Search

Yoshihiro Noda,1,2 Zafiris J Daskalakis,1–3 Jonathan Downar,4 Paul E Croarkin,5 Paul B Fitzgerald,6 Daniel M Blumberger1–3 1Department of Psychiatry, Faculty of Medicine, University of Toronto, 2Temerty Centre for Therapeutic Brain Intervention, 3Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 4MRI-Guided rTMS Clinic, University Health Network, Toronto, ON, Canada; 5Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; 6Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Melbourne, Australia Abstract: Magnetic seizure therapy (MST) has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center of each coil placed over the frontal cortex (ie, each coil centered over F3 and F4). MST was applied at 100 Hz and 100% machine output at progressively increasing train durations. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale and cognitive function was assessed with a comprehensive neuropsychological battery. This adolescent patient achieved full remission of clinical symptoms after an acute course of 18 MST treatments and had no apparent cognitive decline, other than some autobiographical memory impairment that may or may not be related to the MST treatment. This case report suggests that MST may be a safe and well tolerated intervention for adolescents with treatment-resistant bipolar depression. Pilot studies to further evaluate the effectiveness and safety of MST in adolescents warrant consideration. Keywords: brain stimulation, treatment-resistant depression, adolescent depression, cognitive effects

Background: Despite the implementation of cardiac monitoring guidelines, clozapine-induced myocarditis continues to cause deaths in Australia, and the risk is a barrier to prescription of this effective drug for the treatment of schizophrenia. This study was designed to identify clinical and phenotypic risk factors for clozapine-induced myocarditis.Method: Possible cases of clozapine related myocarditis occurring between June 1993 and November 2009 and a comparative group of controls taking clozapine for at least 45days without cardiac disease were documented from the patients' medical records.Results: 105 cases, with time to onset of 10-33days, and 296 controls were included in the study. In multivariate analysis, the risk of myocarditis increased by 26% for each additional 250mg of clozapine administered in the first nine days of clozapine titration (odds ratio 1.26; 95% confidence interval 1.02-1.55; p=0.03) and concomitant sodium valproate more than doubled the risk (2.59; 1.51-4.42; 0.001). Further, each successive decade in age was associated with a 31% increase in risk (1.31; 1.07-1.60; 0.009). Nevertheless, 33 cases received less than 920mg of clozapine during the first nine days of dose titration, did not take sodium valproate and were aged less than 40years; and nine control patients received sodium valproate and more than 920mg of clozapine in the first nine days without developing myocarditis.Conclusions: Clozapine should be initiated by slow dose titration and sodium valproate is best avoided, if clinically feasible, during this period. All patients commencing clozapine should be monitored for myocarditis up to Day 28. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous research has confirmed the presence of increased motor overflow in schizophrenia. There are essentially two theories regarding the cortical origins of overflow. Recent research suggests that both may be correct, and that the cortical origin of overflow is highly dependent upon the population in which it presents. Motor overflow, due to an abnormally active ipsilateral corticospinal tract, may indicate a potentially severe brain abnormality arising in early development. In contrast, bilaterally active corticospinal tracts accounting for overflow probably represent a naturally occurring response during fatiguing contractions. METHOD: The cortical origins of motor overflow in 20 participants with schizophrenia and 20 normal controls were investigated through the use of a number of transcranial magnetic stimulation (TMS) protocols. RESULTS: Each of the experimental protocols employed independently supported the contention that overflow was originating in the hemisphere contralateral to the involuntary movement. CONCLUSIONS: Results indicated that the origins of overflow in schizophrenia are the same as those seen in the normal control group, i.e. motor overflow seems to be due to the presence of bilaterally active corticospinal tracts. Potential explanations for greater motor overflow seen in schizophrenia are discussed. [ABSTRACT FROM AUTHOR]

Is repetitive transcranial magnetic stimulation equivalent to electroconvulsive therapy?METHODSDesign: Randomised controlled equivalence trial.Allocation: Concealed.Blinding: Single blind (assessors blinded).Follow-up period: Six months.Setting: South London and Maudsley National Health Service Trust, London, and Pembury Hospital, Invicta Mental Health Trust, Kent, UK; recruitment January 2002 to August 2004.Patients: Forty six right-handed adults (aged >/= 18 years) referred for electroconvulsive therapy (ECT) for major depression (Structured Clinical Interview for DSM-IV Axis I Disorders). Main exclusions: inability to receive repetitive transcranial magnetic stimulation (rTMS) or ECT (metallic plates in head, unfit for anaesthesia, history of seizures); rTMS or ECT in previous 6 months; dementia or other axis I diagnosis; substance misuse in previous 6 months.Intervention: rTMS (15 sessions: daily for 5 days/week over 3 weeks) or ECT (bilateral or unilateral, twice weekly, number and duration dependent upon patient's response, mean 6 sessions over 22 days).Outcomes: Depression symptoms (17 item Hamilton Depression Rating Scale [HAM-D17] score), remission (defined as HAM-D17 score

Abstract: Repetitive transcranial magnetic stimulation (rTMS) is a promising technology to reduce chronic pain. Investigating the mechanisms of rTMS analgesia holds the potential to improve treatment efficacy. Using a double-blind and placebo-controlled design at both stimulation and pharmacologic ends, this study investigated the opioidergic mechanisms of rTMS analgesia by abolishing and recovering analgesia in 2 separate stages across brain regions and TMS doses. A group of 45 healthy participants were equally randomized to the primary motor cortex (M1), the dorsolateral prefrontal cortex (DLPFC), and the Sham group. In each session, participants received an intravenous infusion of naloxone or saline before the first rTMS session. Participants then received a second dose of rTMS session after the drugs were metabolized at 90 minutes. M1-rTMS-induced analgesia was abolished by naloxone compared with saline and was recovered by the second rTMS run when naloxone was metabolized. In the DLPFC, double but not the first TMS session induced significant pain reduction in the saline condition, resulting in less pain compared with the naloxone condition. In addition, TMS over the M1 or DLPFC selectively increased plasma concentrations of β-endorphin or encephalin, respectively. Overall, we present causal evidence that opioidergic mechanisms are involved in both M1-induced and DLPFC-rTMS-induced analgesia; however, these are shaped by rTMS dosage and the release of different endogenous opioids., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

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.)

