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Abstract Background Major depressive disorder (MDD) is a leading cause of disability worldwide across domains of health and cognition, affecting overall quality of life. Approximately one third of individuals with depression do not fully respond to treatments (e.g., conventional antidepressants, psychotherapy) and alternative strategies are needed. Recent early phase trials suggest psilocybin may be a safe and efficacious intervention with rapid-acting antidepressant properties. Psilocybin is thought to exert therapeutic benefits by altering brain network connectivity and inducing neuroplastic changes that endure for weeks post-treatment. Although early clinical results are encouraging, psilocybin’s acute neurobiological effects on neuroplasticity have not been fully investigated. We aim to examine for the first time how psilocybin acutely (intraday) and subacutely (weeks) alters functional brain networks implicated in depression. Methods Fifty participants diagnosed with MDD or persistent depressive disorder (PDD) will be recruited from a tertiary mood disorders clinic and undergo 1:1 randomization into either an experimental or control arm. Participants will be given either 25 mg psilocybin or 25 mg microcrystalline cellulose (MCC) placebo for the first treatment. Three weeks later, those in the control arm will transition to receiving 25 mg psilocybin. We will investigate whether treatments are associated with changes in arterial spin labelling and blood oxygenation level-dependent contrast neuroimaging assessments at acute and subacute timepoints. Primary outcomes include testing whether psilocybin demonstrates acute changes in (1) cerebral blood flow and (2) functional brain activity in networks associated with mood regulation and depression when compared to placebo, along with changes in MADRS score over time compared to placebo. Secondary outcomes include changes across complementary clinical psychiatric, cognitive, and functional scales from baseline to final follow-up. Serum peripheral neurotrophic and inflammatory biomarkers will be collected at baseline and follow-up to examine relationships with clinical response, and neuroimaging measures. Discussion This study will investigate the acute and additive subacute neuroplastic effects of psilocybin on brain networks affected by depression using advanced serial neuroimaging methods. Results will improve our understanding of psilocybin’s antidepressant mechanisms versus placebo response and whether biological measures of brain function can provide early predictors of treatment response. Trial registration ClinicalTrials.gov Identifier: NCT06072898. Registered on 6 October 2023.

Background: Patient expectations, including both positive (placebo) and negative (nocebo) effects, influence treatment outcomes, yet their impact on acute repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) is unclear. Methods: In this single-center retrospective chart review, 208 TRD patients completed the Stanford Expectation of Treatment Scale (SETS) before starting open-label rTMS treatment. Patients were offered two excitatory rTMS protocols (deep TMS or intermittent theta-burst stimulation), which stimulated the left dorsolateral prefrontal cortex. A minimum of 20 once daily treatments were provided, delivered over 4–6 weeks. Primary outcomes were 1) remission, measured by a post-treatment score of

Summary: Background: Repetitive transcranial magnetic stimulation (rTMS) is frequently used as an adjunctive treatment with antidepressants for depression. We aimed to evaluate the clinical efficacy and safety of antidepressant classes when administered concurrently with rTMS for the management of major depressive disorder (MDD). Methods: In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from inception to April 12th 2024 for terms relating to medication, depression, and rTMS and appraised by 2 independent screeners. All randomized clinical trials that prospectively evaluated a specific antidepressant adjunctively with sham rTMS as a control in MDD were included. The study was registered with PROSPERO (CRD42023418435). The primary outcome measure assessed symptomatic improvement measured by formal depression scales. We used a random-effects model with pooled Standardized Mean Differences (SMDs) and log odds ratios (OR). All studies were assessed for their methodological quality and bias using the Cochrane Collaboration Risk of Bias tool version 2 (RoB2). Findings: 14 articles from 5376 identified studies were included in the systematic review and meta-analysis. There was only sufficient trial data to evaluate the effects of rTMS and combination therapy with selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs). Across studies, 848 participants (mean [SD] age:41.1 [18.7] years for SSRIs, 51.8 [3.8] years for SNRIs) prospectively examined the efficacy of antidepressant medication with rTMS. Combining rTMS with SSRIs led to significantly lower depression scores, (SMD [CI] of −0.65 [−0.98, −0.31], p = 0.0002, I2 = 66.1%), higher response (OR = 0.97 [0.50, 1.44], p

