using transcranial magnetic stimulation and surface electromyography. The influence of various prenatal and postnatal factors on cognitive development was investigated using relative importance regression modeling. RESULTS: Adolescents with greater GA tended to have better cognitive abilities (particularly general intellectual ability, working memory, and cognitive efficiency) and higher corticomotor excitability. Corticomotor excitability explained a higher proportion of the variance in cognitive outcome than GA. But the strongest predictors of cognitive outcome were combinations of prenatal and postnatal factors, particularly degree of social disadvantage at the time of birth, birthweight percentile, and height at assessment. CONCLUSIONS: In otherwise neurologically healthy adolescents, GA accounts for little interindividual variability in cognitive abilities. The association between corticomotor excitability and cognitive performance suggests that reduced connectivity, potentially associated with brain microstructural abnormalities, may contribute to cognitive deficits in preterm children. It remains to be determined if the effects of low GA on cognitive outcomes attenuate over childhood in favor of a concomitant increase in the relative importance of heritability, or alternatively, if cognitive development is more heavily influenced by the quality of the postnatal environment.

Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain.

The cortisol awakening response (CAR) is the most prominent, dynamic and variable part of the circadian pattern of cortisol secretion. Despite this, its precise purpose is unknown. Aberrant patterns of the CAR are associated with impaired physical and mental health and reduced cognitive function, suggesting that it may have a pervasive role or roles. It has been suggested that the CAR primes the brain for the expected demands of the day but the mechanisms underlying this process are unknown. We examined temporal covariation of the CAR and rapid transcranial magnetic stimulation (rTMS)-induced long term depression (LTD)-like responses in the motor cortex. Plasticity was evaluated across 180 measures from five time points on four sessions across nine healthy researcher participants, mean age 25 ± 2.5 years. Plasticity estimates were obtained in the afternoon after measurement of the CAR on 4 days, at least 3 days apart. As both CAR magnitude and rTMS-induced responses are variable across days, we hypothesized that days with larger than individual average CARs would be associated with a greater than individual average plasticity response. This was confirmed by mixed regression modelling where variation in the CAR predicted variation in rTMS-induced responses (df: 1, 148.24; F: 10.41; p = 0.002). As the magnitude of the CAR is regulated by the "master" circadian CLOCK, and synaptic plasticity is known to be modulated by peripheral "slave" CLOCK genes, we suggest that the CAR may be a mediator between the master and peripheral circadian systems to entrain daily levels of synaptic plasticity.

The influence of a single bout of aerobic exercise on short-interval intracortical excitability.

Regular physical activity can have positive effects on brain function and plasticity. Indeed, there is some limited evidence that even a single bout of exercise may promote plasticity within the cortex. However, the mechanisms by which exercise acutely promotes plasticity are not clear. To further explore the effects of acute exercise on cortical function, we examined whether a single bout of exercise was associated with changes in cortical excitability and inhibition. Using standard techniques, cortical stimulus-response curves [90% resting motor threshold (RMT)-150% RMT] were investigated in nine subjects (four females, 31.1 ± 11.7 years) and short-interval intracortical inhibition (SICI) [interstimulus interval 2 ms and 3 ms, conditioning intensities of 80% active motor threshold (AMT) and 90% AMT] in 13 subjects (six females, 28.4 ± 5.1 years) before and at 0 and 15 min following 30 min of ergometer cycling at low-moderate or moderate-high intensity. There were no changes in cortical excitability following exercise but less SICI at both 0 and 15 min post-exercise (F [2, 24] = 7.7, P = 0.003). These findings show that a short period of exercise can transiently reduce SICI. Such a change in inhibition after exercise may contribute to the development of a cortical environment that would be more optimal for plasticity and may partially explain previous findings of enhanced neuroplasticity following low-intensity exercise.

Physiological evidence consistent with reduced neuroplasticity in human adolescents born preterm.

Preterm-born children commonly experience motor, cognitive, and learning difficulties that may be accompanied by altered brain microstructure, connectivity, and neurochemistry. However, the mechanisms linking the altered neurophysiology with the behavioral outcomes are unknown. Here we provide the first physiological evidence that human adolescents born preterm at or before 37 weeks of completed gestation have a significantly reduced capacity for cortical neuroplasticity, the key overall mechanism underlying learning and memory. We examined motor cortex neuroplasticity in three groups of adolescents who were born after gestations of ≤32 completed weeks (early preterm), 33-37 weeks (late preterm), and 38-41 weeks (term) using a noninvasive transcranial magnetic brain stimulation technique to induce long-term depression (LTD)-like neuroplasticity. Compared with term-born adolescents, both early and late preterm adolescents had reduced LTD-like neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels. We also compared neuroplasticity in term-born adolescents with that in term-born young adults, finding that the motor cortex retains a relatively enhanced neuroplastic capacity in adolescence. These findings provide a possible mechanistic link between the altered brain physiology of preterm birth and the subsequent associated behavioral deficits, particularly in learning and memory. They also suggest that altered hypothalamic-pituitary-adrenal axis function due to preterm birth may be a significant modulator of this altered neuroplasticity. This latter finding may offer options in the development of possible therapeutic interventions.

