Noninvasive Brain Stimulation Tool Research Articles

Transcranial photobiomodulation on the left inferior frontal gyrus enhances Mandarin Chinese L1 and L2 complex sentence processing performances

This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty.

Metaplastic neuromodulation via transcranial direct current stimulation has no effect on corticospinal excitability and neuromuscular fatigue

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation tool with potential for managing neuromuscular fatigue, possibly due to alterations in corticospinal excitability. However, inconsistencies in intra- and inter- individual variability responsiveness to tDCS limit its clinical use. Emerging evidence suggests harnessing homeostatic metaplasticity induced via tDCS may reduce variability and boost its outcomes, yet little is known regarding its influence on neuromuscular fatigue in healthy adults. We explored whether cathodal tDCS (ctDCS) prior to exercise combined with anodal tDCS (atDCS) could augment corticospinal excitability and attenuate neuromuscular fatigue. 15 young healthy adults (6 males, 22 ± 4 years) participated in four pseudo-randomised neuromodulation sessions: sham stimulation prior and during exercise, sham stimulation prior and atDCS during exercise, ctDCS prior and atDCS during exercise, ctDCS prior and sham stimulation during exercise. The exercise constituted an intermittent maximal voluntary contraction (MVC) of the right first dorsal interosseous (FDI) for 10 min. Neuromuscular fatigue was quantified as an attenuation in MVC force, while motor evoked potential (MEP) amplitude provided an assessment of corticospinal excitability. MEP amplitude increased during the fatiguing exercise, whilst across time, force decreased. There were no differences in MEP amplitudes or force between neuromodulation sessions. These outcomes highlight the ambiguity of harnessing metaplasticity to ameliorate neuromuscular fatigue in young healthy individuals.

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study

BackgroundTranscranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. Materials and methodsTMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. ResultsPatients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50–160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220–560 ms; 190–420 ms). Patients showed a reduction of both early (50–110 ms) gamma increase and later (180–230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. ConclusionOur findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics.

Transcranial random noise stimulation (tRNS) improves hot and cold executive functions in children with attention deficit-hyperactivity disorder (ADHD)

Children with attention deficit-hyperactivity disorder (ADHD) have impaired hot and cold executive functions, which is thought to be related to impaired ventromedial and dorsolateral prefrontal cortex (vmPFC and dlPFC) functions. The present study aimed to assess the impact concurrent stimulation of dlPFC and vmPFC through transcranial random noise stimulation (tRNS), a non-invasive brain stimulation tool which enhances cortical excitability via application of alternating sinusoidal currents with random frequencies and amplitudes over the respective target regions on hot and cold executive functions. Eighteen children with ADHD received real and sham tRNS over the left dlPFC and the right vmPFC in two sessions with one week interval. The participants performed Circle Tracing, Go/No-Go, Wisconsin Card Sorting, and Balloon Analogue Risk Tasks during stimulation in each session. The results showed improved ongoing inhibition, prepotent inhibition, working memory, and decision making, but not set-shifting performance, during real, as compared to sham stimulation. This indicates that simultaneous stimulation of the dlPFC and the vmPFC improves hot and cold executive functions in children with ADHD.

24.1 Is Repetitive Transcranial Magnetic Stimulation (rTMS) Ready for Clinical Use as a Treatment Tool for Mental Health Targets in Children and Youth With ASD?

ObjectivesRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation tool with potential for broad application in individuals with neuropsychiatric conditions.MethodsBased on a narrative review and editorial that will be published in spring 2022, a limited number of rTMS studies have been conducted in children and youth with other primary diagnoses, including ASD.ResultsThree published rTMS studies have used a rigorous RCT design in individuals with ASD. Much of the available rTMS research in ASD uses inhibitory rTMS protocols to enhance inhibitory function, which is hypothesized to be impaired in ASD. The efficacy of rTMS in treating youth with ASD is currently inconclusive due to the heterogeneity of the treatment protocols and outcomes measured, as well as limited studies designed with a proper blinded, sham-controlled group. However, a handful of studies show that rTMS treatments may reduce repetitive behavior, improve executive functioning, and support enhanced social interaction, with only mild adverse events such as transient headaches or scalp discomfort.ConclusionsResults point to the need for a more robust body of evidence to identify the potential benefit of treating youth with ASD through rTMS, along with the optimal protocols.ASD, ND, NM ObjectivesRepetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation tool with potential for broad application in individuals with neuropsychiatric conditions. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation tool with potential for broad application in individuals with neuropsychiatric conditions. MethodsBased on a narrative review and editorial that will be published in spring 2022, a limited number of rTMS studies have been conducted in children and youth with other primary diagnoses, including ASD. Based on a narrative review and editorial that will be published in spring 2022, a limited number of rTMS studies have been conducted in children and youth with other primary diagnoses, including ASD. ResultsThree published rTMS studies have used a rigorous RCT design in individuals with ASD. Much of the available rTMS research in ASD uses inhibitory rTMS protocols to enhance inhibitory function, which is hypothesized to be impaired in ASD. The efficacy of rTMS in treating youth with ASD is currently inconclusive due to the heterogeneity of the treatment protocols and outcomes measured, as well as limited studies designed with a proper blinded, sham-controlled group. However, a handful of studies show that rTMS treatments may reduce repetitive behavior, improve executive functioning, and support enhanced social interaction, with only mild adverse events such as transient headaches or scalp discomfort. Three published rTMS studies have used a rigorous RCT design in individuals with ASD. Much of the available rTMS research in ASD uses inhibitory rTMS protocols to enhance inhibitory function, which is hypothesized to be impaired in ASD. The efficacy of rTMS in treating youth with ASD is currently inconclusive due to the heterogeneity of the treatment protocols and outcomes measured, as well as limited studies designed with a proper blinded, sham-controlled group. However, a handful of studies show that rTMS treatments may reduce repetitive behavior, improve executive functioning, and support enhanced social interaction, with only mild adverse events such as transient headaches or scalp discomfort. ConclusionsResults point to the need for a more robust body of evidence to identify the potential benefit of treating youth with ASD through rTMS, along with the optimal protocols.ASD, ND, NM Results point to the need for a more robust body of evidence to identify the potential benefit of treating youth with ASD through rTMS, along with the optimal protocols.

Differential evolution method to find optimal location of a single-element transducer for transcranial focused ultrasound therapy

Background and objectiveFocused ultrasound (FUS) has been receiving growing attention as a noninvasive brain stimulation tool because of its superior spatial specificity and depth penetrability. However, the large mismatch of acoustic properties between the skull and water can disrupt and shift the acoustic focus in the brain. In this paper, we present a numerical method to find the optimal location of a single-element FUS transducer, which creates focus on the target region. MethodsThe score function, representing the superposition of acoustic waves according to the relative phase difference and transmissibility, was defined based on time-reversal invariance of acoustic waves and depending on the spatial location of the transducer. The optimal location of the transducer was then determined using a differential evolution algorithm. To assess the proposed method, we conducted a forward simulation and compared the resulting focal location to the desired target point. We also performed experimental validation by measuring the acoustic pressure field through an ex vivo human skull in a water tank. ResultsThe numerical results indicated that the score function had a positive proportional relationship with the acoustic pressure at the target. Moreover, for the optimized transducer location, both the numerical and experimental results showed that the normalized acoustic pressure at the target was higher than 0.9. ConclusionsIn this study, we developed an optimization method to place a single-element transducer that effectively transmits acoustic energy to the targeted region in the brain. Our numerical and experimental results demonstrate that the proposed method can provide an optimal transducer location for safe and efficient FUS treatment.

Assessment of Cortical Plasticity in Schizophrenia by Transcranial Magnetic Stimulation.

