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Despite being widely studied, the underlying mechanisms of transcranial magnetic brain stimulation (TMS) induced motor evoked potential (MEP), early cortical silent period (CSP) and rebound activity are not fully understood. Our aim is to better characterize these phenomena by combining various analysis tools on firing motor units. Responses of 29 tibialis anterior (TA) and 8 abductor pollicis brevis (APB) motor units to TMS pulses were studied using discharge rate and probability-based tools to illustrate the profile of the synaptic potentials as they develop on motoneurons in 24 healthy volunteers. According to probability-based methods, TMS pulse produces a short-latency MEP which is immediately followed by CSP that terminates at rebound activity. Discharge rate analysis, however, revealed not three, but just two events with distinct time courses; a long-lasting excitatory period (71.2 ± 9.0 ms for TA and 42.1 ± 11.2 ms for APB) and a long-latency inhibitory period with duration of 57.9 ± 9.5 ms for TA and 67.3 ± 13.8 ms for APB. We propose that part of the CSP may relate to the falling phase of net excitatory postsynaptic potential induced by TMS. Rebound activity, on the other hand, may represent tendon organ inhibition induced by MEP activated soleus contraction and/or long-latency intracortical inhibition. Due to generation of field potentials when high intensity TMS is used, this study is limited to investigate the events evoked by low intensity TMS only and does not provide information about later parts of much longer CSPs induced by high intensity TMS. Adding discharge rate analysis contributes to obtain a more accurate picture about the characteristics of TMS-induced events. These results have implications for interpreting motor responses following TMS for diagnosis and overseeing recovery from various neurological conditions., Competing Interests: The authors have declared that no competing interests exist.

Objective: We propose a novel cue‐based asynchronous brain–computer interface(BCI) for neuromodulation via the pairing of endogenous motor cortical activity with the activation of somatosensory pathways. Methods: The proposed BCI detects the intention to move from single‐trial EEG signals in real time, but, contrary to classic asynchronous‐BCI systems, the detection occurs only during time intervals when the patient is cued to move. This cue‐based asynchronous‐BCI was compared with two traditional BCI modes (asynchronous‐BCI and offline synchronous‐BCI) and a control intervention in chronic stroke patients. The patients performed ankle dorsiflexion movements of the paretic limb in each intervention while their brain signals were recorded. BCI interventions decoded the movement attempt and activated afferent pathways via electrical stimulation. Corticomotor excitability was assessed using motor‐evoked potentials in the tibialis‐anterior muscle induced by transcranial magnetic stimulation before, immediately after, and 30 min after the intervention. Results: The proposed cue‐based asynchronous‐BCI had significantly fewer false positives/min and false positives/true positives (%) as compared to the previously developed asynchronous‐BCI. Linear‐mixed‐models showed that motor‐evoked potential amplitudes increased following all BCI modes immediately after the intervention compared to the control condition (p <0.05). The proposed cue‐based asynchronous‐BCI resulted in the largest relative increase in peak‐to‐peak motor‐evoked potential amplitudes(141% ± 33%) among all interventions and sustained it for 30 min(111% ± 33%). Interpretation: These findings prove the high performance of a newly proposed cue‐based asynchronous‐BCI intervention. In this paradigm, individuals receive precise instructions (cue) to promote engagement, while the timing of brain activity is accurately detected to establish a precise association with the delivery of sensory input for plasticity induction. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of a single session of chiropractic spinal adjustment on the cortical drive to the lower limb in chronic stroke patients. In a single-blinded, randomized controlled parallel design study, 29 individuals with chronic stroke and motor weakness in a lower limb were randomly divided to receive either chiropractic spinal adjustment or a passive movement control intervention. Before and immediately after the intervention, transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) were recorded from the tibialis anterior (TA) muscle of the lower limb with the greatest degree of motor weakness. Differences in the averaged peak-peak MEP amplitude following interventions were calculated using a linear regression model. Chiropractic spinal adjustment elicited significantly larger MEP amplitude (pre = 0.24 ± 0.17 mV, post = 0.39 ± 0.23 mV, absolute difference = +0.15 mV, relative difference = +92%, p < 0.001) compared to the control intervention (pre = 0.15 ± 0.09 mV, post = 0.16 ± 0.09 mV). The results indicate that chiropractic spinal adjustment increases the corticomotor excitability of ankle dorsiflexor muscles in people with chronic stroke. Further research is required to investigate whether chiropractic spinal adjustment increases dorsiflexor muscle strength and walking function in people with stroke. [ABSTRACT FROM AUTHOR]

