Pharmacotherapies are the most common first-line treatment for depression; however, drugs are not always effective, perhaps because they may not target discrete brain areas or brain circuits. Thus, there is growing interest in refining neurostimulation techniques to treat mental disorders. Neurostimulation has been used to treat depression for many years; electroconvulsive therapy (ECT) has been used since the 1700s and is among the most consistently effective treatments for severe depression, with reported response rates up to 80%. However, electrical current delivered during ECT is relatively high – enough to elicit generalized seizures in treated patients. Thus, despite the fact that ECT is generally well-tolerated, it nevertheless causes unwanted side effects. Transcranial direct current stimulation (tDCS) is an attractive alternative, because it is orders of magnitude more affordable to administer than ECT, DBS, or TMS, and has an excellent safety profile. Several studies have shown tDCS to be effective in reducing the symptoms of depression, though results are variable and effects are not always long-lasting.1,2 Despite promising clinical results, a large knowledge gap remains. In our study, we use fMRI to understand how tDCS affects brain activity. Specifically, we acquire functional connectivity data simultaneously with tDCS of the dorsolateral prefrontal cortex (DLPFC) in patients with major depressive disorder (MDD) and in demographically similar healthy controls. Our two main goals are to: 1. Elucidate the mechanism of action of DLPFC-tDCS therapy for MDD by measuring the effects of tDCS on intrinsic brain-network connectivity in real time using simultaneous tDCS and fMRI. 2. Develop strategies for MRI-guided tDCS therapy by determining the extent to which standard tDCS electrode placement varies with respect to subject-specific neuroanatomy and corresponding brain circuits using high-resolution connectivity MRI. The dorsolateral prefrontal cortex (DLPFC) is common target for tDCS research of depression using a relatively large stimulation/anodal electrode (35cm2) to increase cortical excitability in this region. Stimulation of DLPFC in this manner is thought to restore this hypo-responsive region in depressed patients, allowing DLPFC to exert top-down control of hyper-active ventral limbic regions. However, the evidence to support this is sparse; indeed, it is unclear what effect DLPFC-tDCS has on brain function. With this proposed research, we hope to both better understand and improve this promising and relatively new neurostimulation therapy.
|Effective start/end date||10/1/18 → 1/14/21|
- Brain & Behavior Research Foundation (Agmt 11/28/18)
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