None listed
Conditions
Brief summary
Obesity is a leading contributor to preventable mortality in Australia. While the causes of obesity are multifaceted, epidemiological studies suggest that overconsumption of highly rewarding energy-dense and ultra-processed food is a leading driver of rising obesity rates. Our team has previously shown that obesity is associated with abnormal communication between the brain regions involved in reward responses to food (i.e., the medial prefrontal cortex [mPFC], striatum and insula), and those involved in energy regulation (i.e., the hypothalamus). These regions and their connections have also been linked to food cravings which are a known driver of overconsumption. Therefore, interventions that can modulate neural connectivity between cortico-striatal-hypothalamic regions are promising candidates to reduce food cravings in people with obesity. The connectivity between these brain regions can be modulated using non-invasive brain stimulation, namely a form of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS). rTMS is an FDA approved treatment for depression and is being trialled for multiple psychiatric and neurodegenerative diseases. In this trial we will test if rTMS-cTBS can reduce abnormally increased connections between brain regions involved in food reward responses in obesity. We expect that rTMS-cTBS over the mPFC will reduce abnormally increased connectivity (i.e. neural communication) between the mPFC and regions of the brain reward circuit involved in food cravings.
Interventions
A single-blind, active sham-controlled cross-over design will be used. Participants will undertake two experimental sessions based at the Monash Biomedical Imaging facility, with a six-to-eight day washout period separating these sessions. During each session, participants will receive a single session of continuous theta burst stimulation, a form of non-invasive repetitive transcranial magnetic stimulation (cTBS-rTMS). In each session, participants will either receive real cTBS (active conditio
A single-blind, active sham-controlled cross-over design will be used. Participants will undertake two experimental sessions based at the Monash Biomedical Imaging facility, with a six-to-eight day washout period separating these sessions. During each session, participants will receive a single session of continuous theta burst stimulation, a form of non-invasive repetitive transcranial magnetic stimulation (cTBS-rTMS). In each session, participants will either receive real cTBS (active condition, 45 minute session) or placebo cTBS (sham condition, 45 minute session), with the order of these conditions randomised across participants. Continuous theta burst stimulation will be administered using a figure-of-eight Cool-B65 A/P coil attached to a MagVenture MagPro X100 stimulator (MagVenture, Farum, Denmark). A neuronavigation system will be used to monitor coil placement and personalise the stimulation site based on inter-individual morphological differences (Brainsight, Rogue Research). Resting motor threshold (RMT) will be computed as the minimum stimulator intensity required to evoke a motor evoked potential on 50% of trials from a contralateral hand muscle when stimulating the primary motor cortex. Stimulation will be applied to the left medial prefrontal cortex, using the left frontal pole (Fp1) coordinates detailed in Scrivener et al. (2022) (MNI coordinates: x = -24.54, y = 66.41, z = 11.97) to guide positioning of the coil. Participants will receive two trains of continuous theta burst stimulation over this site, separated by a 10 minute inter-train interval (one train = 40 s; three pulse bursts at 50 Hz repeated at 5 Hz; 600 pulses/train). Stimulation intensity will be set to 70% RMT for each participant, adjusted for scalp-to-cortex distance. Both sessions of rTMS-cTBS will be administered by research staff accredited to operate rTMS-cTBS and who hold a current Provide First Aid certificate. Participants’ adherence to the intervention (i.e., attendance of both sessions) will be recorded using a session attendance form. To assess unintended effects of rTMS-cTBS and awareness of sham/active condition, participants will complete Section IV of the TMSens_Q (Giustiniani et al., 2022). Immediately before and after the stimulation procedure, participants will also receive functional magnetic resonance imaging (fMRI). Specifically, participants will undergo a pre-stimulation scan (45 minutes) and a post-stimulation scan (45 minutes) in each session. During this scan, participants will complete an fMRI compatible food go/no-go task (adapted from He et al., 2015). Giustiniani, A., et al. A questionnaire to collect unintended effects of Transcranial Magnetic Stimulation: A consensus based approach. Clinical Neurophysiology (2022). https://doi.org/10.1016/j.clinph.2022.06.008 He, Q., Xiao, L., Xue, G. et al. Poor ability to resist tempting calorie rich food is linked to altered balance between neural systems involved in urge and self-control. Nutr J 13, 92 (2014). https://doi.org/10.1186/1475-2891-13-92
Sponsors
Turner Institute for Brain and Mental Health
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
• Aged between 18 and 55 years old • Body mass index (BMI) equal to or exceeding 30 kg/m2 • Able to read and converse in English • Weigh less than 200 kg • No current diagnosis of neurological, endocrine, or metabolic disorder affecting brain function
Exclusion criteria
• Body weight of more than 200 kg • Contraindications to brain stimulation identified by the TMS safety screening form, a history of seizures, frequent migraine headaches, or any other diagnosed neurological, endocrine, or metabolic condition affecting brain function • Diagnosis of schizophrenia or psychosis • MRI contraindications indicated by MRI screening procedures • Currently pregnant or breastfeeding • No smartphone device
Outcome results
None listed