Neural plasticity refers to the capability of the brain to modify its structure and/or function and organization in response to a changing environment. Evidence shows that disruption of neuronal plasticity and altered functional connectivity between distinct brain networks contribute significantly to the pathophysiological mechanisms of schizophrenia. Transcranial magnetic stimulation has emerged as a noninvasive brain stimulation tool that can be utilized to investigate cortical excitability with the aim of probing neural plasticity mechanisms. In particular, in pathological disorders, such as schizophrenia, cortical dysfunction, such as an aberrant excitatory-inhibitory balance in cortical networks, altered cortical connectivity, and impairment of critical period timing are very important to be studied using different TMS paradigms. Studying such neurophysiological characteristics and plastic changes would help in elucidating different aspects of the pathophysiological mechanisms underlying schizophrenia. This review attempts to summarize the findings of available TMS studies with diagnostic and characterization aims, but not with therapeutic purposes, in schizophrenia. Findings provide further evidence of aberrant excitatory-inhibitory balance in cortical networks, mediated by neurotransmitter pathways such as the glutamate and GABA systems. Future studies with combining techniques, for instance, TMS with brain imaging or molecular genetic typing, would shed light on the characteristics and predictors of schizophrenia.

Non-invasive brain stimulation and psychiatric symptoms in neurological disorders

Psychiatric disorders are increasingly recognized as resulting from dysfunction in distributed neural circuitry. The ability of noninvasive brain stimulation to selectively target the circuitry underlying psychiatric disorders has made them valuable tools to study and treat a growing list of conditions including treatment resistant depression, obsessive compulsive disorder, and smoking dependence. FDA approved noninvasive devices for clinical treatment in psychiatry include transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and vagus nerve stimulation (VNS). There is also a range of other noninvasive brain stimulation tools at various stages of research that show promise, including transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), and focused ultrasound (FUS). Since the initial approval of TMS in 2008, a growing number of devices, coils, and dosing strategies have become available that have the potential to reach a broader range of brain regions and accelerate therapeutic response. Research demonstrates that certain forms of TMS, when given simultaneously with cognitive training, may improve selected cognitive functions. Given the high degree of co-morbidity between neurological and psychiatric disorders, these development in noninvasive neuromodulation tools offer alternatives for neurological patients experiencing psychiatric symptoms. The availability to target neuromodulation via neuronavigation may be particularly useful in neurological patients with focal brain lesions. This presentation will review the state of the art of non-invasive neuromodulation tools in psychiatric care and will highlight the latest work with TMS for depression and cognitive function in patients with neurological disorders such as traumatic brain injury, stroke, and neurodegenerative disorders.

Heading for Personalized rTMS in Tinnitus: Reliability of Individualized Stimulation Protocols in Behavioral and Electrophysiological Responses.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization. Objective: The aim was to investigate the test–retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus. Methods: Three short verum (1, 10, 20 Hz; 200 pulses) and one sham (0.1 Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG), together with behavioral tinnitus loudness ratings. RTMS individualization was executed on the basis of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/gamma responders) in accordance with the prevalent neurophysiological models for tinnitus. Results: It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder), respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. On the contrary, test–retest correlation analyses per protocol at a group level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were found. Conclusion: RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability at the group level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies, as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.

