Search

Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition that is difficult to treat due to our limited understanding of its pathophysiology. Functional connectivity in brain networks, as evaluated through neuroimaging studies, plays a pivotal role in understanding OCD. While both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been extensively employed in OCD research, few have fully synthesized their findings. To bridge this gap, we reviewed 166 studies (10 EEG, 156 fMRI) published up to December 2023. In EEG studies, OCD exhibited lower connectivity in delta and alpha bands, with inconsistent findings in other frequency bands. Resting-state fMRI studies reported conflicting connectivity patterns within the default mode network (DMN) and sensorimotor cortico-striato-thalamo-cortical (CSTC) circuitry. Many studies observed decreased resting-state connectivity between the DMN and salience network (SN), implicating the 'triple network model' in OCD. Task-related hyperconnectivity within the DMN-SN and hypoconnectivity between the SN and frontoparietal network suggest OCD-related cognitive inflexibility, potentially due to triple network dysfunction. In conclusion, our review highlights diverse connectivity differences in OCD, revealing complex brain network interplay that contributes to symptom manifestation. However, the presence of conflicting findings underscores the necessity for targeted research to achieve a comprehensive understanding of the pathophysiology of OCD., (© The Author(s) 2024. Published by Oxford University Press.)

Brain connectivity can be estimated through many analyses applied to electroencephalography (EEG) data. However, substantial heterogeneity in the implementation of connectivity methods exists. Heterogeneity in conceptualization of connectivity measures, data collection, or data preprocessing may be associated with variability in robustness of measurement. While it is difficult to compare the results of studies using different EEG connectivity measures, standardization of processing and reporting may facilitate the task. We discuss how factors such as referencing, epoch length and number, controls for volume conduction, artifact removal, and statistical control of multiple comparisons influence the EEG connectivity estimate for connectivity measures, and what can be done to control for potential confounds associated with these factors. Based on the results reported in previous literature, this article presents recommendations and a novel checklist developed for quality assessment of EEG connectivity studies. This checklist and its recommendations are made in an effort to draw attention to factors that may influence connectivity estimates and factors that need to be improved in future research. Standardization of procedures and reporting in EEG connectivity may lead to EEG connectivity studies being made more synthesizable and comparable despite variations in the methodology underlying connectivity estimates., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is characterized by a progressive decline in cognitive functioning for which there is a stark lack of effective treatments. Investigating the neurophysiological markers of symptom severity in AD may aid in the identification of alternative treatment targets., Objective: In the current study we used a multimodal approach to investigate the association between functional connectivity (specifically between scalp electrodes placed over frontal and parietal regions) and symptom severity in AD, and to explore the relationship between connectivity and cortical excitability., Methods: 40 people with AD (25 mild severity, 15 moderate severity) underwent neurobiological assessment (resting state electroencephalography (EEG) and prefrontal transcranial magnetic stimulation (TMS) with EEG) and cognitive assessment. Neurobiological outcomes were resting state functional connectivity and TMS-evoked potentials. Cognitive outcomes were scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, and a measure of episodic verbal learning., Results: Greater contralateral functional theta connectivity between frontal scalp electrodes and parietal scalp electrodes was associated with poorer cognitive performance. In addition, significant correlations were seen between the contralateral theta connectivity and the N100 and P60 TMS-evoked potentials measured from electrodes over the left dorsolateral prefrontal cortex., Conclusion: Together these findings provide initial support for the use of multimodal neurophysiological approaches to investigate potential therapeutic targets in AD. Suggestions for future research are discussed.