Competing Interests: This trial involves no commercial input: the findings from this trial will not benefit any commercial manufacturers/suppliers of clinical ECT devices. GLS has collaborated with MagVenture and MECTA as part of investigator-initiated trials, consults for and has equity in the company Trial Catalyst, and has provided consultation to Indivior. Dr Harold A. Sackeim serves as a scientific adviser and receives consulting fees from Cerebral Therapeutics Inc, Holmusk Technologies Inc, LivaNova PLC, MECTA Corporation, Neurolief Ltd, Neuronetics Inc, Parow Entheobiosciences LLC, and SigmaStim LLC. He receives honoraria and royalties from Elsevier Inc and Oxford University Press. He is the inventor on nonremunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by Balance Point LLC. He is also the originator of magnetic seizure therapy (MST). In the last 3 years PBF has received equipment for research from Neurosoft, Nexstim, and Brainsway Ltd. He has served on scientific advisory boards for Magstim and LivaNova and received speaker fees from Otsuka. He has also acted as a founder and board member for TMS Clinics Australia and Resonance Therapeutics. PBF is supported by a National Health and Medical Research Council of Australia Investigator grant (1193596). The other authors have no conflicts of interest or financial disclosures to report.

Attrition is a particular concern in studies examining the efficacy of a treatment for Alzheimer disease. Analyzing reasons for withdrawal in Alzheimer studies is crucial to ruling out attrition bias, which can undermine a study's validity. In contrast, attrition in studies using repetitive transcranial magnetic stimulation (rTMS) has received much less attention. Our goal was to identify any commonalities between participants who withdrew for the same reasons. Three independent coders rated each response concerning the reasons for withdrawal, and frequency tables were generated to characterize the participants within each category. This study was conducted on the 28 withdrawn cases from a 7-month study investigating the short-term and long-term therapeutic effects of rTMS for Alzheimer disease among 156 participants across 3 sites of the study. Seven reasons for withdrawal were identified, with health and medical changes being the most commonly reported reason (7 participants). Personal issues involving family or caregivers were the next most common (5 participants), and the remaining 5 categories consisted of 3 participants each. Although the limited sample size prevented the use of inferential statistics, our findings highlight the need for more transparent reporting of attrition rates and withdrawal reasons by rTMS researchers., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Our previous study synthesized the analgesic effects of repetitive Transcranial Magnetic Stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) trials up to 2019. There has been a significant increase in pain trials in the past few years, along with methodological variabilities such as sample size, stimulation intensity, and rTMS paradigms., Objectives/methods: This study therefore updated the effects of DLPFC-rTMS on chronic pain and quantified the impact of methodological differences across studies., Results: A total of 36 studies were included. Among them, 26 studies were clinical trials (update = 9, 307/711 patients), and 10 (update = 1, 34/249 participants) were provoked pain studies. The updated meta-analysis does not support an effect on neuropathic pain after including the additional trials (p short-term  = 0.20, p mid-term  = 0.50). However, there is medium-to-large analgesic effect in migraine trials extending up to six weeks follow-up (SMD mid-term  = -0.80, SMD long-term  = -0.51), that was not previously reported. Methodological differences wthine the studies were considered. DLPFC-rTMS also induces potential improvement in the emotional aspects of pain (SMD short-term  = -0.28)., Conclusions: The updated systematic meta-analysis continues to support analgesic effects for chronic pain overall. However, the updated results no longer support DLPFC-rTMS for pain relief in neuropathic pain, and do supports DLPFC-rTMS in the management of migraine. There is also evidence for DLPFC-rTMS to improve emotional aspects of pain., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We confirm that we have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. In so doing we confirm that we have followed the regulations of our institutions concerning intellectual property. We further confirm that any aspect of the work covered in this manuscript that has involved either experimental animals or human patients has been conducted with the ethical approval of all relevant bodies and that such approvals are acknowledged within the manuscript. We understand that the Corresponding Author is the sole contact for the Editorial process (including Editorial Manager and direct communications with the office). He is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs. We confirm that we have provided a current, correct email address which is accessible by the Corresponding Author and which has been configured to accept email from xwcheswu@gmail.com., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Suicidal ideation is a substantial clinical challenge in treatment-resistant depression (TRD). Recent work demonstrated promising antidepressant effects in TRD patients with no or mild suicidal ideation using a specific protocol termed intermittent theta burst stimulation (iTBS). Here, we examined the clinical effects of accelerated schedules of iTBS and continuous TBS (cTBS) in patients with moderate to severe suicidal ideation., Methods: Patients with TRD and moderate to severe suicidal ideation (n = 44) were randomly assigned to receive accelerated iTBS or cTBS treatment. Treatments were delivered in 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days (total of 90,000 pulses). Neuronavigation was employed to target accelerated iTBS and cTBS to the left and right dorsolateral prefrontal cortex (DLPFC), respectively. Clinical outcomes were evaluated in a 4-week follow-up period., Results: Accelerated cTBS was superior to iTBS in the management of suicidal ideation (p week 1  = .027) and anxiety symptoms (p week 1  = .01). Accelerated iTBS and cTBS were comparable in antidepressant effects (p < .001; accelerated cTBS: mean change at weeks 1, 3, 5 = 49.55%, 54.99%, 53.11%; accelerated iTBS: mean change at weeks 1, 3, 5 = 44.52%, 48.04%, 51.74%). No serious adverse events occurred during the trial. One patient withdrew due to hypomania. The most common adverse event was discomfort at the treatment site (22.73% in both groups)., Conclusions: These findings provide the first evidence that accelerated schedules of left DLPFC iTBS and right DLPFC cTBS are comparably effective in managing antidepressant symptoms and indicate that right DLPFC cTBS is potentially superior in reducing suicidal ideation and anxiety symptoms., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Applying deep brain stimulation (DBS) to several brain regions has been investigated in attempts to treat highly treatment-resistant depression, with variable results. Our initial pilot data suggested that the bed nucleus of the stria terminalis (BNST) could be a promising therapeutic target., Objective: The aim of this study was to gather blinded data exploring the efficacy of applying DBS to the BNST in patients with highly refractory depression., Method: Eight patients with chronic severe treatment-resistant depression underwent DBS to the BNST. A randomised, double-blind crossover study design with fixed stimulation parameters was followed and followed by a period of open-label stimulation., Results: During the double-blind crossover phase, no consistent antidepressant effects were seen with any of the four stimulation parameters applied, and no patients achieved response or remission criteria during the blinded crossover phase or during a subsequent period of three months of blinded stimulation. Stimulation-related side effects, especially agitation, were reported by a number of patients and were reversible with adjustment of the stimulation parameters., Conclusions: The results of this study do not support the application of DBS to the BNST in patients with highly resistant depression or ongoing research utilising stimulation at this brain site. The blocked randomised study design utilising fixed stimulation parameters was poorly tolerated by the participants and does not appear suitable for assessing the efficacy of DBS at this location.