TMS-EEG indexes abnormal GABAergic signalling in patients with schizophrenia

AimsTranscranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool designed to probe the strength of inhibitory and excitatory neurotransmission in the cortex. Combined with electromyography, paired-pulse TMS paradigms have revealed a deficit in inhibition mediated by GABA-A receptors in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a more detailed examination of cortical excitability and may shed more light into the pathophysiology of schizophrenia. Of the various peaks of the TMS-evoked EEG signal, responses at 45 (N45) and 100 ms (N100) likely reflect GABA-A and GABA-B receptor-mediated inhibition, respectively. Responses at 25 ms (P25) are affected by voltage-gated channel ligands, whereas glutamatergic processes may be related to the P70 component. We here aim to systematically investigate the role of these neural processes in patients with schizophrenia by using TMS-EEG.MethodTMS-evoked EEG potentials (TEPs) were recorded in patients with schizophrenia (n = 19) and in age-matched healthy controls (n = 17). 150 TMS pulses at 90% of resting motor threshold were applied over the left primary motor cortex during EEG recording. Differences in TEPs between the two groups were analysed for all electrodes and for time windows corresponding to each TEP (P25: 0.015-0.035 ms; N45: 0.035-0.06 ms; P70: 0.035-0.06 ms; N100: 0.09-0.14ms) by applying multiple independent sample t-tests. Further, a cluster-based permutation analysis approach was implemented to correct for multiple comparisons.ResultCompared to controls, patients showed amplitude reduction for the P25 (negative and positive cluster; p < 0.001 and p = 0.04, respectively), N45 (negative and positive cluster; p < 0.001 and p = 0.001, respectively) and P70 component (negative and positive cluster; p = 0.04 and p = 0.004, respectively).ConclusionThere results extend on previous literature about impairment of GABA-A receptor mediated inhibition in schizophrenia, as demonstrated by the N45 amplitude reduction, whereas no significant differences in GABA-B index (i.e., N100) were revealed. Our results also showed that, although specific mechanisms underlying P25 and P70 have not been fully elucidated yet, excitatory neurotransmission is altered in this clinical population. To conclude, TMS-EEG may provide a more comprehensive view of the inhibitory and excitatory mechanisms involved in the pathophysiology of schizophrenia.

Method of treating alcohol dependence complicated by amnestic disorders

IntroductionAmnesia and palimpsests occurring and recurring in alcohol addicts due to alcohol intoxication (Ebrietas alcoholica) are accompanied by hazardous memory failures, gradual mental degradation and psychoorganic syndrome, which evidences urgent clinical, therapeutic and therapeutic issue in addictology, psychiatry, forensic medicine, sociology, medical psychology, etc. At EPA initiative (2019), research interest in non-invasive brain stimulation tools and methods for such populations was activated.ObjectivesDevelopment of a patentable method of treatment in addictology using pyracetam and nicotinic acid transcerebral electrophoresis (TCE).MethodsValid clinical-diagnostic, laboratory, biochemical, electrophysiological, psychological (scaling, testing), statistical methods for identification of alcohol dependence complicated by amnestic disorders.ResultsThe method of treatment of alcohol dependence complicated by amnestic disorders (Patent 141785 UA) provides complex pharmacological and drug-free therapy. Antiamnesic drugs are administered by TCE bilaterally; pyracetam 20% solution to the left orbit through active negative electrodes, and nicotinic acid 0.1% solution to the right orbit (positive electrode in the occipital fossa), current of 2-4 mA, 20-30 minutes exposure. The procedure was performed daily with a TCE device, for a 10-day course of treatment along with psychotherapeutic potentiation. TCE provides the ionic implementation of pharmacological agents in the brain and their physiological electrical stimulation.ConclusionsIn a representative clinical trial, using statistical methods and generated bank of patient-specific observations, significant potentiating effects of combined drug-free, non-invasive transcerebral electrical stimulation and electrophoretic implementation of pyracetam and nicotinic acid were demonstrated.

On the Use of TMS to Investigate the Pathophysiology of Neurodegenerative Diseases.