Background: Deep brain stimulation of the subcallosal cingulate area (SCC-DBS) is a promising neuromodulatory therapy for treatment-resistant depression (TRD). Biomarkers of optimal target engagement are needed to guide surgical targeting and stimulation parameter selection and to reduce variance in clinical outcome. Objective/Hypothesis: We aimed to characterize the relationship between stimulation location, white matter tract engagement, and clinical outcome in a large (n = 60) TRD cohort treated with SCC-DBS. A smaller cohort (n = 22) of SCC-DBS patients with differing primary indications (bipolar disorder/anorexia nervosa) was utilized as an out-of-sample validation cohort. Methods: Volumes of tissue activated (VTAs) were constructed in standard space using high-resolution structural MRI and individual stimulation parameters. VTA-based probabilistic stimulation maps (PSMs) were generated to elucidate voxelwise spatial patterns of efficacious stimulation. A whole-brain tractogram derived from Human Connectome Project diffusion-weighted MRI data was seeded with VTA pairs, and white matter streamlines whose overlap with VTAs related to outcome (‘discriminative’ streamlines; Puncorrected < 0.05) were identified using t-tests. Linear modelling was used to interrogate the potential clinical relevance of VTA overlap with specific structures. Results: PSMs varied by hemisphere: high-value left-sided voxels were located more anterosuperiorly and squarely in the lateral white matter, while the equivalent right-sided voxels fell more posteroinferiorly and involved a greater proportion of grey matter. Positive discriminative streamlines localized to the bilateral (but primarily left) cingulum bundle, forceps minor/rostrum of corpus callosum, and bilateral uncinate fasciculus. Conversely, negative discriminative streamlines mostly belonged to the right cingulum bundle and bilateral uncinate fasciculus. The best performing linear model, which utilized information about VTA volume overlap with each of the positive discriminative streamline bundles as well as the negative discriminative elements of the right cingulum bundle, explained significant variance in clinical improvement in the primary TRD cohort (R = 0.46, P

IntroductionThis study explores the relationship between emotional support, perceived risk and mental health outcomes among health care workers, who faced high rates of burnout and mental distress since the beginning of the COVID­19 pandemic. MethodsA cross­sectional, multicentred online survey of health care workers in the Greater Toronto Area, Ontario, Canada, during the first wave of the COVID­19 pandemic evaluated coping strategies, confidence in infection control, impact of previous work during the 2003 SARS outbreak and emotional support. Mental health outcomes were assessed using the Generalized Anxiety Disorder scale, the Impact of Event Scale – Revised and the Patient Health Questionnaire (PHQ­9). ResultsOf 3852 participants, 8.2% sought professional mental health services while 77.3% received emotional support from family, 74.0% from friends and 70.3% from colleagues. Those who felt unsupported in their work had higher odds ratios of experiencing moderate and severe symptoms of anxiety (odds ratio [OR] = 2.23; 95% confidence interval [CI]: 1.84–2.69), PTSD (OR = 1.88; 95% CI: 1.58–2.25) and depression (OR = 1.88; 95% CI: 1.57–2.25). Nearly 40% were afraid of telling family about the risks they were exposed to at work. Those who were able to share this information demonstrated lower risk of anxiety (OR = 0.58; 95% CI: 0.48–0.69), PTSD (OR = 0.48; 95% CI: 0.41–0.56) and depression (OR = 0.55; 95% CI: 0.47–0.65). ConclusionInformal sources of support, including family, friends and colleagues, play an important role in mitigating distress and should be encouraged and utilized more by health care workers.

IntroductionCette 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. MéthodologieUne 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). RésultatsSur 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). ConclusionLes 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.

Background: Aggressive 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. Objectives: To test whether pHyp-DBS reduces aggressive behaviour in mice through mechanisms involving testosterone and 5-HT. Methods: Male mice were housed with females for two weeks. These resident animals become territorial and aggressive towards intruder mice placed in their cages. Residents had electrodes implanted in the pHyp. DBS was administered for 5 h/day for 8 consecutive encounters prior to the interaction with the intruder. After testing, blood and brains were recovered for measuring testosterone and 5-HT receptor density, respectively. In a second experiment, residents received WAY-100635 (5-HT1A antagonist) 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 encounters. Results: DBS-treated mice showed reduced AB that was correlated with testosterone levels and an increase in 5-HT1A receptor density in the orbitofrontal cortex and amygdala. Pre-treatment with WAY-100635 blocked the anti-aggressive effect of pHyp-DBS. Conclusions: This study shows that pHyp-DBS reduces AB in mice via changes in testosterone and 5-HT1A mechanisms.

