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    Connectivity-guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistent moderate to severe depression: Magnetic resonance imaging protocol and SARS-CoV-2-induced changes for a randomized double-blind controlled trial

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    Author
    Briley, Paul M.
    Kaylor-Hughes, Catherine
    Shalabi, Abdulrhman
    Liddle, Peter F.
    Morriss, Richard K.
    Keyword
    Depression
    Magnetic resonance imaging
    Transcranial magnetic stimulation
    Date
    2022
    
    Metadata
    Show full item record
    DOI
    10.2196/31925
    Publisher's URL
    https://www.researchprotocols.org/2022/1/e31925
    Abstract
    Background: Depression 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. Objective: The 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. Methods: The 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. Results: Recruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023. Conclusions: This 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.
    Citation
    Pszczolkowski, S., Cottam, W. J., Briley, P. M., Iwabuchi, S. J., Kaylor-Hughes, C., Shalabi, A., Babourina-Brooks, B., Berrington, A., Barber, S., Di Paolo, A. S., et al. (2022). Connectivity-guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistent moderate to severe depression: Magnetic resonance imaging protocol and SARS-CoV-2-induced changes for a randomized double-blind controlled trial. JMIR Research Protocols, 11(1), pp.e31925.
    Type
    Article
    URI
    http://hdl.handle.net/20.500.12904/15322
    Collections
    Depression

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      To have and to hold: An exploratory qualitative study exploring why research participants with treatment-resistant depression undergoing transcranial magnetic stimulation treatment requested copies of their research brain MRI scans

      Webster, Lucy; Boutry, Clement; Morriss, Richard K. (2023)
      PURPOSE: There has been little research providing an in-depth exploration of the reasons behind research participants, particularly in mental health settings, requesting copies of their research data, such as magnetic resonance imaging (MRI) scans. BRIGhTMIND is a large double blind randomised controlled trial using functional and structural magnetic resonance imaging to create personalised targets for transcranial magnetic stimulation delivery, and a number of trial participants requested copies of these scans. METHODS: Seven participants involved in the BRIGhTMIND trial completed semi-structured interviews exploring their reasons behind their request for copies of their MRI scans. The qualitative data was co-analysed between researchers and patient and public involvement and engagement representatives using inductive thematic analysis. RESULTS: The interviews produced consistent themes concerning curiosity to visualise their MRI scans, and the hope that their participation would result in a better understanding of the nature and future treatment of depression. Concerns around the rights to access their own personal health data emerged as a clear theme as did their own ability to interpret any radiological information. DISCUSSION: This study provides insight into the reasons why research participants with depression would like to retain copies of their MRI scans and the perceived role that such techniques may have for improving research and neuromodulation treatments in depression. Such first-hand experiential accounts emphasises the importance of listening to participants perspectives and lived experience, in order to improve research and health outcomes. Future research could aim to provide greater verbal and written information for participants, including details about the accessibility to their MRI scans, the difference between research and clinical MRI scans, and educational materials to help with the interpretation of MRI images.
    • Thumbnail

      Variability of noninvasive MRI and biological markers in compensated cirrhosis: Insights for assessing disease progression

      Bradley, Christopher R.; Cox, Eleanor F.; Palaniyappan, Naaventhan; Aithal, Guruprasad P.; Francis, Susan T.; Guha, Indra Neil (2022)
      BACKGROUND: We annually monitored stable compensated cirrhosis (CC) patients to evaluate serial variation in blood serum, liver stiffness, and multiparametric magnetic resonance imaging (mpMRI) measures to provide reference change values (RCV) and sample size measures for future studies. METHODS: Patients were recruited from a prospectively followed CC cohort, with assessments at baseline and annually over three years. We report on blood markers, transient elastography liver stiffness measures (LSM) and noninvasive mpMRI (volume, T1 mapping, blood flow, perfusion) of the liver, spleen, kidneys, and heart in a stable CC group and a healthy volunteer (HV) group. Coefficient of variation over time (CoVT) and RCV are reported, along with hazard ratio to assess disease progression. Sample size estimates to power future trials of cirrhosis regression on mpMRI are presented. RESULTS: Of 60 CC patients enrolled, 28 with stable CC were followed longitudinally and compared to 10 HVs. CoVT in mpMRI measures was comparable between CC and HV groups. CoVT of Enhanced Liver Fibrosis score was low ( of Enhanced Liver Fibrosis score was low (T (20.7%) and RCV (48.3%) were observed for LSM. CoVT and RCV were low for liver, spleen, and renal T1 values (CoVT T T 12-25%, RCV 16-47%). CONCLUSIONS: Evidence of low CoVT and RCV in multiorgan T1 values. RCV and sample size estimates are provided for future longitudinal multiorgan monitoring in CC patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02037867 , Registered: 05/01/2013. Copyright © 2022. The Author(s) under exclusive licence to European Society of Radiology.
    • Thumbnail

      Magnetic resonance imaging connectivity features associated with response to transcranial magnetic stimulation in major depressive disorder

      Briley, Paul M.; Webster, Lucy; Liddle, Peter F.; Morriss, Richard K. (2024-06-17)
      Transcranial magnetic stimulation (TMS) is an FDA-approved neuromodulation treatment for major depressive disorder (MDD), thought to work by altering dysfunctional brain connectivity pathways, or by indirectly modulating the activity of subcortical brain regions. Clinical response to TMS remains highly variable, highlighting the need for baseline predictors of response and for understanding brain changes associated with response. This systematic review examined brain connectivity features, and changes in connectivity features, associated with clinical improvement following TMS in MDD. Forty-one studies met inclusion criteria, including 1097 people with MDD. Most studies delivered one of two types of TMS to left dorsolateral prefrontal cortex and measured connectivity using resting-state functional MRI. The subgenual anterior cingulate cortex was the most well-studied brain region, particularly its connectivity with the TMS target or with the "executive control network" of brain regions. There was marked heterogeneity in findings. There is a need for greater understanding of how cortical TMS modulates connectivity with, and the activity of, subcortical regions, and how these effects change within and across treatment sessions.
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