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The last two decades have seen dramatic growth in the application of procedurally based interventions for treating refractory psychiatric conditions, leading to interest in developing the foundations for the subspecialty of “Interventional Psychiatry.” However, there is cause for concern that the rate of expansion of clinical advances in this field may be outpacing the ability of postgraduate curricula to provide sufficient exposure to and teaching and supervision of these treatments. The paucity of adequately trained practitioners in Interventional Psychiatry further exacerbates inequities in the ability of eligible patients to access and benefit from these approaches. This paper explores the rates of utilization of Interventional Psychiatry treatments, the current state of education in these treatments, and the role that training can play in translating scientific advances in this area to ensure equitable access and maximum impact at a population level. The majority of the discussion is centered on electroconvulsive therapy (ECT), the most established and available of these treatments, highlighting how enhancing education and training in ECT can reduce barriers to its utilization. It is argued that innovations in pedagogical approaches for disseminating the learning of these procedures are needed to increase the current low rates of competency in these treatments and can facilitate the more rapid dissemination of other Interventional Psychiatry approaches and neurotechnologies, such as repetitive transcranial magnetic stimulation, ketamine, deep brain stimulation, and focused ultrasound.

History of adverse childhood experiences (ACEs) is associated with poorer treatment outcomes in depression. How ACEs affect outcomes from repetitive transcranial magnetic stimulation (rTMS) is not well-defined. The primary aim was to investigate whether ACEs affect depression outcomes in patients receiving high frequency rTMS, either deep TMS (dTMS) or intermittent theta burst stimulation (iTBS), to the left dorsolateral prefrontal cortex.The Hamilton Depression Rating Scale (HAMD-17) was collected at baseline and every 2 weeks for 4-6 weeks. Outcomes included improvement in HAMD-17 and remission. The ACE-10 questionnaire was used to quantify categories of ACEs. Data from 99 patients with MDD receiving an acute rTMS course were analyzed.Patients had a mean of 2.4 ACEs (SD 2.5). No significant differences in outcomes were found between dTMS or iTBS so these data were pooled. Using a continuous ACE variable showed no significant impact on outcomes. Using a categorical ACE variable (0, 1, 2, 3, 4 or more) did not reveal significant effects of ACEs on outcomes. Higher ACE was associated with steeper decrease in HAMD-17 only from baseline to week 2 but not at other times.This was an open-label study. The well-validated ACE questionnaire does not measure severity or frequency of adversities.Patients with depression receiving rTMS reported on average 2.4 ACEs. ACE scores may lead to a steeper early decline in HAMD-17 but did not otherwise impact depression outcomes. Presence of high levels of ACEs should not preclude consideration of rTMS for depression.

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behaviour, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating the volume of activated tissue modelling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. Ninety-one percent of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral region of the posterior hypothalamic area. Normative connectomic analyses identified fibre tracts and interconnected brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and key limbic areas - together with patient age - were highly predictive of treatment outcome. Transcriptomic analysis showed that genes involved in mechanisms of aggressive behaviour, neuronal communication, plasticity and neuroinflammation might underlie this functional network.

With a high prevalence of posttraumatic stress disorder (PTSD) in females, studying sex differences in preclinical models is of substantial importance. We have previously employed behavioural criteria to identify and characterize a subpopulation of rats that presented impaired fear extinction and long-term fear and anxiety responses following fear conditioning. We now exposed male and female rats to fear conditioning and extinction and segregated the animals into weak- (WE) and strong-extinction (SE) groups based on behavioural scores during extinction. Animals were subsequently tested for tone and context recall, as well as anxiety-like responses in the marble burying and novelty suppression of feeding (NSF) tests. Vaginal lavages were collected to characterize the phase of the estrous cycle during fear extinction. We found that females had reduced freezing during tone recall and a lower latency to feed in the NSF test. No differences were found in females undergoing extinction during high and low estrogen phases of the cycle in any of the performed tests. Overall, the percentage of animals that presented WE and SE phenotypes was similar in males and females. Both, WE males and females had increased freezing during tone and context recall. Along with our previous reports, WE males presented anxiety-like responses, particularly in the NSF compared to SE animals. In contrast, WE females buried less marbles than their SE mates. Future investigation including a larger number of behavioural tests are certainly required to corroborate our findings and ascertain potential mechanisms to explain the differences observed in our study.

Functional neurological disorder and somatic symptom disorder are complex neuropsychiatric conditions that have been linked to circuit-based dysfunction of brain networks. Neuromodulation is a novel therapeutic strategy capable of modulating relevant brain networks, making it a promising potential candidate for the treatment of these patient populations. We conducted a systematic review of Medline, Embase and PsycINFO up to 4 March 2021. Trials investigating neuromodulation devices for the treatment of functional neurological disorder or somatic symptom disorder were selected. Extracted variables included study design, demographic and clinical characteristics, psychiatric comorbidity, neurostimulation protocols, clinical outcome measures and results. 404 studies were identified with 12 meeting inclusion criteria. 221 patients were treated in the included studies with mean study sample size of 18 (4–70). Five studies were randomised clinical trials. Functional motor symptoms (six weakness, four movement disorders) were the most studied subpopulations. Transcranial magnetic stimulation (TMS) was the most frequently used device (10 studies), followed by electroconvulsive therapy (one study) and direct-current stimulation (one study). Treatment protocols varied in intended therapeutic mechanism(s): eight studies aimed to modulate underlying network dysfunction, five aimed to demonstrate movement (one also leveraged the former) and three boosted their primary mechanism with enhanced suggestion/expectation. All but one study reported positive results; however, methodological/outcome heterogeneity, mixed study quality and small sample sizes precluded quantitative meta-analysis. Neuromodulation, particularly TMS for the treatment of functional motor symptoms, shows preliminary promise in a growing line of research. Larger, sham-controlled studies are needed to further establish efficacy and better understand therapeutic mechanisms.

