Changes in the excitability of anterior horn cells in a mental rotation task of body parts.

INTRODUCTION/AIMS: Mental rotation (MR), a tool of implicit motor imagery, is the ability to rotate mental representations of two- or three-dimensional objects. Although many reports have described changes in brain activity during MR tasks, it is not clear whether the excitability of anterior horn cells in the spinal cord can be changed. In this study, we examined whether MR tasks of hand images affect the excitability of anterior horn cells using F-wave analysis. METHODS: Right-handed, healthy participants were recruited for this study. F-waves of the right abductor pollicis brevis were recorded after stimulation of the right median nerve at rest, during a non-MR task, and during an MR task. The F-wave persistence and the F/M amplitude ratio were calculated and analyzed. RESULTS: Twenty participants (11 men and 9 women; mean age, 29.2 ± 4.4 years) were initially recruited, and data from the 18 that met the inclusion criteria were analyzed. The F-wave persistence was significantly higher in the MR task than in the resting condition (p = .001) or the non-MR task (p = .012). The F/M amplitude ratio was significantly higher in the MR task than in the resting condition (p = .019). DISCUSSION: The MR task increases the excitability of anterior horn cells corresponding to the same body part. MR tasks may have the potential for improving motor function in patients with reduced excitability of the anterior horn cells, although this methodology must be further verified in a clinical setting.

Pharmacological adjuncts and transcranial magnetic stimulation-induced synaptic plasticity: a systematic review.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have been used to improve our fundamental understanding of TMS-induced synaptic plasticity. METHODS: We systematically reviewed the literature pairing pharmacological adjuncts with TMS plasticity-induction protocols in humans. We searched MEDLINE, PsycINFO, and Embase from 2013 to Mar. 10, 2023. Studies published before 2013 were extracted from a previous systematic review. We included studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations. RESULTS: Thirty-six studies met our inclusion criteria (28 in healthy and 8 in clinical populations). Most pharmacological agents have targeted the glutamatergic N-methyl-d-aspartate (NMDA; 15 studies) or dopamine receptors (13 studies). The NMDA receptor is necessary for TMS-induced plasticity; however, sufficiency has not been shown across protocols. Dopaminergic modulation of TMS-induced plasticity appears to be dose-dependent. The GABAergic, cholinergic, noradrenergic, and serotonergic neurotransmitter systems have small evidence bases supporting modulation of TMS-induced plasticity, as do voltage-gated calcium and sodium channels. Studies in clinical populations suggest that pharmacological adjuncts to TMS may rescue motor cortex plasticity, with implications for therapeutic applications of TMS and a promising clinical trial in depression. LIMITATIONS: This review is limited by the predominance in the literature of studies with small sample sizes and crossover designs. CONCLUSION: Pharmacologically enhanced TMS largely parallels findings from ex vivo preparations. As this area expands and novel targets are tested, adequately powered samples in healthy and clinical populations will inform the mechanisms of TMS-induced plasticity in health and disease.

Neurotransmitter levels in the basal ganglia are associated with intracortical circuit activity of the primary motor cortex in healthy humans.

BACKGROUND: The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. OBJECTIVE/HYPOTHESIS: The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. METHODS: We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). RESULTS: Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. CONCLUSIONS: Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function.

Motor cortex activation during visuomotor transformations: evoked potentials during overt and imagined movements.

Despite the prevalence of visuomotor transformations in our motor skills, their mechanisms remain incompletely understood, especially when imagery actions are considered such as mentally picking up a cup or pressing a button. Here, we used a stimulus-response task to directly compare the visuomotor transformation underlying overt and imagined button presses. Electroencephalographic activity was recorded while participants responded to highlights of the target button while ignoring the second, non-target button. Movement-related potentials (MRPs) and event-related desynchronization occurred for both overt movements and motor imagery (MI), with responses present even for non-target stimuli. Consistent with the activity accumulation model where visual stimuli are evaluated and transformed into the eventual motor response, the timing of MRPs matched the response time on individual trials. Activity-accumulation patterns were observed for MI, as well. Yet, unlike overt movements, MI-related MRPs were not lateralized, which appears to be a neural marker for the distinction between generating a mental image and transforming it into an overt action. Top-down response strategies governing this hemispheric specificity should be accounted for in future research on MI, including basic studies and medical practice.

