Modulation Of Corticospinal Excitability Research Articles

Short-latency afferent inhibition is reduced with cold-water immersion of a limb and remains reduced after removal from the cold stimulus.

The experience of pain that is induced by extremely cold temperatures can exert a modulatory effect on motor cortex circuitry. Although it is known that immersion of a single limb in very cold water can increase corticomotor excitability it is unknown how afferent input to the cortex shapes excitatory and inhibitory processes. Therefore, the purpose of this study was to examine motor-evoked potentials (MEP), short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI) in response to immersion of a single hand in cold water. Transcranial magnetic stimulation (TMS) was used to assess MEPs, and peripheral nerve stimulation of the median nerve paired with TMS was used to measure SAI and LAI in motor circuits of the ipsilateral hemisphere. Measurements were obtained from electromyography (EMG) of the first dorsal interosseous (FDI) at baseline, during cold-water immersion, and during recovery from cold-water immersion. The intervention caused unconditioned MEPs to increase during exposure to the cold stimulus (P=0.008) which then returned to baseline levels once the hand was removed from the cold water. MEP responses were decoupled from SAI responses, where SAI was reduced during exposure to the cold stimulus (P=0.005) and remained reduced compared to baseline when the hand was removed from the cold water (P=0.002). The intervention had no effect on LAI. The uncoupling of SAI from MEPs during the recovery period suggests that the mechanisms underlying the modulation of corticospinal excitability by sensory input may be distinct from those affecting intracortical inhibitory circuits. HIGHLIGHTS: What is the central question of this study? Does immersion of a limb in very cold water influence corticospinal excitability and the level of afferent inhibition exerted on motor cortical circuits? What is the main finding and its importance? In additional to perception of temperature, immersion in 6°C water also induced perceptions of pain. Motor evoked potential (MEP) amplitude increased during immersion, and short-latency afferent inhibition (SAI) of the motor cortex was reduced during immersion; however, these responses differed after the limb was removed from the cold stimulus, as MEPs returned to normal levels while SAI remained suppressed.

Modulation of Corticospinal Excitability during Action Observation in Patients with Disorders of Consciousness.

Brain imaging studies have recently provided some evidence in favor of covert cognitive processes that are ongoing in patients with disorders of consciousness (DoC) (e.g., a minimally conscious state and vegetative state/unresponsive wakefulness syndrome) when engaged in passive sensory stimulation or active tasks such as motor imagery. In this exploratory study, we used transcranial magnetic stimulation (TMS) of the motor cortex to assess modulations of corticospinal excitability induced by action observation in eleven patients with DoC. Action observation is known to facilitate corticospinal excitability in healthy subjects, unveiling how the observer's motor system maps others' actions onto her/his motor repertoire. Additional stimuli were non-biological motion and acoustic startle stimuli, considering that sudden and loud acoustic stimulation is known to lower corticospinal excitability in healthy subjects. The results indicate that some form of motor resonance is spared in a subset of patients with DoC, with some significant difference between biological and non-biological motion stimuli. However, there was no covariation between corticospinal excitability and the type of DoC diagnosis (i.e., whether diagnosed with VS/UWS or MCS). Similarly, no covariation was detected with clinical changes between admission and discharge in clinical outcome measures. Both motor resonance and the difference between the resonance with biological/non-biological motion discrimination correlated with the amplitude of the N20 somatosensory evoked potentials, following the stimulation of the median nerve at the wrist (i.e., the temporal marker signaling the activation of the contralateral primary somatosensory cortex). Moreover, the startle-evoking stimulus produced an anomalous increase in corticospinal excitability, suggesting a functional dissociation between cortical and subcortical circuits in patients with DoC. Further work is needed to better comprehend the conditions in which corticospinal facilitation occurs and whether and how they may relate to individual clinical parameters.

Determining intracortical, corticospinal and alpha motoneurone excitability in athletes with patellar tendinopathy compared to asymptomatic controls.

