Cortical and subcortical morphological alterations in motor subtypes of Parkinson's disease

Abstract

Parkinson's disease (PD) can be classified into an akinetic-rigid (AR) and a tremor-dominant (TD) subtype based on predominant motor symptoms. Patients with different motor subtypes often show divergent clinical manifestations; however, the underlying neural mechanisms remain unclear. This study aimed to characterize the cortical and subcortical morphological alterations in motor subtypes of PD. T1-weighted MRI images were obtained for 90 patients with PD (64 with the AR subtype and 26 with the TD subtype) and 56 healthy controls (HCs). Cortical surface area, sulcal depth (measured by Freesurfer's Sulc index), and subcortical volume were computed to identify the cortical and subcortical morphological alterations in the two motor subtypes. Compared with HCs, we found widespread surface area reductions in the AR subtype yet sparse surface area reductions in the TD subtype. We found no significant Sulc change in the AR subtype yet increased Sulc in the right supramarginal gyrus in the TD subtype. The hippocampal volumes in both subtypes were lower than those of HCs. In PD patients, the surface area of left posterior cingulate cortex was positively correlated with Mini-Mental State Examination (MMSE) score, while the Sulc value of right middle frontal gyrus was positively correlated with severity of motor impairments. Additionally, the hippocampal volumes were positively correlated with MMSE and Montreal Cognitive Assessment scores and negatively correlated with severity of motor impairments and Hoehn & Yahr scores. Taken together, these findings may contribute to a better understanding of the neural substrates underlying the distinct symptom profiles in the two PD subtypes.

Fig. 1. Brain regions with reduced surface area in the AR and TD subtypes compared with HCs.

a Brain regions showing significantly reduced surface area in patients with the AR subtype compared with HCs. The result was corrected for multiple comparisons using RFT. The color bar indicates the RFT-corrected p-value. b Brain regions showing significantly reduced surface area in patients with the TD subtype compared with HCs. The result was corrected for multiple comparisons using RFT. The color bar indicates the RFT-corrected p-value.

Fig. 2. Brain regions with Sulc changes in the AR and TD subtypes compared with HCs.

a Brain regions showing significant Sulc change in patients with the AR subtype compared with HCs. The result was corrected for multiple comparisons using RFT. The color bar indicates the RFT-corrected p-value. b Brain regions showing significant Sulc change in patients with the TD subtype compared with HCs. The result was corrected for multiple comparisons using RFT. The color bar indicates the RFT-corrected p-value.

Fig. 3. Relationships between cortical morphological parameters and clinical data in patients with PD.

a The left panel shows the brain region where the surface area was positively correlated with the MMSE score in patients with PD. The result was corrected for multiple comparisons using RFT. The color bar indicates the RFT-corrected p-value. The right panel is a scatterplot of the positive correlation. b The left panel shows the brain region where the Sulc value was positively correlated with the UPDRS-III score in patients with PD. The result was corrected for multiple comparisons using RFT. The color bar indicates the RFT-corrected p-value. The right panel is a scatterplot of the positive correlation.