Probing in vivo cortical myeloarchitecture in humans via line-scan diffusion acquisitions at 7 T with 250-500 micron radial resolution.

PURPOSE: The goal of this study was to measure diffusion signals within the cerebral cortex using the line-scan technique to achieve extremely high resolution in the radial direction (ie, perpendicular to the cortical surface) and to demonstrate the utility of these measurements for investigating laminar architecture in the living human brain. METHODS: Line-scan diffusion data with 250-500 micron radial resolution were acquired at 7 T on 8 healthy volunteers, with each line prescribed perpendicularly to primary somatosensory cortex (S1) and primary motor cortex (M1). Apparent diffusion coefficients, fractional anisotropy values, and radiality indices were measured as a function of cortical depth. RESULTS: In the deep layers of S1, we found evidence for high anisotropy and predominantly tangential diffusion, with low anisotropy observed in superficial S1. In M1, moderate anisotropy and predominantly radial diffusion was seen at almost all cortical depths. These patterns were consistent across subjects and were conspicuous without averaging data across different locations on the cortical sheet. CONCLUSION: Our results are in accord with the myeloarchitecture of S1 and M1, known from prior histology studies: in S1, dense bands of tangential myelinated fibers run through the deep layers but not the superficial ones, and in M1, radial myelinated fibers are prominent at most cortical depths. This work therefore provides support for the idea that high-resolution diffusion signals, measured with the line-scan technique and receiving a boost in SNR at 7 T, may serve as a sensitive probe of in vivo laminar architecture.

Improving consolidation by applying anodal transcranial direct current stimulation at primary motor cortex during repetitive practice.

Engagement of primary motor cortex (M1) is important for successful consolidation of motor skills. Recruitment of M1 has been reported to be more extensive during interleaved compared to repetitive practice and this differential recruitment has been proposed to contribute to the long-term retention benefit associated with interleaved practice. The present study administered anodal direct current stimulation (tDCS) during repetitive practice in an attempt to increase M1 activity throughout repetitive practice with the goal to improve the retention performance of individuals exposed to this training format. Fifty-four participants were assigned to one of three experimental groups that included: interleaved-sham, repetitive-sham, and repetitive-anodal tDCS. Real or sham stimulation at M1 was administered during practice of three motor sequences for approximately 20-min. Performance in the absence of any stimulation was evaluated prior to practice, immediately after practice as well as at 6-hr, and 24-h after practice was complete. As expected, for the sham conditions, interleaved as opposed repetitive practice resulted in superior offline gain. This was manifest as more rapid stabilization of performance after 6-h as well as an enhancement in performance with a period of overnight sleep. Administration of anodal stimulation at M1 during repetitive practice improved offline gains assessed at both 6-h and 24-h tests compared to the repetitive practice sham group. These data are consistent with the claims that reduced activation at M1 during repetitive practice impedes offline gain relative to interleaved practice and that M1 plays an important role in early consolidation of novel motor skills even in the context of the simultaneous acquisition of multiple new skills. Moreover, these findings highlight a possible role for M1 during sleep-related consolidation, possibly as part of a network including the dorsal premotor region, which supports delayed performance enhancement.

Repetitive Transcranial Magnetic Stimulation for Treating Chronic Neuropathic Pain: a Systematic Review.

Given pharmacological interventions' limited efficacy and abundance of its adverse effects, the repetitive transcranial magnetic stimulation (rTMS) is considered a viable non-invasive option for managing chronic neuropathic pain of different origins with promising outcomes. PURPOSE OF REVIEW: The provision of a systematic review of current literature on rTMS for managing chronic neuropathic pain of different origins, and assess its efficacy and outcomes, highlighting the need for standard protocols for utilizing rTMS. RECENT FINDINGS: Variable stimulation modalities were trialed targeting the M1, DLPFC, and somatosensory cortices S1 and S2. The M1 yielded the best results in 11 of the studies. Frequency of stimulation was variable; however, optimal outcome was with higher frequencies ranging 10-20 Hz rather than low-frequency 1 Hz. Repetitive TMS can produce significant relief from chronic neuropathic pain. The lack of standard methods for rTMS, stimulatory parameters, and target stimulation site precludes concluding the optimal modality for stimulation. The practical algorithm by Lefaucheur and Nguyen (Neurophysiol Clin. 49(4):301-7, 2019) can guide setting standardized algorithms for rTMS. Defining optimal stimulation sites, frequencies, and pulses to maximize patient's pain relief and minimize required rTMS sessions requires further research.