Lower capacity to generate knee extension maximal voluntary force (MVF) has been observed in individuals affected with patellar tendinopathy (PT) compared to asymptomatic controls. This MVF deficit is hypothesized to emanate from alterations in corticospinal excitability (CSE). The modulation of CSE is intricately linked to the excitability levels at multiple sites, encompassing neurones within the corticospinal tract (CST), intracortical neurones within the primary motor cortex (M1), and the alpha motoneurone. The aim of this investigation was to examine the excitability of intracortical neurones, CST neurones, and the alpha motoneurone, and compare these between volleyball and basketball athletes with PT and matched asymptomatic controls. Nineteen athletes with PT and 18 asymptomatic controls participated in this cross-sectional study. Transcranial magnetic stimulation was utilized to assess CST excitability, corticospinal inhibition (silent period, and short-interval cortical inhibition). Peripheral nerve stimulation was used to evaluate lumbar spine and alpha motoneurone excitability, including the evocation of lumbar-evoked potentials and maximal compound muscle action potential (MMAX ), and CSE with central activation ratio (CAR). Knee extension MVF was also assessed. Athletes with PT exhibited longer silent period duration and greater electrical stimulator output for MMAX , as well as lower MVF, compared to asymptomatic controls (p < 0.05). These findings indicate volleyball and basketball athletes with PT exhibit reduced excitability of the alpha motoneurone or the neuromuscular junction, which may be linked to lower MVF. Subtle alterations at specific sites may represent compensatory changes to excitability aiming to maintain efferent drive to the knee extensors.

Modulation of lower limb muscle corticospinal excitability during various types of motor imagery

Motor imagery (MI) is used for rehabilitation and sports training. Previous studies focusing on the upper limb have investigated the effects of MI on corticospinal excitability in the muscles involved in the imagined movement (i.e., the agonist muscles). The present study focused on several lower-limb movements and investigated the influences of MI on corticospinal excitability in the lower limb muscles. Twelve healthy individuals (ten male and two female individuals) participated in this study. Motor-evoked potentials (MEP) from the rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and soleus (SOL) muscles were elicited through transcranial magnetic stimulation (TMS) to the primary motor cortex during MI of knee extension, knee flexion, ankle dorsiflexion, and ankle plantarflexion and at rest. The results showed that the RF MEPs were significantly increased during MI in knee extension, ankle dorsiflexion, and ankle plantarflexion but not in knee flexion, compared with those at rest. The TA MEPs were significantly increased during MI in knee extension and foot dorsiflexion, while MEPs were not significantly different during MI in knee flexion and foot dorsiflexion than those at rest. For the BF and SOL muscles, there was no significant MEP modulation in either MI. These results demonstrated that corticospinal excitability of the RF and TA muscles was facilitated during MI of movements in which they are active and during MI of lower-limb movements in which they are not involved. On the contrary, corticospinal excitability of the BF and SOL muscles was not facilitated by MI of lower-limb movements. These results suggest that facilitation of corticospinal excitability depends on the muscle and the type of lower-limb MI.

Motor-Respiratory Coupling Improves Endurance Performance during Rhythmic Isometric Handgrip Exercise.

