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Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with cognitive, motor, and emotional symptoms. The thalamus and basal ganglia form circuits with the cortex supporting all three of these behavioral domains. Abnormalities in the structure of subcortical regions may suggest atypical development of these networks, with implications for understanding the neural basis of ASD symptoms. Findings from previous volumetric studies have been inconsistent. Here, using advanced surface-based methodology, we investigated localized differences in shape and surface area in the basal ganglia and thalamus in ASD, using T1-weighted anatomical images from the Autism Brain Imaging Data Exchange (373 male participants aged 7-35 years with ASD and 384 typically developing). We modeled effects of diagnosis, age, and their interaction on volume, shape, and surface area. In participants with ASD, we found expanded surface area in the right posterior thalamus corresponding to the pulvinar nucleus, and a more concave shape in the left mediodorsal nucleus. The shape of both caudal putamen and pallidum showed a relatively steeper increase in concavity with age in ASD. Within ASD participants, restricted, repetitive behaviors were positively associated with surface area in bilateral globus pallidus. We found no differences in overall volume, suggesting that surface-based approaches have greater sensitivity to detect localized differences in subcortical structure. This work adds to a growing body of literature implicating corticobasal ganglia-thalamic circuits in the pathophysiology of ASD. These circuits subserve a range of cognitive, emotional, and motor functions, and may have a broad role in the complex symptom profile in ASD.

Legalization of recreational cannabis in Ontario included the legalization of flower and herbs (Phase 1, October 2018), and was followed by the deregulation of cannabis retailers and sales of edibles (Phase 2, February 2020). Research on the impact of cannabis legalization on acute care utilization is nascet; no research has investigated potential age, gender, and geographically vulnerable subgroup effects. Residents living in Northern Ontario not only have higher levels of substance use problems, but also have inadequate access to primary healthcare. Our study investigated the impact of Ontario’s recreational cannabis policy (including Phase 1 and 2) on cannabis-attributable emergency department (ED) visits, and estimated the impact separately for different age and gender groups, with additional analyses focused on Northern Ontarians. We created a cohort of adults (18 and over) eligible for provincial universal health insurance with continuous coverage from 2015–2021 (n = 14,900,820). An interrupted time series was used to examine the immediate impact and month-to-month changes in cannabis-related ED visits associated with Phase 1 & 2 for each subgroup. While Northern Ontario has higher rates of cannabis-related ED visits, both Northern and Southern Ontario show similar patterns of changes. Phase 1 was associated with significant increases in adults 25–64, with the strongest increases seen in women 45–64. Month-to-month trends were flattened in most groups compared to pre-legalization. Phase 2 was associated with significant immediate increases for adults aged 18–44 in both genders, but the increases were larger in women than men. No significant month-to-month changes were detected in this period. While current preventive efforts are largely focused on reducing cannabis-related harms in youths and younger adults, our results show that adults 25–64, particularly women, have been significantly impacted by cannabis policies. Further research on gender-specific cannabis dosage and targeted interventions for adult women should be investigated. Legalization did not appear to have a differential impact on Northern versus Southern Ontario, but higher rates of ED visits in the North should be addressed.

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that safely modulates brain excitability and has therapeutic potential for many conditions. Several studies have shown that anodal tDCS of the primary motor cortex (M1) facilitates motor learning and plasticity, but there is little information about the underlying mechanisms. Using magnetic resonance spectroscopy (MRS), it has been shown that tDCS can affect local levels of γ-aminobutyric acid (GABA) and Glx (a measure of glutamate and glutamine combined) in adults, both of which are known to be associated with skill acquisition and plasticity; however this has yet to be studied in children and adolescents. This study examined GABA and Glx in response to conventional anodal tDCS (a-tDCS) and high definition tDCS (HD-tDCS) targeting the M1 in a pediatric population. Twenty-four typically developing, right-handed children ages 12-18 years participated in five consecutive days of tDCS intervention (sham, a-tDCS or HD-tDCS) targeting the right M1 while training in a fine motor task (Purdue Pegboard Task) with their left hand. Glx and GABA were measured before and after the protocol (at day 5 and 6 weeks) using a PRESS and GABA-edited MEGA-PRESS MRS sequence in the sensorimotor cortices. Glx measured in the left sensorimotor cortex was higher in the HD-tDCS group compared to a-tDCS and sham at 6 weeks (p = 0.001). No changes in GABA were observed in either sensorimotor cortex at any time. These results suggest that neither a-tDCS or HD-tDCS locally affect GABA and Glx in the developing brain and therefore it may demonstrate different responses in adults.

