Increased Intrinsic Activity of Medial-Temporal Lobe Subregions is Associated with Decreased Cortical Thickness of Medial-Parietal Areas in Patients with Alzheimer’s Disease Dementia

Abstract

In Alzheimer's disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-parietal degeneration and impaired memory in AD. To test this hypothesis, resting-state-functional and structural-MRI was assessed in 22 healthy controls, 22 mild cognitive impairment patients, and 21 AD-dementia patients. Intrinsic activity was measured by power-spectrum density of blood-oxygenation-level-dependent signal, medial-parietal degeneration by cortical thinning. In AD-dementia patients, intrinsic activity was increased for several right MTL subregions. Raised intrinsic activity in dentate gyrus and cornu ammonis 1 was associated with cortical thinning in posterior cingulate cortices, and at-trend with impaired delayed recall. Critically, increased intrinsic activity in the right entorhinal cortex was associated with ipsilateral posterior cingulate degeneration. Our results provide evidence that in AD, intrinsic activity in MTL subregions is increased and associated with medial-parietal atrophy. Results fit a model in which medial-parietal degeneration contributes to MTL dysconnectivity from medial-parietal cortices, potentially underpinning disinhibition-like changes in MTL activity.

Improved Diagnostic Accuracy of Alzheimer's Disease by Combining Regional Cortical Thickness and Default Mode Network Functional Connectivity: Validated in the Alzheimer's Disease Neuroimaging Initiative Set

“…However, studies found potential links between DMN FC and the neocortex, such that the entorhinal cortex mediates the connections between the hippocampus and the DMN-related regions of the neocortex ( 26 27 28 ). Additionally, white matter bundle integrity of the DMN is linked with medial temporal lobe atrophy; it also explains interaction between the medial temporal lobe and parietal lobe ( 29 ). Therefore, we hypothesized that certain locations may be closely linked to DMN FC, and therefore mediate the structural atrophy in the neocortex beyond the medial temporal lobe.…”

Abnormal global functional network connectivity and its relationship to medial temporal atrophy in patients with amnestic mild cognitive impairment

“…In prior studies, the relationship between abnormalities of functional activity in MTL and memory has been investigated [47] and some of them have revealed that MCI patients can exhibit increased fMRI responses in MTL when executing memory-related tasks [11, 12, 14], indicating a compensatory response to accumulating AD pathology. Similarly, using rs-fMRI, some studies also show increased activity or connectivity in components of MTL, which is also related to the cognitive function [16, 18, 48, 49], such as raised intrinsic activity in MTL subregions associated at-trend with impaired delayed recall [17] and the positive correlations between basal functional connectivity within the ATN and performance on declarative memory tasks in patients [50]. However, there are some discrepancies among different studies [26, 51], possibly due to the heterogeneity of aMCI [52] and different types of tasks performed [11].…”

“…The possible mechanism of aberrant MTL activity in aMCI patients may be as follows: Firstly, “hippocampus disconnection hypothesis”, which emphasizes that reduced main cortical input to hippocampus may lead to disinhibition-like changes of intrahippocampal activity, causing the elevated synchrony of hippocampus circuit activity [17, 18, 53]. Pasquini et al also found that increased local intrinsic functional connectivity in the hippocampus was associated with decreased global functional connectivity within the DMN [16].…”

“…Additionally, using resting-state functional MRI (rs-fMRI), similar changes of MTL intrinsic activity were reported in current studies. In AD dementia, hippocampus exhibited raised local functional connectivity [16] and intrinsic activity in several right MTL subregions was increased, latter of which was also at-trend associated with impaired delayed recall [17]. Comparable abnormalities are also found in aMCI patients, such as the raised local intrinsic functional connectivity between entorhinal cortex and MTL subregions [18].…”

Automated segmentation of medial temporal lobe subregions on in vivo T1‐weighted MRI in early stages of Alzheimer's disease

“…However, manual segmentation is infeasible for larger data sets like the AD neuroimaging initiative (ADNI), which includes thousands of MRI scans. Among the automated methods available for MTL subregion segmentation on T1w MRI, the specialized modules for MTL provided by FreeSurfer (Fischl, 2012) are of the most widely used in the literature in older populations (Delli Pizzi et al, 2016; Lehmann et al, 2010; Mah, Binns, & Steffens, 2015; Mishra et al, 2017; Pasquini et al, 2016). FreeSurfer includes a module for labeling hippocampal subfields and hippocampal lamina based on an ex vivo atlas (Iglesias et al, 2015).…”