Relationship between Neuropsychological Outcome and DBS Surgical Trajectory and Electrode Location

Advances in neurosurgical, radiological, and electrophysiological techniques have made it possible to produce marked improvements in the motor symptoms of advanced Parkinson’s disease (PD). (1–8) Deep brain stimulation (DBS) has been shown to be an effective and adaptable treatment for the control of PD-related motor symptoms.(4;5;9) The neuropsychological literature on the outcome of DBS suggests that the cognitive declines associated with the surgery are minimal compared to the robust motor improvements.(4;10;11) However, a large amount of variability exists in the literature regarding the cognitive sequelae following surgery. Further elucidation of the cognitive consequences could lead potentially to a clearer understanding of the surgical mechanisms of DBS. Several studies reported that DBS patients failed to demonstrate cognitive changes on measures tapping memory, visuospatial, executive, and psychomotor functioning three months following implantation of subthalamic nuclei (STN) stimulators.(1;12;13) Significant improvements in delayed verbal recall, psychomotor speed, working memory, and anxiety symptoms following DBS, with only subtle deficits in semantic fluency (14); (15) Although these researchers found significant improvements following DBS, several other centers have reported cognitive declines, particularly when subgroups of patients, most notably older patients, are identified (16;17) Declines in numerous aspects of cognition following implantation of STN stimulators, including working memory, speed of mental processing, set switching, verbal and nonverbal memory, and verbal fluency, have recently been reported. Morrison et al.(18) reported that the surgery itself reduced attention, language, and verbal learning ability, with STN stimulation further reducing verbal recall. Our center reported declines in verbal recall 6-months following STN DBS surgery and information processing speed, naming, verbal fluency, and verbal memory declines 2 years following surgery as compared to a PD control group. (19) The cognitive findings following DBS suggest that verbal fluency and verbal memory abilities, which are believed to be dependent upon intact functioning of the frontostriatal neural system, may decline following implantation of STN stimulators. (19) One hypothesis for the variability in the DBS cognitive outcome literature is the differences in surgical procedures across centers, including the precise placement of the electrodes within the STN and the surgical trajectory. The position of the DBS electrodes can vary from patient to patient based on several factors, including brain size, brain atrophy and planned surgical trajectory. The differences in electrode position may lead to a differential outcome both motorically and neuropsychologically. Tsai and colleagues(20) reported on the location of bilateral STN electrodes in 38 PD patients. They divided patients into a group with and a group without neuropsychological side effects based on the Mini-Mental Status Examination changes one year following DBS. These authors reported that that the neuropsychological effects of chronic STN-DBS were related to the more anteriorly located electrodes within the ventral STN. In addition to the electrode placement, the surgical trajectory may also be a source of cognitive variability. Neurosurgeons may vary the surgical trajectory of STN DBS based on the patient’s brain organization, including the size of the ventricles, degree of brain atrophy and surface vasculature. Although the microelectrodes and DBS electrodes follow the same pathway, it is not known if the surgical trajectory may lead to deficits. We investigated the relationship between neuropsychological performance following bilateral STN DBS for the treatment of PD and DBS electrode position and surgical trajectory on post-operative magnetic resonance imaging (MRI). This study focused on mental status, verbal memory, verbal fluency, and semantic fluency declines following DBS surgery as these are the most robust cognitive changes reported in the literature following the surgery. We also investigated psychological variables including depression and anxiety changes and their relations with differences in the electrode position and surgical trajectory.