Motor Cortical Plasticity Induced by Volitional Muscle Activity-Triggered Transcranial Magnetic Stimulation and Median Nerve Stimulation

Bilateral motor training is a useful method for modifying corticospinal excitability. The effects of bilateral movement that are caused by artificial stimulation on corticospinal excitability have not been reported. We compared motor-evoked potentials (MEPs) of the primary motor cortex (M1) after conventional bilateral motor training and artificial bilateral movements generated by electromyogram activity of abductor pollicis brevis (APB) muscle-triggered peripheral nerve stimulation (c-MNS) and transcranial magnetic stimulation of the ipsilateral M1 (i-TMS). A total of three protocols with different interventions—bilateral finger training, APB-triggered c-MNS, and APB-triggered i-TMS—were administered to 12 healthy participants. Each protocol consisted of 360 trials of 30 min for each trial. MEPs that were induced by single-pulse TMS, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) that were induced by paired-pulse TMS were assessed as outcome measures at baseline and at 0, 20, 40, and 60 min after intervention. MEP amplitude significantly increased up to 40 min post-intervention in all protocols compared to that at the baseline, although there were some differences in the changing pattern of ICF and SICI in each protocol. These findings suggest that artificial bilateral movement has the potential to increase the ipsilateral cortical excitability of the moving finger.

Median Nerve Stimulation Facilitates the Identification of Somatotopy of the Subthalamic Nucleus in Parkinson’s Disease Patients under Inhalational Anesthesia

Deep brain stimulation (DBS) improves Parkinson’s disease (PD) symptoms by suppressing neuropathological oscillations. These oscillations are also modulated by inhalational anesthetics used during DBS surgery in some patients, influencing electrode placement accuracy. We sought to evaluate a method that could avoid these effects. We recorded subthalamic nucleus (STN) neuronal firings in 11 PD patients undergoing DBS under inhalational anesthesia. Microelectrode recording (MER) during DBS was collected under median nerve stimulation (MNS) delivered at 5, 20, and 90 Hz frequencies and without MNS. We analyzed the spike firing rate and neuronal activity with power spectral density (PSD), and assessed correlations between the neuronal oscillation parameters and clinical motor outcomes. No patient experienced adverse effects during or after DBS surgery. PSD analysis revealed that peripheral 20 Hz MNS produced significant differences in the dorsal and ventral subthalamic nucleus (STN) between the beta band oscillation (16.9 ± 7.0% versus 13.5 ± 4.8%, respectively) and gamma band oscillation (56.0 ± 13.7% versus 66.3 ± 9.4%, respectively) (p < 0.05). Moreover, 20-Hz MNS entrained neural oscillation over the dorsal STN, which correlated positively with motor disabilities. MNS allowed localization of the sensorimotor STN and identified neural characteristics under inhalational anesthesia. This paradigm may help identify an alternative method to facilitate STN identification and DBS surgery under inhalational anesthesia.

Identifying and modulating distinct tremor states through peripheral nerve stimulation in Parkinsonian rest tremor

Background Resting tremor is one of the most common symptoms of Parkinson’s disease. Despite its high prevalence, resting tremor may not be as effectively treated with dopaminergic medication as other symptoms, and surgical treatments such as deep brain stimulation, which are effective in reducing tremor, have limited availability. Therefore, there is a clinical need for non-invasive interventions in order to provide tremor relief to a larger number of people with Parkinson’s disease. Here, we explore whether peripheral nerve stimulation can modulate resting tremor, and under what circumstances this might lead to tremor suppression. Methods We studied 10 people with Parkinson’s disease and rest tremor, to whom we delivered brief electrical pulses non-invasively to the median nerve of the most tremulous hand. Stimulation was phase-locked to limb acceleration in the axis with the biggest tremor-related excursion. Results We demonstrated that rest tremor in the hand could change from one pattern of oscillation to another in space. Median nerve stimulation was able to significantly reduce (− 36%) and amplify (117%) tremor when delivered at a certain phase. When the peripheral manifestation of tremor spontaneously changed, stimulation timing-dependent change in tremor severity could also alter during phase-locked peripheral nerve stimulation. Conclusions These results highlight that phase-locked peripheral nerve stimulation has the potential to reduce tremor. However, there can be multiple independent tremor oscillation patterns even within the same limb. Parameters of peripheral stimulation such as stimulation phase may need to be adjusted continuously in order to sustain systematic suppression of tremor amplitude.