Dynamic electrical stimulation enhances the recruitment of spinal interneurons by corticospinal input.

Highly varying patterns of electrostimulation (Dynamic Stimulation, DS) delivered to the dorsal cord through an epidural array with 18 independent electrodes transiently facilitate corticospinal motor responses, even after spinal injury. To partly unravel how corticospinal input are affected by DS, we introduced a corticospinal platform that allows selective cortical stimulation during the multisite acquisition of cord dorsum potentials (CDPs) and the simultaneous supply of DS. Firstly, the epidural interface was validated by the acquisition of the classical multisite distribution of CDPs and their input-output profile elicited by pulses delivered to peripheral nerves. Apart from increased EMGs, DS selectively increased excitability of the spinal interneurons that first process corticospinal input, without changing the magnitude of commands descending from the motor cortex, suggesting a novel correlation between muscle recruitment and components of cortically-evoked CDPs. Finally, DS increases excitability of post-synaptic spinal interneurons at the stimulation site and their responsiveness to any residual supraspinal control, thus supporting the use of electrical neuromodulation whenever the motor output is jeopardized by a weak volitional input, due to a partial disconnection from supraspinal structures and/or neuronal brain dysfunctions.

Effectiveness of Repetitive Transcranial Magnetic Stimulation Combined With Transspinal Electrical Stimulation on Corticospinal Excitability for Individuals With Incomplete Spinal Cord Injury: A Pilot Study.

Repetitive Transcranial Magnetic Stimulation (rTMS) and transspinal electrical stimulation (tsES) have been proposed as a novel neurostimulation modality for individuals with incomplete spinal cord injury (iSCI). In this study, we integrated magnetic and electrical stimulators to provide neuromodulation therapy to individuals with incomplete spinal cord injury (iSCI). We designed a clinical trial comprising an 8-week treatment period and a 4-week treatment-free observation period. Cortical excitability, clinical features, inertial measurement unit and surface electromyography were assessed every 4 weeks. Twelve individuals with iSCI were recruited and randomly divided into a combined therapy group, a magnetic stimulation group, an electrical stimulation group, or a sham stimulation group. The magnetic and electric stimulations provided in this study were intermittent theta-burst stimulation (iTBS) and 2.5-mA direct current (DC) stimulation, respectively. Combined therapy, which involves iTBS and transspinal DC stimulation (tsDCS), was more effective than was iTBS alone or tsDCS alone in terms of increasing corticospinal excitability. In conclusion, the effectiveness of 8-week combined therapy in increasing corticospinal excitability faded 4 weeks after the cessation of treatment. According to the results, combination of iTBS rTMS and tsDCS treatment was more effective than was iTBS rTMS alone or tsDCS alone in enhancing corticospinal excitability. Although promising, the results of this study must be validated by studies with longer interventions and larger sample sizes.

Anodal transcutaneous spinal direct current stimulation influences the amplitude of pain-related evoked potentials in healthy subjects.

It has already been described that transcutaneous spinal direct current stimulation (tsDCS) can selectively influence nociceptive evoked potentials. This study is the first aiming to prove an influence of tsDCS on pain-related evoked potentials (PREP) using concentric surface electrodes (CE), whose nociceptive specificity is still under discussion. 28 healthy subjects participated in this sham-controlled, double-blind cross-over study. All subjects underwent one session of anodal and one session of sham low-thoracic tsDCS. Before and after the intervention, PREP using CE, PREP-induced pain perception and somatosensory evoked potentials (SEP) were assessed on the right upper and lower limb. We found a decrease in PREP amplitude at the lower limb after sham stimulation, but not after anodal tsDCS, while SEP remained unchanged under all studied conditions. There was no difference between the effects of anodal tsDCS and sham stimulation on the studied parameters assessed at the upper limb. PREP-induced pain of the upper and lower limb increased after anodal tsDCS. The ability of influencing PREP using a CE at the spinal level in contrast to SEP suggests that PREP using CE follows the spinothalamic pathway and supports the assumption that it is specifically nociceptive. However, while mainly inhibitory effects on nociceptive stimuli have already been described, our results rather suggest that anodal tsDCS has a sensitizing effect. This may indicate that the mechanisms underlying the elicitation of PREP with CE are not the same as for the other nociceptive evoked potentials. The effects on the processing of different types of painful stimuli should be directly compared in future studies.

