Jonathan Downar

University Health Network | UHN · Department of Psychiatry

Objective: Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the ef...

Background Repetitive transcranial magnetic stimulation (rTMS) can target specific neural circuits, which may allow for personalized treatment of depression. Treatment outcome is typically determined using sum scores from validated measurement scales; however, this may obscure differential improvements within distinct symptom domains. The objective...

The neural substrates of depression may differ in men and women, but the underlying mechanisms are incompletely understood. Here, we show that depression is associated with sex-specific patterns of abnormal functional connectivity in the default mode network and in five regions of interest with sexually dimorphic transcriptional effects. Regional d...

Importance Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right c...

Background and objective Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD). rTMS is in need of a reliable biomarker of treatment response. High frequency (HF) dorsolateral prefrontal cortex (DLPFC) rTMS has been reported to induce significant changes in the cardiac activity of...

Objective: To investigate the effect of 10Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) on suicidality in patients with treatment resistant depression (TRD) METHODS: We used data from a three-site randomized clinical trial comparing 10Hz and iTBS rTMS applied to the left dorsolateral prefron...

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 MR...

Background Repetitive transcranial magnetic stimulation (rTMS) is entering wider use as a therapeutic intervention for many psychiatric illnesses. The efficacy of this therapeutic intervention may depend on accurately localizing target brain regions. Recent work investigating whole-brain maps of circuits associated with depression and its successfu...

Objective: To quantitatively synthesize the literature on the effects of repetitive transcranial magnetic stimulation (rTMS) on suicidal ideation (SI) in patients with treatment-resistant depression. Data Sources: A literature search was conducted using PubMed, SCOPUS, Ovid, MEDLINE, Embase, and Web of Science from inception to January 11, 2021, f...

Background Cognitive dysfunction (CD) is a commonly reported symptom of major depressive disorder (MDD). Patients with treatment-resistant depression (TRD) tend to experience greater rates of CD; however, treatment options are limited. Repetitive transcranial magnetic stimulation (rTMS) is effective in treating affective symptoms in patients with T...

Clinically oriented studies commonly acquire diffusion MRI (dMRI) data with a single non-zero b-value (i.e. single-shell) and diffusion weighting of b =1000 s/mm ² . To produce microstructural parameter maps, the tensor model is usually used, despite known limitations. Although compartment models have demonstrated improved fits in multi-shell dMRI...

Background 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...

BACKGROUND Major depressive disorder (MDD) is now the first cause of disability worldwide. So far, no validated and scalable biomarker has been identified to help with response prediction to antidepressant treatment. Cardiac biomarkers such as heart rate variability (HRV) have been studied in MDD, but few studies have examined its potential use for...

Objective: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD) but may be associated with adverse cognitive effects. Magnetic seizure therapy (MST) is a promising alternative convulsive treatment with a safer cognitive profile. Although there is emerging evidence for the efficacy of MST for TRD as an acute t...

Background Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention for major depressive disorder (MDD). Completing a full treatment course, however, is costly and time-consuming. Biomarkers of clinical outcome such as baseline resting-state brain activity measured with electroencephalography (EEG) may spare people futile tr...

Background: Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD) that can increase treatment capacity. Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly. Objective: /Hypothesis- We compare...

Background Repetitive transcranial magnetic stimulation (rTMS) is an efficacious and well-tolerated intervention for treatment-resistant depression (TRD). A novel rTMS protocol, intermittent theta burst stimulation (iTBS) has been recently implemented in clinical practice, and it is essential to characterize the factors associated to pain and the t...

The literature on the application of repetitive transcranial magnetic stimulation (rTMS) in Borderline Personality Disorder (BPD) is unclear, even though its neuromodulatory effects on underlying neural circuitry involved in BPD symptoms suggest that it could be a potential treatment option. We sought to review the evidence on rTMS as a treatment o...

Background Older adults with late-life depression (LLD) often experience incomplete or lack of response to first-line pharmacotherapy. The treatment of LLD could be improved using objective biological measures to predict response. Transcranial magnetic stimulation (TMS) can be used to measure cortical excitability, inhibition, and plasticity, which...

Objectives: Repetitive transcranial magnetic stimulation (rTMS) is commonly used in unipolar depression; yet there its evidence in bipolar disorder (BD) is limited. We sought to review the evidence on the use of rTMS across the different stages of BD. Methods: MEDLINE database was systematically searched using the PubMed interface following the...

Background Patients with anorexia nervosa (AN) face severe and chronic illness with high mortality rates, despite our best currently available conventional treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown increasing efficacy in treatment-refractory cases across a variety of psychiatric disorders comorbid with AN, including...

Background Despite the advances in the use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD), there is relatively little information about its effect on comorbid anxiety symptoms. Methods Data from a large randomized noninferiority trial comparing intermittent theta‐burst stimulation (iTBS)...

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We em...

Background: There is growing interest in the potential of neuromodulation options in treatment-resistant obsessive-compulsive disorder (OCD). Magnetic seizure therapy (MST), is a new treatment intervention in which generalized seizures are induced with transcranial magnetic stimulation. We conducted a pilot study to assess the efficacy and cogniti...

