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Background: Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood.Methods/design: This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity.Discussion: ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments.Trial Registration: ClinicalTrials.gov NCT03191058 . Registered on June 19, 2017. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure. Methods: In this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach. Discussion: Positive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy. Trial status: Enrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants. Trial registration: ClinicalTrials.gov NCT03191058, Registered on June 19, 2017. Primary sponsor: Daniel Blumberger (DMB), Principal Investigator Daniel.Blumberger@camh.ca, 416-535-8501 x 33662 Contact for public queries: DMB, Daniel.Blumberger@camh.ca Contact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure.Methods: In this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach.Discussion: Positive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy.Trial Status: Enrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants.Trial Registration: ClinicalTrials.gov NCT03191058 , Registered on June 19, 2017. Primary sponsor: Daniel Blumberger (DMB), Principal Investigator Daniel.Blumberger@camh.ca , 416-535-8501 x 33662 Contact for public queries: DMB, Daniel.Blumberger@camh.ca Contact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu. [ABSTRACT FROM AUTHOR]

An editorial is presented on findings on a new treatment protocol developing for rapidly and effectively treating individuals with treatment-resistant depression. Topics include placebo control in the latest study being important giving the relatively high likelihood of a placebo response in treatment-resistant depression; and limiting the generalizability and full adoption of the treatment innovation in the treatment-resistant depression population.

Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder which does not respond to traditional and first-line therapeutic options. There are several definitions and staging models of TRD and a consensus for each has not yet been established. However, in common for each model is the inadequate response to at least 2 trials of antidepressant pharmacotherapy. In this review, a comprehensive analysis of existing literature regarding the challenges and management of TRD has been compiled. A PubMed search was performed to assemble meta-analyses, trials and reviews on the topic of TRD. First, we address the confounds in the definitions and staging models of TRD, and subsequently the difficulties inherent in assessing the illness. Pharmacological augmentation strategies including lithium, triiodothyronine and second-generation antipsychotics are reviewed, as is switching of antidepressant class. Somatic therapies, including several modalities of brain stimulation (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation) are detailed, psychotherapeutic strategies and subsequently novel therapeutics including ketamine, psilocybin, anti-inflammatories and new directions are reviewed in this manuscript. Our review of the evidence suggests that further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD. [ABSTRACT FROM AUTHOR]

In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual's subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non- clinical research to start accounting for participants' subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions. [ABSTRACT FROM AUTHOR]

Background: Approximately 35% of people with depression do not respond to 2 courses of antidepressant medications of adequate dosage, and treatment-resistant depression (TRD) is still a major clinical concern with a great impact on patients, their families, society and the health system. The present meta-analysis evaluates antidepressant efficacy of unilateral and bilateral repetitive transcranial magnetic stimulation (rTMS) in patients with unipolar TRD. Methods: We searched for randomized controlled trials that compared rTMS with sham treatment and were published by Apr. 3, 2017. The primary outcome was improvement in depression scores measured using the Hamilton Rating Scale for Depression. The secondary outcomes were remission and response rates. Two independent review authors screened the studies and extracted the data. Results: Twenty-three studies met the inclusion criteria. Meta-analysis of the depression scores showed a weighted mean difference (WMD) of 3.36 (95% confidence interval [CI] 1.85–4.88) between unilateral rTMS and sham treatment. Stratified data showed that the effect was relatively higher when rTMS was used as an add-on to antidepressant medications (WMD 3.64, 95% CI 1.52–5.76) than when it was used as a stand-alone treatment (WMD 2.47, 95% CI 0.90–4.05). The WMD between bilateral rTMS and sham was 2.67 (95% CI 0.83–4.51), and all studies that contributed to this outcome used rTMS while participants were taking antidepressant medications. The pooled remission and response rates for unilateral rTMS versus sham treatment were 16.0% and 25.1% for rTMS and 5.7% and 11.0% for sham treatment, respectively. The pooled remission and response rates for bilateral rTMS versus sham treatment were 16.6% and 25.4% for rTMS and 2.0% and 6.8% for sham treatment, respectively. Conclusion: This study suggests that rTMS has moderate antidepressant effects and appears to be promising in the short-term treatment of patients with unipolar TRD. [ABSTRACT FROM AUTHOR]

Objective: Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented.Methods: An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing.Conclusions: EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD. [ABSTRACT FROM AUTHOR]

