5 research outputs found
Frontal and insular input to the dorsolateral temporal pole in primates: Implications for auditory memory
The temporal pole (TP) has been involved in multiple functions from emotional and
social behavior, semantic processing,memory, language in humans and epilepsy surgery,
to the fronto-temporal neurodegenerative disorder (semantic) dementia. However, the
role of the TP subdivisions is still unclear, in part due to the lack of quantitative data
about TP connectivity. This study focuses in the dorsolateral subdivision of the TP:
area 38DL. Area 38DL main input originates in the auditory processing areas of the
rostral superior temporal gyrus. Among other connections, area 38DL conveys this
auditory highly processed information to the entorhinal, rostral perirhinal, and posterior
parahippocampal cortices, presumably for storage in long-term memory (Muñoz-López
et al., 2015). However, the connections of the TP with cortical areas beyond the temporal
cortex suggest that this area is part of a wider network. With the aim to quantitatively
determine the topographical, laminar pattern and weighting of the lateral TP afferents
from the frontal and insular cortices, we placed a total of 11 tracer injections of the
fluorescent retrograde neuronal tracers Fast Blue and Diamidino Yellow at different levels
of the lateral TP in rhesus monkeys. The results showed that circa 50% of the total
cortical input to area 38DL originates in medial frontal areas 14, 25, 32, and 24 (25%);
orbitofrontal areas Pro and PAll (15%); and the agranular, parainsular and disgranular
insula (10%). This study sets the anatomical bases to better understand the function of
the dorsolateral division of the TP. More specifically, these results suggest that area 38DL
forms part of the wider limbic circuit that might contribute, among other functions, with
an auditory component to multimodal memory processing
Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions
The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ÎČ and α-synuclein pathology were rated on a scale of 0 (absent)â3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 Ă 0.2 Ă 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearmanâs rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = â 0.27 to r = â 0.46), and (2) tau with BA35 (r = â 0.31) and SRLM thickness (r = â 0.33). In amyloid-ÎČ and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = â 0.40), BA35 (r = â 0.55), subiculum (r = â 0.42) and CA1 thickness (r = â 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ÎČ suggests a role of Primary Age-Related Tauopathy in neurodegeneration
Unfolding the Medial Temporal Lobe Cortex to Characterize Neurodegeneration Due to Alzheimerâs Disease Pathology Using Ex vivo Imaging
Neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimerâs Disease (AD). In this work, we investigate the relationship between MTL morphometry features derived from high-resolution ex vivo imaging and histology-based measures of NFT pathology using a topological unfolding framework applied to a dataset of 18 human postmortem MTL specimens. The MTL has a complex 3D topography and exhibits a high degree of inter-subject variability in cortical folding patterns which poses a significant challenge for volumetric registration methods typically used during MRI template construction. By unfolding the MTL cortex, the proposed framework explicitly accounts for the sheet-like geometry of the MTL cortex and provides a two-dimensional reference coordinate space which can be used to implicitly register cortical folding patterns across specimens based on distance along the cortex despite large anatomical variability. Leveraging this framework in a subset of 15 specimens, we characterize the associations between NFTs and morphological features such as cortical thickness and surface curvature and identify regions in the MTL where patterns of atrophy are strongly correlated with NFT pathology
Ex vivo MRI atlas of the human medial temporal lobe : characterizing neurodegeneration due to tau pathology
Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimerâs disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages
Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe
Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers