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Brain responses to transcranial magnetic stimulation (TMS) as measured with electroencephalography (EEG) have so far been assessed either by TMS-evoked EEG potentials (TEPs), mostly reflecting phase-locked neuronal activity, or time-frequency-representations (TFRs), reflecting oscillatory power arising from a mixture of both evoked (i.e., phase-locked) and induced (i.e., non-phase-locked) responses. Single-pulse TMS of the human primary motor cortex induces a specific pattern of oscillatory changes, characterized by an early (30–200 ms after TMS) synchronization in the α- and β-bands over the stimulated sensorimotor cortex and adjacent lateral frontal cortex, followed by a late (200–400 ms) α- and β-desynchronization over the stimulated and contralateral sensorimotor cortex. As GABAergic inhibition plays an important role in shaping oscillatory brain activity, we sought here to understand if GABAergic inhibition contributes to these TMS-induced oscillations. We tested single oral doses of alprazolam, diazepam, zolpidem (positive modulators of the GABAA receptor), and baclofen (specific GABAB receptor agonist). Diazepam and zolpidem enhanced, and alprazolam tended to enhance while baclofen decreased the early α-synchronization. Alprazolam and baclofen enhanced the early β-synchronization. Baclofen enhanced the late α-desynchronization, and alprazolam, diazepam and baclofen enhanced the late β-desynchronization. The observed GABAergic drug effects on TMS-induced α- and β-band oscillations were not explained by drug-induced changes on corticospinal excitability, muscle response size, or resting-state EEG power. Our results provide first insights into the pharmacological profile of TMS-induced oscillatory responses of motor cortex. •The response to TMS of M1 is composed of evoked and induced oscillatory activity.•TMS induced early α-/β-synchronization and late α-/β-desynchronization in M1.•GABAAergic vs. GABABergic drugs had opposite effects on early α-synchronization.•GABAAergic and GABABergic drugs enhanced the late β-desynchronization.

Size and duration of the neuroplastic effects of tDCS depend on stimulation parameters, including stimulation duration and intensity of current. The impact of stimulation parameters on physiological effects is partially non-linear. To improve the utility of this intervention, it is critical to gather information about the impact of stimulation duration and intensity on neuroplasticity, while expanding the parameter space to improve efficacy. Anodal tDCS of 1–3 mA current intensity was applied for 15–30 minutes to study motor cortex plasticity. Sixteen healthy right-handed non-smoking volunteers participated in 10 sessions (intensity-duration pairs) of stimulation in a randomized cross-over design. Transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEP) were recorded as outcome measures of tDCS effects until next evening after tDCS. All active stimulation conditions enhanced motor cortex excitability within the first 2 hours after stimulation. We observed no significant differences between the three stimulation intensities and durations on cortical excitability. A trend for larger cortical excitability enhancements was however observed for higher current intensities (1 vs 3 mA). These results add information about intensified tDCS protocols and suggest that the impact of anodal tDCS on neuroplasticity is relatively robust with respect to gradual alterations of stimulation intensity, and duration.