Posteroanterior Cervical Transcutaneous Spinal Cord Stimulation: Interactions with Cortical and Peripheral Nerve Stimulation

Transcutaneous spinal cord stimulation (TSCS) has demonstrated potential to beneficially modulate spinal cord motor and autonomic circuitry. We are interested in pairing cervical TSCS with other forms of nervous system stimulation to enhance synaptic plasticity in circuits serving hand function. We use a novel configuration for cervical TSCS in which the anode is placed anteriorly over ~C4–C5 and the cathode posteriorly over ~T2–T4. We measured the effects of single pulses of TSCS paired with single pulses of motor cortex or median nerve stimulation timed to arrive at the cervical spinal cord at varying intervals. In 13 participants with and 15 participants without chronic cervical spinal cord injury, we observed that subthreshold TSCS facilitates hand muscle responses to motor cortex stimulation, with a tendency toward greater facilitation when TSCS is timed to arrive at cervical synapses simultaneously or up to 10 milliseconds after cortical stimulus arrival. Single pulses of subthreshold TSCS had no effect on the amplitudes of median H-reflex responses or F-wave responses. These findings support a model in which TSCS paired with appropriately timed cortical stimulation has the potential to facilitate convergent transmission between descending motor circuits, segmental afferents, and spinal motor neurons serving the hand. Studies with larger numbers of participants and repetitively paired cortical and spinal stimulation are needed.

Scalp attached tangential magnetoencephalography using tunnel magneto-resistive sensors

Non-invasive human brain functional imaging with millisecond resolution can be achieved only with magnetoencephalography (MEG) and electroencephalography (EEG). MEG has better spatial resolution than EEG because signal distortion due to inhomogeneous head conductivity is negligible in MEG but serious in EEG. However, this advantage has been practically limited by the necessary setback distances between the sensors and scalp, because the Dewar vessel containing liquid helium for superconducting sensors requires a thick vacuum wall. Latest developments of high critical temperature (high-Tc) superconducting or optically pumped magnetometers have not allowed scalp-attached MEG due to cold or hot temperatures at the sensing point, respectively. Here we applied tunnel magneto-resistive (TMR) sensors that operate at room temperature. Improvement of TMR sensitivity with magnetic flux concentrators enabled scalp-attached and scalp-tangential MEG to target the largest signal component produced by the neural current below. In a healthy subject, our single-channel TMR-MEG system clearly demonstrated the N20m, the initial cortical component of the somatosensory evoked response after median nerve stimulation. Multisite measurement confirmed a spatially and temporally steep peak of N20m, immediately above the source at a latency around 20 ms, indicating a new approach to non-invasive functional brain imaging with millimeter and millisecond resolutions.

Effect of Neck Muscle Fatigue on Hand Muscle Motor Performance and Early Somatosensory Evoked Potentials

Even on pain free days, recurrent neck pain alters sensorimotor integration (SMI) measured via somatosensory evoked potentials (SEPs). Neck muscle fatigue decreases upper limb proprioception, and thus may interfere with upper limb motor task acquisition and SMI. This study aimed to determine the effect of cervical extensor muscle (CEM) fatigue on upper limb motor acquisition and retention; and SMI, measured via early SEPs. Twenty-four healthy right-handed individuals were randomly assigned to control or CEM fatigue. Baseline SEPs were elicited via median nerve stimulation at the wrist. Participants then lay prone on a padded table. The fatigue group supported a 2 kg weight until they could no longer maintain the position. The control group rested their neck in neutral for 5 min. Participants completed pre- and post-motor skill acquisition while seated, SEPs were again collected. Task retention was measured 24 h later. Accuracy improved post acquisition and at retention for both groups (p < 0.001), with controls outperforming the fatigue group (p < 0.05). The fatigue group had significantly greater increases in the N24 (p = 0.017) and N30 (p = 0.007) SEP peaks. CEM fatigue impaired upper limb motor learning outcomes in conjunction with differential changes in SEP peak amplitudes related to SMI.