Background: Dementia frequently presents with aggression, agitation, and disorganized behavior for which current treatment is partially effective and is associated with significant adverse effects.Objective: The aim of this study was to retrospectively assess the clinical effectiveness and tolerability of electroconvulsive therapy (ECT) in a sample of patients with neuropsychiatric symptoms of dementia (NPS) and to explore factors associated with response and with cognitive adverse effects.Methods: We examined the clinical records of 25 patients with dementia and a pre-existing psychiatric disorder treated with ECT at an academic mental health hospital between April 1, 2010 and January 28, 2016. Twenty-nine acute ECT courses and fifteen maintenance courses were reviewed. We assessed treatment effectiveness and cognitive adverse effects as well as factors associated with response to treatment, including pre-existing psychiatric disorders, concomitant pharmacological treatment and types of dementia.Results: ECT resulted in a clinically meaningful response in 72% of acute treatment courses. Cognitive adverse effects affecting functioning were reported in 7% of the acute treatment courses. Maintenance treatment was effective in sustaining the response in 87% of treatment courses with two reports of significant cognitive adverse effects. One patient fell and experienced a hip fracture a day after treatment. Use of antipsychotic or antidepressant medications, pre-existing psychiatric disorder, or gender were not associated with response.Conclusion: This study shows meaningful clinical effectiveness and good tolerability of ECT in patients with severe NPS of dementia. Furthermore, maintenance ECT was effective in sustaining treatment response. [ABSTRACT FROM AUTHOR]

Biomarkers are essential for understanding the underlying pathologies in brain disorders and for developing effective treatments. Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is an emerging neurophysiological tool that can be used for biomarker development. This method can identify biomarkers associated with the function and dynamics of the inhibitory and excitatory neurotransmitter systems and effective connectivity between brain areas. In this review, we outline the current state of the TMS-EEG biomarker field by summarizing the existing protocols and the possibilities and challenges associated with this methodology. • TMS-EEG is an emerging neurophysiological method for searching biomarkers. • TMS-EEG can measure neurotransmitter functionality and effective connectivity. • The main challenges are various artifacts that may influence the biomarkers. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article describes the history of transcranial direct current stimulation (tDCS) for treating major depression and its potential antidepressant mechanism of action and reviews findings from recent clinical trials and discuses the potential role of tDCS in treating depressive disorders. Topics discussed include an investigation on the utility of tDCS as a treatment for depression in the 1960s and randomized controlled trials conducted to examine the efficacy of tDCS in treating depression.

Long-interval cortical inhibition (LICI) refers to suppression of neuronal activity following paired-pulse transcranial magnetic stimulation (TMS) with interstimulus intervals (ISIs) between 50 and 200 ms. LICI can be measured either from motor-evoked potentials (MEPs) in small hand muscles or directly from the cortex using concurrent electroencephalography (EEG). However, it remains unclear whether EEG inhibition reflects similar mechanisms to MEP inhibition. Eight healthy participants received single- and paired-pulse TMS (ISI = 100 ms) over the motor cortex. MEPs were measured from a small hand muscle (first dorsal interosseus), whereas early (P30, P60) and late (N100) TMS-evoked cortical potentials (TEPs) were measured over the motor cortex using EEG. Conditioning and test TMS intensities were altered, and modulation of LICI strength was measured using both methods. LICI of MEPs and both P30 and P60 TEPs increased in strength with increasing conditioning intensities and decreased with increasing test intensities. LICI of N100 TEPs remained unchanged across all conditions. In addition, MEP and P30 LICI strength correlated with the slope of the N100 evoked by the conditioning pulse. LICI of early and late TEP components was differentially modulated with altered TMS intensities, suggesting independent underlying mechanisms. LICI of P30 is consistent with inhibition of cortical excitation similar to MEPs, whereas LICI of N100 may reflect presynaptic autoinhibition of inhibitory interneurons. The N100 evoked by the conditioning pulse is consistent with the mechanism responsible for LICI, most likely GABAB-mediated inhibition of cortical activity. [ABSTRACT FROM AUTHOR]

Suicidal ideation (SI) is understudied in obsessive-compulsive disorder (OCD). Nonetheless, evidence suggests increased risk for SI in individuals with OCD compared to the general population. Understanding the relationship between SI and OCD involves investigating risk factors associated with SI. Furthering knowledge of links is essential for enhancing outcomes and decreasing experiences of SI through improving treatment interventions. Additionally, increasing awareness of factors that lead SI to suicide attempts (SA) is vital. To best illustrate the current state of knowledge, this scoping review examines risk factors for SI, including symptom profiles or phenotypes, comorbid diagnoses, sociodemographic and lifestyle factors, childhood trauma, and genetic and familial contributions. Important treatment considerations for targeting SI within the context of OCD are detailed with respect to the current evidence for psychotherapy, pharmacology, brain stimulation, and neurosurgery. Gaps in the literature and future directions are identified, broadly with respect to studies examining the treatment of SI within the context of OCD, particular OCD phenotypes, and factors influencing SI in pediatric OCD. Due to the relative novelty of this area of exploration, many unknowns persist regarding onset of SI in OCD, factors contributing to the maintenance of SI in OCD, and relevant treatment protocols. Findings suggest that individuals with previous SI or SA, history of childhood trauma, significant life stress, and psychiatric comorbidities, particularly depression, should be closely monitored and screened for SI. [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]

The article focuses on a psychosis symptom unresponsive to front-line treatment. Auditory hallucinations common in psychotic disorders (AH) is presented and is attributed to a distortion of inner thoughts and speech, as well as to abnormal suppression of past memories. Repetitive transcranial magnetic stimulation (rTMS) is discussed as a treatment studied specifically for AH, and suggests protocols for optimum efficacy. A quiz concerning the contents of the article is offered.

