Blood oxygenation level-dependent activation in basal ganglia nuclei relates to specific symptoms in de novo Parkinson's disease

Abstract

To aid the development of symptomatic and disease modifying therapies in Parkinson's disease (PD), there is a strong need to identify noninvasive measures of basal ganglia (BG) function that are sensitive to disease severity. This study examines the relation between blood oxygenation level-dependent (BOLD) activation in every nucleus of the BG and symptom-specific disease severity in early stage de novo PD. BOLD activation measured at 3 T was compared between 20 early stage de novo PD patients and 20 controls during an established precision grip force task. In addition to the BG nuclei, activation in specific thalamic and cortical regions was examined. There were three novel findings. First, there were significant negative correlations between total motor Unified PD Rating Scale and BOLD activation in bilateral caudate, bilateral putamen, contralateral external segment of the globus pallidus, bilateral subthalamic nucleus, contralateral substantia nigra, and thalamus. Second, bradykinesia was the symptom that most consistently predicted BOLD activation in the BG and thalamus. Also, BOLD activation in the contralateral internal globus pallidus was related to tremor. Third, the reduced cortical activity in primary motor cortex and supplementary motor area in de novo PD did not relate to motor symptoms. These findings demonstrate that BOLD activity in nuclei of the BG relates most consistently to bradykinesia and functional magnetic resonance imaging has strong potential to serve as a noninvasive marker for the state of BG function in de novo PD.

Figure 1

A, grip force transducer and fiber optic device used to collect force data. B, visual display seen during the scan for the grip force task at rest and during force production. The arrow shows movement direction of the white force cursor but was not part of the visual display. C, actual force traces of the motor task performed by one control subject (top) and one PD patient (bottom).

Figure 2

The center diagram shows the basal ganglia and cortical ROIs used. Surrounding plots show percent signal change in the contralateral basal ganglia, medial thalamus, and cortical ROIs for control subjects (black bars) and PD patients (red bars). Error bars indicate standard error for the group mean.

Figure 3

Percent variance accounted for in disease severity from percent signal change in each basal ganglia, medial thalamus, and cortical ROI. r² values for the total motor UPDRS score for contralateral ROIs (black bars) and ipsilateral ROIs (red bars) are shown.