Search

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 MDD patients. Low frequency DLPFC rTMS has many advantages over HF-DLPFC rTMS and thus this study aims to further investigate the effect of low frequency 1 Hz right hemisphere (R)-DLPFC rTMS on the cardiac activity of MDD patients, as well as the potential of using electrocardiogram (ECG) parameters as biomarkers of treatment outcome., Methods: Baseline ECG sessions were performed for 19 MDD patients. All patients then underwent 40 sessions of accelerated 1 Hz R-DLPFC rTMS one week after the baseline session., Results: Heart rate (HR) significantly decreased from the resting period to the first and third minute of the 1 Hz R-DLPFC rTMS period. Resting HR was found to have a significant negative association with treatment outcome. Prior to Bonferroni correction, HR during stimulation and the degree of rTMS-induced HR reduction were significantly negatively associated with treatment outcome. No significant changes were observed for the heart rate variability (HRV) parameters., Limitations: Sample size (n = 19); the use of electroencephalography equipment for ECG; lack of respiration monitoring; relatively short recording duration for HRV parameters., Conclusion: This novel study provides further preliminary evidence that ECG may be utilized as a biomarker of rTMS treatment response in MDD., Trial Registration: ClinicalTrials.gov Identifier: NCT04376697., Competing Interests: Conflict of interest JZS, FM, KD, TR, RZ, MH, LF, HV do not report any conflict of interest. DMB receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he has been the site principal investigator for sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and Magventure Inc. His work has been supported by the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), Brain Canada and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. JD has received research support from the Arrell Family Foundation, the Buchan Family Foundation, Brain Canada, the Canadian Biomarker Integration Network in Depression, the Canadian Institutes of Health Research (CIHR), the Klarman Family Foundation, NIH, the Ontario Brain Institute, the Toronto General and Western Hospital Foundation, and the Weston Family Foundation; he has received travel stipends from Lundbeck and ANT Neuro; he has served as an advisor for BrainCheck, Restorative Brain Clinics, and TMS Neuro Solutions. JPM reports research grants from the Brain & Behavior Research Foundation (BBRF) Young Investigator Award and the Réseau Québécois sur le Suicide, les troubles de l'Humeur et les troubles Associés (RQSHA) as well as salary support for his graduate studies from the Branch Out Neurological Foundation. JDG has received research support from the Labatt Family Network, the CAMH Discovery Fund, the University of Toronto EMHSeed program, and the Tri-Council Canada-UK AI Initiative., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Posttraumatic stress disorder (PTSD) is a common comorbid condition in anorexia nervosa (AN) and bulimia nervosa (BN), and may be associated with reduced response to treatment. We report on a case series employing repetitive transcranial magnetic stimulation (rTMS) with a novel target, the dorsomedial prefrontal cortex (DMPFC). Fourteen subjects with eating disorders and comorbid PTSD received 20-30 neuronavigated DMPFC-rTMS treatments on an open-label basis. PTSD symptoms were assessed pretreatment and posttreatment with the PTSD checklist-Civilian (PCL-C) and the Difficulties in Emotional Regulation Scale (DERS). PCL-C scores were reduced by 51.99% ± 27.24% overall, from a mean of 54.29 ± 19.34 pretreatment to 24.86 ± 17.43 posttreatment (p < .001). Of the 14, 8 showed an improvement of >50%. DERS scores improved by 36.02% ± 24.24% overall, from 140.00 ± 22.09 at pretreatment to 89.29 ± 38.31 at posttreatment (p < .001). OF the 14 subjects, 5 achieved >50% improvement. These data may suggest that DMPFC-rTMS could be helpful in the treatment of PTSD in some ED patients., (© 2017 Wiley Periodicals, Inc.)