Background: Transcranial magnetic stimulation (TMS) (including the theta burst stimulation (TBS) form of TMS used in this study) is a non-invasive means to stimulate nerve cells in superficial areas of the brain. In recent years, there has been a growth in the application of TMS to investigate the modulation of neural networks involved in substance use disorders. This study examines the feasibility of novel TMS protocols for the treatment of methamphetamine (MA) use disorder in an ambulatory drug and alcohol treatment setting., Methods: Thirty participants meeting the criteria for moderate to severe MA use disorder will be recruited in community drug and alcohol treatment settings and randomised to receive active TMS or sham (control) intervention. The treatment is intermittent TBS (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC), then continuous TBS (cTBS) to the left orbitofrontal cortex (OFC). Twelve sessions are administered over 4 weeks with opt-in weekly standardized cognitive behaviour therapy (CBT) counselling and a neuroimaging sub-study offered to participants. Primary outcomes are feasibility measures including recruitment, retention and acceptability of the intervention. Secondary outcomes include monitoring of safety and preliminary efficacy data including changes in substance use, cravings (cue reactivity) and cognition (response inhibition)., Discussion: This study examines shorter TBS protocols of TMS for MA use disorder in real-world drug and alcohol outpatient settings where withdrawal and abstinence from MA, or other substances, are not eligibility requirements. TMS is a relatively affordable treatment and staff of ambulatory health settings can be trained to administer TMS. It is a potentially scalable and translatable treatment for existing drug and alcohol clinical settings. TMS has the potential to provide a much-needed adjuvant treatment to existing psychosocial interventions for MA use disorder. A limitation of this protocol is that the feasibility of follow-up is only examined at the end of treatment (4 weeks)., Trial Registration: Australia New Zealand Clinical Trial Registry ACTRN12622000762752. Registered on May 27, 2022, and retrospectively registered (first participant enrolled) on May 23, 2022, with protocol version 7 on February 24, 2023., (© 2024. Crown.)

Considering the advantages of brain stimulation techniques in detecting the role of different areas of the brain in human sensorimotor behaviors, we used anodal transcranial direct-current stimulation (a-tDCS) over three different brain sites of the frontoparietal cortex (FPC) in healthy participants to elucidate the role of these three brain areas of the FPC on reaction time (RT) during a sequential visual isometric pinch task (SVIPT). We also aimed to assess if the stimulation of these cortical sites affects the transfer of learning during SVIPT. A total of 48 right-handed healthy participants were randomly assigned to one of the four a-tDCS groups: (1) left primary motor cortex (M1), (2) left dorsolateral prefrontal cortex (DLPFC), (3) left posterior parietal cortex (PPC), and (4) sham. A-tDCS (0.3 mA, 20 min) was applied concurrently with the SVIPT, in which the participants precisely controlled their forces to reach seven different target forces from 10 to 40% of the maximum voluntary contraction (MVC) presented on a computer screen with the right dominant hand. Four test blocks were randomly performed at the baseline and 15 min after the intervention, including sequence and random blocks with either hand. Our results showed significant elongations in the ratio of RTs between the M1 and sham groups in the sequence blocks of both the right-trained and left-untrained hands. No significant differences were found between the DLPFC and sham groups and the PPC and sham groups in RT measurements within the SVIPT. Our findings suggest that RT improvement within implicit learning of an SVIPT is not mediated by single-session a-tDCS over M1, DLPFC, or PPC. Further research is needed to understand the optimal characteristics of tDCS and stimulation sites to modulate reaction time in a precision control task such as an SVIPT.