This study aimed to evaluate whether motor-respiratory coupling exists in rhythmic isometric handgrip exercises and its effect on endurance performance. In addition, the mechanism underlying observed effects was to be investigated if higher motor-respiratory coupling rate could enhance endurance performance. Eleven subjects completed three rhythmic isometric handgrip trials to task failure in a randomized manner. After one pretraining session to determine personal grip frequency, one trial was performed without respiration requirement (CON), and two trials were performed with inspiration-motor coupling (IMC) or expiration-motor coupling. Changes in maximal voluntary contraction (MVC) and EMG were used to measure neuromuscular fatigue. Force data during test were used to assess exercise intensity. Another 10 subjects completed electrical stimulation-induced finger flexion and extension during normal inspiration, normal expiration, fast inspiration, fast expiration, and breath holding. Force changes of different breathing conditions were compared. Normalized exercise time to exhaustion was significantly longer in IMC (1.27 ± 0.23) compared with expiration-motor coupling (0.82 ± 0.18) and CON (0.91 ± 0.18, P < 0.001). ΔMVC, grip frequency, force, and EMG indices were not different among conditions (all P > 0.05). Electrical stimulation-induced finger extensor force was significant higher during fast inspiration (1.11 ± 0.09) than normal respiration (1.00 ± 0.05) and fast expiration (0.94 ± 0.08, P < 0.05). IMC is an effective way to improve endurance performance of rhythmic handgrip exercise. This is likely due to a reduction in the energy consumption of motion control, as evidenced by similar peripheral fatigue in different conditions and modulation of corticospinal excitability by respiration.

Variation of corticospinal excitability during kinesthetic illusion induced by musculotendinous vibration.

Despite being studied for more than 50 years, the neurophysiological mechanisms underlying vibration (VIB)-induced kinesthetic illusions are still unclear. The aim of this study was to investigate how corticospinal excitability tested by transcranial magnetic stimulation (TMS) is modulated during VIB-induced illusions. Twenty healthy adults received vibration over wrist flexor muscles (80 Hz, 1 mm, 10 s). TMS was applied over the primary motor cortex representation of wrist extensors at 120% of resting motor threshold in four random conditions (10 trials/condition): baseline (without VIB), 1 s, 5 s, and 10 s after VIB onset. Means of motor-evoked potential (MEP) amplitudes and latencies were calculated. Statistical analysis found a significant effect of conditions (stimulation timings) on MEP amplitudes (P = 0.035). Paired-comparisons demonstrated lower corticospinal excitability during VIB at 1 s compared with 5 s (P = 0.025) and 10 s (P = 0.003), although none of them differed from baseline values. Results suggest a time-specific modulation of corticospinal excitability in muscles antagonistic to those vibrated, i.e., muscles involved in the perceived movement. An early decrease of excitability was observed at 1 s followed by a stabilization of values near baseline at subsequent time points. At 1 s, the illusion is not yet perceived or not strong enough to upregulate corticospinal networks coherent with the proprioceptive input. Spinal mechanisms, such as reciprocal inhibition, could also contribute to lower the corticospinal drive of nonvibrated muscles in short period before the illusion emerges. Our results suggest that neuromodulatory effects of VIB are likely time-dependent, and that future work is needed to further investigate underlying mechanisms.NEW & NOTEWORTHY The modulation of corticospinal excitability when perceiving a vibration (VIB)-induced kinesthetic illusion evolves dynamically over time. This modulation might be linked to the delayed occurrence and progressive increase in strength of the illusory perception in the first seconds after VIB start. Different spinal/cortical mechanisms could be at play during VIB, depending on the tested muscle, presence/absence of an illusion, and the specific timing at which corticospinal drive is tested pre/post VIB.

Differential Corticospinal Excitability and Cortical Functional Connectivity Modulation by Spinal Cord Transcutaneous Stimulation-based Motor Training versus Motor Training alone in Able-bodied and SCI participants: A Multiple Case Study.

Spinal cord transcutaneous stimulation (scTS) has shown its potential for boosting motor, sensory, and autonomic function recovery after a spinal cord injury. Despite the demonstrated benefits, little is known about the exact neuromodulatory mechanisms triggered by scTS and the cortex involvement in the beneficial effects observed. Here, we examine the effects of scTS-based motor training and motor training alone on sensorimotor cortical functional connectivity and corticospinal excitability in able-bodied and SCI participants.Clinical Relevance- The results show preliminary evidence of differential cortical involvement and modulation by scTS-based motor training in uninjured and spinal-cord injured individuals. A better understanding of scTS mechanisms of action could help optimize the intervention design and potentiate its benefits.