Neurodegenerative diseases are a collection of disorders that result in the progressive degeneration and death of neurons. They are clinically heterogenous and can present as deficits in movement, cognition, executive function, memory, visuospatial awareness and language. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool that allows for the assessment of cortical function in vivo. We review how TMS has been used for the investigation of three neurodegenerative diseases that differ in their neuroanatomical axes: (1) Motor cortex—corticospinal tract (motor neuron diseases), (2) Non-motor cortical areas (dementias), and (3) Subcortical structures (parkinsonisms). We also make four recommendations that we hope will benefit the use of TMS in neurodegenerative diseases. Firstly, TMS has traditionally been limited by the lack of an objective output and so has been confined to stimulation of the motor cortex; this limitation can be overcome by the use of concurrent neuroimaging methods such as EEG. Given that neurodegenerative diseases progress over time, TMS measures should aim to track longitudinal changes, especially when the aim of the study is to look at disease progression and symptomatology. The lack of gold-standard diagnostic confirmation undermines the validity of findings in clinical populations. Consequently, diagnostic certainty should be maximized through a variety of methods including multiple, independent clinical assessments, imaging and fluids biomarkers, and post-mortem pathological confirmation where possible. There is great interest in understanding the mechanisms by which symptoms arise in neurodegenerative disorders. However, TMS assessments in patients are usually carried out during resting conditions, when the brain network engaged during these symptoms is not expressed. Rather, a context-appropriate form of TMS would be more suitable in probing the physiology driving clinical symptoms. In all, we hope that the recommendations made here will help to further understand the pathophysiology of neurodegenerative diseases.

Transcranial Focused Ultrasound Neuromodulation of Voluntary Movement-Related Cortical Activity in Humans.

Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation tool for safely and reversibly modulating brain circuits. The effectiveness of tFUS on human brain has been demonstrated, but how tFUS influences the human voluntary motor processing in the brain remains unclear. We apply low-intensity tFUS to modulate the movement-related cortical potential (MRCP) originating from human subjects practicing a voluntary foot tapping task. 64-channel electroencephalograph (EEG) is recorded concurrently and further used to reconstruct the brain source activity specifically at the primary leg motor cortical area using the electrophysiological source imaging (ESI). The ESI illustrates the ultrasound modulated MRCP source dynamics with high spatiotemporal resolutions. The MRCP source is imaged and its source profile is further evaluated for assessing the tFUS neuromodulatory effects on the voluntary MRCP. Moreover, the effect of ultrasound pulse repetition frequency (UPRF) is further assessed in modulating the MRCP. The ESI results show that tFUS significantly increases the MRCP source profile amplitude (MSPA) comparing to a sham ultrasound condition, and further, a high UPRF enhances the MSPA more than a low UPRF does. The present results demonstrate the neuromodulatory effects of the low-intensity tFUS on enhancing the human voluntary movement-related cortical activities evidenced through the ESI. This work provides the first evidence of tFUS enhancing the human endogenous motor cortical activities through excitatory modulation.

6 Hz transcranial alternating current stimulation of mPFC improves sustained attention and modulates alpha phase synchronization and power in dorsal attention network

ABSTRACT Transcranial alternating current stimulation (tACS) is a noninvasive brain stimulation tool appropriate to modulate cortical oscillations and activity via the application of weak currents. The major goal of this study was to investigate the effects of medial Prefrontal Cortex (mPFC) stimulation on sustained attention task performance measured by Rapid Visual Information Processing (RVIP) task and the brain networks assumed to be critical to sustained attention. mPFC has been shown to be involved in sustained attention performance and as a main hub in default mode network (DMN). mPFC activity modulation via theta tACS was implemented in this study. This was a single blind study with 21 participants receiving active and sham stimulation with the electrodes on FPz and the Inion. tACS was able to impact different RVIP measures (total hits, A’ (sensitivity to target), total correct rejection, etc.). Relative power spectrum density (PSD) analysis yielded significant increases in theta frequency mostly in the fronto-central regions after active tACS and current source density (CSD) analysis yielded significant power modulations in theta frequency band in post-central gyrus. Furthermore, phase locking value (PLV) analysis showed that there were significant changes in cortical connections in the Dorsal Attention Network (DAN) in alpha frequency band. This study showed that theta frequency tACS over mPFC, was able to produce significant modulations in an RVIP task and its associated brain networks in healthy participants.

Impact of tDCS and HD-tDCS on tinnitus perception: A scoping review.

