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Neurodevelopmental disorders such as attention deficit and/or hyperactivity disorder (ADHD) and schizophrenia are characterized by core impairment in executive functions (EF). Despite the development of various behavioral interventions to enhance EF, the evidence is still scarce. Alternatively, non-invasive brain stimulation tools such as transcranial alternating current stimulation (tACS) has emerged as a potential strategy to alleviate cognitive deficits. Previous studies have demonstrated the safety, feasibility, and efficacy of one single tACS session in different clinical populations. However, the effects of tACS appear limited and need to be sustained to be considered an effective cognitive neurorehabilitation tool. Recent studies have used home-based, repeated tACS sessions in individuals with neurodegenerative diseases. To our knowledge, the safety and feasibility of such an intensive protocol remains to be tested in a younger population with neurodevelopmental disorders. Using a randomized double-blind sham-controlled design, we administered home-based, repeated tACS sessions to seven individuals aged 14–25 with 22q11.2 deletion syndrome (22q11.2DS), which confers an increased risk for neurodevelopmental disorders. We aimed to assess the safety, tolerability, and feasibility of tACS. Findings from this ongoing clinical trial revealed a favorable safety profile, with frequent yet transient and mainly mild adverse effects. The intervention proved to be feasible, shown by very high adherence rates and positive user experiences. Future studies should therefore investigate whether prolonged exposure to tACS can lead to long-lasting cognitive outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT05664412. [ABSTRACT FROM AUTHOR]

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1 and T2-weighted MRIbased anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased shortinterval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow. [ABSTRACT FROM AUTHOR]

Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders such as attention deficit and/or hyperactivity disorder (ADHD) and schizophrenia are characterized by core impairment in executive functions (EF). Despite the development of various behavioral interventions to enhance EF, the evidence is still scarce. Alternatively, non-invasive brain stimulation tools such as transcranial alternating current stimulation (tACS) has emerged as a potential strategy to alleviate cognitive deficits. Previous studies have demonstrated the safety, feasibility, and efficacy of one single tACS session in different clinical populations. However, the effects of tACS appear limited and need to be sustained to be considered an effective cognitive neurorehabilitation tool. Recent studies have used home-based, repeated tACS sessions in individuals with neurodegenerative diseases. To our knowledge, the safety and feasibility of such an intensive protocol remains to be tested in a younger population with neurodevelopmental disorders. Using a randomized double-blind sham-controlled design, we administered home-based, repeated tACS sessions to seven individuals aged 14–25 with 22q11.2 deletion syndrome (22q11.2DS), which confers an increased risk for neurodevelopmental disorders. We aimed to assess the safety, tolerability, and feasibility of tACS. Findings from this ongoing clinical trial revealed a favorable safety profile, with frequent yet transient and mainly mild adverse effects. The intervention proved to be feasible, shown by very high adherence rates and positive user experiences. Future studies should therefore investigate whether prolonged exposure to tACS can lead to long-lasting cognitive outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT05664412.

Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.

IntroductionTranscranial direct current stimulation (tDCS) has shown positive but inconsistent results in stroke rehabilitation. This could be attributed to inter-individual variations in brain characteristics and stroke lesions, which limit the use of a single tDCS protocol for all post-stroke patients. Optimizing the electrode location in tDCS for each individual using magnetic resonance imaging (MRI) to generate three-dimensional computer models and calculate the electric field (E-field) induced by tDCS at a specific target point in the primary motor cortex may help reduce these inconsistencies. In stroke rehabilitation, locating the optimal position that generates a high E-field in a target area can influence motor recovery. Therefore, this study was designed to determine the effect of personalized tDCS electrode positions on hand-knob activation in post-stroke patients.MethodThis is a crossover study with a sample size of 50 participants, who will be randomly assigned to one of six groups and will receive one session of either optimized-active, conventional-active, or sham tDCS, with 24 h between sessions. The tDCS parameters will be 1 mA (5 × 5 cm electrodes) for 20 min. The motor-evoked potential (MEP) will be recorded before and after each session over the target area (motor cortex hand-knob) and the MEP hotspot. The MEP amplitude at the target location will be the primary outcome.DiscussionWe hypothesize that the optimized-active tDCS session would show a greater increase in MEP amplitude over the target area in patients with subacute and chronic stroke than conventional and sham tDCS sessions.Clinical trial registration:https://cris.nih.go.kr, identifier KCT0007536.

Background: Parkinson's disease (PD) is a neurodegenerative disorder defined by progressive motor and non-motor symptoms. Currently, the pro-cognitive effects of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) are well-supported in previous literatures. However, controversy surrounding the optimal therapeutic target for motor symptom improvement remains. Objective: This network meta-analysis (NMA) was conducted to comprehensively evaluate the optimal strategy to use rTMS and tDCS to improve motor symptoms in PD. Methods: We searched PubMed, Embase, and Cochrane electronic databases for eligible randomized controlled studies (RCTs). The primary outcome was the changes of Unified Parkinson's Disease Rating Scale (UPDRS) part III score, the secondary outcomes were Time Up and Go Test (TUGT) time, and Freezing of Gait Questionnaire (FOGQ) score. The safety outcome was indicated by device-related adverse events (AEs). Result: We enrolled 28 studies that investigated various strategies, including high-frequency rTMS (HFrTMS), low-frequency rTMS (LFrTMS), anodal tDCS (AtDCS), AtDCS_ cathode tDCS (CtDCS), HFrTMS_LFrTMS, and Sham control groups. Both HFrTMS (short-term: mean difference (MD) −5.21, 95% credible interval (CrI) −9.26 to −1.23, long-term: MD −4.74, 95% CrI −6.45 to −3.05), and LFrTMS (long-term: MD −4.83, 95% CrI −6.42 to −3.26) were effective in improving UPDRS-III score compared with Sham stimulation. For TUGT time, HFrTMS (short-term: MD −2.04, 95% CrI −3.26 to −0.8, long-term: MD −2.66, 95% CrI −3.55 to −1.77), and AtDCS (short-term: MD −0.8, 95% CrI −1.26 to −0.34, long-term: MD −0.69, 95% CrI −1.31 to −0.08) produced a significant difference compared to Sham stimulation. However, no statistical difference was found in FOGQ score among the various groups. According to the surface under curve ranking area, HFrTMS ranked first in short-term UPDRS-III score (0.77), short-term (0.82), and long-term (0.84) TUGT time, and short-term FOGQ score (0.73). With respect to the safety outcomes, all strategies indicated few and self-limiting AEs. Conclusion: HFrTMS may be the optimal non-invasive brain stimulation (NIBS) intervention to improve motor function in patients with PD while NIBS has generally been well tolerated. However, further studies focusing on the clinical outcomes resulting from the different combined schedules of tDCS and rTMS are required. [ABSTRACT FROM AUTHOR]

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD. Methods: After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH. Results: Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS. Discussion: In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms. [ABSTRACT FROM AUTHOR]

Objective: Multiple studies have explored the use of visual cortex non-invasive brain stimulation (NIBS) to enhance visual function. These studies vary in sample size, outcome measures, and methodology. We conducted a systematic review and meta-analyses to assess the effects of NIBS on visual functions in human participants with normal vision. Methods: We followed the PRISMA guidelines, and a review protocol was registered with PROSPERO before study commencement (CRD42021255882). We searched Embase, Medline, PsychInfo, PubMed, OpenGrey and Web of Science using relevant keywords. The search covered the period from 1st January 2000 until 1st September 2021. Comprehensive meta-analysis (CMA) software was used for quantitative analysis. Results: Fifty studies were included in the systematic review. Only five studies utilized transcranial magnetic stimulation (TMS) and no TMS studies met our prespecified criteria for meta-analysis. Nineteen transcranial electrical stimulation studies (tES, 38%) met the criteria for meta-analysis and were the focus of our review. Meta-analysis indicated acute effects (Hedges's g = 0.232, 95% CI: 0.023- 0.442, p = 0.029) and aftereffects (0.590, 95% CI: 0.182-0.998, p = 0.005) of tES on contrast sensitivity. Visual evoked potential (VEP) amplitudes were significantly enhanced immediately after tES (0.383, 95% CI: 0.110-0.665, p = 0.006). Both tES (0.563, 95% CI: 0.230-0.896, p = 0.001) and anodal-transcranial direct current stimulation (a-tDCS) alone (0.655, 95% CI: 0.273-1.038, p = 0.001) reduced crowding in peripheral vision. The effects of tES on visual acuity, motion perception and reaction time were not statistically significant. Conclusion: There are significant effects of visual cortex tES on contrast sensitivity, VEP amplitude, an index of cortical excitability, and crowding among normally sighted individuals. Additional studies are required to enable a comparable meta-analysis of TMS effects. Future studies with robust experimental designs are needed to extend these findings to populations with vision loss. [ABSTRACT FROM AUTHOR]

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD.MethodsAfter completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH.ResultsOur results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual–spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS.DiscussionIn conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.

