Search

Background: Magnetic seizure therapy (MST) is a potential alternative to electroconvulsive therapy (ECT). However, reports on the use of MST for patients with schizophrenia, particularly in developing countries, which is a main indication for ECT, are limited. Methods: From February 2017 to July 2018, 79 inpatients who met the DSM-5 criteria for schizophrenia were randomized to receive 10 sessions of MST (43 inpatients) or ECT (36 inpatients) over the course of 4 weeks. At baseline and 4-week follow-up, the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to assess symptom severity and cognitive functions, respectively. Results: Seventy-one patients who completed at least half of the treatment protocol were included in the per-protocol analysis. MST generated a non-significant larger antipsychotic effect in terms of a reduction in PANSS total score [ g = 0.17, 95% confidence interval (CI) = -0.30, 0.63] and response rate [relative risk (RR) = 1.41, 95% CI = 0.83-2.39]. Twenty-four participants failed to complete the cognitive assessment as a result of severe psychotic symptoms. MST showed significant less cognitive impairment over ECT in terms of immediate memory ( g = 1.26, 95% CI = 0.63-1.89), language function ( g =1.14, 95% CI = 0.52-1.76), delayed memory ( g = 0.75, 95% CI = 0.16-1.35), and global cognitive function ( g = 1.07, 95% CI = 0.45-1.68). The intention-to-treat analysis generated similar results except for the differences in delayed memory became statistically insignificant. Better baseline cognitive performance predicted MST and ECT response. Conclusions: Compared to bitemporal ECT with brief pulses and age-dose method, MST had similar antipsychotic efficacy with fewer cognitive impairments, indicating that MST is a promising alternative to ECT as an add-on treatment for schizophrenia. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT02746965., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiang, Li, Xu, Zhang, Sheng, Liu, Wang, Yang, Guo, Li, Zhang, Tang, Jia, Daskalakis, Wang and Li.)

The World Health Organization characterized COVID-19 (coronavirus disease 2019) as a pandemic on March 11, 2020 (WHO). Within a couple of days, all Canadian provinces announced the implementation of social distancing measures. We evaluated the immediate effect of COVID-19 on psychiatric emergency and inpatient services in Canada's largest psychiatric hospital in the first month of the pandemic. We extracted data from the electronic medical records of the Center for Addiction and Mental Health in Toronto, Canada. We compared emergency department visits, inpatient occupancy rates, and length of stay in March 2019 and March 2020, and during the first and second half of March 2020. There was a decrease in the number of emergency department visits and inpatient occupancy rates in March 2020 compared to March 2019. There was also a significant decrease in the number of emergency department visits and inpatient occupancy rates in the second half of March 2020 compared to the first half. Our findings suggest that the pandemic was followed by a rapid decrease in the usage of psychiatric emergency and inpatient services in a large mental health hospital. Future studies will need to assess whether this decrease will be followed by a return to baseline or an increase in need for these services., Competing Interests: MH is a PI for a trial sponsored by COMPASS Pathways Limited for which he receives salary support. MH has been awarded grants from the Brain and Behavior Research Foundation, Physician's Services Incorporated Foundation, Stanley Medical Research Institute and University of Toronto. BM reports research financial support from Brain Canada, CAMH Foundation, Canadian Institutes for Health Research, and US National Institutes of Health; nonfinancial support from Pfizer (medication for an NIH-funded trial), Eli Lilly (medication and matching placebo for an NIH-funded trial), Capital Solution Design LLC (software for a trial funded by the CAMH Foundation), and HAPPYneuron (software for a trial funded by Brain Canada). In the last 5 years, ZD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc and Magventure Inc. ZD work is supported by the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), Brain Canada, and the Temerty Family and Grant Family through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. AW's funding sources include CIHR and Miner's Lamp Award. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kim, Carvalho, Gratzer, Wong, Gutzin, Husain, Mulsant, Stergiopoulos and Daskalakis.)

Impaired early auditory processing is a well characterized finding in schizophrenia that is theorized to contribute to clinical symptoms, cognitive impairment, and social dysfunction in patients. Two neurophysiological measures of early auditory processing, P50 gating ("P50") and mismatch negativity (MMN), which measure sensory gating and detection of change in auditory stimuli, respectively, are consistently shown to be impaired in patients with schizophrenia. Transcranial magnetic stimulation (TMS) may also be a potential method by which sensory processing can be assessed, since TMS paradigms can be used to measure GABA B -mediated cortical inhibition that is linked with sensory gating. In this review, we examine the potential of P50, MMN and two TMS paradigms, cortical silent period (CSP) and long-interval intracortical inhibition (LICI), as endophenotypes as well as their ability to be used as predictive markers for interventions targeted at cognitive and psychosocial functioning. Studies consistently support a link between MMN, P50, and cognitive dysfunction, with robust evidence for a link between MMN and psychosocial functioning in schizophrenia as well. Importantly, studies have demonstrated that MMN can be used to predict performance in social and cognitive training tasks. A growing body of studies also supports the potential of MMN to be used as an endophenotype, and future studies are needed to determine if MMN can be used as an endophenotype specifically in schizophrenia. P50, however, has weaker evidence supporting its use as an endophenotype. While CSP and LICI are not as extensively investigated, growing evidence is supporting their potential to be used as an endophenotype in schizophrenia. Future studies that assess the ability of P50, MMN, and TMS neurophysiological measures to predict performance in cognitive and social training programs may identify markers that inform clinical decisions in the treatment of neurocognitive impairments in schizophrenia., (Copyright © 2020 Kim, Blumberger and Daskalakis.)

Background: Amotivation is a prevalent symptom in schizophrenia (SZ) and depression (MDD), and is linked to poor functional outcomes in affected individuals. Conceptualizations of motivation have outlined a multi-faceted construct comprised of reward responsiveness, reward expectancy, reward valuation, effort valuation, and action selection/preference-based decision making. To date, findings from studies utilizing variable-centered approaches to examining isolated facets of motivation in SZ and MDD have been inconsistent. Thus, the present study adopted a person-centered approach, and comprehensively examined the reward system in a non-clinical sample in an attempt to explore potential subtypes of motivation impairments, while minimizing the effects of illness-related confounds. Methods: Ninety-six healthy undergraduate students were evaluated for amotivation, schizotypal traits, depressive symptoms, and cognition, and administered objective computerized tasks to measure the different facets of motivation. Cluster analysis was performed to explore subgroups of individuals based on similar motivation task performance. Additionally, correlational analyses were conducted in order to examine inter-relationships between motivation facets, and relations between clinical measures and facets of motivation. Results: Cluster analysis identified two subgroups of individuals with differential motivation performance profiles. Correlational analyses revealed that reward responsiveness was associated with amotivation, depressive symptoms, and negative schizotypy. Further, significant inter-correlations were found between reward responsiveness and reward expectancy, as well as between reward valuation and effort valuation. Conclusions: Our results mark important steps forward in understanding motivation in a non-clinical sample, and guide future dimensional and comprehensive analyses of the multi-faceted reward system. It remains to be seen whether these patterns of results will be similar in clinical populations such as SZ and MDD.

Objective: Electroconvulsive therapy is effective in treatment-resistant schizophrenia (TRS) but use is limited due to stigma and concerns around cognitive adverse effects. Magnetic seizure therapy (MST) is a promising new neuromodulation technique that uses transcranial magnetic stimulation to induce therapeutic seizures. Studies of MST in depression have shown clinical improvement with a favorable adverse effect profile. No studies have examined the clinical utility of MST in schizophrenia., Methods: We conducted an open-label pilot clinical trial of MST in eight TRS patients. Up to 24 MST treatments were delivered depending on treatment response. We assessed clinical outcome through the Brief Psychiatric Rating Scale (BPRS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Cognitive testing included a neuropsychological test battery, the Autobiographical Memory Inventory (AMI), Montreal Cognitive Assessment (MoCA), and reorientation time., Results: Four patients completed the trial as per protocol. For all patients and for trial completers alone, there was a significant clinical and quality of life improvement. Three met pre-determined criteria for remission (total score ≤25 on the BPRS) and one met criteria for response (i.e., ≥25% BPRS improvement from baseline for two consecutive assessments). Pre and post neurocognitive data showed no significant cognitive adverse effects apart from a decrease in AMI scores., Conclusion: In this pilot study, MST demonstrated evidence for feasibility in patients with TRS, with promise for clinical efficacy and negligible cognitive side effects. Further study in larger clinical populations is needed., Clinical Trial Registration: www.ClinicalTrials.gov, Identifier NCT01596608.

