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ObjectiveTo compare the interhemispheric asymmetry of the motor cortex excitability of chronic stroke patients with healthy and to observe if the magnitude of this asymmetry is associated to sensory-motor impairment and stroke chronicity.MethodsThis cross-sectional study was performed with chronic stroke and aged and sex-matched healthy individuals. The interhemispheric asymmetry index was calculated by the difference of rest motor threshold (rMT) of the brain hemispheres. The rMT was assessed by transcranial magnetic stimulation over the cortical representation of the first dorsal interosseous muscle. To investigate the relationship of the asymmetry with sensory-motor impairment and injury chronicity, the stroke patients were grouped according to the level of sensory-motor impairment (mild/moderate, moderate/severe, and severe) and different chronicity stages (> 3–12, 13–24, 25–60, and > 60 months since stroke).ResultsFifty-six chronic stroke and twenty-six healthy were included. We found higher interhemispheric asymmetry in stroke patients (mean, 27.1 ± 20.9) compared to healthy (mean, 4.9 ± 4.7). The asymmetry was higher in patients with moderate/severe (mean, 35.4 ± 20.4) and severe (mean, 32.9 ± 22.7) impairment. No difference was found between patients with mild/moderate impairment (mean, 15.5 ± 12.5) and healthy. There were no differences of the interhemispheric asymmetry between patients with different times since stroke (> 3–12, mean, 32 ± 18.1; > 13–24, mean, 20.7 ± 16.2; > 25–60, mean, 29.6 ± 18.1; > 60 months, mean, 25.9 ± 17.5).ConclusionStroke patients showed higher interhemispheric asymmetry of the motor cortex excitability when compared to healthy, and the magnitude of this asymmetry seems to be correlated with the severity of sensory-motor impairment, but not with stroke chronicity.SignificanceHigher interhemispheric asymmetry was found in stroke patients with greatest sensory-motor impairment.

Dopamine (DA) is a neurotransmitter with an important influence on learning and memory, which is thought to be due to its modulatory effect on plasticity at central synapses, which in turn depends on activation of D1 and D2 receptors. Methods of brain stimulation (transcranial direct current stimulation, tDCS; paired associative stimulation, PAS) lead to after-effects on cortical excitability that are thought to resemble long-term potentization (LTP)/long-term depression (LTD) in reduced preparations. In a previous study we found that block of D2 receptors abolished plasticity induced by tDCS but had no effect on the facilitatory plasticity induced by PAS. We postulated that the different effect of D2 receptor block on tDCS- and PAS-induced plasticity may be due to the different focality and associativity of the stimulation techniques. However, alternative explanations for this difference could not be ruled out. tDCS also differs from PAS in other aspects, as tDCS induces plasticity by subthreshold neuronal activation, modulating spontaneous activity, whereas PAS induces plasticity via phasic suprathreshold stimulation. The present study in 12 volunteers examined effects of D2 receptor blockade (sulpiride (SULP) 400 mg), on the LTP/LTD-like effects of theta burst transcranial magnetic stimulation (TBS), which has less restricted effects on cortical synapses than that of PAS, and does not induce associative plasticity, similar to tDCS, but on the other hand induces cortical excitability shifts by suprathreshold (rhythmic) activation of cortical neurons similarly to PAS. Administration of SULP blocked both the excitatory and inhibitory effects of intermittent (iTBS) and continuous TBS (cTBS), respectively. As the reduced response to TBS following SULP resembles its effect on tDCS, the results support an effect of DA on plasticity, which might be related to the focality and associativity of the plasticity induced.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique used to modulate neural tissue. Neuromodulation apparently improves cognitive functions in several neurologic diseases treatment and sports performance. In this study, we present a comprehensive, integrative review of tDCS for motor rehabilitation and motor learning in healthy individuals, athletes and multiple neurologic and neuropsychiatric conditions. We also report on neuromodulation mechanisms, main applications, current knowledge including areas such as language, embodied cognition, functional and social aspects, and future directions. We present the use and perspectives of new developments in tDCS technology, namely high-definition tDCS (HD-tDCS) which promises to overcome one of the main tDCS limitation (i.e., low focality) and its application for neurological disease, pain relief, and motor learning/rehabilitation. Finally, we provided information regarding the Transcutaneous Spinal Direct Current Stimulation (tsDCS) in clinical applications, Cerebellar tDCS (ctDCS) and its influence on motor learning, and TMS combined with electroencephalography (EEG) as a tool to evaluate tDCS effects on brain function.