ObjectiveMultiple studies have explored the use of visual cortex non-invasive brain stimulation (NIBS) to enhance visual function. These studies vary in sample size, outcome measures, and methodology. We conducted a systematic review and meta-analyses to assess the effects of NIBS on visual functions in human participants with normal vision.MethodsWe followed the PRISMA guidelines, and a review protocol was registered with PROSPERO before study commencement (CRD42021255882). We searched Embase, Medline, PsychInfo, PubMed, OpenGrey and Web of Science using relevant keywords. The search covered the period from 1st January 2000 until 1st September 2021. Comprehensive meta-analysis (CMA) software was used for quantitative analysis.ResultsFifty studies were included in the systematic review. Only five studies utilized transcranial magnetic stimulation (TMS) and no TMS studies met our pre-specified criteria for meta-analysis. Nineteen transcranial electrical stimulation studies (tES, 38%) met the criteria for meta-analysis and were the focus of our review. Meta-analysis indicated acute effects (Hedges’s g = 0.232, 95% CI: 0.023–0.442, p = 0.029) and aftereffects (0.590, 95% CI: 0.182–0.998, p = 0.005) of tES on contrast sensitivity. Visual evoked potential (VEP) amplitudes were significantly enhanced immediately after tES (0.383, 95% CI: 0.110–0.665, p = 0.006). Both tES (0.563, 95% CI: 0.230–0.896, p = 0.001) and anodal-transcranial direct current stimulation (a-tDCS) alone (0.655, 95% CI: 0.273–1.038, p = 0.001) reduced crowding in peripheral vision. The effects of tES on visual acuity, motion perception and reaction time were not statistically significant.ConclusionThere are significant effects of visual cortex tES on contrast sensitivity, VEP amplitude, an index of cortical excitability, and crowding among normally sighted individuals. Additional studies are required to enable a comparable meta-analysis of TMS effects. Future studies with robust experimental designs are needed to extend these findings to populations with vision loss.Clinical trial registrationClinicalTrials.gov/, identifier CRD42021255882.

Objectives: Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation. Materials and methods: Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model. Results: Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 – 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI –0.20 – 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI –0.49 – 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R. Conclusion: One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia. [ABSTRACT FROM AUTHOR]

ObjectivesApraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation.Materials and methodsNineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model.ResultsPairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 – 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI –0.20 – 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI –0.49 – 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R.ConclusionOne single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.

The deleterious effects of insufficient sleep have been well-established in the literature and can lead to a wide range of adverse health outcomes. Some of the most replicated findings demonstrate significant declines in cognitive functions such as vigilance and executive attention, psychomotor and cognitive speed, and working memory. Consequently, these decrements often lead individuals who are in a fatigued state to engage in substandard performance on everyday tasks. In the interest of curtailing these effects, prior work has attempted to identify mechanisms that predict fatigue onset and develop techniques to mitigate its negative consequences. Nonetheless, these results are often confounded by variables such as an individual’s resistance to fatigue, sleep history, and unclear distinctions about whether certain performance decrements are present due to fatigue or due to other confounding factors. Similar areas of research have provided approaches to produce models for the prediction of cognitive performance decrements due to fatigue through the use of multi-modal recording and analysis of fatigue-related responses. Namely, gathering and combining response information from multiple sources (i.e., physiological and behavioral) at multiple timescales may provide a more comprehensive representation of what constitutes fatigue onset in the individual. Therefore, the purpose of this review is to discuss the relevant literature on the topic of fatigue-related performance effects with a special emphasis on a variety of physiological and behavioral response variables that have shown to be sensitive to changes in fatigue. Furthermore, an increasing reliance on sleep loss, meant to assist in meeting the demands of modern society, has led to an upsurge in the relevance of identifying dependable countermeasures for fatigued states. As such, we will also review methods for the mitigation of performance effects due to fatigue and discuss their usefulness in regulating these effects. In sum, this review aims to inspire future work that will create opportunities to detect fatigue and mitigate its effects prior to the onset of cognitive impairments. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a non-invasive modality of focal brain stimulation in which a fluctuating magnetic field induces electrical currents within the cortex. It remains unclear to what extent TMS alters EEG biomarkers and how EEG biomarkers may guide treatment of focal epilepsy. We present a case of a 48-year-old man with focal epilepsy, refractory to multiple medication trials, who experienced a dramatic reduction in seizures after targeting the area of seizure onset within the left parietal-occipital region with low-frequency repetitive TMS (rTMS). Prior to treatment, he experienced focal seizures that impacted cognition including apraxia at least 50–60 times daily. MRI of the brain showed a large focal cortical dysplasia with contrast enhancement involving the left occipital-parietal junction. Stimulation for 5 consecutive days was well-tolerated and associated with a day-by-day reduction in seizure frequency. In addition, he was monitored with continuous video EEG, which showed continued and progressive changes in spectral power (decreased broadband power and increased infraslow delta activity) and a gradual reduction in seizure frequency and duration. One month after initial treatment, 2-day ambulatory EEG demonstrated seizure-freedom and MRI showed resolution of focal contrast enhancement. He continues to receive 2–3 days of rTMS every 2–4 months. He was seizure-free for 6 months, and at last follow-up of 17 months was experiencing auras approximately every 2 weeks without progression to disabling seizures. This case demonstrates that rTMS can be a well-tolerated and effective means of controlling medication-refractory seizures, and that EEG biomarkers change gradually in a fashion in association with seizure frequency. TMS influences cortical excitability, is a promising non-invasive means of treating focal epilepsy, and has measurable electrophysiologic effects. [ABSTRACT FROM AUTHOR]

The deleterious effects of insufficient sleep have been well-established in the literature and can lead to a wide range of adverse health outcomes. Some of the most replicated findings demonstrate significant declines in cognitive functions such as vigilance and executive attention, psychomotor and cognitive speed, and working memory. Consequently, these decrements often lead individuals who are in a fatigued state to engage in substandard performance on everyday tasks. In the interest of curtailing these effects, prior work has attempted to identify mechanisms that predict fatigue onset and develop techniques to mitigate its negative consequences. Nonetheless, these results are often confounded by variables such as an individual’s resistance to fatigue, sleep history, and unclear distinctions about whether certain performance decrements are present due to fatigue or due to other confounding factors. Similar areas of research have provided approaches to produce models for the prediction of cognitive performance decrements due to fatigue through the use of multi-modal recording and analysis of fatigue-related responses. Namely, gathering and combining response information from multiple sources (i.e., physiological and behavioral) at multiple timescales may provide a more comprehensive representation of what constitutes fatigue onset in the individual. Therefore, the purpose of this review is to discuss the relevant literature on the topic of fatigue-related performance effects with a special emphasis on a variety of physiological and behavioral response variables that have shown to be sensitive to changes in fatigue. Furthermore, an increasing reliance on sleep loss, meant to assist in meeting the demands of modern society, has led to an upsurge in the relevance of identifying dependable countermeasures for fatigued states. As such, we will also review methods for the mitigation of performance effects due to fatigue and discuss their usefulness in regulating these effects. In sum, this review aims to inspire future work that will create opportunities to detect fatigue and mitigate its effects prior to the onset of cognitive impairments.

