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Current diagnosis and treatment of psychiatric illnesses are still based on behavioral observations and self-reports, commonly leading to prolonged untreated illness. Biological markers (biomarkers) may offer an opportunity to revolutionize clinical psychiatry practice by helping provide faster and potentially more effective therapies. Transcranial magnetic stimulation concurrent with electroencephalography (TMS-EEG) is a noninvasive brain mapping methodology that can assess the functions and dynamics of specific brain circuitries in awake humans and aid in biomarker discovery. This article provides an overview of TMS-EEG–based biomarkers that may hold potential in psychiatry. The methodological readiness of the TMS-EEG approach and steps in the validation of TMS-EEG biomarkers for clinical utility are discussed. Biomarker discovery with TMS-EEG is in the early stages, and several validation steps are still required before clinical implementations are realized. Thus far, TMS-EEG predictors of response to magnetic brain stimulation treatments in particular have shown promise for translation to clinical practice. Larger-scale studies can confirm validation followed by biomarker-informed trials to assess added value compared to existing practice. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) evokes neuronal activity in the targeted cortex and connected brain regions. The evoked brain response can be measured with electroencephalography (EEG). TMS combined with simultaneous EEG (TMS−EEG) is widely used for studying cortical reactivity and connectivity at high spatiotemporal resolution. Methodologically, the combination of TMS with EEG is challenging, and there are many open questions in the field. Different TMS−EEG equipment and approaches for data collection and analysis are used. The lack of standardization may affect reproducibility and limit the comparability of results produced in different research laboratories. In addition, there is controversy about the extent to which auditory and somatosensory inputs contribute to transcranially evoked EEG. This review provides a guide for researchers who wish to use TMS−EEG to study the reactivity of the human cortex. A worldwide panel of experts working on TMS−EEG covered all aspects that should be considered in TMS−EEG experiments, providing methodological recommendations (when possible) for effective TMS−EEG recordings and analysis. The panel identified and discussed the challenges of the technique, particularly regarding recording procedures, artifact correction, analysis, and interpretation of the transcranial evoked potentials (TEPs). Therefore, this work offers an extensive overview of TMS−EEG methodology and thus may promote standardization of experimental and computational procedures across groups. • TMS−EEG is a powerful technique for basic research and clinical applications. • The methodological combination of TMS−EEG is challenging. • The lack of standardization may affect reproducibility and limit the comparability of results produced across groups. • This article covers all aspects that should be considered in TMS−EEG experiments. • We provide methodological recommendations for effective TMS−EEG recordings and analysis. [ABSTRACT FROM AUTHOR]

The concurrent combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) can unveil functional neural mechanisms with applications in basic and clinical research. In particular, TMS-evoked potentials (TEPs) potentially allow studying excitability and connectivity of the cortex in a causal manner that is not easily or non-invasively attainable with other neuroimaging techniques. The TEP waveform is obtained by isolating the EEG responses phase-locked to the time of TMS application. The intended component in a TEP waveform is the cortical activation by the TMS-induced electric current, free of instrumental and physiological artifact sources. This artifact-free cortical activation can be referred to as 'true' TEP. However, due to many unwanted auxiliary effects of TMS, the interpretation of 'true' TEPs has not been free of controversy. This paper reviews the most recent understandings of 'true' TEPs and their application. In the first part of the paper, TEP components are defined according to recommended methodologies. In the second part, the verification of 'true' TEP is discussed along with its sensitivity to brain-state, age, and disease. The various proposed origins of TEP components are then presented in the context of existing literature. Throughout the paper, lessons learned from the past TMS-EEG studies are highlighted to guide the identification and interpretation of 'true' TEPs in future studies. • True TEP is the artifact-free cortical activation by TMS-induced electric current. • There are online and offline strategies to uncover true TEPs. • TEPs potentially allow studying excitability and connectivity. [ABSTRACT FROM AUTHOR]

Background Deep brain stimulation (DBS) has treatment efficacy in neurological and psychiatric disorders such as Parkinson's disease and major depression. Electroencephalography (EEG) is a versatile neurophysiological tool that can be used to better understand DBS treatment mechanisms. DBS causes artifacts in EEG recordings that preclude meaningful neurophysiological activity from being quantified during stimulation. New method In this study, we modeled the DBS stimulation artifact and illustrated a technique for removing the artifact using matched filters. The approach was validated using a synthetically generated DBS artifact superimposed on EEG data. Mean squared error (MSE) between the recovered signal and the artifact-free signal was used to quantify the effectiveness of the approach. Results The DBS artifact was characterized by a series of narrow band components at the harmonic frequencies of DBS stimulation. The filtering approach successfully removed the DBS artifact with MSE value being less than 2% of base signal power for the typical stimulation and recording setups. General guidelines on how to setup DBS EEG studies and configure the subsequent artifact removal process are described. Comparison with previous method To avoid stimulus artifacts, a number of EEG studies with DBS subjects have resorted to turning the stimulator off during recording, while other studies have used low pass filters to remove artifacts and look at frequencies well below 50 Hz. Conclusions This study establishes a method through which DBS artifact in EEG recordings can be reliably eliminated, thereby preserving a meaningful neurophysiological signal through which to better understand DBS treatment mechanisms. [ABSTRACT FROM AUTHOR]