Deep brain stimulation targeting the posterior hypothalamus (pHyp-DBS) is being investigated as a treatment for refractory aggressive behavior, 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. 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 fiber tracts and functionally connected with 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 behavior, neuronal communication, plasticity and neuroinflammation might underlie this functional network.

Introduction Esketamine 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 analysis This 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 dissemination Approval 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: Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. Objective: The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. Methods: 120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. Results: Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians’ treatment arm guesses were significantly above chance. Conclusion: DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted.

The habenula (Hb) is a small, evolutionarily conserved epithalamic structure implicated in functions such as reward and mood regulation. Prior imaging work suggests that Hb's structural and functional properties may relate to treatment response in depression and other mood disorders. We used multimodal MRI techniques to investigate the potential involvement of Hb in response to subcallosal cingulate area deep brain stimulation (SCC-DBS) for treatment-resistant mood disorders. Using an automated segmentation technique, we compared Hb volume at baseline and at a subsequent post-operative timepoint (4.4 ± 3.0 years after surgery) in a cohort of 32 patients who received SCC-DBS. Clinical response to treatment (≥50% decrease in HAMD-17 from baseline to 12 months post-operation) was significantly associated with longitudinal Hb volume change: responders tended to have increased Hb volume over time, while non-responders showed decreased Hb volume (t = 2.4, p = 0.021). We additionally used functional MRI (fMRI) in a subcohort of SCC-DBS patients (n = 12) to investigate immediate within-patient changes in Hb functional connectivity associated with SCC-DBS stimulation. Active DBS was significantly associated with increased Hb connectivity to several prefrontal and corticolimbic regions (TFCE-adjusted pBonferroni < 0.0001), many of which have been previously implicated in the neurocircuitry of depression. Taken together, our results suggest that Hb may play an important role in the antidepressant effect of SCC-DBS.

Background: Panic attacks affect a sizeable proportion of the population. The neurocircuitry of panic remains incompletely understood. Objective: To investigate the neuroanatomical underpinnings of panic attacks induced by deep brain stimulation (DBS) through (1) connectomic analysis of an obsessive-compulsive disorder patient who experienced panic attacks during inferior thalamic peduncle DBS; (2) appraisal of existing clinical reports on DBS-induced panic attacks. Methods: Panicogenic, ventral contact stimulation was compared with benign stimulation at other contacts using volume of tissue activated (VTA) modelling. Networks associated with the panicogenic zone were investigated using state-of-the-art normative connectivity mapping. In addition, a literature search for prior reports of DBS-induced panic attacks was conducted. Results: Panicogenic VTAs impinged primarily on the tuberal hypothalamus. Compared to non-panicogenic VTAs, panicogenic loci were significantly functionally coupled to limbic and brainstem structures, including periaqueductal grey and amygdala. Previous studies found stimulation of these areas can also provoke panic attacks. Conclusions: DBS in the region of the tuberal hypothalamus elicited panic attacks in a single obsessive-compulsive disorder patient and recruited a network of structures previously implicated in panic pathophysiology, reinforcing the importance of the hypothalamus as a hub of panicogenic circuitry.

Objective Explore how previous work during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak affects the psychological response of clinical and non-clinical healthcare workers (HCWs) to the current COVID-19 pandemic. Methods A cross-sectional, multi-centered hospital online survey of HCWs in the Greater Toronto Area, Canada. Mental health outcomes of HCWs who worked during the COVID-19 pandemic and the SARS outbreak were assessed using Impact of Events—Revised scale (IES-R), Generalized Anxiety Disorder scale (GAD-7), and Patient Health Questionnaire (PHQ-9). Results Among 3852 participants, moderate/severe scores for symptoms of post- traumatic stress disorder (PTSD) (50.2%), anxiety (24.6%), and depression (31.5%) were observed among HCWs. Work during the 2003 SARS outbreak was reported by 1116 respondents (29.1%), who had lower scores for symptoms of PTSD (P = .002), anxiety (P < .001), and depression (P < .001) compared to those who had not worked during the SARS outbreak. Multivariable logistic regression analysis showed non-clinical HCWs during this pandemic were at higher risk of anxiety (OR, 1.68; 95% CI, 1.19–2.15, P = .01) and depressive symptoms (OR, 2.03; 95% CI, 1.34–3.07, P < .001). HCWs using sedatives (OR, 2.55; 95% CI, 1.61–4.03, P < .001), those who cared for only 2–5 patients with COVID-19 (OR, 1.59; 95% CI, 1.06–2.38, P = .01), and those who had been in isolation for COVID-19 (OR, 1.36; 95% CI, 0.96–1.93, P = .05), were at higher risk of moderate/severe symptoms of PTSD. In addition, deterioration in sleep was associated with symptoms of PTSD (OR, 4.68, 95% CI, 3.74–6.30, P < .001), anxiety (OR, 3.09, 95% CI, 2.11–4.53, P < .001), and depression (OR 5.07, 95% CI, 3.48–7.39, P < .001). Conclusion Psychological distress was observed in both clinical and non-clinical HCWs, with no impact from previous SARS work experience. As the pandemic continues, increasing psychological and team support may decrease the mental health impacts.

