Over 350 million people worldwide suffer from depression, a third of whom are medication resistant. Seizure therapy remains the most
effective treatment in depression, even when many treatments fail. The utility of seizure therapy is limited due to its cognitive side effects and stigma. The biological targets of seizure therapy remain unknown, hindering design of new treatments with comparable
efficacy. Seizures
impact the brains temporal dynamicity observed through
electroencephalography. This dynamicity reflects richness of
information processing across distributed brain networks subserving affective and cognitive processes. We investigated the
hypothesis that seizure therapy impacts
mood (
depressive symptoms) and
cognition by modulating brain temporal dynamicity. We obtained resting-state EEG from thirty-four patients (age=46.0±14.0, 21 females) receiving two types of seizure treatments—electroconvulsive therapy or magnetic seizure therapy. We employed multi-scale entropy to quantify the complexity of brain's temporal dynamics before and after seizure therapy. We discovered that reduction of complexity in fine time scales underlined successful therapeutic response to both seizure treatments. Greater reduction in complexity of fine time scales in parieto-occipital and central brain regions was significantly linked with greater improvement in
depressive symptoms. Greater increase in complexity of coarse time scales was associated with greater decline in
cognition including the autobiographical memory. These findings were region- and time-scale specific. That is, change in complexity in occipital regions (e.g., O2
electrode or right occipital pole) at fine time-scales was only associated with change in
depressive symptoms, and not change in
cognition, and change in complexity in parieto-central regions (e.g., Pz
electrode or intra and transparietal sulcus) at coarser time-scale was only associated with change in cognition, and not depressive symptoms. Finally, region and time-scale specific changes in complexity classified both
antidepressant and cognitive response to seizure therapy with good (80%) and excellent (95%) accuracy, respectively. In this study, we discovered a novel
biological target of seizure therapy; complexity of the brain resting-state dynamics. Region and time-
scale dependent changes in complexity of the brain resting-state dynamics is a novel mechanistic marker of response to seizure therapy that explains both the
antidepressant response and cognitive changes associated with this treatment. This marker has tremendous potential to guide design of the new generation of
antidepressant treatments.