Background: Anxiety disorders are highly prevalent and cause substantial personal, social and economic burden. Altered attentional control has been shown to be present across anxiety disorders and is associated with specific changes in brain activity which can be recorded by electroencephalogram (EEG). These include changes in the EEG markers of error-related negativity (ERN) and correct-response negativity (CRN), both believed to reflect response monitoring and attentional control pathophysiology in anxiety. The aim of this review was to systematically assess the research on ERN and CRN in attentional control in individuals with clinical anxiety and healthy controls, across emotional and non-emotional attentional control., Methods: A comprehensive literature search was conducted for studies published prior to October 22 nd , 2020. Details of the protocol for this systematic review were registered on PROSPERO (CRD42019144885)., Results: 66 studies had their data extracted. All 66 studies measured ERN, with 85% finding significantly increased ERN amplitudes associated with clinical anxiety. Only 44 of the extracted studies analysed CRN and only ~20% of these found significant changes in CRN amplitude associated with individuals with clinical anxiety., Limitations: There were several anxiety disorders that had either limited literature (i.e. specific phobia, separation anxiety disorder or agoraphobia) or nil literature (i.e. selective mutism) available. No extracted studies included samples of older adults (i.e. aged 60+ years), and only six extracted studies included measures of emotional attentional control., Conclusions: Findings indicate the promising utility of ERN of attentional control as a robust, transdiagnostic trait marker of clinical anxiety., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Magnetic seizure therapy (MST) is emerging as a safe and well-tolerated experimental intervention for major depressive disorder (MDD), with very minimal cognitive side-effects. However, the underlying mechanism of action of MST remains uncertain. Here, we used resting-state electroencephalography (RS-EEG) to characterise the physiological effects of MST for treatment resistant MDD. We recorded RS-EEG in 21 patients before and after an open label trial of MST applied over the prefrontal cortex using a bilateral twin coil. RS-EEG was analysed for changes in functional connectivity, network topology, and spectral power. We also ran further baseline comparisons between the MDD patients and a cohort of healthy controls (n = 22). Network-based connectivity analysis revealed a functional subnetwork of significantly increased theta connectivity spanning frontal and parieto-occipital channels following MST. The change in theta connectivity was further found to predict clinical response to treatment. An additional widespread subnetwork of reduced beta connectivity was also elucidated. Graph-based topological analyses showed an increase in functional network segregation and reduction in integration in the theta band, with a decline in segregation in the beta band. Finally, delta and theta power were significantly elevated following treatment, while gamma power declined. No baseline differences between MDD patients and healthy subjects were observed. These results highlight widespread changes in resting-state brain dynamics following a course of MST in MDD patients, with changes in theta connectivity providing a potential physiological marker of treatment response. Future prospective studies are required to confirm these initial findings., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Our previous research showed high predictive accuracy at differentiating responders from non-responders to repetitive transcranial magnetic stimulation (rTMS) for depression using resting electroencephalography (EEG) and clinical data from baseline and one-week following treatment onset using a machine learning algorithm. In particular, theta (4-8 Hz) connectivity and alpha power (8-13 Hz) significantly differed between responders and non-responders. Independent replication is a necessary step before the application of potential predictors in clinical practice. This study attempted to replicate the results in an independent dataset., Methods: We submitted baseline resting EEG data from an independent sample of participants who underwent rTMS treatment for depression (N = 193, 128 responders) (Krepel et al., 2018) to the same between group comparisons as our previous research (Bailey et al., 2019)., Results: Our previous results were not replicated, with no difference between responders and non-responders in theta connectivity (p = 0.250, Cohen's d = 0.1786) nor alpha power (p = 0.357, η p 2  = 0.005)., Conclusions: These results suggest that baseline resting EEG theta connectivity or alpha power are unlikely to be generalisable predictors of response to rTMS treatment for depression., Significance: These results highlight the importance of independent replication, data sharing and using large datasets in the prediction of response research., Competing Interests: Declaration of Competing Interest MA is unpaid research director of the Brainclinics Foundation, a minority shareholder in neuroCare Group (Munich, Germany), and a co-inventor on 4 patent applications related to EEG, neuromodulation and psychophysiology, but receives no royalties related to these patents; Brainclinics Foundation received research funding from Brain Resource (Sydney, Australia), Urgotech (France) and neuroCare Group (Munich, Germany), and equipment support from Deymed, neuroConn, Brainsway and Magventure. FVR receives research support from Canadian Institutes of Health Research, Brian Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute, and in-kind equipment support for investigator-initiated trial from MagVenture. He has participated in an advisory board for Janssen. PBF is supported by a NHMRC Practitioner Fellowship (1078567). PBF has received equipment for research from MagVenture A/S, Medtronic Ltd, Neuronetics and Brainsway Ltd and funding for research from Neuronetics. He is on scientific advisory boards for Bionomics Ltd and LivaNova and is founder of TMS Clinics Australia. AFL discloses that he has received research support from NIH, Neuronetics, Breast Cancer Foundation, Department of Defense, CHDI Foundation, and Neurosigma. He has served as a consultant to Ionis Pharmaceuticals, CHDI Foundation, and NeoSync, Inc. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). He has stock options in NeoSync, Inc. and equity interest in BBA. DMB has received research support from the CIHR, NIH, Brain Canada and the Temerty Family Foundation through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd., and he is the principal site investigator for three sponsor-initiated studies for Brainsway Ltd. He received in-kind equipment support from Magventure for investigator-initiated research. He received medication supplies for an investigator-initiated trial from Indivior.He has participated in an advisory board for Janssen. LLC discloses that she has received research support from NIH, Neuronetics, Nexstim, Janssen, Neosync, and Affect Neuro. She has received consulting income from Janssen and Affect Neuro. In the last 5 years, ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH) and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. JC, NK, HvD, NWB, and CR have nothing to disclose., (Copyright © 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Increasing evidence points to an analgesic influence of social support context, in which the dorsomedial prefrontal cortex (dmPFC) may play a key role. Transcranial Magnetic Stimulation (TMS) has the capacity to causally modulate brain activity. This study was designed to investigate the potential role of dmPFC in orchestrating the behavioral and neural effects of social context during pain. Twenty-three healthy participants underwent a three-session cross-over, single-blinded, sham-controlled protocol in which they received Theta Burst Stimulation (TBS) (facilitatory intermittent TBS, suppressive continuous TBS, or Sham) delivered to the dmPFC. In each session, participants underwent cold pain while viewing an image of a romantic partner or a stranger. Effects of TBS to the dmPFC were assessed using a measure of pain perception, neural activity and network connectivity using electroencephalography (EEG) and TMS-EEG. In the stranger condition, pain experience increased following iTBS. This was associated with increased connectivity between central regions and fronto-parietal regions. In contrast, in the romantic partner condition, iTBS increased connectivity only between frontal and occipital regions and did not modulate pain experience. In line with recent studies, neither cTBS nor Sham stimulation elicited neural or behavioral changes. Together these findings suggest that the dmPFC has the capacity to causally modulate pain-related information integration and network configuration in a context-dependent manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS-EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS-EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS-EEG methodology and discuss the current state of knowledge regarding the use of TMS-EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS-EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS-EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS-EEG as a clinical tool., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Recent studies have highlighted variability in response to theta burst stimulation (TBS) in humans. TBS paradigm was originally developed in rodents to mimic gamma bursts coupled with theta rhythms, and was shown to elicit long-term potentiation. The protocol was subsequently adapted for humans using standardised frequencies of stimulation. However, each individual has different rhythmic firing pattern. The present study sought to explore whether individualised intermittent TBS (Ind iTBS) could outperform the effects of two other iTBS variants. Twenty healthy volunteers received iTBS over left prefrontal cortex using 30 Hz at 6 Hz, 50 Hz at 5 Hz, or individualised frequency in separate sessions. Ind iTBS was determined using theta-gamma coupling during the 3-back task. Concurrent use of transcranial magnetic stimulation and electroencephalography (TMS-EEG) was used to track changes in cortical plasticity. We also utilised mood ratings using a visual analogue scale and assessed working memory via the 3-back task before and after stimulation. No group-level effect was observed following either 30 or 50 Hz iTBS in TMS-EEG. Ind iTBS significantly increased the amplitude of the TMS-evoked P60, and decreased N100 and P200 amplitudes. A significant positive correlation between neurophysiological change and change in mood rating was also observed. Improved accuracy in the 3-back task was observed following both 50 Hz and Ind iTBS conditions. These findings highlight the critical importance of frequency in the parameter space of iTBS. Tailored stimulation parameters appear more efficacious than standard paradigms in neurophysiological and mood changes. This novel approach presents a promising option and benefits may extend to clinical applications., (© 2018 Wiley Periodicals, Inc.)

