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INTRINSIC CONNECTIVITY NETWORKS IN POSTERIOR CORTICAL ATROPHY: A ROLE FOR THE PULVINAR?

      Background

      Amnestic Alzheimer’s disease (AD) is characterized by disrupted default mode network (DMN) connectivity with corresponding increased salience network (SN) connectivity. Posterior cortical atrophy (PCA) is an uncommon AD variant presenting with progressive visuospatial symptoms, and the relationships between functional networks in PCA are unknown. We hypothesized that PCA patients would show early decreased integrity within the visual network, with corresponding increases in SN connectivity, despite relative preservation of DMN. As the medial and lateral pulvinar are anatomically interconnected with SN, DMN, and visual structures, we further hypothesized that the pulvinar nucleus might play a key role in these networks.

      Methods

      26 individuals diagnosed with PCA (all amyloid-positive or with AD-consistent CSF) and 64 matched controls were recruited through UCSF Memory and Aging Center research programs. Each completed a standardized neuropsychological battery, structural imaging, and task-free fMRI. We used voxel-based morphometry (VBM) to assess structural atrophy. For fMRI, time series from seeds for networks of interest were regressed across the whole brain and fitted to a second-level regression model for group effects analysis. Functional data analyses were atrophy-corrected using the BPM toolbox.

      Results

      PCA patients show relatively preserved memory in the early stages of illness despite poor visuospatial performance; like others with AD, they also show preserved social sensitivity. As expected, VBM revealed highly significant parieto-occipital atrophy (Figure 1). PCA patients showed widespread decreased connectivity within the visual network, increased connectivity between some structures in SN, and increased connectivity between key nodes of the DMN compared to controls. Medial pulvinar connectivity mirrored SN connectivity, while lateral pulvinar connectivity mirrored DMN connectivity (Figure 2).

      Conclusions

      Individuals with PCA show relatively preserved connectivity in SN and DMN despite widespread parietooccipital atrophy and decreased visual network connectivity. The striking similarity of medial and lateral pulvinar-derived connectivity maps to SN and DMN suggests an important role for the pulvinar within these networks, particularly given the close anatomic relationship between medial pulvinar and SN, and lateral pulvinar and DMN and visual regions. Thalamic subnuclei are well-poised to serve as network switches, and different subnuclei may be differentially implicated in different subtypes of AD.
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      Figure 2Seed-based analyses, PCA>HC. Joint height and extent probability threshold of p < 0.05, corrected at the whole brain level. BPM-corrected for voxelwise atrophy.