Constraints on hand-foot coordination associated with phase dependent modulation of corticospinal excitability during motor imagery.

Interlimb coordination involving cyclical movements of hand and foot in the sagittal plane is more difficult when the limbs move in opposite directions compared with the same direction (directional constraint). Here we first investigated whether the directional constraint on hand-foot coordination exists in motor imagery (imagined motion). Participants performed 10 cyclic coordinated movements of right wrist flexion-extension and right ankle dorsiflexion-plantarflexion as quickly and precisely as possible, in the following three conditions; (1) actual movements of the two limbs, (2) imaginary movements of the two limbs, and (3) actual movement of one limb combined with imaginary movement of the other limb. Each condition was performed under two directions; the same and the opposite direction. Task execution duration was measured as the time between the first and second press of a button by the participants. The opposite directional movement took a significantly longer time than did the same directional movement, irrespective of the condition type. This suggests that directional constraint of hand-foot coordination occurs even in motor imagery without actual motor commands or kinesthetic signals. We secondarily examined whether the corticospinal excitability of wrist muscles is modulated in synchronization with an imaginary foot movement to estimate the neural basis of directional constraint on imaginary hand-foot coordination. The corticospinal excitability of the forearm extensor in resting position increased during dorsiflexion and decreased during plantarflexion similarly in both actual and imaginary foot movements. This corticospinal modulation depending on imaginary movement phase likely produces the directional constraint on the imaginary hand-foot coordination.

Multi-scale and cross-dimensional TMS mapping: A proof of principle in patients with Parkinson's disease and deep brain stimulation.

Transcranial magnetic stimulation (TMS) mapping has become a critical tool for exploratory studies of the human corticomotor (M1) organization. Here, we propose to gather existing cutting-edge TMS-EMG and TMS-EEG approaches into a combined multi-dimensional TMS mapping that considers local and whole-brain excitability changes as well as state and time-specific changes in cortical activity. We applied this multi-dimensional TMS mapping approach to patients with Parkinson's disease (PD) with Deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) ON and OFF. Our goal was to identifying one or several TMS mapping-derived markers that could provide unprecedent new insights onto the mechanisms of DBS in movement disorders. Six PD patients (1 female, mean age: 62.5 yo [59-65]) implanted with DBS-STN for 1 year, underwent a robotized sulcus-shaped TMS motor mapping to measure changes in muscle-specific corticomotor representations and a movement initiation task to probe state-dependent modulations of corticospinal excitability in the ON (using clinically relevant DBS parameters) and OFF DBS states. Cortical excitability and evoked dynamics of three cortical areas involved in the neural control of voluntary movements (M1, pre-supplementary motor area - preSMA and inferior frontal gyrus - IFG) were then mapped using TMS-EEG coupling in the ON and OFF state. Lastly, we investigated the timing and nature of the STN-to-M1 inputs using a paired pulse DBS-TMS-EEG protocol. In our sample of patients, DBS appeared to induce fast within-area somatotopic re-arrangements of motor finger representations in M1, as revealed by mediolateral shifts of corticomuscle representations. STN-DBS improved reaction times while up-regulating corticospinal excitability, especially during endogenous motor preparation. Evoked dynamics revealed marked increases in inhibitory circuits in the IFG and M1 with DBS ON. Finally, inhibitory conditioning effects of STN single pulses on corticomotor activity were found at timings relevant for the activation of inhibitory GABAergic receptors (4 and 20 ms). Taken together, these results suggest a predominant role of some markers in explaining beneficial DBS effects, such as a context-dependent modulation of corticospinal excitability and the recruitment of distinct inhibitory circuits, involving long-range projections from higher level motor centers and local GABAergic neuronal populations. These combined measures might help to identify discriminative features of DBS mechanisms towards deep clinical phenotyping of DBS effects in Parkinson's Disease and in other pathological conditions.

Corticospinal excitability and reflex modulation in a contralateral non-stretched muscle following unilateral stretching.