Multiple structural and functional neuroimaging measures vary over the course of the lifespan and can be used to predict chronological age. Accelerated brain aging, as quantified by deviations in the MRI-based predicted age with respect to chronological age, is associated with risk for neurodegenerative conditions, bipolar disorder, and mortality....

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention in major depressive disorder (MDD) but requires daily travel to a treatment clinic over several weeks. Shorter rTMS courses retaining similar effectiveness would thus increase the practicality and scalability of the technique, and therefore its accessibility...

Background Treatment resistant depression (TRD) is one of the leading causes of disability in Canada and is associated with significant societal costs. Repetitive transcranial magnetic stimulation (rTMS) is an approved, safe, and well-tolerated intervention for TRD. In the setting of the COVID-19 pandemic, reducing the number of visits to the clini...

Objective: The aim of the current study was to attempt to replicate the finding that the individual alpha frequency (IAF) as well as the absolute difference between IAF and 10 Hz stimulation frequency (IAF-prox) is related to treatment outcome. Methods: Correlations were performed to investigate the relationship between IAF-prox and percentage sym...

Objective Repetitive transcranial magnetic stimulation (rTMS) is an evidenced based treatment for depression and an emerging treatment for several other neuropsychiatric disorders. The objective of this systematic review was to assess molecular changes produced by rTMS or molecular markers that predict treatment response in neuropsychiatric disorde...

Objective Our previous research showed high predictive accuracy at differentiating responders from non-responders to repetitive transcranial magnetic stimulation (rTMS) for depression using resting electroencephalography (EEG) and clinical data from baseline and one-week following treatment onset using a machine learning algorithm. In particular, t...

Background: Late-life depression is often associated with non-response or relapse following conventional antidepressant treatment. The pathophysiology of late-life depression likely involves a complex interplay between aging and depression, and may include abnormalities in cortical inhibition and plasticity. However, the extent to which these cort...

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is an effective intervention in major depressive disorder (MDD) but requires daily travel to a treatment clinic over several weeks. Shorter rTMS courses retaining similar effectiveness would thus increase the practicality and scalability of the technique, and therefore its accessibility...

Objectives: Magnetic seizure therapy (MST) is a novel investigational brain stimulation modality for patients with treatment-resistant depression (TRD). MST is a potential alternative seizure-based treatment to electroconvulsive therapy (ECT), given that it may offer equivalent antidepressant efficacy, yet with a relative sparing of cognitive func...

Importance There is an unmet need for effective treatments for suicidality in mental disorders. Magnetic seizure therapy (MST) has been investigated as an alternative to electroconvulsive therapy, a known effective treatment for suicidality, in the management of treatment-resistant major depressive disorder, with promising findings. Yet, there are...

Objectives Electroconvulsive therapy (ECT) is an essential psychiatric service that has an important role in treating older adult patients with severe or treatment-resistant depression (TRD). During the COVID-19 pandemic, ECT services may be limited due to infection control measures. We report a case of a 66-year-old female patient with a severe ma...

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is effective in major depressive disorder (MDD). However, technical complexity and operational costs might have been barriers for its wide use and implementation in some jurisdictions, thereby decreasing accessibility. OBJECTIVE Our main goal was to test the feasibility of a novel rTMS...

Transcranial magnetic stimulation (TMS) is an effective treatment for depression but is limited in that the optimal therapeutic target remains unknown. Early TMS trials lacked a focal target, and thus positioned the TMS coil over the prefrontal cortex using scalp measurements. Over time, it became clear that this method leads to variation in the st...

Background Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), treatment selection is still mainly a process of trial-and-error. The present study aimed to identify clinical predictors of remission after a course of rTMS delivered to the left DLPFC to improve patient selection....

To our knowledge, this is the first case report of TEM with psychosis precipitated by iTBS applied to the left DLPFC in bipolar depression that has been reported in the literature. With the recent approval of iTBS for major depressive disorder by the FDA in 2018 [ 5 • MagVenture Another FDA clearance for MagVenture: 3 minute depression treatment n...

Background : Cognitive impairment is a well-recognized symptom of major depressive disorder; however, contributing factors are not fully characterized. The present study examined the neurocognitive profiles and predictors of cognitive impairment in patients with treatment-resistant depression (TRD). Methods : Moderate to severely depressed TRD pat...

Anhedonia is thought to reflect deficits in reward processing that are associated with abnormal activity in mesocorticolimbic brain regions. It is expressed clinically as a deficit in the interest or pleasure in daily activities. More severe anhedonia in major depressive disorder (MDD) is a negative predictor of antidepressant response. It is unkno...

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcra...

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...

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are...

Background: Currently, the mainstay of treatment in patients diagnosed with major depressive disorder (MDD) requiring medical attention is second generation anti-depressants. However, about 40% of patients treated with second-generation anti-depressants do not respond to initial treatment and approximately 70% do not achieve remission during the f...

Background: Identifying objective biomarkers can assist in predicting remission/non-remission to treatment, improving remission rates, and reducing illness burden in major depressive disorder (MDD). Methods: Sixteen MDD 8-week remitters (MDD-8), twelve 16-week remitters (MDD-16), 14 non-remitters (MDD-NR) and 30 healthy comparison participants (...