Prabhjot Dhami1,2,3, Sravya Atluri2,3,4, Jonathan Lee2,3,5, Yuliya Knyahnytska2,6, Paul E Croarkin7, Daniel M Blumberger2,3,6, Zafiris J Daskalakis2,3,6, Faranak Farzan1,2,3,6. 1. eBrain Lab, School of Mechatronic Systems Engineering, Faculty of Applied Science, Simon Fraser University, Surrey, British Columbia, Canada. 2. Temerty Centre for Therapeutic Brain Intervention, General Adult Psychiatry and Health Systems Division, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 3. Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. 4. Institute of Biomaterial and Biomedical Engineering, Faculty of Applied Science & Engineering, University of Toronto, Toronto, Ontario, Canada. 5. Neuromodulation Division, Department of Psychiatry and Biobehavioral Sciences, TMS Clinical and Research Program, Semel Institute for Neuroscience and Human Behavior at UCLA, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. 6. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 7. Mayo Clinic Depression Center, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
BACKGROUND: Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated. METHODS: Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16-24 years old). In 16 age-matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS-evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting-state functional magnetic resonance imaging (fMRI) data was also collected at baseline. RESULTS: Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC. CONCLUSIONS: TMS-probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre-treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population.
BACKGROUND: Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated. METHODS: Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16-24 years old). In 16 age-matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS-evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting-state functional magnetic resonance imaging (fMRI) data was also collected at baseline. RESULTS: Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC. CONCLUSIONS: TMS-probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre-treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population.
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