Background: Previous research has typically focussed on the neuromodulatory effects of direct currents applied over single regions of the cortex. However, complex processes such as working memory (WM) strongly rely on activations across a wider neural network and therefore might benefit from stimulation administered over multiple cortical targets., Objective: We examined the neurobiological and cognitive effects of High-Definition transcranial direct current stimulation (HD-tDCS) montages that either targeted the dorsolateral prefrontal cortex (DLPFC) alone, or simultaneously stimulated the DLPFC and parietal cortex (DLPFC + PC)., Methods: In a within-subjects design, 16 healthy participants completed three experimental sessions in which they received HD-tDCS over either the DLPFC, the DLPFC + PC or sham stimulation. Changes in cortical reactivity were examined using transcranial magnetic stimulation combined with electroencephalography (TMS-EEG), while oscillatory power was measured via EEG recorded during n-back tasks. WM performance was also examined across several separate tasks., Results: Stimulation using both the DLPFC or DLPFC + PC montages modulated cortical reactivity, as indexed by potentiation of the P60 TMS-evoked potential. However, only the dual-site DLPFC + PC stimulation produced a reduction in the amplitude of the N100 component, relative to baseline. Increases in theta and gamma power were also observed following this montage, when compared to baseline, but were not present following HD-tDCS over the DLPFC alone. Despite these neurophysiological changes, WM performance was not significantly modulated by HD-tDCS, regardless of stimulation montage., Conclusion: These results provide important initial insight into the behavioural and biological effects of stimulation over key cortical regions linked to WM and attest to the sensitivity of TMS-EEG and EEG in detecting subtle neurophysiological changes induced by HD-tDCS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: To examine the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) on cortical reactivity in the dorsolateral prefrontal cortex., Methods: 10 healthy participants were stimulated with either iTBS, cTBS or sham at F3 electrode. Single- and paired-pulse TMS and concurrent electroencephalography (EEG) were used to assess change in cortical reactivity and long-interval intracortical inhibition (LICI) via TMS-evoked potentials (TEPs) and TMS-evoked oscillations., Results: Significant increases in N120 amplitudes (p<0.01) were observed following iTBS over prefrontal cortex. Changes in TMS-evoked theta oscillations and LICI of theta oscillations were also observed following iTBS (increase) and cTBS (decrease). Change in LICI of theta oscillations correlated with change in N120 amplitude following TBS (r=-0.670, p=0.001)., Conclusions: This study provides preliminary evidence that TBS produces direct changes in cortical reactivity in the prefrontal cortex. Combining TBS with TMS-EEG may be a useful approach to optimise stimulation paradigms prior to the conduct of clinical trials., Significance: TBS is able to modulate cortical reactivity and cortical inhibition in the prefrontal cortex., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The concurrent use of transcranial magnetic stimulation with electroencephalography (TMS-EEG) is growing in popularity as a method for assessing various cortical properties such as excitability, oscillations and connectivity. However, this combination of methods is technically challenging, resulting in artifacts both during recording and following typical EEG analysis methods, which can distort the underlying neural signal. In this article, we review the causes of artifacts in EEG recordings resulting from TMS, as well as artifacts introduced during analysis (e.g. as the result of filtering over high-frequency, large amplitude artifacts). We then discuss methods for removing artifacts, and ways of designing pipelines to minimise analysis-related artifacts. Finally, we introduce the TMS-EEG signal analyser (TESA), an open-source extension for EEGLAB, which includes functions that are specific for TMS-EEG analysis, such as removing and interpolating the TMS pulse artifact, removing and minimising TMS-evoked muscle activity, and analysing TMS-evoked potentials. The aims of TESA are to provide users with easy access to current TMS-EEG analysis methods and to encourage direct comparisons of these methods and pipelines. It is hoped that providing open-source functions will aid in both improving and standardising analysis across the field of TMS-EEG research., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Preclinical studies suggest that cortical alterations within the prefrontal cortex (PFC) are critical to the pathophysiology of alcohol dependence. Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows direct assessment of cortical excitability and inhibition within the PFC of human subjects. We report the first application of TMS-EEG to measure these indices within the PFC of alcohol-dependent (ALD) patients post-detoxification., Methods: Cortical inhibition was assessed in 12 ALD patients and 14 healthy controls through single and paired-pulse TMS paradigms. Long-interval cortical inhibition indexed cortical inhibition in the PFC. In the motor cortex (MC), short- interval intracortical inhibition and cortical silent period determined inhibition, while intracortical facilitation measured facilitation, resting and active motor threshold indexed cortical excitability., Results: ALD patients demonstrated altered cortical inhibition across the bilateral frontal cortices relative to controls. There was evidence of altered cortical excitability in ALD patients; however, no significant differences in MC inhibition., Conclusions: Our study provides first direct evidence of reduced cortical inhibition in the PFC of ALD patients post-detoxification. Altered cortical excitability in the MC may reflect hyper-excitability within the cortex associated with chronic alcohol consumption. These findings provide initial neurophysiological evidence of disrupted cortical excitability within the PFC of ALD patients.

Objective: Neuroimaging and electrophysiological research have revealed a range of neural abnormalities in autism spectrum disorder (ASD), but a comprehensive understanding remains elusive. We utilized a novel methodology among individuals with ASD and matched controls, combining transcranial magnetic stimulation (TMS) with concurrent electroencephalogram (EEG) recording (TMS-EEG) to explore cortical function and connectivity in three sites implicated in the neuropathophysiology of ASD (dorsolateral prefrontal cortex, primary motor cortex, and temporoparietal junction). As there is evidence for neurobiological gender differences in ASD, we also examined the influence of biological sex., Methods: TMS pulses were applied to each of the three sites (right lateralized) during 20-channel EEG recording., Results: We did not identify any differences in the EEG response to TMS between ASD and control groups. This finding remained when data were stratified by sex. Nevertheless, traits and characteristics associated with ASD were correlated with the neurophysiological response to TMS., Conclusion: While TMS-EEG did not appear to clarify the neuropathophysiology of ASD, the relationships identified between the neurophysiological response to TMS and clinical characteristics warrant further investigation.

Transcranial electrical stimulation (tES) techniques are able to induce changes in cortical excitability and plasticity through the administration of weak currents to the brain and are currently being used to manipulate a vast array of cognitive processes. Despite the widespread use of tES technologies within both research and remedial settings, their precise neurophysiological mechanisms of action are not well established outside of the motor cortex. The expanding use of tES within non-motor brain regions highlights the growing need for a more comprehensive understanding of the effects of stimulation across a diversity of cortical locations. The combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) provides a method of directly probing both local and widespread changes in brain neurophysiology, through the recording of TMS-evoked potentials and cortical oscillations. In this review we explore TMS-EEG as a tool for examining the impact of tES on cortical function and argue that multimodal approaches which combine tES with TMS-EEG could lead to a deeper understanding of the mechanisms which underlie tES-induced cognitive modulation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Importance: Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder., Objective: To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG)., Design, Setting, and Participants: Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site., Interventions: The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used., Main Outcomes and Measures: Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP., Results: Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex-but not in the motor cortex-were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003)., Conclusions and Relevance: These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response.

