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This article is from Developmental Cognitive Neuroscience , volume 6 . Abstract •Transcranial electrical stimulation (TES) can improve cognitive training effects in adults.•TES can enhance neuroplasticity from the molecular level to the system level.•We discuss the usage of TES with cognitive training in atypically developing children.•We discuss the possible cognitive and physical side effects of TES.

This article is from PLoS ONE , volume 9 . Abstract Transcranial Magnetic Stimulation (TMS) is an important tool for testing causal relationships in cognitive neuroscience research. However, the efficacy of TMS can be variable across individuals and difficult to measure. This variability is especially a challenge when TMS is applied to regions without well-characterized behavioral effects, such as in studies using TMS on multi-modal areas in intrinsic networks. Here, we examined whether perfusion fMRI recordings of Cerebral Blood Flow (CBF), a quantitative measure sensitive to slow functional changes, reliably index variability in the effects of stimulation. Twenty-seven participants each completed four combined TMS-fMRI sessions during which both resting state Blood Oxygen Level Dependent (BOLD) and perfusion Arterial Spin Labeling (ASL) scans were recorded. In each session after the first baseline day, continuous theta-burst TMS (TBS) was applied to one of three locations: left dorsolateral prefrontal cortex (L dlPFC), left anterior insula/frontal operculum (L aI/fO), or left primary somatosensory cortex (L S1). The two frontal targets are components of intrinsic networks and L S1 was used as an experimental control. CBF changes were measured both before and after TMS on each day from a series of interleaved resting state and perfusion scans. Although TBS led to weak selective increases under the coil in CBF measurements across the group, individual subjects showed wide variability in their responses. TBS-induced changes in rCBF were related to TBS-induced changes in functional connectivity of the relevant intrinsic networks measured during separate resting-state BOLD scans. This relationship was selective: CBF and functional connectivity of these networks were not related before TBS or after TBS to the experimental control region (S1). Furthermore, subject groups with different directions of CBF change after TBS showed distinct modulations in the functional interactions of targeted networks. These results suggest that CBF is a marker of individual differences in the effects of TBS.

This article is from Current Opinion in Neurology , volume 27 . Abstract Purpose of review: Noninvasive brain stimulation (NIBS) is increasingly used to enhance the recovery of function after stroke. The purpose of this review is to highlight and discuss some unresolved questions that need to be addressed to better understand and exploit the potential of NIBS as a therapeutic tool. Recent findings: Recent meta-analyses showed that the treatment effects of NIBS in patients with stroke are rather inconsistent across studies and the evidence for therapeutic efficacy is still uncertain. This raises the question of how NIBS can be developed further to improve its therapeutic efficacy. Summary: This review addressed six questions: How does NIBS facilitate the recovery of function after stroke? Which brain regions should be targeted by NIBS? Is there a particularly effective NIBS modality that should be used? Does the location of the stroke influence the therapeutic response? How often should NIBS be repeated? Is the functional state of the brain during or before NIBS relevant to therapeutic efficacy of NIBS? We argue that these questions need to be tackled to obtain sufficient mechanistic understanding of how NIBS facilitates the recovery of function. This knowledge will be critical to fully unfold the therapeutic effects of NIBS and will pave the way towards adaptive NIBS protocols, in which NIBS is tailored to the individual patient.

This contains the extended data for the manuscript in WellcomeOpenResearch journal: "Identification of resting brain functional connectivity markers of response to continuous Theta Burst Stimulation and cathodal transcranial Direct Current Stimulation in schizophrenia patients with persistent auditory hallucinations."

