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Artikel ; Online: Differential symptom cluster responses to repetitive transcranial magnetic stimulation treatment in depressionResearch in context

Tyler S. Kaster / Jonathan Downar / Fidel Vila-Rodriguez / Danielle A. Baribeau / Kevin E. Thorpe / Zafiris J. Daskalakis / Daniel M. Blumberger

EClinicalMedicine, Vol 55, Iss , Pp 101765- (2023)

1480

Abstract: Summary: 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 ... ...

Abstract	Summary: 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 objectives for this work were to determine: (1) whether a standard depression measure can be represented using a four symptom cluster model and (2) whether these symptom clusters had a differential response to rTMS treatment. Methods: Data were obtained from two multi-centre randomized controlled trials of rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC) for participants with treatment-resistant depression (TRD) conducted in Canada (THREE-D [Conducted between Sept 2013, and Oct 2016] and CARTBIND [Conducted between Apr 2016 and Feb 2018]). The first objective used confirmatory factor analytic techniques, and the second objective used a linear mixed effects model. Trial Registration: NCT01887782, NCT02729792. Findings: In the total sample of 596 participants with TRD, we found a model consisting of four symptom clusters adequately fit the data. The primary analysis using the THREE-D treatment trial found that symptom clusters demonstrated a differential response to rTMS treatment (F(3,5984) = 31.92, p < 0.001). The anxiety symptom cluster was significantly less responsive to treatment than other symptom clusters (t(6001) = -8.02, p < 0.001). These findings were replicated using data from the CARTBIND trial. Interpretation: There are distinct symptom clusters experienced by individuals with TRD that have a differential response to rTMS. Future work will determine whether differing rTMS treatment targets have distinct patterns of symptom cluster responses with the eventual goal of personalizing rTMS protocols based on an individual's clinical presentation. Funding: Canadian Institutes of Health Research, Brain Canada.
Schlagwörter	Depressive disorders ; Repetitive transcranial magnetic stimulation ; Cluster analysis ; Treatment outcomes ; Medicine (General) ; R5-920
Thema/Rubrik (Code)	150
Sprache	Englisch
Erscheinungsdatum	2023-01-01T00:00:00Z
Verlag	Elsevier
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of major depressive disorder

Alisson P. Trevizol / Jonathan Downar / Fidel Vila-Rodriguez / Kevin E. Thorpe / Zafiris J. Daskalakis, Prof / Daniel M. Blumberger

EClinicalMedicine, Vol 22, Iss , Pp - (2020)

An analysis from the randomised non-inferiority THREE-D trial

2020

Abstract: 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 ... ...

Abstract	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. Methods: Data from a large randomised non-inferiority trial comparing standard 10 Hz and intermittent theta burst stimulation (iTBS) for the treatment of MDD were used for the exploratory analyses. Individual variables were assessed for their association with remission and then included in a logistic regression model to determine odds ratios (OR) and corresponding 95% confidence intervals. Model discrimination (internal validation) was carried out to assess model optimism using the c-index. ClinicalTrials.gov identifier: NCT01887782. Findings: 388 subjects were included in the analysis (199-iTBS and 189-10 Hz, respectively). Higher baseline severity of both depressive and anxiety symptoms were associated with a lower chance of achieving remission (OR=0.64, 95% CI 0.46–0.88; and 0.78, 95% CI 0·60–0.98, respectively). Current employment was a positive predictor for remission (OR=1.69, 95% CI 1.06–2.7), while greater number of treatment failures was associated with lower odds of achieving remission (OR=0.51, 95% CI 0.27–0.98). A non-linear effect of age and remission was observed. An analysis to allow an estimate of the probability of remission using all variables was assessed. The c-index for the fitted model was 0.687. Interpretation: Our results suggest that measuring depression symptom severity, employment status, and refractoriness are important in prognosticating outcome to a course of rTMS in MDD. Funding: Canadian Institutes of Health Research MOP-136801.
Schlagwörter	Repetitive transcranial magnetic stimulation ; Intermittent theta burst stimulation ; Major depressive disorder ; Brain stimulation ; Medicine (General) ; R5-920
Thema/Rubrik (Code)	310 ; 150
Sprache	Englisch
Erscheinungsdatum	2020-05-01T00:00:00Z
Verlag	Elsevier
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression

Andrew B Mendlowitz / Alaa Shanbour / Jonathan Downar / Fidel Vila-Rodriguez / Zafiris J Daskalakis / Wanrudee Isaranuwatchai / Daniel M Blumberger

PLoS ONE, Vol 14, Iss 9, p e

A cost analysis.

2019 Band 0222546

Abstract: Background Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for depression that is increasingly implemented in healthcare systems across the world. A new form of rTMS called intermittent theta burst stimulation (iTBS) ... ...