We report results of a large multisite double-blind randomized trial investigating the short and long-term efficacy of repetitive transcranial magnetic stimulation (rTMS) applied to patients with Alzheimer's disease (AD) at mild to moderate stages, in doses of either 2 or 4 weeks of treatment (5 days/week), whilst compared with 4 weeks of sham rTMS. Randomization to treatment group was stratified based on age and severity. The objectives of this study were to: 1) investigate the efficacy of active rTMS versus sham, 2) investigate the effect of dose of treatment (2 or 4 weeks), and 3) investigate the length of benefits from treatment. The rTMS pulses (20 ​Hz, 30 pulses/train, 25 trains, 10-s intertrain interval) were applied serially to the left and right dorsolateral prefrontal cortex using neuro-navigation. We compared the primary outcome measure's (ADAS-Cog) score changes from pre- to post-treatment, with assessments at baseline and 4 more times up to 6 months post-treatment. Data of 135 patients were analyzed. The mean total ADAS-Cog score at baseline did not differ between the active and sham treatment groups, nor across the three study sites. The overall results show significant cognitive improvement after treatment up to two months post-treatment with either sham or active coils. The results show both short and long-term benefits of active rTMS treatment but also show similar benefits for sham coil treatment of mild/moderate AD. We discuss this finding in the context of the existing literature on rTMS therapy for AD, as well as evidence of the sham coil's potential to induce a low-level current in the brain. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02908815., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zahra Moussavi reports financial support was provided by Weston Brain Institute. Paul B Fitzgerald reports a relationship with National Health and Medical Research Council of Australia Investigator grant (1193596) that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Abstract: Electroconvulsive therapy (ECT) is a complex medical procedure, the delivery of which requires specialist knowledge and skills. We reviewed the standards required for ECT credentialing in different jurisdictions in Australia. We reviewed the Chief Psychiatrist guidelines and statewide policy standards on ECT and focused on standards required for initial credentialing and ongoing privileging in ECT. We compared the credentialing requirements within these documents with the standards specified in the Royal Australian and New Zealand College of Psychiatrists professional practice guideline for ECT. Most of the jurisdictions had specific standards for initial credentialing and maintenance of this credentialing; however, there was significant variance in the credentialing process and standards required. It would be useful to have a minimum standard for credentialing for ECT psychiatrists and prescribers. This standard would be relevant for practice of ECT internationally. States and territories would have the responsibility for implementation of these standards. Appropriate training and establishing good clinical governance processes are essential to the provision of high quality ECT., Competing Interests: Conflict of Interest and Source of Funding: In the last 3 years, P.B.F. has received equipment for research from Medtronic Ltd, Neurosoft, Nexstim and Brainsway Ltd. He has served on scientific advisory boards for Magstim and LivaNova and acted as a founder for TMS Clinics Australia and Resonance Therapeutics. P.B.F. is supported by a National Health and Medical Research Council of Australia Investigator grant (1193596). The authors did not receive any funding for this review paper., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Previous research has examined resting electroencephalographic (EEG) data to explore brain activity related to meditation. However, previous research has mostly examined power in different frequency bands. The practical objective of this study was to comprehensively test whether other types of time-series analysis methods are better suited to characterize brain activity related to meditation. To achieve this, we compared >7000 time-series features of the EEG signal to comprehensively characterize brain activity differences in meditators, using many measures that are novel in meditation research. Eyes-closed resting-state EEG data from 49 meditators and 46 non-meditators was decomposed into the top eight principal components (PCs). We extracted 7381 time-series features from each PC and each participant and used them to train classification algorithms to identify meditators. Highly differentiating individual features from successful classifiers were analysed in detail. Only the third PC (which had a central-parietal maximum) showed above-chance classification accuracy (67 %, p FDR  = 0.007), for which 405 features significantly distinguished meditators (all p FDR  < 0.05). Top-performing features indicated that meditators exhibited more consistent statistical properties across shorter subsegments of their EEG time-series (higher stationarity) and displayed an altered distributional shape of values about the mean. By contrast, classifiers trained with traditional band-power measures did not distinguish the groups (p FDR  > 0.05). Our novel analysis approach suggests the key signatures of meditators' brain activity are higher temporal stability and a distribution of time-series values suggestive of longer, larger, or more frequent non-outlying voltage deviations from the mean within the third PC of their EEG data. The higher temporal stability observed in this EEG component might underpin the higher attentional stability associated with meditation. The novel time-series properties identified here have considerable potential for future exploration in meditation research and the analysis of neural dynamics more broadly., Competing Interests: Declaration of Competing Interest In the last 3 years PBF has received equipment for research from Neurosoft, Nexstim and Brainsway Ltd. He has served on scientific advisory boards for Magstim and LivaNova and received speaker fees from Otsuka. He has also acted as a founder and board member for TMS Clinics Australia and Resonance Therapeutics. The other authors declare that they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study is a post-hoc examination of baseline MRI data from a clinical trial investigating the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for patients with mild-moderate Alzheimer's disease (AD). Herein, we investigated whether the analysis of baseline MRI data could predict the response of patients to rTMS treatment. Whole-brain T1-weighted MRI scans of 75 participants collected at baseline were analyzed. The analyses were run on the gray matter (GM) and white matter (WM) of the left and right dorsolateral prefrontal cortex (DLPFC), as that was the rTMS application site. The primary outcome measure was the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). The response to treatment was determined based on ADAS-Cog scores and secondary outcome measures. The analysis of covariance showed that responders to active treatment had a significantly lower baseline GM volume in the right DLPFC and a higher GM asymmetry index in the DLPFC region compared to those in non-responders. Logistic regression with a repeated five-fold cross-validated analysis using the MRI-driven features of the initial 75 participants provided a mean accuracy of 0.69 and an area under the receiver operating characteristic curve of 0.74 for separating responders and non-responders. The results suggest that GM volume or asymmetry in the target area of active rTMS treatment (DLPFC region in this study) may be a weak predictor of rTMS treatment efficacy. These results need more data to draw more robust conclusions.