Non-invasive transcranial direct current stimulation (tDCS) has recently received substantial attention in experimental and clinical science, because it allows modulation of human brain function without significant adverse effects. However, despite widespread and often successful use of this technique, little systematic research into the mechanisms underlying frequently observed highly variable effects of tDCS has been accomplished. Currently, this results in suboptimal use of this promising technique in experimental and clinical contexts. The overarching objective of the proposed Research Unit (RU) is to address this knowledge gap by investigating tDCS effects for the first time in a systematic, comprehensive and coordinated way, by a multidisciplinary and complementary team of leading experts in their respective fields. Due to its exceptional relevance for experimental and translational research, human learning and memory function will serve as a model to study tDCS effects across four functional domains (i.e., visual-spatial, language, motor, and executive) and across the human lifespan. Eight empirical projects (Projects P1-8; two per domain) will use comparable methods, individualized and targeted stimulation, highly controlled experimental settings, and tDCS application during concurrent functional imaging to investigate behavioral and neural mechanisms and predictors of stimulation response. Two overarching projects (P9, P10) will (1) relate the outcomes of biophysical models of individualized current flow to behavioral and neural modulations using the large, coordinated dataset acquired in the empirical projects and (2) cross-validate and improve current flow simulations by using in-vivo magnetic current density imaging measurements. Collaborative activities within the RU will be facilitated by the coordination project that is also responsible for crossproject data management and sharing by adhering to highest standards in the field. In sum, the proposed RU will generate fundamental insights into the neural mechanisms and predictors of tDCS response across the human lifespan, thereby informing theoretical concepts of the mechanisms-of-action by which current flow alters neural activity. From a methodological point of view, we will be able to optimize and validate biophysical models of current flow using an unprecedented dataset. Together, this will substantially advance future experimental and translational applications of tDCS in health and disease.

This article is from Annals of Rehabilitation Medicine , volume 35 . Abstract Objective: To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on recovery of the swallowing function in patients with a brain injury. Method: Patients with a brain injury and dysphagia were enrolled. Patients were randomly assigned to sham, and low and high frequency stimulation groups. We performed rTMS at 100% of motor evoked potential (MEP) threshold and a 5 Hz frequency for 10 seconds and then repeated this every minute in the high frequency group. In the low frequency group, magnetic stimulation was conducted at 100% of MEP threshold and a 1 Hz frequency. The sham group was treated using the same parameters as the high frequency group, but the coil was rotated 90° to create a stimulus noise. The treatment period was 2 weeks (5 days per week, 20 minutes per session). We evaluated the Functional Dysphagia Scale (FDS) and the Penetration Aspiration Scale (PAS) with a videofluoroscopic swallowing study before and after rTMS. Results: Thirty patients were enrolled, and mean patient age was 68.2 years. FDS and PAS scores improved significantly in the low frequency group after rTMS, and American Speech-Language Hearing Association National Outcomes Measurements System Swallowing Scale scores improved in the sham and low frequency groups. FDS and PAS scores improved significantly in the low frequency group compared to those in the other groups. Conclusion: We demonstrated that low frequency rTMS facilitated the recovery of swallowing function in patients with a brain injury, suggesting that rTMS is a useful modality to recover swallowing function.

Abstract: Background: Transcranial Magnetic Stimulation – Electroencephalography (TMS-EEG) is a non-operative technique that allows for magnetic cortical stimulation (TMS) and analysis of the electrical currents generated in the brain (EEG). Despite the regular utilization of both techniques independently, little is known about the potential impact of their combination in neurosurgical prac-tice. Methods: This scoping review, conducted following PRISMA guidelines, focused on TMS-EEG in epilepsy, neuro-oncology, and general neurosurgery. A literature search in Embase and Ovid MEDLINE returned 3596 records, which were screened based on predefined inclusion and exclusion criteria. After full-text review, three studies met the inclusion criteria. Two independent investiga-tors conducted study selection and data extraction, with mediators resolving disagreements. The NHLBI tool was used to assess risk of bias in the included studies. Results: 3596 articles were screened following the above-mentioned criteria: 2 articles and 1 abstract met the inclusion criteria. TMS-EEG is mentioned as a promising tool to evaluate tumour-brain interaction, improve preoper-ative speech mapping and for lateralization epileptic focus in patients undergoing epilepsy surgery. Lack of detailed patient and outcome information preclude further considerations about TMS-EEG use beyond the potential applications of this technique. Conclusions: TMS-EEG research in neuro-surgery is required to establish the role of this non-invasive brain stimulation-recording technique. Tumour-brain interaction, preoperative mapping and seizure lateralization are in the front row for its future applications.