Simultaneous calcium recordings of hippocampal CA1 and primary motor cortex M1 and their relations to behavioral activities in freely moving epileptic mice.

Epilepsy is a common neurological disorder characterized by recurrent epileptic seizures. The cause of most cases of epilepsy is unknown. Although changes of calcium events in a single brain region during seizures have been reported before, there have been few studies on relations between calcium events of two different brain regions and epileptic behaviors in freely moving mice. To analyze calcium events simultaneously recorded in hippocampal CA1 (CA1) and primary motor cortex M1 (M1), and to explore their relations to various epileptic behaviors in freely moving epileptic models. Epileptic models were induced by Kainic acid (KA), a direct agonist of glutamatergic receptor, on adult male C57/BL6J mice. Calcium events of neurons and glia in CA1 and M1 labeled by a calcium indicator dye were recorded simultaneously with a multi-channel fiber photometry system. Three typical types of calcium events associated with KA-induced seizures were observed, including calcium baseline-rising, cortical spreading depression (CSD) and calcium flashing with a steady rate. Our results showed that the calcium baseline-rising occurred in CA1 was synchronized with that in M1, but the CSD waves were not. However, synchronization of calcium flashing in the two areas was uncertain, because it was only detected in CA1. We also observed that different calcium events happened with different epileptic behaviors. Baseline-rising events were accompanied by clonus of forelimbs or trembling, CSD waves were closely related to head movements (15 out of 18, 6 mice). Calcium flashing occurred definitely with drastic convulsive motor seizures (CMS, 6 mice). The results prove that the synchronization of calcium event exists in CA1 and M1, and different calcium events are related with different seizure behaviors. Our results suggest that calcium events involve in the synchronization of neural network and behaviors in epilepsy.

Muscle-specific modulation of indirect inputs to primary motor cortex during action observation.

Single-pulse transcranial magnetic stimulation (spTMS) studies report that movement observation facilitates corticospinal excitability in primary motor cortex (M1) in a muscle-specific manner. However, motor evoked potentials (MEPs) elicited by spTMS are known to reflect the summation of several descending volleys in corticospinal neurons which are evoked via mono- and polysynaptic inputs (so-called indirect waves or I-waves). It is unclear which of these components contribute to the muscle-specific modulation of M1 during action observation. The interactions between different I-waves are reflected in the facilitatory peaks elicited with a short-intracortical facilitation (SICF) protocol when two pulses are sent to M1 at precise intervals (i.e., 1.3, 2.5 or 4.1 ms). Here, we explored the modulation of early and late SICF peaks during action observation by measuring highly specific MEP amplitude changes measured in two muscles (index, FDI and little finger, ADM) while participants observed two different actions (precision and whole-hand grip). Our results demonstrate that both early (1.3 ms) and late (2.5 and 4.1 ms) SICF peaks are modulated in the context of movement observation. However, only the second peak (ISI 2.5 ms) was significantly associated with the muscle-specific modulation of corticospinal excitability as measured with spTMS. This late SICF peak is believed to reflect the activity cortico-cortical pathways involved in the facilitation of muscle-specific representations in M1. Thus, our findings suggest that movement observation leads to widespread activation of different neural circuits within M1, including those mediating cortico-cortical communication.