Transcranial magnetic stimulation (TMS) is a non-invasive modality of focal brain stimulation in which a fluctuating magnetic field induces electrical currents within the cortex. It remains unclear to what extent TMS alters EEG biomarkers and how EEG biomarkers may guide treatment of focal epilepsy. We present a case of a 48-year-old man with focal epilepsy, refractory to multiple medication trials, who experienced a dramatic reduction in seizures after targeting the area of seizure onset within the left parietal-occipital region with low-frequency repetitive TMS (rTMS). Prior to treatment, he experienced focal seizures that impacted cognition including apraxia at least 50–60 times daily. MRI of the brain showed a large focal cortical dysplasia with contrast enhancement involving the left occipital-parietal junction. Stimulation for 5 consecutive days was well-tolerated and associated with a day-by-day reduction in seizure frequency. In addition, he was monitored with continuous video EEG, which showed continued and progressive changes in spectral power (decreased broadband power and increased infraslow delta activity) and a gradual reduction in seizure frequency and duration. One month after initial treatment, 2-day ambulatory EEG demonstrated seizure-freedom and MRI showed resolution of focal contrast enhancement. He continues to receive 2–3 days of rTMS every 2–4 months. He was seizure-free for 6 months, and at last follow-up of 17 months was experiencing auras approximately every 2 weeks without progression to disabling seizures. This case demonstrates that rTMS can be a well-tolerated and effective means of controlling medication-refractory seizures, and that EEG biomarkers change gradually in a fashion in association with seizure frequency. TMS influences cortical excitability, is a promising non-invasive means of treating focal epilepsy, and has measurable electrophysiologic effects.

Objective: This study aims to systematically evaluate the effect of non-invasive brain stimulation (NIBS) on neuropathic pain (NP) after spinal cord injury and compare the effects of two different NIBS. Methods: Randomized controlled trials (RCTs) about the effect of NIBS on NP after spinal cord injury (SCI) were retrieved from the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM from inception to September 2021. The quality of the trials was assessed, and the data were extracted according to the Cochrane handbook of systematic review. Statistical analysis was conducted with Stata (version 16) and R software (version 4.0.2). Results: A total of 17 studies involving 507 patients were included. The meta-analysis showed that NIBS could reduce the pain score (SMD = −0.84, 95% CI −1.27 −0.40, P = 0.00) and the pain score during follow-up (SMD = −0.32, 95%CI −0.57 −0.07, P = 0.02), and the depression score of the NIBS group was not statistically significant than that of the control group (SMD = −0.43, 95%CI −0.89–0.02, P = 0.06). The network meta-analysis showed that the best probabilistic ranking of the effects of two different NIBS on the pain score was repetitive transcranial magnetic stimulation (rTMS) (P = 0.62) > transcranial direct current stimulation (tDCS) (P = 0.38). Conclusion: NIBS can relieve NP after SCI. The effect of rTMS on NP is superior to that of tDCS. We suggest that the rTMS parameters are 80–120% resting motion threshold and 5–20 Hz, while the tDCS parameters are 2 mA and 20 min. However, it is necessary to carry out more large-scale, multicenter, double-blind, high-quality RCT to explore the efficacy and mechanism of NIBS for NP after SCI. [ABSTRACT FROM AUTHOR]

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated. Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1). Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation. Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential. Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aims to systematically evaluate the effect of non-invasive brain stimulation (NIBS) on neuropathic pain (NP) after spinal cord injury and compare the effects of two different NIBS.MethodsRandomized controlled trials (RCTs) about the effect of NIBS on NP after spinal cord injury (SCI) were retrieved from the databases of PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM from inception to September 2021. The quality of the trials was assessed, and the data were extracted according to the Cochrane handbook of systematic review. Statistical analysis was conducted with Stata (version 16) and R software (version 4.0.2).ResultsA total of 17 studies involving 507 patients were included. The meta-analysis showed that NIBS could reduce the pain score (SMD = −0.84, 95% CI −1.27 −0.40, P = 0.00) and the pain score during follow-up (SMD = −0.32, 95%CI −0.57 −0.07, P = 0.02), and the depression score of the NIBS group was not statistically significant than that of the control group (SMD = −0.43, 95%CI −0.89–0.02, P = 0.06). The network meta-analysis showed that the best probabilistic ranking of the effects of two different NIBS on the pain score was repetitive transcranial magnetic stimulation (rTMS) (P = 0.62) > transcranial direct current stimulation (tDCS) (P = 0.38).ConclusionNIBS can relieve NP after SCI. The effect of rTMS on NP is superior to that of tDCS. We suggest that the rTMS parameters are 80–120% resting motion threshold and 5–20 Hz, while the tDCS parameters are 2 mA and 20 min. However, it is necessary to carry out more large-scale, multicenter, double-blind, high-quality RCT to explore the efficacy and mechanism of NIBS for NP after SCI.

Background: Temporal interference (TI) stimulation is a new technique of non-invasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidated.Objective: To assess the effectiveness of the envelope-modulated waveform of TI stimulation on the human primary motor cortex (M1).Methods: Participants attended three sessions of 30-min TI stimulation during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.Results: In the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.Conclusion: These results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and paving the way for further explorations.

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1and T2-weighted MRI-based anatomical models, on motor performance and cortical excitability in healthy individuals., Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total)., Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased short-interval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training., Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sato, Katagiri, Suganuma, Laakso, Tanabe, Osu, Tanaka and Yamaguchi.)

Objectives: To investigate the effect of multi-session transcranial direct current stimulation (tDCS) over the prefrontal area, left dorsolateral prefrontal cortex (DLPFC), and bilateral fronto-temporo-parietal cortices (FTPCs) in patients with prolonged disorders of consciousness (DOC) and to examine the altered cortical interconnections using non-linear electroencephalography (EEG). Methods: In this open-label controlled study, conventional treatments were implemented in both the control and tDCS groups, together with 80 tDCS sessions only in the tDCS group. The order of tDCS targets was as follows: prefrontal area, left FTPC, right FTPC, and left DLPFC. The Coma Recovery Scale-Revised (CRS-R) and non-linear EEG index were evaluated before and after the treatment. Additionally, the modified Glasgow Outcome Scale (mGOS) was used as a follow-up evaluation at 12 months after the disease onset. Results: The CRS-R improved significantly in both groups after the treatment. However, the CRS-R and mGOS were more significantly improved in the tDCS group than in the control group. Among the cross approximate entropy (C-ApEn) indices, the local CA-PA and CA-FA under the affected painful stimulus condition and all local and remote indices of the unaffected side under the unaffected painful stimulus condition were significantly higher in the tDCS group than in the control group. Multivariate logistic regression analysis revealed that group and type were the main relevant factors based on mGOS improvement. Multivariate linear regression analysis revealed that group, CA-FA, and CU-MTU were the main relevant factors based on CRS-R improvement under the affected painful stimulus conditions, whereas only CU-MTU and CU-FPU were relevant under the unaffected painful stimulus condition. Conclusion: Multi-target and multi-session tDCS could improve the cortical connections between the primary sensorimotor and frontal cortices of the affected hemisphere and the prefrontal-parietal and temporo-parietal associative cortical networks of the unaffected hemisphere. Thus, this tDCS protocol may be used as an add-on treatment for prolonged DOC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effect of multi-session transcranial direct current stimulation (tDCS) over the prefrontal area, left dorsolateral prefrontal cortex (DLPFC), and bilateral fronto-temporo-parietal cortices (FTPCs) in patients with prolonged disorders of consciousness (DOC) and to examine the altered cortical interconnections using non-linear electroencephalography (EEG).Methods: In this open-label controlled study, conventional treatments were implemented in both the control and tDCS groups, together with 80 tDCS sessions only in the tDCS group. The order of tDCS targets was as follows: prefrontal area, left FTPC, right FTPC, and left DLPFC. The Coma Recovery Scale-Revised (CRS-R) and non-linear EEG index were evaluated before and after the treatment. Additionally, the modified Glasgow Outcome Scale (mGOS) was used as a follow-up evaluation at 12 months after the disease onset.Results: The CRS-R improved significantly in both groups after the treatment. However, the CRS-R and mGOS were more significantly improved in the tDCS group than in the control group. Among the cross approximate entropy (C-ApEn) indices, the local CA-PA and CA-FA under the affected painful stimulus condition and all local and remote indices of the unaffected side under the unaffected painful stimulus condition were significantly higher in the tDCS group than in the control group. Multivariate logistic regression analysis revealed that group and type were the main relevant factors based on mGOS improvement. Multivariate linear regression analysis revealed that group, CA-FA, and CU-MTU were the main relevant factors based on CRS-R improvement under the affected painful stimulus conditions, whereas only CU-MTU and CU-FPU were relevant under the unaffected painful stimulus condition.Conclusion: Multi-target and multi-session tDCS could improve the cortical connections between the primary sensorimotor and frontal cortices of the affected hemisphere and the prefrontal-parietal and temporo-parietal associative cortical networks of the unaffected hemisphere. Thus, this tDCS protocol may be used as an add-on treatment for prolonged DOC.