Tinnitus is the auditory phantom perception of a sound that severely affects the quality of life of over 300,000 people in the United Kingdom alone. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool, which has been investigated as a potential tinnitus management option since 2006. This study aimed to investigate the impact of tDCS and high-definition transcranial direct current stimulation (HD-tDCS) on tinnitus perception. A scoping review was undertaken using the framework by Arksey and O'malley (2005). After consideration of relevance, 38 primary research studies were included in the data charting to examine the impact of (HD-)tDCS on tinnitus. Twenty-two of the primary research studies reported significant therapeutic effects of (HD)-tDCS on tinnitus perception. However, only eight of these included a sham-control condition. The tDCS protocols in the studies were highly heterogeneous and sample sizes were generally small. More double-blind, sham-controlled trials are needed that use similar protocols and outcome measures before definitive conclusions about the efficacy of (HD-)tDCS for tinnitus can be drawn.

RTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders.

Cocaine use disorder and methamphetamine use disorder are chronic, relapsing disorders with no US Food and Drug Administration-approved interventions. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool that has been increasingly investigated as a possible therapeutic intervention for substance use disorders. rTMS may have the ability to induce beneficial neuroplasticity in abnormal circuits and networks in individuals with addiction. The aim of this review is to highlight the rationale and potential for rTMS to treat cocaine and methamphetamine dependence: we synthesize the outcomes of studies in healthy humans and animal models to identify and understand the neurobiological mechanisms of rTMS that seem most involved in addiction, focusing on the dopaminergic and glutamatergic systems. rTMS-induced changes to neurotransmitter systems include alterations to striatal dopamine release and metabolite levels, as well as to glutamate transporter and receptor expression, which may be relevant for ameliorating the aberrant plasticity observed in individuals with substance use disorders. We also discuss the clinical studies that have used rTMS in humans with cocaine and methamphetamine use disorders. Many such studies suggest changes in network connectivity following acute rTMS, which may underpin reduced craving following chronic rTMS. We suggest several possible future directions for research relating to the therapeutic potential of rTMS in addiction that would help fill current gaps in the literature. Such research would apply rTMS to animal models of addiction, developing a translational pipeline that would guide evidence-based rTMS treatment of cocaine and methamphetamine use disorder.

Modulating Neuronal Networks to Enhance Postural Control: A Review of Transcranial Direct Current Stimulation Approach

Context: Postural stability is essential for performing everyday activities. The central nervous system (CNS) must modify balance control to provide stability to intrinsic and external perturbations. Methods considered as the main candidates for ultimate promotion of neural plasticity could be used for rehabilitation to enhance motor performance. The Transcranial Direct Current Stimulation (tDCS) as a non-invasive brain stimulation tool is applied over the cortex to accentuate and/or accelerate neural effects on network connectivity. Objectives: This study aimed to address the impact of tDCS intervention on balance recovery. We postulated that tDCS induces neuroplasticity that is fundamental for refining motor behaviors such as postural stability during rehabilitation. Methods: The present review discusses the tDCS application over the important areas of the CNS that are responsible for the sensorimotor processing of balance-relevant information. We searched ProQuest, PubMed, Science Direct, Cochrane, and Google Scholar for randomized, controlled trials that assessed the efficacy of tDCS intervention in improving balance impairment following neurologic disorders and enhancing postural stability in a healthy population. Results: Recent studies provide insights into the effects of tDCS on postural stability. Based on the defined criteria, there is a positive response to tDCS, but the underlying neural mechanisms are yet unknown. We suggest that interventions promoting more neural plasticity are crucial for better balance training outcomes and improved effectiveness of rehabilitation programs. Conclusions: Balance recovery after tDCS needs to be more investigated. The tDCS might be considered as an adjunct preventive strategy to provide functional recovery and reduce the adverse effects of balance impairment.

Physiology of Transcranial Direct Current Stimulation.