The severity of acute hypoxaemia determines distinct changes in intracortical and spinal neural circuits.

The purpose of this study was to examine how two common methods of continuous hypoxaemia impact the activity of intracortical circuits responsible for inhibition and facilitation of motor output, and spinal excitability. Ten participants were exposed to 2 h of hypoxaemia at 0.13 fraction of inspired oxygen ( F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol) and 80% of peripheral capillary oxygen saturation ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol) using a simulating altitude device on two visits separated by a week. Using transcranial magnetic and peripheral nerve stimulation, unconditioned motor evoked potential (MEP) area, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and F-wave persistence and area were assessed in the first dorsal interosseous (FDI) muscle before titration, after 1 and 2 h of hypoxic exposure, and at reoxygenation. The clamping protocols resulted in differing reductions in S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ by 2 h ( S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol: 81.9 ± 1.3%, F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol: 90.6 ± 2.5%). Although unconditioned MEP peak to peak amplitude and area did not differ between the protocols, SICI during F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping was significantly lower at 2 h compared to S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping (P = 0.011) and baseline (P < 0.001), whereas ICF was higher throughout the F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping compared to S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping (P = 0.005). Furthermore, a negative correlation between SICI and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (rrm  = -0.56, P = 0.002) and a positive correlation between ICF and S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (rrm  = 0.69, P = 0.001) were determined, where greater reductions in S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ correlated with less inhibition and less facilitation of MEP responses. Although F-wave area progressively increased similarly throughout the protocols (P = 0.037), persistence of responses was reduced at 2 h and reoxygenation (P < 0.01) during the S p O 2 ${S_{{\mathrm{p}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol compared to the F I O 2 ${F_{{\mathrm{I}}{{\mathrm{O}}_{\mathrm{2}}}}}$ clamping protocol. After 2 h of hypoxic exposure, there is a reduction in the activity of intracortical circuits responsible for inhibiting motor output, as well as excitability of spinal motoneurones. However, these effects can be influenced by other physiological responses to hypoxia (i.e., hyperventilation and hypocapnia). NEW FINDINGS: What is the central question of this study? How do two common methods of acute hypoxic exposure influence the excitability of intracortical networks and spinal circuits responsible for motor output? What is the main finding and its importance? The excitability of spinal circuits and intracortical networks responsible for inhibition of motor output was reduced during severe acute exposure to hypoxia at 2 h, but this was not seen during less severe exposure. This provides insight into the potential cause of variance seen in motor evoked potential responses to transcranial magnetic stimulation (corticospinal excitability measures) when exposed to hypoxia.

The acute effects of motor imagery and cervical transcutaneous electrical stimulation on manual dexterity and neural excitability.