Neuromodulatory brain stimulation can induce plastic reorganization of cortical circuits that persist beyond the period of stimulation. Most of our current knowledge about the physiological properties has been derived from the motor cortex. The integration of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) is a valuable method for directly probing excitability, connectivity and oscillatory dynamics of regions throughout the brain. Offering in depth measurement of cortical reactivity, TMS-EEG allows the evaluation of TMS-evoked components that may act as a marker for cortical excitation and inhibition. A growing body of research is using concurrent TMS and EEG (TMS-EEG) to explore the effects of different neuromodulatory techniques such as repetitive TMS and transcranial direct current stimulation on cortical function, particularly in non-motor regions. In this review, we outline studies examining TMS-evoked potentials and oscillations before and after, or during a single session of brain stimulation. Investigating these studies will aid in our understanding of mechanisms involved in the modulation of excitability and inhibition by neuroplasticity following different stimulation paradigms., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Introduction: The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a powerful tool for causally investigating cortical mechanisms and networks. However, various artefacts contaminate TMS-EEG recordings, particularly over regions such as the dorsolateral prefrontal cortex (DLPFC). The aim of this study was to substantiate removal of artefacts from TMS-EEG recordings following stimulation of the DLPFC and motor cortex using independent component analysis (ICA)., Methods: 36 healthy volunteers (30.8 ± 9 years, 9 female) received 75 single TMS pulses to the left DLPFC or left motor cortex while EEG was recorded from 57 electrodes. A subset of 9 volunteers also received 50 sham pulses. The large TMS artefact and early muscle activity (-2 to ~15 ms) were removed using interpolation and the remaining EEG signal was processed in two separate ICA runs using the FastICA algorithm. Five sub-types of TMS-related artefacts were manually identified: remaining muscle artefacts, decay artefacts, blink artefacts, auditory-evoked potentials and other noise-related artefacts. The cause of proposed blink and auditory-evoked potentials was assessed by concatenating known artefacts (i.e. voluntary blinks or auditory-evoked potentials resulting from sham TMS) to the TMS trials before ICA and evaluating grouping of resultant independent components (ICs). Finally, we assessed the effect of removing specific artefact types on TMS-evoked potentials (TEPs) and TMS-evoked oscillations., Results: Over DLPFC, ICs from proposed muscle and decay artefacts correlated with TMS-evoked muscle activity size, whereas proposed TMS-evoked blink ICs combined with voluntary blinks and auditory ICs with auditory-evoked potentials from sham TMS. Individual artefact sub-types characteristically distorted each measure of DLPFC function across the scalp. When free of artefact, TEPs and TMS-evoked oscillations could be measured following DLPFC stimulation. Importantly, characteristic TEPs following motor cortex stimulation (N15, P30, N45, P60, N100) could be recovered from artefactual data, corroborating the reliability of ICA-based artefact correction., Conclusions: Various different artefacts contaminate TMS-EEG recordings over the DLPFC and motor cortex. However, these artefacts can be removed with apparent minimal impact on neural activity using ICA, allowing the study of TMS-evoked cortical network properties., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) is an emerging method for studying cortical network properties. However, various artifacts affect measurement of TMS-evoked cortical potentials (TEPs), especially within 30 ms of stimulation., Objective/hypothesis: The aim of this study was to assess the origin and recovery of short-latency TMS-EEG artifacts (<30 ms) using different stimulators and under different experimental conditions., Methods: EEG was recorded during TMS delivered to a phantom head (melon) and 12 healthy volunteers with different TMS machines, at different scalp positions, at different TMS intensities, and following paired-pulse TMS. Recovery from the TMS artifact and other short-latency artifacts were compared between conditions., Results: Following phantom stimulation, the artifact resulting from different TMS machines (Magstim 200, Magventure MagPro R30 and X100) and pulse shapes (monophasic and biphasic) resulted in different artifact profiles. After accounting for differences between machines, TMS artifacts recovered within ∼12 ms. This was replicated in human participants, however a large secondary artifact (peaks at 5 and 10 ms) became prominent following stimulation over lateral scalp positions, which only recovered after ∼25-40 ms. Increasing TMS intensity increased secondary artifact amplitude over both motor and prefrontal cortex. There was no consistent modulation of the secondary artifact following inhibitory paired-pulse TMS (interstimulus interval = 100 ms) over motor cortex., Conclusions: The secondary artifact observed in humans is consistent with activation of scalp muscles following TMS. TEPs can be recorded within a short period of time (10-12 ms) following TMS, however measures must be taken to avoid muscle stimulation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The past decade has seen significant developments in the concurrent use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to directly assess cortical network properties such as excitability and connectivity in humans. New hardware solutions, improved EEG amplifier technology, and advanced data processing techniques have allowed substantial reduction of the TMS-induced artifact, which had previously rendered concurrent TMS-EEG impossible. Various physiological artifacts resulting from TMS have also been identified, and methods are being developed to either minimize or remove these sources of artifact. With these developments, TMS-EEG has unlocked regions of the cortex to researchers that were previously inaccessible to TMS. By recording the TMS-evoked response directly from the cortex, TMS-EEG provides information on the excitability, effective connectivity, and oscillatory tuning of a given cortical area, removing the need to infer such measurements from indirect measures. In the following review, we investigate the different online and offline methods for reducing artifacts in TMS-EEG recordings and the physiological information contained within the TMS-evoked cortical response. We then address the use of TMS-EEG to assess different cortical mechanisms such as cortical inhibition and neural plasticity, before briefly reviewing studies that have utilized TMS-EEG to explore cortical network properties at rest and during different functional brain states., (Copyright © 2012 Wiley Periodicals, Inc.)

