Neuropsychological outcomes from deep brain stimulation—stimulation versus micro-lesion

As one of the most pivotal innovations in neurotherapeutics, deep brain stimulation (DBS) has transformed the treatment of patients with Parkinson’s disease over the last 30 years (1). The most common targets of DBS used to treat symptoms of Parkinson’s disease include the globus pallidus pars internus (GPi), subthalamic nucleus (STN) and to a lesser extent the ventral-intermediate nucleus of the thalamus (VIM). Since the development of STN DBS for Parkinson’s disease in 1993, numerous studies have demonstrated the many motor benefits of stimulation (2,3). DBS of the STN results in lessening motor fluctuations, reduction of dyskinesias by more than 50%, and marked improvements up to 40–60% in OFF symptoms such as tremor, bradykinesia and rigidity, which results in improvement in the patients’ quality of life (4,5). DBS is typically well tolerated but can be associated with side effects. Although reports vary, STN DBS has been associated with multiple areas of cognitive decline, most consistently demonstrated in changes in verbal fluency. In a recent meta-analysis of available data, patients with STN stimulation were found to have mild deficits in psychomotor speed, memory, attention, executive functions, and overall cognition with more moderate declines in both semantic and phonemic verbal fluency (6). The etiology of these cognitive declines is likely multifactorial with a contribution from the underlying neurodegenerative nature of Parkinson’s disease. However, patients with DBS regardless of the target (STN or GPi), show more cognitive decline when compared to patients undergoing treatment with best medical therapy as measured in processing speed, working memory, and other neuropsychological testing (7). Attempts to topographically map the human STN have suggested that placement of the DBS electrodes within the anterior aspect of the ventral STN is related to additional neuropsychological sequelae (8).