Transcranial direct-current stimulation combined with attention increases cortical excitability and improves motor learning in healthy volunteers.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has the potential to induce motor cortical plasticity in humans. It is well known that motor cortical plasticity plays an essential role in motor learning and recovery in patients with stroke and neurodegenerative disorders. However, it remains unclear how cognitive function influences motor cortical plasticity induced by tDCS. The present study aimed to investigate whether anodal tDCS combined with attention to a target muscle could enhance motor cortical plasticity and improve motor learning in healthy individuals. METHODS: Thirty-three healthy volunteers were assigned to two experiments. In experiment 1, there were three interventional conditions: 1) anodal tDCS was applied while participants paid attention to the first dorsal interosseous (FDI) muscle, 2) anodal tDCS was applied while participants paid attention to the sound, and 3) anodal tDCS was applied without the participants paying attention to the FDI muscle or the sound. Anodal tDCS (2 mA, 10 min) was applied over the primary motor cortex (M1). Changes in motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were assessed before and immediately after (0 min), and then 10 min, 30 min, and 60 min after each intervention. In experiment 2, we investigated whether the combination of anodal tDCS and attention to the abductor pollicis brevis (APB) muscle could facilitate the learning of a ballistic thumb movement. RESULTS: Anodal tDCS increased cortical excitability in all conditions immediately after the stimulation. Significant increases in MEPs and significant decreases in SICI were observed for at least 60 min after anodal tDCS, but only when participants paid attention to the FDI muscle. In contrast, no significant changes in ICF were observed in any condition. In experiment 2, the combination of tDCS and attention to the APB muscle significantly enhanced the acquisition of a ballistic thumb movement. The higher performance was still observed 7 days after the stimulation. CONCLUSIONS: This study shows that anodal tDCS over M1 in conjunction with attention to the target muscle enhances motor cortex plasticity and improves motor learning in healthy adults. These findings suggest that a combination of attention and tDCS may be an effective strategy to promote rehabilitation training in patients with stroke and neurodegenerative disorders. TRIAL REGISTRATION: Retrospectively registered (UMIN000036848).

Effect of neuromuscular electrical stimulation on motor cortex excitability upon release of tonic muscle contraction.

The aim of the present study was to investigate the neurophysiological triggers underlying muscle relaxation from the contracted state, and to examine the mechanisms involved in this process and their subsequent modification by neuromuscular electrical stimulation (NMES). Single-pulse transcranial magnetic stimulation (TMS) was used to produce motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI) in 23 healthy participants, wherein motor cortex excitability was examined at the onset of voluntary muscle relaxation following a period of voluntary tonic muscle contraction. In addition, the effects of afferent input on motor cortex excitability, as produced by NMES during muscle contraction, were examined. In particular, two NMES intensities were used for analysis: 1.2 times the sensory threshold and 1.2 times the motor threshold (MT). Participants were directed to execute constant wrist extensions and to release muscle contraction in response to an auditory "GO" signal. MEPs were recorded from the flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, and TMS was applied at three different time intervals (30, 60, and 90 ms) after the "GO" signal. Motor cortex excitability was greater during voluntary ECR and FCR relaxation using high-intensity NMES, and relaxation time was decreased. Each parameter differed significantly between 30 and 60 ms. Moreover, in both muscles, SICI was larger in the presence than in the absence of NMES. Therefore, the present findings suggest that terminating a muscle contraction triggers transient neurophysiological mechanisms that facilitate the NMES-induced modulation of cortical motor excitability in the period prior to muscle relaxation. High-intensity NMES might facilitate motor cortical excitability as a function of increased inhibitory intracortical activity, and therefore serve as a transient trigger for the relaxation of prime mover muscles in a therapeutic context.

Augmenting mirror visual feedback-induced performance improvements in older adults.