Direct current stimulation is a neuromodulatory noninvasive brain stimulation tool, which was first introduced in animal and human experiments in the 1950s, and added to the standard arsenal of methods to alter brain physiology as well as psychological, motor, and behavioral processes and clinical symptoms in neurological and psychiatric diseases about 20 years ago. In contrast to other noninvasive brain stimulation tools, such as transcranial magnetic stimulation, it does not directly induce cerebral activity, but rather alters spontaneous brain activity and excitability by subthreshold modulation of neuronal membranes. Beyond acute effects on brain functions, specific protocols are suited to induce long-lasting alterations of cortical excitability and activity, which share features with long-term potentiation and depression. These neuroplastic processes are important foundations for various cognitive functions such as learning and memory formation and are pathologically altered in numerous neurological and psychiatric diseases. This explains the increasing interest to investigate transcranial direct current stimulation (tDCS) as a therapeutic tool. However, for tDCS to be used effectively, it is crucial to be informed about physiological mechanisms of action. These have been increasingly elucidated during the last years. This review gives an overview of the current knowledge available regarding physiological mechanisms of tDCS, spanning from acute regional effects, over neuroplastic effects to its impact on cerebral networks. Although knowledge about the physiological effects of tDCS is still not complete, this might help to guide applications on a scientifically sound foundation.

Transcranial DC stimulation modifies functional connectivity of large-scale brain networks in abstinent methamphetamine users.

BackgroundTranscranial direct current stimulation (tDCS) is a noninvasive brain stimulation tool suited to alter cortical excitability and activity via the application of weak direct electrical currents. An increasing number of studies in the addiction literature suggests that tDCS modulates subjective self‐reported craving through stimulation of dorsolateral prefrontal cortex (DLPFC). The major goal of this study was to explore effects of bilateral DLPFC stimulation on resting state networks (RSNs) in association with drug craving modulation. We targeted three large‐scale RSNs; the default mode network (DMN), the executive control network (ECN), and the salience network (SN).MethodsFifteen males were recruited after signing written informed consent. We conducted a double‐blinded sham‐controlled crossover study. Twenty‐minute “real” and “sham” tDCS (2 mA) were applied over the DLPFC on two separate days in random order. Each subject received both stimulation conditions with a 1‐week washout period. The anode and cathode electrodes were located over the right and left DLPFC, respectively. Resting state fMRI was acquired before and after real and sham stimulation. Subjective craving was assessed before and after each fMRI scan. The RSNs were identified using seed‐based analysis and were compared using a generalized linear model.ResultsSubjective craving decreased significantly after real tDCS compared to sham stimulation (p = .03). Moreover, the analysis shows significant modulation of DMN, ECN, and SN after real tDCS compared to sham stimulation. Additionally, alteration of subjective craving score was correlated with modified activation of the three networks.DiscussionGiven the observed alteration of the targeted functional brain networks in methamphetamine users, new potentials are highlighted for tDCS as a network intervention strategy and rsfMRI as a suitable monitoring method for these interventions.

Chapter 22 - Noninvasive brain stimulation of the parietal lobe for improving neurologic, neuropsychologic, and neuropsychiatric deficits

Transcranial magnetic stimulation (TMS) and transcranial electric stimulation (tES) are noninvasive brain stimulation (NIBS) tools that are now widely used in neuroscientific research in humans. The fact that both TMS and tES are able to modulate brain plasticity and, in turn, affect behavior is opening up new horizons in the treatment of brain circuit and plasticity disorders. In the present chapter, we will first provide the reader with a brief background on the basic principles of NIBS, describing the electromagnetic and physical foundations of TMS and tES, as well as the current knowledge of the neurophysiologic basis of their effects on brain activity and plasticity. In the main part, we will outline studies aimed at improving persistent symptoms and deficits in patients suffering from neurologic and neuropsychiatric disorders featured by dysfunction of the parietal lobe. The emerging view is that NIBS of parietal areas holds the promise to overcome various sensory, motor, and cognitive disorders that are often refractory to standard medical or behavioral therapies. The chapter closes with an outlook on further developments in this realm, discussing novel therapeutic approaches that could lead to more effective rehabilitation procedures, better suited for the specific parietal lobe dysfunction.