Group-guided individual functional parcellation of the hippocampus and application to normal aging.
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ABSTRACT:
SUBMITTER: Zhang J
PROVIDER: S-EPMC8596973 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cortical parcellation based on resting fMRI is an important tool for investigating the functional organization and connectivity of the cerebral cortex. Group parcellation based on co-registration of anatomical images to a common atlas will inevitably result in errors in the locations of the boundaries of functional parcels when they are mapped back from the atlas to the individual. This is because areas of functional specialization vary across individuals in a manner that cannot be fully determined from the sulcal and gyral anatomy that is used for mapping between atlas and individual. We describe a method that avoids this problem by refining an initial group parcellation so that for each subject the parcel boundaries are optimized with respect to that subject's resting fMRI. Initialization with a common parcellation results in automatic correspondence between parcels across subjects. Further, by using a group sparsity constraint to model connectivity, we exploit group similarities in connectivity between parcels while optimizing their boundaries for each individual. We applied this approach with initialization on both high and low density group cortical parcellations and used resting fMRI data to refine across a group of individuals. Cross validation studies show improved homogeneity of resting activity within the refined parcels. Comparisons with task-based localizers show consistent reduction of variance of statistical parametric maps within the refined parcels relative to the group-based initialization indicating improved delineation of regions of functional specialization. This method enables a more accurate estimation of individual subject functional areas, facilitating group analysis of functional connectivity, while maintaining consistency across individuals with a standardized topological atlas.
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Project description:Data-driven parcellations are widely used for exploring the functional organization of the brain, and also for reducing the high dimensionality of fMRI data. Despite the flurry of methods proposed in the literature, functional brain parcellations are not highly reproducible at the level of individual subjects, even with very long acquisitions. Some brain areas are also more difficult to parcellate than others, with association heteromodal cortices being the most challenging. An important limitation of classical parcellations is that they are static, that is, they neglect dynamic reconfigurations of brain networks. In this paper, we proposed a new method to identify dynamic states of parcellations, which we hypothesized would improve reproducibility over static parcellation approaches. For a series of seed voxels in the brain, we applied a cluster analysis to regroup short (3 min) time windows into "states" with highly similar seed parcels. We split individual time series of the Midnight scan club sample into two independent sets of 2.5 hr (test and retest). We found that average within-state parcellations, called stability maps, were highly reproducible (over 0.9 test-retest spatial correlation in many instances) and subject specific (fingerprinting accuracy over 70% on average) between test and retest. Consistent with our hypothesis, seeds in heteromodal cortices (posterior and anterior cingulate) showed a richer repertoire of states than unimodal (visual) cortex. Taken together, our results indicate that static functional parcellations are incorrectly averaging well-defined and distinct dynamic states of brain parcellations. This work calls to revisit previous methods based on static parcellations, which includes the majority of published network analyses of fMRI data. Our method may, thus, impact how researchers model the rich interactions between brain networks in health and disease.
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Project description:We have previously shown that the connectivity of the hippocampus to other regions of the default mode network (DMN) is a strong indicator of memory ability in people with temporal lobe epilepsy (TLE). Recent work in the cognitive neuroscience literature has suggested that the anterior and posterior aspects of the hippocampus have distinct connections to the rest of the DMN and may support different memory operations. Further, structural analysis of epileptogenic hippocampi has found greater atrophy, characterized by mesial temporal sclerosis, in the anterior region of the hippocampus. Here, we used resting state FMRI data to parcellate the hippocampus according to its functional connectivity to the rest of the brain in people with left lateralized TLE (LTLE) and right lateralized TLE (RTLE), and in a group of neurologically healthy controls. We found similar anterior and posterior compartments in all groups. However, there was weaker connectivity of the epileptogenic hippocampus to multiple regions of the DMN. Both TLE groups showed reduced connectivity of the posterior hippocampus to key hubs of the DMN, the posterior cingulate cortex (PCC) and the medial pre-frontal cortex (mPFC). In the LTLE group, the anterior hippocampus also showed reduced connectivity to the DMN, and this effect was influenced by the presence of mesial temporal sclerosis. When we explored brain-behavior relationships, we found that reduced connectivity of the left anterior hippocampus to the DMN hubs related to poorer verbal memory ability in people with LTLE, and reduced connectivity of the right posterior hippocampus to the PCC related to poorer visual memory ability in those with RTLE. These findings may inform models regarding functional distinctions of the hippocampal anteroposterior axis.
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Project description:Cognitive functions show many alternative outcomes and great individual variation during normal aging. We examined learning over the adult life span in CBA mice, along with morphological and electrophysiological substrates. Our aim was to compare cerebellum-dependent delay eyeblink classical conditioning and hippocampus-dependent contextual fear conditioning in the same animals using the same conditioned and unconditioned stimuli for eyeblink and fear conditioning. In a subset of the behaviorally tested mice, we used unbiased stereology to estimate the total number of Purkinje neurons in cerebellar cortex and pyramidal neurons in the hippocampus. Several forms of synaptic plasticity were assessed at different ages in CBA mice: long-term depression (LTD) in both cerebellum and hippocampus and NMDA-mediated long-term potentiation (LTP) and voltage-dependent calcium channel LTP in hippocampus. Forty-four CBA mice tested at one of five ages (4, 8, 12, 18, or 24 months) demonstrated statistically significant age differences in cerebellum-dependent delay eyeblink conditioning, with 24-month mice showing impairment in comparison with younger mice. These same CBA mice showed no significant differences in contextual or cued fear conditioning. Stereology indicated significant loss of Purkinje neurons in the 18- and 24-month groups, whereas pyramidal neuron numbers were stable across age. Slice electrophysiology recorded from an additional 48 CBA mice indicated significant deficits in LTD appearing in cerebellum between 4 and 8 months, whereas 4- to 12-month mice demonstrated similar hippocampal LTD and LTP values. Our results demonstrate that processes of aging impact brain structures and associated behaviors differentially, with cerebellum showing earlier senescence than hippocampus.