Background: Working memory represents a core cognitive domain that is impaired in schizophrenia for which there are currently no satisfactory treatments. Repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex has been shown to modulate neurophysiological mechanisms linked to working memory in schizophrenia and improves working memory performance in healthy subjects and might therefore represent a treatment modality for schizophrenia patients. The objectives were to evaluate the effects of rTMS on working memory performance in schizophrenia patients and evaluate whether rTMS normalizes performance to healthy subject levels. Methods: In a 4-week randomized double-blind sham-controlled pilot study design, 27 medicated schizophrenia patients were tested at the Centre for Addiction and Mental Health (a university teaching hospital that provides psychiatric care to a large urban catchment area and serves as a tertiary referral center for the province of Ontario). Patients performed the verbal working memory n-back task before and after rTMS magnetic resonance image targeted bilaterally sequentially to left and right dorsolateral prefrontal cortex 750 pulses/side at 20 Hz for 20 treatments. The main outcome measure was mean magnitude of change in the n-back accuracy for target responses with active (n=13) or sham (n=12) rTMS treatment course. Results: The rTMS significantly improved 3-back accuracy for targets compared with placebo sham (Cohen’s d=.92). The improvement in 3-back accuracy was also found to be at a level comparable to healthy subjects. Conclusions: These pilot data suggest that bilateral rTMS might be a novel, efficacious, and safe treatment for working memory deficits in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) has been investigated for its treatment efficacy for the negative symptoms of schizophrenia. Previous studies have targeted the dorsolateral prefrontal cortex (DLPFC), which is associated with the pathophysiology of this disorder. Several rTMS parameters have been explored in the treatment of negative symptoms and include stimulating the left and bilateral DLPFC at several different frequencies and number of sessions. Results of such studies have been inconsistent, while high-frequency rTMS has shown greatest promise. Objective/Hypothesis: The objective of this study was to evaluate the efficacy of bilateral high-frequency rTMS in the treatment of negative symptoms in schizophrenia. It was hypothesized rTMS would alleviate negative symptoms in schizophrenia. Methods: Twenty-five patients were enrolled in this double-blind placebo-controlled randomized trial. Bilateral 20 Hz rTMS was MRI-targeted to the DLPFC at 90% RMT administered daily for 4 weeks for a total of 20 treatments. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS), the Positive and Negative symptom scale (PANSS), and controlling for depression as measured with the Calgary Depression Scale (CDS) at baseline, 1, 2, 3, 4, and 2 weeks after the treatment course. Results: No significant group or time differences were found on negative symptoms or depressive symptoms after rTMS. Bilateral high-frequency rTMS did not alleviate negative symptoms in patients with schizophrenia. Conclusions: These findings indicate that such symptoms are unresponsive to rTMS treatment or that more optimized parameters are needed to achieve improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

Background: Several lines of evidence suggest that cognitive behavioral therapy (CBT) is an effective treatment for depression and anxiety disorders. Evidence suggests that the therapeutic effects of CBT are related to neurophysiologic changes in the cortex, particularly γ-aminobutyric acid (GABA) potentiation. Transcranial magnetic stimulation (TMS) represents a noninvasive method of measuring cortical inhibition, which is a neurophysiologic mechanism associated with the pathophysiology of several psychiatric disorders. Objective/Hypothesis: To demonstrate the effectiveness of a 12-week CBT intervention compared with a wait list control group measuring cortical inhibition in participants with pathologic perfectionism. Participants within the CBT group would demonstrate increases in cortical inhibition and improvements on clinical outcomes relative to the wait list control group. Methods: Twenty-four right-handed perfectionists were randomly assigned to a 12-week CBT intervention or a wait list control group. Cortical inhibition was measured at pre- and postintervention with TMS paradigms specifically short-interval cortical inhibition and the cortical silent period, which index GABAA and GABAB receptor-mediated inhibitory neurotransmission, respectively. Results: The CBT group demonstrated a significant potentiation of the cortical silent period when compared with the wait list control group. The CBT group demonstrated a decrease in anxiety sensitivity and automatic thoughts relative to the control group. Conclusions: These findings demonstrate that CBT tailored for perfectionism is accompanied by an increase in cortical inhibition of the motor cortex and positive changes on clinical outcomes. These findings provide compelling evidence for an association between positive CBT effects and a potentiation of GABAergic inhibitory neurotransmission. [Copyright &y& Elsevier]