Muscle stretching effect on the range of motion (ROM) and force deficit in non-stretched muscle, and the underlying mechanisms, is an ongoing issue. This study aimed to investigate crossover stretching effects and mechanisms on the plantar flexor muscles. Fourteen recreationally active females (n = 5) and males (n = 9) performed six sets of 45-s static stretching (SS) (15-s recovery) to the point of discomfort of the dominant leg (DL) plantar flexors or control (345-s rest). Participants were tested for a single 5-s pre- and post-test maximal voluntary isometric contraction (MVIC) with each plantar flexor muscle and were tested for DL and non-DL ROM. They were tested pre- and post-test (immediate, 10-s, 30-s) for the Hoffman (H)-reflex and motor-evoked potentials (MEP) from transcranial magnetic stimulation in the contralateral, non-stretched muscle. Both the DL and non-DL-MVIC force had large magnitude, significant (↓10.87%, p = 0.027, pƞ2 = 0.4) and non-significant (↓9.53%, p = 0.15, pƞ2 = 0.19) decreases respectively with SS. The SS also significantly improved the DL (6.5%, p < 0.001) and non-DL (5.35%, p = 0.002) ROM. The non-DL MEP/MMax and HMax/MMax ratio did not change significantly. Prolonged static stretching improved the stretched muscle's ROM. However, the stretched limb's force was negatively affected following the stretching protocol. The ROM improvement and large magnitude force impairment (statistically non-significant) were transferred to the contralateral muscles. The lack of significant changes in spinal and corticospinal excitability confirms that the afferent excitability of the spinal motoneurons and corticospinal excitability may not play a substantial role in non-local muscle's ROM or force output responses.

Corticospinal and spinal adaptations following lower limb motor skill training: a meta-analysis with best evidence synthesis.

Motor skill training alters the human nervous system; however, lower limb motor tasks have been less researched compared to upper limb tasks. This meta-analysis with best evidence synthesis aimed to determine the cortical and subcortical responses that occur following lower limb motor skill training, and whether these responses are accompanied by improvements in motor performance. Following a literature search that adhered to the PRISMA guidelines, data were extracted and analysed from six studies (n = 172) for the meta-analysis, and 11 studies (n = 257) were assessed for the best evidence synthesis. Pooled data indicated that lower limb motor skill training increased motor performance, with a standardised mean difference (SMD) of 1.09 being observed. However, lower limb motor skill training had no effect on corticospinal excitability (CSE), Hoffmann's reflex (H-reflex) ormuscle compound action potential (MMAX)amplitude. The best evidence synthesis found strong evidence for improved motor performance and reduced short-interval cortical inhibition (SICI) following lower limb motor skill training, with conflicting evidence towards the modulation of CSE. Taken together, this review highlights the need for further investigation on how motor skill training performed with the lower limb musculature canmodulate corticospinal responses. This will also help us to better understand whether these neuronal measures are underpinning mechanisms that support an improvement in motor performance.

Resolving equivocal gain modulation of corticospinal excitability

The ratio between the input and output of neuronal populations, usually referred to as gain modulation, is rhythmically modulated along the oscillatory cycle. Previous research on spinal neurons, however, revealed contradictory findings: both uni- and bimodal patterns of increased responsiveness for synaptic input have been proposed for the oscillatory beta rhythm.In this study, we compared previous approaches of phase estimation directly on simulated data and empirically tested the corresponding predictions in healthy males and females. We applied single-pulse transcranial magnetic stimulation over the primary motor cortex at rest, and assessed the spinal output generated by this input. Specifically, the peak-to-peak amplitude of the motor evoked potential in the contralateral forearm was estimated as a function of the EMG phase at which the stimulus was applied. The findings indicated that human spinal neurons adhere to a unimodal pattern of increased responsiveness, and suggest that the rising phase of the upper beta band maximizes gain modulation. Importantly, a bimodal pattern of increased responsiveness was shown to result in an artifact during data analysis and filtering. This observation of invalid preprocessing could be generalized to other frequency bands (i.e., delta, theta, alpha, and gamma), different task conditions (i.e., voluntary muscle contraction), and EEG-based phase estimations. Appropriate analysis algorithms, such as broad-band filtering, enable us to accurately determine gain modulation of neuronal populations and to avoid erroneous phase estimations. This may facilitate novel phase-specific interventions for targeted neuromodulation.

