Ultrahigh-resolution fMRI of age-altered hippocampal subfield-cortical interactions

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PROJECT SUMMARY The hippocampus plays a major role in learning and memory, and it is the earliest and most severely affected structure in neurodegenerative disorders such as Alzheimer's disease (AD). The hippocampal formation consists of several distinct subfields, which contribute to different aspects of memory function, as well as exhibit different brain network topologies. A better understanding of how aging affects functional cortical-hippocampal subfield networks is an important step towards the development of an early AD biomarker. Resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) has been widely used to study large-scale functional networks noninvasively. However, the brain-wide functional connectivity of hippocampal subfields in human brain remains poorly understood mainly due to the technical limitation. The physical constraint of excitation slice thickness and insufficient acceleration capability has led to compromises of spatial resolution, field-of-view (FOV), or scan time per volume in several early attempts. We developed a new approach capable of mitigating the aforementioned limitations. The novel technique, named Partition-encoded Simultaneous Multi-slab (PRISM) imaging, achieves sub-millimeter isotropic resolution, while maintaining a high temporal resolution and whole-brain coverage, highly critical for interrogating hippocampal-subfield whole-brain functional networks. Our preliminary results of resting-state FC not only were consistent with the findings that the hippocampus is connected with several cortical regions including parietal association, temporal association and frontal cortices, but also suggested that different hippocampal subfields are associated with different sets of cortical regions. Additionally, the task-based functional connectivity (FC) suggested that the visual association cortex connected stronger with CA4/DG rather than with CA1 during the mnemonic similarity task. Given the preliminary results and previous findings, we hypothesize that 1) the age-dependent effects are heterogeneous between cortical-hippocampal subfield networks, and 2) more neocortical regions show stronger connections with CA4/DG than with CA1 as the age increases. To address these hypotheses, we will further refine the PRISM approach by alleviating signal loss resulting from the T1-saturation effect at the slab boundary and by reducing the sensitivity to head motion. In addition, we will implement the PRISM sequence on the Siemens Prisma 3T system to maximize its future clinical impacts. Thereby, we will investigate the dependency of connectivity strength on age across different cortical-hippocampal subfield networks. Successful implementation of this proposal will fill the gap between local and global hippocampal-subfield circuitry and identify a novel biomarker for early diagnosis of AD in the future.