Dopamine, a key neuromodulator in the central nervous system, regulates cortical excitability and plasticity by interacting with glutamate and GABA receptors, which are affected by dopamine receptor subtypes (D1‐ and D2‐like). Non‐invasive brain stimulation techniques can induce plasticity and monitor cortical facilitation and inhibition in humans. In a randomized, placebo‐controlled, double‐blinded study, we investigated how dopamine and D1‐ and D2‐like receptors impact transcranial direct current stimulation (tDCS)‐induced plasticity concerning glutamatergic and GABAergic mechanisms. Eighteen healthy volunteers received 1 mA anodal (13 min) and cathodal tDCS (9 min) over the left motor cortex combined with the dopaminergic agents l‐dopa (general dopamine activation), bromocriptine (D2‐like receptor agonist), combined D2 antagonism via sulpiride and general dopaminergic activation via l‐dopa to activate D1‐like receptors, and placebo medication. Glutamate‐related cortical facilitation and GABA‐related cortical inhibition were monitored using transcranial magnetic stimulation techniques, including I–O curve, intracortical facilitation (ICF), short‐interval intracortical inhibition (SICI), and I‐wave facilitation protocols. Our results indicate that anodal tDCS alone enhanced the I–O curve and ICF while decreasing SICI. Conversely, cathodal tDCS decreased the I‐O curve and ICF while increasing SICI. General dopamine and D2 receptor activation combined with anodal tDCS decreased the I‐O curve and ICF, but enhanced SICI compared to tDCS alone. When paired with cathodal tDCS, general dopamine and D2‐like receptor activity enhancement prolonged the cathodal tDCS effect on excitability. After anodal tDCS, D1‐like receptor activation increased the I‐O curve and ICF while reducing SICI. These effects were abolished with cathodal tDCS. Dopaminergic substances combined with anodal and cathodal tDCS did not have a significant effect on I‐wave facilitation. These results suggest that D1‐like receptor activation enhanced LTP‐like plasticity and abolished LTD‐like plasticity via glutamatergic NMDA receptor enhancement, while global dopaminergic and D2‐like receptor enhancement weakened LTP‐like but strengthened LTD‐like plasticity primarily via glutamatergic NMDA receptor activity diminution. Background: Dopamine modulates cortical excitability and plasticity by influencing glutamate and GABA receptor activity. This study investigates the impact of general dopaminergic activation and D1‐ and D2‐like receptor modulation on transcranial direct current stimulation (tDCS)‐induced plasticity in humans.Methods:• Pharmacological intervention: l‐dopa (general DA activation), Bromocriptine (D2 agonist), Sulpiride + l‐dopa (D1‐like activation), and placebo.• tDCS: Anodal (1 mA, 13 min) and Cathodal (1 mA, 9 min) over the left motor cortex.• Neurophysiological measures: Glutamatergic activity (I‐O curve, ICF) and GABAergic activity (SICI, I‐wave facilitation).Results:• D2‐like receptor and global dopamine activation + anodal tDCS: decreased the I‐O curve and ICF, but enhanced SICI• D2‐like receptor and global dopamine activation + cathodal tDCS: prolonged the cathodal tDCS effect on SICI‐ICF and IO‐curve• D1‐like receptor activation + anodal tDCS: increased the I‐O curve and ICF while reducing SICI• D1‐like receptor activation + cathodal tDCS: abolished cathodal tDCS effects• No significant effect of dopaminergic substances combined with anodal and on I‐wave facilitationConclusion:D1‐like receptor activation enhanced LTP‐like plasticity and abolished LTD‐like plasticity via glutamatergic NMDA receptor enhancement, while global dopaminergic and D2‐like receptor enhancement weakened LTP‐like but strengthened LTD‐like plasticity primarily via glutamatergic NMDA receptor activity diminution.

Transcranial direct current stimulation (tDCS) uses a weak electric current to modulate neuronal activity. A neurophysiologic outcome measure to demonstrate reliable tDCS modulation at the group level is transcranial magnetic stimulation engendered motor evoked potentials (MEPs). Here, we conduct a study testing the reliability of individual MEP response patterns following a common tDCS protocol. Fourteen participants (7m/7f) each underwent nine randomized sessions of 1 mA, 10 min tDCS (3 anode; 3 cathode; 3 sham) delivered using an M1/orbito-frontal electrode montage (sessions separated by an average of ~5.5 days). Fifteen MEPs were obtained prior to, immediately following and in 5 min intervals for 30 min following tDCS. TMS was delivered at 130 % resting motor threshold using neuronavigation to ensure consistent coil localization. A number of non-experimental variables were collected during each session. At the individual level, considerable variability was seen among different testing sessions. No participant demonstrated an excitatory response ≥20 % to all three anodal sessions, and no participant demonstrated an inhibitory response ≥20 % to all three cathodal sessions. Intra-class correlation revealed poor anodal and cathodal test–retest reliability [anode: ICC (2,1)  = 0.062; cathode: ICC (2,1)  = 0.055] and moderate sham test–retest reliability [ICC (2,1)  = 0.433]. Results also revealed no significant effect of tDCS at the group level. Using this common protocol, we found the effects of tDCS on MEP amplitudes to be highly variable at the individual level. In addition, no significant effects of tDCS on MEP amplitude were found at the group level. Future studies should consider utilizing a more strict experimental protocol to potentially account for intra-individual response variations.

