Alterations in learning-related cortical activation and functional connectivity by high-definition transcranial direct current stimulation after stroke: an fNIRS study.

Introduction: Motor learning is a key component of stroke neurorehabilitation. High-definition transcranial direct current stimulation (HD-tDCS) was recently developed as a tDCS technique that increases the accuracy of current delivery to the brain using arrays of small electrodes. The purpose of this study was to investigate whether HD-tDCS alters learning-related cortical activation and functional connectivity in stroke patients using functional near-infrared spectroscopy (fNIRS). Methods: Using a sham-controlled crossover study design, 16 chronic stroke patients were randomly assigned to one of two intervention conditions. Both groups performed the sequential finger tapping task (SFTT) on five consecutive days, either with (a) real HD-tDCS or (b) with sham HD-tDCS. HD-tDCS (1 mA for 20 min, 4 × 1) was administered to C3 or C4 (according to lesion side). fNIRS signals were measured during the SFTT with the affected hand before (baseline) and after each intervention using fNIRS measurement system. Cortical activation and functional connectivity of NIRS signals were analyzed using a statistical parametric mapping open-source software package (NIRS-SPM), OptoNet II®. Results: In the real HD-tDCS condition, oxyHb concentration increased significantly in the ipsilesional primary motor cortex (M1). Connectivity between the ipsilesional M1 and the premotor cortex (PM) was noticeably strengthened after real HD-tDCS compared with baseline. Motor performance also significantly improved, as shown in response time during the SFTT. In the sham HD-tDCS condition, functional connectivity between contralesional M1 and sensory cortex was enhanced compared with baseline. There was tendency toward improvement in SFTT response time, but without significance. Discussion: The results of this study indicated that HD-tDCS could modulate learning-related cortical activity and functional connectivity within motor networks to enhance motor learning performance. HD-tDCS can be used as an additional tool for enhancing motor learning during hand rehabilitation for chronic stroke patients.

Dynamic sensitivity analysis: Defining personalised strategies to drive brain state transitions via whole brain modelling.

Traditionally, in neuroimaging, model-free analyses are used to find significant differences between brain states via signal detection theory. Depending on the a priori assumptions about the underlying data, different spatio-temporal features can be analysed. Alternatively, model-based techniques infer features from the data and compare significance from model parameters. However, to assess transitions from one brain state to another remains a challenge in current paradigms. Here, we introduce a "Dynamic Sensitivity Analysis" framework that quantifies transitions between brain states in terms of stimulation ability to rebalance spatio-temporal brain activity towards a target state such as healthy brain dynamics. In practice, it means building a whole-brain model fitted to the spatio-temporal description of brain dynamics, and applying systematic stimulations in-silico to assess the optimal strategy to drive brain dynamics towards a target state. Further, we show how Dynamic Sensitivity Analysis extends to various brain stimulation paradigms, ultimately contributing to improving the efficacy of personalised clinical interventions.

Treatment efficacy of tDCS and predictors of treatment response in patients with post-traumatic stress disorder.

BACKGROUND: Although transcranial direct stimulation (tDCS) has been proposed as an alternative treatment option for various psychiatric disorders, there is inconsistent information regarding the treatment effects of tDCS for patients with post-traumatic stress disorder (PTSD). This study aimed to investigate the tDCS efficacy and identify predictors of treatment response to tDCS in patients with PTSD. METHOD: Fifty-one patients received 10 sessions of tDCS involving the position of the anode over the F3 area and cathode over the F4 as a condition of 2.0 mA and 20 min duration. Digit span test and 10 questionnaires (Clinician-Administered PTSD Scale (CAPS), Cognitive Emotion Regulation Questionnaire (CERQ), Multidimensional Experiential Avoidance Questionnaire (MEAQ), etc.) were used to measure tDCS effects on PTSD symptoms and identify predictors of response to tDCS. RESULTS: 1) 50.9 % of patients had a significant reduction in the frequency and severity of PTSD symptoms, 2) PTSD-related symptoms such as depression, anxiety, rumination, and quality of life were significantly improved, 3) baseline scores on rumination and digit span test significantly predicted treatment response to tDCS. LIMITATIONS: This study was open design without a sham control group. Also, the patients' medications were not controlled. CONCLUSION: This study highlighted the efficacy of frontal tDCS for the treatment of patients with PTSD and identified rumination and digit span as favorable predictive factors for the outcomes of tDCS.