Chronic pain is debilitating disorder in which the underlying pathophysiology is still unknown. Impaired cortical inhibition is one mechanism that is associated with chronic pain. Cortical inhibition refers to a neurophysiological process in which gamma-aminobutyric acid (GABA) inhibitory interneurons selectively attenuate the activity of pyramidal neurons in the cortex. Previous studies have capitalized on the ability of transcranial magnetic stimulation (TMS) to index cortical inhibition by stimulating the motor cortex and measuring the resulting peripheral motor evoked potentials with electromyography. Chronic pain has been shown to induce changes in cortical inhibition within the motor cortex using TMS. Electroencephalography (EEG) studies also demonstrate that gamma (30-50 Hz) oscillations in the prefrontal and somatosensory cortex are associated with the experience of pain. As gamma oscillations are mediated by GABA, the combination of TMS with EEG allows for the examination of the relationship between cortical inhibition, gamma and chronic pain. In this paper, we summarize the evidence of impaired GABAergic and gamma oscillations in chronic pain patients. We then demonstrate TMS-EEG as a reliable method in which to record cortical inhibition directly from the prefrontal cortex to examine the modulatory effect of GABAB receptor inhibition on cortical oscillations. Finally, the modulation of GABA and gamma oscillations with repetitive TMS will be suggested as the possible mechanism through which rTMS exerts its therapeutic effects in the treatment of pain. The aim of this paper, therefore, is to present the TMS-EEG as a potential method through which to better classify, diagnose and treat chronic pain.

Cognitive dysfunction is suggested to be the best predictor of functional outcome in schizophrenia. Therefore, new diagnostic and treatment strategies are needed to both ascertain the biological underpinning of cognitive deficits and to restore them. Modulation of gamma oscillations (30-50 Hz) has been associated with cognitive performance, particularly in the dorsolateral prefrontal cortex (DLPFC). In this manuscript, we review evidence for gamma modulation deficits during cognitive performance in schizophrenia. We demonstrate that transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) is a reliable method that permits systematic quantification of gamma modulation in the cortex. Using TMS-EEG, we show that patients with schizophrenia have selective gamma inhibition deficits in the DLPFC. Finally, we demonstrate that repetitive TMS therapy over the DLPFC can normalize excessive gamma oscillations and ultimately cognitive performance in patients. We suggest that restoring gamma impairments in the DLPFC may be a potential strategy for improving cognitive deficits in schizophrenia., (© 2012 New York Academy of Sciences.)

Transcranial magnetic stimulation (TMS) is used to index several neurophysiological processes including excitability, inhibition and plasticity. However, these measures are conventionally limited to the motor cortex and recorded from peripheral muscles. This represents a significant limitation when non-motor neurophysiological processes are of primary interest. In the last several years, TMS has been combined with electroencephalography (EEG) to derive such measures directly from the cortex. Initial studies demonstrated that meaningful recordings could be derived without being substantially affected by TMS stimulus artifact due to advancements in EEG amplifier technology. Subsequently, TMS measures of cortical excitability were reliably recorded and found to be related with more conventional TMS electromyography recordings of excitability in the cortex. More recently, other key neurophysiological indices including cortical inhibition and interhemispheric connectivity have also been reported. In this article, such findings will be reviewed and their importance discussed vis à vis healthy and disease states. We will conclude by highlighting the limitations of this work and discuss their potential future applications as a biomarker of disease states., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Cortical inhibition (CI) is measured by transcranial magnetic stimulation (TMS) combined with electromyography (EMG) through long-interval CI (LICI) and cortical silent period (CSP) paradigms. Recently, we illustrated that LICI can be measured from the dorsolateral prefrontal cortex (DLPFC) through combined TMS with electroencephalography (EEG). We further demonstrated that LICI had different effects on cortical oscillations in the DLPFC compared with motor cortex. The purpose of this study was to establish the validity and reliability of TMS-EEG indices of CI and to replicate our previous findings in an extended sample. The validity of TMS-EEG was examined by evaluating its relationship to standard EMG measures of LICI and the CSP in the left motor cortex in 36 and 16 subjects, respectively. Test-retest reliability was examined in 14 subjects who returned for a repeat session within 7 days of the first session. LICI was applied to the left DLPFC in 30 subjects to compare LICI in the DLPFC with that in the motor cortex. In the motor cortex, EEG measures of LICI correlated with EMG measures of LICI and CSP. All indices of LICI showed high test-retest reliability in motor cortex and DLPFC. Gamma and beta oscillations were significantly inhibited in the DLPFC but not in the motor cortex, confirming previous findings in an extended sample. These findings demonstrate that indexing LICI through TMS combined with EEG is a valid and reliable method to evaluate inhibition from motor and prefrontal regions.

Background: Major Depressive Disorder is widely recognised to be a heterogeneous syndrome with numerous depressive phenotypes, one of which is melancholic depression. Patients with melancholic depression exhibit treatment responses and outcomes that differ from patients with non-melancholic depression. The current study aimed to assess whether differences existed between melancholic and non-melancholic subtypes of depression, as measured by the event related potential, intensity dependence of the auditory evoked potential (IDAEP)., Methods: IDAEP was assessed in 14 melancholic and 13 non-melancholic depressed subjects and 14 controls., Results: The melancholic patients had a significantly shallower IDAEP slope than the non-melancholic patients not explained by depression severity or age., Limitations: Antidepressants were taken by all patients in this study and the effect of continual use of these drugs on the IDAEP slopes has yet to be confirmed., Conclusions: These results provide support for neurobiological differences between melancholic and non-melancholic depressive subtypes. Melancholic depression may be characterized by ongoing over function of the serotonin system in spite of medication treatment.

Objective: The induction of long interval cortical inhibition (LICI) in motor cortex with paired pulse transcranial magnetic stimulation (ppTMS) is an established paradigm for the assessment of cortical inhibition, proposed to be related to GABA(B) receptor inhibitory neurotransmission. This study aimed to further evaluate recent methods of the assessment of LICI in non motor regions with ppTMS and electroencephalography (EEG)., Methods: ppTMS was applied using a single coil to the motor and dorsolateral prefrontal cortex (DLPFC) in 14 healthy subjects, and in the parietal lobe in 5 of those subjects., Results: In the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250 ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250 ms in DLPFC, and between 50 and 175 ms in the parietal lobe., Conclusions: ppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABA(B) activity., Significance: ppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABA(B) activity.

Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8+/-30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1+/-26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.

A number of studies using paired pulse transcranial magnetic stimulation (TMS) have demonstrated that cortical inhibition (CI) of the motor cortex can be recorded and also gauged through surface electromyography. However, recording CI from other brain regions that are more directly related with the pathophysiology of some neurologic and psychiatric disorders (e.g., dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously fraught with technical difficulties. This study was therefore designed to examine, through a combination of TMS with EEG, whether CI could be measured directly from the motor cortex, DLPFC, and another non-motor region. To index CI, long interval cortical inhibition (LICI; a TMS paradigm) was used in the motor cortex and DLPFC in 14 healthy subjects, and in the parietal lobe in 5 of those subjects. In the motor cortex, LICI resulted in a significant suppression in mean cortical evoked activity on EEG (37.31 +/- 47.51%). In the DLPFC, LICI resulted in a significant suppression (32.45 +/- 47.86%) in mean cortical evoked activity and did not correlate with LICI in the motor cortex although they did not significantly differ. In the parietal lobe, LICI resulted in significant suppression (47.76 +/- 44.70%) in mean cortical evoked activity. In conclusion, CI in the dorsolateral prefrontal cortex, motor cortex and parietal cortex were similar at 120% of motor threshold. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurologic and psychiatric disorders.