Transcutaneous electrical stimulation (TCES) of the spinal cord induces changes in spinal excitability. Motor imagery (MI) elicits plasticity in the motor cortex. It has been suggested that plasticity occurring in both cortical and spinal circuits might underlie the improvements in performance observed when training is combined with stimulation. We investigated the acute effects of cervical TCES and MI delivered in isolation or combined on corticospinal excitability, spinal excitability and manual performance. Participants (N = 17) completed three sessions during which they engaged in 20 min of: 1) MI, listening to an audio recording instructing to complete the purdue pegboard test (PPT) of manual performance; 2) TCES at the spinal level of C5-C6; 3) MI + TCES, listening to the MI script while receiving TCES. Before and after each condition, we measured corticospinal excitability via transcranial magnetic stimulation (TMS) at 100% and 120% motor threshold (MT), spinal excitability via single-pulse TCES and manual performance with the PPT. Manual performance was not improved by MI, TCES or MI + TCES. Corticospinal excitability assessed at 100% MT intensity increased in hand and forearm muscles after MI and MI + TCES, but not after just TCES. Conversely, corticospinal excitability assessed at 120% MT intensity was not affected by any of the conditions. The effects on spinal excitability depended on the recorded muscle: it increased after all conditions in biceps brachii (BB) and flexor carpi radialis (FCR); did not change after any conditions in the abductor pollicis brevis (APB); increased after TCES and MI + TCES, but not after just MI in the extensor carpi radialis (ECR). These findings suggest that MI and TCES increase the excitability of the central nervous system through different but complementary mechanisms, inducing changes in the excitability of spinal and cortical circuits. MI and TCES can be used in combination to modulate spinal/cortical excitability, an approach particularly relevant for people with limited residual dexterity who cannot engage in motor practice.

Excitatory-inhibitory modulation of transcranial focus ultrasound stimulation on human motor cortex.

AIMS: Transcranial focus ultrasound stimulation (tFUS) is a promising non-invasive neuromodulation technology. This study aimed to evaluate the modulatory effects of tFUS on human motor cortex (M1) excitability and explore the mechanism of neurotransmitter-related intracortical circuitry and plasticity. METHODS: Single pulse transcranial magnetic stimulation (TMS)-eliciting motor-evoked potentials (MEPs) were used to assessed M1 excitability in 10 subjects. Paired-pulse TMS was used to measure the effects of tFUS on GABA- and glutamate-related intracortical excitability and 1 H-MRS was used to assess the effects of repetitive tFUS on GABA and Glx (glutamine + glutamate) neurometabolic concentrations in the targeting region in nine subjects. RESULTS: The etFUS significantly increased M1 excitability, decreased short interval intracortical inhibition (SICI) and long interval intracortical inhibition (LICI). The itFUS significantly suppressed M1 excitability, increased SICI, LICI, and decreased intracortical facilitation (ICF). Seven times of etFUS decreased the GABA concentration (6.32%), increased the Glx concentration (12.40%), and decreased the GABA/Glx ratio measured by MRS, while itFUS increased the GABA concentration (18.59%), decreased Glx concentration (0.35%), and significantly increased GABA/Glx ratio. CONCLUSION: The findings support that tFUS with different parameters can exert excitatory and inhibitory neuromodulatory effects on the human motor cortex. We provide novel insights that tFUS change cortical excitability and plasticity by regulating excitatory-inhibition balance related to the GABAergic and glutamatergic receptor function and neurotransmitter metabolic level.

Transtraumatic Epidural Electrostimulation of the Spinal Cord in a Pig Model.

The effect of transtraumatic epidural electrostimulation (TEES) above (T5) and below (L2) spinal cord injury in the lower thoracic region (T8-T9) in combination with treadmill exercise in pigs was evaluated using electrophysiological examination methods and behavioral tests. Two weeks after spinal cord injury, motor evoked potentials of m. soleus were recorded during electrostimulation at the level of T5 and L2 segments, which indicated activation of spinal cord structures above and below the focus of injury. After 6 weeks of TEES in combination with physical training, restoration of the characteristics of M-response and H-reflex of the soleus muscle in response to stimulation of the sciatic nerve, improvement of joint mobility, and appearance of voluntary motor activity in the hindlimbs were observed. Neuromodulation with TEES had been proven to be an effective way to stimulate posttraumatic spinal cord regeneration and can be used in the development of a neurorehabilitation protocol for patients with spinal cord injury.

The touch in action: exploring sensorimotor interactions with motor imagery.