Background: Although low-intensity transcranial ultrasound stimulation (LI-TUS) has received more recognition for its neuromodulation potential, there remains a crucial knowledge gap regarding the neuromodulatory effects of LI-TUS and its potential for translation as a therapeutic tool in humans.Objective: In this review, we summarized the findings reported by recently published studies regarding the effect of LI-TUS on neuromodulation in both animals and humans. We also aim to identify challenges and opportunities for the translation process.Methods: A literature search of PubMed, Medline, EMBASE, and Web of Science was performed from January 2019 to June 2020 with the following keywords and Boolean operators: [transcranial ultrasound OR transcranial focused ultrasound OR ultrasound stimulation] AND [neuromodulation]. The methodological quality of the animal studies was assessed by the SYRCLE's risk of bias tool, and the quality of human studies was evaluated by the PEDro score and the NIH quality assessment tool.Results: After applying the inclusion and exclusion criteria, a total of 26 manuscripts (24 animal studies and two human studies) out of 508 reports were included in this systematic review. Although both inhibitory (10 studies) and excitatory (16 studies) effects of LI-TUS were observed in animal studies, only inhibitory effects have been reported in primates (five studies) and human subjects (two studies). The ultrasonic parameters used in animal and human studies are different. The SYRCLE quality score ranged from 25 to 43%, with a majority of the low scores related to performance and detection bias. The two human studies received high PEDro scores (9/10).Conclusion: LI-TUS appears to be capable of targeting both superficial and deep cerebral structures to modulate cognitive or motor behavior in both animals and humans. Further human studies are needed to more precisely define the effective modulation parameters and thereby translate this brain modulatory tool into the clinic.

Background: Although low-intensity transcranial ultrasound stimulation (LI-TUS) has received more recognition for its neuromodulation potential, there remains a crucial knowledge gap regarding the neuromodulatory effects of LI-TUS and its potential for translation as a therapeutic tool in humans. Objective: In this review, we summarized the findings reported by recently published studies regarding the effect of LI-TUS on neuromodulation in both animals and humans. We also aim to identify challenges and opportunities for the translation process. Methods: A literature search of PubMed, Medline, EMBASE, and Web of Science was performed from January 2019 to June 2020 with the following keywords and Boolean operators: [transcranial ultrasound OR transcranial focused ultrasound OR ultrasound stimulation] AND [neuromodulation]. The methodological quality of the animal studies was assessed by the SYRCLE's risk of bias tool, and the quality of human studies was evaluated by the PEDro score and the NIH quality assessment tool. Results: After applying the inclusion and exclusion criteria, a total of 26 manuscripts (24 animal studies and two human studies) out of 508 reports were included in this systematic review. Although both inhibitory (10 studies) and excitatory (16 studies) effects of LI-TUS were observed in animal studies, only inhibitory effects have been reported in primates (five studies) and human subjects (two studies). The ultrasonic parameters used in animal and human studies are different. The SYRCLE quality score ranged from 25 to 43%, with a majority of the low scores related to performance and detection bias. The two human studies received high PEDro scores (9/10). Conclusion: LI-TUS appears to be capable of targeting both superficial and deep cerebral structures to modulate cognitive or motor behavior in both animals and humans. Further human studies are needed to more precisely define the effective modulation parameters and thereby translate this brain modulatory tool into the clinic. [ABSTRACT FROM AUTHOR]

Studies on weak current stimulation (1–2 mA) examine effects on neuronal cells for the treatment of neurological diseases, like depression. Ocular current stimulation showed positive effects on retinal nerve cells which indicate that neurodegenerative ocular diseases, e.g., glaucoma, can be treated with current stimulation of the eye. However, up to now it remains unclear which exact retinal cells can be influenced. During an ocular direct current stimulation, a significant reduction of the characteristic P50 amplitude of a pattern-reversal electroretinogram (PERG) was found for an anodal and a cathodal stimulation. This current stimulation effect could originate from the modulation of pre-ganglion cell activity or by changes in local ON and OFF responses of ganglion cells. For clarification, we investigate acute direct current stimulation effects on a full field electroretinogram (ERG), which represents the activity of pre-ganglion cells (specifically cones and bipolar cells). The ERG from 15 subjects was evaluated before (ERG 1) and during (ERG 2) an ocular direct current stimulation with 800 μA over 5 min. The current was applied through a ring rubber electrode placed around the eye and a 25 cm2 rubber electrode placed at the ipsilateral temple. For ERG measurements, sintered Ag/AgCl skin-electrodes were positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). The volunteers were stimulated in three independent sessions, each with a different current application (randomized order): cathodal polarity, anodal polarity (referred to the electrode around the eye), or sham stimulation. The changes between the two ERG measurements of the characteristic full field ERG amplitudes, a-wave, b-wave, and b′-wave (b-wave measured from zero line) were tested with the Wilcoxon signed-rank test (α = 0.05). Comparing before to during the current stimulation for all applications, the ERG waves showed no effects on amplitudes or latencies. Furthermore, no significant difference between the cathodal, anodal, and sham stimulation could be found by a Friedman test. These results indicate an unlikely contribution of pre-ganglion cells to the previously reported stimulation effect on PERG signals.