Deficient inhibitory neurotransmission has been demonstrated in schizophrenia through electroencephalography (e.g. P50 suppression) and transcranial magnetic stimulation (e.g. short-interval cortical inhibition and the cortical silent period). It is not known whether these inhibitory paradigms are related despite evidence suggesting that both are coordinated through gamma-aminobutyric acid inhibitory neurotransmission. We explored the relationship between P50 suppression, short-interval cortical inhibition and the cortical silent period in 21 healthy participants using previously published methods. P50 suppression was significantly correlated with cortical silent period (r=-0.49, P=0.02) but not with short-interval cortical inhibition. As both P50 suppression and the cortical silent period have been linked to gamma-aminobutyric acidB receptor-mediated inhibitory neurotransmission, these data highlight the importance of this receptor subtype in the pathophysiology of schizophrenia.

Electroconvulsive therapy (ECT) is a highly effective neuromodulatory intervention for treatment-resistant major depressive disorder (MDD). Presently, however, understanding of its neurophysiological effects remains incomplete. In the present study, we utilised resting-state electroencephalography (RS-EEG) to explore changes in functional connectivity, network topology, and spectral power elicited by an acute open-label course of ECT in a cohort of 23 patients with treatment-resistant MDD. RS-EEG was recorded prior to commencement of ECT and again within 48 h following each patient's final treatment session. Our results show that ECT was able to enhance connectivity within lower (delta and theta) frequency bands across subnetworks largely confined to fronto-central channels, while, conversely, more widespread subnetworks of reduced connectivity emerged within faster (alpha and beta) bands following treatment. Graph-based topological analyses revealed changes in measures of functional segregation (clustering coefficient), integration (characteristic path length), and small-world architecture following ECT. Finally, post-treatment enhancement of delta and theta spectral power was observed, which showed a positive association with the number of ECT sessions received. Overall, our findings indicate that RS-EEG can provide a sensitive measure of dynamic neural activity following ECT and highlight network-based analyses as a promising avenue for furthering mechanistic understanding of the effects of convulsive therapies.

Background: Obsessive–compulsive disorder (OCD) is a psychiatric condition leading to significant distress and poor quality of life. Successful treatment of OCD is restricted by the limited knowledge about its pathophysiology. This study aimed to investigate the pathophysiology of OCD using electroencephalographic (EEG) event-related potentials (ERPs), elicited from multiple tasks to characterise disorder-related differences in underlying brain activity across multiple neural processes. Methods: ERP data were obtained from 25 OCD patients and 27 age- and sex-matched healthy controls (HCs) by recording EEG during flanker and go/nogo tasks. Error-related negativity (ERN) was elicited by the flanker task, while N200 and P300 were generated using the go/nogo task. Primary comparisons of the neural response amplitudes and the topographical distribution of neural activity were conducted using scalp field differences across all time points and electrodes. Results: Compared to HCs, the OCD group showed altered ERP distributions. Contrasting with the previous literature on ERN and N200 topographies in OCD where fronto-central negative voltages were reported, we detected positive voltages. Additionally, the P300 was found to be less negative in the frontal regions. None of these ERP findings were associated with OCD symptom severity. Conclusions: These results indicate that individuals with OCD show altered frontal neural activity across multiple executive function-related processes, supporting the frontal dysfunction theory of OCD. Furthermore, due to the lack of association between altered ERPs and OCD symptom severity, they may be considered potential candidate endophenotypes for OCD. [ABSTRACT FROM AUTHOR]

Although previous research in alcohol dependent populations identified alterations within local structures of the addiction 'reward' circuitry, there is limited research into global features of this network, especially in early recovery. Transcranial magnetic stimulation (TMS) is capable of non-invasively perturbing the brain network while electroencephalography (EEG) measures the network response. The current study is the first to apply a TMS inhibitory paradigm while utilising network science (graph theory) to quantify network anomalies associated with alcohol dependence. Eleven individuals with alcohol-dependence (ALD) in early recovery and 16 healthy controls (HC) were administered 75 single pulses and 75 paired-pulses (inhibitory paradigm) to both the left and right prefrontal cortex (PFC). For each participant, Pearson cross-correlation was applied to the EEG data and correlation matrices constructed. Global network measures (mean degree, clustering coefficient, local efficiency and global efficiency) were extracted for comparison between groups. Following administration of the inhibitory paired-pulse TMS to the left PFC, the ALD group exhibited altered mean degree, clustering coefficient, local efficiency and global efficiency compared to HC. Decreases in local efficiency increased the prediction of being in the ALD group, while all network metrics (following paired-pulse left TMS) were able to adequately discriminate between the groups. In the ALD group, reduced mean degree and global clustering was associated with increased severity of past alcohol use. Our study provides preliminary evidence of altered network topology in patients with alcohol dependence in early recovery. Network anomalies were predictive of high alcohol use and correlated with clinical features of alcohol dependence. Further research using this novel brain mapping technique may identify useful network biomarkers of alcohol dependence and recovery. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a well-established and effective treatment for depression, though response rates are suboptimal. Personalising TMS for depression with neuroimaging can take into account inter-individual differences in anatomical and electrophysiological characteristics; and thereby provide a potentially more efficacious form of treatment. The current systematic review aimed to critically appraise the literature relating to personalising TMS for depression with neuroimaging. PubMed, PsycINFO and Embase databases were used to identify relevant literature published up to November 2020. A total of 37 studies were included in the review. Across these studies, a total of 1451 patients with depression received TMS that was personalised using neuroimaging. The majority of the studies used structural or functional neuroimaging to personalise treatment target (n = 30), primarily through neuronavigation methodologies. Fewer studies used electroencephalography to personalise treatment frequency or stimulus timing (n = 7). Only 6 studies directly compared neuroimaging-personalised TMS to standard TMS. The findings from this review suggest that personalising TMS with neuroimaging may be more effective in the treatment of depression compared to standard TMS. Further research is required to directly compare neuroimaging-personalised TMS with standard TMS, and to identify the optimal parameters for treatment personalisation. [ABSTRACT FROM AUTHOR]