Brain-computer interfaces have been proposed for stroke rehabilitation. Motor cortical activity derived from the electroencephalography (EEG) can trigger external devices that provide congruent sensory feedback. However, many stroke patients regain residual muscle (EMG: electromyography) control due to spontaneous recovery and rehabilitation; therefore, EEG may not be necessary as a control signal. In this paper, a direct comparison was made between the induction of corticospinal plasticity using either EEG- or EMG-controlled electrical nerve stimulation. Twenty healthy participants participated in two intervention sessions consisting of EEG- and EMG-controlled electrical stimulation. The sessions consisted of 50 pairings between foot dorsiflexion movements (decoded through either EEG or EMG) and electrical stimulation of the common peroneal nerve. Before, immediately after and 30 minutes after the intervention, 15 motor evoked potentials (MEPs) were elicited in tibialis anterior through transcranial magnetic stimulation. Increased MEPs were observed immediately after (62 ± 26%, 73 ± 27% for EEG- and EMG-triggered electrical stimulation, respectively) and 30 minutes after each of the two interventions (79 ± 26% and 72 ± 27%) compared to the pre-intervention measurement. There was no difference between the interventions. Both EEG- and EMG-controlled electrical stimulation can induce corticospinal plasticity which suggests that stroke patients with residual EMG can use that modality instead of EEG to trigger stimulation. [ABSTRACT FROM AUTHOR]

The objective of this study was to construct peristimulus time histogram (PSTH) and peristimulus frequencygram (PSF) using single motor unit recordings to further characterize the previously documented immediate sensorimotor effects of spinal manipulation. Single pulse transcranial magnetic stimulation (TMS) via a double cone coil over the tibialis anterior (TA) motor area during weak isometric dorsiflexion of the foot was used on two different days in random order; pre/post spinal manipulation (in eighteen subjects) and pre/post a control (in twelve subjects) condition. TA electromyography (EMG) was recorded with surface and intramuscular fine wire electrodes. Three subjects also received sham double cone coil TMS pre and post a spinal manipulation intervention. From the averaged surface EMG data cortical silent periods (CSP) were constructed and analysed. Twenty-one single motor units were identified for the spinal manipulation intervention and twelve single motor units were identified for the control intervention. Following spinal manipulations there was a shortening of the silent period and an increase in the single unit I-wave amplitude. No changes were observed following the control condition. The results provide evidence that spinal manipulation reduces the TMS-induced cortical silent period and increases low threshold motoneurone excitability in the lower limb muscle. These finding may have important clinical implications as they provide support that spinal manipulation can be used to strengthen muscles. This could be followed up on populations that have reduced muscle strength, such as stroke victims. [ABSTRACT FROM AUTHOR]

The cerebellum processes pain inputs and is important for motor learning. Yet, how the cerebellum interacts with the motor cortex in individuals with recurrent pain is not clear. Functional connectivity between the cerebellum and motor cortex can be measured by a twin coil transcranial magnetic stimulation technique in which stimulation is applied to the cerebellum prior to stimulation over the motor cortex, which inhibits motor evoked potentials (MEPs) produced by motor cortex stimulation alone, called cerebellar inhibition (CBI). Healthy individuals without pain have been shown to demonstrate reduced CBI following motor acquisition. We hypothesized that CBI would not reduce to the same extent in those with mild-recurrent neck pain following the same motor acquisition task. We further hypothesized that a common treatment for neck pain (spinal manipulation) would restore reduced CBI following motor acquisition. Motor acquisition involved typing an eight-letter sequence of the letters Z,P,D,F with the right index finger. Twenty-seven neck pain participants received spinal manipulation (14 participants, 18–27 years) or sham control (13 participants, 19–24 years). Twelve healthy controls (20–27 years) also participated. Participants had CBI measured; they completed manipulation or sham control followed by motor acquisition; and then had CBI re-measured. Following motor acquisition, neck pain sham controls remained inhibited (58 ± 33% of test MEP) vs. healthy controls who disinhibited (98 ± 49% of test MEP, P<0.001), while the spinal manipulation group facilitated (146 ± 95% of test MEP, P<0.001). Greater inhibition in neck pain sham vs. healthy control groups suggests that neck pain may change cerebellar-motor cortex interaction. The change to facilitation suggests that spinal manipulation may reverse inhibitory effects of neck pain. [ABSTRACT FROM AUTHOR]

