Changes in Cortical Activation by Transcranial Magnetic Stimulation Due to Coil Rotation Are Not Attributable to Cranial Muscle Activation.

Transcranial magnetic stimulation coupled with electroencephalography (TMS-EEG) allows for the study of brain dynamics in health and disease. Cranial muscle activation can decrease the interpretability of TMS-EEG signals by masking genuine EEG responses and increasing the reliance on preprocessing methods but can be at least partly prevented by coil rotation coupled with the online monitoring of signals; however, the extent to which changing coil rotation may affect TMS-EEG signals is not fully understood. Our objective was to compare TMS-EEG data obtained with an optimal coil rotation to induce motor evoked potentials (M1standard) while rotating the coil to minimize cranial muscle activation (M1emg). TMS-evoked potentials (TEPs), TMS-related spectral perturbation (TRSP), and intertrial phase clustering (ITPC) were calculated in both conditions using two different preprocessing pipelines based on independent component analysis (ICA) or signal-space projection with source-informed reconstruction (SSP-SIR). Comparisons were performed with cluster-based correction. The concordance correlation coefficient was computed to measure the similarity between M1standard and M1emg TMS-EEG signals. TEPs, TRSP, and ITPC were significantly larger in M1standard than in M1emg conditions; a lower CCC than expected was also found. These results were similar across the preprocessing pipelines. While rotating the coil may be advantageous to reduce cranial muscle activation, it may result in changes in TMS-EEG signals; therefore, this solution should be tailored to the specific experimental context.

Investigating Cerebellar Modulation of Premovement Beta-Band Activity during Motor Adaptation.

Enhancing cerebellar activity influences motor cortical activity and contributes to motor adaptation, though it is unclear which neurophysiological mechanisms contributing to adaptation are influenced by the cerebellum. Pre-movement beta event-related desynchronization (ß-ERD), which reflects a release of inhibitory control in the premotor cortex during movement planning, is one mechanism that may be modulated by the cerebellum through cerebellar-premotor connections. We hypothesized that enhancing cerebellar activity with intermittent theta burst stimulation (iTBS) would improve adaptation rates and increase ß-ERD during motor adaptation. Thirty-four participants were randomly assigned to an active (A-iTBS) or sham cerebellar iTBS (S-iTBS) group. Participants performed a visuomotor task, using a joystick to move a cursor to targets, prior to receiving A-iTBS or S-iTBS, following which they completed training with a 45° rotation to the cursor movement. Behavioural adaptation was assessed using the angular error of the cursor path relative to the ideal trajectory. The results showed a greater adaptation rate following A-iTBS and an increase in ß-ERD, specific to the high ß range (20-30 Hz) during motor planning, compared to S-iTBS, indicative of cerebellar modulation of the motor cortical inhibitory control network. The enhanced release of inhibitory activity persisted throughout training, which suggests that the cerebellar influence over the premotor cortex extends beyond adaptation to other stages of motor learning. The results from this study further understanding of cerebellum-motor connections as they relate to acquiring motor skills and may inform future skill training and rehabilitation protocols.

Standard intensities of transcranial alternating current stimulation over the motor cortex do not entrain corticospinal inputs to motor neurons.

