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Objective: We investigated if theta burst stimulation could enhance recovery by reducing key symptoms when implemented acutely post fracture in participants with an isolated upper limb fracture. Methods/Design: This was a pilot study with a randomized matched pair, sham-controlled, participant-blind design of a 10-day prolonged continuous theta burst stimulation protocol. Two main groups were included: I) participants with isolated upper limb fracture receiving active theta burst stimulation and II) patients with isolated upper limb fracture receiving SHAM/placebo. Another group (III) of healthy individuals was the reference group. Disability and pain intensity were collected through questionnaires (disabilities of the Arm, Shoulder, and Hand as well as numerical rating scale (NRA)) at three time points (baseline; 72 hrs after intervention, 3 mos after injury). Group III completed the baseline assessment. Results: Seventy-nine participants were enrolled. Individuals in the ACTIVE and SHAM groups had similar baseline measures. For disability, the interaction between intervention and time approached significance (F = 2.33; P = 0.11), whereas it was significant for pain (F = 3.42; P = 0.04). At 3 mos after injury, the ACTIVE group reported reduced disability (F = 4.71; P = 0.04) and pain (F = 5.84; P = 0.02) at 3 mos after injury compared to the SHAM group, with clinical measures from ACTIVE group being like controls. Conclusions: In isolated upper limb fracture patients, a 10-day theta burst stimulation intervention implemented acutely posttraumatic had beneficial effects on symptoms of functional recovery and pain at 3 mos after trauma. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system with common symptoms of rapid onset of eye pain, loss of vision, neck/back pain, paralysis, bowel and bladder dysfunction and heat sensitivity. The rare, unpredictable, and debilitating nature of NMOSD constitutes a unique psychological burden for patients and their caregivers, the specific nature and extent of which is not yet known. This mixed methods study, informed by both quantitative and qualitative data collected via self-report measures, focus groups, and in-depth interviews, aims to investigate and understand the psychological burden of patients with NMOSD and their caregiver/loved ones, so as to inform a specialized intervention. 31 adults living with NMOSD and 22 caregivers of people with NMOSD in the United States and Canada, recruited from NMOSD patient advocacy groups, social media groups, and through word of mouth from other participants, completed a battery of standardized self-report measures of anxiety, depression, trauma, cognitive fusion, valued living, and coping styles. Semi-structured focus group sessions were conducted via HIPAA-compliant Zoom with 31 patients, and separate focus groups were conducted with 22 caregivers. A subset of these samples, comprised of 16 patients and 11 caregivers, participated in individual semi-structured interviews, prioritizing inclusion of diverse perspectives. Descriptive statistics and bivariate correlations were run on quantitative self-report data using SPSS [Version 28.0.1]; data were stored in REDCap. Reflexive thematic analysis was employed regarding qualitative individual interview data. The majority of patients reported experiencing anxiety, depression, cognitive fusion, over-controlled coping, and lack of values-based living. Caregivers also reported heightened anxiety, cognitive fusion, and over-controlled coping, although they did not endorse clinically significant depression. Patient and caregiver degree of anxiety and of overcontrolled coping were both strongly positively correlated, likely affecting how both parties manage NMOSD-related stressors, both individually and as a dyad. Patients reported more anxiety, depression, psychological inflexibility, and lack of values-based living, compared with caregivers. Patient and caregiver narrative themes included mistrust of medical professionals, lack of support immediately following diagnosis, changes in relationships, deviation from values-based living, internalization of feelings, and avoidant coping strategies to manage the psychological burden of NMOSD. A novel mental health intervention targeting the specific psychological burden of life with NMOSD is proposed. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is recommended in Canadian guidelines as a first-line treatment for major depressive disorder. With the shift towards competency-based medical education, it remains unclear how to determine when a resident is considered competent in applying knowledge of rTMS to patient care. Given inconsistencies between postgraduate training programmes with regards to training requirements, defining competencies will improve the standard of care in rTMS delivery. Objective: The goal of this study was to develop competencies for rTMS that can be implemented into a competency-based training curriculum in postgraduate training programmes. Methods: A working group drafted competencies for postgraduate psychiatry trainees. Fourteen rTMS experts from across Canada were invited to participate in the modified Delphi process. Results: Ten experts participated in all three rounds of the modified Delphi process. A total of 20 items reached a consensus. There was improvement in the Cronbach's alpha over the rounds of modified Delphi process (Cronbach's alpha increased from 0.554 to 0.824) suggesting improvement in internal consistency. The intraclass correlation coefficient (ICC) increased from 0.543 to 0.805 suggesting improved interrater agreement. Conclusions: This modified Delphi process resulted in expert consensus on competencies to be acquired during postgraduate medical education programmes where a learner is training to become competent as a consultant and/or practitioner in rTMS treatment. This is a field that still requires development, and it is expected that as more evidence emerges the competencies will be further refined. These results will help the development of other curricula in interventional psychiatry. [ABSTRACT FROM AUTHOR]