Response to repetitive transcranial magnetic stimulation (rTMS) among individuals with major depressive disorder (MDD) varies widely. The neural mechanisms underlying rTMS are thought to involve changes in large-scale networks. Whether structural network integrity and plasticity are associated with response to rTMS therapy is unclear. Structural MRIs were acquired from a series of 70 adult healthy controls and 268 persons with MDD who participated in two arms of a large randomized, non-inferiority trial, THREE-D, comparing intermittent theta-burst stimulation to high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). Patients were grouped according to percentage improvement on the 17-item Hamilton Depression Rating Score at treatment completion. For the entire sample and then for each treatment arm, multivariate analyses were used to characterize structural covariance networks (SCN) from cortical gray matter thickness, volume, and surface area maps from T1-weighted MRI. The association between SCNs and clinical improvement was assessed. For both study arms, cortical thickness and volume SCNs distinguished healthy controls from MDD (p = 0.005); however, post-hoc analyses did not reveal a significant association between pre-treatment SCN expression and clinical improvement. We also isolated an anticorrelated SCN between the left DLPFC rTMS target site and the subgenual anterior cingulate cortex across cortical measures (p = 0.0004). Post-treatment change in cortical thickness SCN architecture was associated with clinical improvement in treatment responders (p = 0.001), but not in non-responders. Structural network changes may underpin clinical response to rTMS, and SCNs are useful for understanding the pathophysiology of depression and neural mechanisms of plasticity and response to circuit-based treatments.

BackgroundAggressive behaviour (AB) may occur in patients with different neuropsychiatric disorders. Although most patients respond to conventional treatments, a small percentage continue to experience AB despite optimized pharmacological management and are considered to be treatment-refractory. For these patients, hypothalamic deep brain stimulation (pHyp-DBS) has been investigated. The hypothalamus is a key structure in the neurocircuitry of AB. An imbalance between serotonin (5-HT) and steroid hormones seems to exacerbate AB.ObjectivesTo test whether pHyp-DBS reduces aggressive behavior in mice through mechanisms involving testosterone and 5-HT.MethodsMale mice were housed with females for two weeks. These resident animals tend to become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5h/day for 8 consecutive days prior to daily encounters with the intruder. After testing, blood and brain were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT1Aantagonist) or saline injections prior to pHyp-DBS. After the first 4 encounters, the injection allocation was crossed, and animals received the alternative treatment during the next 4 days.ResultsDBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1Areceptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS.ConclusionsThis study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1Amechanisms.HIGHLIGHTS-Posterior hypothalamus DBS reduces aggressive behavior in mice-Aggressive behavior was correlated with plasma testosterone levels-DBS increased 5-HT1A receptor density in the orbitofrontal cortex and amygdala-Pre-treatment with 5-HT1A antagonist (WAY) blocked the anti-aggressive effect of DBS

Deep brain stimulation (DBS) has been investigated for neuropsychiatric disorders. In this phase 1 trial, we treated four posttraumatic stress disorder (PTSD) patients with DBS delivered to the subgenual cingulum and the uncinate fasciculus. In addition to validated clinical scales, patients underwent neuroimaging studies and psychophysiological assessments of fear conditioning, extinction, and recall. We show that the procedure is safe and potentially effective (55% reduction in Clinical Administered PTSD Scale scores). Posttreatment imaging data revealed metabolic activity changes in PTSD neurocircuits. During psychophysiological assessments, patients with PTSD had higher skin conductance responses when tested for recall compared to healthy controls. After DBS, this objectively measured variable was significantly reduced. Last, we found that a ratio between recall of extinguished and nonextinguished conditioned responses had a strong correlation with clinical outcome. As this variable was recorded at baseline, it may comprise a potential biomarker of treatment response.

Tremor is a debilitating symptom that can lead to functional impairment. Pharmacotherapy is often successful, but up to 50% of patients are resistant to medications or cannot tolerate side effects. Thalamotomy to the ventral intermediate nucleus of the thalamus is a surgical intervention for refractory tremor. Thalamotomy surgeries include radiofrequency and incisionless procedures, such as Gamma Knife radiosurgery and magnetic resonance-guided focused ultrasound. Cognitive changes following thalamotomy have been inconsistently reported across studies. We performed a meta-analysis to summarize the impact of unilateral thalamotomy to the ventral intermediate nucleus of the thalamus across multiple cognitive domains. We searched MEDLINE, Embase Classic, Embase and EBM Reviews for relevant studies. Neuropsychological tests were categorized into seven cognitive domains: global cognition, verbal memory, non-verbal memory, executive function, phonemic fluency, semantic fluency and visuospatial processing. We calculated standardized mean differences as Hedges’ g and 95% confidence intervals of the change between pre- and postoperative cognitive scores. Pooling of standardized mean differences across studies was performed using random-effects models. Risk of bias across studies and quality of evidence for each cognitive domain were assessed with the National Institute of Health quality assessment tool and the GRADEpro Guideline Development Tool, respectively. Of the 1251 records reviewed, eight studies met inclusion criteria. We included 193 patients with essential tremor, Parkinson’s disease, or multiple sclerosis in the meta-analysis. There was a small significant decline in phonemic fluency [standardized mean difference = −0.29, 95% confidence interval: (−0.52, −0.05), P = 0.017] and a trend towards a decline in semantic fluency [standardized mean difference = −0.19, 95% confidence interval: (−0.40, 0.01), P = 0.056]. No postoperative changes were observed in the other cognitive domains (P values >0.14). In secondary analyses, we restricted the analyses to studies using magnetic resonance-guided focused ultrasound given its growing popularity and more precise targeting. In those analyses, there was no evidence of cognitive decline across any domain (P values >0.37). In terms of risk of bias, five studies were rated as ‘good’ and three studies were rated as ‘fair’. According to GRADEpro guidelines, the certainty of the effect for all cognitive domains was low. This study provides evidence that unilateral thalamotomy to the ventral intermediate nucleus of the thalamus is relatively safe from a cognitive standpoint, however, there may be a small decline in verbal fluency. Magnetic resonance-guided focused ultrasound might have a more favourable postoperative cognitive profile compared with other thalamotomy techniques.