Studies on weak current stimulation (1–2 mA) examine effects on neuronal cells for the treatment of neurological diseases, like depression. Ocular current stimulation showed positive effects on retinal nerve cells which indicate that neurodegenerative ocular diseases, e.g., glaucoma, can be treated with current stimulation of the eye. However, up to now it remains unclear which exact retinal cells can be influenced. During an ocular direct current stimulation, a significant reduction of the characteristic P50 amplitude of a pattern-reversal electroretinogram (PERG) was found for an anodal and a cathodal stimulation. This current stimulation effect could originate from the modulation of pre-ganglion cell activity or by changes in local ON and OFF responses of ganglion cells. For clarification, we investigate acute direct current stimulation effects on a full field electroretinogram (ERG), which represents the activity of pre-ganglion cells (specifically cones and bipolar cells). The ERG from 15 subjects was evaluated before (ERG 1) and during (ERG 2) an ocular direct current stimulation with 800 μA over 5 min. The current was applied through a ring rubber electrode placed around the eye and a 25 cm2 rubber electrode placed at the ipsilateral temple. For ERG measurements, sintered Ag/AgCl skin-electrodes were positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). The volunteers were stimulated in three independent sessions, each with a different current application (randomized order): cathodal polarity, anodal polarity (referred to the electrode around the eye), or sham stimulation. The changes between the two ERG measurements of the characteristic full field ERG amplitudes, a-wave, b-wave, and b′-wave (b-wave measured from zero line) were tested with the Wilcoxon signed-rank test (α = 0.05). Comparing before to during the current stimulation for all applications, the ERG waves showed no effects on amplitudes or latencies. Furthermore, no significant difference between the cathodal, anodal, and sham stimulation could be found by a Friedman test. These results indicate an unlikely contribution of pre-ganglion cells to the previously reported stimulation effect on PERG signals. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS) has been used as a tool to induce synaptic plasticity and improve neurological disorders. However, there is high interindividual variability in the magnitude of the plastic changes observed after TBS, which hinders its clinical applications. The electric field induced by transcranial magnetic stimulation (TMS) is strongly affected by the depth of the stimulated brain region. Therefore, it is possible that the variability in the response to TBS over the lower-limb motor cortex is different for the hand area. This study investigated the variability of TBS-induced synaptic plasticity in the lower-limb motor cortex, for intermittent TBS (iTBS), continuous TBS (cTBS), and sham iTBS, in 48 healthy young participants. The motor cortical and intracortical excitability of the tibialis anterior was tested before and after TBS using TMS. The results showed that iTBS had facilitatory effects on motor cortex excitability and intracortical inhibition, whereas cTBS exerted opposite effects. Twenty-seven percent of individuals exhibited enhanced motor cortical plasticity after iTBS, whereas 63% of participants showed enhanced plasticity after cTBS. In addition, the amount of TBS-induced plasticity was correlated with the intracortical excitability and the variability of the motor evoked potential prior to TBS. Our study demonstrated the high variability of the iTBS-induced lower-limb motor cortical plasticity, which was affected by the sensitivity of intracortical interneuronal circuits. These findings provide further insights into the variation of the response to TBS according to the anatomy of the stimulated brain region and the excitability of the intracortical circuit.

Background: Gambling disorder (GD) is the most common behavioral addiction and shares pathophysiological and clinical features with substance use disorders (SUDs). Effective therapeutic interventions for GD are lacking. Non-invasive brain stimulation (NIBS) may represent a promising treatment option for GD.Objective: This systematic review aimed to provide a comprehensive and structured overview of studies applying NIBS techniques to GD and problem gambling.Methods: A literature search using Pubmed, Web of Science, and Science Direct was conducted from databases inception to December 19, 2019, for studies assessing the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (t-DCS) on subjects with GD or problem gambling. Studies using NIBS techniques on healthy subjects and those without therapeutic goals but only aiming to assess basic neurophysiology measures were excluded.Results: A total of 269 articles were title and abstract screened, 13 full texts were assessed, and 11 were included, of which six were controlled and five were uncontrolled. Most studies showed a reduction of gambling behavior, craving for gambling, and gambling-related symptoms. NIBS effects on psychiatric symptoms were less consistent. A decrease of the behavioral activation related to gambling was also reported. Some studies reported modulation of behavioral measures (i.e., impulsivity, cognitive and attentional control, decision making, cognitive flexibility). Studies were not consistent in terms of NIBS protocol, site of stimulation, clinical and surrogate outcome measures, and duration of treatment and follow-up. Sample size was small in most studies.Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the efficacy of NIBS interventions for GD. Further methodologically sound, robust, and well-powered studies are needed.

Studies on transcranial current stimulation have shown that a direct current stimulation of the occipital cortex can influence the amplitude size of a visual evoked potential (VEP). The current direction (cathodal or anodal) determines whether the VEP amplitudes increase or decrease. The aim of this study was to design a new experimental setup that will enable a simultaneous ocular direct current stimulation and electroretinogram (ERG) recording which will broaden our understanding of current stimulation effects on the visual system. Furthermore, we examined whether a direct current stimulation on the eye has a similar effect on an ERG as on a VEP. The pattern-reversal ERG was measured with sintered Ag/AgCl skin-electrodes, positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). Direct current was applied through a ring rubber electrode placed around the eye and a 5 cm × 5 cm rubber electrode placed at the ipsilateral temple with a current strength of 500 μA and a duration time of 5 min. Fifty-seven healthy volunteers were divided into three groups depending on the current direction (cathodal, anodal, and sham stimulation, n = 19 each). One ERG measurement (ERG 1) was performed before and another (ERG 2) during the direct current stimulation. The difference between ERG 1 and ERG 2 measurements for the characteristic P50, N95 and N95′ (N95 minimum measured from zero line) amplitudes were evaluated by both confidence interval analysis and t-test for related samples (α = 0.05, after Bonferroni correction p∗ = 0.0055). The P50 amplitude was significantly decreased for ERG 2 measurement in the cathodal and anodal stimulation group (cathodal p = 0.001, anodal p = 0.000). No significant changes could be found in the N95 and N95′ amplitudes as well as in the sham-stimulation group. Additionally, the latencies did not undergo any significant changes. In conclusion, the newly designed experimental setup enables simultaneous current stimulation and ERG recording. The current influenced P50 amplitude although not the N95 and N95′ amplitudes. Furthermore, the amplitude size decreased for both current directions and did not lead to contrary effects as expected.

Static magnetic fields have been shown to induce effects on the human brain. Different experiments seem to support the idea that moderate static magnetic field can exert some influence on the gating processes of the membrane channels. In this article we visit the order of magnitude of the energy magnetic terms associated with moderate applied field (between 10 and 200 milliteslas). It is shown that gradients of the Zeeman energy associated with the inhomogeneous applied fields can induce pressures of the order of 10–2Pa. The surface tension generated by the magnetic pressure, on the surface delimiting the brain region subject to relevant field and gradients, is found to range between 10–1 and 1 mN⋅m–1. These pressures seem to be strong enough to interfere with the elastic and electrostatic energies involved in the channel activation-inactivation-deactivation mechanisms of biological membranes. It has been described that small mechanical force can activate voltage gated potassium channels. Moreover, stretch-activated ion channels are widely described in different biological tissues. Virtually, all these channels can modify their activity if stressed by a sufficient pressure delivered for enough time. We propose mechanical stimulation – possibly not exclusively – as a candidate mechanism how static magnetic field can produce effects in biological systems. It must be emphasized, that such field gradients were not previously proposed as a possible source of neural activity modification.

BackgroundNon-invasive neuromodulation is an emerging therapy for children with early brain injury but is difficult to apply to preschoolers when windows of developmental plasticity are optimal. Transcranial static magnetic field stimulation (tSMS) decreases primary motor cortex (M1) excitability in adults but effects on the developing brain are unstudied.Objective/HypothesisWe aimed to determine the effects of tSMS on cortical excitability and motor learning in healthy children. We hypothesized that tSMS over right M1 would reduce cortical excitability and inhibit contralateral motor learning.MethodsThis randomized, sham-controlled, double-blinded, three-arm, cross-over trial enrolled 24 healthy children aged 10–18 years. Transcranial Magnetic Stimulation (TMS) assessed cortical excitability via motor-evoked potential (MEP) amplitude and paired pulse measures. Motor learning was assessed via the Purdue Pegboard Test (PPT). A tSMS magnet (677 Newtons) or sham was held over left or right M1 for 30 min while participants trained the non-dominant hand. A linear mixed effect model was used to examine intervention effects.ResultsAll 72 tSMS sessions were well tolerated without serious adverse effects. Neither cortical excitability as measured by MEPs nor paired-pulse intracortical neurophysiology was altered by tSMS. Possible behavioral effects included contralateral tSMS inhibiting early motor learning (p < 0.01) and ipsilateral tSMS facilitating later stages of motor learning (p < 0.01) in the trained non-dominant hand.ConclusiontSMS is feasible in pediatric populations. Unlike adults, tSMS did not produce measurable changes in MEP amplitude. Possible effects of M1 tSMS on motor learning require further study. Our findings support further exploration of tSMS neuromodulation in young children with cerebral palsy.