Studies of patients with major depressive disorder (MDD) and schizophrenia (SCH) have revealed reduced hippocampal volumes, but findings have been inconsistent due to sample and measurement differences. The current study sought to measure this structure in a large sample of MDD, SCH, and healthy subjects, using a strict measurement protocol, to elucidate morphological-specific volumetric differences. Patients with treatment-resistant MDD ( N = 182) and treatment-resistant SCH with auditory-verbal hallucinations ( N = 52), and healthy controls ( N = 76) underwent psychiatric assessments and brain MRI. The findings indicate that (1) MDD and SCH patients have reduced total hippocampal volume which was marked in the tails (more so in patients with MDD), (2) region of interest estimation protocols and sample characteristics may help explain volumetric differences between previous SCH studies. © 2010 Wiley Periodicals, Inc., Inc. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Concentration changes in hemoglobin following single and paired pulse (2 and 15ms inter-stimulus interval) transcranial magnetic stimulation (TMS) was investigated using near infra-red spectroscopy (NIRS). Methods: TMS was delivered to left pre-frontal cortex at typical intensities used in neuroscience research and concentrations of deoxyhemoglobin (Hb), oxyhemoglobin (HbO) and total hemoglobin (HbT) were measured. Results: Significant drops in concentration of HbO and HbT were observed and while there was no effect of the different pulse types on amplitude, there was a difference in the time taken to return to baseline. Conclusions: The changes observed imply that in pre-frontal cortex, the different TMS pulse types result in differential effects on oxygen consumption. Significance: This study aids our understanding of the physiological effects of single and paired pulse TMS. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8±30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1±26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.Neuropsychopharmacology (2008) 33, 2860–2869; doi:10.1038/npp.2008.22; published online 5 March 2008 [ABSTRACT FROM AUTHOR]

It has been previously demonstrated that unmedicated persons with schizophrenia have deficits in cortical inhibition (CI) as indexed with transcranial magnetic stimulation (TMS). This inhibition is largely mediated by cortical GABAergic mechanisms. It has also been demonstrated that these inhibitory deficits may be normalized with the use of atypical antipsychotic medications. The purpose of this study, therefore, was to examine the effects of clozapine on TMS measures of CI and to compare these effects to unmedicated persons with schizophrenia and healthy subjects. We used two TMS inhibitory paradigms: short interval intra-cortical inhibition (SICI) and the cortical silent period (CSP) to evaluate CI in 10 clozapine-treated persons with schizophrenia, 6 unmedicated persons with schizophrenia and 10 healthy subjects. Clozapine-treated persons with schizophrenia had significantly longer CSPs compared with healthy subjects and unmedicated persons with schizophrenia. There were no significant differences in SICI between groups, however, the severity of psychotic symptoms was correlated with reduced SICI across all persons with schizophrenia. Our findings suggest that clozapine treatment is associated with greater CI in persons with schizophrenia and this increase may be related to potentiation of cortical GABAergic receptor mediated inhibitory neurotransmission. Our results also confirm previous findings suggesting that deficits in CI are related to the severity of psychotic symptoms in persons with schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Dysfunctional cortical inhibition (CI) has been suggested as a mechanism through which symptoms of schizophrenia (SCZ) are mediated. Cortical inhibition refers to a neurophysiological process in which γ-aminobutyric acid (GABA) inhibitory interneurons selectively attenuate the activity of other neurons (e.g., pyramidal neurons) in the cortex. Here we review the neuroanatomic and neurophysiological evidence suggesting CI deficits among persons with SCZ. We also review genetic studies that have linked CI deficits to a polymorphism in the α7-nicotinic cholinergic receptor, thereby positing that a specific genetic mechanism underlies SCZ-related GABA interneuron dysfunction. We will conclude by reviewing the role of CI as a mechanism mediating the therapeutic action of antipsychotic medications. [Copyright &y& Elsevier]