Previous studies have indicated that age-related behavioral alterations are not irreversible but are subject to amelioration through specific training interventions. Both training paradigms and non-invasive brain stimulation (NIBS) can be used to modulate age-related brain alterations and thereby influence behavior. It has been shown that mirror visual feedback (MVF) during motor skill training improves performance of the trained and untrained hands in young adults. The question remains of whether MVF also improves motor performance in older adults and how performance improvements can be optimised via NIBS. Here, we sought to determine whether anodal transcranial direct current stimulation (a-tDCS) can be used to augment MVF-induced performance improvements in manual dexterity. We found that older adults receiving a-tDCS over the right primary motor cortex (M1) during MVF showed superior performance improvements of the (left) untrained hand relative to sham stimulation. An additional control experiment in participants receiving a-tDCS over the right M1 only (without MVF/motor training of the right hand) revealed no significant behavioral gains in the left (untrained) hand. On the basis of these findings, we propose that combining a-tDCS with MVF might be relevant for future clinical studies that aim to optimise the outcome of neurorehabilitation.

Outcome-dependent coactivation of lip and tongue primary somatosensory representation following hypoglossal-facial transfer after peripheral facial palsy.

A hypoglossal-facial transfer is a common surgical strategy for reanimating the face after persistent total hemifacial palsy. We were interested in how motor recovery is associated with cortical reorganization of lip and tongue representation in the primary sensorimotor cortex after the transfer. Therefore, we used functional magnetic resonance imaging (fMRI) in 13 patients who underwent a hypoglossal-facial transfer after unilateral peripheral facial palsy. To identify primary motor and somatosensory tongue and lip representation sites, we measured repetitive tongue and lip movements during fMRI. Electromyography (EMG) of the perioral muscles during tongue and lip movements and standardized evaluation of lip elevation served as outcome parameters. We found an association of cortical representation sites in the pre- and postcentral gyrus (decreased distance of lip and tongue representation) with symmetry of recovered lip movements (lip elevation) and coactivation of the lip during voluntary tongue movements (EMG-activity of the lip during tongue movements). Overall, our study shows that hypoglossal-facial transfer resulted in an outcome-dependent cortical reorganization with activation of the cortical tongue area for restituded movement of the lip.

Midbrain dopaminergic degeneration differentially modulates primary motor cortex activity and motor behavior in hemi-parkinsonian rats.

Parkinson's disease (PD) is marked by degeneration in the nigrostriatal dopaminergic pathway, affecting motor control via complex changes in the cortico-basal ganglia-thalamic motor network, including the primary motor cortex (M1). The modulation of M1 neuronal activity by dopaminergic inputs, particularly from the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), plays a crucial role in PD pathophysiology. This study investigates how nigrostriatal dopaminergic degeneration influences M1 neuronal activity in rats using in vivo calcium imaging. Histological analysis confirmed dopaminergic lesion severity, with high lesion level rats showing significant motor deficits. Levodopa treatment improved fine motor abilities, particularly in high lesion level rats. Analysis of M1 calcium signals based on dopaminergic lesion severity revealed distinct M1 activity patterns. Animals with low dopaminergic lesion showed increased calcium events, while high lesion level rats exhibited decreased activity, partially restored by levodopa. These findings suggest that M1 activity is more sensitive to transient fluctuations in dopaminergic transmission, rather than to chronic high or low dopaminergic signaling. This study underscores the complex interplay between dopaminergic signaling and M1 neuronal activity in PD symptoms development. Further research integrating behavioral and calcium imaging data can elucidate mechanisms underlying motor deficits and therapeutic responses in PD.

Management of Episodic Migraine with Neuromodulation: A Case Report.

Migraine is a highly prevalent neurovascular disorder that affects approximately 15% of the global population. Migraine attacks are a complex cascade of neurologic events that lead to debilitating symptoms and are often associated with inhibitory behavior. The constellation of severe signs and symptoms during the ictal phase (headache attack) makes migraine the third most common cause of disability globally in both sexes under the age of 50. Misuse of pharmaceuticals, such as opiates, can lead to devastating outcomes and exacerbation of pain and headache attacks. A safe and well-tolerated non-pharmacological research approach is high-definition transcranial direct current stimulation over the M1.

