PT - JOURNAL ARTICLE AU - Amritha Gourisankar AU - Sarah A. Eisenstein AU - Nicholas T. Trapp AU - Jonathan M. Koller AU - Meghan C. Campbell AU - Mwiza Ushe AU - Joel S. Perlmutter AU - Tamara Hershey AU - Kevin J. Black TI - Mapping Movement, Mood, Motivation, and Mentation in the Subthalamic Nucleus AID - 10.1101/168302 DP - 2017 Jan 01 TA - bioRxiv PG - 168302 4099 - http://biorxiv.org/content/early/2017/07/27/168302.short 4100 - http://biorxiv.org/content/early/2017/07/27/168302.full AB - The motor and non-motor response to deep brain stimulation of the subthalamic nucleus (STN DBS) varies significantly among people with Parkinson disease (PD). One common hypothesis about what underlies this variability is that the precise anatomical location of STN DBS may determine the degree or type of response. Our previous study tested that hypothesis by treating location as a three-dimensional (3D) variable, based on the acute effect of unilateral DBS at the clinically optimized DBS settings and active contact of each participant. Here, in a new data set, we investigated whether the 3D location of stimulation in ventral and dorsal STN significantly affected motor and non-motor responses, with standardized DBS parameters. In 74 individuals with PD and STN DBS, 44-84 years old, contacts were selected, blind to clinical response, near the dorsal and ventral border of the STN contralateral to the more affected side of the body. Participants were tested after PD medications were withdrawn for > 8 hours in each of 3 conditions (ventral STN DBS, dorsal STN DBS and DBS off) for acute effects on mood, working memory, response inhibition and motor function. Voltage, frequency, and pulse width were standardized across DBS conditions and individuals, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function and had no cognitive effects, with dorsal STN DBS inducing greater improvement in rigidity than ventral STN DBS; there were some mood effects with ventral STN DBS inducing greater improvement in anxiety and mood than dorsal STN DBS. In the 3D analysis, contact location was significant for bradykinesia and resting tremor, with greatest improvement occurring with dorsal STN and zona incerta DBS. These results provide new, direct functional evidence for the anatomically-derived model of STN using the novel 3D analysis, in which motor function is most represented in dorsal STN. However, our data suggest that any functional segregation between motor and non-motor areas of the STN is limited, since locations that induce improvements in motor and mood function overlapped substantially.