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as treatment for refractory aggressive behaviour, but its mechanisms of action remain elusive. We conducted an integrated imaging analysis of a large multi-centre dataset, incorporating volume of activated tissue modeling, probabilistic mapping, normative connectomics, and atlas-derived transcriptomics. 91% of the patients responded positively to treatment, with a more striking improvement recorded in the pediatric population. Probabilistic mapping revealed an optimized surgical target within the posterior-inferior-lateral posterior hypothalamic area and normative connectomic analyses identified fiber tracts and interconnected brain areas associated with sensorimotor function, emotional regulation, and monoamine production. Functional connectivity between the target, periaqueductal gray and the amygdala – together with patient age – was highly predictive of treatment outcome. Finally, transcriptomic analysis showed that genes involved in mechanisms of aggressive behaviour, neuronal communication, plasticity and neuroinflammation may underlie this functional network.SIGNIFICANCE STATEMENTThis study investigated the brain mechanisms associated with symptom improvement following deep brain stimulation of the posterior hypothalamus for severe and refractory aggressive behavior. Conducting an integrated imaging analysis of a large international multi-center dataset of patients treated with hypothalamic deep brain stimulation, we were able to show for the first time that treatment is highly efficacious across various patients with an average improvement greater than 70%. Leveraging this unique dataset allowed us to demonstrate that some patient characteristics are important for treatment success, describe the optimal target zone for maximal benefit, that engagement of distinct fiber tracts and networks within the emotional neurocircuitry are key for positive outcome, and - using imaging transcriptomics - elucidate some potential molecular underpinnings. The provided optimal stimulation site allows for direct clinical application.

Body dysmorphic disorder (BDD), hoarding disorder (HD), skin-picking disorder (SPD), and hair-pulling disorder (HPD) are characterized by compulsive behaviours leading to distress and impairment. Current treatments attain only partial or non-response. Interventional psychiatric approaches may target specific regions of the brain for treatment. This scoping review maps the current literature and synthesizes key findings. Databases were searched up to June 27, 2022 for studies examining interventional psychiatric treatments for BDD, HD, SPD, and HPD, producing 910 results. Twenty were included; 16 were case reports, two were case series, and two were randomized controlled trials. Studies reported on electroconvulsive therapy (ECT) (n=7), deep brain stimulation (DBS) (n=1), and intermittent theta-burst stimulation repetitive transcranial magnetic stimulation (rTMS) (n=1) for BDD; rTMS (n=1) and transcranial direct current stimulation (n=1) for HD; gamma knife capsulotomy (n=1) and rTMS (n=1) for SPD; and rTMS (n=2) and ECT (n=1) for HPD. Four studies reported on DBS for other indications complicated by SPD or HPD. The current literature consists mainly of case reports. Future studies should be randomized, controlled, adequately powered and blinded, examining rTMS localized to the anatomical targets for each disorder. Presently, the mainstay of treatment remains disorder-specific psychotherapy with limited evidence for medications.

BackgroundFour ablative neurosurgical procedures are used in the treatment of refractory psychiatric illness. The long-term effects of these procedures on psychiatric symptoms across disorders has never been synthesised and meta-analysed.MethodsA preregistered systematic review was performed on studies reporting clinical results following ablative psychiatric neurosurgery. Four possible outcome measures were extracted for each study: depression, obsessive–compulsive symptoms, anxiety and clinical global impression. Effect sizes were calculated using Hedge’s g. Equipercentile linking was used to convert symptom scores to a common metric. The main outcome measures were the magnitude of improvement in depression, obsessive compulsive symptoms, anxiety and clinical global impression. The secondary outcome was a subgroup analysis comparing the magnitude of symptom changes between the four procedures.ResultsOf 943 articles, 43 studies reporting data from 1414 unique patients, were included for pooled effects estimates with a random-effects meta-analysis. Results showed that there was a large effect size for improvements in depression (g=1.27; pConclusionsContemporary ablative neurosurgical procedures were significantly associated with improvements in depression, obsessive–compulsive symptoms, anxiety and clinical global impression.PROSPERO registration numberCRD42020164784.

BACKGROUND Post-concussive symptoms (PCSs) are common, disabling, and challenging to manage. Evolving models of concussion pathophysiology suggest evidence of brain network dysfunction that may be amenable to neuromodulation. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential novel treatment option for PCSs. OBJECTIVES To systematically review rTMS trials for the treatment of symptoms following concussion/mild traumatic brain injury (mTBI). MATERIALS AND METHODS We conducted a systematic review of Pubmed/Medline, Embase, and PsychINFO databases were searched up to May 19, 2020. Studies were included if they were prospective rTMS treatment studies of patients with mTBI/concussion. Variables including patient demographics, study design, rTMS protocol parameters, primary outcome measures, and efficacy data were extracted and qualitatively synthesized. rTMS methodology and study quality were also evaluated. RESULTS Of the 342 studies identified, 11 met eligibility criteria and were included for synthesis. Forty-one percent of patients were female and age ranged from 18 to 65 (average age = 38.5 years). Post-concussive depression (seven studies) and headache (four studies) were the most commonly investigated symptoms. The majority of trials were sham-controlled with randomized control trial (RCT) designs, but all were small pilot samples (n

Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment. The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy. We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery–Asberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement. Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain. The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms. ClinicalTrials.gov identifier: NCT016557.