It has been suggested that the therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) are mediated through changes in cortical inhibition (CI). However, in healthy human subjects the effects of rTMS on CI have been inconsistent. Therefore, this study sought to improve on the methodological limitations of previous studies by exploring several different rTMS-stimulus conditions on inhibition in the human motor cortex. In the first experiment, 12 healthy control subjects were randomly assigned to receive regular 1, 10 or 20 Hz rTMS in a counterbalanced order with sessions separated by at least 1 week. In the second experiment, 10 of these 12 subjects received priming rTMS (600 stimuli at 6 Hz followed by 600 stimuli at 1 Hz). Cortical inhibition was indexed using short-interval intracortical inhibition (SICI) and cortical silent period (CSP). Corticospinal excitability was indexed using motor threshold and MEP amplitude. We found no significant overall change in SICI, although there was a significant correlation between changes in SICI with baseline SICI. Subjects with greater SICI at baseline tended to have reduction in SICI post-rTMS, whereas subjects with less SICI tended to have increase in SICI post-rTMS. There was also a significant lengthening of the CSP with higher stimulation frequencies compared to lower stimulation frequencies. These findings suggest that rTMS increases CI, particularly in subjects with reduced baseline inhibition, a finding consistent with the concept of homeostatic plasticity. Baseline physiological characteristics may be further explored as a method to select patients who may benefit from rTMS treatment. [ABSTRACT FROM AUTHOR]

Animal studies have shown that cerebellar projections influence both excitatory and inhibitory neurones in the motor cortex but this connectivity has yet to be demonstrated in human subjects. In human subjects, magnetic or electrical stimulation of the cerebellum 5-7 ms before transcranial magnetic stimulation (TMS) of the motor cortex decreases the TMS-induced motor-evoked potential (MEP), indicating a cerebellar inhibition of the motor cortex (CBI). TMS also reveals inhibitory and excitatory circuits of the motor cortex, including a short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). This study used magnetic cerebellar stimulation to investigate connections between the cerebellum and these cortical circuits. Three experiments were performed on 11 subjects. The first experiment showed that with increasing test stimulus intensities, LICI, CBI and ICF decreased, while SICI increased. The second experiment showed that the presence of CBI reduced SICI and increased ICE The third experiment showed that the interaction between CBI and LICI reduced CBI. Collectively, these findings suggest that cerebellar stimulation results in changes to both inhibitory and excitatory neurones in the human motor cortex. [ABSTRACT FROM AUTHOR]

Previous studies suggest that antipsychotic medications may alter cortical inhibition (CI). The current study was designed to determine if typical or atypical antipsychotics indeed alter CI in healthy subjects using three CI paradigms as measured with transcranial magnetic stimulation (TMS): short interval intracortical inhibition (SICI), cortical silent period (CSP) and transcallosal inhibition (TCI). CI was measured before, 6 and 24 h after being randomly assigned to receive a single dose of 2 mg haloperidol (n=8), 10 mg olanzapine (n=10) or placebo (n=9). There was no significant effect on any measure of CI at 6 and 24 h after receiving olanzapine, haloperidol or placebo. Moreover, no significant change in the motor threshold was observed across the three medication groups. Therefore, single administration of an antipsychotic has no effect on CI or resting motor threshold. Whether chronic, repeated administration of antipsychotics has effects on CI requires further investigation. [ABSTRACT FROM AUTHOR]

Background: The transcranial magnetic stimulation (TMS)-induced contralateral silent period (CSP) refers to a period of interruption of voluntary muscle activity measured in tonically active muscles. The length of the CSP is generally interpreted to reflect cortical inhibition. The determination of the return of voluntary motor activity is typically accomplished via visual inspection of the electromyography (EMG) waveform and may be subject to inaccuracy on the part of the rater.Objective: To present and evaluate an automated method (AM) to determine the CSP.Methods: The CSP of 11 healthy controls was recorded using stimulus intensities 20 and 50% above the resting motor threshold (RMT). The mean CSP duration obtained by the two raters using visual inspection and our automated approach were compared.Results: The interclass correlation coefficient (ICC) between the two raters and the AM was 0.99 at 150% of RMT and was 0.97 at 120% of RMT. The level of pre-stimulus EMG amplitude and sampling rate did not affect agreement between the AM and more conventional visually guided methods.Conclusions: Our study demonstrates that this AM is a simple, objective and reliable approach for CSP determination.Significance: The CSP is an important neurophysiological measure of cortical inhibition and its determination by our AM provides a more objective and automated approach compared to visually guided methods. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Suicidality is increased in autism spectrum disorder (ASD), yet effective interventions are lacking. Developing biologically based approaches for preventing and treating suicidality in ASD hinges on the identification of biomarkers of suicidal ideation (SI). Here, we assessed magnetic resonance spectroscopy (MRS) markers of glutamatergic neurotransmission in ASD youth and young adults. Twenty-eight ASD participants (16–33 years) underwent 1H-MRS, and metabolites were quantified using LCModel. N-acetylaspartate (NAA), glutamate (Glu), and the NAA/Glu ratio from the left dorsolateral prefrontal cortex were compared between ASD SI+ (n = 13) and ASD SI− (n = 15) participants. We found that ASD SI+ participants had a higher NAA/Glu ratio compared ASD SI− participants. The NAA/Glu ratio also predicted SI and significantly discriminated between ASD SI+/SI− participants. All analyses including NAA and Glu alone were non-significant. Here, we provide preliminary evidence for the importance of NAA/Glu in ASD with SI, with implications for biomarker discovery. Further mechanistic research into risk and interventional approaches to address SI in ASD are needed. [ABSTRACT FROM AUTHOR]