This study investigates whether spinal manipulation leads to changes in motor control by measuring the recruitment pattern of motor units in both an upper and lower limb muscle and to see whether such changes may at least in part occur at the cortical level by recording movement related cortical potential (MRCP) amplitudes. In experiment one, transcranial magnetic stimulation input-output (TMS I/O) curves for an upper limb muscle (abductor pollicus brevis; APB) were recorded, along with F waves before and after either spinal manipulation or a control intervention for the same subjects on two different days. During two separate days, lower limb TMS I/O curves and MRCPs were recorded from tibialis anterior muscle (TA) pre and post spinal manipulation. Dependent measures were compared with repeated measures analysis of variance, with p set at 0.05. Spinal manipulation resulted in a 54.5% ± 93.1% increase in maximum motor evoked potential (MEPmax) for APB and a 44.6% ± 69.6% increase in MEPmax for TA. For the MRCP data following spinal manipulation there were significant difference for amplitude of early bereitschafts-potential (EBP), late bereitschafts potential (LBP) and also for peak negativity (PN). The results of this study show that spinal manipulation leads to changes in cortical excitability, as measured by significantly larger MEPmax for TMS induced input-output curves for both an upper and lower limb muscle, and with larger amplitudes of MRCP component post manipulation. No changes in spinal measures (i.e., F wave amplitudes or persistence) were observed, and no changes were shown following the control condition. These results are consistent with previous findings that have suggested increases in strength following spinal manipulation were due to descending cortical drive and could not be explained by changes at the level of the spinal cord. Spinal manipulation may therefore be indicated for the patients who have lost tonus of their muscle and/or are recovering from muscle degrading dysfunctions such as stroke or orthopaedic operations and/or may also be of interest to sports performers. These findings should be followed up in the relevant populations. [ABSTRACT FROM AUTHOR]

Learning new motor skills has been correlated with increased cortical excitability. In this study, different location of electrical stimulation (ES), nerve, or muscle, was paired with voluntary movement to investigate if ES paired with voluntary movement (a) would increase the excitability of cortical projections to tibialis anterior and (b) if stimulation location mattered. Cortical excitability changes were quantified using motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) at varying intensities during four conditions. Twelve healthy subjects performed 50 dorsiflexions at the ankle during nerve or muscle ES at motor threshold (MTh). ES alone was delivered 50 times and the movement was performed 50 times. A significant increase in the excitability from pre- to post-intervention (P = 0.0061) and pre- to 30 min post-intervention (P = 0.017) measurements was observed when voluntary movement was paired with muscle ES located at tibialis anterior. An increase of 50 ± 57 and 28 ± 54% in the maximum MEPs was obtained for voluntary movement paired with muscle-located and nerve-located ES, respectively. The maximum MEPs for voluntary movement alone and muscle-located ES alone were -5 ± 28 and 2 ± 42%, respectively. Pairing voluntary movement with muscle-located ES increases excitability of corticospinal projections of tibialis anterior in healthy participants. This finding suggests that active participation during muscle-located ES protocols increases cortical excitability to a greater extent than stimulation alone. The next stage of this research is to investigate the effect in people with stroke. The results may have implications for motor recovery in patients with motor impairments following neurological injury. [ABSTRACT FROM AUTHOR]