Transcranial magnetic stimulation (TMS) is a non-invasive treatment for adolescent major depressive disorder (MDD). Existing evidence on the efficacy of TMS in adolescent MDD awaits quantitative synthesis. A systematic literature search was conducted, and data from eligible studies were synthesized using random-effects models. Treatment-covariate interactions were examined in exploratory analyses of individual-patient data (IPD). Systematic search of the literature yielded 1264 hits, of which 10 individual studies (2 randomized trials) were included for quantitative synthesis of mainly uncontrolled studies. Individual patient data (IPD) were available from five trials (all uncontrolled studies). Quantitative synthesis of aggregated data revealed a statistically significant negative overall standardized mean change (pooled SMCC = 2.04, 95% CI [1.46; 2.61], SE = 0.29, p < .001), as well as a significant overall treatment response rate (Transformed Proportion = 41.30%, 95% CI [31.03; 51.57], SE = 0.05; p < 0.001), considering data from baseline to post-treatment. Exploratory IPD analyses suggests TMS might be more effective in younger individuals and individuals with more severe depression, and efficacy might be enhanced with certain treatment modality settings, including higher number of TMS sessions, longer treatment durations, and unilateral and not bilateral stimulation. Existing studies exhibit methodological shortcomings, including small-study effects and lack of control group, blinding, and randomization—compromising the credibility of the present results. To date, two randomized controlled trials on TMS in adolescent depression have been published, and the only large-scale randomized trial suggests TMS is not more effective than sham stimulation. Future large-scale, randomized, and sham-controlled trials are warranted. Future trials should ensure appropriate selection of patients for TMS treatment and guide precision medicine approaches for stimulation protocols.

Transcranial magnetic stimulation (TMS) motor mapping is a safe, non-invasive method used to study corticomotor organization and intervention-induced plasticity. Reliability of resting maps is well established, but understudied for active maps and unestablished for active maps obtained using robotic TMS techniques. The objective of this study was to determine the reliability of robotic neuro-navigated TMS motor map measures during active muscle contraction. We hypothesized that map area and volume would show excellent short- and medium-term reliability. Twenty healthy adults were tested on 3 days. Active maps of the first dorsal interosseous muscle were created using a 12 × 12 grid (7 mm spacing). Short- (24 h) and medium-term (3–5 weeks) relative (intra-class correlation coefficient) and absolute (minimal detectable change (MDC); standard error of measure) reliabilities were evaluated for map area, volume, center of gravity (CoG), and hotspot magnitude (peak-to-peak MEP amplitude at the hotspot), along with active motor threshold (AMT) and maximum voluntary contraction (MVC). This study found that AMT and MVC had good-to-excellent short- and medium-term reliability. Map CoG (x and y) were the most reliable map measures across sessions with excellent short- and medium-term reliability (p < 0.001). Map area, hotspot magnitude, and map volume followed with better reliability medium-term than short-term, with a change of 28%, 62%, and 78% needed to detect a true medium-term change, respectively. Therefore, robot-guided neuro-navigated TMS active mapping is relatively reliable but varies across measures. This, and MDC, should be considered in interventional study designs.