Objectives: Repetitive transcranial magnetic stimulation (rTMS) is a level 1a evidence-based treatment for major depression, but high cost of care and limited effectiveness in naturalistic cohorts have been lingering criticisms. This naturalistic, retrospective cohort analysis compares the effect of once and twice daily treatment protocols of rTMS using quality assurance data collected at an Australian private psychiatric hospital., Methods: A total of 210 inpatients self-selected into two groups receiving up to 30 sessions of either daily (n = 101) or twice daily (n = 109) 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). The a priori primary outcome measure was remission rate as measured by pre and post treatment HAMD-17 scores. Length of hospital stay was a secondary post hoc outcome adopted due to the importance to cost of acute psychiatric care., Results: Remission rates were similar across groups, with 44.9% and 45.4% for twice daily and daily rTMS groups respectively, although these may be confounded by patient expectations, other treatments and medication changes given the naturalistic setting. The length of hospital stay was 10.11 days and 18.44 days for twice daily and daily rTMS respectively - the twice daily rTMS length of hospital stay was 45.1% shorter 95% CI [38.7% - 51.56%]. Dropout rates were high; Twenty-seven (24.77%) twice daily participants dropped out before 20 sessions were completed, and 35 (34.65%) of daily participants., Conclusions: Twice daily 10 Hz left sided rTMS remission outcomes were similar to traditional once daily rTMS but required a shorter length of hospital stay. This finding has substantial cost of care implications. If these findings are independently replicated, twice daily rTMS may become the standard of care for inpatient rTMS., Competing Interests: Declaration of Competing Interest RB has no conflicts of interest to declare. DRS is a current investigator with the NHMRC Medical Research Future Fund (APP1200214), and has no conflicts of interest to declare. PBF has received equipment for research from Medtronic Ltd., Neurosoft, Nexstim and Brainsway Ltd. He has served on scientific advisory boards for Magstim and LivaNova and acted as a founder for TMS Clinics Australia and Resonance Therapeutics. MB is supported by a NHMRC Senior Principal Research Fellowship (1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eisai, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier—all unrelated to this work. OMD has received grant/research support from the Brain and Behaviour Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, NHMRC, and Australasian Society for Bipolar and Depressive Disorders (ASBDD)/Servier. OMD has also received in kind support from BioMedica Nutracuticals, NutritionCare and Bioceuticals. SD has received grant support from the Stanley Medical Research Institute, NHMRC, Beyond Blue, ARHRF, Simons Foundation, Geelong Medical Research Foundation, Harry Windsor Foundation, Fondation FondaMental, Eli Lilly, Glaxo SmithKline, Organon, Mayne Pharma and Servier, speaker's fees from Eli Lilly, advisory board fees from Eli Lilly and Novartis, and conference travel support from Servier. ABS has shares/options in Baycrest Biotechnology Pty Ltd. and Greenfield Medicinal Cannabis, founder equity in CNSDose, and has received speaking honoraria from Servier, Lundbeck and Otsuka Australia., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

There is growing evidence that neural network dysfunction is a likely proximate cause of cognitive impairment in Alzheimer's disease and may represent a promising therapeutic target. Here, we investigated whether a course of intermittent theta burst stimulation (iTBS) could modulate functional connectivity and cognition in mild to moderate Alzheimer's. In a double-blind parallel randomized sham-controlled trial, 58 participants were randomized to either active or sham iTBS. Stimulation was applied to the left dorsolateral prefrontal cortex, right dorsolateral prefrontal cortex, left posterior parietal cortex, and right posterior parietal cortex in every treatment session. Neurobiological (electroencephalography), cognitive, and behavioral functional assessments were undertaken at baseline and end of treatment. Cognitive and functional assessments were also conducted at 3 (blinded) and 6 month (active group only) follow-ups. Active iTBS increased resting-state gamma connectivity and improved delayed recall on an episodic memory task. Both baseline gamma connectivity and change in gamma connectivity predicted improved delayed recall following active treatment. These findings support future research into iTBS for Alzheimer's focusing on protocol optimization., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To compare effects of transcranial direct current stimulation (tDCS) and transcranial random noise stimulation with a direct-current offset (tRNS + DC-offset) on working memory (WM) performance and task-related electroencephalography (EEG) in individuals with Major Depressive Disorder (MDD)., Methods: Using a sham-controlled, parallel-groups design, 49 participants with MDD received either anodal tDCS (N = 16), high-frequency tRNS + DC-offset (N = 16), or sham stimulation (N = 17) to the left dorsolateral prefrontal cortex (DLPFC) for 20-minutes. The Sternberg WM task was completed with concurrent EEG recording before and at 5- and 25-minutes post-stimulation. Event-related synchronisation/desynchronisation (ERS/ERD) was calculated for theta, upper alpha, and gamma oscillations during WM encoding and maintenance., Results: tDCS significantly increased parieto-occipital upper alpha ERS/ERD during WM maintenance, observed on EEG recorded 5- and 25-minutes post-stimulation. tRNS + DC-offset did not significantly alter WM-related oscillatory activity when compared to sham stimulation. Neither tDCS nor tRNS + DC-offset improved WM performance to a significantly greater degree than sham stimulation., Conclusions: Although tDCS induced persistent effects on WM-related oscillatory activity, neither tDCS nor tRNS + DC-offset enhanced WM performance in MDD., Significance: This reflects the first sham-controlled comparison of tDCS and tRNS + DC-offset in MDD. These findings directly contrast with evidence of tRNS-induced enhancements in WM in healthy individuals., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the last three years PBF has received equipment for research from Neurosoft, Nexstim and Brainsway Ltd. PBF has served on scientific advisory boards for Magstim and LivaNova and acted as a founder and board member for TMS Clinics Australia and Resonance Therapeutics. All other authors have no conflicts to report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

In the last century, prescribing electroconvulsive therapy usually involved considering the relative merits of unilateral versus bilateral electroconvulsive therapy, with most other parameters fixed. However, research over the last 30 years has discovered that several parameters of the electroconvulsive therapy stimulus can have a significant impact on efficacy and cognitive side effects. The stimulus dose relative to seizure threshold was shown to significantly affect efficacy, especially for right unilateral electroconvulsive therapy, where suprathreshold doses in the vicinity of 5-6 times seizure threshold were far more efficacious than doses closer to threshold. However, this did not hold for bitemporal electroconvulsive therapy, where near-threshold stimuli were equally effective as suprathreshold stimuli. Then, changes in stimulus pulse width were found to also have a significant impact on both efficacy and side effects, with ultrabrief pulse widths of 0.3 ms having significantly fewer cognitive side effects in unilateral electroconvulsive therapy than standard brief pulse widths of 1.0 ms, with only slightly reduced efficacy. Therefore, choosing the optimum electroconvulsive therapy prescription for an individual patient now requires consideration of placement, pulse width and stimulus dose relative to seizure threshold, and how these three interact with each other. This viewpoint aims to raise awareness of these issues for psychiatrists involved in electroconvulsive therapy practice.