Our group set out to develop a sensitive technique, capable of detecting output changes from the posterior fossa following a motor acquisition task. Transcranial magnetic stimulation (TMS) was applied over the right cerebellar cortex 5 ms in advance of test stimuli over the left cerebral motor cortex (M1), suppressing test motor-evoked potentials (MEPs) recorded in a distal hand muscle. Ten participants typed the letters Z, D, F, and P in randomized 8-letter sequences for ~15 min, and 10 participants took part in the control condition. Cerebellar-M1 recruitment curves were established before and after the motor acquisition task. Cerebellar inhibition at 50% (CBI50) was defined as the intensity of cerebellar-M1 stimulations that produced MEPs that were 50% of the initial test MEP. Collection also occurred at stimulator intensities 5 and 10% above CBI50. A significant interaction effect of group (experimental and control) vs. time (pre- and postintervention) was observed [F(1,18) = 4.617, P = 0.046]. Post hoc tests showed a significant effect for the learning task in the experimental group [F(1,9) = 10.28, P = 0.01]. Further analysis showed specific disinhibition at CBI50 (P = 0.04), CBI505% (P = 0.008), and CBI5010% (P = 0.01) for the experimental group only. Reaction time (P | 0.001) and accuracy (P = 0.006) improved significantly following practice, implying that disinhibition coincides with motor learning. No changes, however, were seen in the control condition. We conclude that this protocol is a sensitive technique that may be used to study cerebellar disinhibition with motor acquisition in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this study was investigate whether there are alterations in cerebellar output in a subclinical neck pain (SCNP) group and whether spinal manipulation before motor sequence learning might restore the baseline functional relationship between the cerebellum and motor cortex. Methods: Ten volunteers were tested with SCNP using transcranial magnetic stimulation before and after a combined intervention of spinal manipulation and motor sequence learning. In a separate experiment, we tested 10 healthy controls using the same measures before and after motor sequence learning. Our transcranial magnetic stimulation measurements included short-interval intracortical inhibition, long-interval intracortical inhibition, and cerebellar inhibition (CBI). Results: The SCNP group showed a significant improvement in task performance as indicated by a 19% decrease in mean reaction time (P < .0001), which occurred concurrently with a decrease in CBI following the combined spinal manipulation and motor sequence learning intervention (F1,6 = 7.92, P < .05). The control group also showed an improvement in task performance as indicated by a 25% increase in reaction time (P < .001) with no changes to CBI. Conclusions: Subclinical neck pain patients have altered CBI when compared with healthy controls, and spinal manipulation before a motor sequence learning task changes the CBI pattern to one similar to healthy controls. [Copyright &y& Elsevier]

To investigate the effects of a single session of spinal manipulation (SM) on voluntary activation of the elbow flexors in participants with subclinical neck pain using an interpolated twitch technique with transcranial magnetic stimulation (TMS), eighteen volunteers with subclinical neck pain participated in this randomized crossover trial. TMS was delivered during elbow flexion contractions at 50%, 75% and 100% of maximum voluntary contraction (MVC) before and after SM or control intervention. The amplitude of the superimposed twitches evoked during voluntary contractions was recorded and voluntary activation was calculated using a regression analysis. Dependent variables were analyzed with two-way (intervention × time) repeated measures ANOVAs. Significant intervention effects for SM compared to passive movement control were observed for elbow flexion MVC (p = 0.04), the amplitude of superimposed twitch (p = 0.04), and voluntary activation of elbow flexors (p =0.03). Significant within-group post-intervention changes were observed for the superimposed twitch (mean group decrease of 20.9%, p < 0.01) and voluntary activation (mean group increase of 3.0%, p < 0.01) following SM. No other significant within-group changes were observed. Voluntary activation of the elbow flexors increased immediately after one session of spinal manipulation in participants with subclinical neck pain. A decrease in the amplitude of superimposed twitch during elbow flexion MVC following spinal manipulation suggests a facilitation of motor cortical output. [ABSTRACT FROM AUTHOR]

Brain–computer interfaces (BCIs), operated in a cue-based (offline) or self-paced (online) mode, can be used for inducing cortical plasticity for stroke rehabilitation by the pairing of movement-related brain activity with peripheral electrical stimulation. The aim of this study was to compare the difference in cortical plasticity induced by the two BCI modes. Fifteen healthy participants participated in two experimental sessions: cue-based BCI and self-paced BCI. In both sessions, imagined dorsiflexions were extracted from continuous electroencephalogram (EEG) and paired 50 times with the electrical stimulation of the common peroneal nerve. Before, immediately after, and 30 min after each intervention, the cortical excitability was measured through the motor-evoked potentials (MEPs) of tibialis anterior elicited through transcranial magnetic stimulation. Linear mixed regression models showed that the MEP amplitudes increased significantly (p < 0.05) from pre- to post- and 30-min post-intervention in terms of both the absolute and relative units, regardless of the intervention type. Compared to pre-interventions, the absolute MEP size increased by 79% in post- and 68% in 30-min post-intervention in the self-paced mode (with a true positive rate of ~75%), and by 37% in post- and 55% in 30-min post-intervention in the cue-based mode. The two modes were significantly different (p = 0.03) at post-intervention (relative units) but were similar at both post timepoints (absolute units). These findings suggest that immediate changes in cortical excitability may have implications for stroke rehabilitation, where it could be used as a priming protocol in conjunction with another intervention; however, the findings need to be validated in studies involving stroke patients. [ABSTRACT FROM AUTHOR]