The current research investigates the role of tactile information and its associated neural substrates in controlling the action. We employ a combination of motor and sensory components by asking participants to imagine exerting force with the index finger while either touching or not touching a surface. Assuming action imagination and action performance present similar patterns of activation along the motor system, we applied single-pulse transcranial magnetic stimulation over the primary motor cortex (M1) during action imagination. We observed increased amplitude of motor-evoked potentials (MEPs) of the relevant muscle when imagined actions were performed concurrently with tactile stimulation, suggesting a facilitatory effect of touch on the motor system. The motor system activity was scaled-based on the different amounts of force required, and crucially, this effect was specific to the body part involved in the action imagined. An intriguing positive correlation was observed between participants' ratings of their imagery level of vividness and the activation of the motor system, indicating that those participants exhibiting MEPs scaled correctly also had strong visualization abilities, as reflected by their capacity to accurately distinguish between varying levels of force.

A C-shaped miniaturized coil for transcranial magnetic stimulation in rodents.

Objective.Transcranial magnetic stimulation (TMS) is a non-invasive technique widely used for neuromodulation. Animal models are essential for investigating the underlying mechanisms of TMS. However, the lack of miniaturized coils hinders the TMS studies in small animals, since most commercial coils are designed for humans and thus incapable of focal stimulation in small animals. Furthermore, it is difficult to perform electrophysiological recordings at the TMS focal point using conventional coils.Approach.We designed, fabricated, and tested a novel miniaturized TMS coil (4-by-7 mm) that consisted of a C-shaped iron powder core and insulated copper wires (30 turns). The resulting magnetic and electric fields were characterized with experimental measurements and finite element modeling. The efficacy of this coil in neuromodulation was validated with electrophysiological recordings of single-unit activities (SUAs), somatosensory evoked potentials (SSEPs), and motor evoked potentials (MEPs) in rats (n= 32) following repetitive TMS (rTMS; 3 min, 10 Hz).Main results.This coil could generate a maximum magnetic field of 460 mT and an electric field of 7.2 V m-1in the rat brain according to our simulations. With subthreshold rTMS focally delivered over the sensorimotor cortex, mean firing rates of primary somatosensory and motor cortical neurons significantly increased (154±5% and 160±9% from the baseline level, respectively); MEP and SSEP amplitude significantly increased (136±9%) and decreased (74±4%), respectively.Significance.This miniaturized C-shaped coil enabled focal TMS and concurrent electrophysiological recording/stimulation at the TMS focal point. It provided a useful tool to investigate the neural responses and underlying mechanisms of TMS in small animal models. Using this paradigm, we for the first time observed distinct modulatory effects on SUAs, SSEPs, and MEPs with the same rTMS protocol in anesthetized rats. These results suggested that multiple neurobiological mechanisms in the sensorimotor pathways were differentially modulated by rTMS.

F-waves induced by motor point stimulation are facilitated during handgrip and motor imagery tasks.

The F-wave is a motor response elicited via the antidromic firings of motor nerves by the electrical stimulation of peripheral nerves, which reflects the motoneuron pool excitability. However, the F-wave generally has low robustness i.e., low persistence and small amplitude. We recently found that motor point stimulation (MPS), which provides the muscle belly with electrical stimulation, shows different neural responses compared to nerve stimulation, e.g., MPS elicits F-waves more robustly than nerve stimulation. Here, we investigated whether F-waves induced by MPS can identify changes in motoneuron pool excitability during handgrip and motor imagery. Twelve participants participated in the present study. We applied MPS on their soleus muscle and recorded F-waves during eyes-open (EO), eyes-closed (EC), handgrip (HG), and motor imagery (MI) conditions. In the EO and EC conditions, participants relaxed with their eyes open and closed, respectively. In the HG, participants matched the handgrip force level to 30% of the maximum voluntary force with visual feedback. In the MI, they performed kinesthetic MI of plantarflexion at the maximal strength with closed eyes. In the HG and MI, the amplitudes of the F-waves induced by MPS were increased compared with those in the EO and EC, respectively. These results indicate that the motoneuron pool excitability was facilitated during the HG and MI conditions, consistent with findings in previous studies. Our findings suggest that F-waves elicited by MPS can be a good tool in human neurophysiology to assess the motoneuron pool excitability during cognitive and motor tasks.