Neuronal representation of bimanual arm motor imagery in the motor cortex of a tetraplegia human, a pilot study.

Introduction: How the human brain coordinates bimanual movements is not well-established. Methods: Here, we recorded neural signals from a paralyzed individual's left motor cortex during both unimanual and bimanual motor imagery tasks and quantified the representational interaction between arms by analyzing the tuning parameters of each neuron. Results: We found a similar proportion of neurons preferring each arm during unimanual movements, however, when switching to bimanual movements, the proportion of contralateral preference increased to 71.8%, indicating contralateral lateralization. We also observed a decorrelation process for each arm's representation across the unimanual and bimanual tasks. We further confined that these changes in bilateral relationships are mainly caused by the alteration of tuning parameters, such as the increased bilateral preferred direction (PD) shifts and the significant suppression in bilateral modulation depths (MDs), especially the ipsilateral side. Discussion: These results contribute to the knowledge of bimanual coordination and thus the design of cutting-edge bimanual brain-computer interfaces.

Dual-hemisphere anodal transcranial direct current stimulation improves bilateral motor synergies.

Transcranial direct current stimulation (tDCS) is one of the non-invasive brain stimulation techniques that can improve motor functions. As bimanual motor actions require high motor cortical activations between hemispheres, applying bilateral anodal stimulation on left and right sides of primary motor cortex (M1) can improve for improvements in bimanual motor tasks. This study investigated which bilateral tDCS protocol effectively improves bimanual hand-grip force control capabilities in healthy young adults. We used three different bilateral tDCS protocols: (a) dual-anodal stimulation on the M1 of bilateral hemispheres (Bi-AA), (b) anodal-cathodal stimulation on the M1 of dominant and nondominant hemispheres (Bi-AC), and (c) sham stimulation (Sham). The results indicated that applying the Bi-AA significantly improved bilateral motor synergies estimated by uncontrolled manifold analysis relative to Sham. However, these differences were not observed in the comparison between Bi-AA and Bi-AC as well as between Bi-AC and Sham. These findings suggest that facilitating motor cortical activations between both hemispheres may be an additional option for advancing interlimb motor coordination patterns.

Challenging inhibitory control with high- and low-calorie food: A behavioural and TMS study.

Most people are often tempted by their impulses to "indulge" in high-calorie food, even if this behaviour is not consistent with their goal to control weight in the long term and might not be healthy. The outcome of this conflict is strongly dependent on inhibitory control. It has already been reported that individuals with weaker inhibitory control consume more high-calorie food, are more often unsuccessful dieters, overweight or obese compared to people with more effective inhibitory control. In the present study, we aimed at investigating inhibitory control in the context of human eating behaviour. A sample of 20 healthy normal-weight adults performed a 50% probability visual affective Go/NoGo task involving food (high- and low-calorie) and non-food images as stimuli. Single-pulse transcranial magnetic stimulation (TMS) was administered over the right primary motor cortex (M1) either 300 ms after image presentation to measure corticospinal excitability during the different stimulus categories or 300 ms after the appearance of a fixation point, as a control stimulation condition. The experimental session consisted of a food target and a non-food target block. Behavioural outcomes showed a natural implicit inclination towards high-calorie food in that participants were faster and more accurate compared to the other categories. This advantage was selectively deleted by TMS, which slowed down reaction times. MEPs did not differ according to the stimulus category, but, as expected, were bigger for Go compared to NoGo trials. Participants judged high-calorie food also as more appetising than low-calorie food images. Overall, our results point to a differential modulation when targeting inhibitory control, in favour of the more palatable food category (high-calorie). Present data suggest that the activity of the motor system is modulated by food nutritional value, being more engaged by appetising food. Future work should explore to what extent these processes are affected in patients with eating disorders and should aim to better characterise the related dynamics of cortical connectivity within the motor network.