Background: Prolonged intermittent theta-burst stimulation (iTBS) is effective for major depressive disorder (MDD). However, whether longer piTBS treatment in a single session could have antidepressant efficacy remains elusive. Therefore, this double-blind, randomized, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily piTBS sessions for treating MDD patients with a history of poor responses to at least 1 adequate antidepressant trial in the current episode., Methods: All patients received 2 uninterrupted sessions per day for 10 weekdays (i.e., 2 weeks; a total of 20 sessions). Seventy-two patients were recruited and 1:1:1 randomly assigned to one of three groups: piTBS (piTBSx2), 10-Hz rTMS (rTMSx2), or sham treatment (shamx2, randomly assigned to piTBS or rTMS). 10-Hz rTMS group was included as an active comparison group to enhance assay sensitivity., Results: piTBSx2 group had significantly more responders at week 2 than shamx2 group, but it did not yield better antidepressant effects regarding the %depression changes. The changes of antidepressant scores were not different among the three groups at week 1 (-26.2% vs. -23.3% vs. -22.%) or at week 2 (-34.1% vs. -37.1% vs. -30.1%). Longer treatment duration did not result in stronger placebo effects [sham(piTBS)x2: - 31.7% vs. sham(rTMS)x2: - 26.7%]., Conclusion: The present sham-controlled study confirmed that piTBS is an effective antidepressant option, but found no evidence to support that longer piTBS treatment duration resulted in more rapid or better antidepressant effects. A high placebo effect was observed, but longer treatment duration of brain stimulation was not linearly associated with stronger placebo effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To find sensitive neurophysiological correlates of non-motor symptoms in Huntington's disease (HD), which are essential for the development and assessment of novel treatments., Methods: We used resting state EEG to examine differences in oscillatory activity (analysing the isolated periodic as well as the complete EEG signal) and functional connectivity in 22 late premanifest and early stage people with HD and 20 neurotypical controls. We then assessed the correlations between these neurophysiological markers and clinical measures of apathy and processing speed., Results: Significantly lower theta and greater delta resting state power was seen in the HD group, as well as significantly greater delta connectivity. There was a significant positive correlation between theta power and processing speed, however there were no associations between the neurophysiological and apathy measures., Conclusions: We speculate that these changes in oscillatory power and connectivity reflect ongoing, frontally concentrated degenerative and compensatory processes associated with HD., Significance: Our findings support the potential utility of quantitative EEG as a proximate marker of processing speed, but not apathy in HD., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

