Altered resting-state functional connectivity of the putamen and internal globus pallidus is related to speech impairment in Parkinson's disease

Abstract

Introduction: Speech impairment in Parkinson's disease (PD) is pervasive, with life-impacting consequences. Yet, little is known about how functional connections between the basal ganglia and cortex relate to PD speech impairment (PDSI). Whole-brain resting-state connectivity analyses of basal ganglia nuclei can expand the understanding of PDSI pathophysiology.

Methods: Resting-state data from 89 right-handed subjects were downloaded from the Parkinson's Progression Markers Initiative database. Subjects included 12 older healthy controls ("OHC"), 42 PD patients without speech impairment ("PDN"), and 35 PD subjects with speech impairment ("PDSI"). Subjects were assigned to PDN and PDSI groups based on the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III speech item scores ("0" vs. "1-4"). Whole-brain functional connectivity was calculated for four basal ganglia seeds in each hemisphere: putamen, caudate, external globus pallidus (GPe), and internal globus pallidus (GPi). For each seed region, group-averaged connectivity maps were compared among OHC, PDN, and PDSI groups using a multivariate ANCOVA controlling for the effects of age and sex. Subsequent planned pairwise t-tests were performed to determine differences between the three groups using a voxel-wise threshold of p < 0.001 and cluster-extent threshold of 272 mm³ (FWE<0.05).

Results: In comparison with OHCs, both PDN and PDSI groups demonstrated significant differences in cortical connectivity with bilateral putamen, bilateral GPe, and right caudate. Compared to the PDN group, the PDSI subjects demonstrated significant differences in cortical connectivity with left putamen and left GPi. PDSI subjects had lower connectivity between the left putamen and left superior temporal gyrus compared to PDN. In addition, PDSI subjects had greater connectivity between left GPi and three cortical regions: left dorsal premotor/laryngeal motor cortex, left angular gyrus, and right angular gyrus.

Conclusions: The present findings suggest that speech impairment in PD is associated with altered cortical connectivity with left putamen and left GPi.

Keywords: Parkinson's disease; basal ganglia; dysarthria; fMRI; speech disorders.