Application Of Non-invasive Brain Stimulation Research Articles

A 3D-Printed helmet for precise and repeatable neuromodulation targeting in awake non-human primates

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

Dual activation of the reward system using sensory-based intervention and non-invasive brain stimulation in depression: A way to move forward?

Major depressive disorder (MDD) is characterized by symptoms such as low mood and anhedonia related to altered dopamine transmission in the reward system. In addition, approximately one-third of patients with MDD develop treatment-resistance to the pharmaceutical treatment, necessitating alternative therapeutic strategies. While non-invasive brain stimulation (NIBS) holds promise for improving treatment-resistant MDD, remission rates are still relatively modest. It has been demonstrated that NIBS effects not only depend of the stimulation properties but are also “state-dependent”, meaning that when patients engage in specific tasks or states that involve similar neural networks targeted by NIBS, a synergistic and additive therapeutic effect may occur. Therefore, a recent strategy to improve treatment outcomes is to combine NIBS with other types of interventions targeting the same network.Numerous studies have demonstrated a clinically meaningful antidepressant effects when NIBS are combined with psychotherapy, cognitive-behavioral approaches, or cognitive remediation programs for patients with MDD. However, widespread use of this combination may be hindered by barriers such as cost and accessibility for both clinicians and patients. Alternatively, sensory-based interventions alone (such as music therapy or exposure to specific odors) represent a promising, easy-to-implement, cost-effective and innovative therapeutic approach for MDD. These interventions are known to activate the meso-cortico-limbic system, triggering dopamine release, or modulating dopaminergic tone in various brain structures, similar to what is observed with NIBS. In this paper, the hypothesis that combining sensory-based interventions with NIBS is a compelling approach to alleviating MDD symptoms is tested. Specifically, it is hypothesized that the dual activation of the reward system induced by sensory-based interventions, combined with the concurrent application of NIBS, will result in a synergistic effect, ultimately leading to enhanced alleviation of MDD symptoms.

Direct Current Stimulation over the Primary Motor Cortex, Cerebellum, and Spinal Cord to Modulate Balance Performance: A Randomized Placebo-Controlled Trial.

Existing applications of non-invasive brain stimulation in the modulation of balance ability are focused on the primary motor cortex (M1). It is conceivable that other brain and spinal cord areas may be comparable or more promising targets in this regard. This study compares transcranial direct current stimulation (tDCS) over (i) the M1, (ii) the cerebellum, and (iii) trans-spinal direct current stimulation (tsDCS) in the modulation of balance ability. Forty-two sports students were randomized in this placebo-controlled study. Twenty minutes of anodal 1.5 mA t/tsDCS over (i) the M1, (ii) the cerebellum, and (iii) the spinal cord, as well as (iv) sham tDCS were applied to each subject. The Y Balance Test, Single Leg Landing Test, and Single Leg Squat Test were performed prior to and after each intervention. The Y Balance Test showed significant improvement after real stimulation of each region compared to sham stimulation. While tsDCS supported the balance ability of both legs, M1 and cerebellar tDCS supported right leg stand only. No significant differences were found in the Single Leg Landing Test and the Single Leg Squat Test. Our data encourage the application of DCS over the cerebellum and spinal cord (in addition to the M1 region) in supporting balance control. Future research should investigate and compare the effects of different stimulation protocols (anodal or cathodal direct current stimulation (DCS), alternating current stimulation (ACS), high-definition DCS/ACS, closed-loop ACS) over these regions in healthy people and examine the potential of these approaches in the neurorehabilitation.

Application of Noninvasive Brain Stimulation for Sleep Quality Enhancement and Cognitive Improvement.

Sleep is a fundamental process for maintaining our physical and mental health by adjusting brain homeostasis and repairing axons to refresh memories. Due to its essentiality, sleep disorders and insufficiency can cause both physiological and behavioral risks. This report diverges from traditional medical treatments and focuses mainly on physiotherapy-based neuroregulatory techniques for sleep treatment. Noninvasive brain stimulation (NiBS) techniques have been developed to enhance patients' sleep and memory, including transcranial electrical stimulation (tES), transcranial magnetic stimulation (TMS), closed-loop stimulation, and Slow-wave sleep (SWS) brain-wave music. These techniques not only facilitate sleep but also improve and manipulate patients' cognitive performance in areas such as addiction, post-traumatic stress disorder (PTSD), and Alzheimer's Disease (AD). However, brain stimulation during sleep has not yet been widely applied due to inconvenience of the large machines for long-term usage. Future research and engineering designs should focus on developing portable devices to restore sleep quality and cognitive performance. Insomnia can have multiple and interactive causes, including environmental, psychological, and physiological factors. Thus, case-by-case analyses are required, and neuroregulatory techniques play a supportive role in assisting sleep. To cure sleep problems completely, a combination of psychotherapy, medical treatments, and environmental adjustments may be necessary. There are still many puzzles to be solved in the study of sleep problems, and neurostimulation therapy provides new ideas for solving sleep problems and studying sleep behavior.