Single voxel magnetic resonance spectroscopy (MRS) quantifies metabolites within a specified volume of interest. MRS voxels are constrained to rectangular prism shapes. Therefore, they must define a small voxel contained within the anatomy of interest or include not of interest neighbouring tissue. When studying cortical regions without clearly demarcated boundaries, e.g. the dorsolateral prefrontal cortex (DLPFC), it is unclear how representative a larger voxel is of a smaller volume within it. To determine if a large voxel is representative of a small voxel placed within it, this study quantified total N-Acetylaspartate (tNAA), choline, glutamate, Glx (glutamate and glutamine combined), myo -inositol, and creatine in two overlapping MRS voxels in the DLPFC, a large (30×30x30 mm) and small (15×15x15 mm) voxel. Signal-to-noise ratio (SNR) and tissue type factors were specifically investigated. With water-referencing, only myo -inositol was significantly correlated between the two voxels, while all metabolites showed significant correlations with creatine-referencing. SNR had a minimal effect on the correspondence between voxels, while tissue type showed substantial influence. This study demonstrates substantial variability of metabolite estimates within the DLPFC. It suggests that when small anatomical structures are of interest, it may be valuable to spend additional acquisition time to obtain specific, localized data.

Although much is known about cognitive dysfunction in attention-deficit/hyperactivity disorder (ADHD), few studies have examined the pathophysiology of disordered motor circuitry. We explored differences in neurometabolite levels and transcranial magnetic stimulation (TMS)–derived corticomotor representations among children with ADHD and typically developing children. We used magnetic resonance spectroscopy (MRS) protocols to measure excitatory (glutamate + glutamine [Glx]) and inhibitory (γ-aminobutyric acid [GABA]) neurometabolite levels in the dominant primary motor cortex (M1) and the supplementary motor area (SMA) in children with ADHD and typically developing children. We used robotic neuronavigated TMS to measure corticospinal excitability and create corticomotor maps. We collected data from 26 medication-free children with ADHD (aged 7–16 years) and 25 typically developing children (11–16 years). Children with ADHD had lower M1 Glx (p = 0.044, d = 0.6); their mean resting motor threshold was lower (p = 0.029, d = 0.8); their map area was smaller (p = 0.044, d = 0.7); and their hotspot density was higher (p = 0.008, d = 0.9). M1 GABA levels were associated with motor map area (p = 0.036). Limitations: Some TMS data were lost because the threshold of some children exceeded 100% of the machine output. The relatively large MRS voxel required to obtain sufficient signal-to-noise ratio and reliably measure GABA levels encompassed tissue beyond the M1, making this measure less anatomically specific. The neurochemistry and neurophysiology of key nodes in the motor network may be altered in children with ADHD, and the differences appear to be related to each other. These findings suggest potentially novel neuropharmacological and neuromodulatory targets for ADHD.

Background Individuals discharged from inpatient psychiatry units have the highest readmission rates of all hospitalized patients. These readmissions are often due to unmet need for mental health care compounded by limited human resources. Reducing the need for hospital admissions by providing alternative effective care will mitigate the strain on the healthcare system and for people with mental illnesses and their relatives. We propose implementation and evaluation of an innovative program which augments Mental Health Peer Support with an evidence-based supportive text messaging program developed using the principles of cognitive behavioral therapy. Methods A pragmatic stepped-wedge cluster-randomized trial, where daily supportive text messages (Text4Support) and mental health peer support are the interventions, will be employed. We anticipate recruiting 10,000 participants at the point of their discharge from 9 acute care psychiatry sites and day hospitals across four cities in Alberta. The primary outcome measure will be the number of psychiatric readmissions within 30 days of discharge. We will also evaluate implementation outcomes such as reach, acceptability, fidelity, and sustainability. Our study will be guided by the Consolidated Framework for Implementation Research, and the Reach-Effectiveness-Adoption-Implementation-Maintenance framework. Data will be extracted from administrative data, surveys, and qualitative methods. Quantitative data will be analysed using machine learning. Qualitative interviews will be transcribed and analyzed thematically using both inductive and deductive approaches. Conclusions To our knowledge, this will be the first large-scale clinical trial to assess the impact of a daily supportive text message program with and without mental health peer support for individuals discharged from acute psychiatric care. We anticipate that the interventions will generate significant cost-savings by reducing readmissions, while improving access to quality community mental healthcare and reducing demand for acute care. It is envisaged that the results will shed light on the effectiveness, as well as contextual barriers and facilitators to implementation of automated supportive text message and mental health peer support interventions to reduce the psychological treatment and support gap for patients who have been discharged from acute psychiatric care. Trial registration clinicaltrials.gov, NCT05133726 . Registered 24 November 2021

