Mapping movement, mood, motivation, and mentation in the subthalamic nucleus

The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) determines the variability of motor and non-motor responses across Parkinson disease (PD) patients. We previously tested that hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patient’s clinically optimized DBS settings and active contact. Here we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral border of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of 3 conditions (ventral STN DBS, dorsal STN DBS and DBS off) for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency, and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Dorsal STN DBS induced greater improvement in rigidity than ventral STN DBS, whereas ventral STN DBS was more effective for improving anxiety and mood. In the 3D analysis, contact location was significant only for bradykinesia and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. 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 functional segregation between motor and non-motor areas of the STN is limited, since locations that induced improvements in motor function and mood overlapped substantially.