Epidural Cortical Stimulation of the Left DLPFC Leads to Dose-Dependent Enhancement of Working Memory in Patients with MDD

Abstract

Background: Cognitive deficits are common across neuropsychiatric disorders, and a primary cause of functional disability. Nevertheless, clinicians have limited therapeutic options to facilitate cognitive enhancement, particularly of executive functions. We present results from a multicenter clinical trial of epidural cortical stimulation in patients with Major Depressive Disorder (MDD). The initial dose determination algorithm revealed acute dose-dependent facilitation of working memory function, suggesting specific therapeutic targets for device-based interventions. Methods: Ten patients with recurrent MDD without psychotic features were enrolled. Electrodes were surgically implanted in the left DLPFC. In order to determine the stimulation parameters, an algorithm was used to assess changes in working memory, mood and anxiety as a function of parametric variations in current amplitude. The Paced Visual Serial Addition Task was used to assess working memory, and Visual Analogue Scales for “Sadness” and “Anxiety”. Data were analyzed using repeated measures ANOVAs. Results: Patients tolerated the intervention well without significant side-effects. We observed a statistically significant relationship between current amplitude and working memory performance (p¼0.020) and reaction times (p¼0.035): higher current led to improved performance and reduced reaction times. We observed a nonsignificant trend for “sadness” and “anxiety”: higher current led to reduced scores for both. Conclusion: These data highlight the relevance of the left DLPFC as a therapeutic target for cognitive enhancement in neuropsychiatric populations. In addition, it confirms the capacity of brain stimulation to improve executive function in compromised patients. Similar strategies may be effective in otherclinical populations with compromised cognition, possibly with noninvasive interventions.