Adolescent depression is a prevalent disorder with substantial morbidity and mortality. Current treatment interventions do not target relevant pathophysiology and are frequently ineffective, thereby leading to a substantial burden for individuals, families, and society. During adolescence, the prefrontal cortex undergoes extensive structural and functional changes. Recent work suggests that frontolimbic development in depressed adolescents is delayed or aberrant. The judicious application of non-invasive brain stimulation techniques to the prefrontal cortex may present a promising opportunity for durable interventions in adolescent depression. Transcranial direct current stimulation (tDCS) applies a low-intensity, continuous current that alters cortical excitability. While this modality does not elicit action potentials, it is thought to manipulate neuronal activity and neuroplasticity. Specifically, tDCS may modulate N -methyl-d-aspartate receptors and L-type voltage-gated calcium channels and effect changes through long-term potentiation or long-term depression-like mechanisms. This mini-review considers the neurobiological rationale for developing tDCS protocols in adolescent depression, reviews existing work in adult mood disorders, surveys the existing tDCS literature in adolescent populations, reviews safety studies, and discusses distinct ethical considerations in work with adolescents.

Objective: The objective of this study was to evaluate the feasibility of using paired-associative stimulation (PAS) to study excitatory and inhibitory plasticity in adolescents while examining variables that may moderate plasticity (such as sex and environment)., Methods: We recruited 34 healthy adolescents (aged 13-19, 13 males, 21 females). To evaluate excitatory plasticity, we compared mean motor-evoked potentials (MEPs) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after PAS at 0, 15, and 30 min. To evaluate inhibitory plasticity, we evaluated the cortical silent period (CSP) elicited by single-pulse TMS in the contracted hand before and after PAS at 0, 15, and 30 min., Results: All participants completed PAS procedures. No adverse events occurred. PAS was well tolerated. PAS-induced significant increases in the ratio of post-PAS MEP to pre-PAS MEP amplitudes ( p  < 0.01) at all post-PAS intervals. Neither socioeconomic status nor sex was associated with post-PAS MEP changes. PAS induced significant CSP lengthening in males but not females., Conclusion: PAS is a feasible, safe, and well-tolerated index of adolescent motor cortical plasticity. Gender may influence PAS-induced changes in cortical inhibition. PAS is safe and well tolerated by healthy adolescents and may be a novel tool with which to study adolescent neuroplasticity.

Background: Several lines of evidence implicate dysfunctional neuronal plasticity in the pathophysiology of schizophrenia (SCZ). Aberrant glutamatergic and gamma amino--butyric acid neurotransmission are thought to underlie core cognitive deficits and negative symptoms of SCZ. Non-invasive brain stimulation (NIBS) allows for the in vivo study of cortical plasticity and excitability at the systems level of the human motor cortex. This review will focus on summarizing the available neurophysiological evidence for impaired motor cortical plasticity in SCZ assessed by NIBS., Methods: A search of MEDLINE, Embase, and PubMed was performed on the use of NIBS techniques to investigate neuroplasticity in the motor cortex of SCZ patients. The relevant articles were summarized., Conclusion: Our review of the literature reveals evidence for disrupted neuroplasticity in SCZ and its close association to alterations in cortical inhibition and dysfunctional intracortical connectivity. Further investigations are required to elucidate the neurobiological mechanisms that underlie dysfunctional plasticity in SCZ in order to develop more targeted therapeutic interventions for SCZ patients.