Deep Brain Stimulation (DBS) has been investigated as a treatment option for patients with refractory psychiatric illness. Over the past two decades, neuroimaging developments have helped to advance the field, particularly the use of diffusion tensor imaging (DTI) and tractographic reconstruction of white-matter pathways. In this article, we review translational considerations and how DTI and tractography have been used to improve targeting during DBS surgery for depression, obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD).

Antidepressant drugs are the most common treatment for depressive episodes but only a fraction of patients experience adequate response. Here the authors find dysregulation of miRNAs in peripheral blood samples from depressed patients after antidepressant treatment, and show that the miRNAs are regulators of psychiatrically relevant signalling pathways.

Non-invasive brain stimulation techniques are entering widespread use for the investigation and treatment of a range of neurological and neuropsychiatric disorders. However, most current techniques are ‘open-loop’, without feedback from target brain region activity; this limitation could contribute to heterogeneous effects seen for nominally ‘inhibitory’ and ‘excitatory’ protocols across individuals. More potent and consistent effects may ensue from closed-loop and, in particular, phase-locked brain stimulation. In this work, a closed-loop brain stimulation system is introduced that can analyze EEG data in real-time, provide a forecast of the phase of an underlying brain rhythm of interest, and control pulsed transcranial electromagnetic stimulation to deliver pulses at a specific phase of the target frequency band. The technique was implemented using readily available equipment such as a basic EEG system, a low-cost Arduino board and MATLAB scripts. The phase-locked brain stimulation method was tested in 5 healthy volunteers and its phase-locking performance evaluated at 0, 90, 180, and 270 degree phases in theta and alpha frequency bands. On average phase locking values of 0.55° ± 0.11° and 0.52° ± 0.14° and error angles of 11° ± 11° and 3.3° ± 18° were achieved for theta and alpha stimulation, respectively. Despite the low-cost hardware implementation, signal processing time generated a phase delay of only 3.8° for theta and 57° for alpha stimulation, both readily accommodated in the pulse trigger algorithm. This work lays the methodological steps for achieving phase-locked brain stimulation for brief-pulse transcranial electrical stimulation (tES) and repetitive transcranial magnetic stimulation (rTMS), facilitating further research on the effect of stimulation phase for these techniques.

Electroconvulsive therapy (ECT) has been around since the 1930’s, yet it is still associated with passionate controversy. A large contributing factor to the current perception of ECT include the negative and grossly inaccurate portrayals in various forms of media. Through a literature review, the mechanisms, safety, efficacy, and side effects of the therapy are presented in a graphic narrative. Using both words and art to present a more accurate and holistic depiction of ECT, it was decided to use this visual medium so that the information could be accessed by a wide range of readers and counter incorrect depictions. In particular, this narrative could be read by individuals who are interested in learning more about ECT or are considering the treatment, allowing this comic to be a tool to help others make informed decisions. The findings from the review suggest that while the mechanism of action has still yet to be elucidated for ECT, it is an effective treatment in certain severe psychiatric illnesses. Specifically, it can improve symptoms and the quality of life of patients, especially for those who may be resistant to pharmacotherapy.