MNI2CPC: A probabilistic cortex-to-scalp mapping for non-invasive brain stimulation targeting

BackgroundSynthesis of neural imaging information from many studies is valuable for identifying stable cortical targets for non-invasive brain stimulation (NIBS). Typically, these targets are specified in Montreal Neurological Institute (MNI) standard brain space. However, in practical NIBS applications, localizing MNI cortical targets often relies on the International 10–20 system or heuristic scalp approaches, which often lacks precision or applies only to specific targets. Objective/hypothesisWe aim to establish a probabilistic mapping from any cortical target in MNI space to continuous proportional coordinate (CPC) standard scalp space (MNI2CPC) and assess the performance of this mapping for NIBS targeting. MethodsThe MNI2CPC mapping was calculated based on a large MRI dataset (n = 114). Its targeting error was evaluated via cross-individual validation using a leave-one-out approach, as well as through independent validation across race (n = 27) and across patient (n = 58) cohorts. ResultsThe cross-individual validation demonstrated targeting errors of 4.03 ± 0.69 mm on the scalp and 3.30 ± 0.59 mm in the cortex. For independent cohorts, targeting errors were 4.71 ± 0.81 mm (scalp) and 3.85 ± 0.64 mm (cortex) across race, and 4.66 ± 0.77 mm (scalp) and 3.77 ± 0.61 mm (cortex) across patient. We publish a free online tool to enable querying of the CPC coordinate for any given MNI cortical target. The resulting CPC coordinates enable rapid and accurate manual localization on the scalp in a user-friendly manner. ConclusionsThe MNI2CPC mapping developed in this study allows for manual localization of any MNI cortical target, which improves the accessibility and ease of application of NIBS in diverse settings.

Non-Invasive Brain Stimulation and Sex/Polypeptide Hormones in Reciprocal Interactions: A Systematic Review.

A better understanding of interindividual differences and the development of targeted therapies is one of the major challenges of modern medicine. The sex of a person plays a crucial role in this regard. This systematic review aimed to summarise and analyse available evidence on the mutual interactions between non-invasive brain stimulation and sex/polypeptide hormones. The PubMed database was searched from its inception to 31 March 2023, for (i) studies that investigated the impact of sex and/or polypeptide hormones on the effects induced by non-invasive brain stimulation, or (ii) studies that investigated non-invasive brain stimulation in the modulation of sex and/or polypeptide hormones. Eighteen studies (319 healthy and 96 disabled participants) were included. Most studies focused on female sex hormone levels during the menstrual cycle. The later follicular phase is associated with a weak between hemispheric and intracortical inhibition, strong intracortical facilitation, and high stimulation-induced neural and behavioural changes. The opposite effects are observed during the luteal phase. In addition, the participant's sex, presence and/or absence of real ovulation and increase in oestradiol level by chorionic gonadotropin injection influence the stimulation-induced neurophysiological and behavioural effects. In Parkinson's disease and consciousness disorders, the repetitive application of non-invasive brain stimulation increases oestradiol and dehydroepiandrosterone levels and reduces disability. To date, male hormones have not been sufficiently included in these studies. Here, we show that the sex and/or polypeptide hormones and non-invasive brain stimulation methods are in reciprocal interactions. This may be used to create a more effective and individualised approach for healthy individuals and individuals with disabilities.

Improved brain stimulation targeting by optimising image acquisition parameters

Functional connectivity analysis from rs-fMRI data has been used for determining cortical targets in therapeutic applications of non-invasive brain stimulation using transcranial magnetic stimulation (TMS). Reliable connectivity measures are therefore essential for every rs-fMRI-based TMS targeting approach. Here, we examine the effect of echo time (TE) on the reproducibility and spatial variability of resting-state connectivity measures. We acquired multiple runs of single-echo fMRI data with either short (TE = 30 ms) or long (TE = 38 ms) echo time to investigate inter-run spatial reproducibility of a clinically relevant functional connectivity map, i.e., originating from the sgACC. We find that connectivity maps obtained from TE = 38 ms rs-fMRI data are significantly more reliable than those obtained from TE = 30 ms data sets. Our results clearly show that optimizing sequence parameters can be beneficial for ensuring high-reliability resting-state acquisition protocols to be used for TMS targeting. The differences between reliability in connectivity measures for different TEs could inform future clinical research in optimising MR sequences.

Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients.

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.

Application of non-invasive brain stimulation with the use of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in the treatment of dysphagia following an ischemic stroke – analysis of research reports

Stroke is one of the significant problems and causes of death, in particular in highly developed countries. It is also the most common cause of dysphagia. This study is devoted to the analysis of publications from the last decade concerning research on the use of non-invasive brain stimulation (TMS, tDCS) in the treatment of dysphagia following an ischemic stroke. The following databases were searched for publications: PUBMED, Polish Scientific Journals Database, EBSCO, ScienceDirect. Out of 358 articles found, only two met all the inclusion conditions. The studies discussed in this article included patients who had their first unilateral ischemic stroke, followed by dysphagia. Findings from pilot studies on the effectiveness of the use of tDCS in the treatment of dysphagia following an ischemic stroke were analysed. Fourteen patients aged 50-92 were randomly assigned to two groups. The study group was treated with anodic stimulation, and the control group with sham brain stimulation. The results showed that patients in the study group obtained a statistically significant result, indicating an improvement in the swallowing function as measured by the Dysphagia Score and Severity Scale. The above data may indicate the effectiveness of the use of tDCS in the treatment of dysphagia. Fifty patients were qualified for the research on the effectiveness of rTMS in the treatment of dysphagia. Three groups were created: the first group treated with high frequency rTMS, where patients received rTMS stimulation – 3Hz; the second group with low frequency rTMS – 1Hz; and the control group. The effectiveness of the therapy used was assessed on the fifth day and after 1, 2 and 3 months. After 5 days the groups where active rTMS stimulation was used showed greater improvement in the swallowing function compared to the sham stimulation group. Improved results in the Standardized Swallowing Assessment were also recorded after 3 months in the 1Hz and 3Hz groups, but this did not apply to the control group. In three groups, the results of the water swallow test and the degree of dysphagia improved after 3 months. This analysis shows that non-invasive brain stimulation using tDCS and rTMS in the treatment of dysphagia is associated with improved swallowing function. However, the small number of studies conducted in this area does not allow for extrapolation of their results.

Non-invasive brain stimulation for osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease, the prevalence of OA is increasing, and the elderly are the most common in patients with OA. OA has a severe impact on the daily life of patients, this increases the demand for treatment of OA. In recent years, the application of non-invasive brain stimulation (NIBS) has attracted extensive attention. It has been confirmed that NIBS plays an important role in regulating cortical excitability and oscillatory rhythm in specific brain regions. In this review, we summarized the therapeutic effects and mechanisms of different NIBS techniques in OA, clarified the potential of NIBS as a treatment choice for OA, and provided prospects for further research in the future.

Remotely monitored transcranial direct current stimulation in pediatric cerebral palsy: open label trial protocol

BackgroundPediatric applications of non-invasive brain stimulation using transcranial direct current stimulation (tDCS) have demonstrated its safety with few adverse events reported. Remotely monitored tDCS, as an adjuvant intervention to rehabilitation, may improve quality of life for children with cerebral palsy (CP) through motor function improvements, reduced treatment costs, and increased access to tDCS therapies. Our group previously evaluated the feasibility of a remotely monitored mock tDCS setup in which families and children successfully demonstrated the ability to follow tDCS instructional guidance.Methods and designHere, we designed a protocol to investigate the feasibility, safety, and tolerability of at-home active transcranial direct current stimulation in children with CP with synchronous supervision from laboratory investigators. Ten participants will be recruited to participate in the study for 5 consecutive days with the following sessions: tDCS setup practice on day 1, sham tDCS on day 2, and active tDCS on days 3-5. Sham stimulation will consist of an initial 30-second ramp up to 1.5 mA stimulation followed by a 30-second ramp down. Active stimulation will be delivered at 1.0 - 1.5 mA for 20 minutes and adjusted based on child tolerance. Feasibility will be evaluated via photographs of montage setup and the quality of stimulation delivery. Safety and tolerability will be assessed through an adverse events survey, the Box and Blocks Test (BBT) motor assessment, and a setup ease/comfort survey.DiscussionWe expect synchronous supervision of at-home teleneuromodulation to be tolerable and safe with increasing stimulation quality over repeated sessions when following a tDCS setup previously determined to be feasible. The findings will provide opportunity for larger clinical trials exploring efficacy and illuminate the potential of remotely monitored tDCS in combination with rehabilitation interventions as a means of pediatric neurorehabilitation. This will demonstrate the value of greater accessibility of non-invasive brain stimulation interventions and ultimately offer the potential to improve care and quality of life for children and families with CP.Trial RegistrationOctober 8, 2021(https://clinicaltrials.gov/ct2/show/NCT05071586)