Startling Acoustic Stimulation Has Task-Specific Effects on Intracortical Facilitation and Inhibition at Rest and During Visually Guided Isometric Elbow Flexion in Healthy Individuals.

Startling acoustic stimulation (SAS) causes a transient effect on the primary motor cortex (M1) nonreflexively. It reduces the cortical excitability at rest, but not during voluntary contraction. However, the effect of SAS on intracortical activity is not clear. The purpose of this study was to investigate the SAS effect on short-interval intracortical inhibition and intracortical facilitation using transcranial magnetic stimulation (TMS). Eleven healthy individuals performed isometric elbow flexion at 10% of maximum voluntary contraction on the dominant side with a real-time visual target (i.e., M1 preactivation) or at rest. TMS was delivered to the M1 ipsilateral to elbow flexion without or with SAS delivered 90 ms prior to TMS. There were three TMS delivery conditions: (a) single pulse, (b) short-interval intracortical inhibition, and (c) intracortical facilitation. TMS-induced motor-evoked potential (MEP) was compared between predetermined TMS and SAS conditions at rest and during ipsilateral voluntary contraction. We confirmed that SAS decreased the MEP amplitude at rest, but not during M1 preactivation. SAS caused task-specific effects on intracortical excitability. Specifically, SAS increased intracortical facilitation at rest and during voluntary contraction. However, SAS decreased short-interval intracortical inhibition only during M1 preactivation. Collectively, our results suggest that SAS transiently influences the motor cortex excitability, possibly via its activation of higher centers, to achieve a visually guided goal-directed task.

Assessing the interaction between L-dopa and γ-transcranial alternating current stimulation effects on primary motor cortex plasticity in Parkinson's disease.

L-dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA-A-ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta-burst stimulation (iTBS). However, it is unknown whether L-dopa modifies the beneficial effects of iTBS-γ-tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS-γ-tACS and iTBS-sham-tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short-interval intracortical inhibition (SICI) were assessed before and after iTBS-tACS. We also evaluated possible SICI changes during γ-tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS-γ-tACS. The amount of change produced by iTBS-γ-tACS was similar in patients OFF and ON therapy. Finally, γ-tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA-A-ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L-dopa and γ-tACS effects at the M1 level. The possible neural substrate underlying iTBS-γ tACS effects, that is, γ-resonant GABA-A-ergic interneurons activity, may explain our findings.

The recruitment of indirect waves within primary motor cortex during motor imagery: A directional transcranial magnetic stimulation study.

Motor imagery (MI) refers to the mental simulation of an action without overt movement. While numerous transcranial magnetic stimulation (TMS) studies provided evidence for a modulation of corticospinal excitability and intracortical inhibition during MI, the neural signature within the primary motor cortex is not clearly established. In the current study, we used directional TMS to probe the modulation of the excitability of early and late indirect waves (I-waves) generating pathways during MI. Corticospinal responses evoked by TMS with posterior-anterior (PA) and anterior-posterior (AP) current flow within the primary motor cortex evoke preferentially early and late I-waves, respectively. Seventeen participants were instructed to stay at rest or to imagine maximal isometric contractions of the right flexor carpi radialis. We demonstrated that the increase of corticospinal excitability during MI is greater with PA than AP orientation. By using paired-pulse stimulations, we confirmed that short-interval intracortical inhibition (SICI) increased during MI in comparison to rest with PA orientation, whereas we found that it decreased with AP orientation. Overall, these results indicate that the pathways recruited by PA and AP orientations that generate early and late I-waves are differentially modulated by MI.

Neural data-driven model of spinal excitability changes induced by transcutaneous electrical stimulation in spinal cord injury subjects.