Introduction Many individuals with major depressive disorder (MDD) do not respond to initial antidepressant monotherapy. Adjunctive aripiprazole is recommended for treatment non-response; however, the impacts on quality of life (QoL) for individuals who receive this second-line treatment strategy have not been described. Methods We evaluated secondary QoL outcomes in patients with MDD (n=179). After 8 weeks of escitalopram, non-responders ( Results Escitalopram responders experienced the most QoL improvements in the first treatment phase. For non-responders, QoL improved with a large effect during adjunctive aripiprazole treatment. At the endpoint, 47% of patients achieving symptomatic remission still had impaired QoL. Discussion Individuals who were treated with adjunctive aripiprazole after non-response to escitalopram experienced improved QoL, but a substantial degree of QoL impairment persisted. Since QoL deficits may predict MDD recurrence, attention to ways to support this outcome is required.

Background Treatment‐resistant depression (TRD) is a debilitating chronic mental illness that confers increased morbidity and mortality, decreases the quality of life, impairs occupational, social, and offspring development, and translates into increased costs on the healthcare system. The goal of this study is to reach an agreement on the concept, definition, staging model, and assessment of TRD. Methods This study involved a review of the literature and a modified Delphi process for consensus agreement. The Appraisal of Guidelines for Research & Evaluation II guidelines were followed for the literature appraisal. Literature was assessed for quality and strength of evidence using the grading, assessment, development, and evaluations system. Canadian national experts in depression were invited for the modified Delphi process based on their prior clinical and research expertize. Survey items were considered to have reached a consensus if 80% or more of the experts supported the statement. Results Fourteen Canadian experts were recruited for three rounds of surveys to reach a consensus on a total of 27 items. Experts agreed that a dimensional definition for treatment resistance was a useful concept to describe the heterogeneity of this illness. The use of staging models and clinical scales was recommended in evaluating depression. Risk factors and comorbidities were identified as potential predictors for treatment resistance. Conclusions TRD is a meaningful concept both for clinical practice and research. An operational definition for TRD will allow for opportunities to improve the validity of predictors and therapeutic options for these patients.

Introduction Cette étude explore la relation entre le soutien émotionnel, le risque perçu et les résultats en matière de santé mentale chez les travailleurs de la santé, qui font face à des taux élevés d’épuisement professionnel et de détresse mentale depuis le début de la pandémie de COVID-19. Méthodologie Une enquête transversale a été menée en ligne au cours de la première vague de la pandémie de COVID-19 auprès de travailleurs de la santé de divers centres de la région du Grand Toronto (Ontario, Canada) pour évaluer les stratégies d’adaptation, la confiance dans les mesures de lutte contre les infections, l’impact du travail antérieur lors de l’épidémie de SRAS survenue en 2003 et le soutien émotionnel. Les résultats en matière de santé mentale ont été évalués au moyen de l’échelle du trouble d’anxiété généralisée (GAD-7), de l’échelle d’impact des événements – révisée (IES-R) et du questionnaire sur la santé des patients (PHQ-9). Résultats Sur les 3 852 participants, 8,2 % ont eu recours à des services professionnels en santé mentale, 77,3 % ont reçu du soutien émotionnel de la part de membres de leur famille, 74,0 % de la part d’amis et 70,3 % de la part de collègues. Les personnes qui ne se sont pas senties soutenues dans leur travail présentaient des probabilités plus élevées d’éprouver des symptômes d’anxiété modérés et sévères (rapport de cotes [RC] = 2,23; intervalle de confiance [IC] à 95 % : 1,84 à 2,69), de trouble de stress post-traumatique (TSPT) (RC = 1,88; IC à 95 % : 1,58 à 2,25) et de dépression (RC = 1,88; IC à 95 % : 1,57 à 2,25). Près de 40 % avaient peur de parler à leur famille des risques auxquels ils étaient exposés au travail. Ceux qui ont pu partager cette information faisaient état d’un risque plus faible d’anxiété (RC = 0,58; IC à 95 % : 0,48 à 0,69), de TSPT (RC = 0,48; IC à 95 % : 0,41 à 0,56) et de dépression (RC = 0,55; IC à 95 % : 0,47 à 0,65). Conclusion Les sources informelles de soutien, en particulier la famille, les amis et les collègues, jouent un rôle important dans l’atténuation de la détresse et devraient être encouragées et utilisées davantage par les travailleurs de la santé.

Major depressive disorder is a common and debilitating disorder. Although most patients with this disorder benefit from established treatments, a subset of patients have symptoms that remain treatment resistant. Novel treatment approaches, such as deep brain stimulation, are urgently needed for patients with treatment-resistant major depressive disorder. These novel treatments are currently being tested in clinical trials in which success hinges on how accurately and comprehensively the primary outcome measure captures the treatment effect. In this Personal View, we argue that current measures used to assess outcomes in neurosurgical trials of major depressive disorder might be missing clinically important treatment effects. A crucial problem of continuing to use suboptimal outcome measures is that true signals of efficacy might be missed, thereby disqualifying potentially effective treatments. We argue that a re-evaluation of how outcomes are measured in these trials is much overdue and describe several novel approaches that attempt to better capture meaningful change.