This scientific commentary refers to ‘Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study’, by Li et al. (doi:10.1093/brain/awu109). [ABSTRACT FROM AUTHOR]

The article describes the case of a 34-year old female patient with a history of treatment-resistant depression who underwent a course of electroconvulsive therapy (ECT). The patient experienced improvement in depressive symptoms following 10 right-unilateral ulrabrief ECT treatments, but marked worsening of depressed mood within one month of discontinuing ECT. She received magnetic seizure treatment and experienced remission of her depressive symptoms.

An individualized model that predicts trial‐by‐trial working memory performance is instrumental for personalized interventions. Here, we propose a single‐trial electroencephalography (EEG) classification process predicting individuals' responses, that is, target correct versus target non‐correct during a working memory task, N‐back. We used event‐related (de‐)synchronization (ERD and ERS) prior to an anticipatory cue as features. The proposed comprehensive process addresses single‐trial EEG classification challenges such as temporal overlap between training and testing datasets, feature selection's stability, and significance of the classification accuracy which have been often overlooked. Our model identified for the first time a few (ranged between 4 and 10) brain regions and oscillations where ERD and ERS predicted an individual's performance. Mean (SD) prediction accuracy across 50 participants (mean age [SD] = 28.56 [7.55]) was 69.51% (8.41). Accuracy was significantly above chance in 34 participants. This machine learning‐based approach provides a proof of principle for individualizing EEG targets for potential interventions. [ABSTRACT FROM AUTHOR]

A latter to the editor is presented in response to the article "Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study," by J. A. Frazier, A. J. Giuliano, J. L. Johnson, et al. presented in a previous issue of the "Journal of the American Academy of Child and Adolescent Psychiatry" (JAACAP).

A case study is presented on a 37-year-old female with a history of mental disorders who had experienced psychiatric symptoms at the age of eight. The patient encountered depressive episodes and psychotic symptoms including auditory and olfactory hallucinations. She was treated with antidepressants, electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) that was effective in improving her mood. The article discusses the use of rTMS and some psychiatric symptoms.

Objective: Postmortem and structural imaging studies suggest that patients with schizophrenia have disrupted cerebellar activity. It has been speculated that these abnormalities mediate disorganized thought processes and psychosis. The authors' goal was to use transcranial magnetic stimulation to measure cerebellar inhibition, a proxy of cerebellar activity, as the principal output of the cerebellum is inhibitory. Method: Cerebellar inhibition was accomplished by delivering a magnetic cerebellar conditioning stimulus 5-15 msec before a magnetic test stimulus to the motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor evoked potential produced by the test stimulus by approximately 50%. Ten patients with schizophrenia and 10 healthy comparison subjects completed the cerebellar inhibition protocol. Results: Patients with schizophrenia demonstrated significant deficits in cerebellar inhibition compared with healthy subjects. Conclusions: The authors conclude that deficits in cerebellar inhibitory activity in schizophrenia may be the result of an abnormality in the cerebellum or disrupted cerebellar-thalamic.. cortical connectivity. [ABSTRACT FROM AUTHOR]

Considerable research has demonstrated the efficacy of repetitive transcranial magnetic stimulation treatment (rTMS) in patients with major depressive disorder (MDD) with differences in effects related to laterality of stimulation. However, no systematic research has explored whether left-handed subjects respond in the same way as right-handed subjects. Data from 6 clinical trials (n = 310) were pooled and we explored whether left-handed patients with MDD responded in a similar manner to rTMS, including how they responded to both high-frequency left and low-frequency right-sided forms of treatment. Overall, patients with MDD who were left-handed responded to a greater degree than right-handed patients to rTMS therapy. On subgroup analysis, notably limited by small numbers in the left handed groups, this effect was seen with high-frequency left-sided treatment but not with low-frequency right-sided treatment. The overall effect of a greater response in left-handed patients was not attributable to other clinical or study variables. Standard forms of rTMS treatment appear to be effective in patients with MDD who are left-handed and there seems no justification for modifying the laterality of treatment application in these patients. [ABSTRACT FROM AUTHOR]