This article is from Sensors (Basel, Switzerland) , volume 14 . Abstract The occurrence of epileptiform discharges (ED) in electroencephalographic (EEG) recordings of patients with epilepsy signifies a change in brain dynamics and particularly brain connectivity. Transcranial magnetic stimulation (TMS) has been recently acknowledged as a non-invasive brain stimulation technique that can be used in focal epilepsy for therapeutic purposes. In this case study, it is investigated whether simple time-domain connectivity measures, namely cross-correlation and partial cross-correlation, can detect alterations in the connectivity structure estimated from selected EEG channels before and during ED, as well as how this changes with the application of TMS. The correlation for each channel pair is computed on non-overlapping windows of 1 s duration forming weighted networks. Further, binary networks are derived by thresholding or statistical significance tests (parametric and randomization tests). The information for the binary networks is summarized by statistical network measures, such as the average degree and the average path length. Alterations of brain connectivity before, during and after ED with or without TMS are identified by statistical analysis of the network measures at each state.

The purpose of this study is to investigate the effects of an rTMS-induced lesion targeted at a central node in a multilayer network on brain activation using fMRI. This study uses data from a related study in which such individualized rTMS targets in the DLPFC were identified using multilayer network modeling. In that study, it was hypothesized that such multilayer network targeting would disrupt the broader network involved in planning, impairing performance on a neuropsychological planning task. However, the impact of such targeted neuromodulation on task-based brain activation in the DLPFC and the propagation of these effects across the brain regions associated with planning has not yet been examined.

