UBC Theses and Dissertations
Neuromodulatory effects of theta burst stimulation, a molecular and functional assessment Aceves Serrano, Lucero Guadalupe
Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a therapeutic tool to alleviate symptoms of neurological and psychiatric disorders. Although the therapeutic potential of rTMS has been widely explored, the neurobiological basis of its effects is still not fully understood. This thesis used in vivo imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) in parallel with post-mortem evaluations to investigate the effects of a clinical course of theta burst stimulation (TBS) – a patterned form of rTMS – at the molecular and functional level in non-human primates (NHP). These techniques were employed to investigate rTMS-induced modulation of dopaminergic and glutamatergic neurotransmission, its effects on brain activity and connectivity, and glial reactivity modulation. Specifically, we evaluated the effects of rTMS in the healthy brain of NHP. Neuroimaging evaluations and cortical excitability assessments were performed before and one day after a clinical course of intermittent (iTBS), continuous (cTBS), or sham stimulation over the left motor cortex. Dopaminergic assessment using PET was also acquired immediately after the first stimulation session. Neurotransmission assessment revealed a decrease in dopamine release in the left and right putamen immediately after cTBS delivery, while no changes in neurotransmission were found in the striatum after multiple cTBS, iTBS, or sham sessions. Functional MRI revealed modulatory effects of cTBS and iTBS, but not sham delivery, between the regions of the cortico-striatal-thalamo-cortical motor loop. We found increased connectivity between the stimulated and the contralateral motor cortex. Furthermore, we found that baseline connectivity measurements were correlated to changes in dopamine release after a single stimulation session. Assessment of metabolic connectivity with PET revealed a brain-wide effect post-iTBS with no effects observed after cTBS and sham delivery. Finally, evaluation of glial reactivity with PET-PBR28 and MRS-myoinositol suggested no significant changes in glial activation after stimulation that would suggest neuroinflammation. Overall, this work suggests TBS induced long lasting changes in cortical excitability, functional and metabolic connectivity in the absence of neuroinflammatory response and lasting changes in striatal dopamine and glutamate.
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