The minimally conscious state: an analysis of current clinical trials registered in ClinicalTrials.gov.

The minimally conscious state (MCS) is a disorder of consciousness described in recent years for patients who have behavioral responses to stimuli that do not meet the classification of chronic vegetative state (CVS) or coma. This distinction is valuable in clinical practice, as minimally conscious patients may require different treatments and may have different long-term outcomes when compared to vegetative states or coma. In this report, we analyzed the ClinicalTrials.gov database to systematically assess all clinical trials regarding MCS. The database was queried using the term "minimally conscious state" in the "condition or disease" search parameter. Of the studies identified, those that had suspended, terminated, or otherwise unknown statuses were excluded. In total, 41 studies were analyzed. The included studies were initiated between 2008 and 2020, with the majority (63%) beginning in 2015 or later. Of the primary intervention modalities included, 15 (37%) evaluated stimulation modalities such as transcranial magnetic stimulation, transcranial direct current stimulation, implantable neurostimulation, vagus nerve stimulation, focused ultrasound and median nerve stimulation. Additionally, 5 (12%) used some form of behavioral therapy. A total of 4 (10%) studies involved pharmaceutical intervention, including dopamine agonists, analgesics and sedatives. Finally, 4 (10%) studies sought to determine the validity of current diagnostic methods and systems used to assess the status of patients in MCSs. Since the definition and criteria for CVS and MCS have been established, these two conditions remain closely associated despite evidence of different patient outcomes and treatment options. Many clinical trials are underway assessing interventions with stimulation. However, the trials are lacking with respect to diagnostic methods and pharmaceutical treatment.

Task-Related Hemodynamic Changes Induced by High-Definition Transcranial Direct Current Stimulation in Chronic Stroke Patients: An Uncontrolled Pilot fNIRS Study.

High-definition transcranial direct current stimulation (HD-tDCS) has recently been proposed as a tDCS approach that can be used on a specific cortical region without causing undesirable stimulation effects. In this uncontrolled pilot study, the cortical hemodynamic changes caused by HD-tDCS applied over the ipsilesional motor cortical area were investigated in 26 stroke patients. HD-tDCS using one anodal and four cathodal electrodes at 1 mA was administered for 20 min to C3 or C4 in four daily sessions. Cortical activation was measured as changes in oxyhemoglobin (oxyHb) concentration, as found using a functional near-infrared spectroscopy (fNIRS) system during the finger tapping task (FTT) with the affected hand before and after HD-tDCS. Motor-evoked potential and upper extremity functions were also measured before (T0) and after the intervention (T1). A group statistical parametric mapping analysis showed that the oxyHb concentration increased during the FTT in both the affected and unaffected hemispheres before HD-tDCS. After HD-tDCS, the oxyHb concentration increased only in the affected hemisphere. In a time series analysis, the mean and integral oxyHb concentration during the FTT showed a noticeable decrease in the channel closest to the hand motor hotspot (hMHS) in the affected hemisphere after HD-tDCS compared with before HD-tDCS, in accordance with an improvement in the function of the affected upper extremity. These results suggest that HD-tDCS might be helpful to rebalance interhemispheric cortical activity and to reduce the hemodynamic burden on the affected hemisphere during hand motor tasks. Noticeable changes in the area adjacent to the affected hMHS may imply that personalized HD-tDCS electrode placement is needed to match each patient's individual hMHS location.

Cerebellar Transcranial Direct Current Stimulation Reconfigures Brain Networks Involved in Motor Execution and Mental Imagery.

