Brain gray matter abnormalities in progressive supranuclear palsy revisited

Abstract

Whole-brain voxel-based morphometry (VBM) studies of progressive supranuclear palsy (PSP) have demonstrated heterogeneous findings regarding gray matter (GM) abnormalities. Here, we used Seed-based d Mapping, a coordinate-based meta-analytic approach to identify consistent regions of GM anomalies across studies of PSP. Totally, 18 original VBM studies, comprising 284 patients with PSP and 367 healthy controls were included. As compared to healthy controls, patients with PSP demonstrated significant GM reductions in both cortical and subcortical regions, including the frontal motor cortices, medial (including anterior cingulate cortex) and lateral frontal cortices, insula, superior temporal gyrus, striatum (putamen and caudate nucleus), thalamus, midbrain, and anterior cerebellum. Our study further suggests that many confounding factors, such as age, male ratio, motor severity, cognitive impairment severity, and illness duration of PSP patients, and scanner field-strength, could contribute to the heterogeneity of GM alterations in PSP across studies. Our comprehensive meta-analysis demonstrates a specific neuroanatomical pattern of GM atrophy in PSP with the involvement of the cortical-subcortical circuitries that mediate vertical supranuclear gaze palsy, motor disabilities (postural instability with falls and parkinsonism), and cognitive-behavioral disturbances. Confounding factors merit attention in future studies.

Keywords: cortical-subcortical circuitries; meta-analysis; progressive supranuclear palsy; seed-based d mapping; voxel-based morphometry.

Figure 1. Flowchart to identify the eligible studies for the meta-analysis

Key: PSP, Progressive Supranuclear Palsy; GM, Gray Matter; VBM, Voxel-Based Morphometry; ROI, Region Of Interest.

Figure 2. Meta-analytic results of gray matter reductions in patients with PSP compared to healthy controls

Key: (A), Left inferior frontal gyrus/insula/superior temporal gyrus/precentral gyrus (premotor cortex)/putamen/ orbitofrontal cortex; (B), Right/Left thalamus/midbrain/caudate nucleus; (C), Right/Left anterior cingulate cortex/(pre-) supplementary motor area/superior medial frontal cortex/medial orbitofrontal cortex; (D), Right inferior frontal gyrus/insula/superior temporal gyrus/putamen/precentral gyrus (premotor cortex); (E), Left anterior cerebellum (lobule III/IV/V); PSP, Progressive Supranuclear Palsy; HC, healthy controls; SDM, Seed-based d Mapping. The color bar indicates the maximum and the minimum SDM-Z values.

Figure 3. Funnel plots of the peak coordinates of gray matter abnormalities in progressive supranuclear palsy

Figure 4. Results of the meta-regression analyses

Key: UPDRS-III, Unified Parkinson's Disease Rating Scale-motor examination; MMSE, Mini-Mental State Examination. Each study is represented as a dot, with a larger dot indicating a larger sample size. (A) and (B), meta-regression with mean age; (C), meta-regression with male ratio of patients; (D), meta-regression with mean UPDRS-III score; (E), meta-regression with mean MMSE score; (F), meta-regression with illness duration; (G) and (H), meta-regression with scanner field-strength.