Theta burst stimulation (TBS) has been used as a tool to induce synaptic plasticity and improve neurological disorders. However, there is high interindividual variability in the magnitude of the plastic changes observed after TBS, which hinders its clinical applications. The electric field induced by transcranial magnetic stimulation (TMS) is strongly affected by the depth of the stimulated brain region. Therefore, it is possible that the variability in the response to TBS over the lower-limb motor cortex is different for the hand area. This study investigated the variability of TBS-induced synaptic plasticity in the lower-limb motor cortex, for intermittent TBS (iTBS), continuous TBS (cTBS), and sham iTBS, in 48 healthy young participants. The motor cortical and intracortical excitability of the tibialis anterior was tested before and after TBS using TMS. The results showed that iTBS had facilitatory effects on motor cortex excitability and intracortical inhibition, whereas cTBS exerted opposite effects. Twenty-seven percent of individuals exhibited enhanced motor cortical plasticity after iTBS, whereas 63% of participants showed enhanced plasticity after cTBS. In addition, the amount of TBS-induced plasticity was correlated with the intracortical excitability and the variability of the motor evoked potential prior to TBS. Our study demonstrated the high variability of the iTBS-induced lower-limb motor cortical plasticity, which was affected by the sensitivity of intracortical interneuronal circuits. These findings provide further insights into the variation of the response to TBS according to the anatomy of the stimulated brain region and the excitability of the intracortical circuit. [ABSTRACT FROM AUTHOR]

Background: Gambling disorder (GD) is the most common behavioral addiction and shares pathophysiological and clinical features with substance use disorders (SUDs). Effective therapeutic interventions for GD are lacking. Non-invasive brain stimulation (NIBS) may represent a promising treatment option for GD. Objective: This systematic review aimed to provide a comprehensive and structured overview of studies applying NIBS techniques to GD and problem gambling. Methods: A literature search using Pubmed, Web of Science, and Science Direct was conducted from databases inception to December 19, 2019, for studies assessing the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (t-DCS) on subjects with GD or problem gambling. Studies using NIBS techniques on healthy subjects and those without therapeutic goals but only aiming to assess basic neurophysiology measures were excluded. Results: A total of 269 articles were title and abstract screened, 13 full texts were assessed, and 11 were included, of which six were controlled and five were uncontrolled. Most studies showed a reduction of gambling behavior, craving for gambling, and gambling-related symptoms. NIBS effects on psychiatric symptoms were less consistent. A decrease of the behavioral activation related to gambling was also reported. Some studies reported modulation of behavioral measures (i.e., impulsivity, cognitive and attentional control, decision making, cognitive flexibility). Studies were not consistent in terms of NIBS protocol, site of stimulation, clinical and surrogate outcome measures, and duration of treatment and follow-up. Sample size was small in most studies. Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the efficacy of NIBS interventions for GD. Further methodologically sound, robust, and well-powered studies are needed. [ABSTRACT FROM AUTHOR]

Studies on transcranial current stimulation have shown that a direct current stimulation of the occipital cortex can influence the amplitude size of a visual evoked potential (VEP). The current direction (cathodal or anodal) determines whether the VEP amplitudes increase or decrease. The aim of this study was to design a new experimental setup that will enable a simultaneous ocular direct current stimulation and electroretinogram (ERG) recording which will broaden our understanding of current stimulation effects on the visual system. Furthermore, we examined whether a direct current stimulation on the eye has a similar effect on an ERG as on a VEP. The pattern-reversal ERG was measured with sintered Ag/AgCl skin-electrodes, positioned on the lower eyelid (active), the earlobe (reference), and the forehead (ground). Direct current was applied through a ring rubber electrode placed around the eye and a 5 cm × 5 cm rubber electrode placed at the ipsilateral temple with a current strength of 500 μA and a duration time of 5 min. Fifty-seven healthy volunteers were divided into three groups depending on the current direction (cathodal, anodal, and sham stimulation, n = 19 each). One ERG measurement (ERG 1) was performed before and another (ERG 2) during the direct current stimulation. The difference between ERG 1 and ERG 2 measurements for the characteristic P50, N95 and N95′ (N95 minimum measured from zero line) amplitudes were evaluated by both confidence interval analysis and t -test for related samples (α = 0.05, after Bonferroni correction p ∗ = 0.0055). The P50 amplitude was significantly decreased for ERG 2 measurement in the cathodal and anodal stimulation group (cathodal p = 0.001, anodal p = 0.000). No significant changes could be found in the N95 and N95′ amplitudes as well as in the sham-stimulation group. Additionally, the latencies did not undergo any significant changes. In conclusion, the newly designed experimental setup enables simultaneous current stimulation and ERG recording. The current influenced P50 amplitude although not the N95 and N95′ amplitudes. Furthermore, the amplitude size decreased for both current directions and did not lead to contrary effects as expected. [ABSTRACT FROM AUTHOR]

Background: Non-invasive neuromodulation is an emerging therapy for children with early brain injury but is difficult to apply to preschoolers when windows of developmental plasticity are optimal. Transcranial static magnetic field stimulation (tSMS) decreases primary motor cortex (M1) excitability in adults but effects on the developing brain are unstudied. Objective/Hypothesis: We aimed to determine the effects of tSMS on cortical excitability and motor learning in healthy children. We hypothesized that tSMS over right M1 would reduce cortical excitability and inhibit contralateral motor learning. Methods: This randomized, sham-controlled, double-blinded, three-arm, cross-over trial enrolled 24 healthy children aged 10–18 years. Transcranial Magnetic Stimulation (TMS) assessed cortical excitability via motor-evoked potential (MEP) amplitude and paired pulse measures. Motor learning was assessed via the Purdue Pegboard Test (PPT). A tSMS magnet (677 Newtons) or sham was held over left or right M1 for 30 min while participants trained the non-dominant hand. A linear mixed effect model was used to examine intervention effects. Results: All 72 tSMS sessions were well tolerated without serious adverse effects. Neither cortical excitability as measured by MEPs nor paired-pulse intracortical neurophysiology was altered by tSMS. Possible behavioral effects included contralateral tSMS inhibiting early motor learning (p < 0.01) and ipsilateral tSMS facilitating later stages of motor learning (p < 0.01) in the trained non-dominant hand. Conclusion: tSMS is feasible in pediatric populations. Unlike adults, tSMS did not produce measurable changes in MEP amplitude. Possible effects of M1 tSMS on motor learning require further study. Our findings support further exploration of tSMS neuromodulation in young children with cerebral palsy. [ABSTRACT FROM AUTHOR]

Static magnetic fields have been shown to induce effects on the human brain. Different experiments seem to support the idea that moderate static magnetic field can exert some influence on the gating processes of the membrane channels. In this article we visit the order of magnitude of the energy magnetic terms associated with moderate applied field (between 10 and 200 milliteslas). It is shown that gradients of the Zeeman energy associated with the inhomogeneous applied fields can induce pressures of the order of 10–2Pa. The surface tension generated by the magnetic pressure, on the surface delimiting the brain region subject to relevant field and gradients, is found to range between 10–1 and 1 mN⋅m–1. These pressures seem to be strong enough to interfere with the elastic and electrostatic energies involved in the channel activation-inactivation-deactivation mechanisms of biological membranes. It has been described that small mechanical force can activate voltage gated potassium channels. Moreover, stretch-activated ion channels are widely described in different biological tissues. Virtually, all these channels can modify their activity if stressed by a sufficient pressure delivered for enough time. We propose mechanical stimulation – possibly not exclusively – as a candidate mechanism how static magnetic field can produce effects in biological systems. It must be emphasized, that such field gradients were not previously proposed as a possible source of neural activity modification. [ABSTRACT FROM AUTHOR]