We investigated the effects of transcranial alternating current stimulation (tACS) targeted to the bilateral medial prefrontal cortex (mPFC) and administered at either delta or alpha frequencies, on brain activity and apathy in people with Huntington's disease (HD) (n = 17). Given the novelty of the protocol, neurotypical controls (n = 20) were also recruited. All participants underwent three 20-min sessions of tACS; one session at alpha frequency (Individualised Alpha Frequency (IAF), or 10 Hz when an IAF was not detected); one session at delta frequency (2 Hz); and a session of sham tACS. Participants completed the Monetary Incentive Delay (MID) task with simultaneous recording of EEG immediately before and after each tACS condition. The MID task presents participants with cues signalling potential monetary gains or losses that increase activity in key regions of the cortico-basal ganglia-thalamocortical networks, with dysfunction of the latter network being implicated in the pathophysiology of apathy. We used the P300 and Contingent Negative Variation (CNV) event-related potentials elicited during the MID task as markers of mPFC engagement. HD participants' CNV amplitude significantly increased in response to alpha-tACS, but not delta-tACS or sham. Neurotypical controls' P300 and CNV were not modulated by any of the tACS conditions, but they did demonstrate a significant decrease in post-target response times following alpha-tACS. We present this as preliminary evidence of the ability of alpha-tACS to modulate brain activity associated with apathy in HD., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We investigated the effects of transcranial alternating current stimulation (tACS) targeted to the medial prefrontal cortex (mPFC) on resting electroencephalographic (EEG) indices of oscillatory power, aperiodic exponent and offset, and functional connectivity in 22 late premanifest and early manifest stage individuals with HD and 20 neurotypical controls. Participants underwent three 20-minute sessions of tACS at least 72 hours apart; one session at alpha frequency (either each participant's Individualised Alpha Frequency (IAF), or 10 Hz when an IAF was not detected); one session at delta frequency (2 Hz); and a session of sham tACS. Session order was randomised and counterbalanced across participants. EEG recordings revealed a reduction of the spectral exponent ('flattening' of the 1/f slope) of the eyes-open aperiodic signal in participants with HD following alpha-tACS, suggestive of an enhancement in excitatory tone. Contrary to expectation, there were no changes in oscillatory power or functional connectivity in response to any of the tACS conditions in the participants with HD. By contrast, alpha-tACS increased delta power in neurotypical controls, who further demonstrated significant increases in theta power and theta functional connectivity in response to delta-tACS. This study contributes to the rapidly growing literature on the potential experimental and therapeutic applications of tACS by examining neurophysiological outcome measures in people with HD as well as neurotypical controls., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Obsessive-Compulsive Disorder (OCD) is a mental health condition causing significant decline in the quality of life of sufferers and the limited knowledge on the pathophysiology hinders successful treatment. The aim of the current study was to examine electroencephalographic (EEG) findings of OCD to broaden our understanding of the disease. Resting-state eyes-closed EEG data was recorded from 25 individuals with OCD and 27 healthy controls (HC). The 1/f arrhythmic activity was removed prior to computing oscillatory powers of all frequency bands (delta, theta, alpha, beta, gamma). Cluster-based permutation was used for between-group statistical analyses, and comparisons were performed for the 1/f slope and intercept parameters. Functional connectivity (FC) was measured using coherence and debiased weighted phase lag index (d-wPLI), and statistically analyzed using the Network Based Statistic method. Compared to HC, the OCD group showed increased oscillatory power in the delta and theta bands in the fronto-temporal and parietal brain regions. However, there were no significant between-group findings in other bands or 1/f parameters. The coherence measure showed significantly reduced FC in the delta band in OCD compared to HC but the d-wPLI analysis showed no significant differences. OCD is associated with raised oscillatory power in slow frequency bands in the fronto-temporal brain regions, which agrees with the previous literature and therefore is a potential biomarker. Although delta coherence was found to be lower in OCD, due to inconsistencies found between measures and the previous literature, further research is required to ascertain definitive conclusions., Competing Interests: Declaration of competing interest In the last 3 years PBF has received equipment for research from Medtronic Ltd, Neurosoft, Nexstim and Brainsway Ltd. He has served on scientific advisory boards for Magstim and LivaNova and acted as a founder and board member for TMS Clinics Australia and Resonance Therapeutics. All other authors report no biomedical financial interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Despite efforts to improve targeting accuracy of the dorsolateral prefrontal cortex (DLPFC) as a repetitive transcranial magnetic stimulation (rTMS) target for Major Depressive Disorder (MDD), the heterogeneity in clinical response remains unexplained., Objective: We sought to compare the patterns of functional connectivity from the DLPFC treatment site in patients with MDD who were TMS responders to those who were TMS non-responders., Methods: Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI, and diffusion weighted imaging scans were obtained from 37 participants before they underwent a course of rTMS to left Brodmann area 46. A novel machine learning method was utilized to identify brain regions associated with each item of the Beck's Depression Inventory II (BDI-II), and for 26 participants who underwent rTMS treatment over the left Brodmann area 46, identify regions differentiating rTMS responders and non-responders., Results: Nine parcels of the Human Connectome Project Multimodal Parcellation Atlas matched to at least three items of the Beck's Depression Inventory II (BDI-II) as predictors of response to rTMS, with many in the temporal, parietal and cingulate cortices. Additionally, pre-treatment mapping for 17 items of the BDI-II demonstrated significant variability in symptom to parcel mapping. When parcels associated with symptom presence and symptom resolution were compared, 15 parcels were uniquely associated with resolution (potential targets), and 12 parcels were associated with both symptom presence and resolution (blockers or biomarkers)., Conclusions: Machine learning approaches show promise for the development of pathoanatomical diagnosis and treatment algorithms for MDD. Prospective studies are required to facilitate clinical translation., Competing Interests: Conflict of interest Seven authors (HT, PN, OT, IY, LD, SD and MS) are employees of Omniscient Neurotechnology. SD and MS are also stakeholders of Omniscient Neurotechnology., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Repetitive transcranial magnetic stimulation (rTMS) may be a relevant method to assist postoperative pain. However, studies to date have only used conventional 10 Hz rTMS and targeted the DLPFC for postoperative pain. A more recent form of rTMS, termed intermittent Theta Burst Stimulation (iTBS), enables to increase cortical excitability in a short period of time. This preliminary double-blind, randomised, sham controlled study was designed to evaluate the efficacy of iTBS in postoperative care across two distinct stimulation targets., Methods: A group of 45 patients post laparoscopic surgery were randomised to receive a single session of iTBS over either the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), or Sham stimulation (1:1:1 ratio). Outcome measurements were number of pump attempts, total anaesthetic volume used, and self-rated pain experience, assessed at 1 hour, 6 hours, 24 hours, and 48 hours post stimulation. All randomised patients were analysed (n = 15 in each group)., Results: Compared to Sham stimulation, DLPFC-iTBS reduced pump attempts at 6 (DLPFC = 0.73 ± 0.88, Sham = 2.36 ± 1.65, P = 0.031), 24 (DLPFC = 1.40 ± 1.24, Sham = 5.03 ± 3.87, P = 0.008), and 48 (DLPFC = 1.47 ± 1.41, Sham = 5.87 ± 4.34, P = 0.014) hours post-surgery, whereby M1 stimulation had no effect. No group effect was observed on total anaesthetics, which was mainly provided through the continuous administration of opioids at a set speed for each group. There was also no group or interaction effect on pain ratings. Pump attempts were positively associated with pain ratings in the DLPFC (r = 0.59, P = 0.02) and M1 (r = 0.56, P = 0.03) stimulation., Conclusions: Our findings show that iTBS to the DLPFC reduces pump attempts for additional anaesthetics following a laparoscopic surgery. However, reduced pump attempts by DLPFC stimulation did not translate into a significantly smaller volume of total anaesthetic, due to the continuous administration of opioids at a set speed for each group., Significance: Our findings therefore provide preliminary evidence for iTBS targeting the DLPFC to be used to improve postoperative pain management., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Repetitive transcranial magnetic stimulation (rTMS) is an effective and evidence-based therapy for treatment-resistant major depressive disorder. A conventional course of rTMS applies 20-30 daily sessions over 4-6 weeks. The schedule of rTMS delivery can be accelerated by applying multiple stimulation sessions per day, which reduces the duration of a treatment course with a predefined number of sessions. Accelerated rTMS reduces time demands, improves clinical efficiency, and potentially induces faster onset of antidepressant effects. However, considerable heterogeneity exists across study designs. Stimulation protocols vary in parameters such as the stimulation target, frequency, intensity, number of pulses applied per session or over a course of treatment, and duration of intersession intervals. In this article, clinician-researchers and neuroscientists who have extensive research experience in accelerated rTMS synthesize a consensus based on two decades of investigation and development, from early studies ("Past") to contemporaneous theta burst stimulation, a time-efficient form of rTMS gaining acceptance in clinical settings ("Present"). We propose descriptive nomenclature for accelerated rTMS, recommend avenues to optimize therapeutic and efficiency potential, and suggest using neuroimaging and electrophysiological biomarkers to individualize treatment protocols ("Future"). Overall, empirical studies show that accelerated rTMS protocols are well tolerated and not associated with serious adverse effects. Importantly, the antidepressant efficacy of accelerated rTMS appears comparable to conventional, once daily rTMS protocols. Whether accelerated rTMS induces antidepressant effects more quickly remains uncertain. On present evidence, treatment protocols incorporating high pulse dose and multiple treatments per day show promise and improved efficacy., (Copyright © 2023 President and Fellows of Harvard College.)