Interaction of the Left–Right Somatosensory Pathways in Patients With Thalamic Hemorrhage: A Case Report

Neural plasticity compensates for the loss of motor function after stroke. However, whether neural plasticity occurs in the somatosensory pathways after stroke is unknown. We investigated the left–right somatosensory interaction in two hemorrhagic patients using a paired somatosensory evoked potentials (p-SEPs) recorded at CP3 and CP4, which was defined as an amplitude difference between the SEPs of paired median nerve stimulations to both sides and that of single stimulation to the affected side. Patient 1 (61-year-old, left thalamic hemorrhage) has a moderate motor impairment, severe sensory deficit, and complained of pain in the affected right upper limb. Patient 2 (72-year-old, right thalamic hemorrhage) had slight motor and sensory impairments with no complaints of pain. Single SEPs (s-SEPs) were obtained by stimulation of the right and left median nerves, respectively. For paired stimulations, 1 ms after the first stimulation to the non-affected side, followed by a second stimulation to the affected side. In patient 1, a s-SEP with stimulation to the non-affected side and a p-SEP were observed in CP4. However, a s-SEP was not observed in either hemisphere with stimulation to the affected side. On the other hand, in patient 2, a s-SEP in CP3 with stimulation to the non-affected side and in CP4 with stimulation to the affected side were observed; however, a p-SEP was not observed. In addition, to investigate the mechanism by which ipsilateral median nerve stimulation enhances contralateral p-SEP in patient 1, we compared the SEP averaged over the first 250 epochs with the SEP averaged over the second 250 epochs (total number of epochs recorded: 500). The results showed that in the patient 1, when the bilateral median nerve was stimulated continuously, the habituation did not occur and the response was larger than that of the s-SEP with unilateral median nerve stimulation. In the current case report, the damage to the thalamus may cause neuroplasticity in terms of the left–right interaction (e.g., left and right S1). The somatosensory input from the affected side may interfere with the habituation of the contralateral somatosensory system and conversely increase the response.

Cerebral haemodynamic response to somatosensory stimulation in preterm lambs and 7–10-day old lambs born at term: Direct synchrotron microangiography assessment

Neurovascular coupling has been well-defined in the adult brain, but variable and inconsistent responses have been observed in the neonatal brain. The mechanisms that underlie functional haemodynamic responses in the developing brain are unknown. Synchrotron radiation (SR) microangiography enables in vivo high-resolution imaging of the cerebral vasculature. We exploited SR microangiography to investigate the microvascular changes underlying the cerebral haemodynamic response in preterm (n = 7) and 7–10-day old term lambs (n = 4), following median nerve stimulation of 1.8, 4.8 and 7.8 sec durations. Increasing durations of somatosensory stimulation significantly increased the number of cortical microvessels of ≤200 µm diameter in 7–10-day old term lambs (p < 0.05) but not preterm lambs where, in contrast, stimulation increased the diameter of cerebral microvessels with a baseline diameter of ≤200 µm. Preterm lambs demonstrated positive functional responses with increased oxyhaemoglobin measured by near infrared spectroscopy, while 7–10-day old term lambs demonstrated both positive and negative responses. Our findings suggest the vascular mechanisms underlying the functional haemodynamic response differ between the preterm and 7–10-day old term brain. The preterm brain depends on vasodilatation of microvessels without recruitment of additional vessels, suggesting a limited capacity to mount higher cerebral haemodynamic responses when faced with prolonged or stronger neural stimulation.