Background Psychiatric surgery is an important domain of functional neurosurgery and involves deep brain stimulation (DBS) or lesional procedures performed for treatment-resistant psychiatric illness. It has recently become possible to use magnetic-guided focused ultrasound (MRgFUS) to perform bilateral capsulotomy, a lesional technique commonly carried out with surgical radiofrequency ablation or stereotactic radiosurgery. MRgFUS offers several advantages, including improved safety and real-time imaging of the lesions. Objective To describe the clinical and technical aspects of performing bilateral MRgFUS capsulotomy in patients with severe refractory depression and obsessive-compulsive disorder. Methods We describe the clinical and technical considerations of performing MRgFUS capsulotomy. Topics discussed include patient selection, headframe application, targeting, sonication strategies, and follow-up procedures. Results MRgFUS capsulotomy was performed in 16 patients without serious clinical or radiographic adverse events. Conclusion MRgFUS allows for a safe, less invasive technique for performing a well-studied psychiatric surgery procedure-the anterior capsulotomy.

Post-traumatic stress disorder (PTSD) is a prevalent and debilitating illness. While standard treatment with pharmacotherapy and psychotherapy may be effective, approximately 20 to 30% of patients remain symptomatic. These individuals experience depression, anxiety, and elevated rates of suicide. For treatment-resistant patients, there is a growing interest in the use of neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). We conducted a systematic review on the use of neuromodulation strategies for PTSD and pooled 13 randomized clinical trials (RCTs), 11 case series, and 6 case reports for analysis. Overall, most studies reported favorable outcomes in alleviating both PTSD and depressive symptoms. Although several RCTs described significant differences when active and sham stimulations were compared, others found marginal or nonsignificant differences between groups. Also positive were studies comparing PTSD symptoms before and after treatment. The side effect profile with all 3 modalities was found to be low, with mostly mild adverse events being reported. Despite these encouraging data, several aspects remain unknown. Given that PTSD is a highly heterogeneous condition that can be accompanied by distinct psychiatric diagnoses, defining a unique treatment for this patient population can be quite challenging. There has also been considerable variation across trials regarding stimulation parameters, symptomatic response, and the role of adjunctive psychotherapy. Future studies are needed to address these issues. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00871-0) contains supplementary material, which is available to authorized users.

Obsessive compulsive disorder (OCD) and major depressive disorder (MDD) are common, often refractory, neuropsychiatric conditions for which new treatment approaches are urgently needed. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel surgical technique permitting incisionless ablative neurosurgery. We examined the safety profile, clinical response, and imaging correlates of MRgFUS bilateral anterior capsulotomy in patients with refractory obsessive compulsive disorder (OCD, N = 6) and major depressive disorder (MDD, n = 6). There were no serious adverse events. Nonserious adverse events included headaches and pin-site swelling in 7/12 patients. The response rate was 4/6 and 2/6 in the OCD and MDD cohorts respectively. To delineate the white-matter tracts impacted by capsulotomy, a normative diffusion MRI-based structural connectome was used, revealing tracts terminating primarily in the frontal pole, medial thalamus, striatum, and medial-temporal lobe. Positron emission tomography (PET) analysis (nine subjects) revealed widespread decreases in metabolism bilaterally in the cerebral hemispheres at 6 months post treatment, as well as in the right hippocampus, amygdala, and putamen. A pretreatment seed-to-voxel resting-state functional magnetic resonance imaging (rs-fMRI) analysis (12 subjects) revealed three voxel clusters significantly associated with eventual clinical response. MRgFUS capsulotomy appears to be safe, well tolerated, and according to these initial results, may be an important treatment option for patients with refractory OCD and MDD. MRgFUS capsulotomy results in both targeted and widespread changes in neural activity, and neuroimaging may hold potential for the prediction of outcome.

Introduction Although the antidepressant efficacy of rTMS is well documented, patient reported outcomes (PROs) with rTMS are poorly characterized. The aim of the current study is to assess short and long-term changes in self-reported quality of life and disability following a 6-week course of rTMS. Methods We performed a secondary analysis of data from the multi-centre THREE-D trial of 10 Hz high-frequency (HF) rTMS (n = 192) vs. intermittent theta-burst stimulation (iTBS) (n = 193) of the left dorsolateral prefrontal cortex (DLPFC). We assessed changes in the Quality of Life Enjoyment and Satisfaction Questionnaire and Sheehan Disability Scale pre-treatment, at 1-week post-rTMS treatment (Acute Follow-up), and at 12-weeks post-treatment (Long-Term Follow-Up). Results PROs significantly improved with rTMS. There were no differences in PROs between iTBS and HF left DLPFC rTMS at either the Acute or Long-Term Follow-Up. The magnitude of the change in effect sizes seen for the PROs were significantly greater in those who achieved greater resolution their depressive symptoms, with remitters demonstrating very large effect size improvements in PROs compared to small-to-medium effect sizes in non-remitters. Conclusions This study is the largest in the literature exploring at the effect of rTMS on PROs. rTMS yielded acute and sustained improvements in PROs. The improvements in PROs were strongly associated with the degree of resolution of depressive symptoms. The magnitude of the change in remitters was comparable to those reported with ECT. The goal of a course of rTMS should be for full remission of depressive symptoms in order to achieve optimal functional outcomes.

Deep brain stimulation (DBS) delivered to the ventromedial prefrontal cortex (vmPFC) induces antidepressant- and anxiolytic-like responses in various animal models. Electrophysiology and neurochemical studies suggest that these effects may be dependent, at least in part, on the serotonergic system. In rodents, vmPFC DBS reduces raphe cell firing and increases serotonin (5-HT) release and the expression of serotonergic receptors in different brain regions.We examined whether the behavioural responses of chronic vmPFC DBS are mediated by 5-HTWe found that chronic DBS delivered to stressed animals reduced the latency to feed in the novelty suppressed feeding test (NSF) and immobility in the forced swim test (FST). Though no significant changes were observed in receptor expression, 5-HTThe antidepressant- and anxiolytic-like effects of DBS in rodents may be partially mediated by 5-HT1

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.

Background: Obsessive-compulsive disorder (OCD) is a debilitating disease with a lifetime prevalence of 2–3%. Neuromodulatory treatments have been successfully used in severe cases. Deep brain stimulation (DBS) targeting the inferior thalamic peduncle (ITP) has been shown to successfully alleviate symptoms in OCD patients; however, the brain circuits implicated remain unclear. Here, we investigate the efficacious neural substrates following ITP-DBS for OCD. Methods: High-quality normative structural and functional connectomics and voxel-wise probabilistic mapping techniques were applied to assess the neural substrates of OCD symptom alleviation in a cohort of 5 ITP-DBS patients. Results: The region of most efficacious stimulation was located in the regions of the ITP and bed nucleus of the stria terminalis. Both functional and structural connectomics analyses demonstrated that successful symptom alleviation involved a brain network encompassing the bilateral amygdala and prefrontal regions. Limitations: The main limitation is the small size of the ITP-DBS cohort. While the findings are highly consistent and significant, these should be validated in larger studies. Conclusions: These results identify a tripartite brain network – composed of the bilateral amygdala and prefrontal regions 24 and 46 – whose engagement is associated with greater symptom improvement. They also provide information for optimizing targeting and identifying network components critically involved in ITP-DBS treatment response. Amygdala engagement in particular seems to be a key component for clinical benefits and could constitute a biomarker for treatment optimization.

This chapter explores the complex neuroethical aspects of neurosurgery and neuromodulation in the context of Canadian healthcare and innovation, as seen through the lens of the Pan Canadian Neurotechnology Ethics Consortium (PCNEC). Highlighted are key areas of ethical focus, each with its own unique challenges: technical advances, readiness and risk, vulnerable populations, medico-legal issues, training, and research. Through an exploration of Canadian neurotechnological practice from these various clusters, we provide a critical review of progress, describe opportunities to address areas of debate, and seek to foster ethical innovation. Underpinning this comprehensive review are the fundamental principles of solution-oriented, practical neuroethics, with beneficence and justice at the core. In our view, it is a moral imperative that neurotechnological advancements include a delineation of ethical priorities for future guidelines, oversight, and interactions.

The global prevalence of obesity increases yearly along with a rising demand for efficacious, safe, and accessible treatments. Neuromodulation interventions (i.e., deep brain stimulation [DBS], transcranial magnetic stimulation [TMS], transcranial direct current stimulation [tDCS], percutaneous neurostimulation [PENS], vagus nerve stimulation [VNS], and gastric electrical stimulation [GES]) have been proposed as novel therapies. This systematic review sought to examine the safety and efficacy of neuromodulation therapies in reducing body weight in patients with obesity. Using PRISMA guidelines, we performed a systematic review for studies on neuromodulation for the treatment of obesity, resulting in 60 trials included (7 DBS, 5 TMS, 7 tDCS, 17 PENS and VNS, and 24 GES; a total of 3,042 participants). While promising results have been reported in open label studies, double-blinded randomized clinical trials often did not reach their primary endpoints, with no technique inducing a striking reduction in body weight. Bearing in mind the complexity and multifactorial nature of obesity, it is possible that a single treatment may not be enough for patients to lose or maintain the weight lost at long term.

Major depressive disorder (MDD) is one of the leading causes of disability worldwide. Conventional treatment consists of psychotherapy and pharmacotherapy. Severity, improvement, and remission of d...

Background: Deep brain stimulation targeting the subcallosal cingulate gyrus (SCG DBS) improves the symptoms of treatment-resistant depression in some patients, but not in others. We hypothesized that there are pre-existing structural brain differences between responders and nonresponders to SCG DBS, detectable using structural MRI. Methods: We studied preoperative, T1-weighted MRI scans of 27 patients treated with SCG DBS from 2003 to 2011. Responders (n = 15) were patients with a > 50% improvement in Hamilton Rating Scale for Depression score following 12 months of SCG DBS. Preoperative subcallosal cingulate gyrus grey matter volume was obtained using manual segmentation by a trained observer blinded to patient identity. Volumes of hippocampus, thalamus, amygdala, whole-brain cortical grey matter and white matter volume were obtained using automated techniques. Results: Preoperative subcallosal cingulate gyrus, thalamic and amygdalar volumes were significantly larger in patients who went on to respond to SCG-DBS. Hippocampal volume did not differ between groups. Cortical grey matter volume was significantly smaller in responders, and cortical grey matter:white matter ratio distinguished between responders and nonresponders with high sensitivity and specificity. Limitations: Normalization by intracranial volume nullified some between-group differences in volumetric measures. Conclusion: There are structural brain differences between patients with treatment-resistant depression who respond to SCG DBS and those who do not. Specifically, the structural integrity of the subcallosal cingulate gyrus target region and its connected subcortical areas, and variations in cortical volume across the entire brain, appear to be important determinants of response. Structural MRI shows promise as a biomarker in deep brain stimulation for depression, and may play a role in refining patient selection for future trials.