Theta burst stimulation (TBS), a specific form of repetitive transcranial magnetic stimulation (TMS), is a promising treatment for youth with Major Depressive Disorder (MDD) who do not respond to conventional therapies. However, given the variable response to TBS, a greater understanding of how baseline features relate to clinical response is needed to identify which patients are most likely to benefit from this treatment. In the current study, we sought to determine if baseline neurophysiology, specifically cortical excitation and/or inhibition, is associated with antidepressant response to TBS. In two independent open-label clinical trials, youth (aged 16–24 years old) with MDD underwent bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment. Clinical trial one and two consisted of 10 and 20 daily sessions of bilateral DLPFC TBS, respectively. At baseline, single-pulse TMS combined with electroencephalography was used to assess the neurophysiology of 4 cortical sites: bilateral DLPFC and inferior parietal lobule. Measures of cortical excitation and inhibition were indexed by TMS-evoked potentials (i.e., P30, N45, P60, N100, and P200). Depression severity was measured before, during and after treatment completion using the Hamilton Rating Scale for Depression—17. In both clinical trials, the baseline left DLPFC N45 and P60, which are believed to reflect inhibitory and excitatory mechanisms respectively, were predictors of clinical response. Specifically, greater (i.e., more negative) N45 and smaller P60 baseline values were associated with greater treatment response to TBS. Accordingly, cortical excitation and inhibition circuitry of the left DLPFC may have value as a TBS treatment response biomarker for youth with MDD. Clinical trial 1 registration number: NCT02472470 (June 15, 2015). Clinical trial 2 registration number: NCT03708172 (October 17, 2018). [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) can offer therapeutic benefits and provide value in neurophysiological research. One of the newer TMS paradigms is theta burst stimulation (TBS) which can be delivered in two patterns: continuous (cTBS – inducing LTD-like effects) and intermittent (iTBS – inducing LTP-like effects). This review paper aims to explore studies that have utilized TBS protocols over different areas of the cortex to study the neurophysiological functions and treatment of patients with schizophrenia. PubMed was searched using the following keywords "schizophrenia", "schizoaffective", or "psychosis", and "theta burst stimulation". Out of the 90 articles which were found, thirty met review inclusion criteria. The inclusion criteria included studying the reported effect (clinical, physiological, or both) of at least one session of TBS on human subjects, and abstracts (at minimum) must have been in English. The main target areas included prefrontal cortex (12 studies - 10 dorsolateral prefrontal cortex (DLPFC), 2 dorsomedial prefrontal cortex (DMPFC)) vermal cerebellum (5), and temporo-parietal cortex (8). Other target areas included inferior parietal lobe (2), and motor cortex (3). TBS neurophysiological effect was explored in 5 studies using functional magnetic resonance image (fMRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), electromyography (EMG) and positron emission topography (PET) scan. Overall, TBS can offer great therapeutic potential as it is well-tolerated, feasible, and has few, if any, adverse effects. TBS may be targeted to treat specific symptomatology, as an augmenting intervention to pharmacotherapy, or even improving patient's insight into their diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Anorexia nervosa (AN) is a complex disorder of unknown etiology, characterized by obsessions and compulsions around body shape, weight, and calorie intake. In the course of AN, 10%–30% will recover, while the rest will develop a treatment-resistant course with a high mortality rate due to AN-related complications. The insula is a region in the brain of considerable interest to its role in gustatory modulation, feeding behavior, and processing of interoceptive stimuli. Objective: Recent advances in the neurophysiology of AN suggest insula dysfunction as a potential biomarker for people with severe and enduring AN (SE-AN). Deep transcranial magnetic stimulation (dTMS) is of particular interest in SE-AN because of its ability to target deep areas of the brain. Design: We conducted a pilot study to investigate the feasibility and safety of insula dTMS in subjects with SE-AN. Results: We found that dTMS is a safe and well-tolerated treatment. We also found a reduction in AN-related obsessions and compulsions, as well as depression and anxiety scores from baseline to the end of the trial. Due to small sample size, the results of this study should be interpreted with great caution. Discussion: The results suggest that dTMS is safe and well tolerated and may be of some clinical interest in patients with SE-AN. However, to determine the true efficacy of dTMS for SE-AN, there is a need to conduct a randomized controlled trial comparing real versus sham dTMS in a larger number of AN subjects. [ABSTRACT FROM AUTHOR]

