Increased functional connectivity of thalamic subdivisions in patients with Parkinson's disease

Abstract

Parkinson's disease (PD) affects 2-3% of the population over the age of 65 with loss of dopaminergic neurons in the substantia nigra impacting the functioning of basal ganglia-thalamocortical circuits. The precise role played by the thalamus is unknown, despite its critical role in the functioning of the cerebral cortex, and the abnormal neuronal activity of the structure in PD. Our objective was to more clearly elucidate how functional connectivity and morphology of the thalamus are impacted in PD (n = 32) compared to Controls (n = 20). To investigate functional connectivity of the thalamus we subdivided the structure into two important regions-of-interest, the first with putative connections to the motor cortices and the second with putative connections to prefrontal cortices. We then investigated potential differences in the size and shape of the thalamus in PD, and how morphology and functional connectivity relate to clinical variables. Our data demonstrate that PD is associated with increases in functional connectivity between motor subdivisions of the thalamus and the supplementary motor area, and between prefrontal thalamic subdivisions and nuclei of the basal ganglia, anterior and dorsolateral prefrontal cortices, as well as the anterior and paracingulate gyri. These results suggest that PD is associated with increased functional connectivity of subdivisions of the thalamus which may be indicative alterations to basal ganglia-thalamocortical circuitry.

Fig 1. Positioning and likelihood-map of seed voxels for VLp/VA and MD/A thalamic masks.

This figure displays the voxels used in seed-ROI masks for the functional connectivity analyses, overlaid on MNI T1 0.5mm images. This image was produced by combining all of the binary masks of each participant into one unified mask, with warm (yellow—red) colors indicating the positioning of the VLp/VA voxels and cold colors (light blue—dark blue) indicating the positioning of the MD/A voxels. Darker tones are indicative of a greater proportion of voxels in that region being included in the relevant seed-ROI mask. VLp/VA, ventral lateral posterior and ventral anterior thalamic voxels; MD/A, mediodorsal and anterior thalamic voxels.

Fig 2. VLp/VA thalamus functional connectivity.

p-value images showing neuroanatomical regions with significant between-group changes in functional connectivity with the VLp/VA thalamus in PD subjects compared to Controls. Warm colors (yellow-orange) represent areas of increased functional connectivity in PD and cool colors (light-dark blue) represent areas of decreased functional connectivity in PD. Spacing between each slice in the z-direction is 4.2mm beginning at z = -3.18 in the top left slice (MNI T1 2mm image). R, right; A, anterior; PCG, paracingulate gyrus; SMA, supplementary motor area; LOC, lateral occipital cortex.

Fig 3. MD/A thalamus functional connectivity.

p-value images showing neuroanatomical regions with significant between-group changes in functional connectivity of the MD/A thalamus in PD subjects compared to Controls. Warm colors (yellow-orange) represent areas of increased functional connectivity in PD. Spacing between each slice in the z-direction is 4mm beginning at z = -2.3 in the top left slice (MNI T1 2mm image). R, right; A, anterior; Put, putamen; GP, globus pallidus; CN, caudate nucleus; PCG, paracingulate gyrus; ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; APFC, anterior prefrontal cortex.

Fig 4. Shape analysis of thalamus in PD compared to Controls.

Displayed are superior and inferior views of bilateral thalami overlaid on axial MNI T1 0.5mm images. Warmer colors indicate regions of greater inflation in the PD group compared to Controls using point-wise significance tests (p < 0.05, uncorrected). No regions were significant after false-discovery rate correction.