Abstract	Background Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for depression that is increasingly implemented in healthcare systems across the world. A new form of rTMS called intermittent theta burst stimulation (iTBS) can be delivered in 3 min and has demonstrated comparable effectiveness to the conventional 37.5 min 10Hz rTMS protocol in patients with depression. Objectives To compare the direct treatment costs per course and per remission for iTBS compared to 10Hz rTMS treatment in depression. Methods We conducted a cost analysis from a healthcare system perspective using patient-level data from a large randomized non-inferiority trial (THREE-D). Depressed adults 18 to 65 received either 10Hz rTMS or iTBS treatment. Treatment costs were calculated using direct healthcare costs associated with equipment, coils, physician assessments and technician time over the course of treatment. Cost per remission was estimated using the proportion of patients achieving remission following treatment. Deterministic sensitivity analyses and non-parametric bootstrapping was used to estimate uncertainty. Results From a healthcare system perspective, the average cost per patient was USD$1,108 (SD 166) for a course of iTBS and $1,844 (SD 304) for 10Hz rTMS, with an incremental net savings of $735 (95% CI 688 to 783). The average cost per remission was $3,695 (SD 552) for iTBS and $6,146 (SD 1,015) for 10Hz rTMS, with an average incremental net savings of $2,451 (95% CI 2,293 to 2,610). Conclusions The shorter session durations and treatment capacity increase associated with 3 min iTBS translate into significant cost-savings per patient and per remission when compared to 10Hz rTMS.
Schlagwörter	Medicine ; R ; Science ; Q
Thema/Rubrik (Code)	616
Sprache	Englisch
Erscheinungsdatum	2019-01-01T00:00:00Z
Verlag	Public Library of Science (PLoS)
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Unanticipated rapid remission of refractory bulimia nervosa, during high-dose repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex

JonathanDownar / AshwinSankar / BlakeWoodside

Frontiers in Psychiatry, Vol

a case report

2012 Band 3

Abstract: A woman with severe, refractory bulimia nervosa underwent treatment for comorbid depression using repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (DMPFC) using a novel technique. Unexpectedly, she showed a rapid, ... ...

Abstract	A woman with severe, refractory bulimia nervosa underwent treatment for comorbid depression using repetitive transcranial magnetic stimulation (rTMS) of the dorsomedial prefrontal cortex (DMPFC) using a novel technique. Unexpectedly, she showed a rapid, dramatic remission from bulimia nervosa. For 5 months pre-treatment, she had reported two 5-hour binge-purge episodes per day. After rTMS session 2 the episodes stopped entirely for 1 week; after session 10 there were no further recurrences. Depression scores improved more gradually to remission at session 10. Full remission from depression and binge-eating/purging episodes was sustained more than 2 months after treatment completion. In neuroimaging studies, the DMPFC is important in impulse control, and is underactive in bulimia nervosa. DMPFC-rTMS may have enhanced the patient’s ability to deploy previously acquired strategies to avoid binge-eating and purging via a reduction in her impulsivity. A larger sham-controlled trial of DMPFC-rTMS for binge-eating and purging behavior may be warranted.
Schlagwörter	Anorexia ; Bulimia ; Depression ; impulsivity ; prefrontal ; rTMS ; dorsomedial ; transcranial ; Psychiatry ; RC435-571 ; Neurology. Diseases of the nervous system ; RC346-429 ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Internal medicine ; RC31-1245 ; Medicine ; R
Thema/Rubrik (Code)	150
Sprache	Englisch
Erscheinungsdatum	2012-04-01T00:00:00Z
Verlag	Frontiers
Dokumenttyp	Artikel ; Online
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Artikel ; Online: Neural correlates of effective learning in experienced medical decision-makers.

Jonathan Downar / Meghana Bhatt / P Read Montague

PLoS ONE, Vol 6, Iss 11, p e

2011 Band 27768

Abstract: Accurate associative learning is often hindered by confirmation bias and success-chasing, which together can conspire to produce or solidify false beliefs in the decision-maker. We performed functional magnetic resonance imaging in 35 experienced ... ...