Objective: To investigate whether a higher number of transcranial direct current stimulation (tDCS) sessions results in a greater improvement in upper limb function in chronic post-stroke patients. Materials and methods: A randomized, sham-controlled, double-blind clinical trial was conducted in 57 chronic post-stroke patients (≥ 3 months after their injuries). The patients were allocated to receive sessions of tDCS combined with physiotherapy and divided into three groups (anodal, cathodal, and sham). The Fugl-Meyer Assessment of Upper Extremity (FMA-UE) was used to assess the sensorimotor impairment of the patients’ upper limbs before (baseline) and after five and ten sessions. The percentage of patients who achieved a clinically significant improvement (> five points on the FMA-UE) was also analyzed. Results: The FMA-UE score increased after five and ten sessions in both the anodal and cathodal tDCS groups, respectively, compared to the baseline. However, in the sham group, the FMA-UE score increased only after ten sessions. When compared to the sham group, the mean difference from the baseline after five sessions was higher in the anodal tDCS group. The percentage of individuals who achieved greater clinical improvement was higher in the stimulation groups than in the sham group and after ten sessions when compared to five sessions. Conclusions: Our results suggest that five tDCS sessions are sufficient to augment the effect of standard physiotherapy on upper limb function recovery in chronic post-stroke patients, and ten sessions resulted in greater gains.

Chronic exposure to nicotine is related to low activity in the prefrontal cortex and insular hyperactivity in smokers. Therefore, addiction has been the target of experimental studies in aerobic exercise (AE) and transcranial direct current stimulation (tDCS). Thus, the objective of this study was to verify the effect of AE and anodal tDCS at F4 and cathodal at T3 on craving, motivation to change smoking behaviour (MCSB) and brain reactivity (BR) in smokers. The sample consisted of 41 chronic smokers distributed into four groups: tDCS (G1), AE (G2), tDCS combined with AE (G3) and sham tDCS combined with AE (G4). All volunteers underwent 5 consecutive sessions of the intended intervention. Before starting the intervention protocol and after the last intervention session, the volunteers answered questionnaires and underwent an electroencephalogram exam, to evaluate the variables investigated. The results demonstrated that AE, when associated with active tDCS, was effective in promoting a reduction in craving ( p  < 0,05), cigarette consumption ( p  < 0,05), and BR ( p  < 0,05) during exposure to smoking cues, in addition to increasing MCSB ( p  < 0,05). Therefore, only when associated with AE, tDCS was able to modulate positive effects on smoking.

Background Electroencephalography (EEG) is a promising tool for identifying the physiological biomarkers of fibromyalgia (FM). Evidence suggests differences in power band and density between individuals with FM and healthy controls. EEG changes appear to be associated with pain intensity; however, their relationship with the quality of pain has not been examined. We aimed to investigate whether abnormal EEG in the frontal and central points of the 10–20 EEG system in individuals with FM is associated with pain’s sensory-discriminative and affective-motivational dimensions. The association between EEG and the two dimensions of emotional disorders (depression and anxiety) was also investigated. Methods In this cross-sectional pilot study, pain experience (pain rating index [PRI]) and two dimensions of emotional disorders (depression and anxiety) were assessed using the McGill Pain Questionnaire (PRI-sensory and PRI-affective) and Hospital Anxiety and Depression Scale (HADS), respectively. In quantitative EEG analysis, the relative spectral power of each frequency band (delta, theta, alpha, and beta) was identified in the frontal and central points during rest. Results A negative correlation was found between the relative spectral power for the delta bands in the frontal ( r = -0.656; p  = 0.028) and central points ( r = -0.624; p  = 0.040) and the PRI-affective scores. A positive correlation was found between the alpha bands in the frontal ( r  = 0.642; p  = 0.033) and central points ( r  = 0.642; p  = 0.033) and the PRI-affective scores. A negative correlation between the delta bands in the central points and the anxiety subscale of the HADS ( r = -0.648; p  = 0.031) was detected. Conclusion The affective-motivational dimension of pain and mood disorders may be related to abnormal patterns of electrical activity in patients with FM. Trial registration Retrospectively registered on ClinicalTrials.gov (NCT05962658).