Corticospinal interface to restore voluntary control of joint torque in a paralyzed forearm following spinal cord injury in non-human primates.

The corticospinal tract plays a major role in the control of voluntary limb movements, and its damage impedes voluntary limb control. We investigated the feasibility of closed-loop brain-controlled subdural spinal stimulation through a corticospinal interface for the modulation of wrist torque in the paralyzed forearm of monkeys with spinal cord injury at C4/C5. Subdural spinal stimulation of the preserved cervical enlargement activated multiple muscles on the paralyzed forearm and wrist torque in the range from flexion to ulnar-flexion. The magnitude of the evoked torque could be modulated by changing current intensity. We then employed the corticospinal interface designed to detect the firing rate of an arbitrarily selected "linked neuron" in the forearm territory of the primary motor cortex (M1) and convert it in real time to activity-contingent electrical stimulation of a spinal site caudal to the lesion. Linked neurons showed task-related activity that modulated the magnitude of the evoked torque and the activation of multiple muscles depending on the required torque. Unlinked neurons, which were independent of spinal stimulation and located in the vicinity of the linked neurons, exhibited task-related or -unrelated activity. Thus, monkeys were able to modulate the wrist torque of the paralyzed forearm by modulating the firing rate of M1 neurons including unlinked and linked neurons via the corticospinal interface. These results suggest that the corticospinal interface can replace the function of the corticospinal tract after spinal cord injury.

Erratum: Accounting for stimulations that do not elicit motor-evoked potentials when mapping cortical representations of multiple muscles.

[This corrects the article DOI: 10.3389/fnhum.2022.920538.].

Accounting for Stimulations That Do Not Elicit Motor-Evoked Potentials When Mapping Cortical Representations of Multiple Muscles.

The representation of muscles in the cortex can be mapped using navigated transcranial magnetic stimulation. The commonly employed measure to quantify the mapping are the center of gravity or the centroid of the region of excitability as well as its size. Determining these measures typically relies only on stimulation points that yield motor-evoked potentials (MEPs); stimulations that do not elicit an MEP, i.e., non-MEP points, are ignored entirely. In this study, we show how incorporating non-MEP points may affect the estimates of the size and centroid of the excitable area in eight hand and forearm muscles after mono-phasic single-pulse TMS. We performed test-retest assessments in twenty participants and estimated the reliability of centroids and sizes of the corresponding areas using inter-class correlation coefficients. For most muscles, the reliability turned out good. As expected, removing the non-MEP points significantly decreased area sizes and area weights, suggesting that conventional approaches that do not account for non-MEP points are likely to overestimate the regions of excitability.

Bimanual motor skill learning after stroke: Combining robotics and anodal tDCS over the undamaged hemisphere: An exploratory study.

Background: Since a stroke can impair bimanual activities, enhancing bimanual cooperation through motor skill learning may improve neurorehabilitation. Therefore, robotics and neuromodulation with transcranial direct current stimulation (tDCS) are promising approaches. To date, tDCS has failed to enhance bimanual motor control after stroke possibly because it was not integrating the hypothesis that the undamaged hemisphere becomes the major poststroke hub for bimanual control. Objective: We tested the following hypotheses: (I) In patients with chronic hemiparetic stroke training on a robotic device, anodal tDCS applied over the primary motor cortex of the undamaged hemisphere enhances bimanual motor skill learning compared to sham tDCS. (II) The severity of impairment correlates with the effect of tDCS on bimanual motor skill learning. (III) Bimanual motor skill learning is less efficient in patients than in healthy individuals (HI). Methods: A total of 17 patients with chronic hemiparetic stroke and 7 healthy individuals learned a complex bimanual cooperation skill on the REAplan® neurorehabilitation robot. The bimanual speed/accuracy trade-off (biSAT), bimanual coordination (biCo), and bimanual force (biFOP) scores were computed for each performance. In patients, real/sham tDCS was applied in a crossover, randomized, double-blind approach. Results: Compared to sham, real tDCS did not enhance bimanual motor skill learning, retention, or generalization in patients, and no correlation with impairment was noted. The healthy individuals performed better than patients on bimanual motor skill learning, but generalization was similar in both groups. Conclusion: A short motor skill learning session with a robotic device resulted in the retention and generalization of a complex skill involving bimanual cooperation. The tDCS strategy that would best enhance bimanual motor skill learning after stroke remains unknown. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02308852, identifier: NCT02308852.