Neuromodulation, pain, neurofeedback, acupuncture, non-invasive brain stimulation, TMS, tDCS While a significant decrease in pain across sessions was found for the NFB group, a near identical decrease was found for the sham group, consistent with the idea that any therapeutic effects of NFB could be at least in part attributable to a non-specific component. Keywords: neuromodulation; pain; neurofeedback; acupuncture; non-invasive brain stimulation; TMS; tDCS EN neuromodulation pain neurofeedback acupuncture non-invasive brain stimulation TMS tDCS 1 3 3 08/17/21 20210813 NES 210813 The opioid crisis has prompted a renewed interest in non-pharmacological interventions for pain, with recent promising evidence for their effectiveness (Pillai Riddell et al., [3]; Veehof et al., [6]; Thompson et al., [4], [5]; Franco et al., [1]; Owen et al., [2]). [Extracted from the article]

Dopamine system plays a pivotal role in specific kinds of substance use disorders (SUD, i. e., cocaine and methamphetamine use disorders). Many studies addressed whether dopamine-involved craving could be alleviated by non-invasive brain stimulation (NIBS) techniques. Nevertheless, the outcomes were highly inconsistent and the stimulating parameters were highly variable. In the current study, we ran a meta-analysis to identify an overall effect size of NIBS and try to find stimulating parameters of special note. We primarily find 2,530 unduplicated studies in PubMed, Psychology and Behavioral Sciences Collection, PsycARTICLES, PsycINFO, and Google Scholar database involving “Cocaine”/“Amphetamine”/“Methamphetamine” binded with “TMS”/“tDCS”/“non-invasive stimulation” in either field. After visual screening, 26 studies remained. While 16 studies were further excluded due to the lack of data, invalid craving scoring or the absence of sham condition. At last, 16 units of analysis in 12 eligible studies were coded and forwarded to a random-effect analysis. The results showed a large positive main effect of stimulation (Hedge's g = 1.116, CI = [0.597, 1.634]). Further subgroup analysis found that only high-frequency repetitive transcranial magnetic stimulation (rTMS) could elicit a significant decrease in craving, while the outcome of low-frequency stimulation was relatively controversial. Moreover, univariate meta regression revealed that the number of pulses per session could impose negative moderation toward the intervention. No significant moderation effect was found in types of abuse, overall days of stimulation and other variables of stimulating protocol. In conclusion, this meta-analysis offered a persuasive evidence for the feasibility of using NIBS to remit substance addictive behavior directly based on dopamine system. We also give clear methodological guidance that researchers are expected to use high-frequency, sufficiently segmented rTMS to improve the efficacy in future treatments.

Background: Despite a growing literature and commercial market, the effectiveness of transcranial direct current stimulation (tDCS) remains questionable. Notably, studies rarely examine factors such as expectations of outcomes, which may influence tDCS response through placebo-like effects. Here we sought to determine whether expectations could influence the behavioral outcomes of a tDCS intervention.Methods: Through an initial study and self-replication, we recruited 121 naïve young adults 18–34 years of age (M = 21.14, SD = 3.58; 88 women). We evaluated expectations of tDCS and of motor and cognitive performance at three times: (i) at baseline; (ii) after being primed to have High or Low expectations of outcomes; and (iii) after a single session of sham-controlled anodal tDCS over the left or right motor cortex. Before and after stimulation, participants performed the Grooved Pegboard Test and a choice reaction time task as measures of motor dexterity, response time, and response inhibition.Results: Repeated measures ANOVA revealed that participants had varying, largely uncertain, expectations regarding tDCS effectiveness at baseline. Expectation ratings significantly increased or decreased in response to High or Low priming, respectively, and decreased following the intervention. Response times and accuracy on motor and cognitive measures were largely unaffected by expectation or stimulation conditions. Overall, our analysis revealed no effect attributable to baseline expectations, belief of group assignment, or experimental condition on behavioral outcomes. Subjective experience did not differ based on expectation or stimulation condition.Conclusions: Our results suggest no clear effects of tDCS or of expectations on our performance measures, highlighting the need for further investigations of such stimulation methods.

Introduction: Transcranial direct current stimulation (tDCS) has shown positive but inconsistent results in stroke rehabilitation. This could be attributed to inter-individual variations in brain characteristics and stroke lesions, which limit the use of a single tDCS protocol for all post-stroke patients. Optimizing the electrode location in tDCS for each individual using magnetic resonance imaging (MRI) to generate three-dimensional computer models and calculate the electric field (E-field) induced by tDCS at a specific target point in the primary motor cortex may help reduce these inconsistencies. In stroke rehabilitation, locating the optimal position that generates a high E-field in a target area can influence motor recovery. Therefore, this study was designed to determine the effect of personalized tDCS electrode positions on hand-knob activation in post-stroke patients., Method: This is a crossover study with a sample size of 50 participants, who will be randomly assigned to one of six groups and will receive one session of either optimized-active, conventional-active, or sham tDCS, with 24 h between sessions. The tDCS parameters will be 1 mA (5 × 5 cm electrodes) for 20 min. The motor-evoked potential (MEP) will be recorded before and after each session over the target area (motor cortex hand-knob) and the MEP hotspot. The MEP amplitude at the target location will be the primary outcome., Discussion: We hypothesize that the optimized-active tDCS session would show a greater increase in MEP amplitude over the target area in patients with subacute and chronic stroke than conventional and sham tDCS sessions. Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007536., Competing Interests: TK, JCSF, HJ, and DK were employed by the company Neurophet (Seoul, Republic of Korea). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Salazar Fajardo, Jang, Lee, Kim, Kim and Kim.)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation method commonly used in the disciplines of neuroscience, neurology, and neuropsychiatry to examine or modulate brain function. Low frequency rTMS (e.g., 1 Hz) is associated with a net suppression of cortical excitability, whereas higher frequencies (e.g., 5 Hz) purportedly increase excitability. Magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rsfMRI) allow investigation of neurochemistry and functional connectivity, respectively, and can assess the influence of rTMS in these domains. This pilot study investigated the effects of rTMS on the primary motor cortex using pre and post MRS and rsfMRI assessments at 7 T. Seven right-handed males (age 27 ± 7 y.o.) underwent single-voxel MRS and rsfMRI before and about 30-min after rTMS was administered outside the scanner for 20-min over the primary motor cortex of the left (dominant) hemisphere. All participants received 1-Hz rTMS; one participant additionally received 5-Hz rTMS in a separate session. Concentrations of 17 neurochemicals were quantified in left and right motor cortices. Connectivity metrics included fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) of both motor cortices, strength of related brain networks, and inter-hemispheric connectivity. The group-analysis revealed few trends (i.e., uncorrected for multiple comparisons), including a mean increase in the concentration of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) after the inhibitory rTMS protocol as compared to baseline in the stimulated (left) motor cortex (+8%, p = 0.043), along with a slight increase of total creatine (+2%, p = 0.018), and decrease of aspartate (−18%, p = 0.016). Additionally, GABA tended to decrease in the contralateral hemisphere (−6%, p = 0.033). No other changes of metabolite concentrations were found. Whereas functional connectivity outcomes did not exhibit trends of significant changes induced by rTMS, the percent changes of few connectivity metrics in both hemispheres were negatively correlated with GABA changes in the contralateral hemisphere. While studies in larger cohorts are needed to confirm these preliminary findings, our results indicate the safety and feasibility of detecting changes in key metabolites associated with neurotransmission after a single 1-Hz rTMS session, establishing the construct for future exploration of the neurochemical, and connectivity mechanisms of cortical responses to neuromodulation. [ABSTRACT FROM AUTHOR]