Background. We investigated whether transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex (S1) and sensory stimulation (SS) could promote upper limb recovery in participants with subacute stroke. Methods. Participants were randomized into four groups: rTMS/Sham SS, Sham rTMS/SS, rTMS/SS, and control group (Sham rTMS/Sham SS). Participants underwent ten sessions of sham or active rTMS over S1 (10 Hz, 1,500 pulses, 120% of resting motor threshold, 20 min), followed by sham or active SS. The SS involved active sensory training (exploring features of objects and graphesthesia, proprioception exercises), mirror therapy, and Transcutaneous electrical nerve stimulation (TENS) in the region of the median nerve in the wrist (he stimulation intensity was determined as the minimum intensity at which the participants reported paresthesia), five electrical pulses of 1 ms duration each at 10 Hz were delivered every second over 45 min. Sham stimulations occurred as follows Sham rTMS: coil was held while disconnected from the stimulator, and rTMS noise was presented with computer loudspeakers with recorded sound from a real stimulation. The Sham SS received therapy in the unaffected upper limb, did not use the mirror and also received TENS stimulation for only 60 seconds. The primary outcome was the Body Structure/Function: Fugl-Meyer Assessment (FMA) and Nottingham Sensory Assessment (NSA); the secondary outcome was the Activity/Participation domains, assessed with Box and Block Test, Motor Activity Log scale, Jebsen-Taylor Test, and Functional Independence Measure. Results. Forty participants with stroke ischemic (n=38) and hemorrhagic (n=2), men (n=19) and women (n=21), in the subacute stage (10.6±6 weeks) had a mean age of 62.2±9.6 years, were equally divided into four groups (10 participants in each group). Significant somatosensory improvements were found in participants receiving active rTMS and active SS, compared with those in the control group (sham rTMS with sham SS). Motor function improved only in participants who received active rTMS, with greater effects when active rTMS was combined with active SS. Conclusion. The combined use of SS with rTMS over S1 represents a more effective therapy for increasing sensory and motor recovery, as well as functional independence, in participants with subacute stroke

Repetitive transcranial magnetic stimulation (rTMS) over motor cortex and trans-spinal direct current stimulation (tsDCS) modulate corticospinal circuits in healthy and injured subjects. However, their associated effects with physical exercise is still not defined. This study aimed to investigate the effect of three different settings of rTMS and tsDCS combined with treadmill exercise on spinal cord and cortical excitability of healthy subjects. We performed a triple blind, randomized, sham-controlled crossover study with 12 healthy volunteers who underwent single sessions of rTMS (1Hz, 20Hz and Sham) and tsDCS (anodal, cathodal and Sham) associated with 20 minutes of treadmill walking. Cortical excitability was assessed by motor evoked potential (MEP) and spinal cord excitability by the Hoffmann reflex (Hr), nociceptive flexion reflex (NFR) and homosynaptic depression (HD). All measures were assessed before, immediately, 30 and 60 minutes after the experimental procedures. Our results demonstrated that anodal tsDCS/treadmill exercise reduced MEP's amplitude and NFR's area compared to sham condition, conversely, cathodal tsDCS/treadmill exercise increased NFR's area. High-frequency rTMS increased MEP's amplitude and NFR's area compared to sham condition. Anodal tsDCS/treadmill exercise and 20Hz rTMS/treadmill exercise reduced Hr amplitude up to 30 minutes after stimulation offset and no changes were observed in HD measures. We demonstrated that tsDCS and rTMS combined with treadmill exercise modulated cortical and spinal cord excitability through different mechanisms. tsDCS modulated spinal reflexes in a polarity-dependent way acting at local spinal circuits while rTMS probably promoted changes in the presynaptic inhibition of spinal motoneurons. In addition, the association of two neuromodulatory techniques induced long-lasting changes.

