Depression Clinical Trial
Official title:
Enhancing Cognition in Patients With Late-Life Depression: A Randomized Controlled Trial of Transcranial Direct Current Stimulation
Late Life Depression (LLD) is a serious health problem which not only causes depressed mood but also results in impairments in memory and attention. These impairments are likely to be resistant to treatment, which increases the chances of developing dementia even after successful treatment of mood.This study is a randomized controlled trial of transcranial Direct Current Stimulation (tDCS) in people with LLD to enhance their cognition after successful treatment of mood with established medications. tDCS is non invasive, relatively inexpensive and portable, and has been found to be safe.This study also serves as a pilot study to assess the effects of tDCS on cognition and neurophysiologic markers of cognition among patients with LLD. Primary study hypothesis is that participants Participants randomized to tDCS will perform better on a working memory task 2 weeks and 3 months following the tDCS course.
tDCS is a non-invasive brain stimulation method that utilizes low intensity electrical
current either to increase cortical excitability with an anodal electrode or to suppress
cortical excitability with a cathodal electrode. tDCS produces its effects through long
lasting changes in neuroplasticity: in animal studies, tDCS results in long-term potentiation
and brain-derived neurotrophic factor secretion; in human studies, tDCS results in
potentiation of neurophysiologic markers of neuroplasticity. Consistent with these
preclinical findings, tDCS to the temporoparietal cortex or left DLPFC improves memory in
patients with mild to moderate Alzheimer disease(AD). tDCS has also been tested among
patients with depression - including by our group - but mainly as a treatment for depressive
symptoms. In one recent large study one session of bilateral anodal tDCS was shown to enhance
working memory among midlife participants with major depression prior to receiving any
treatment. However, it is still not known (1) whether tDCS improves cognition beyond the
partial improvement that is associated with resolution of depressive symptoms; or (2) whether
it has a more fundamental and long lasting effect on cognition.
This trial will assess the acute and long-term effects of a 2-week course of daily (5
days/week) bilateral anodal tDCS of the DLPFC on cognition, and in particular working memory
among 36 patients with LLD. We will recruit and randomize participants who have already been
treated for LLD prior to consenting to the study and who still meet criteria for remission
while on antidepressant medications.
This trial will also be used as a platform to explore the effect of tDCS on neurophysiologic
measures of plasticity during working memory performance. Working memory is supported by
re-entrant circuits, some are local within the DLPFC and others are long-range connecting the
DLPFC to more posterior cortices. These networks result in high and low frequency neuronal
oscillations that can be captured by electroencephalography (EEG). Using novel
neurophysiologic analyses, our group and others have demonstrated that the modulation of
high-frequency (particularly gamma) oscillations by low-frequency (particularly theta)
oscillations - "theta-gamma coupling" - is a neurophysiologic marker of working memory. Thus,
we will explore the effect of tDCS on theta-gamma coupling.
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