Effects of Non-Invasive Brain Stimulation on Post-Stroke Spasticity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

In recent years, the potential of non-invasive brain stimulation (NIBS) for the therapeutic effect of post-stroke spasticity has been explored. There are various NIBS methods depending on the stimulation modality, site and parameters. The purpose of this study is to evaluate the efficacy of NIBS on spasticity in patients after stroke. This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PUBMED (MEDLINE), Web of Science, Cochrane Library and Excerpta Medica Database (EMBASE) were searched for all randomized controlled trials (RCTs) published before December 2021. Two independent researchers screened relevant articles and extracted data. This meta-analysis included 14 articles, and all included articles included 18 RCT datasets. The results showed that repetitive transcranial magnetic stimulation (rTMS) (MD = −0.40, [95% CI]: −0.56 to −0.25, p < 0.01) had a significant effect on improving spasticity, in which low-frequency rTMS (LF-rTMS) (MD = −0.51, [95% CI]: −0.78 to −0.24, p < 0.01) and stimulation of the unaffected hemisphere (MD = −0.58, [95% CI]: −0.80 to −0.36, p < 0.01) were beneficial on Modified Ashworth Scale (MAS) in patients with post-stroke spasticity. Transcranial direct current stimulation (tDCS) (MD = −0.65, [95% CI]: −1.07 to −0.22, p < 0.01) also had a significant impact on post-stroke rehabilitation, with anodal stimulation (MD = −0.74, [95% CI]: −1.35 to −0.13, p < 0.05) being more effective in improving spasticity in patients. This meta-analysis revealed moderate evidence that NIBS reduces spasticity after stroke and may promote recovery in stroke survivors. Future studies investigating the mechanisms of NIBS in addressing spasticity are warranted to further support the clinical application of NIBS in post-stroke spasticity.

Sleep-dependent upscaled excitability, saturated neuroplasticity, and modulated cognition in the human brain.

Sleep strongly affects synaptic strength, making it critical for cognition, especially learning and memory formation. Whether and how sleep deprivation modulates human brain physiology and cognition is not well understood. Here we examined how overnight sleep deprivation vs overnight sufficient sleep affects (a) cortical excitability, measured by transcranial magnetic stimulation, (b) inducibility of long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity via transcranial direct current stimulation (tDCS), and (c) learning, memory, and attention. The results suggest that sleep deprivation upscales cortical excitability due to enhanced glutamate-related cortical facilitation and decreases and/or reverses GABAergic cortical inhibition. Furthermore, tDCS-induced LTP-like plasticity (anodal) abolishes while the inhibitory LTD-like plasticity (cathodal) converts to excitatory LTP-like plasticity under sleep deprivation. This is associated with increased EEG theta oscillations due to sleep pressure. Finally, we show that learning and memory formation, behavioral counterparts of plasticity, and working memory and attention, which rely on cortical excitability, are impaired during sleep deprivation. Our data indicate that upscaled brain excitability and altered plasticity, due to sleep deprivation, are associated with impaired cognitive performance. Besides showing how brain physiology and cognition undergo changes (from neurophysiology to higher-order cognition) under sleep pressure, the findings have implications for variability and optimal application of noninvasive brain stimulation.

Perspectives on Rehabilitation Using Non-invasive Brain Stimulation Based on Second-Person Neuroscience of Teaching-Learning Interactions.