The ability to produce coordinated movement is dependent on dynamic interactions through transcallosal fibers between the two cerebral hemispheres of the brain. Although typically unilateral, stroke induces changes in functional and effective connectivity across hemispheres, which are related to sensorimotor impairment and stroke recovery. Previous studies have focused almost exclusively on interhemispheric interactions in the primary motor cortex (M1). To identify the presence of interhemispheric asymmetry (ASY) of somatosensory cortex (S1) excitability and to investigate whether S1 repetitive transcranial magnetic stimulation (rTMS) combined with sensory stimulation (SS) changes excitability in S1 and M1, as well as S1 ASY, in individuals with subacute stroke. A randomized clinical trial. Participants with a single episode of stroke, in the subacute phase, between 35 and 75 years old, were allocated, randomly and equally balanced, to four groups: rTMS/sham SS, sham rTMS/SS, rTMS/SS, and sham rTMS/Sham SS. Participants underwent 10 sessions of S1 rTMS of the lesioned hemisphere (10 Hz, 1,500 pulses) followed by SS. SS was applied to the paretic upper limb (UL) (active SS) or non-paretic UL (sham SS). TMS-induced motor evoked potentials (MEPs) of the paretic UL and somatosensory evoked potential (SSEP) of both ULs assessed M1 and S1 cortical excitability, respectively. The S1 ASY index was measured before and after intervention. Evaluator, participants and the statistician were blinded. Thirty-six participants divided equally into groups (nine participants per group). Seven patients were excluded from MEP analysis because of failure to produce consistent MEP. One participant was excluded in the SSEP analysis because no SSEP was detected. All somatosensory stimulation groups had decreased S1 ASY except for the sham rTMS/Sham SS group. When compared with baseline, M1 excitability increased only in the rTMS/SS group. S1 rTMS and SS alone or in combination changed S1 excitability and decreased ASY, but it was only their combination that increased M1 excitability. clinicaltrials.gov, identifier (NCT03329807).

Background Approximately 80% of individuals with chronic stroke present with long lasting upper extremity (UE) impairments. We designed the perSonalized UPper Extremity Rehabilitation (SUPER) intervention, which combines robotics, virtual reality activities, and neuromuscular electrical stimulation (NMES). The objectives of our study were to determine the feasibility and the preliminary efficacy of the SUPER intervention in individuals with moderate/severe stroke. Methods Stroke participants (n = 28) received a 4-week intervention (3 × per week), tailored to their functional level. The functional integrity of the corticospinal tract was assessed using the Predict Recovery Potential algorithm, involving measurements of motor evoked potentials and manual muscle testing. Those with low potential for hand recovery (shoulder group; n = 18) received a robotic-rehabilitation intervention focusing on elbow and shoulder movements only. Those with a good potential for hand recovery (hand group; n = 10) received EMG-triggered NMES, in addition to robot therapy. The primary outcomes were the Fugl-Meyer UE assessment and the ABILHAND assessment. Secondary outcomes included the Motor Activity Log and the Stroke Impact Scale. Results Eighteen participants (64%), in either the hand or the shoulder group, showed changes in the Fugl-Meyer UE or in the ABILHAND assessment superior to the minimal clinically important difference. Conclusions This indicates that our personalized approach is feasible and may be beneficial in improving UE function in individuals with moderate to severe impairments due to stroke. Trial registration ClinicalTrials.gov NCT03903770. Registered 4 April 2019. Registered retrospectively.