Dopamine system plays a pivotal role in specific kinds of substance use disorders (SUD, i. e., cocaine and methamphetamine use disorders). Many studies addressed whether dopamine-involved craving could be alleviated by non-invasive brain stimulation (NIBS) techniques. Nevertheless, the outcomes were highly inconsistent and the stimulating parameters were highly variable. In the current study, we ran a meta-analysis to identify an overall effect size of NIBS and try to find stimulating parameters of special note. We primarily find 2,530 unduplicated studies in PubMed, Psychology and Behavioral Sciences Collection, PsycARTICLES, PsycINFO, and Google Scholar database involving "Cocaine"/"Amphetamine"/"Methamphetamine" binded with "TMS"/"tDCS"/"non-invasive stimulation" in either field. After visual screening, 26 studies remained. While 16 studies were further excluded due to the lack of data, invalid craving scoring or the absence of sham condition. At last, 16 units of analysis in 12 eligible studies were coded and forwarded to a random-effect analysis. The results showed a large positive main effect of stimulation (Hedge's g = 1.116, CI = [0.597, 1.634]). Further subgroup analysis found that only high-frequency repetitive transcranial magnetic stimulation (rTMS) could elicit a significant decrease in craving, while the outcome of low-frequency stimulation was relatively controversial. Moreover, univariate meta regression revealed that the number of pulses per session could impose negative moderation toward the intervention. No significant moderation effect was found in types of abuse, overall days of stimulation and other variables of stimulating protocol. In conclusion, this meta-analysis offered a persuasive evidence for the feasibility of using NIBS to remit substance addictive behavior directly based on dopamine system. We also give clear methodological guidance that researchers are expected to use high-frequency, sufficiently segmented rTMS to improve the efficacy in future treatments. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to change cortical excitability. Its effects are shown for cognitive processing, and behavior in the motor and perceptual domains. However, evidence of tDCS effects in the perceptual domain particularly for auditory processing is rare. Therefore, and in the context of disturbances in auditory processing in psychiatric populations, e.g., in patients with auditory verbal hallucinations, we aimed to investigate the potential modulatory effect of tDCS on the excitability of left posterior temporal cortex in detail. We included 24 healthy participants in a crossover design, applying sham and anodal stimulation in two measurement sessions 1 week apart. Electroencephalography (EEG) was recorded while participants listened to tones before, during, and after stimulation. Amplitudes and latencies of P50, N100, and P200 auditory-evoked potentials (AEP) were compared between anodal and sham stimulation, and between time points before, during, and after tDCS. In contrast to previous studies, results demonstrate no significant differences between stimulation types or time points for any of the investigated AEP amplitudes or latencies. Furthermore, a topographical analysis did not show any topographical differences during peak time periods of the investigated AEP for stimulation types and time points besides a habituation effect. Thus, our results suggest that tDCS modulation of excitability of the left posterior temporal cortex, targeting the auditory cortex, does not have any effect on AEP. This is particularly interesting in the context of tDCS as a potential treatment for changed electrophysiological parameters and symptoms of psychiatric diseases, e.g., lower N100 or auditory verbal hallucinations in schizophrenia.

Background: Transcranial direct current stimulation (tDCS) can improve motor learning in children. High-definition approaches (HD-tDCS) have not been examined in children.Objectives/Hypothesis: We hypothesized that primary motor cortex HD-tDCS would enhance motor learning but be inferior to tDCS in children.Methods: Twenty-four children were recruited for a randomized, sham-controlled, double-blinded interventional trial (NCT03193580, clinicaltrials.gov/ct2/show/NCT03193580) to receive (1) right hemisphere (contralateral) primary motor cortex (M1) 1 mA anodal conventional 1 × 1 tDCS (tDCS), (2) right M1 1 mA anodal 4 × 1 HD-tDCS (HD-tDCS), or (3) sham. Over five consecutive days, participants trained their left hand using the Purdue Pegboard Test (PPTL). The Jebsen–Taylor Test, Serial Reaction Time Task, and right hand and bimanual PPT were also tested at baseline, post-training, and 6-week retention time (RT).Results: Both the tDCS and HD-tDCS groups demonstrated enhanced motor learning compared to sham with effects maintained at 6 weeks. Effect sizes were moderate-to-large for tDCS and HD-tDCS groups at the end of day 4 (Cohen’s d tDCS = 0.960, HD-tDCS = 0.766) and day 5 (tDCS = 0.655, HD-tDCS = 0.851). Enhanced motor learning effects were also seen in the untrained hand. HD-tDCS was well tolerated and safe with no adverse effects.Conclusion: HD-tDCS and tDCS can enhance motor learning in children. Further exploration is indicated to advance rehabilitation therapies for children with motor disabilities such as cerebral palsy.Clinical Trial Registration:clinicaltrials.gov, identifier NCT03193580.

This study explored the effect of corticospinal activity on spinal plasticity by examining the interactions between intermittent theta burst transcranial magnetic stimulation (iTBS) of the motor cortex and peripheral patterned electrical stimulation (PES) of the common peroneal nerve (CPN). Healthy volunteers (n = 10) received iTBS to the tibialis anterior (TA) muscle zone of the motor cortex and PES of the CPN in three separate sessions: (1) iTBS-before-PES, (2) iTBS-after-PES, and (3) sham iTBS-before-PES. The PES protocol used 10 100-Hz pulses every 2 s for 20 min. Reciprocal inhibition (RI) from the TA to soleus muscle and motor cortical excitability of the TA and soleus muscles were assessed at baseline, before PES, and 0, 15, 30, and 45 min after PES. When compared to the other protocols, iTBS-before-PES significantly increased changes in disynaptic RI for 15 min and altered long-loop presynaptic inhibition immediately after PES. Moreover, the iTBS-induced cortical excitability changes in the TA before PES were correlated with the enhancement of disynaptic RI immediately after PES. These results demonstrate that spinal plasticity can be modified by altering cortical excitability. This study provides insight into the interactions between modulation of corticospinal excitability and spinal RI, which may help in developing new rehabilitation strategies.

Non-invasive brain stimulation (NIBS) has been widely used as a research tool to modulate cortical excitability of motor as well as non-motor areas, including auditory or language-related areas. NIBS, especially transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, have also been used in clinical settings, with however variable therapeutic outcome, highlighting the need to better understand the mechanisms underlying NIBS techniques. TMS was initially used to address causality between specific brain areas and related behavior, such as language production, providing non-invasive alternatives to lesion studies. Recent literature however suggests that the relationship is not as straightforward as originally thought, and that TMS can show both linear and non-linear modulation of brain responses, highlighting complex network dynamics. In particular, in the last decade, NIBS studies have enabled further advances in our understanding of auditory processing and its underlying functional organization. For instance, NIBS studies showed that even when only one auditory cortex is stimulated unilaterally, bilateral modulation may result, thereby highlighting the influence of functional connectivity between auditory cortices. Additional neuromodulation techniques such as transcranial alternating current stimulation or transcranial random noise stimulation have been used to target frequency-specific neural oscillations of the auditory cortex, thereby providing further insight into modulation of auditory functions. All these NIBS techniques offer different perspectives into the function and organization of auditory cortex. However, further research should be carried out to assess the mode of action and long-term effects of NIBS to optimize their use in clinical settings.

Induction of neuroplasticity by transcranial direct current stimulation (tDCS) applied to the primary motor cortex facilitates motor learning of the upper extremities in healthy humans. The impact of tDCS on lower limb functions has not been studied extensively so far. In this study, we applied a system identification approach to investigate the impact of anodal transcranial direct current stimulation of the leg area of the motor cortex via the human visuo-myoelectric controller. The visuo-myoelectric reaching task (VMT) involves ballistic muscle contraction after a visual cue. We applied a black box approach using a linear ARX (Auto-regressive with eXogenous input) model for a visuomotor myoelectric reaching task. We found that a 20th order finite impulse response (FIR) model captured the TARGET (single input)—CURSOR (single output) dynamics during a VMT. The 20th order FIR model was investigated based on gain/phase margin analysis, which showed a significant (p < 0.01) effect of anodal tDCS on the gain margin of the VMT system. Also, response latency and the corticomuscular coherence (CMC) time delay were affected (p < 0.05) by anodal tDCS when compared to sham tDCS. Furthermore, gray box simulation results from a Simplified Spinal-Like Controller (SSLC) model demonstrated that the input-output function for motor evoked potentials (MEP) played an essential role in increasing muscle activation levels and response time improvement post-tDCS when compared to pre-tDCS baseline performance. This computational approach can be used to simulate the behavior of the neuromuscular controller during VMT to elucidate the effects of adjuvant treatment with tDCS.