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Project description:Neuroimaging studies have reported that the right cerebellar lobule VI is engaged in reading, but its role is unclear. The goal of our study was to identify functionally-dissociable subregions in the right lobule VI and how these subregions contribute to reading in children with normal or impaired reading. In Experiment I, typically developing children performed an orthographic task and a phonological task during functional magnetic resonance imaging (fMRI). We classified the voxels in the right lobule VI into seven zones based on the patterns of functional connectivity with the cerebrum across both tasks. In Experiment II, we compared the brain activation and cerebro-cerebellar connectivities of each subregion between children readers with different reading levels. We did not find significant group differences in cerebellar activation. However, we found that impaired readers had considerably higher functional connectivity between R1 and the right angular gyrus and the right precuneus compared to the control group in the phonological task. These findings show that the right cerebellar lobule VI is functionally parceled and its subregions might be differentially connected with the cerebrum between children with normal reading abilities and those with impaired reading.
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Project description:Understanding the link between structure, function and development in the brain is a key topic in neuroimaging that benefits from the tremendous progress of multi-modal MRI and its computational analysis. It implies, inter alia, to be able to parcellate the brain volume or cortical surface into biologically relevant regions. These parcellations may be inferred from existing atlases (e.g., Desikan) or sets of rules, as would do a neuroanatomist for lobes, but also directly driven from the data (e.g., functional or structural connectivity) with minimum a priori. In the present work, we aimed at using the intrinsic geometric information contained in the eigenfunctions of Laplace-Beltrami Operator to obtain parcellations of the cortical surface based only on its description by triangular meshes. We proposed a framework adapted from spectral clustering, which is general in scope and suitable for the co-parcellation of a group of subjects. We applied it to a dataset of 62 adults, optimized it and revealed a striking agreement between parcels produced by this unsupervised clustering and Freesurfer lobes (Desikan atlas), which cannot be explained by chance. Constituting the first reported attempt of spectral-based fully unsupervised segmentation of neuroanatomical regions such as lobes, spectral analysis of lobes (Spanol) could conveniently be fitted into a multimodal pipeline to ease, optimize or speed-up lobar or sub-lobar segmentation. In addition, we showed promising results of Spanol on smoother brains and notably on a dataset of 15 fetuses, with an interest for both the understanding of cortical ontogeny and the applicative field of perinatal computational neuroanatomy.
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Project description:AbstractThe ability of virally suppressive antiretroviral therapy use to extend the life span of people with HIV (PWH) implies that the age of PWH will also increase. Among PWH, extended survival comes at a cost of earlier onset and increased rates of aging-associated comorbidities and geriatric syndromes, with persistent inflammation and immune dysregulation consequent to chronic HIV infection and to antiretroviral therapy use contributing to an overall decrease in health span. The geroscience hypothesis proposes that the root causes of most aging-related chronic diseases and conditions is the aging process itself. Hence, therapeutically targeting fundamental aging processes could have a greater impact on alleviating or delaying aging-associated comorbidities than addressing each disease individually. Extending the geroscience hypothesis to PWH, we speculate that targeting basic mechanisms of aging will improve overall health with age. Clinical features and pathophysiologic mechanisms of chronic diseases in PWH qualitatively resemble those seen in older adults without HIV. Therefore, drugs that target any of the pillars of aging, including metformin, rapamycin, and nicotinamide adenine dinucleotide precursors, may also slow the rate of onset of age-associated comorbidities and geriatric syndromes in PWH. Drugs that selectively induce apoptosis of senescent cells, termed senolytics, may also improve health span among PWH. Preliminary evidence suggests that senescent cell burden is increased in PWH, implying that senescent cells are an excellent therapeutic target for extending health span. Recently initiated clinical trials evaluating senolytics in age-related diseases offer insights into the design and potential implementation of similar trials for PWH.
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Project description:The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that adult- and older infant-derived parcels are a poor fit with neonatal data, emphasizing the need for neonatal-specific parcels. We next derive a set of 283 cortical surface parcels from a sample of n=261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.
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Project description:The primate hippocampus includes the dentate gyrus, cornu ammonis (CA), and subiculum. CA is subdivided into four fields (CA1-CA3, plus CA3h/hilus of the dentate gyrus) with specific pyramidal cell morphology and connections. Work in non-human mammals has shown that hippocampal connectivity is precisely patterned both in the laminar and longitudinal axes. One of the main handicaps in the study of neuropathological semiology in the human hippocampus is the lack of clear laminar and longitudinal borders. The aim of this study was to explore a histochemical segmentation of the adult human hippocampus, integrating field (medio-lateral), laminar, and anteroposterior longitudinal patterning. We provide criteria for head-body-tail field and subfield parcellation of the human hippocampus based on immunodetection of Rabphilin3a (Rph3a), Purkinje-cell protein 4 (PCP4), Chromogranin A and Regulation of G protein signaling-14 (RGS-14). Notably, Rph3a and PCP4 allow to identify the border between CA3 and CA2, while Chromogranin A and RGS-14 give specific staining of CA2. We also provide novel histological data about the composition of human-specific regions of the anterior and posterior hippocampus. The data are given with stereotaxic coordinates along the longitudinal axis. This study provides novel insights for a detailed region-specific parcellation of the human hippocampus useful for human brain imaging and neuropathology.
| S-EPMC10917878 | biostudies-literature