The superordinate aim of this project is to investigate memory-related plasticity induced by transcranial direct current stimulation (tDCS) using multimodal magnetic resonance imaging (MRI) in young healthy adults (age range: 18-30 years). Specifically, we aim to delineate changes of gray and white matter microstructure, metabolite concentration, brain activity and memory task performance. The results will add to the mechanistic understanding of brain stimulation effects and the architecture of memory processes. Further information can be found in the hypotheses section (updated version). Study design The study consists of four sessions for each participant: 1. A behavioral baseline session a. to access the general cognitive ability and baseline memory task performance of each participant 2. A baseline MRI session a. to acquire structural images in order to prospectively individualize electrode positioning based on anatomical information and electric field modeling b. to acquire resting-state functional MRI (fMRI) in order to quantify baseline functional connectivity 3. Two experimental intra-scanner sessions (descripted in more detail below) a. to measure gray and white matter microstructure b. to measure metabolite concentration c. to measure brain activity during an object-location memory (OLM) task d. to measure memory function Participants will be invited to two consecutive experimental sessions, separated by a wash-out period (at least 1 week). Self-reported well-being as well as potential stress factors (e.g. physical activity) up to two hours before the session will be assessed via questionnaires. We will perform neuronavigation based on the acquired structural images (baseline MRI session) to identify the individual stimulation target (based on a prospective targeting approach using anatomical and electric field information, see “Focal non-invasive transcranial electrical stimulation”) in the right occipito-temporal cortex (OTC) and determine individual electrode placements. Participants will receive anodal and sham tDCS in a counterbalanced order. After electrode placement, participants will start with the intra-scanner assessment: • T1 (~3 min) • Magnetic resonance spectroscopy (MRS) (~13 min) • Neurite orientation dispersion and density imaging (NODDI) (~6 min) • Object-location memory task + task fMRI) (~30 min, incl. concurrent / “online” tDCS of 20 min duration, see below) • NODDI (~6 min) • MRS (~13 min) Memory task The task is a modified version of the paradigm “LOCATO” for assessing object-location learning (Flöel et al., 2012). The task consists of four learning trials and two control trials. Within the learning trial participants have to learn the correct position of pictures of real-life buildings on a two-dimensional street map. Each trial consists of 7 correct building-position-associations with 3 incorrect distractor positions, on the whole participants have to learn 28 correct building-position-associations. Participants have to answer “yes” or “no” with a response grip and will get visual feedback directly after each stimulus. In the control trials, participants have to answer whether the house is on the left respectively right side of the map (with 14 stimuli). Task duration is 30 min. We developed two parallel versions (A and B), each one with a different set of buildings and with the street map rotated for 180° for version B. A short version of the task will be applied outside of the scanner to access baseline OLM performance. Variables of interest will be the accuracy as well as reaction time. Focal non-invasive transcranial electrical stimulation A weak direct current (NeuroConn DC-Stimulator MC MR) will be applied via a multi-electrode set-up that allow for focal delivery of electrical current during task performance. We will use MRI compatible electrodes (2 cm diameter) as well as cables and filter boxes for intra-scanner tDCS. Prospective planning of individual electrode positions will utilize anatomical and electric field information from the baseline MRI session. The anode will be positioned over the target region during both active and sham stimulation. To define the target region, an iterative approach was employed, incorporating anatomical landmarks and task-related imaging studies on OLM (Flöel et al., 2012; Gillis et al., 2016). These regions were then overlaid with atlas-based brain areas (Desikan et al., 2006), identifying the right OCT as the region of interest (ROI) for anode placement. Three cathodes will be arranged in a circular way around the anode with a distance of 40 mm to constrain the current flow to the target region at the right OTC. Electrodes will be held in place using an adhesive conductive gel (Weaver Ten20 conductive paste) and an EEG cap, to ensure stable conductive adhesion with the skin. Placement of individualized montages on the scalp will be guided by neuronavigation (Brainsight 2 Navigation system, Rogue Research). Stimulation will be administered with 2 mA and a local anesthetic (Emlá cream) will be applied prior to stimulation to ensure participant blinding. Stimulation will consist of 20 min of continuous stimulation with 20 additional seconds of ramping at the beginning and end of stimulation, respectively. In the sham tDCS group, the same electrode montage and ramp-time will be used, but current will only be applied for 30 s to elicit the typical tingling sensation of stimulation on the scalp and to blind participants regarding the stimulation condition. Perception of adverse events related to the stimulation will be prompted in the end of each stimulation condition using a standardized questionnaire (Antal et al., 2017). MR sequences MRI will be conducted with a 3T Siemens Vida MR-System at the Baltic Imaging Center in Greifswald (using a 64-channel head coil). T1/T2. A 3D structural scanning protocol using high-resolution T1 -weighted magnetization prepared rapid gradient echo (MPRAGE) imaging (0.9 x 0.9 x 0.9 mm³, TR = 2700 ms, TE = 3.7 ms, TI = 1090 ms, flip angle = 9°; using selective water excitation for fat suppression) and a T2 -weighted sequence (0.9 x 0.9 x 0.9 mm³, TR = 2500 ms, TE = 349 ms, flip angle = 120°) will be recorded. NODDI. For diffusion MRI we will use a NODDI sequence. The imaging will be performed using multi-band sequence (MB factor 4) with the following parameter setup: voxel size: 2 x 2 x 2 mm³, 72 slices, 128 directions, b-value of 2500 s/mm², TR: 2800 ms, TE: 89.60 ms, flip-angle 90°). To enable the use of distortion correction tools, different acquisition phase encoding directions will be acquired (totaling up to six acquisitions of a monoplanar sequence). MRS. A single MRS voxel (30 x12 x 12 mm³) will be positioned in the right hippocampus. The voxel will be manually defined at the first scan and automatically aligned in the following scans to assure reproducible voxel positioning within the sessions. Single-voxel spectra will be acquired using a semi-LASER sequence (TR: 3000 ms, TE: 135 ms, averages: 128) with integrated water suppression (VAPOR). Additionally, a non-water-suppressed spectrum will be acquired as reference (averages: 8). task fMRI. Functional MRI data will be acquired using a blood-oxygen-level-dependent (BOLD) echo-planar imaging (EPI) sequence (2 x 2 x 2 mm³, TR: 1000 ms, TE: 30.80 ms, flip angle: 60, slices: 72, slice thickness: 2 mm). The task will be presented on a screen with participant responses recorded via a response grip. The task design includes alternating blocks of active task performance and a control task (see memory task description above).

This scoping review aims to summarize and characterize currently available protocols for preoperative language and cognitive nTMS-based mappings in brain tumor patients. While providing an overview of the current “state of the art”, the results will be used to identify functions thus far neglected in the preoperative nTMS-based mapping context and discuss the development of innovative neurocognitive testing batteries extending thus far available protocols. The overall aim is to advance the understanding of utilizing nTMS for cortical mappings for neurosurgical patients.

This scoping review aims to summarize and characterize currently available protocols for preoperative language and cognitive nTMS-based mappings in brain tumor patients. While providing an overview of the current “state of the art”, the results will be used to identify functions thus far neglected in the preoperative nTMS-based mapping context and discuss the development of innovative neurocognitive testing batteries extending thus far available protocols. The overall aim is to advance the understanding of utilizing nTMS for cortical mappings for neurosurgical patients.