Background Whereas transient, self-limiting seizures are an infrequent but known complication of deep brain stimulation (DBS) implantation surgery, stimulation itself has occasionally been reported to result in seizure activity at delayed time points. The neural circuitry implicated in stimulation-induced seizures is unknown. Case Description A 47-year-old woman underwent chronic subcallosal cingulate DBS for treatment of refractory anorexia nervosa and experienced seizure with stimulation onset. Supratherapeutic voltage caused a generalized seizure. The patient subsequently experienced a full recovery. We reviewed the literature for other cases of delayed postoperative DBS seizures associated with stimulation. We also investigated whether the higher voltage may have recruited networks implicated in epilepsy. The supratherapeutic voltage stimulated a larger area and engaged vulnerable networks, including bilateral hippocampi, cingulate gyrus, and temporal lobes. Literature review identified 20 studies reporting delayed seizure after DBS surgery, 13 of which demonstrated a robust association with mostly nonmotor DBS stimulation. Conclusions Nonmotor DBS targets, particularly in patients with epilepsy, may be more vulnerable to stimulation-induced seizures; as such, extra caution should be used when programming stimulation parameters at these DBS targets.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics.This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics.Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory.Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols.

Background: Several different surgical procedures targeting the limbic circuit have been utilized for severe, treatment resistant obsessive-compulsive disorder; however, there has only been limited exploration of the inferior thalamic peduncle (ITP). The aim of this study was to determine the safety and initial efficacy of ITP deep brain stimulation (DBS) in patients with severe obsessive-compulsive disorder. Methods: Patients with severe, treatment-refractory obsessive-compulsive disorder were enrolled into this open-label phase 1 DBS pilot study. Bilateral ITP DBS devices were implanted between November 2010 and December 2015. The primary outcome was safety. The initial efficacy was determined by Yale-Brown Obsessive-Compulsive scale (YBOCs) scores. Component Y-BOCs scores, Hamilton Depression Severity Scale, Quality of Life Assessment (SF-36), Oxford Happiness Questionnaire, Warwick-Edinburgh Mental Well-Being Scale, and Sheehan Disability Scale were also analyzed for a minimum of 2 years after surgery. Additionally, preoperative and three-month postoperative FDG-PET studies were performed on two patients. Results: Five patients (2 males, 3 females; age range 25–48 years) received ITP DBS. All five patients were considered responders at one year (52% improvement in YBOCs scores compared to baseline (range 39–73%, p

IntroductionEsketamine is the S-enantiomer of racemic ketamine and has been approved by the Food and Drug Administration for the management of treatment resistant depression, demonstrating effective and long-lasting benefits. The objective of this observational study is to elucidate the association of intranasal (IN) esketamine with beneficial and negative outcomes in the management of treatment resistant major depressive disorder.Methods and analysisThis is a multicentre prospective cohort observational study of naturalistic clinical practice. We expect to recruit 10 patients per research centre (6 centres, total 60 subjects). After approval to receive IN esketamine as part of their standard of care management of moderate to severe treatment resistant depression, patients will be invited to participate in this study. Association of esketamine treatment with outcomes in the management of depression will be assessed by measuring the severity of depression symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS), and tolerability by systematically tracking common side effects of ketamine treatment, dissociation using the simplified 6-Item Clinician Administered Dissociative Symptom Scale and potential for abuse using the Likeability and Craving Questionnaire (LCQ). Change in depressive symptoms (MADRS total scores) over time will be evaluated by within-subject repeated measures analysis of variance. We will calculate the relative risk associated with the beneficial (reduction in total scores for depression) outcomes, and the side effect and dropout rates (tolerability) of adding IN esketamine to patients’ current pharmacological treatments. Covariate analysis will assess the impact of site and demographic variables on treatment outcomes.Ethics and disseminationApproval to perform this study was obtained through the Health Sciences Research Ethics Board at Queen’s University. Findings will be shared among collaborators, through departmental meetings, presented on different academic venues and publishing our manuscript.

Background Major Depressive Disorder (MDD) is characterized by objective and subjective cognitive deficits. Discrepancies between objective and subjective cognitive performance can reflect under- to over-estimations of cognitive abilities, and these discrepancies are referred to as cognitive self-appraisals. Despite evidence that low self-appraisals are associated with depression, the modifiability of self-appraisals and their association with treatment outcome remains unclear. The current study examined whether self-appraisals change following antidepressant treatment. Furthermore, we investigated the association of self-appraisals with treatment outcome. Methods As part of the CAN-BIND-1 clinical trial, 154 patients with MDD completed measures of objective and subjective cognitive abilities, depressive symptoms, and functional outcomes (work productivity, psychosocial functioning, and quality of life) at baseline and post-escitalopram treatment. Self-appraisals were calculated based on discrepancies between objective and subjective cognitive abilities, with higher scores indicating overestimation of cognitive abilities. Results Baseline self-appraisals were not predictive of treatment outcomes. However, self-appraisals increased from pre- to post-treatment. Moreover, pre-post treatment increases in self-appraisals were associated with positive treatment response and remission, decreases in depressive symptoms, and improvements in work productivity, psychosocial functioning, and quality of life. Limitations The pre-post intervention design precluded examining the temporal precedence of change in self-appraisals versus depressive symptoms and functional outcomes. Conclusions Findings are the first to demonstrate that self-appraisals are treatment-sensitive and are associated with treatment outcomes and recovery from MDD. Cognitive self-appraisals may represent a key marker of treatment response and a valuable target for assessment and intervention, as well as a potential mechanism underlying risk and recovery.

