Somatotopic organization in the internal segment of the globus pallidus in Parkinson's disease

Abstract

Ablation or deep brain stimulation in the internal segment of the globus pallidus (GPi) is an effective therapy for the treatment of Parkinson's disease (PD). Yet many patients receive only partial benefit, including varying levels of improvement across different body regions, which may relate to a differential effect of GPi surgery on the different body regions. Unfortunately, our understanding of the somatotopic organization of human GPi is based on a small number of studies with limited sample sizes, including several based upon only a single recording track or plane. To fully address the three-dimensional somatotopic organization of GPi, we examined the receptive field properties of pallidal neurons in a large cohort of patients undergoing stereotactic surgery. The response of neurons to active and passive movements of the limbs and orofacial structures was determined, using a minimum of three tracks across at least two medial-lateral planes. Neurons (3183) were evaluated from 299 patients, of which 1972 (62%) were modulated by sensorimotor manipulation. Of these, 1767 responded to a single, contralateral body region, with the remaining 205 responding to multiple and/or ipsilateral body regions. Leg-related neurons were found dorsal, medial and anterior to arm-related neurons, while arm-related neurons were dorsal and lateral to orofacial-related neurons. This study provides a more detailed map of individual body regions as well as specific joints within each region and provides a potential explanation for the differential effect of lesions or DBS of the GPi on different body parts in patients undergoing surgical treatment of movement disorders.

Fig. 1

Illustrative depiction of the relative distribution of neuronal responses observed within the GPi. Data are shown only for those neurons responsive to a single body region (red = lower limb; blue = upper limb; green = orofacial). The numbers above each section reflect its mediolateral position relative to midline. The data for neurons identified 0.5 mm medial or lateral to the indicated section have been collapsed onto the closest section (e.g., data for neurons determined to be between mediolateral 20.0 and 22.0 are represented on plane section 21.5).

Fig. 2

A series of two-dimensional plots depicting the mean coordinates for each body region (bold, dark points), along with the mean coordinates for each specific joint (grey), collapsed across the axial, coronal and sagittal planes (“▲” = Lower limb, “●” = Upper limb, “■” = Orofacial). X, Y and Z represent the mediolateral, anteroposterior and dorsoventral planes, respectively, with the zero point of the Y and Z planes representing the mid-commissural point (positive values for Y and Z are anterior and dorsal, respectively).

Fig. 3

A series of unidimensional histograms depicting the percentage of neurons responsive to upper limb (blue), lower limb (red) or orofacial (green) manipulation as a function of distance along the anteroposterior (a), mediolateral (b) and ventrodorsal (c) dimension. For each dimension, the relative percentage of neurons responsive to manipulation of the upper, lower and orofacial regions of the body as well as non-responsive units (gray) are displayed across the length of the explored region, as displayed in millimeters. One millimeter bins were applied for the anteroposterior and dorsoventral dimensions, while half millimeter bins were used in the mediolateral dimension. The zero point along each dimension represents the mid-commissural point of the AC–PC line, while the numbers shown in yellow at the bottom of each column represent the number of units sampled at that level.