Transcranial alternating current stimulation (TACS) is commonly used to synchronize a cortical area and its outputs to the stimulus waveform, but gathering evidence for this based on brain recordings in humans is challenging. The corticospinal tract transmits beta oscillations (∼21 Hz) from the motor cortex to tonically contracted limb muscles linearly. Therefore, muscle activity may be used to measure the level of beta entrainment in the corticospinal tract due to TACS over the motor cortex. Here, we assessed whether TACS is able to modulate the neural inputs to muscles, which would provide indirect evidence for TACS-driven neural entrainment. In the first part of the study, we ran simulations of motor neuron (MN) pools receiving inputs from corticospinal neurons with different levels of beta entrainment. Results suggest that MNs are highly sensitive to changes in corticospinal beta activity. Then, we ran experiments on healthy human subjects (N = 10) in which TACS (at 1 mA) was delivered over the motor cortex at 21 Hz (beta stimulation), or at 7 Hz or 40 Hz (control conditions) while the abductor digiti minimi or the tibialis anterior muscle were tonically contracted. Muscle activity was measured using high-density electromyography, which allowed us to decompose the activity of pools of motor units innervating the muscles. By analysing motor unit pool activity, we observed that none of the TACS conditions could consistently alter the spectral contents of the common neural inputs received by the muscles. These results suggest that 1 mA TACS over the motor cortex given at beta frequencies does not entrain corticospinal activity. KEY POINTS: Transcranial alternating current stimulation (TACS) is commonly used to entrain the communication between brain regions. It is challenging to find direct evidence supporting TACS-driven neural entrainment due to the technical difficulties in recording brain activity during stimulation. Computational simulations of motor neuron pools receiving common inputs in the beta (∼21 Hz) band indicate that motor neurons are highly sensitive to corticospinal beta entrainment. Motor unit activity from human muscles does not support TACS-driven corticospinal entrainment.

Acute Exercise Modulates the Excitability of Specific Interneurons in Human Motor Cortex.

Acute exercise can modulate the excitability of the non-exercised upper-limb representation in the primary motor cortex (M1). Accumulating evidence demonstrates acute exercise affects measures of M1 intracortical excitability, with some studies also showing altered corticospinal excitability. However, the influence of distinct M1 interneuron populations on the modulation of intracortical and corticospinal excitability following acute exercise is currently unknown. We assessed the impact of an acute bout of leg cycling exercise on unique M1 interneuron excitability of a non-exercised intrinsic hand muscle using transcranial magnetic stimulation (TMS) in young adults. Specifically, posterior-to-anterior (PA) and anterior-to-posterior (AP) TMS current directions were used to measure the excitability of distinct populations of interneurons before and after an acute bout of exercise or rest. Motor evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) were measured in the PA and AP current directions in M1 at two time points separated by 25 min of rest, as well as immediately and 30 min after a 25-minute bout of moderate-intensity cycling exercise. Thirty minutes after exercise, MEP amplitudes were significantly larger than other timepoints when measured with AP current, whereas MEP amplitudes derived from PA current did not show this effect. Similarly, SICI was significantly decreased immediately following acute exercise measured with AP but not PA current. Our findings suggest that the excitability of unique M1 interneurons are differentially modulated by acute exercise. These results indicate that M1 interneurons preferentially activated by AP current may play an important role in the exercise-induced modulation of intracortical and corticospinal excitability.

Long-term effects of concussion on relevancy-based modulation of somatosensory-evoked potentials.

OBJECTIVE: The purpose of this investigation was to better understand the effects of concussions on the ability to selectively up or down-regulate incoming somatosensory information based on relevance. METHODS: Median nerve somatosensory-evoked potentials (SEPs) were elicited from electrical stimulation and recorded from scalp electrodes while participants completed tasks that altered the relevance of specific somatosensory information being conveyed along the stimulated nerve. RESULTS: Within the control group, SEP amplitudes for task-relevant somatosensory information were significantly greater than for non-relevant somatosensory information at the earliest cortical processing potentials (N20-P27). Alternatively, the concussion history group showed similar SEP amplitudes for all conditions at early processing potentials, however a pattern similar to controls emerged later in the processing stream (P100) where both movement-related gating and facilitation of task-relevant information were present. CONCLUSIONS: Previously concussed participants demonstrated impairments in the ability to up-regulate relevant somatosensory information at early processing stages. These effects appear to be chronic, as this pattern was observed on average several years after participants' most recent concussion. SIGNIFICANCE: Given the role of the prefrontal cortex in relevancy-based facilitation during movement-related gating, these findings lend support to the notion that this brain area may be particularly vulnerable to concussive forces.

Evidence of altered interhemispheric communication after pediatric concussion.