Real-time EEG-triggered TMS of M1 during sleep to characterize the phasic modulation of corticospinal excitability during the thalamocortical sleep spindle

Real-time EEG-triggered TMS of M1 during sleep to characterize the phasic modulation of corticospinal excitability during the thalamocortical sleep spindle

External and internal focus of attention differentially modulate corticospinal excitability in anticipatory postural adjustments

Whether attentional focus modulates the corticospinal excitability of the lower limb muscles in anticipatory postural adjustments (APAs) when performing a ballistic movement of the upper limb remains unclear. The present study used transcranial magnetic stimulation (TMS) to examine the corticospinal excitability of the lower limb muscles along with the kinematic profiles during dart throwing with different attentional foci, external focus (EF) and internal focus (IF). In 13 healthy participants, TMS was applied immediately before electromyographic onset of the tibialis anterior (TA) muscle, and the motor evoked potential (MEP) was recorded in the TA and soleus (SOL) muscles. The performance accuracy was significantly higher in the EF condition than in the IF condition. In both EF and IF conditions, MEP amplitude in the TA muscle, but not the SOL muscle, was significantly higher immediately before TA muscle onset (− 100, − 50, and 0 ms) compared to the control. In particular, the MEP increment in the TA muscle before TA muscle onset (− 50 and 0 ms) was significantly larger in the EF condition than in the IF condition. Our findings provide the first evidence for the modulation of corticospinal excitability in APA by changing attentional focus.

The interaction between metaplastic neuromodulation and fatigue in multiple sclerosis

Background and objectiveNeuromuscular fatigue contributes to decrements in quality of life in Multiple Sclerosis (MS), yet available treatments demonstrate limited efficacy. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique which presents promise in managing fatigue, possibly related to its capacity to modulate corticospinal excitability. There is evidence for capitalising on metaplasticity using tDCS for improving outcomes. However, this remains to be explored with fatigue in people with MS (pwMS). We investigated cathodal tDCS (ctDCS) priming on anodal tDCS (atDCS)-induced corticospinal excitability and fatigue modulation in pwMS. Methods15 pwMS and 15 healthy controls completed fatiguing exercise whilst receiving either ctDCS or sham (stDCS) primed atDCS to the motor cortex. We assessed change in contraction force and motor evoked potential (MEP) amplitude across time to represent changes in fatigue and corticospinal excitability. Results and conclusionctDCS primed atDCS induced MEP elevation in healthy participants but not in pwMS, possibly indicating impaired metaplasticity in pwMS. No tDCS-mediated change in the magnitude of fatigue was observed, implying that development of fatigue may not rely on changes in corticospinal excitability. SignificanceThese findings expand understanding of tDCS effects in pwMS, highlighting differences that may be relevant in the disease pathophysiology.

The effects of explicit and implicit information on modulation of corticospinal excitability during hand-object interactions