Transcranial direct current stimulation (tDCS) is growingly applied to the cerebellum to modulate the activity of cerebellar circuitry, affecting both motor and cognitive performances in a polarity-specific manner. The remote effects of tDCS are mediated in particular via the dentato-thalamo-cortical pathway. We showed recently that tDCS of the cerebellum exerts dynamic effects on resting state networks. We tested the neural hypothesis that tDCS reconfigurates brain networks involved in motor execution (ME) and motor mental imagery (MMI). We combined tDCS applied over the right cerebellum and fMRI to investigate tDCS-induced reconfiguration of ME- and MMI-related networks using a randomized, sham-controlled design in 21 right-handed healthy volunteers. Subjects were instructed to draw circles at comfortable speed and to imagine drawing circles with their right hand. fMRI data were recorded after real anodal stimulation (1.5 mA, 20 min) or sham tDCS. Real tDCS compared with SHAM specifically reconfigurated the functional links between the main intrinsic connected networks, especially the central executive network, in relation with lobule VII, and the salience network. The right cerebellum mainly influenced prefrontal and anterior cingulate areas in both tasks, and improved the overt motor performance. During MMI, the cerebellum also modulated the default-mode network and associative visual areas. These results demonstrate that tDCS of the cerebellum represents a novel tool to modulate cognitive brain networks controlling motor execution and mental imagery, tuning the activity of remote cortical regions. This approach opens novel doors for the non-invasive neuromodulation of disorders involving cerebello-thalamo-cortical paths.

Cerebellar transcranial direct current stimulation reconfigurates static and dynamic functional connectivity of the resting-state networks.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the cerebellum dynamically modulates cerebello-thalamo-cortical excitability in a polarity-specific manner during motor, visuo- motor and cognitive tasks. It remains to be established whether tDCS of the cerebellum impact also on resting-state intrinsically connected networks (ICNs). Such impact would open novel research and therapeutical doors for the neuromodulation of ICNs in human. METHOD: We combined tDCS applied over the right cerebellum and fMRI to investigate tDCS- induced resting-state intrinsic functional reconfiguration, using a randomized, sham-controlled design. fMRI data were recorded both before and after real anodal stimulation (2 mA, 20 min) or sham tDCS in 12 right-handed healthy volunteers. We resorted to a region-of-interest static correlational analysis and to a sliding window analysis to assess temporal variations in resting state FC between the cerebellar lobule VII and nodes of the main ICNs. RESULTS: After real tDCS and compared with sham tDCS, functional changes were observed between the cerebellum and ICNs. Static FC showed enhanced or decreased correlation between cerebellum and brain areas belonging to visual, default-mode (DMN), sensorimotor and salience networks (SN) (p-corrected < 0.05). The temporal variability (TV) of BOLD signal was significantly modified after tDCS displaying in particular a lesser TV between the whole lobule VII and DMN and central executive network and a greater TV between crus 2 and SN. Static and dynamic FC was also modified between cerebellar lobuli. CONCLUSION: These results demonstrate short- and long-range static and majorly dynamic effects of tDCS stimulation of the cerebellum affecting distinct resting-state ICNs, as well as intracerebellar functional connectivity, so that tDCS of the cerebellum appears as a non-invasive tool reconfigurating the dynamics of ICNs.

Effect of Modulating DLPFC Activity on Antisocial and Prosocial Behavior: Evidence From a tDCS Study.

Antisocial behavior and prosocial behavior in the condition of inequality have long been observed in daily life. Understanding the neurological mechanisms and brain regions associated with antisocial and prosocial behavior and the development of new interventions are important for reducing violence and inequality. Fortunately, neurocognitive research and brain imaging research have found a correlation between antisocial or prosocial behavior and the prefrontal cortex. Recent brain stimulation research adopting transcranial direct current stimulation or transcranial magnetic stimulation has shown a causal relationship between brain regions and behaviors, but the findings are mixed. In the present study, we aimed to study whether stimulation of the DLPFC can change participants' antisocial and prosocial behavior in the condition of inequality. We integrated antisocial and prosocial behavior in a unified paradigm. Based on this paradigm, we discussed costly and cost-free antisocial and prosocial behavior. In addition, we also measured participants' disadvantageous and advantageous inequality aversion. The current study revealed an asymmetric effect of bilateral stimulation over the DLPFC on costly antisocial behavior, while such an effect of antisocial behavior without cost and prosocial behavior with and without cost were not observed. Moreover, costly antisocial behavior exhibited by men increased after receiving right anodal/left cathodal stimulation and decreased after receiving right cathodal anodal/left anodal stimulation compared with the behavior observed under sham stimulation. However, subjects' inequality aversion was not influenced by tDCS.

Effect of Modulating Activity in the Right DLPFC on Revenge Behavior: Evidence From a Noninvasive Brain Stimulation Investigation.