Motor cortex plasticity induced by theta burst stimulation is impaired in patients with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a respiratory condition occurring during sleep characterised by repeated collapse of the upper airway. Patients with OSA show altered brain structure and function that may manifest as impaired neuroplasticity. We assessed this hypothesis in 13 patients with moderate-to-severe OSA and 11 healthy control subjects. Transcranial magnetic stimulation was used to induce and measure neuroplastic changes in the motor cortex by assessing changes in motor-evoked potentials (MEPs) in a hand muscle. Baseline measurements of cortical excitability included active (AMT) and resting motor thresholds (RMT), and the maximal stimulator output producing a 1-mV MEP. Intracortical inhibition (ICI) was investigated with short- and long-interval ICI paradigms (SICI and LICI, respectively), and neuroplastic changes were induced using continuous theta burst stimulation (cTBS). At baseline, differences were found between groups for RMT (9.5% maximal stimulator output higher in OSA) and 1-mV MEPs (10.3% maximal stimulator output higher in OSA), but not AMT. No differences were found between groups for SICI or LICI. The response to cTBS was different between groups, with control subjects showing an expected reduction in MEP amplitude after cTBS, whereas the MEPs in patients with OSA did not change. The lack of response to cTBS suggests impaired long-term depression-like neuroplasticity in patients with OSA, which may be a consequence of sleep fragmentation or chronic blood gas disturbance in sleep. This reduced neuroplastic capacity may have implications for the learning, retention or consolidation of motor skills in patients with OSA.

Chronic tension-type headache is associated with impaired motor learning.

BACKGROUND: Supraspinal activity-dependent neuroplasticity may be important in the transition from acute to chronic pain. We examined neuroplasticity in a cortical region not considered to be a primary component of the central pain matrix in chronic tension-type headache (CTTH) patients. We hypothesised that neuroplasticity would be exaggerated in CTTH patients compared to healthy controls, which might explain (in part) the development of chronic pain in these individuals. METHODS: Neuroplasticity was examined following a ballistic motor training task in CTTH patients and control subjects (CS). Changes in peak acceleration (motor learning) and motor-evoked potential (MEP) amplitude evoked by single-pulse transcranial magnetic stimulation were compared. RESULTS: CTTH patients showed significantly less motor learning on the training task than CS (mean acceleration increase 87% CTTH, 204% CS, P < .05), and CS but not CTTH patients showed a significant increased MEP amplitude following training (CS: F = 2.9, P < .05; CTTH: F = 1.6, P > .05). CONCLUSIONS: These findings suggest a deficit in use-dependent neuroplasticity within networks responsible for task performance in CTTH patients which might reflect reciprocal influences between primary motor cortex and interconnected pain processing networks. These findings may help explain the positive effects of facilitatory non-invasive brain stimulation targeting motor areas on chronic pain and help elucidate the mechanisms mediating chronic pain.

Time of day does not modulate improvements in motor performance following a repetitive ballistic motor training task.

Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity. The present study investigated whether performance changes following a motor training task are modulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30 minutes of repeated maximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8 AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb abduction acceleration, significantly increased by 28% following training. Neuroplastic changes in corticomotor excitability of abductor pollicis brevis, quantified with TMS, increased significantly by 23% following training. Training-related motor performance improvements and neuroplasticity were unaffected by time of day and salivary cortisol concentration. Although similar neural elements and processes contribute to motor learning, training-induced neuroplasticity, and TMS-induced neuroplasticity, our findings suggest that the influence of time of day and cortisol differs for these three interventions.

The effect of electrical stimulation on corticospinal excitability is dependent on application duration: a same subject pre-post test design.

BACKGROUND: In humans, corticospinal excitability is known to increase following motor electrical stimulation (ES) designed to mimic a voluntary contraction. However, whether the effect is equivalent with different application durations and whether similar effects are apparent for short and long applications is unknown. The aim of this study was to investigate whether the duration of peripheral motor ES influenced its effect on corticospinal excitability. METHODS: The excitability of the corticomotor pathway to abductor pollicis brevis (APB) was measured in fourteen health subjects using transcranial magnetic stimulation before, immediately after and 10 minutes after three different durations (20-, 40-, 60-min) of motor ES (30Hz, ramped). This intervention was designed to mimic a voluntary contraction in APB. To control for effects of motor ES on the peripheral elements (muscle fibre, membrane, neuromuscular junction), maximum compound muscle actions potentials (M-waves) were also recorded at each time point. Results were analysed using a repeated measures analysis of variance. RESULTS: Peripheral excitability was reduced following all three motor ES interventions. Conversely, corticospinal excitability was increased immediately following 20- and 40-min applications of motor ES and this increase was maintained at least 20-min following the intervention. A 60-min application of motor ES did not alter corticospinal excitability. CONCLUSIONS: A 20-min application of motor ES that is designed to mimic voluntary muscle contraction is as effective as that applied for 40-min when the aim of the intervention is to increase corticospinal excitability. Longer motor ES durations of 60-min do not influence corticospinal excitability, possibly as a result of homeostatic plasticity mechanisms.

Reduced corticomotor excitability and motor skills development in children born preterm.

The mechanisms underlying the altered neurodevelopment commonly experienced by children born preterm, but without brain lesions, remain unknown. While individuals born the earliest are at most risk, late preterm children also experience significant motor, cognitive and behavioural dysfunction from school age, and reduced income and educational attainment in adulthood. We used transcranial magnetic stimulation and functional assessments to examine corticomotor development in 151 children without cerebral palsy, aged 10-13 years and born after gestations of 25-41 completed weeks. We hypothesized that motor cortex and corticospinal development are altered in preterm children, which underpins at least some of their motor dysfunction. We report for the first time that every week of reduced gestation is associated with a reduction in corticomotor excitability that remains evident in late childhood. This reduced excitability was associated with poorer motor skill development, particularly manual dexterity. However, child adiposity, sex and socio-economic factors regarding the child's home environment soon after birth were also powerful influences on development of motor skills. Preterm birth was also associated with reduced left hemisphere lateralization, but without increasing the likelihood of being left handed per se. These corticomotor findings have implications for normal motor development, but also raise questions regarding possible longer term consequences of preterm birth on motor function.