Children with severe acquired brain injury (ABI) require early and effective neurorehabilitation provision to promote a good long-term functional outcome. Transcranial magnetic stimulation (TMS) has been used to improve motor skills for children with cerebral palsy but there is limited material supporting its use in children with ABI who have a motor disorder. In this article, we wrote our scoping review protocol to systematically answer what are the TMS intervention effects on motor function in children with ABI as reported in the literature? This scoping review will follow Arksey and O’Malley’s scoping review methodological framework. A comprehensive computerised bibliographic databases search will be performed in MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine, British Nursing Index, Ovid Emcare, PsychINFO, Physiotherapy Evidence Database, Cochrane Central Register using keywords related to TMS and children with ABI. Studies that examine the effect of TMS intervention on motor function as either a primary or secondary objective will be included for this review. Study design and publication detail, participant demographic details, type and severity of ABI and other clinical information, TMS procedure, associated therapy intervention, comparator/control parameters, and the outcome measure used data will be gathered. The International Classification of Functioning, Disability and Health for Children and Youth (ICF-CY) framework will be used to report the TMS effect in children with ABI. A narrative synthesis of the findings describing the therapeutic effects of TMS intervention, limitations, and adverse effects will be synthesized and reported. This review will help to summarise the existing knowledge base and to guide further research areas.

Meta-Analysis Protocol Deep Brain Stimulation vs. Transcranial Magnetic Stimulation in Patients with Treatment-resistant Obsessive-compulsive Disorder.

The dorsolateral prefrontal cortex (DLPFC) is a prominent stimulation target for the treatment of Major Depressive disorder (MDD) with repetitive transcranial magnetic stimulation (rTMS). The therapeutic effect of DLPFC stimulation likely stems from the DLPFC–subgenual anterior cingulate cortex (sgACC) connectivity. A recent study suggested that there is an overlap of the hubs in the depression network, including the DLPFC, sgACC, and vagus nerve (VN), with the heart-brain axis, and that stimulation of these hubs consequently leads to heart rate (HR) decelerations. A specific 10 Hz Dash rTMS protocol (‘neuro-cardiac guided rTMS version 2.0’, NGC-2.0 rTMS) has been proposed to induce coupling of TMS and HR changes (heart-brain coupling; HBC). This research encompasses two studies aimed at exploring the effects of NGC-TMS targeting the DLPFC. In the Study-1, we will replicate and corroborate previous findings with a larger cohort of twenty healthy young participants. These participants will undergo NGC-TMS sessions targeting the DLPFC, supplemented by sham TMS, across three sessions. Following these findings, the Study-2 will examine the robustness of HBC by assessing various stimulation intensities by targeting the most effective target identified in the Study-1.

This article is from Frontiers in Human Neuroscience , volume 7 . Abstract The interest in transcranial alternating current stimulation (tACS) has significantly increased in the past decade. It has potential to modulate brain oscillations in a frequency specific manner, offering the possibility to demonstrate a causal nature of oscillation behavior relationships. TACS is a strong candidate as a tool for clinical applications, however, to fulfill this potential, certain parameters have yet to be evaluated. First, little is known about long-lasting after-effects of tACS with respect to the modulations of rhythmic brain activity. Second, the power of endogenous brain oscillations might play a crucial role in the efficacy of tACS. We hypothesize that the after-effects of tACS depend on the endogenous power of oscillations. To this end, we modulated the power of endogenous occipital alpha oscillations via tACS. In two experiments, participants either had their eyes open or closed to keep endogenous alpha power either low or high while they were stimulated for 20 min with their individual alpha frequency (IAF) and simultaneously performing a vigilance task. After-effects on IAF power were evaluated over a course of 30 min with a pre stimulation period serving as baseline. After-effects were strongly dependent on IAF power. Enhanced IAF power was observed for at least 30 min after tACS under conditions of low endogenous IAF power, whereas, IAF power could not be further enhanced by tACS under conditions of high IAF power. The current study demonstrates, for the first time, a long lasting effect after tACS on endogenous EEG power in the range of the stimulation frequency. Additionally, we present conclusive evidence that the power of the endogenous oscillations has a critical impact on tACS efficacy. Long lasting after-effects foster the role of tACS as a tool for non-invasive brain stimulation and demonstrate the potential for therapeutic application to reestablish the balance of altered brain oscillations.