Fingertip force scaling during hand-object interactions typically relies on visual information about the object and sensorimotor memories from previous object interactions. Here, we investigated whether contextual information, that is not explicitly linked to the intrinsic object properties (e.g., size or weight) but that is informative for motor control requirements, can mediate force scaling. For this, we relied on two separate behavioral tasks during which we applied transcranial magnetic stimulation (TMS) to probe corticospinal excitability (CSE), as a window onto the primary motor cortex role in controlling fingertip forces. In experiment 1, participants performed a force tracking task, where we manipulated available implicit and explicit visual information. That is, either the force target was fully visible, or only the force error was displayed as a deviation from a horizontal line. We found that participants’ performance was better when the force target was fully visible, i.e., when they had explicit access to predictive information. However, we did not find differences in CSE modulation based on the type of visual information. On the other hand, CSE was modulated by the change in muscle contraction, i.e., contraction vs. relaxation and fast vs. slow changes. In sum, these findings indicate that CSE only reflects the ongoing motor command. In experiment 2, other participants performed a sequential object lifting task of visually identical objects that were differently weighted, in a seemingly random order. Within this task, we hid short series of incrementally increasing object weights. This allowed us to investigate whether participants would scale their forces for specific object weights based on the previously lifted object (i.e., sensorimotor effect) or based on the implicit information about the hidden series of incrementally increasing weights (i.e., extrapolation beyond sensorimotor effects). Results showed that participants did not extrapolate fingertip forces based on the hidden series but scaled their forces solely on the previously lifted object. Unsurprisingly, CSE was not modulated differently when lifting series of random weights versus series of increasing weights. Altogether, these results in two different grasping tasks suggest that CSE encodes ongoing motor components but not sensorimotor cues that are hidden within contextual information.

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.

PO210 / #753 TOLERABILITY AND EFFECTS OF A THERAPEUTIC HIGH-FREQUENCY RTMS PROTOCOL IN CHRONIC COMPLETE AND INCOMPLETE SPINAL CORD INJURY: E-POSTER VIEWING

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) was shown to induce corticospinal excitability (CSE) modulation and motor performance improvements in individuals with Spinal Cord Injury (SCI) 1–3. The therapeutic potential of rTMS as an adjunct rehabilitation intervention has yet to be confirmed.

Phase matters when there is power: Phasic modulation of corticospinal excitability occurs at high amplitude sensorimotor mu-oscillations

Prior studies have suggested that oscillatory activity in cortical networks can modulate stimulus-evoked responses through time-varying fluctuations in neural excitation-inhibition dynamics. Studies combining transcranial magnetic stimulation (TMS) with electromyography (EMG) and electroencephalography (EEG) can provide direct measurements to examine how instantaneous fluctuations in cortical oscillations contribute to variability in TMS-induced corticospinal responses. However, the results of these studies have been conflicting, as some reports showed consistent phase effects of sensorimotor mu-rhythms with increased excitability at the negative mu peaks, while others failed to replicate these findings or reported unspecific mu-phase effects across subjects. Given the lack of consistent results, we systematically examined the modulatory effects of instantaneous and pre-stimulus sensorimotor mu-rhythms on corticospinal responses with offline EEG-based motor evoked potential (MEP) classification analyses across five identical visits. Instantaneous sensorimotor mu-phase or pre-stimulus mu-power alone did not significantly modulate MEP responses. Instantaneous mu-power analyses showed weak effects with larger MEPs during high-power trials at the overall group level analyses, but this trend was not reproducible across visits. However, TMS delivered at the negative peak of high magnitude mu-oscillations generated the largest MEPs across all visits, with significant differences compared to other peak-phase combinations. High power effects on MEPs were only observed at the trough phase of ongoing mu oscillations originating from the stimulated region, indicating site and phase specificity, respectively. More importantly, such phase-dependent power effects on corticospinal excitability were reproducible across multiple visits. We provide further evidence that fluctuations in corticospinal excitability indexed by MEP amplitudes are partially driven by dynamic interactions between the magnitude and the phase of ongoing sensorimotor mu oscillations at the time of TMS, and suggest promising insights for (re)designing neuromodulatory TMS protocols targeted to specific cortical oscillatory states.

TU-103. Real-time EEG-triggered TMS of M1 during sleep to characterize the phasic modulation of corticospinal excitability during the thalamocortical sleep spindle

TU-103. Real-time EEG-triggered TMS of M1 during sleep to characterize the phasic modulation of corticospinal excitability during the thalamocortical sleep spindle