Network connectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has revealed the contribution of distinct cerebellar lobules to an array of brain wide networks sub-serving motor and cognitive processes. As distinct cerebellar lobules form relatively accessible nodes of different brain networks, this raises the possibility for site-specific modulation of network connectivity using non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS). Continuous theta burst transcranial magnetic stimulation (cTBS) induces long-lasting inhibition of cortical areas. Although previous studies have shown that cTBS of the lateral cerebellum modulates motor cortical excitability and improves symptoms in several movement disorders, the effect on cognitive domains has not been examined. We explored the immediate effects of cTBS in a sham-controlled study on the strength of intrinsic functional connectivity between cerebellar and cortical motor and cognitive regions in 12 participants. Lateral cerebellar cTBS significantly decreased functional connectivity with frontal and parietal cognitive regions, while connectivity with motor regions remained unaltered. Sham stimulation had no effect on either motor or cognitive connectivity. These results show that inhibitory cerebellar stimulation reduces intrinsic functional connectivity between different cortical areas, in keeping with the known connectivity pattern of the cerebellum. The results highlight the plasticity of cerebello-cerebral networks and indicate for the first time that this functional connectivity can be downregulated using an inhibitory neurostimulation paradigm. This may shed light on the pathophysiology of network dysfunction and is a potential treatment for cognitive and movement disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Major depressive disorder (MDD) and substance use disorders (SUDs) are prevalent, disabling, and challenging illnesses for which new treatment options are needed, particularly in comorbid cases. Neuroimaging studies of the functional architecture of the brain suggest common neural substrates underlying MDD and SUDs. Intrinsic brain activity is organized into a set of functional networks, of which two are particularly relevant to psychiatry. The salience network (SN) is crucial for cognitive control and response inhibition, and deficits in SN function are implicated across a wide variety of psychiatric disorders, including MDD and SUDs. The ventromedial network (VMN) corresponds to the classic reward circuit, and pathological VMN activity for drug cues/negative stimuli is seen in SUDs/MDD. Noninvasive brain stimulation (NIBS) techniques, including rTMS and tDCS, have been used to enhance cortico-striatal-thalamic activity through the core SN nodes in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and anterior insula. Improvements in both MDD and SUD symptoms ensue, including in comorbid cases, via enhanced cognitive control. Inhibition of the VMN also appears promising in preclinical studies for quenching the pathological incentive salience underlying SUDs and MDD. Evolving techniques may further enhance the efficacy of NIBS for MDD and SUD cases that are unresponsive to conventional treatments., (© 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.)

Obsessive-compulsive disorder (OCD) is a disabling illness with high rates of nonresponse to conventional treatments. OCD pathophysiology is believed to involve abnormalities in cortico-striatal-thalamic-cortical circuits through regions such as dorsomedial prefrontal cortex (dmPFC) and ventral striatum. These regions may constitute therapeutic targets for neuromodulation treatments, such as repetitive transcranial magnetic stimulation (rTMS). However, the neurobiological predictors and correlates of successful rTMS treatment for OCD are unclear. Here, we used resting-state functional magnetic resonance imaging (fMRI) to identify neural predictors and correlates of response to 20-30 sessions of bilateral 10 Hz dmPFC-rTMS in 20 treatment-resistant OCD patients, with 40 healthy controls as baseline comparators. A region of interest in the dmPFC was used to generate whole-brain functional connectivity maps pre-treatment and post treatment. Ten of 20 patients met the response criteria (⩾50% improvement on Yale-Brown Obsessive-Compulsive Scale, YBOCS); response to dmPFC-rTMS was sharply bimodal. dmPFC-rTMS responders had higher dmPFC-ventral striatal connectivity at baseline. The degree of reduction in this connectivity, from pre- to post-treatment, correlated to the degree of YBOCS symptomatic improvement. Baseline clinical and psychometric data did not predict treatment response. In summary, reductions in fronto-striatal hyperconnectivity were associated with treatment response to dmPFC-rTMS in OCD. This finding is consistent with previous fMRI studies of deep brain stimulation in OCD, but opposite to previous reports on mechanisms of dmPFC-rTMS in major depression. fMRI could prove useful in predicting the response to dmPFC-rTMS in OCD.

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

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.

Background: Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain's emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes., Methods: Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode., Results: Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region., Conclusions: The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)

Despite its high toll on society, there has been little recent improvement in treatment efficacy for major depressive disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting-state functional connectivity predicted response to treatment with repetitive transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty-five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting-state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal, and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased subgenual cingulate cortex-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.