This article is from Frontiers in Neuroscience , volume 7 . Abstract Sustaining brain and cognitive function across the lifespan must be one of the main biomedical goals of the twenty-first century. We need to aim to prevent neuropsychiatric diseases and, thus, to identify and remediate brain and cognitive dysfunction before clinical symptoms manifest and disability develops. The brain undergoes a complex array of changes from developmental years into old age, putatively the underpinnings of changes in cognition and behavior throughout life. A functionally “normal” brain is a changing brain, a brain whose capacity and mechanisms of change are shifting appropriately from one time-point to another in a given individual's life. Therefore, assessing the mechanisms of brain plasticity across the lifespan is critical to gain insight into an individual's brain health. Indexing brain plasticity in humans is possible with transcranial magnetic stimulation (TMS), which, in combination with neuroimaging, provides a powerful tool for exploring local cortical and brain network plasticity. Here, we review investigations to date, summarize findings, and discuss some of the challenges that need to be solved to enhance the use of TMS measures of brain plasticity across all ages. Ultimately, TMS measures of plasticity can become the foundation for a brain health index (BHI) to enable objective correlates of an individual's brain health over time, assessment across diseases and disorders, and reliable evaluation of indicators of efficacy of future preventive and therapeutic interventions.

Transcranial magnetic stimulation of the brain for depression

This article is from Frontiers in Behavioral Neuroscience , volume 8 . Abstract Objective: Transcranial direct current stimulation (tDCS) improves motor learning and can affect emotional processing and attention. However, it is unclear whether learned electroencephalography (EEG)-based brain-machine interface (BMI) control during tDCS is feasible, how application of transcranial electric currents during BMI control would interfere with feature-extraction of physiological brain signals and how it affects brain control performance. Here we tested this combination and evaluated stimulation-dependent artifacts across different EEG frequencies and stability of motor imagery-based BMI control.Approach: Ten healthy volunteers were invited to two BMI-sessions, each comprising two 60-trial blocks. During the trials, learned desynchronization of mu-rhythms (8–15 Hz) associated with motor imagery (MI) recorded over C4 was translated into online cursor movements on a computer screen. During block 2, either sham (session A) or anodal tDCS (session B) was applied at 1 mA with the stimulation electrode placed 1 cm anterior of C4.Main results: tDCS was associated with a significant signal power increase in the lower frequencies most evident in the signal spectrum of the EEG channel closest to the stimulation electrode. Stimulation-dependent signal power increase exhibited a decay of 12 dB per decade, leaving frequencies above 9 Hz unaffected. Analysis of BMI control performance did not indicate a difference between blocks and tDCS conditions.Conclusion: Application of tDCS during learned EEG-based self-regulation of brain oscillations above 9 Hz is feasible and safe, and might improve applicability of BMI systems.

This study aims to test whether the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) differs between patients who developed tinnitus following a traumatic brain injury (TBI), and those without a history of TBI. This was a parallel pilot, open-label, non-randomized, clinical trial to compare the efficacy of low frequency rTMS on tinnitus symptoms in patients with and without a TBI history. Patients with moderate to severe tinnitus symptoms based on the Tinnitus Handicap Inventory (THI) and the Tinnitus Functional Index (TFI) were enrolled in the study. Validated questionnaires (THI and TFI) were used to quantify the severity of tinnitus symptoms and hearing impairment (Hearing Handicap Index – HHI) before and after ten sessions of rTMS of the left primary auditory cortex. Hearing threshold levels as well as speech reception and speech discrimination thresholds were also compared. The number of patients who experienced a reduction in their subjective tinnitus symptoms was greater and sustained longer in patients without a history of TBI. The same was seen with subjective symptoms of hearing impairment. In conclusion, our preliminary results suggest tinnitus patients without a history of TBI respond better to low frequency rTMS than those with a history of TBI, suggesting that treatments could be more effective if tailored to tinnitus etiology.