Objective: Electroencephalographic (EEG) data are often contaminated with non-neural artifacts which can confound experimental results. Current artifact cleaning approaches often require costly manual input. Our aim was to provide a fully automated EEG cleaning pipeline that addresses all artifact types and improves measurement of EEG outcomes METHODS: We developed RELAX (the Reduction of Electroencephalographic Artifacts). RELAX cleans continuous data using Multi-channel Wiener filtering [MWF] and/or wavelet enhanced independent component analysis [wICA] applied to artifacts identified by ICLabel [wICA&#95;ICLabel]). Several versions of RELAX were compared using three datasets (N = 213, 60 and 23 respectively) against six commonly used pipelines across a range of artifact cleaning metrics, including measures of remaining blink and muscle activity, and the variance explained by experimental manipulations after cleaning., Results: RELAX with MWF and wICA&#95;ICLabel showed amongst the best performance at cleaning blink and muscle artifacts while preserving neural signal. RELAX with wICA&#95;ICLabel only may perform better at differentiating alpha oscillations between working memory conditions., Conclusions: RELAX provides automated, objective and high-performing EEG cleaning, is easy to use, and freely available on GitHub., Significance: We recommend RELAX for data cleaning across EEG studies to reduce artifact confounds, improve outcome measurement and improve inter-study consistency., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The brain works as an organised, network-like structure of functionally interconnected regions. Disruptions to interconnectivity in certain networks have been linked to symptoms of depression and impairments in cognition. Electroencephalography (EEG) is a low-burden tool by which differences in functional connectivity (FC) can be assessed. This systematic review aims to provide a synthesis of evidence relating to EEG FC in depression. A comprehensive electronic literature search for terms relating to depression, EEG, and FC was conducted on studies published before the end of November 2021, according to PRISMA guidelines. Studies comparing EEG measures of FC of individuals with depression to that of healthy control groups were included. Data was extracted by two independent reviewers, and the quality of EEG FC methods was assessed. Fifty-two studies assessing EEG FC in depression were identified: 36 assessed resting-state FC, and 16 assessed task-related or other (i.e., sleep) FC. Somewhat consistent findings in resting-state studies suggest for no differences between depression and control groups in EEG FC in the delta and gamma frequencies. However, while most resting-state studies noted a difference in alpha, theta, and beta, no clear conclusions could be drawn about the direction of the difference, due to considerable inconsistencies between study design and methodology. This was also true for task-related and other EEG FC. More robust research is needed to understand the true differences in EEG FC in depression. Given that the FC between brain regions drives behaviour, cognition, and emotion, characterising how FC differs in depression is essential for understanding the aetiology of depression., Competing Interests: Conflict of interest Authors AM, NWB, OWM, and MPNP report no financial or potential conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Electroencephalography (EEG) is often used to examine neural activity time-locked to stimuli presentation, referred to as Event-Related Potentials (ERP). However, EEG is influenced by non-neural artifacts, which can confound ERP comparisons. Artifact cleaning reduces artifacts, but often requires time-consuming manual decisions. Most automated methods filter frequencies <1 Hz out of the data, so are not recommended for ERPs (which contain frequencies <1 Hz). Our aim was to test the RELAX (Reduction of Electroencephalographic Artifacts) pre-processing pipeline for use on ERP data., Methods: The cleaning performance of multiple versions of RELAX were compared to four commonly used EEG cleaning pipelines across both artifact cleaning metrics and the amount of variance in ERPs explained by different conditions in a Go-Nogo task. Results RELAX with Multi-channel Wiener Filtering (MWF) and wavelet-enhanced independent component analysis applied to artifacts identified with ICLabel (wICA&#95;ICLabel) cleaned data most effectively and produced amongst the most dependable ERP estimates. RELAX with wICA&#95;ICLabel only or MWF&#95;only may detect effects better for some ERPs., Conclusions: RELAX shows high artifact cleaning performance even when data is high-pass filtered at 0.25 Hz (applicable to ERP analyses)., Significance: RELAX is easy to implement via EEGLAB in MATLAB and freely available on GitHub. Given its performance and objectivity we recommend RELAX to improve artifact cleaning and consistency across ERP research., Competing Interests: Declaration of Interest PBF has received equipment for research from MagVenture A/S, Nexstim, Neuronetics and Brainsway Ltd and funding for research from Neuronetics. He is a founder of TMS Clinics Australia and Resonance Therapeutics. NWB, ATH, MB, OWM, NCR, BM, and AM have no competing interests to declare., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)