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Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer's Disease.

ABSTRACT: Very early Alzheimer's disease (AD) - i.e., AD at stages of mild cognitive impairment (MCI) and mild dementia - is characterized by progressive structural and neuropathologic changes, such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex and also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC) patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n?=?33) and patients with AD in the stages of MCI (AD-MCI, n?=?38) and mild dementia (AD-D, n?=?36). Outcome measures were voxel-based morphometry (VBM) values and region-of-interest-based iFC maps of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON?>?AD-MCI and AD-D). Amygdala iFC was progressively reduced along impairment severity (CON?>?AD-MCI?>?AD-D), particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions, including that of amygdala.

SUBMITTER: Ortner M

PROVIDER: S-EPMC5027206 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer's Disease.

Ortner Marion M Pasquini Lorenzo L Barat Martina M Alexopoulos Panagiotis P Grimmer Timo T Förster Stefan S Diehl-Schmid Janine J Kurz Alexander A Förstl Hans H Zimmer Claus C Wohlschläger Afra A Sorg Christian C Peters Henning H

Frontiers in neurology 20160919

Very early Alzheimer's disease (AD) - i.e., AD at stages of mild cognitive impairment (MCI) and mild dementia - is characterized by progressive structural and neuropathologic changes, such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex and also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD ...[more]

PMID: 27698649

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Project description:The amygdala, a subcortical structure known for social and emotional processing, consists of multiple subnuclei with unique functions and connectivity patterns. Tracer studies in adult macaques have shown that the basolateral subnuclei differentially connect to parts of visual cortex, with stronger connections to anterior regions and weaker connections to posterior regions; infant macaques show robust connectivity even with posterior visual regions. Do these developmental differences also exist in the human amygdala, and are there specific functional regions that undergo the most pronounced developmental changes in their connections with the amygdala? To address these questions, we explored the functional connectivity (from resting-state fMRI data) of the basolateral amygdala to occipitotemporal cortex in human neonates scanned within one week of life and compared the connectivity patterns to those observed in young adults. Specifically, we calculated amygdala connectivity to anterior-posterior gradients of the anatomically-defined occipitotemporal cortex, and also to putative occipitotemporal functional parcels, including primary and high-level visual and auditory cortices (V1, A1, face, scene, object, body, high-level auditory regions). Results showed a decreasing gradient of functional connectivity to the occipitotemporal cortex in adults-similar to the gradient seen in macaque tracer studies-but no such gradient was observed in neonates. Further, adults had stronger connections to high-level functional regions associated with face, body, and object processing, and weaker connections to primary sensory regions (i.e., A1, V1), whereas neonates showed the same amount of connectivity to primary and high-level sensory regions. Overall, these results show that functional connectivity between the amygdala and occipitotemporal cortex is not yet differentiated in neonates, suggesting a role of maturation and experience in shaping these connections later in life.

Dataset Information

Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer's Disease.

Publications

Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer's Disease.

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