Exciting developments have taken place in the neuroscience research in autism spectrum disorder (ASD), and results from these studies indicate that brain in ASD is associated with aberrant neuroplasticity. Transcranial magnetic stimulation (TMS) has rapidly evolved to become a widely used, safe, and non-invasive neuroscientific tool to investigate a variety of neurophysiological processes, including neuroplasticity. The diagnostic and therapeutic potential of TMS in ASD is beginning to be realized. In this article, we briefly reviewed evidence of aberrant neuroplasticity in ASD, suggested future directions in assessing neuroplasticity using repetitive TMS (rTMS), and discussed the potential of rTMS in rectifying aberrant neuroplasticity in ASD.

Electroconvulsive therapy (ECT) is the most effective treatment for a refractory major depression in the context of both unipolar and bipolar affective disorders. However, the relapse rate within the first 6 months after a successful course of ECT to treat a depressive episode can be as high 50%. Evidence-based strategies to prevent relapse have partial efficacy and are associated with problematic adverse effects limiting their use as long-term treatments. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in treatment-resistant depression with a favorable adverse effect profile. Herein, we describe six patients, four with unipolar and two with bipolar depression, where rTMS was used to maintain response after a successful course of acute and continuation ECT. rTMS was administered once or twice weekly, at 120% of the resting motor threshold. Patients received sequential bilateral rTMS (low frequency right: 600 pulses, then high frequency left: 3000 pulses). The site of stimulation was 6 cm anterior and 1 cm lateral from the site of maximum stimulation of the abductor pollicis brevis muscle. Depressive symptoms were monitored with the quick inventory of depressive symptoms-self rated. Five of the six patients were able to maintain their response status from 6 to 13 months at the time of last observation. The use of rTMS may be an important relapse prevention strategy following an acute course of ECT. Controlled studies comparing rTMS to current evidence-based relapse prevention strategies are warranted.

Objectives: Transcranial direct current stimulation (tDCS) has demonstrated some efficacy in treatment-resistant major depression (TRD). The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC) and a control location such as the supraorbital region for the cathode. Several open-label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS., Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Rating Scale for Depression greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups., Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated., Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD. ClinicalTrials.gov Identifier: NCT01078948.

Transcranial direct current stimulation (tDCS) is a brain stimulation technique that has the potential to improve working memory (WM) deficits in many clinical disorders. The aim of this study was to investigate the role of current strength on the ability of anodal tDCS to improve WM, and secondly to investigate the time course of effects. Twelve healthy participants underwent three stimulation sessions consisting of 20 min of either 1 mA anodal tDCS, 2 mA anodal tDCS, or sham tDCS to the left dorsolateral prefrontal cortex (DLPFC) localized via F3, all whilst completing a WM task. Intra-stimulation and post-stimulation WM performances were measured using the n-back and Sternberg tasks respectively. Results revealed no significant improvements in participants' accuracy, but a significant interaction was found with respect to current strength and time for accurate reaction time. The finding provides partial support for the hypothesis, in that it appears current strength may affect aspects of WM performance. However, more research is needed, and a higher difficulty level of WM tasks is one of the suggestions discussed for future research.

Throughout the development of psychology the delineation of personality has played a central role. Together with the NEO-PI-R, a questionnaire derived from the Five Factor Model of Personality, and recent advances in research technology it is now possible to investigate the relationship between personality features and neurophysiological brain processes. The NEO-FFI, the short version of the NEO-PI-R, reliably measures five main personality traits: Neuroticism, Extraversion, Openness to experience, Agreeableness, and Conscientiousness. As behavior and some psychiatric disorders have been related to interhemispheric connectivity, the present study used the combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to measure frontal interhemispheric connectivity and its association with personality as indexed by the NEO-FFI. Results demonstrated that prefrontal interhemispheric connectivity between the left and right dorsolateral prefrontal cortex correlates with Agreeableness in healthy subjects. This is the first study to relate personality features to interhemispheric connectivity through TMS-EEG and suggests that Agreeableness relates to the effectiveness of prefrontal communication between hemispheres.