Recent advances in second-person neuroscience have allowed the underlying neural mechanisms involved in teaching-learning interactions to be better understood. Teaching is not merely a one-way transfer of information from teacher to student; it is a complex interaction that requires metacognitive and mentalizing skills to understand others’ intentions and integrate information regarding oneself and others. Physiotherapy involving therapists instructing patients on how to improve their motor skills is a clinical field in which teaching-learning interactions play a central role. Accumulating evidence suggests that non-invasive brain stimulation (NIBS) modulates cognitive functions; however, NIBS approaches to teaching-learning interactions are yet to be utilized in rehabilitation. In this review, I evaluate the present research into NIBS and its role in enhancing metacognitive and mentalizing abilities; I then review hyperscanning studies of teaching-learning interactions and explore the potential clinical applications of NIBS in rehabilitation. Dual-brain stimulation using NIBS has been developed based on findings of brain-to-brain synchrony in hyperscanning studies, and it is delivered simultaneously to two individuals to increase inter-brain synchronized oscillations at the stimulated frequency. Artificial induction of brain-to-brain synchrony has the potential to promote instruction-based learning. The brain-to-brain interface, which induces inter-brain synchronization by adjusting the patient’s brain activity, using NIBS, to the therapist’s brain activity, could have a positive effect on both therapist-patient interactions and rehabilitation outcomes. NIBS based on second-person neuroscience has the potential to serve as a useful addition to the current neuroscientific methods used in complementary interventions for rehabilitation.

Chapter 30 - Multiple sclerosis: Inflammation, autoimmunity and plasticity

In recent years, experimental studies have clarified that immune system influences the functioning of the central nervous system (CNS) in both physiologic and pathologic conditions. The neuro-immune crosstalk plays a crucial role in neuronal development and may be critically involved in mediating CNS response to neuronal damage. Multiple sclerosis (MS) represents a good model to investigate how the immune system regulates neuronal activity. Accordingly, a growing body of evidence has demonstrated that increased levels of pro-inflammatory mediators may significantly impact synaptic mechanisms, influencing overall neuronal excitability and synaptic plasticity expression. In this chapter, we provide an overview of preclinical data and clinical studies exploring synaptic functioning noninvasively with transcranial magnetic stimulation (TMS) in patients with MS. Moreover, we examine how inflammation-driven synaptic dysfunction could affect synaptic plasticity expression, negatively influencing the MS course. Contrasting CSF inflammation together with pharmacologic enhancement of synaptic plasticity and application of noninvasive brain stimulation, alone or in combination with rehabilitative treatments, could improve the clinical compensation and prevent the accumulating deterioration in MS.

Differences in electric field strength between clinical and non-clinical populations induced by prefrontal tDCS: A cross-diagnostic, individual MRI-based modeling study

IntroductionPrefrontal cortex (PFC) regions are promising targets for therapeutic applications of non-invasive brain stimulation, e.g. transcranial direct current stimulation (tDCS), which has been proposed as a novel intervention for major depressive disorder (MDD) and negative symptoms of schizophrenia (SCZ). However, the effects of tDCS vary inter-individually, and dose–response relationships have not been established. Stimulation parameters are often tested in healthy subjects and transferred to clinical populations. The current study investigates the variability of individual MRI-based electric fields (e-fields) of standard bifrontal tDCS across individual subjects and diagnoses. MethodThe study included 74 subjects, i.e. 25 patients with MDD, 24 patients with SCZ, and 25 healthy controls (HC). Individual e-fields of a common tDCS protocol (i.e. 2 mA stimulation intensity, bifrontal anode-F3/cathode-F4 montage) were modeled by two investigators using SimNIBS (2.0.1) based on structural MRI scans. ResultOn a whole-brain level, the average e-field strength was significantly reduced in MDD and SCZ compared to HC, but MDD and SCZ did not differ significantly. Regions of interest (ROI) analysis for PFC subregions showed reduced e-fields in Sallet areas 8B and 9 for MDD and SCZ compared to HC, whereas there was again no difference between MDD and SCZ. Within groups, we generally observed high inter-individual variability of e-field intensities at a higher percentile of voxels. ConclusionMRI-based e-field modeling revealed significant differences in e-field strengths between clinical and non-clinical populations in addition to a general inter-individual variability. These findings support the notion that dose–response relationships for tDCS cannot be simply transferred from healthy to clinical cohorts and need to be individually established for clinical groups. In this respect, MRI-based e-field modeling may serve as a proxy for individualized dosing.

Personalised, image-guided, noninvasive brain stimulation in gliomas: Rationale, challenges and opportunities.