OBJECTIVES: To investigate neurophysiological alterations within the typical symptomatic period after concussion (1-month) and throughout recovery (6-months) in adolescents; and (2) to examine relationships between neurophysiological and upper limb kinematic outcomes.METHODS: 18 adolescents with concussion were compared to 17 healthy controls. Transcranial magnetic stimulation (TMS) was used to assess neurophysiological differences between groups including: short- and long-interval intracortical inhibition, intracortical facilitation, short- and long-latency afferent inhibition, afferent facilitation, and transcallosal inhibition (TCI). Behavioral measures of upper limb kinematics were assessed with a robotic device.RESULTS: Mixed model analysis of neurophysiological data identified two key findings. First, participants with concussion demonstrated delayed onset of interhemispheric inhibition, as indexed by TCI, compared to healthy controls. Second, our exploratory analysis indicated that the magnitude of TCI onset delay in adolescents with concussion was related to upper limb kinematics.CONCLUSIONS: Our findings indicate that concussion in adolescence alters interhemispheric communication. We note relationships between neurophysiological and kinematic data, suggesting an affinity for individuals with less concussion-related physiological change to improve their motor behavior over time. These data serve as an important step in future development of assessments (neurobiological and clinical) and interventions for concussion.

Evidence for a Window of Enhanced Plasticity in the Human Motor Cortex Following Ischemic Stroke.

BACKGROUND: In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. OBJECTIVE: To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. METHODS: We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. RESULTS: Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions (P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere (P = .903). CONCLUSIONS: Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery.

Influence of post-stroke fatigue on reaction times and corticospinal excitability during movement preparation.

OBJECTIVES: Reduced corticospinal excitability at rest is associated with post-stroke fatigue (PSF). However, it is not known if corticospinal excitability prior to a movement is also altered in fatigue which may then influence subsequent behaviour. We hypothesized that the levels of PSF can be explained by differences in modulation of corticospinal excitability during movement preparation. METHODS: 73 stroke survivors performed an auditory reaction time task. Corticospinal excitability was measured using transcranial magnetic stimulation. Fatigue was quantified using the fatigue severity scale. The effect of time and fatigue on corticospinal excitability and reaction time was analysed using a mixed effects model. RESULTS: Those with greater levels of PSF showed reduced suppression of corticospinal excitability during movement preparation and increased facilitation immediately prior to movement onset (ß = -0.0066, t = -2.22, p = 0.0263). Greater the fatigue, slower the reaction times the closer the stimulation time to movement onset (ß = 0.0024, t = 2.47, p = 0.0159). CONCLUSIONS: Lack of pre-movement modulation of corticospinal excitability in high fatigue may indicate poor sensory processing supporting the sensory attenuation model of fatigue. SIGNIFICANCE: We take a systems-based approach and investigate the motor system and its role in pathological fatigue allowing us to move towards gaining a mechanistic understanding of chronic pathological fatigue.

The influence of an acute bout of moderate-intensity cycling exercise on sensorimotor integration.

Acute cycling exercise can modulate motor cortical circuitry in the non-exercised upper-limb. Within the primary motor cortex, measures of intracortical inhibition are reduced and intracortical facilitation is enhanced following acute exercise. Further, acute cycling exercise decreases interhemispheric inhibition between the motor cortices and lowers cerebellar-to-motor cortex inhibition. Yet, investigations into the effects of acute exercise on sensorimotor integration, referring to the transfer of incoming afferent information from the primary somatosensory cortex to motor cortex, are lacking. The current work addresses this gap in knowledge with two experimental sessions. In the first session, we tested the exercise-induced changes in somatosensory and motor excitability by assessing somatosensory (SEP) and motor evoked potentials (MEPs). In the second session, we explored the effects of acute cycling exercise on short- (SAI) and long-latency afferent inhibition (LAI), and afferent facilitation. In both experimental sessions, neurophysiological measures were obtained from the non-exercised upper-limb muscle, tested at two time points pre-exercise separated by a 25-min period of rest. Next, a 25-min bout of moderate-intensity lower-limb cycling was performed with measures assessed at two time points post-exercise. Acute lower-limb cycling increased LAI, without modulation of SAI or afferent facilitation. Further, there were no exercise-induced changes to SEP or MEP amplitudes. Together, these results suggest that acute exercise has unique effects on sensorimotor integration, which are not accompanied by concurrent changes in somatosensory or motor cortical excitability.