Evaluating Cognitive and Affective Changes after Responsive Neurostimulation of the Centromedian Thalamus

Responsive electrical stimulation of the centromedian nucleus of the thalamus (CMN) is an emerging therapy for reducing seizures in individuals with multifocal or generalized drug-resistant epilepsy (DRE). Prior studies have reported significant neuropsychiatric side effects associated with thalamic stimulation, particularly in the anterior nucleus of the thalamus. Despite its growing popularity, little is known about the effects of CMN stimulation on neurocognitive and mood outcomes. To address this knowledge gap, we performed a retrospective analysis of patients who underwent responsive neurostimulation (RNS) of the CMN at our institution.

We identified 8 patients with multifocal or unresectable focal DRE who participated in a comprehensive evaluation before and ∼12 months after surgery to implant an RNS device. Neuropsychological testing spanned multiple functional domains (i.e., attention and working memory, learning, retrieval, phonemic fluency, semantic fluency, motor dexterity, mood, and anxiety), and 9 distinct functional metrics were analyzed.

In this small retrospective cohort, closed-loop stimulation of the CMN was associated with modest improvements in verbal learning and retrieval and a slight decline in phonemic verbal fluency. Although there was no robust group-level effect on mood, the proportion of patients with clinically significant depression decreased from 43% before stimulation to 0% at last follow-up and from 71% to 57% for clinically significant anxiety. Our analyses did not identify changes in attention and working memory, semantic fluency, or motor dexterity.

Our results suggest that closed-loop CMN stimulation was not associated with major adverse cognitive or affective changes over 12 months.