Malignant brain tumours are among the most aggressive human cancers, and despite intensive efforts made over the last decades, patients’ survival has scarcely improved. Recently, high-grade gliomas (HGG) have been found to be electrically integrated with healthy brain tissue, a communication that facilitates tumour mitosis and invasion. This link to neuronal activity has provided new insights into HGG pathophysiology and opened prospects for therapeutic interventions based on electrical modulation of neural and synaptic activity in the proximity of tumour cells, which could potentially slow tumour growth. Noninvasive brain stimulation (NiBS), a group of techniques used in research and clinical settings to safely modulate brain activity and plasticity via electromagnetic or electrical stimulation, represents an appealing class of interventions to characterise and target the electrical properties of tumour-neuron interactions. Beyond neuronal activity, NiBS may also modulate function of a range of substrates and dynamics that locally interacts with HGG (e.g., vascular architecture, perfusion and blood-brain barrier permeability). Here we discuss emerging applications of NiBS in patients with brain tumours, covering potential mechanisms of action at both cellular, regional, network and whole-brain levels, also offering a conceptual roadmap for future research to prolong survival or promote wellbeing via personalised NiBS interventions.

Symposium (SY) Symposium 1: Non-invasive brain stimulation SY1.1. The effects of non-invasive brain stimulation and neuroplasticity

The recent development of non-invasive brain stimulation (NIBS) techniques, e.g. repetitive transcranial magnetic stimulation (rTMS) and transcranial direct/alternating current stimulation, are capable of suppress or enhance the brain excitability outlasting the period of stimulation for up to one hour or more. These protocols mimic the repetitive or constant electrical stimulation that is commonly used to change the synaptic efficiency forming the basic concept of synaptic plasticity mechanism in animal brain slices. Neuroplasticity or plasticity is generally believed as the fundamental mechanism of many aspects of brain function, e.g. learning, memory and recovery. Several lines of evidence based on pharmacological physiological and behavioural studies in humans and protein analysis in animals have confirmed that the after effects of NIBS are induced through a plasticity-like mechanisms. In this talk, the basic concept of plasticity will be introduced and how the effects of NIBS are linked to the mechanisms of plasticity will be explained. The audience will understand how NIBS works on the brain and how to design their applications of NIBS based on the knowledge.

Causal modulation of right hemisphere\xa0fronto-parietal phase synchrony with Transcranial Magnetic Stimulation during a conscious visual detection task

Correlational evidence in non-human primates has reported increases of fronto-parietal high-beta (22–30 Hz) synchrony during the top-down allocation of visuo-spatial attention. But may inter-regional synchronization at this specific frequency band provide a causal mechanism by which top-down attentional processes facilitate conscious visual perception? To address this question, we analyzed electroencephalographic (EEG) signals from a group of healthy participants who performed a conscious visual detection task while we delivered brief (4 pulses) rhythmic (30 Hz) or random bursts of Transcranial Magnetic Stimulation (TMS) to the right Frontal Eye Field (FEF) prior to the onset of a lateralized target. We report increases of inter-regional synchronization in the high-beta band (25–35 Hz) between the electrode closest to the stimulated region (the right FEF) and right parietal EEG leads, and increases of local inter-trial coherence within the same frequency band over bilateral parietal EEG contacts, both driven by rhythmic but not random TMS patterns. Such increases were accompained by improvements of conscious visual sensitivity for left visual targets in the rhythmic but not the random TMS condition. These outcomes suggest that high-beta inter-regional synchrony can be modulated non-invasively and that high-beta oscillatory activity across the right dorsal fronto-parietal network may contribute to the facilitation of conscious visual perception. Our work supports future applications of non-invasive brain stimulation to restore impaired visually-guided behaviors by operating on top-down attentional modulatory mechanisms.

From adults to pediatrics: A review noninvasive brain stimulation (NIBS) to facilitate recovery from brain injury.

Stroke is a major problem worldwide that impacts over 100 million adults and children annually. Rehabilitation therapy is the current standard of care to restore functional impairments post-stroke, however its effects are limited and many patients suffer persisting functional impairments and life-long disability. Noninvasive Brain Stimulation (NIBS) has emerged as a potential rehabilitation treatment option in both adults and children with brain injury. In the last decade, Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCS) and Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) have been investigated to improve motor recovery in adults post-stroke. These promising adult findings using NIBS, however, have yet to be widely translated to the area of pediatrics. The limited studies exploring NIBS in children have demonstrated safety, feasibility, and utility of stimulation-augmented rehabilitation. This chapter will describe the mechanism of NIBS therapy (cortical excitability, neuroplasticity) that underlies its use in stroke and motor function and how TMS, tDCS, and taVNS are applied in adult stroke treatment paradigms. We will then discuss the current state of NIBS in early pediatric brain injury and will provide insight regarding practical considerations and future applications of NIBS in pediatrics to make this promising treatment option a viable therapy in children.