Background: Peripartum depression (PPD) is a serious public health issue associated with severe and potentially long-term adverse maternal and child developmental outcomes. Suicide and overdose, for example, accounts for up to a third of maternal deaths. A current depression diagnosis with no active treatment is a common risk factor for maternal suicide. Repetitive transcranial magnetic stimulation (rTMS) is a non-pharmacological treatment that has recently shown some promise as an effective treatment with limited side effects for PPD, but more research is required. This study aims to identify current barriers and potential facilitators for women with PPD accessing treatment in general, and rTMS specifically. Methods: This study will consist of two anonymous, self-administered surveys, focus groups, and interviews. A descriptive interpretative approach will be employed, and thematic analysis will be completed for the focus groups and interviews. Participants who are currently, or have previously experienced depressive symptoms, as well as health providers will be recruited. Our study will follow an equity, diversity, and inclusion (EDI) perspective on sex, gender, and ethnicity and the gender-based analysis plus (GBA+) analytic tool will be used. Both a qualitative and quantitative analysis of the data will be conducted. Discussion: We expect to find education and accessibility to be primary treatment barriers for persons with PPD. Identifying and addressing barriers is a critical first step towards the devolvement of initiatives that can work towards improving mental health in this population. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS)., Methods: Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations., Results: Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05)., Conclusions: Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging — alone or in combination with other variables — can predict the outcomes of various treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.Methods: In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782.Findings: Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208).Interpretation: In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness.Funding: Canadian Institutes of Health Research. [ABSTRACT FROM AUTHOR]

Importance: The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known.Objectives: To determine whether participants with AD had impaired DLPFC plasticity compared with healthy control participants, to compare working memory between participants with AD and controls, and to determine whether DLPFC plasticity was associated with working memory.Design, Setting, and Participants: This cross-sectional study included 32 participants with AD who were 65 years or older and met diagnostic criteria for dementia due to probable AD with a score of at least 17 on the Mini-Mental State Examination and 16 age-matched control participants. Participants were recruited from a university teaching hospital from May 2013 to October 2016.Main Outcomes and Measures: Plasticity of the DLPFC measured as potentiation of cortical-evoked activity using paired associative stimulation (a combination of peripheral nerve electrical stimulation and transcranial magnetic stimulation) combined with electroencephalography. Working memory was assessed with the n-back task (1- and 2-back) and measured using the A' statistic.Results: Among the 32 participants with AD, 17 were women and 15 were men (mean [SD] age, 76.3 [6.3] years); among the 16 controls, 8 were men and 8 were women (mean [SD] age, 76.4 [5.1] years). Participants with AD had impaired DLPFC plasticity (mean [SD] potentiation, 1.18 [0.25]) compared with controls (mean [SD] potentiation, 1.40 [0.35]; F1,44 = 5.90; P = .02; between-group comparison, Cohen d = 0.77; P = .01). Participants with AD also had impaired performances on the 1-back condition (mean [SD] A' = 0.47 [0.30]) compared with controls (mean [SD] A' = 0.96 [0.01]; Cohen d = 1.86; P < .001), with similar findings for participants with AD on the 2-back condition (mean [SD] A' = 0.29 [0.2]) compared with controls (mean [SD], A' = 0.85 [0.18]; Cohen d = 2.83; P < .001). Plasticity of DLPFC was positively associated with working memory performance on the 1-back A' (parameter estimate B [SE] = 0.32 [0.13]; standardized β = 0.29; P = .02) and 2-back A' (B [SE] = 0.43 [0.15]; β = 0.39; P = .006) across both groups after controlling for age, education, and attention.Conclusions and Relevance: This study demonstrated impaired in vivo DLPFC plasticity in patients with AD. The findings support the use of DLPFC plasticity as a measure of DLPFC function and a potential treatment target to enhance DLPFC function and working memory in patients with AD. [ABSTRACT FROM AUTHOR]

• Evidence for repetitive transcranial magnetic stimulation (rTMS) for smoking cessation is increasing. • One rTMS coil has recently received regulatory approval, signaling the potential for clinical adoption. • Implementation and dissemination into clinical practice requires planning and preparation. • Accessibility, technological, economical, and social challenges remain to be addressed. • Real-world effectiveness studies are needed, including the prevalence of comorbidities and vaping. Tobacco smoking is a significant determinant of preventable morbidity and mortality worldwide. It is now possible to modulate the activity of the neurocircuitry associated with nicotine dependence using repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive neurostimulation approach, which has recently demonstrated efficacy in clinical trials and received regulatory approval in the US and Canada. However there remains a paucity of replication studies and real-world patient effectiveness data as access to this intervention is extremely limited. There are a number of unique challenges related to the delivery of rTMS that need to be addressed prior to widespread adoption and implementation of this treatment modality for smoking cessation. In this paper, we review the accessibility, scientific, technological, economical, and social challenges that remain before this treatment can be translated into clinical practice. By addressing these remaining barriers and scientific challenges with rTMS for smoking cessation and delineating implementation strategies, we can greatly reduce the burden of tobacco-related disease worldwide. [ABSTRACT FROM AUTHOR]