Alteration of network connectivity in stroke patients with apraxia of speech after tDCS: A randomized controlled study.

Objective: This study aimed to examine the changes in the functional connectivity of the cortical speech articulation network after anodal transcranial direct current stimulation (A-tDCS) over the left lip region of the primary motor cortex (M1) in subacute post-stroke patients with apraxia of speech (AoS), and the effect of A-tDCS on AoS. Methods: A total of 24 patients with post-stroke AoS were randomized into two groups and received A-tDCS over the left lip region of M1 (tDCS group)/ sham tDCS (control group) as well as speech and language therapy two times per day for 5 days. Before and after the treatment, the AoS assessments and electroencephalogram (EEG) were evaluated. The cortical interconnections were measured using the EEG non-linear index of cross approximate entropy (C-ApEn). Results: The analysis of EEG showed that, after the treatment, the activated connectivity was all in the left hemisphere, and not only regions in the speech articulation network but also in the dorsal lateral prefrontal cortex (DLPFC) in the domain-general network were activated in the tDCS group. In contrast, the connectivity was confined to the right hemisphere and between bilateral DLPFC and bilateral inferior frontal gyrus (IFG) in the control group. In AoS assessments, the tDCS group improved significantly more than the control group in four of the five subtests. The results of multivariate linear regression analyses showed that only the group was significantly associated with the improvement of word repetition (P = 0.002). Conclusion: A-tDCS over the left lip region of M1 coupled with speech therapy could upregulate the connectivity of both speech-specific and domain-general networks in the left hemisphere. The improved articulation performance in patients with post-stroke AoS might be related to the enhanced connectivity of networks in the left hemisphere induced by tDCS. Clinical trial registration: ChiCTR-TRC-14005072.

Effects of High-Definition Transcranial Direct Current Stimulation Over the Primary Motor Cortex on Cold Pain Sensitivity Among Healthy Adults.

Some clinical studies have shown promising effects of transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) on pain relief. Nevertheless, a few studies reported no significant analgesic effects of tDCS, likely due to the complexity of clinical pain conditions. Human experimental pain models that utilize indices of pain in response to well-controlled noxious stimuli can avoid many confounds that are present in the clinical data. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) stimulation over M1 on sensitivity to experimental pain and assess whether these effects could be influenced by the pain-related cognitions and emotions. A randomized, double-blinded, crossover, and sham-controlled design was adopted. A total of 28 healthy participants received anodal, cathodal, or sham HD-tDCS over M1 (1 mA for 20 min) in different sessions, in which montage has the advantage of producing more focal stimulation. Using a cold pressor test, several indices reflecting the sensitivity to cold pain were measured immediately after HD-tDCS stimulation, such as cold pain threshold and tolerance and cold pain intensity and unpleasantness ratings. Results showed that only anodal HD-tDCS significantly increased cold pain threshold when compared with sham stimulation. Neither anodal nor cathodal HD-tDCS showed significant analgesic effects on cold pain tolerance, pain intensity, and unpleasantness ratings. Correlation analysis revealed that individuals that a had lower level of attentional bias to negative information benefited more from attenuating pain intensity rating induced by anodal HD-tDCS. Therefore, single-session anodal HD-tDCS modulates the sensory-discriminative aspect of pain perception as indexed by the increased pain threshold. In addition, the modulating effects of HD-tDCS on attenuating pain intensity to suprathreshold pain could be influenced by the participant's negative attentional bias, which deserves to be taken into consideration in the clinical applications.