Abstract: Brain oscillations are increasingly used for understanding complex psychiatric disorders. Gamma (30–50Hz) oscillations have warranted special attention due to their omnipresence in cognitive tasks. For patients with schizophrenia (SCZ), a disease associated with poor cognition, abnormal gamma oscillations have been reported in many experimental paradigms. The goal of this paper is to review the literature on gamma oscillations in SCZ. The review is structured into four sections. First, the functional role, neurobiology, and analysis of brain oscillations, especially gamma oscillations will be outlined. Second, the neurobiological abnormalities of SCZ in relation to gamma oscillations will be reviewed. Third, selected paradigms for investigating irregular gamma oscillations in SCZ will be discussed in detail. Finally, a discussion on the limitations of current findings and potential future research directions will be provided. The reviewed evidence suggests that gamma oscillations are disrupted in SCZ and could account for cognitive disturbances in this disorder. With additional analysis and experimentation, these indices may ultimately serve as endophenotypes that facilitate the development of etiologically based diagnostic methods, foster early identification and treatment, and advance our understanding of the complex genetic mechanisms involved in this disorder. [Copyright &y& Elsevier]

Background: The corpus callosum, the main interhemispheric connection in the brain, may serve to preserve functional asymmetry between homologous cortical regions. Methods: To test this hypothesis, 30 healthy adult subjects underwent combined transcranial magnetic stimulation (TMS)–electroencephalography procedures. Nineteen of these subjects also completed diffusion tensor imaging and tractography procedures. We examined the relationship between microstructural integrity of subdivisions of the corpus callosum with TMS-induced interhemispheric signal propagation. Results: We found a significant inverse relationship between microstructural integrity of callosal motor fibers with TMS-induced interhemispheric signal propagation from left to right motor cortex. We also found a significant inverse relationship between microstructural integrity of genu fibers of the corpus callosum and TMS-induced interhemispheric signal propagation from left to right dorsolateral prefrontal cortex (DLPFC). We then demonstrated neuroanatomic specificity of these relationships. Conclusions: Taken together, our findings suggest that TMS-induced interhemispheric signal propagation is transcallosally mediated and neuroanatomically specific and support a role for the corpus callosum in preservation of functional asymmetry between homologous cortical regions. Delineation of the relationship between corpus callosum microstructure and interhemispheric signal propagation in neuropsychiatric disorders, such as schizophrenia, may reveal novel mechanisms of pathophysiology. [ABSTRACT FROM AUTHOR]

Few studies have examined transcranial magnetic stimulation (TMS) measures of motor cortical neural plasticity and cortical inhibition in youth with MDD. This study reports on neurophysiology indices, including paired associative stimulation (PAS) and cortical silent period (CSP) in depressed and age- and sex-matched healthy youth. We found a main effect of health condition (depressed vs healthy) on post-PAS MEP ratios [F(1,16) = 7.392, p = 0.015], suggesting that depressed youth had lower PAS-induced motor cortical neural plasticity. [Extracted from the article]

Cognitive behavioural therapy (CBT) is an established first-line treatment for depression; however, it remains unclear which factors predict a positive outcome with this approach. Prior work suggests that co-morbid obesity predicts a poorer response to antidepressant medication. The current study examined whether there is an association between weight parameters and improvement of depressive symptoms with CBT. This was a secondary analysis of data from the "Clinical and Biological Markers of Response to Cognitive Behavioural Therapy for Depression – 6" (CANBIND-6; https://clinicaltrials.gov/ct2/show/NCT02883257) study. Adult participants (n = 41) with a diagnosis of Major Depressive Disorder (MDD) or Persistent Depressive Disorder (PDD) were recruited from an outpatient tertiary psychiatric centre in Canada. Participants completed 20 individual sessions of CBT over 16 weeks. The primary measure for treatment outcome was the Montgomery–Åsberg Depression Rating Scale (MADRS) total score at week 16. Thirty-seven participants completed assessments pre and post CBT. Baseline weight parameters were not correlated with treatment response to CBT in the entire group. There was a significant sex*waist circumference (WC) (B:-1.34; p = 0.004) and sex*body mass index (BMI) interaction (B:-2.03; p:0.009). In female participants, baseline waist circumference, but not BMI, significantly predicted week 16 MADRS after controlling for age and baseline MADRS (B:0.422 p:0.049). The major limitation of our preliminary finding is the small sample size. Our preliminary findings suggest that higher waist circumference may be associated with a better treatment response to CBT for depression in females. This result could be of clinical relevance and warrants further investigation in larger and independent samples. [ABSTRACT FROM AUTHOR]

