Biology subjects

Adams, J. N.

Publications and source records attributed to Adams, J. N..

7 recordsLinked to original sources

bioRxiv2024

Age-related constraints on the spatial geometry of the brain

Age-related structural brain changes may be better captured by assessing complex spatial geometric differences rather than isolated changes to individual regions. We applied a novel analytic method to quantify age-related changes to the spatial anatomy of the brain by measuring expansion and compression of global brain shape and the distance between cross-hemisphere homologous regions. To test how global brain shape and regional distances are affected by aging, we analyzed 2,603 structural MRIs (range: 30-97 years). Increasing age was associated with global shape expansion across inferior-anterior gradients, global compression across superior-posterior gradients, and regional expansion between frontotemporal homologues. Specific patterns of global and regional expansion and compression were further associated with clinical impairment and distinctly related to deficits in various cognitive domains. These findings suggest that changes to the complex spatial anatomy and geometry of the aging brain may be associated with reduced efficiency and cognitive dysfunction in older adults.

neuroscience↗

bioRxiv2023

A (Sub)field Guide to Quality Control in Hippocampal Subfield Segmentation on High-resolution T2-weighted MRI

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

neuroscience↗

bioRxiv2023

Medial temporal lobe functional network architecture supports sleep-related emotional memory processing in older adults

Memory consolidation occurs via reactivation of a hippocampal index during non-rapid eye movement slow-wave sleep (NREM SWS) which binds attributes of an experience existing within cortical modules. For memories containing emotional content, hippocampal-amygdala dynamics facilitate consolidation over a sleep bout. This study tested if modularity and centrality--graph theoretical measures that index the level of segregation/integration in a system and the relative import of its nodes--map onto central tenets of memory consolidation theory and sleep-related processing. Findings indicate that greater network integration is tied to overnight emotional memory retention via NREM SWS expression. Greater hippocampal and amygdala influence over network organization supports emotional memory retention, and hippocampal or amygdala control over information flow are differentially associated with distinct stages of memory processing. These centrality measures are also tied to the local expression and coupling of key sleep oscillations tied to sleep-dependent memory consolidation. These findings suggest that measures of intrinsic network connectivity may predict the capacity of brain functional networks to acquire, consolidate, and retrieve emotional memories.

neuroscience↗

bioRxiv2023

NODDI-derived measures of microstructural integrity in medial temporal lobe white matter pathways are associated with Alzheimer's disease pathology and cognitive outcomes

INTRODUCTIONDiffusion tensor imaging has been used to assess white matter (WM) changes in the early stages of Alzheimers disease (AD). However, the tensor model is necessarily limited by its assumptions. Neurite Orientation Dispersion and Density Imaging (NODDI) can offer insights into microstructural features of WM change. We assessed whether NODDI more sensitively detects AD-related changes in medial temporal lobe WM than traditional tensor metrics. METHODSStandard diffusion and NODDI metrics were calculated for medial temporal WM tracts from 199 older adults drawn from ADNI3 who also received PET to measure pathology and neuropsychological testing. RESULTSNODDI measures in medial temporal tracts were more strongly correlated to cognitive performance and pathology than standard measures. The combination of NODDI and standard metrics exhibited the strongest prediction of cognitive performance in random forest analyses. CONCLUSIONSNODDI metrics offer additional insights into contributions of WM degeneration to cognitive outcomes in the aging brain.

neuroscience↗

bioRxiv2023

Pathological brain states in Alzheimer's disease

Dynamic and rapid reconfigurations of neural activation patterns, known as brain states, support cognition. Recent analytic advances applied to functional magnetic resonance imaging now enable the quantification of brain states, which offers a substantial methodological improvement in characterizing spatiotemporal dynamics of activation over previous functional connectivity methods. Dysfunction to the persistence and temporal transitions between discrete brain states may be proximal factors reflecting neurophysiological disruptions in Alzheimers disease, although this has not yet been established. Here, we identified six distinct brain states, representing spatiotemporal trajectories of coactivation at single time points, in older adults across the Alzheimers disease continuum. Critically, we identified a pathological brain state that reflects coactivation within limbic regions. Higher persistence within and transitions to this limbic state, at the expense of other brain states, is associated with an increased likelihood of a clinically impaired diagnosis, worse cognitive performance, greater Alzheimers pathology, and neurodegeneration. Together, our results provide compelling evidence that neural activity settling into a pathological limbic state reflects the progression to Alzheimers disease. As brain states have recently been shown to be modifiable targets, this work may inform the development of novel neuromodulation techniques to reduce limbic state persistence. This application would be an innovative clinical approach to rescue cognitive decline in the early stages of Alzheimers disease.

neuroscience↗

bioRxiv2023

Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories

The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimers disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 {micro}m thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.

neuroscience↗

bioRxiv2022

Entorhinal-hippocampal circuit integrity is related to mnemonic discrimination and amyloid-β pathology in older adults

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimers disease. We tested if functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and A{beta} pathology, measured with PET, in nondemented older adults. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC-DG/CA3 was related to A{beta} pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. A{beta} was further associated with decreased FC and volume within hippocampal subfields. Our findings suggest that A{beta} may indirectly lead to memory impairment through entorhinal-hippocampal circuit dysfunction and neurodegeneration, and provide a mechanism for vulnerability of object mnemonic discrimination.

neuroscience↗