Revenge is common in our daily lives, and people feel good when engaging in revenge behavior. However, revenge behavior is a complex process and remains somewhat of a puzzle of human behavior. Neuroimaging studies have revealed that revenge behaviors are associated with activation of a neural network containing the anterior cingulate cortex, ventral striatum, inferior frontal gyrus, and dorsolateral prefrontal cortex (DLPFC). Recent brain stimulation research using transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation has shown a causal relationship between brain regions and revenge behaviors, but the findings have been mixed. In the present study, we aimed to study whether stimulation in the DLPFC can change participants' revenge behavior in conditions where participants' wealth was taken away in different ways. We adapted the moonlighting game and designed a new paradigm. Our study revealed that revenge behavior increased following activation in the right DLPFC, suggesting that the right DLPFC plays an important role in overriding self-interest and retaliation. In addition, our results revealed that the right DLPFC is crucial in revenge behavior related to the motivation of invasion.

Bilateral Transcranial Direct Stimulation Over the Primary Motor Cortex Alters Motor Modularity of Multiple Muscles.

Transcranial direct current stimulation (tDCS) over the primary motor cortex (M1) has been demonstrated to modulate the motor performance of both healthy individuals and patients with neuromuscular disorders. However, the effect of tDCS on motor control of multiple muscles, which is a prerequisite to change in motor performance, is currently unknown. Using dimensionality reduction analysis, we investigated whether bilateral tDCS over M1 modulates the coordinated activity of 12 muscles. Fifteen healthy men participated in this randomized, double-blind crossover study. Each participant received a 20-min sham and 2-mA stimulation bilaterally over M1 (anode on the right M1 and cathode on the left M1), with a minimum washout period of 4 days. Muscle activation and end-point kinematics were evaluated during a task where participants reached out to a marked target with non-dominant hand as fast as possible, before and immediately after tDCS application. We found decreased similarity in motor modularity and significant changes in muscle activation in a specific motor module, particularly when reaching out to a target placed within arm's length and improved smoothness index of movement only following 2-mA stimulation. These findings indicate that clinicians and researchers need to consider the simultaneous effect of bilateral tDCS over M1 on multiple muscles when they establish tDCS protocol to change in motor performance of patients with neuromuscular deficits.

[Interest of transcranial stimulation in pelvic and perineal disorders]. / Intérêt de la stimulation transcrânienne dans les troubles pelvi-périnéaux.

OBJECTIVE: The aim of this article was to describe the diagnostic and therapeutic value of transcranial stimulation in pelvic and perineal disorders. METHODS: A literature review (Medline database and Google scholar) with no time limit was performed using keywords: "transcranial direct stimulation", "transcranial magnetic stimulation", "neurogenic bladder", "urinary incontinence", "Parkinson disease", "multiple sclerosis", "stroke", "muscle spasticity", "pelvic pain", "visceral pain". RESULTS: Twelve articles have been selected. Transcranial magnetic or electrical stimulation is a noninvasive neuromodulation technique widely used to establish brain maps to highlight causal relationships between brain and function. Regarding pelvic-perineal disorders, repeated transcranial stimulation has shown significant effects for the treatment of overactive bladder in Parkinson's disease (P<0.05) and multiple sclerosis, but also for the treatment of refractory chronic pelvic pain (P=0.026). Finally, therapeutic effects have also been demonstrated in irritable bowel syndrome. No evidence of efficacy was found on genito-sexual disorders. CONCLUSION: Data from the literature suggest that transcranial stimulation is a noninvasive treatment that may have a role in the management of pelvic and perineal disorders. Its promising field of action would require prospective and randomized studies on a larger scale.

Cerebellar Cortex as a Therapeutic Target for Neurostimulation.

Non-invasive stimulation of the cerebellum is growingly applied both in the clinic and in research settings to modulate the activities of cerebello-cerebral loops. The anatomical location of the cerebellum, the high responsiveness of the cerebellar cortex to magnetic/electrical stimuli, and the implication of the cerebellum in numerous cerebello-cerebral networks make the cerebellum an ideal target for investigations and therapeutic purposes. In this mini-review, we discuss the potentials of cerebellar neuromodulation in major brain disorders in order to encourage large-scale sham-controlled research and explore this therapeutic aid further.