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) conducted a revision of the 2009 guidelines by updating the evidence and recommendations. The scope of the 2016 guidelines remains the management of major depressive disorder (MDD) in adults, with a target audience of psychiatrists and other mental health professionals.Methods: Using the question-answer format, we conducted a systematic literature search focusing on systematic reviews and meta-analyses. Evidence was graded using CANMAT-defined criteria for level of evidence. Recommendations for lines of treatment were based on the quality of evidence and clinical expert consensus. "Neurostimulation Treatments" is the fourth of six sections of the 2016 guidelines.Results: Evidence-informed responses were developed for 31 questions for 6 neurostimulation modalities: 1) transcranial direct current stimulation (tDCS), 2) repetitive transcranial magnetic stimulation (rTMS), 3) electroconvulsive therapy (ECT), 4) magnetic seizure therapy (MST), 5) vagus nerve stimulation (VNS), and 6) deep brain stimulation (DBS). Most of the neurostimulation treatments have been investigated in patients with varying degrees of treatment resistance.Conclusions: There is increasing evidence for efficacy, tolerability, and safety of neurostimulation treatments. rTMS is now a first-line recommendation for patients with MDD who have failed at least 1 antidepressant. ECT remains a second-line treatment for patients with treatment-resistant depression, although in some situations, it may be considered first line. Third-line recommendations include tDCS and VNS. MST and DBS are still considered investigational treatments. [ABSTRACT FROM AUTHOR]

Context: The known detrimental effects of sport concussions on motor system function include balance problems, slowed motor execution, and abnormal motor cortex excitability. Objective: To assess whether these concussion-related alterations of motor system function are still evident in collegiate football players who sustained concussions but returned to competition more than 9 months before testing. Design: Case-control study. Setting: University laboratory. Patients or Other Participants: A group of 21 active, university-level football players who had experienced concussions was compared with 15 university football players who had not sustained concussions. Intervention(s): A force platform was used to assess center-of-pressure (COP) displacement and COP oscillation regularity (approximate entropy) as measures of postural stability in the upright position. A rapid alternating-movement task was also used to assess motor execution speed. Transcranial magnetic stimulation over the motor cortex was used to measure long- interval intracortical inhibition and the cortical silent period, presumably reflecting γ-aminobutyric acid subtype B receptor- mediated intracortical inhibition. Main Outcome Measure(s): COP displacement and oscillation regularity, motor execution speed, long-interval intracortical inhibition, cortical silent period. Results: Relative to controls, previously concussed athletes showed persistently lower COP oscillation randomness, normal performance on a rapid alternating-movement task, and more M1 intracortical inhibition that was related to the number of previous concussions. Conclusions: Sport concussions were associated with pervasive changes in postural control and more M1 intracortical inhibition, providing neurophysiologic and behavioral evidence of lasting, subclinical changes in motor system integrity in concussed athletes. [ABSTRACT FROM AUTHOR]

Mixed depression is probably different in terms of clinical course and response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively. Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, -0.06 [95% CI, - 3.39 to 3.51; P = 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps > 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression. ClinicalTrials.govIdentifier: NCT04123301., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

This is an historical account of Canadian pioneers working in amyotrophic lateral sclerosis (ALS) in the 1970s and 1980s. Key contributions included the development of specialized clinics, the ALS Society of Canada, human motor unit estimates in vivo, use of transcranial magnetic stimulation (TMS), the dementias of ALS, the importance of neurofilaments and axonal flow, neuroinflammation and immunity related to ALS, use of tissue culture to study pathogenesis, and the story of ALS in Guam. Their work set the stage for future generations of ALS physicians and scientists to bring about meaningful therapies and hopefully a cure for ALS.

Objective . To develop consensus recommendations for the use of repetitive transcranial magnetic stimulation (rTMS) as an adjunct intervention for upper extremity motor recovery in stroke rehabilitation clinical trials. Participants . The Canadian Platform for Trials in Non-Invasive Brain Stimulation (CanStim) convened a multidisciplinary team of clinicians and researchers from institutions across Canada to form the CanStim Consensus Expert Working Group. Consensus Process . Four consensus themes were identified: (1) patient population, (2) rehabilitation interventions, (3) outcome measures, and (4) stimulation parameters. Theme leaders conducted comprehensive evidence reviews for each theme, and during a 2-day Consensus Meeting, the Expert Working Group used a weighted dot-voting consensus procedure to achieve consensus on recommendations for the use of rTMS as an adjunct intervention in motor stroke recovery rehabilitation clinical trials. Results . Based on best available evidence, consensus was achieved for recommendations identifying the target poststroke population, rehabilitation intervention, objective and subjective outcomes, and specific rTMS parameters for rehabilitation trials evaluating the efficacy of rTMS as an adjunct therapy for upper extremity motor stroke recovery. Conclusions . The establishment of the CanStim platform and development of these consensus recommendations is a first step toward the translation of noninvasive brain stimulation technologies from the laboratory to clinic to enhance stroke recovery.