Abstract	Accurate associative learning is often hindered by confirmation bias and success-chasing, which together can conspire to produce or solidify false beliefs in the decision-maker. We performed functional magnetic resonance imaging in 35 experienced physicians, while they learned to choose between two treatments in a series of virtual patient encounters. We estimated a learning model for each subject based on their observed behavior and this model divided clearly into high performers and low performers. The high performers showed small, but equal learning rates for both successes (positive outcomes) and failures (no response to the drug). In contrast, low performers showed very large and asymmetric learning rates, learning significantly more from successes than failures; a tendency that led to sub-optimal treatment choices. Consistently with these behavioral findings, high performers showed larger, more sustained BOLD responses to failed vs. successful outcomes in the dorsolateral prefrontal cortex and inferior parietal lobule while low performers displayed the opposite response profile. Furthermore, participants' learning asymmetry correlated with anticipatory activation in the nucleus accumbens at trial onset, well before outcome presentation. Subjects with anticipatory activation in the nucleus accumbens showed more success-chasing during learning. These results suggest that high performers' brains achieve better outcomes by attending to informative failures during training, rather than chasing the reward value of successes. The differential brain activations between high and low performers could potentially be developed into biomarkers to identify efficient learners on novel decision tasks, in medical or other contexts.
Schlagwörter	Medicine ; R ; Science ; Q
Thema/Rubrik (Code)	150
Sprache	Englisch
Erscheinungsdatum	2011-01-01T00:00:00Z
Verlag	Public Library of Science (PLoS)
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Increases in frontostriatal connectivity are associated with response to dorsomedial repetitive transcranial magnetic stimulation in refractory binge/purge behaviors

Katharine Dunlop / Blake Woodside / Eileen Lam / Marion Olmsted / Patricia Colton / Peter Giacobbe / Jonathan Downar

NeuroImage: Clinical, Vol 8, Iss C, Pp 611-

2015 Band 618

Abstract: 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 ...

Abstract	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.
Schlagwörter	Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Thema/Rubrik (Code)	150
Sprache	Englisch
Erscheinungsdatum	2015-01-01T00:00:00Z
Verlag	Elsevier
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Precision non-implantable neuromodulation therapies

Lucas Borrione / Helena Bellini / Lais Boralli Razza / Ana G. Avila / Chris Baeken / Anna-Katharine Brem / Geraldo Busatto / Andre F. Carvalho / Adam Chekroud / Zafiris J. Daskalakis / Zhi-De Deng / Jonathan Downar / Wagner Gattaz / Colleen Loo / Paulo A. Lotufo / Maria da Graça M. Martin / Shawn M. McClintock / Jacinta O’Shea / Frank Padberg /

Ives C. Passos / Giovanni A. Salum / Marie-Anne Vanderhasselt / Renerio Fraguas / Isabela Benseñor / Leandro Valiengo / Andre R. Brunoni

Brazilian Journal of Psychiatry, Vol 42, Iss 4, Pp 403-

a perspective for the depressed brain

2020 Band 419

Abstract: 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 ... ...

Abstract	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 transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more “precision-oriented” practice.
Schlagwörter	Major depressive disorder ; transcranial magnetic stimulation ; transcranial direct current stimulation ; electroconvulsive therapy ; precision medicine ; Psychiatry ; RC435-571
Thema/Rubrik (Code)	610
Sprache	Englisch
Erscheinungsdatum	2020-03-01T00:00:00Z
Verlag	Associação Brasileira de Psiquiatria (ABP)
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Artikel ; Online: Functional neuroimaging of conversion disorder

Matthew J. Burke, MD / Omar Ghaffar, MD, MSc / W. Richard Staines, PhD / Jonathan Downar, MD, PhD / Anthony Feinstein, MD, MPhil, PhD

NeuroImage: Clinical, Vol 6, Iss C, Pp 333-

The role of ancillary activation

2014 Band 339

Abstract: Background: Previous functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to ... ...

Abstract	Background: Previous functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to better define the functional neuroanatomical correlates of conversion disorder. Methods: Ten subjects meeting clinical criteria for unilateral sensory conversion disorder underwent fMRI during which a vibrotactile stimulus was applied to anesthetic and sensate areas. A block design was used with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times. Event-related group averages of the BOLD response were compared between conditions. Results: All subjects were right-handed females, with a mean age of 41. Group analyses revealed 10 areas that had significantly greater activation (p < .05) when stimulation was applied to the anesthetic body part compared to the contralateral sensate mirror region. They included right paralimbic cortices (anterior cingulate cortex and insula), right temporoparietal junction (angular gyrus and inferior parietal lobule), bilateral dorsolateral prefrontal cortex (middle frontal gyri), right orbital frontal cortex (superior frontal gyrus), right caudate, right ventral-anterior thalamus and left angular gyrus. There was a trend for activation of the somatosensory cortex contralateral to the anesthetic region to be decreased relative to the sensate side. Conclusions: Sensory conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder.
Schlagwörter	Conversion disorder ; Functional neuroimaging ; Sensory ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
Thema/Rubrik (Code)	150
Sprache	Englisch
Erscheinungsdatum	2014-01-01T00:00:00Z
Verlag	Elsevier
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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