Rewiring the Brain

Abstract

Depressive disorders are a group of debilitating and at times life-threatening diseases affecting millions of individuals worldwide. They interfere with most aspects of everyday life, such as social behavior, affective experiences, and cognition. As our understanding of the disorder increases, available treatments change or are being refined. Five studies are presented that address the effect of brain stimulation treatment on cognitive performance (Studies 1 and 2), altered processing of touch as a measure of social reward (Study 3), a novel and individualized parieto-hippocampal target for intermittent theta-burst stimulation (iTBS; Study 4), and a composition of clinical trials investigating non-invasive brain stimulation for treatment refractoriness (Study 5) in patients with major depressive disorder (MDD). Contrary to expectations, the results of study 1 suggest a positive impact of increasing electroconvulsive therapy (ECT) treatments on verbal fluency performance in the bitemporally treated group while a decrease in performance was observed in the right-unilaterally treated group. As we found no evidence of cognitive impairment associated with bitemporal electrode placement in any cognitive domain, we recommend a standardized battery of robust cognitive measures with strong psychometrics and minimal subject burden to facilitate multisite investigation. As digital tracking of all ECT data has recently become available, we also present research on the role of treatment stimulus charge on cognitive performance. As hypothesized, we show that increased stimulus charge predicts decreased delayed memory performance after ECT treatment, independent of age and number of treatments applied. Comparison of this effect with other cognitive domains assessed indicates that this finding is specific to delayed memory recall (Study 2). However, this result should be replicated in a larger sample. As depressive disorders are well known to impede social functioning, we show that the perceived pleasantness of social touch is decreased in patients with depression when compared to healthy controls and that their neural processing is altered (Study 3). These effects indicate altered reward-dependent processing of social touch in MDD. Moreover, in the context of personalizing depression treatments, a novel target for iTBS is evaluated for its clinical potential (Study 4). After individual selection of a target in the parietal cortex most strongly functionally connected to the hippocampus, antidepressant iTBS treatment was augmented with this 6 novel parieto-hippocampal stimulation. Although we found no stronger clinical response in patients randomized to receive the novel target stimulation, increased functional connectivity between the hippocampus and the dorsolateral-prefrontal cortex was significant. This finding may be clinically relevant in conditions associated with prefrontal-hippocampal dysconnectivity. Lastly, by reexamining the study composition of a meta-analysis investigating the efficacy and acceptability of non-invasive brain stimulation for the treatment of adult unipolar and bipolar depression, we showed that most trials include only patients with higher levels of treatment-refractoriness (Study 5). In light of the different compositions of clinical trials regarding this characteristic between evidence-based treatment options, more studies investigating the potential of repetitive transcranial magnetic stimulation in patients with lower degrees of treatment refractoriness are needed