Medial Perirhinal Cortex Research Articles

Can you find it? Novel oddity detection task for the early detection of Alzheimer's disease.

We aimed to develop a measure to specifically assess the functioning of the perirhinal cortex (PRC), a brain structure affected very early in Alzheimer's disease (AD) pathology. In this novel task, participants were shown arrays of six complex figures and had to identify the "odd-one." The pilot study included 50 normal controls (NCs) and 50 patients in very early stages of AD. Participants completed the task and received MRI scanning. Best differentiating items were determined and applied in a validation study including 25 NCs, 27 early-stage AD patients, and 26 patients with major depression. Logistic regression models investigated if task performance predicted group membership. Task performance was then related to whole-brain gray matter integrity. As proof of concept, cortical thickness values of four regions of interest (ROIs; e.g., medial PRC and entorhinal cortex [ERC]) were compared between the groups. The associations of task performance and cortical thickness of the ROIs were investigated using linear models. Task performance showed good discriminative ability between early-stage AD patients and NCs. Whole-brain analyses revealed four significant clusters (p < .001) with peak voxels in parahippocampal regions including PRC and ERC. ROI analyses showed distinctly reduced cortical thickness in the AD group compared to both other groups in the medial PRC and ERC (p ≤ .001). Task performance modeled by ROI cortical thickness did not achieve significant results. Although further validation is needed, especially with age-matched participant groups, these findings indicate that the task detects early cognitive impairment related to AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Very high interrater reliability for manual segmentation of the medial perirhinal cortex

AbstractBackgroundIntracellular neurofibrillary tangles (NFT) belong to the main characteristics of Alzheimer’s disease (AD) pathology and occur first in the medial perirhinal cortex (mPRC; also referred to as “transentorhinal region”). Adjacent regions such as lateral perirhinal cortex (lPRC), entorhinal cortex (ERC), and hippocampus are affected at a later stage of NFT progression. Therefore, mPRC integrity potentially serves as a promising imaging biomarker in early AD. Due to the high anatomic variability of the collateral sulcus, which defines mPRC boundaries, it is important to evaluate the interrater reliability of manual segmentation. Today, automated segmentation protocols only exist for the whole PRC (i.e. mPRC and lPRC together). However, discrete analysis of mPRC integrity is crucial to detect AD related pathology as early as possible.MethodForty‐four adults (20 men; mean age = 69.2 ± 10.4 years) from different diagnostic groups (e.g. normal controls, mild cognitive impairment, Alzheimer's dementia or major depression) were included in the analyses. All subjects received structural magnetic resonance imaging in a 3‐Tesla scanner (MAGNETOM Verio, Siemens). Regions of interest (mPRC, lPRC, and ERC) were drawn by‐hand by two raters (SK, NAH) blinded for diagnoses. Bilateral cortical thickness estimates were extracted using FreeSurfer. Intraclass correlation coefficients (ICC) were calculated in SPSS based on a single‐rating, absolute‐agreement, 2‐way mixed‐effects model.ResultA high degree of reliability was found between both raters with an average measure ICC of .876 for the left mPRC (F[43,43]=14.954, p&lt;.001, 95% confidence interval [CI] =.784 ‐ .930) and .873 for the right mPRC (F[43,43]=14.472, p&lt;.001, 95% CI=.779 ‐ .929). Similar results were found for lPRC (left: ICC=.984; F[43,43]=118.834, p&lt;.001, 95% CI=.970 ‐ .991; right: ICC=.953; F[43,43]=40.344, p&lt;.001, 95% CI=.915 ‐ .974) and ERC (left: ICC=.969; F[43,43]=62.657, p&lt;.001, 95% CI=.944 ‐ .983; right: ICC=.961; F[43,43]=49.390, p&lt;.001, 95% CI=.930 ‐ .979).ConclusionThe ICC analysis showed a very high interrater reliability for manual mPRC segmentation as well as for lPRC and ERC. These results indicate that the applied segmentation protocol, which considers collateral sulcus variability, allows different raters to achieve highly similar results and may serve as a reference to establish future automated segmentation protocols.