• The N100, associated with GABA B receptor mediated inhibition, decreased in amplitude after rTMS in association with improvement in depressive symptoms. • Cortical activity in the DLPFC (the site of rTMS stimulation) decreased after active rTMS. • TMS-EEG markers of cortical inhibition and excitation demonstrate high potential as biomarkers of response to rTMS. Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment resistant depression (TRD), but little is known about rTMS' effects on neurophysiological markers. We previously identified neurophysiological markers in depression (N45 and N100) of GABA receptor mediated inhibition. Here, we indexed TMS-electroencephalographic (TMS-EEG) effects of rTMS. TMS-EEG data was analyzed from a double blind 2:1 randomized active (10 Hz left/bilateral):sham rTMS TRD trial. Participants underwent TMS-EEG over left dorsolateral prefrontal cortex (DLPFC) before and after 6 weeks of rTMS. 30 had useable datasets. TMS-evoked potentials (TEP) and components (N45, N100, P60) were examined with global mean field analysis (GMFA) and locally in DLPFC regions of interest. The N45 amplitude differed between active and sham groups over time, N100 amplitude did not. N45 (t = 2.975, p = 0.007) and N100 amplitudes (t = 2.177, p = 0.042) decreased after active rTMS, demonstrating alterations in cortical inhibition. TEP amplitudes decreased after active rTMS in left (t = 4.887, p < 0.001) and right DLPFC (t = 4.403, p < 0.001) not sham rTMS, demonstrating alterations in cortical excitability. Our results provide important new knowledge regarding rTMS effects on TMS-EEG measures in TRD, suggesting rTMS reduces neurophysiological markers of inhibition and excitability. These findings uncover potentially important neurophysiological mechanisms of rTMS action. [ABSTRACT FROM AUTHOR]

Abstract Background The neurophysiology of major depressive disorder (MDD) has become a particular focus of transcranial magnetic stimulation (TMS) investigational studies. TMS combined with electroencephalography (TMS-EEG) affords a window to directly measure evoked activity from the dorsolateral prefrontal cortex (DLPFC), which is of considerable interest in MDD. Our study examined TMS-EEG responses from the DLPFC in persons with MDD compared with those in healthy participants. Specifically, we examined TMS-EEG markers linked to inhibitory and excitatory neurophysiological processes and their balance. Methods In all, 30 participants with MDD and 30 age- and sex-matched healthy participants underwent single-pulse TMS-EEG to assess inhibition and excitation from DLPFC. TMS-EEG waveforms were analyzed through global mean field amplitude. Results MDD participants demonstrated abnormalities in TMS-EEG markers in the DLPFC. Inhibitory measures—N45 and N100—were larger in the MDD group than in healthy participants (N45 [ t = −4.894, p <.001] and N100 [ t = −3.496, p =.001]). In a receiver operating characteristic analysis, N45 amplitude predicted depression illness state with 80% sensitivity, 73.3% specificity, and 76.6% accuracy (area under the curve = 0.829, p <.001). The global mean field amplitude area under the curve, a neurophysiological measure of cortical reactivity, was significantly larger in persons with MDD (t = −3.114, p =.003), as was P60 (t = −3.260, p =.002). In healthy participants, there was a positive correlation between inhibitory N45 and excitatory global mean field amplitude area under the curve (r =.711, p <.001) that was not present in persons with MDD (r =.149, p =.43), demonstrating a potential imbalance between inhibition and excitation in MDD. Conclusions As the TMS-EEG waveform and its components index inhibitory and excitatory activity from the cortex, our results suggest abnormalities in these neurophysiological processes of DLPFC in persons with MDD. [ABSTRACT FROM AUTHOR]