After-effects of anodal transcranial direct current stimulation on the excitability of the motor cortex in rats.

PURPOSE: Transcranial direct current stimulation (tDCS) is increasingly seen as a useful tool for noninvasive cortical neuromodulation. A number of studies in humans have shown that when tDCS is applied to the motor cortex it can modulate cortical excitability. It is especially interesting to note that when applied with sufficient duration and intensity, tDCS can enable long-lasting neuroplastic effects. However, the mechanism by which tDCS exerts its effects on the cortex is not fully understood. We investigated the effects of anodal tDCS under urethane anesthesia on field potentials in in vivo rats. METHODS: These were measured on the skull over the right motor cortex of rats immediately after stimulating the left corpus callosum. RESULTS: Evoked field potentials in the motor cortex were gradually increased for more than one hour after anodal tDCS. To induce these long-lasting effects, a sufficient duration of stimulation (20 minutes or more) was found to may be required rather than high stimulation intensity. CONCLUSION: We propose that anodal tDCS with a sufficient duration of stimulation may modulate transcallosal plasticity.

Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury.

There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. This article is part of a Special Issue entitled SI:Brain injury and recovery.

The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients.

BACKGROUND AND PURPOSE: To investigate whether transcranial direct-current stimulation (tDCS) can improve cognition in stroke patients. METHODS: Forty-five stroke patients (20 males and 25 females, average age: 62.7 years) with cognitive dysfunction were included in this prospective, double-blinded, randomized case-control study. All patients were right-handed and the mean elapsed time after stroke was 39.3 days. Three different treatments groups were used: (1) anodal stimulation of the left anterior temporal lobe, (2) anodal stimulation of the right anterior temporal lobe, and (3) sham stimulation. tDCS was delivered for 30 minutes at 2 mA with 25 cm(2) electrodes, five times/week, for a total of 3 weeks, using a Phoresor II Auto Model PM 850 (IOMED(®)). The evaluation of cognitive impairment was based on a Computerized Neuropsychological Test (CNT), Korean Mini-Mental State Examination (K-MMSE). The Korean version of the Modified Barthel Index (K-MBI) was used to assess activities of daily living functionality. These evaluations were conducted in all patients before and after treatment. RESULTS: Each group included 15 patients. Pre-treatment evaluation showed no significant differences between the three groups for any of the parameters. There was significant improvement in the verbal learning test on the CNT in the left anodal stimulation group (P < 0.05). There were, however, no significant differences in the K-MMSE or K-MBI scores among the three groups. CONCLUSIONS: These results demonstrated the beneficial effects of anodal tDCS on memory function. Thus, tDCS can successfully be used as a treatment modality for patients with cognitive dysfunction after stroke.

The Effects of Transcranial Direct-Current Stimulation on Cognition in Stroke Patients / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: To investigate whether transcranial direct-current stimulation (tDCS) can improve cognition in stroke patients. METHODS: Forty-five stroke patients (20 males and 25 females, average age: 62.7 years) with cognitive dysfunction were included in this prospective, double-blinded, randomized case-control study. All patients were right-handed and the mean elapsed time after stroke was 39.3 days. Three different treatments groups were used: (1) anodal stimulation of the left anterior temporal lobe, (2) anodal stimulation of the right anterior temporal lobe, and (3) sham stimulation. tDCS was delivered for 30 minutes at 2 mA with 25 cm2 electrodes, five times/week, for a total of 3 weeks, using a Phoresor II Auto Model PM 850 (IOMED(R)). The evaluation of cognitive impairment was based on a Computerized Neuropsychological Test (CNT), Korean Mini-Mental State Examination (K-MMSE). The Korean version of the Modified Barthel Index (K-MBI) was used to assess activities of daily living functionality. These evaluations were conducted in all patients before and after treatment. RESULTS: Each group included 15 patients. Pre-treatment evaluation showed no significant differences between the three groups for any of the parameters. There was significant improvement in the verbal learning test on the CNT in the left anodal stimulation group (P < 0.05). There were, however, no significant differences in the K-MMSE or K-MBI scores among the three groups. CONCLUSIONS: These results demonstrated the beneficial effects of anodal tDCS on memory function. Thus, tDCS can successfully be used as a treatment modality for patients with cognitive dysfunction after stroke.