Attention is vital for optimal behavioural performance in every-day life. Mindfulness meditation has been shown to enhance attention. However, the components of attention altered by meditation and the related neural activities are underexplored. In particular, the contributions of inhibitory processes and sustained attention are not well understood. To address these points, 34 meditators were compared to 28 age and gender matched controls during electroencephalography (EEG) recordings of neural activity during a Go/Nogo response inhibition task. This task generates a P3 event related potential, which is related to response inhibition processes in Nogo trials, and attention processes across both trial types. Compared with controls, meditators were more accurate at responding to Go and Nogo trials. Meditators showed a more frontally distributed P3 to both Go and Nogo trials, suggesting more frontal involvement in sustained attention rather than activity specific to response inhibition. Unexpectedly, meditators also showed increased positivity over the right parietal cortex prior to visual information reaching the occipital cortex (during the pre-C1 window). Both results were positively related to increased accuracy across both groups. The results suggest that meditators show altered engagement of neural regions related to attention, including both higher order processes generated by frontal regions, and sensory anticipation processes generated by poster regions. This activity may reflect an increased capacity to modulate a range of neural processes in order to meet task requirements. This increased capacity may underlie the improved attentional function observed in mindfulness meditators. [ABSTRACT FROM AUTHOR]

Introduction: Bipolar patients have abnormalities in cognitive functions and emotional processing. Two resting state networks (RSNs), the default mode network (DMN) and the sensorimotor network (SMN), play a decisive role in these two functions. Dorsolateral prefrontal cortex (DLPFC) is one of the main areas in the central executive network (CEN), which is linked to the activities of each of the two networks. Studies have found DLPFC abnormalities in both hemispheres of patients with bipolar depression. We hypothesized that the bilateral repetitive transcranial magnetic stimulation (rTMS) of DLPFC would produce changes in the activity of both the SMN and DMN as well as relevant cognitive function in patients with bipolar depression that responded to treatment. Methods: 20 patients with bipolar depression underwent 10 sessions of 1 Hz rTMS on right DLPFC with subsequent 10 Hz rTMS on left DLPFC. Changes in electroencephalography resting networks between pre and post rTMS were evaluated utilizing low-resolution electromagnetic tomography (eLORETA). Depression symptom was assessed using the Beck Depression Inventory (BDI-II) and cognitive function was assessed by Verbal Fluency Test (VFT), Rey Auditory Verbal Learning Test (RAVLT), Stroop Test, and Wisconsin Card Sorting Test (WCST). Results: Responders to rTMS showed significantly lower DMN activity at baseline and a significant decrease in SMN connectivity after treatment. Non-responders did not significantly differ from the control group at the baseline and they showed higher activity in the SMN, visual network, and visual perception network compared to control group following treatment. Bilateral rTMS resulted in significant changes in the executive functions, verbal memory, and depression symptoms. No significant changes were observed in selective attention and verbal fluency. Conclusion: Bilateral stimulation of DLPFC, as the main node of CEN, results in changes in the activity of the SMN and consequently improves verbal memory and executive functions in patients with bipolar depression. [ABSTRACT FROM AUTHOR]

Primary objective: Alterations to functional connectivity following a traumatic brain injury (TBI) may lead to impaired cognitive performance and major depressive disorder (MDD). In particular, functional gamma band connectivity is thought to reflect information binding important for working memory. The objective of this study was to determine whether altered functional gamma connectivity may be a factor in MDD following TBI (TBI-MDD). Research design: This study assessed individuals with TBI-MDD, as well as individuals with TBI alone and MDD alone using electroencephalographic recordings while participants performed a working memory task to assess differences in functional connectivity between these groups. Methods and procedures: Functional connectivity was compared using the debiased weighted phase lag index (wPLI). wPLI was measured from a group of healthy controls (n = 31), participants with MDD (n = 17), participants with TBI (n = 20) and participants with TBI-MDD (n = 15). Main outcomes and results: Contrary to the predictions, this study found both the groups with TBI and TBI-MDD showed higher gamma connectivity from posterior regions during WM retention. Conclusions: This may reflect dysfunctional functional connectivity in these groups, as a result of maladaptive neuroplastic reorganization. [ABSTRACT FROM AUTHOR]

Importance: Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder.Objective: To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG).Design, Setting, and Participants: Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site.Interventions: The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used.Main Outcomes and Measures: Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP.Results: Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex-but not in the motor cortex-were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003).Conclusions and Relevance: These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response. [ABSTRACT FROM AUTHOR]

Social cognitive difficulties are common in the acute phase of bipolar disorder and, to a lesser extent, during the euthymic stage, and imaging studies of social cognition in euthymic bipolar disorder have implicated mirror system brain regions. This study aimed to use a novel multimodal approach (i.e., including both transcranial magnetic stimulation (TMS) and electroencephalogram (EEG)) to investigate mirror systems in bipolar disorder. Fifteen individuals with euthymic bipolar disorder and 16 healthy controls participated in this study. Single-pulse TMS was applied to the optimal site in the primary motor cortex (M1), which stimulates the muscle of interest during the observation of hand movements (goal-directed or interacting) designed to elicit mirror system activity. Single EEG electrodes (C3, CZ, C4) recorded mu rhythm modulation concurrently. Results revealed that the patient group showed significantly less mu suppression compared to healthy controls. Surprisingly, motor resonance was not significantly different overall between groups; however, bipolar disorder participants showed a pattern of reduced reactivity on some conditions. Although preliminary, this study indicates a potential mirror system deficit in euthymic bipolar disorder, which may contribute to the pathophysiology of the disorder. [ABSTRACT FROM PUBLISHER]

