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

Abstract

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) contributes to the variability of motor and non-motor responses across patients with Parkinson's disease (PD). We previously tested the 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 borders of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of three unilateral DBS 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. Ventral STN DBS induced greater improvement in rigidity and anxiety than dorsal STN DBS. In the 3D analysis, contact location was significant for body hypokinesia, rigidity and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. The 3D results provide new, direct functional evidence for the anatomically derived model of STN, in which motor function is best represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, because locations that induced improvements in motor function and mood overlapped substantially.

Keywords: Parkinson's disease; deep brain stimulation; emotions; inhibition (psychology); short-term memory; subthalamic nucleus.

Figure 1.

Distribution of contacts included in the analyses shown as green (dorsal) and purple (ventral) spheres, with paired contacts of each participant indicated by yellow connecting rods, and blue transparent regions indicating the subthalamic nucleus (STN).

Figure 2.

Weighted mean image (i), p-image (ii) and 3D p-image (iii) for measures with significant effect of contact location in the 3D analyses. (a) Body bradykinesia and hypokinesia item. (b) Rigidity. (c) Tremor at rest. For the weighted mean images, the cooler shades indicate where, on average, the difference scores (ventral-OFF and dorsal-OFF) are more negative (improvement relative to OFF, for motor measures). For the 2D p-image, warmer shades indicate more significant p-values, while the cooler shades indicate less significant p-values. White squares indicate peak coordinates. The 3D image is shown as viewed from anteriorly, and the blue volume indicates values less than 0.05 in the p-image. STN, subthalamic nucleus; ZI, zona incerta, D, dorsal, V, ventral, L, lateral, M, medial.