The efficacy of trans-spinal direct current stimulation (tsDCS) as neurorehabilitation technology remains sub-optimal, partly due to the variability introduced by subject-specific neurophysiological features and stimulation conditions (e.g. electrode placement, stimulating amplitude, polarity, etc.) Hence, current therapies apply tsDCS in an open-loop fashion, resulting in a lack of standardized protocols for controlling elicited neuronal adaptations in closed-loop. Through the combination of high-density electromyogram (HD-EMG) decomposition, biophysical neuronal modelling and metaheuristic optimization, this work presents a novel neural data-driven framework for estimating subject-specific features and quantifying acute neuronal adaptations elicited by tsDCS on incomplete spinal cord injury subjects. This approach consists of calibrating the anatomical parameters (e.g. soma diameter) of in silico $\alpha-$motoneuron (MN) models for firing similarly to in vivo MNs decoded from HD-EMG. Assuming that cathodal-tsDCS elicits excitability changes in the MN pool, while preserving their anatomical parameters, optimization of an excitability gain common to the entire pool was performed to minimize discrepancies in firing rate and recruitment time between in vivo and in silico MNs after cathodal-tsDCS. This quantification of excitability changes on MN models calibrated in a person specific way enables closing the loop with neuro-modulation devices to tailor neurorehabilitation therapies. Clinical Relevance - This framework addresses a key limitation in non-invasive neuro-modulative technologies via a novel model-assisted framework that enables quantifying acute excitability changes induced on a person-specific in silico MN pool calibrated using in vivo neural data. This will enable the development of advanced controllers for modulating targeted neuronal adaptations in closed-loop.

Continuous theta-burst stimulation to the sensorimotor cortex affects contralateral gamma-aminobutyric acid level and resting-state networks.

Continuous theta-burst stimulation (cTBS) is a noninvasive repetitive brain stimulation protocol that suppresses the excitability of the primary motor cortex. It induces cerebral cortical inhibition by increasing inhibitory interneuronal excitability that is associated with increases in gamma-aminobutyric acid (GABA) concentration in the stimulated cortices. cTBS has been applied in the rehabilitation of stroke patients to modulate interhemispheric imbalance. However, the precise mechanisms of cTBS in remote brain areas remain uncertain. We evaluated cTBS-induced GABA level changes in bilateral sensorimotor cortices using GABA-edited magnetic resonance spectroscopy, alternations of motor evoked potentials (MEPs), and resting-state networks (RSNs) using resting-state functional magnetic resonance imaging in 24 healthy right-handed adults (mean age: 34.4 ± 5.0 years). GABA levels in the stimulated left hemisphere significantly increased from baseline (p = 0.013), which was comparable with those of previous reports. GABA levels in the unstimulated right hemisphere showed a trend decrease. cTBS induced a significant decrease in right hand-MEP amplitudes (22.06% ± 43.50%) from baseline (p = 0.026) in accordance with GABA concentrations. However, multiple RSNs, including the default mode and primary motor networks, did not show any obvious differences between pre- and post-stimulus comparisons in the sensorimotor network using the dual regression approach. These results suggest that cTBS simultaneously increases ipsilateral GABA in the stimulated left hemisphere and decreases contralateral GABA in the unstimulated right hemisphere. Neuromodulation following cTBS may be associated with the interhemispheric inhibition because of alterations in GABA levels between the stimulated and unstimulated cortices.

Differences in motor imagery strategy change behavioral outcome.

Kinesthetic motor imagery (KMI) involves imagining the feeling and experience of movements. We examined the effects of KMI, number visualizing, and KMI with number visualizing on the excitability of spinal motor neurons and a behavioral outcome measure in a pinch force task. Healthy participants (13 men and 8 women; mean age: 24.8 ± 5.5 years) were recruited. We compared the F-waves of the left thenar muscles after stimulating the left median nerve at the wrist during each motor imagery condition after a practice session. The KMI condition consisted of imagining muscle contraction, the number visualizing condition consisted of imagining the pinch force increasing numerically, and the KMI with number visualizing consisted of alternating between the KMI and imagining the pinch force increasing numerically. Before and after motor imagery, the time required to adjust to the target pinch force was compared. The time required to adjust the pinch force was shorter in the KMI with number visualizing condition than in the KMI and number visualizing conditions. There was no difference in the F/M amplitude ratio between each MI strategy condition, indicating the excitability of spinal motor neurons. Numerical information helped to improve the ability of participants to perform KMI.