Tactile Imagery (TI) remains a fairly understudied phenomenon despite growing attention to this topic in recent years. Here, we investigated the effects of TI on corticospinal excitability by measuring motor evoked potentials (MEPs) induced by single-pulse transcranial magnetic stimulation (TMS). The effects of TI were compared with those of tactile stimulation (TS) and kinesthetic motor imagery (kMI). Twenty-two participants performed three tasks in randomly assigned order: imagine finger tapping (kMI); experience vibratory sensations in the middle finger (TS); and mentally reproduce the sensation of vibration (TI). MEPs increased during both kMI and TI, with a stronger increase for kMI. No statistically significant change in MEP was observed during TS. The demonstrated differential effects of kMI, TI and TS on corticospinal excitability have practical implications for devising the imagery-based and TS-based brain–computer interfaces (BCIs), particularly the ones intended to improve neurorehabilitation by evoking plasticity changes in sensorimotor circuitry.

The effects of transcranial direct current stimulation (tDCS) on motor cortical excitability are highly variable between individuals. Inter-individual differences in the electric fields generated in the brain by tDCS might play a role in the variability. Here, we explored whether these fields are related to excitability changes following anodal tDCS of the primary motor cortex (M1). Motor evoked potentials (MEPs) were measured in 28 healthy subjects before and after 20 min sham or 1 mA anodal tDCS of right M1 in a double-blind crossover design. The electric fields were individually modelled based on magnetic resonance images. Statistical analysis indicated that the variability in the MEPs could be partly explained by the electric fields, subjects with the weakest and strongest fields tending to produce opposite changes in excitability. To explain the findings, we hypothesized that the likely locus of action was in the hand area of M1, and the effective electric field component was that in the direction normal to the cortical surface. Our results demonstrate that a large part of inter-individual variability in tDCS may be due to differences in the electric fields. If this is the case, electric field dosimetry could be useful for controlling the neuroplastic effects of tDCS.

Current clinical practice lacks quantitative assessment methods for elbow joint movements. In response to existing research limitations, this study introduces the innovative elbow joint torque measurement device (EJTMD), which concurrently measures muscle strength and active range of motion (AROM) using a five-bar linkage system governed by a sliding mode control algorithm. Healthy subjects ( n  = 22) and stroke patients ( n  = 22) were recruited in a randomized trial. Each participant underwent two measurement. EJTMD or traditional tools like a protractor and a muscle strength tester. Participants were randomly allocated to EJTMD first or traditional tools first. The efficacy of EJTMD was assessed by comparing muscle strength and AROM with traditional tools. Integrated electromyography (iEMG) and root mean square (RMS) were used to assess the intensity of muscle activity during elbow movements. The peak torque (PT) and the ratio of peak torque to body weight (PT/BW) were examined to explore the differences in mechanical characteristics of bilateral elbow joints. Motor evoked potential (MEP) and central motor conduction time (CMCT) were employed to investigate the potential mechanisms underlying motor discrepancies post-stroke. EJTMD demonstrates superior muscle strength, AROM, iEMG, and RMS during elbow movements compared to traditional tools ( P  < 0.05). Repeated EJTMD measurement outcomes have a good correlation on the same day ( r  ≥ 0.999, P  < 0.001). EJTMD exhibits significant differences in measurement outcomes among stroke patients before and after treatment ( P  < 0.05), compared to traditional tools. Stroke patients exhibit reduced PT and PT/BW on the lesion side across low, medium, and high-speed tests, with a more pronounced decline observed during low-speed testing ( P  < 0.001). Stroke patients show decreased iEMG and RMS on the affected side during elbow movements ( P  < 0.05), with prolonged MEP latency and CMCT ( P  < 0.001), and reduced MEP amplitude ( P  < 0.001). Based on the results, EJTMD demonstrates reliability and effectiveness in assessing elbow movements in both healthy subjects and stroke patients, showing sensitivity to minor joint changes. Stroke patients exhibit reduced flexor and extensor function on the lesion side, potentially resulting from impaired corticospinal tract conduction.