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer's Dementia.

Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g., semantic object memory impairments) may predate or accompany ERC (i.e., episodic memory) dysfunction in the preclinical course of typical AD. We developed formulae estimating mPRC and ERC integrity (i.e., cortical thickness) using common neuropsychological tests in 31 healthy individuals and 58 early AD patients. These formulae estimated the longitudinal courses of mPRC and ERC functioning in independent groups of 28 optimally healthy individuals who developed AD (NC-AD) over 2.8-13.4 years and 28 pairwise-matched, stable, healthy individuals (NC-NC). Mixed models demonstrated significantly worse NC-AD than NC-NC estimated mPRC and ERC functioning at the earliest observation, 12 years preceding diagnosis, and a significant decline 4 years preceding the AD diagnosis. These findings demonstrate that specific neuropsychological impairments occur early in the course of preclinical AD and that tasks measuring mPRC functioning may serve as additional, powerful markers of preclinical AD.

Cortical thinning of parahippocampal subregions in very early Alzheimer's disease

The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimer's dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination score = 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination score = 28) compared to demographically matched controls. PHG structures were manually segmented (blinded rater) and cortical thicknesses extracted. ERC and mPRC were similarly atrophied in both patient groups. The lPRC was atrophied in the AD group only. Thus, atrophic changes in very early AD broadly map onto the pattern of neurofibrillary tangle spreading and suggest that mPRC, ERC, and lPRC, but not PHC-associated functional impairments, characterize very early-stage AD.

Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer’s disease

Alzheimer’s disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled.

Medial perirhinal cortex disambiguates confusable objects

Our brain disambiguates the objects in our cluttered visual world seemingly effortlessly, enabling us to understand their significance and to act appropriately. The role of anteromedial temporal structures in this process, particularly the perirhinal cortex, is highly controversial. In some accounts, the perirhinal cortex is necessary for differentiating between perceptually and semantically confusable objects. Other models claim that the perirhinal cortex neither disambiguates perceptually confusable objects nor plays a unique role in semantic processing. One major hurdle to resolving this central debate is the fact that brain damage in human patients typically encompasses large portions of the anteromedial temporal lobe, such that the identification of individual substructures and precise neuroanatomical locus of the functional impairments has been difficult. We tested these competing accounts in patients with Alzheimer’s disease with varying degrees of atrophy in anteromedial structures, including the perirhinal cortex. To assess the functional contribution of each anteromedial temporal region separately, we used a detailed region of interest approach. From each participant, we obtained magnetic resonance imaging scans and behavioural data from a picture naming task that contrasted naming performance with living and non-living things as a way of manipulating perceptual and semantic confusability; living things are more similar to one another than non-living things, which have more distinctive features. We manually traced neuroanatomical regions of interest on native-space cortical surface reconstructions to obtain mean thickness estimates for the lateral and medial perirhinal cortex and entorhinal cortex. Mean cortical thickness in each region of interest, and hippocampal volume, were submitted to regression analyses predicting naming performance. Importantly, atrophy of the medial perirhinal cortex, but not lateral perirhinal cortex, entorhinal cortex or hippocampus, significantly predicted naming performance on living relative to non-living things. These findings indicate that one specific anteromedial temporal lobe region—the medial perirhinal cortex—is necessary for the disambiguation of perceptually and semantically confusable objects. Taken together, these results support a hierarchical account of object processing, whereby the perirhinal cortex at the apex of the ventral object processing system is required to bind properties of not just perceptually, but also semantically confusable objects together, enabling their disambiguation from other similar objects and thus comprehension. Significantly, this model combining a hierarchical object processing architecture with a semantic feature statistic account explains why category-specific semantic impairments for living things are associated with anteromedial temporal lobe damage, and pinpoints the root of this syndrome to perirhinal cortex damage.