Deep brain stimulation targeting the subcallosal cingulate area, a hub with multiple axonal projections, has shown therapeutic potential for treatment-resistant mood disorders. While subcallosal cingulate deep brain stimulation drives long-term metabolic changes in corticolimbic circuits, the brain areas that are directly modulated by electrical stimulation of this region are not known. We used 3.0 T functional MRI to map the topography of acute brain changes produced by stimulation in an initial cohort of 12 patients with fully implanted deep brain stimulation devices targeting the subcallosal cingulate area. Four additional subcallosal cingulate deep brain stimulation patients were also scanned and employed as a validation cohort. Participants underwent resting state scans (n = 78 acquisitions overall) during (i) inactive deep brain stimulation; (ii) clinically optimal active deep brain stimulation; and (iii) suboptimal active deep brain stimulation. All scans were acquired within a single MRI session, each separated by a 5-min washout period. Analysis of the amplitude of low-frequency fluctuations in each sequence indicated that clinically optimal deep brain stimulation reduced spontaneous brain activity in several areas, including the bilateral dorsal anterior cingulate cortex, the bilateral posterior cingulate cortex, the bilateral precuneus and the left inferior parietal lobule (PBonferroni These results provide insight into the network-level mechanisms of subcallosal cingulate deep brain stimulation and point towards potential acute biomarkers of clinical response that could help to optimize and personalize this therapy.

Recently, a small literature has emerged suggesting that repetitive transcranial magnetic stimulation (rTMS) may offer benefit for MDD even in BPD patients, perhaps by enhancing cognitive control, and/or disrupting excessive 'non-reward' activity in right orbitofrontal regions. This study aimed primarily to assess the therapeutic effects of dorsomedial prefrontal cortex (DMPFC)-rTMS against MDD symptoms in BPD patients, and secondarily to assess whether the therapeutic effects ensued via mechanisms of reduced impulsivity and core BPD pathology on clinical scales (BIS-11, ZAN-BPD) or of reduced alpha- and theta-band activity on EEG recordings of right orbitofrontal cortex..In a crossover-design trial, 20 BPD patients with MDD underwent 2 × 30 session/15 day blocks of either active-then-sham or sham-then-active bilateral 20 Hz DMPFC-rTMS.Sixteen out of 20 patients completed treatment. A significant (p = 0.00764) crossover effect was detected, with overall reductions in HamD17 score from 23.1±SD3.1 to 10.75±SD5.8. Nine out of 16 (56.3%) treatment completers achieved response (50% improvement) and 6/16 (37.5%) achieved remission (HamD≤7), maintained at 1 month followup. BIS-11 scores remained unchanged, and ZAN-BPD scores improved similarly in both groups with no significant crossover effect. Change in low-band power over right orbitofrontal regions correlated with clinical improvement.This was a crossover study with a small sample size. A randomized controlled trial with larger sample size will be needed to establish the efficacy more definitively.The results suggest efficacy for DMPFC-rTMS in treating MDD in BPD, and provide a foundation for a larger future trial.

Subcallosal cingulate deep brain stimulation produces long-term clinical improvement in approximately half of patients with severe treatment-resistant depression. We hypothesized that both structural and functional brain attributes may be important in determining responsiveness to this therapy.In a treatment-resistant depression subcallosal cingulate deep brain stimulation cohort, we retrospectively examined baseline and longitudinal differences in MRI-derived brain volume (n = 65) and 18F-fluorodeoxyglucose-PET glucose metabolism (n = 21) between responders and non-responders. Support vector machines were subsequently trained to classify patients’ response status based on extracted baseline imaging features. A machine learning model incorporating preoperative frontopolar, precentral/frontal opercular and orbitofrontal local volume values classified binary response status (12 months) with 83% accuracy [leave-one-out cross-validation (LOOCV): 80% accuracy] and explained 32% of the variance in continuous clinical improvement. It was also predictive in an out-of-sample subcallosal cingulate deep brain stimulation cohort (n = 21) with differing primary indications (bipolar disorder/anorexia nervosa; 76% accuracy). Adding preoperative glucose metabolism information from rostral anterior cingulate cortex and temporal pole improved model performance, enabling it to predict response status in the treatment-resistant depression cohort with 86% accuracy (LOOCV: 81% accuracy) and explain 67% of clinical variance. Response-related patterns of metabolic and structural post-deep brain stimulation change were also observed, especially in anterior cingulate cortex and neighbouring white matter. Areas where responders differed from non-responders—both at baseline and longitudinally—largely overlapped with depression-implicated white matter tracts, namely uncinate fasciculus, cingulum bundle and forceps minor/rostrum of corpus callosum. The extent of patient-specific engagement of these same tracts (according to electrode location and stimulation parameters) also served as an independent predictor of treatment-resistant depression response status (72% accuracy; LOOCV: 70% accuracy) and augmented performance of the volume-based (88% accuracy; LOOCV: 82% accuracy) and combined volume/metabolism-based support vector machines (100% accuracy; LOOCV: 94% accuracy).Taken together, these results indicate that responders and non-responders to subcallosal cingulate deep brain stimulation exhibit differences in brain volume and metabolism, both pre- and post-surgery. Moreover, baseline imaging features predict response to treatment (particularly when combined with information about local tract engagement) and could inform future patient selection and other clinical decisions.

This chapter explores the complex neuroethical aspects of neurosurgery and neuromodulation in the context of Canadian healthcare and innovation, as seen through the lens of the Pan Canadian Neurotechnology Ethics Consortium (PCNEC). Highlighted are key areas of ethical focus, each with its own unique challenges: technical advances, readiness and risk, vulnerable populations, medico-legal issues, training, and research. Through an exploration of Canadian neurotechnological practice from these various clusters, we provide a critical review of progress, describe opportunities to address areas of debate, and seek to foster ethical innovation. Underpinning this comprehensive review are the fundamental principles of solution-oriented, practical neuroethics, with beneficence and justice at the core. In our view, it is a moral imperative that neurotechnological advancements include a delineation of ethical priorities for future guidelines, oversight, and interactions.