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Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study.

ABSTRACT: Intermittent theta burst stimulation (iTBS) is a novel treatment approach for post-traumatic stress disorder (PTSD), and recent neuroimaging work indicates that functional connectivity profiles may be able to identify those most likely to respond. However, prior work has relied on functional magnetic resonance imaging, which is expensive and difficult to scale. Alternatively, electroencephalography (EEG) represents a different approach that may be easier to implement in clinical practice. To this end, we acquired an 8-channel resting-state EEG signal on participants before (n?=?47) and after (n?=?43) randomized controlled trial of iTBS for PTSD (ten sessions, delivered at 80% of motor threshold, 1,800 pulses, to the right dorsolateral prefrontal cortex). We used a cross-validated support vector machine (SVM) to track changes in EEG functional connectivity after verum iTBS stimulation. We found that an SVM classifier was able to successfully separate patients who received active treatment vs. sham treatment, with statistically significant findings in the Delta band (1-4 Hz, p?=?0.002). Using Delta coherence, the classifier was 75.0% accurate in detecting sham vs. active iTBS, and observed changes represented an increase in functional connectivity between midline central/occipital and a decrease between frontal and central regions. The primary limitations of this work are the sparse electrode system and a modest sample size. Our findings raise the possibility that EEG and machine learning may be combined to provide a window into mechanisms of action of TMS, with the potential that these approaches can inform the development of individualized treatment methods.

SUBMITTER: Zandvakili A

PROVIDER: S-EPMC7867551 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study.

Zandvakili Amin A Swearingen Hannah R HR Philip Noah S NS

European archives of psychiatry and clinical neuroscience 20200727 1

Intermittent theta burst stimulation (iTBS) is a novel treatment approach for post-traumatic stress disorder (PTSD), and recent neuroimaging work indicates that functional connectivity profiles may be able to identify those most likely to respond. However, prior work has relied on functional magnetic resonance imaging, which is expensive and difficult to scale. Alternatively, electroencephalography (EEG) represents a different approach that may be easier to implement in clinical practice. To thi ...[more]

PMID: 32719969

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Project description:OBJECTIVE:Posttraumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder associated with disruption in social and occupational function. Transcranial magnetic stimulation (TMS) represents a novel approach to PTSD, and intermittent theta-burst stimulation (iTBS) is a new, more rapid administration protocol with data supporting efficacy in depression. The authors conducted a sham-controlled study of iTBS for PTSD. METHODS:Fifty veterans with PTSD received 10 days of sham-controlled iTBS (1,800 pulses/day), followed by 10 unblinded sessions. Primary outcome measures included acceptability (retention rates), changes in PTSD symptoms (clinician- and self-rated), quality of life, social and occupational function, and depression, obtained at the end of 2 weeks; analysis of variance was used to compare active with sham stimulation. Secondary outcomes were evaluated 1 month after treatment, using mixed-model analyses. Resting-state functional MRI was acquired at pretreatment baseline on an eligible subset of participants (N=26) to identify response predictors. RESULTS:Retention was high, side effects were consistent with standard TMS, and blinding was successful. At 2 weeks, active iTBS was significantly associated with improved social and occupational function (Cohen's d=0.39); depression was improved with iTBS compared with the sham treatment (d=-0.45), but the difference fell short of significance, and moderate nonsignificant effect sizes were observed on self-reported PTSD symptoms (d=-0.34). One-month outcomes, which incorporated data from the unblinded phase of the study, indicated superiority of active iTBS on clinician- and self-rated PTSD symptoms (d=-0.74 and -0.63, respectively), depression (d=-0.47), and social and occupational function (d=0.93) (all significant). Neuroimaging indicated that clinical improvement was significantly predicted by stronger (greater positive) connectivity within the default mode network and by anticorrelated (greater negative) cross-network connectivity. CONCLUSIONS:iTBS appears to be a promising new treatment for PTSD. Most clinical improvements from stimulation occurred early, which suggests a need for further investigation of optimal iTBS time course and duration. Consistent with previous neuroimaging studies of TMS, default mode network connectivity played an important role in response prediction.

Project description:BackgroundDepression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment-a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses.ObjectiveThe aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment.MethodsThe study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity.ResultsRecruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023.ConclusionsThis trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients.Trial registrationISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644.International registered report identifier (irrid)DERR1-10.2196/31925.

Dataset Information

Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study.

Publications

Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study.

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