IntroductionTourette’s syndrome (TS) affects approximately 1% of children. This study will determine the efficacy and safety of paired comprehensive behavioural intervention for tics (CBIT) plus repetitive transcranial magnetic stimulation (rTMS) treatment in children with Tourette’s syndrome. We hypothesise that CBIT and active rTMS to the supplementary motor area (SMA) will (1) decrease tic severity, and (2) be associated with changes indicative of enhanced neuroplasticity (eg, changes in in vivo metabolite concentrations and TMS neurophysiology measures).Methods and analysisThis study will recruit 50 youth with TS, aged 6–18 for a phase II, double-blind, block randomised, sham-controlled trial comparing active rTMS plus CBIT to sham rTMS plus CBIT in a 1:1 ratio. The CBIT protocol is eight sessions over 10 weeks, once a week for 6 weeks and then biweekly. The rTMS protocol is 20 sessions of functional MRI-guided, low-frequency (1 Hz) rTMS targeted to the bilateral SMA over 5 weeks (weeks 2–6). MRI, clinical and motor assessments and neurophysiological evaluations including motor mapping will be performed 1 week before CBIT start, 1 week after rTMS treatment and 1 week after CBIT completion. The primary outcome measure is Tourette’s symptom change from baseline to post-CBIT treatment, as measured by the Yale Global Tic Severity Scale. Secondary outcomes include changes in imaging, neurophysiological and behavioural markers.Ethics and disseminationEthical approval by the Conjoint Health Research Ethics Board (REB18-0220). The results of this study will be published in peer-reviewed scientific journals, on ClinicalTrials.gov and shared with the Tourette and OCD Alberta Network. The results will also be disseminated through the Alberta Addictions and Mental Health Research Hub.Trial registrationNCT03844919.

Transcranial magnetic stimulation (TMS) motor mapping is a safe, non‐invasive method that can be used to study corticomotor organization. Motor maps are typically acquired at rest, and comparisons to maps obtained during muscle activation have been both limited and contradictory. Understanding the relationship between functional activation of the corticomotor system as recorded by motor mapping is crucial for their use clinically and in research. The present study utilized robotic TMS paired with personalized neuro‐navigation to examine the relationship between resting and active motor map measures and their relationship with motor performance. Twenty healthy right‐handed participants underwent resting and active robotic TMS motor mapping of the first dorsal interosseous to 10% maximum voluntary contraction. Motor map parameters including map area, volume, and measures of map centrality were compared between techniques using paired sample tests of difference and Bland–Altman plots and analysis. Map area, volume, and hotspot magnitude were larger in the active motor maps, while map center of gravity and hotspot locations remained consistent between both maps. No associations were observed between motor maps and motor performance as measured by the Purdue Pegboard Test. Our findings support previous suggestions that maps scale with muscle contraction. Differences in mapping outcomes suggest rest and active motor maps may reflect functionally different corticomotor representations. Advanced analysis methods may better characterize the underlying neurophysiology of both types of motor mapping. Understanding the relationship between functional activation of the corticomotor system as recorded by transcranial magnetic stimulation (TMS) motor mapping is crucial for their use clinically and in research. The present study utilized robotic TMS paired with personalized neuro‐navigation to examine the relationship between resting and active motor map measures and their relationship with motor performance. Map area, volume, and hotspot magnitude were larger in the active motor maps, while map centre of gravity and hotspot locations remained consistent between both maps, suggesting that they may reflect functionally different corticomotor representations.