This article is from Brain Sciences , volume 3 . Abstract Several cross-sectional functional Magnetic Resonance Imaging (fMRI) studies reported a negative correlation between auditory verbal hallucination (AVH) severity and amplitude of the activations during language tasks. The present study assessed the time course of this correlation and its possible structural underpinnings by combining structural, functional MRI and repetitive Transcranial Magnetic Stimulation (rTMS). Methods: Nine schizophrenia patients with AVH (evaluated with the Auditory Hallucination Rating scale; AHRS) and nine healthy participants underwent two sessions of an fMRI speech listening paradigm. Meanwhile, patients received high frequency (20 Hz) rTMS. Results: Before rTMS, activations were negatively correlated with AHRS in a left posterior superior temporal sulcus (pSTS) cluster, considered henceforward as a functional region of interest (fROI). After rTMS, activations in this fROI no longer correlated with AHRS. This decoupling was explained by a significant decrease of AHRS scores after rTMS that contrasted with a relative stability of cerebral activations. A voxel-based-morphometry analysis evidenced a cluster of the left pSTS where grey matter volume negatively correlated with AHRS before rTMS and positively correlated with activations in the fROI at both sessions. Conclusion: rTMS decreases the severity of AVH leading to modify the functional correlate of AVH underlain by grey matter abnormalities.

This article is from Frontiers in Human Neuroscience , volume 8 . Abstract None

This article is from Frontiers in Human Neuroscience , volume 7 . Abstract Rhythmic neuronal activity is ubiquitous in the human brain. These rhythms originate from a variety of different network mechanisms, which give rise to a wide-ranging spectrum of oscillation frequencies. In the last few years an increasing number of clinical research studies have explored transcranial alternating current stimulation (tACS) with weak current as a tool for affecting brain function. The premise of these interventions is that tACS will interact with ongoing brain oscillations. However, the exact mechanisms by which weak currents could affect neuronal oscillations at different frequency bands are not well known and this, in turn, limits the rational optimization of human experiments. Here we review the available in vitro and in vivo animal studies that attempt to provide mechanistic explanations. The findings can be summarized into a few generic principles, such as periodic modulation of excitability, shifts in spike timing, modulation of firing rate, and shifts in the balance of excitation and inhibition. These effects result from weak but simultaneous polarization of a large number of neurons. Whether this can lead to an entrainment or a modulation of brain oscillations, or whether AC currents have no effect at all, depends entirely on the specific dynamic that gives rise to the different brain rhythms, as discussed here for slow wave oscillations (∼1 Hz) and gamma oscillations (∼30 Hz). We conclude with suggestions for further experiments to investigate the role of AC stimulation for other physiologically relevant brain rhythms.

This article is from Dialogues in Clinical Neuroscience , volume 16 . Abstract Synchronized neuronal activity in the cortex generates weak electric fields that are routinely measured in humans and animal models by electroencephalography and local field potential recordings. Traditionally, these endogenous electric fields have been considered to be an epiphenomenon of brain activity. Recent work has demonstrated that active cortical networks are surprisingly susceptible to weak perturbations of the membrane voltage of a large number of neurons by electric fields. Simultaneously, noninvasive brain stimulation with weak, exogenous electric fields (transcranial current stimulation, TCS) has undergone a renaissance due to the broad scope of its possible applications in modulating brain activity for cognitive enhancement and treatment of brain disorders. This review aims to interface the recent developments in the study of both endogenous and exogenous electric fields, with a particular focus on rhythmic stimulation for the modulation of cortical oscillations. The main goal is to provide a starting point for the use of rational design for the development of novel mechanism-based TCS therapeutics based on transcranial alternating current stimulation, for the treatment of psychiatric illnesses.

This article is from Frontiers in Human Neuroscience , volume 7 . Abstract Major depressive disorder (MDD) is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive transcranial magnetic stimulation (rTMS) is a robust treatment for MDD, but the mechanism of action (MOA) of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this MOA and achieve better antidepressant effectiveness. We propose that rTMS can be administered: (1) synchronized to a patient's individual alpha frequency (IAF), or synchronized rTMS (sTMS); (2) as a low magnetic field strength sinusoidal waveform; and, (3) broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

This article is from PLoS ONE , volume 9 . Abstract Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.