Guidance on Major Depressive Disorder (MDD) treatment in those with comorbid Alcohol Use Disorder (AUD) is limited. We performed a secondary analysis on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, examining the association between comorbid AUD and depression outcomes. STAR*D was a real-world effectiveness trial starting with citalopram in level 1. Non-responding participants progressed through 3 other sequential treatment levels with different switch or augmentation options. Antidepressant outcomes were compared between MDD (n = 2826) and comorbid MDD and AUD (n = 864). Logistic regressions were performed to evaluate remission and response predictors in the total STAR*D sample and the AUD-comorbidity interaction. Chi-squared tests showed no significant difference in response or remission rates from depression between groups across treatment levels. Higher Hamilton Rating Scale for Depression (HRSD) score was associated with overall lower odds of remission in treatment level 1 (OR = 0.93, p < 0.001) and 2 (OR = 0.95, p < 0.001), with no significant interaction with comorbid AUD. Higher baseline suicidality had overall lower odds of remission in level 1 (OR = 0.82, p < 0.001) and 2 (OR = 0.1, p < 0.001), but with comorbid AUD compared to no AUD, suicidality increased odds of level 1 remission (OR = 1.30, p = 0.012). In comorbid AUD in level 2, venlafaxine was associated with lower odds of remission (OR = 0.13, p = 0.013) and response (OR = 0.12, p = 0.006); bupropion with lower odds of response (OR = 0.22, p = 0.024). Open label study design and lack of alcohol use data. Comorbid AUD may interact with predictors of antidepressant response in MDD and using venlafaxine or bupropion may be less effective. Addressing this comorbidity requires unique assessment and treatment approaches. • In STAR*D, comorbid MDD + AUD did not differ from MDD alone in remission. • In MDD + AUD, baseline suicidality may be associated with better outcomes. • In MDD + AUD, treatment with either venlafaxine or bupropion may be less effective. • No apparent difference of AUD on the effect of depression severity with remission. • When treating MDD + AUD, prognostic factors and treatment may be different. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a prevalent mental health condition affecting millions worldwide, leading to disability and reduced quality of life. MDD poses a global health priority due to its early onset and association with other disabling conditions. Available treatments for MDD exhibit varying effectiveness, and a substantial portion of individuals remain resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS), applied to the left and/or right dorsolateral prefrontal cortex (DLPFC), is an alternative treatment strategy for those experiencing treatment-resistant MDD. The objective of this study is to investigate whether this newer form of rTMS, namely theta burst stimulation (TBS), when performed unilaterally or bilaterally, is efficacious in treatment-resistant MDD. Methods: In this naturalistic, randomized double-blinded non-inferiority trial, participants with a major depressive episode will be randomized to receive either unilateral (i.e., continuous TBS [cTBS] to the right and sham TBS to the left DLPFC) or bilateral sequential TBS (i.e., cTBS to the right and intermittent TBS [iTBS] to the left DLPFC) delivered 5 days a week for 4–6 weeks. Responders will move onto a 6-month flexible maintenance phase where TBS treatment will be delivered at a decreasing frequency depending on degree of symptom mitigation. Several clinical assessments and neuroimaging and neurophysiological biomarkers will be collected to investigate treatment response and potential associated biomarkers. A non-inferiority analysis will investigate whether bilateral sequential TBS is non-inferior to unilateral TBS and regression analyses will investigate biomarkers of treatment response. We expect to recruit a maximal of 256 participants. This trial is approved by the Research Ethics Board of The Royal's Institute of Mental Health Research (REB# 2,019,071) and will follow the Declaration of Helsinki. Findings will be published in peer-reviewed journals. Discussion: Comprehensive assessment of symptoms and neurophysiological biomarkers will contribute to understanding the differential efficacy of the tested treatment protocols, identifying biomarkers for treatment response, and shedding light into underlying mechanisms of TBS. Our findings will inform future clinical trials and aid in personalizing treatment selection and scheduling for individuals with MDD. Trial registration: The trial is registered on https://clinicaltrials.gov/ct2/home (#NCT04142996). [ABSTRACT FROM AUTHOR]

Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation–electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders. TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for treatment-resistant depression, comparing a separated (54-minute interval) and contiguous (0-minute interval) schedule of 2 × 600-pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the left dorsolateral prefrontal cortex at baseline and posttreatment. One hundred fourteen participants had usable TMS-EEG at baseline, and 98 at posttreatment. TMS-evoked potential components (N45, N100) were examined via global mean field analysis. The N100 amplitude decreased from baseline to posttreatment, regardless of the treatment group (F 1,106 = 5.20, p =.02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F 1,102 = 11.30, p =.001, p corrected =.0004). Responders showed higher posttreatment N45 amplitude than nonresponders (F 1,94 = 4.11, p =.045, p corrected =.016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F 4,106 = 6.28, p =.00014). These results provide further evidence for an association between the neurophysiological effects of iTBS and treatment efficacy in treatment-resistant depression. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers. [ABSTRACT FROM AUTHOR]

Presents an introduction to a series of articles related to treatment of depression published in the March 1, 2005 issue of "Journal of Psychiatry & Neuroscience."