Background Deep brain stimulation (DBS) in the subcallosal cingulate gyrus (SCG) is becoming an effective therapeutic option for treatment resistant depression (TRD). Objective/hypothesis Identifying the neurophysiological mechanisms altered by DBS may lead to more tailored treatment parameters and enhanced efficacy. Methods Twenty TRD patients with implanted DBS in the SCG were recruited. Patients participated in three EEG recording sessions, one with DBS ON, one with DBS randomized to ON or OFF, and one with DBS OFF. During each session, subjects performed N-back working memory tasks, namely the 0-back and 3-back. Fourteen subjects with valid EEG were included in the analysis. Changes in frontal gamma oscillations (30–50 Hz) and coupling between theta (4–7 Hz) and gamma oscillations as a result of DBS stimulation were quantified and correlated with depressive symptoms. Results DBS stimulation resulted in suppression of frontal oscillations in the ON state relative to the OFF state during the N-back tasks. Greatest suppression was demonstrated in beta and gamma oscillations and most pronounced during the 3-back. Suppression of gamma oscillations in the 3-back correlated with a reduction in depressive symptoms. DBS ON relative to OFF in the 3-back also resulted in an increase in theta-gamma coupling that correlated with a reduction in depressive symptoms. Conclusion Suppression of gamma oscillations and increased theta-gamma coupling through DBS is likely mediated by both SCG activation of inhibitory circuits and an enhancement of plasticity in the frontal cortex. Activation of both pathways may explain the therapeutic properties of DBS in TRD. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a common debilitating condition where only one third of patients achieve remission after the first antidepressant treatment. Inadequate efficacy and adverse effects of current treatment strategies call for more effective and tolerable treatment options. Transcranial magnetic stimulation (TMS) is a noninvasive approach to manipulate brain activity and alter cortical excitability. There has been more than 15 years of research on the use of repetitive form of TMS (rTMS) for the treatment of patients with depression, which has shown it to be an effective antidepressant treatment. Even though rTMS treatment has shown efficacy in treating depression, there is a high degree of interindividual variability in response. A newer form of rTMS protocol, known as theta-burst stimulation (TBS), has been shown to produce similar if not greater effects on brain activity than standard rTMS. TBS protocols have a major advantage over standard rTMS approaches in their reduced administration duration. Conventional rTMS procedures last between 20 and 45 min, as compared to TBS paradigms that require 1 to 3 min of stimulation. Recently, a small number of studies have suggested that TBS has similar or better efficacy in treating depression compared to rTMS. Optimization, identification of response predictors, and clarification of neurobiological mechanisms of TBS is required if it is to be further developed as a less time intensive, safe, and effective treatment for MDD. [ABSTRACT FROM AUTHOR]

Using TMS and EEG, Radhu et al. reveal reductions in long-interval cortical inhibition specific to the dorsolateral prefrontal cortex in patients with schizophrenia compared to healthy subjects and individuals with obsessive-compulsive disorder (OCD). The absence of such changes in OCD confirms that reductions in inhibition are not a generalized deficit associated with severe psychopathology.Abnormal gamma-aminobutyric acid inhibitory neurotransmission is a key pathophysiological mechanism underlying schizophrenia. Transcranial magnetic stimulation can be combined with electroencephalography to index long-interval cortical inhibition, a measure of GABAergic receptor-mediated inhibitory neurotransmission from the frontal and motor cortex. In previous studies we have reported that schizophrenia is associated with inhibitory deficits in the dorsolateral prefrontal cortex compared to healthy subjects and patients with bipolar disorder. The main objective of the current study was to replicate and extend these initial findings by evaluating long-interval cortical inhibition from the dorsolateral prefrontal cortex in patients with schizophrenia compared to patients with obsessive-compulsive disorder. A total of 111 participants were assessed: 38 patients with schizophrenia (average age: 35.71 years, 25 males, 13 females), 27 patients with obsessive-compulsive disorder (average age: 36.15 years, 11 males, 16 females) and 46 healthy subjects (average age: 33.63 years, 23 females, 23 males). Long-interval cortical inhibition was measured from the dorsolateral prefrontal cortex and motor cortex through combined transcranial magnetic stimulation and electroencephalography. In the dorsolateral prefrontal cortex, long-interval cortical inhibition was significantly reduced in patients with schizophrenia compared to healthy subjects (P = 0.004) and not significantly different between patients with obsessive-compulsive disorder and healthy subjects (P = 0.5445). Long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex were also significantly greater in patients with schizophrenia compared to patients with obsessive-compulsive disorder (P = 0.0465). There were no significant differences in long-interval cortical inhibition across all three groups in the motor cortex. These results demonstrate that long-interval cortical inhibition deficits in the dorsolateral prefrontal cortex are specific to patients with schizophrenia and are not a generalized deficit that is shared by disorders of severe psychopathology. [ABSTRACT FROM AUTHOR]

Schizophrenia (SCZ) is a debilitating mental illness with an elusive pathophysiology. Over the last decade, theories emphasizing cortical dysfunction have received increasing attention to explain the heterogeneous symptoms experienced in SCZ. Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation that is particularly suited to probing the fidelity of specific excitatory and inhibitory neuronal populations in conscious humans. In this study, we review the contribution of TMS in assessing inhibitory and excitatory neuronal populations and their long-range connections in SCZ. In addition, we discuss insights from combined TMS and electroencephalography into the functional consequences of impaired excitation/inhibition on cortical oscillations in SCZ. [ABSTRACT FROM PUBLISHER]

Neuroplasticity and long-term potentiation (LTP) in the dorsolateral prefrontal cortex (DLPFC) are considered important mechanisms in learning and memory, and their disruption may be related to the pathophysiology of several neuropsychiatric disorders. Paired associative stimulation (PAS) is a brain stimulation paradigm that produces enhanced activity in the human motor cortex that may be related to LTP. In a group of 15 healthy participants, we report on the potentiation of cortical-evoked activity in the human DLPFC using the combination of PAS and electroencephalography. In contrast, a PAS control condition did not result in potentiation in another group of nine healthy participants. We also demonstrate that PAS-induced potentiation of cortical-evoked activity is characterized by anatomical specificity that is largely confined to the site of stimulation. Finally, we show that PAS results in potentiation of θ- and γ-activity and θ-phase-γ-amplitude coupling. These neurophysiological indices may be related to working memory, an important function of the DLPFC. To our knowledge, this is the first report of potentiation of cortical-evoked activity in the DLPFC. As this potentiation may be related to LTP, our findings provide a model through which neuroplasticity in health and disease states in the frontal cortex can be studied. [ABSTRACT FROM AUTHOR]

Highlights: [•] Neuroimaging tools have been critical for understanding pre- and symptomatic HD. [•] The relationship between pathophysiology and phenotype in HD is poorly understood. [•] TMS can inform causal relationships between neural circuitry and behaviour. [•] TMS–EEG can assess the integrity of neural networks in non-motor brain areas. [•] Neurophysiological measures may prove sensitive markers of progression in HD. [ABSTRACT FROM AUTHOR]