Background: Conventional treatments for eating disorders are associated with poor response rates and frequent relapse. Novel treatments are needed, in combination with markers to characterize and predict treatment response. Here, resting-state functional magnetic resonance imaging (rs-fMRI) was used to identify predictors and correlates of response to repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (dmPFC) at 10 Hz for eating disorders with refractory binge/purge symptomatology. Methods: 28 subjects with anorexia nervosa, binge−purge subtype or bulimia nervosa underwent 20–30 sessions of 10 Hz dmPFC rTMS. rs-fMRI data were collected before and after rTMS. Subjects were stratified into responder and nonresponder groups using a criterion of ≥50% reduction in weekly binge/purge frequency. Neural predictors and correlates of response were identified using seed-based functional connectivity (FC), using the dmPFC and adjacent dorsal anterior cingulate cortex (dACC) as regions of interest. Results: 16 of 28 subjects met response criteria. Treatment responders had lower baseline FC from dmPFC to lateral orbitofrontal cortex and right posterior insula, and from dACC to right posterior insula and hippocampus. Responders had low baseline FC from the dACC to the ventral striatum and anterior insula; this connectivity increased over treatment. However, in nonresponders, frontostriatal FC was high at baseline, and dmPFC-rTMS suppressed FC in association with symptomatic worsening. Conclusions: Enhanced frontostriatal connectivity was associated with responders to dmPFC-rTMS for binge/purge behavior. rTMS caused paradoxical suppression of frontostriatal connectivity in nonresponders. rs-fMRI could prove critical for optimizing stimulation parameters in a future sham-controlled trial of rTMS in disordered eating.

A growing body of research suggests that non-invasive electrical brain stimulation can more effectively modulate neural activity when phase-locked to the underlying brain rhythms. Transcranial alternating current stimulation (tACS) can potentially stimulate the brain in-phase to its natural oscillations as recorded by electroencephalography (EEG), but matching these oscillations is a challenging problem due to the complex and time-varying nature of the EEG signals. Here we address this challenge by developing and testing a novel approach intended to deliver tACS phase-locked to the activity of the underlying brain region in real-time. This novel approach extracts phase and frequency from a segment of EEG, then forecasts the signal to control the stimulation. A careful tuning of the EEG segment length and prediction horizon is required and has been investigated here for different EEG frequency bands. The algorithm was tested on EEG data from 5 healthy volunteers. Algorithm performance was quantified in terms of phase-locking values across a variety of EEG frequency bands. Phase-locking performance was found to be consistent across individuals and recording locations. With current parameters, the algorithm performs best when tracking oscillations in the alpha band (8–13 Hz), with a phase-locking value of 0.77 ± 0.08. Performance was maximized when the frequency band of interest had a dominant frequency that was stable over time. The algorithm performs faster, and provides better phase-locked stimulation, compared to other recently published algorithms devised for this purpose. The algorithm is suitable for use in future studies of phase-locked tACS in preclinical and clinical applications.

Post-traumatic stress disorder (PTSD) is an often debilitating disease with a lifetime prevalence rate between 5⁻8%. In war veterans, these numbers are even higher, reaching approximately 10% to 25%. Although most patients benefit from the use of medications and psychotherapy, approximately 20% to 30% do not have an adequate response to conventional treatments. Neuromodulation strategies have been investigated for various psychiatric disorders with promising results, and may represent an important treatment option for individuals with difficult-to-treat forms of PTSD. We review the relevant neurocircuitry and preclinical stimulation studies in models of fear and anxiety, as well as clinical data on the use of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) for the treatment of PTSD.

Objectives: To assess the acceptability and quality of web-based videoconferencing telemedicine consultation platform in the treatment of opioid use disorder at TrueNorth Medical Centre. Methods: We conducted an interview based quality improvement initiative using an investigator-designed questionnaire. The questionnaire consisted of 17 Agree/Disagree questions, measured on a 7-point Likert scale and 2 questions where patients had the ability to elaborate qualitatively on their perceptions and experiences with their telemedicine service. Content-style analysis was performed on qualitative responses. Results: The majority of patients (n=14; 47%) preferred face-to-face over telemedicine consultations. The number of patients that preferred telemedicine consultations over face-to-face consultations was lower (n=6; 20%). A notable number of patients (n=10; 33%) indicated no specific preference for either telemedicine or face-to-face consultations. Patients preferring face-to-face consultations rated their clinical outcome and patient-physician relationship following telemedicine consultations similarly as those who preferred telemedicine consultations. Patients preferring telemedicine rated their experience and overall perceptions of the service significantly higher than those preferring face-to-face consultations. Patients who preferred telemedicine consultations identified the efficient and timesaving nature of telemedicine consultations as primary advantages whereas those preferring face-to-face consultations reported lower levels of empathy from their physician during telemedicine consultations as a major disadvantage. Conclusions: The majority of patients at TrueNorth Medical Centre viewed telemedicine consultations as an acceptable treatment modality. Patients preferring telemedicine consultations and those preferring face-to-face consultations evaluated the majority of the measured indices of care in a similar fashion.