Background Transcranial alternating current stimulation (tACS) is a non-invasive technique that modulates neural oscillations, yet its specific effects on cortical excitability are not well-understood. This study investigated the effects of tACS on neuroplasticity in the primary motor cortex (M1) across different frequencies. Methods In this randomized, sham-controlled, crossover study, 18 healthy young adults received β-tACS γ-tACS, and sham stimulation over the M1. Neurophysiological responses were assessed using motor evoked potentials (MEPs), electroencephalograms (EEG), and transcranial evoked potentials (TEPs) to determine the frequency-specific effects of tACS on cortical excitability and neuroplasticity. Results γ-tACS significantly enhanced cortical excitability, as reflected by larger MEP amplitudes compared to both β-tACS and sham stimulation. In addition, γ-tACS resulted in significantly smaller M1-P15 amplitudes in TEP than other stimulation conditions. In contrast, β-tACS did not produce significant changes in either MEPs or TEPs compared to sham stimulation. Conclusion These findings provide evidence that tACS induces frequency-dependent effects on cortical excitability and neuroplasticity within the M1. This selective modulation of cortical excitability with γ-tACS suggests its potential as a therapeutic intervention for optimizing motor function and rehabilitation. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2300074898, date of registration: 2023/08/18).

Chronic low back pain (CLBP) is linked to reduced excitability in the primary motor (M1) and sensory (S1) cortices. Combining sensory-motor exercises with transcranial direct current stimulation (tDCS) to boost M1 and S1 excitability may improve treatment outcomes. This combined approach aligns with the neurophysiological mechanisms underlying CLBP and may target the neuroplastic changes induced by low back pain. This study aimed to assess whether enhancing M1 and S1 excitability via tDCS, alongside sensory-motor exercises, offers additional benefits for CLBP patients. Participants were randomly assigned to receive either real or sham tDCS alongside sensory-motor exercises. Outcome measures included pain intensity, disability level, motor control ability, amplitudes of N80 and N150, and the amplitude of motor-evoked potential (MEP) and active motor threshold (AMT) for the multifidus (MF) and transversus abdominis/internal oblique (TrA/IO) muscles. A linear mixed-effects model (LMM) analyzed group, time, and interaction effects, while Spearman's correlation assessed relationships between neurophysiological and clinical outcomes. The results showed significant reductions in pain intensity and disability levels (P < 0.001) and improved motor control (P < 0.001) in both groups. Both groups also exhibited increase in MF MEP amplitude (P = 0.042) and N150 amplitude (P = 0.028). The tDCS group demonstrated a significant decrease in AMT of MF and TrA/IO muscles (P < 0.05) and an increase in N80 amplitude (P = 0.027), with no significant changes in the control group. Additionally, the tDCS group had significantly lower AMT for the TrA/IO muscle in the post-test compared to the sham group (P = 0.001). Increased N150 amplitude was correlated with improved motor control. The findings showed that sensory-motor exercises combined with either tDCS or sham tDCS effectively reduced pain intensity, decreased disability, and improved lumbar motor control in lumbosacral radiculopathy patients. No significant differences were observed between groups, indicating no added clinical benefit from tDCS over exercises alone. However, both groups demonstrated increased N150 and MF MEP amplitudes, suggesting enhanced cortical excitability in motor and sensory regions. While clinical outcomes were similar, neurophysiological data indicate that sensory-motor exercises play a central role in boosting cortical excitability, with tDCS further amplifying this effect, as evidenced by a significant AMT reduction in MF and TrA/IO muscles and an increase in N80 amplitude.

ObjectiveThe role of ipsilateral descending motor pathways in voluntary movement of humans is still a matter of debate, with partly contradictory results. The aim of our study therefore was to examine the excitability of ipsilateral motor evoked potentials (iMEPs) regarding site and the specificity for unilateral and bilateral elbow flexion extension tasks.MethodsMR-navigated transcranial magnetic stimulation mapping of the dominant hemisphere was performed in twenty healthy participants during tonic unilateral (iBB), bilateral homologous (bBB) or bilateral antagonistic elbow flexion-extension (iBB-cAE), the map center of gravity (CoG) and iMEP area from BB were obtained.ResultsThe map CoG of the ipsilateral BB was located more anterior-laterally than the hotspot of the contralateral BB within the primary motor cortex, with a significant difference in CoG in iBB and iBB-cAE, but not bBB compared to the hotspot for the contralateral BB (each p < 0.05). However, different tasks had no effect on the size of the iMEPs.ConclusionOur data demonstrated that excitability of ipsilateral and contralateral MEP differ spatially in a task-specific manner suggesting the involvement of different motor networks within the motor cortex.