Background Recent increase in the size and complexity of electrophysiological data from multidimensional electroencephalography (EEG) and magnetoencephalography (MEG) studies has prompted the development of sophisticated statistical frameworks for data analysis. One of the main challenges for such frameworks is the multiple comparisons problem, where the large number of statistical tests performed within a high-dimensional dataset lead to an increased risk of Type I errors (false positives). A solution to this problem, cluster analysis, applies the biologically-motivated knowledge of correlation between adjacent voxels in one or more dimensions of the dataset to correct for the multiple comparisons problem and detect true neurophysiological effects. Cluster-based methods provide increased sensitivity towards detecting neurophysiological events compared to conservative methods such as Bonferroni correction, but are limited by their dependency on an initial cluster-forming statistical threshold (e.g. t-score, alpha) obstructing precise comparisons of results across studies. New method Rather than selecting a single threshold value, unbiased cluster estimation (UCE) computes a significance distribution across all possible threshold values to provide an unbiased overall significance value. Comparison to existing methods UCE functions as a novel extension to existing cluster analysis methods. Results Using data from EEG combined with brain stimulation study, we showed the impact of statistical threshold on outcome measures and introduction of bias. We showed the application of UCE for different study designs (e.g., within-group, between-group comparisons). Conclusion We propose that researchers consider employing UCE for multidimensional EEG/MEG datasets toward an unbiased comparison of results between subjects, groups, and studies. [ABSTRACT FROM AUTHOR]

Electroencephalography (EEG) is a powerful method of studying the electrophysiology of the brain with high temporal resolution. Several analytical approaches to extract information from the EEG signal have been proposed. One method, termed microstate analysis , considers the multichannel EEG recording as a series of quasi-stable “microstates” that are each characterized by a unique topography of electric potentials over the entire channel array. Because this technique simultaneously considers signals recorded from all areas of the cortex, it is capable of assessing the function of large-scale brain networks whose disruption is associated with several neuropsychiatric disorders. In this review, we first introduce the method of EEG microstate analysis. We then review studies that have discovered significant changes in the resting-state microstate series in a variety of neuropsychiatric disorders and behavioral states. We discuss the potential utility of this method in detecting neurophysiological impairments in disease and monitoring neurophysiological changes in response to an intervention. Finally, we discuss how the resting-state microstate series may reflect rapid switching among neural networks while the brain is at rest, which could represent activity of resting-state networks described by other neuroimaging modalities. We conclude by commenting on the current and future status of microstate analysis, and suggest that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease. [ABSTRACT FROM AUTHOR]

Abstract: 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 GABAB 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 250ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250ms in DLPFC, and between 50 and 175ms in the parietal lobe. Conclusions: ppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABAB activity. Significance: ppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABAB activity. [Copyright &y& Elsevier]

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is considered one of the mechanisms underlying the development of major depressive disorder (MDD), but the exact nature of this dysfunction is unknown. We investigated the relationship between hypothalamus volume (HV) and blood-derived DNA methylation in MDD. We obtained brain MRI, clinical and molecular data from 181 unmedicated MDD and 90 healthy control (HC) participants. MDD participants received a 16-week standardized antidepressant treatment protocol, as part of the first Canadian Biomarker Integration Network in Depression (CAN-BIND) study. We collected bilateral HV measures via manual segmentation by two independent raters. DNA methylation and RNA sequencing were performed for three key HPA axis-regulating genes coding for the corticotropin-binding protein (CRHBP), glucocorticoid receptor (NR3C1) and FK506 binding protein 5 (FKBP5). We used elastic net regression to perform variable selection and assess predictive ability of methylation variables on HV. Left HV was negatively associated with duration of current episode (ρ = −0.17, p = 0.035). We did not observe significant differences in HV between MDD and HC or any associations between HV and treatment response at weeks 8 or 16, overall depression severity, illness duration or childhood maltreatment. We also did not observe any differentially methylated CpG sites between MDD and HC groups. After assessing functionality by correlating methylation levels with RNA expression of the respective genes, we observed that the number of functionally relevant CpG sites differed between MDD and HC groups in FKBP5 (χ2 = 77.25, p < 0.0001) and NR3C1 (χ2 = 7.29, p = 0.007). Cross-referencing functionally relevant CpG sites to those that were highly ranked in predicting HV in elastic net modeling identified one site from FKBP5 (cg03591753) and one from NR3C1 (cg20728768) within the MDD group. Stronger associations between DNA methylation, gene expression and HV in MDD suggest a novel putative molecular pathway of stress-related sensitivity in depression. Future studies should consider utilizing the epigenome and ultra-high field MR data which would allow the investigation of HV sub-fields. • cg03591753, cg20728768 were highly predictive of hypothalamus volume in elastic net. • Greater numssber of CpG sites correlated with RNA expression in MDD. • Hypothalamus volume not found to be different between MDD and HC. [ABSTRACT FROM AUTHOR]

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. • We utilised rest EEG to characterise physiological changes following MST in MDD. • MST significantly altered functional connectivity, network topology, and spectral power. • Changes in theta connectivity predicted clinical response to MST. • Rest EEG is a sensitive marker of neural response to MST. [ABSTRACT FROM AUTHOR]