Thalamic Contributions to Functional Circuitry in Preclinical Alzheimer’s Disease

Abstract

AbstractBackgroundThalamic nuclei are heterogeneously impacted by Alzheimer’s disease (AD) pathology. The anterior thalamus shows tau deposition early on in AD, while other nuclei, such as the mediodorsal (MD) thalamus are spared by tau until much later in the disease process (Braak and Braak, 1991). Furthermore, anterior and MD thalamus have dissociable roles in memory performance – the anterior has a greater role in recollective memory, while the MD plays a role in familiarity. Additionally, the anterior thalamus has direct anatomical links to brain regions implicated in poor short‐term memory performance in AD, while MD thalamus connectivity is primarily to regions spared of AD pathology until late. We sought to identify differences in functional connectivity between the anterior and MD thalamus in amyloid negative and positive individuals.MethodWe examined resting‐state functional MRI data from the A4 study (n = 569), including 254 healthy controls and 315 individuals with preclinical AD based on amyloid SUVR>1.14 (Table 1). We assessed functional connectivity of anterior and MD thalamus to the whole brain using 2mm radius spherical seeds at the center of mass of Morel atlas nuclei. All results were covaried for age, sex, handedness, and years of education.ResultsAnterior thalamic activity was positively correlated with parahippocampal gyrus, fusiform, and insula, and negatively with the striatum and thalamus. MD thalamic activity was positively correlated with the amygdala, ventral striatum, and anterior cingulate, and negatively correlated to the superior temporal gyrus and regions of the parieto‐occipital lobe. In preclinical AD, compared with HCs, the positive correlations in either thalamic nuclei were lost.ConclusionThe thalamic functional connectivity observed agrees with preexisting literature dissociating structures related to the anterior and MD thalamus. Our results provide a basis for further exploration of thalamic nuclei to AD‐involved functional networks, as well as future analysis of the observed connectivity measures to cognition.