Concurrent transcranial magnetic stimulation with functional MRI (concurrent TMS‐fMRI) allows real‐time causative probing of brain connectivity. However, technical challenges, safety, and tolerability may limit the number of trials employed during a concurrent TMS‐fMRI experiment. We leveraged an existing data set with 100 trials of active TMS compared to a sub‐threshold control condition to assess the reliability of the evoked BOLD response during concurrent TMS‐fMRI. This data will permit an analysis of the minimum number of trials that should be employed in a concurrent TMS‐fMRI protocol in order to achieve reliable spatial changes in activity. Single‐subject maps of brain activity were created by splitting the trials within the same experimental session into groups of 50, 40, 30, 25, 20, 15, or 10 trials, correlations (R) between t‐maps derived from paired subsets of trials within the same individual were calculated as reliability. R was moderate‐high for 50 trials (mean R =.695) and decreased as the number of trials decreased. Consistent with previous findings of high individual variability in the spatial patterns of evoked neuronal changes following a TMS pulse, the spatial pattern of Rs differed across participants, but regional R was correlated with the magnitude of TMS‐evoked activity. These results demonstrate concurrent TMS‐fMRI produces a reliable pattern of activity at the individual level at higher trial numbers, particularly within localized regions. The spatial pattern of reliability is individually idiosyncratic and related to the individual pattern of evoked changes. Reliability has become a central issue in fMRI research. While TMS‐fMRI can be a powerful tool to probe brain function, the reliability of the evoked signal has not yet been assessed. Within session reliability of the fMRI‐evoked response following TMS was assessed. Reliability was moderate‐high with 50 trials and moderate with 30 trials. This is higher than typical fMRI measurements, which has important implications for study design and interpretation. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). Methods: A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). Results: Clinical operations of ECT programs were disrupted across all four regions – however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. Conclusions: The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians' activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments. [ABSTRACT FROM AUTHOR]

Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is an effective way to evaluate neurophysiological processes at the level of the cortex. To further characterize the TMS-evoked potential (TEP) generated with TMS-EEG, beyond the motor cortex, we aimed to distinguish between cortical reactivity to TMS versus non-specific somatosensory and auditory co-activations using both single-pulse and paired-pulse protocols at suprathreshold stimulation intensities over the left dorsolateral prefrontal cortex (DLPFC). Fifteen right-handed healthy participants received six blocks of stimulation including single and paired TMS delivered as active-masked (i.e., TMS-EEG with auditory masking and foam spacing), active-unmasked (TMS-EEG without auditory masking and foam spacing) and sham (sham TMS coil). We evaluated cortical excitability following single-pulse TMS, and cortical inhibition following a paired-pulse paradigm (long-interval cortical inhibition (LICI)). Repeated measure ANOVAs revealed significant differences in mean cortical evoked activity (CEA) of active-masked, active-unmasked, and sham conditions for both the single-pulse (F(1.76, 24.63) = 21.88, p < 0.001, η2 = 0.61) and LICI (F(1.68, 23.49) = 10.09, p < 0.001, η2 = 0.42) protocols. Furthermore, global mean field amplitude (GMFA) differed significantly across the three conditions for both single-pulse (F(1.85, 25.89) = 24.68, p < 0.001, η2 = 0.64) and LICI (F(1.8, 25.16) = 14.29, p < 0.001, η2 = 0.5). Finally, only active LICI protocols but not sham stimulation ([active-masked (0.78 ± 0.16, P < 0.0001)], [active-unmasked (0.83 ± 0.25, P < 0.01)]) resulted in significant signal inhibition. While previous findings of a significant somatosensory and auditory contribution to the evoked EEG signal are replicated by our study, an artifact attenuated cortical reactivity can reliably be measured in the TMS-EEG signal with suprathreshold stimulation of DLPFC. Artifact attenuation can be accomplished using standard procedures, and even when masked, the level of cortical reactivity is still far above what is produced by sham stimulation. Our study illustrates that TMS-EEG of DLPFC remains a valid investigational tool. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation has been employed to treat drug dependence, reduce drug use and improve cognition. The aim of the study was to analyze the effectiveness of intermittent theta-burst stimulation (iTBS) on cognition in individuals with methamphetamine use disorder (MUD). Methods: This was a secondary analysis of 40 MUD subjects receiving left dorsolateral prefrontal cortex (L-DLPFC) iTBS or sham iTBS for 20 times over 10 days (twice-daily). Changes in working memory (WM) accuracy, reaction time, and sensitivity index were analyzed before and after active and sham rTMS treatment. Resting-state EEG was also acquired to identify potential biological changes that may relate to any cognitive improvement. Results: The results showed that iTBS increased WM accuracy and discrimination ability, and improved reaction time relative to sham iTBS. iTBS also reduced resting-state delta power over the left prefrontal region. This reduction in resting-state delta power correlated with the changes in WM. Conclusions: Prefrontal iTBS may enhance WM performance in MUD subjects. iTBS induced resting EEG changes raising the possibility that such findings may represent a biological target of iTBS treatment response. [ABSTRACT FROM AUTHOR]