Investigating the properties of hippocampal subfield networks.
Poster No:
1586
Submission Type:
Abstract Submission
Authors:
Samuel Berry1, Marie-Lucie Read2, Jiaxiang Zhang3, Kim Graham4, Andrew Lawrence4, John Aggleton2, Carl Hodgetts5
Institutions:
1Royal Holloway University of London, London, London, 2Cardiff University, Cardiff, United Kingdom, 3Swansea University, Swansea, United Kingdom, 4The University of Edinburgh, Edinburgh, United Kingdom, 5Royal Holloway University of London, London, United Kingdom
First Author:
Co-Author(s):
Introduction:
Studies in animal models suggest that the subicular complex of the hippocampus (HC) may act as a hub within an extended event memory system, serving as the primary source of HC outputs to several key regions in this network, including retrosplenial cortex, mammillary bodies and anterior thalamic nuclei(1). Despite its privileged position in this system, we have limited knowledge of subicular network properties in the human brain. Addressing this, we applied network analysis approaches to both structural and functional 7T MRI data, comparing subiculum connectivity to CA1 and CA2/3. A key challenge for MRI network analysis (particularly with diffusion-based tractography) is the proliferation of false positives. Therefore, we contextualise our results with regards to historical anatomical tract-tracing data. This cross-modality and cross-species approach helps us to interrogate this network whilst understanding the anatomical validity of these MRI-constructed connectomes.
Methods:
Subjects were 50 adults from the Young Adults Human Connectome Project. All samples had 7T task-free functional, diffusion, and sub-millimetre structural scans. Fourteen extended HC network ROIs were defined with reference to a comprehensive review of HC tract-tracing data by Aggleton & Christiansen, 2015. Human HC segmentation was performed using the automated segmentation of hippocampal subfields (ASHS)(2) tool, with the other human ROI's defined using freesurfer(3,8,9). Registrations were performed using FS(4)L flirt, fnirt and ANTs(5) syn algorithms. Functional connectivity (FC) was measured via BOLD correlations and structural connectivity (SC) was estimated using anatomically constrained probabilistic tractography analysis via MRTRIX6. SC and FC connectivity measures were then used as inputs for GT analysis via the brain connectivity toolbox(7), in Matlab. Descriptive network statistics (such as connectivity strength) were calculated. Additionally, we performed a series of 'virtual lesions' by iteratively removing and HC ROIs and re-calculating global efficiency scores.
Results:
Tractography results demonstrated that the subiculum had the highest connectivity strength, followed by CA1 (vs subiculum d = 0.56, p = 0.01) and CA2/3 (vs subiculum d = 3.13, p <0.0001) (figure 1). Differences with CA1 were mostly driven by connections to the entorhinal cortex (t = 11.76, p <0001). Structural virtual lesion analysis showed that removing CA1 had the greatest effect on the network (d = 0.27, p < 0.001), followed by subiculum (d = 0.16, p <0.001), whereas CA2/3 removal increased network efficiency (d = 0.21, p < 0.001)(figure 1). All statistical comparisons between the ROIs were statistically significant (p<0.001, Bonferroni corrected). Functional connectivity results showed CA1 to have the highest connectivity strength, followed by the subiculum (vs CA1 d = 1.56, p < 0.001), and CA2/3 (vs subiculum d =4.48, p < 0.001) (figure 2). Functional virtual lesion analysis showed that removing the subiculum had a significantly larger effect (d = 0.47, p < 0.001) than CA1 (d = 0.22, p < 0.001) and CA2/3 (0.42, p<0.001 (figure 2).
Conclusions:
We provide novel high resolution structural and functional evidence for the subiculum, and CA1's, role as key regions within the extended HC network. This work largely corroborates previous anatomical tract-tracing studies in animal models, endorsing the role of the subiculum as a key HC hub. Interestingly, while our findings align with expectations regarding the subiculum's role as the principal structural output region of the hippocampus, they reveal a higher degree of functional connectivity with CA1 than anticipated based solely on anatomical data. Future work will focus on the interrogation of specific tracts generated through the diffusion analysis with direct comparisons to macaque MRI data.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 1
fMRI Connectivity and Network Modeling
Segmentation and Parcellation
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures 2
Keywords:
FUNCTIONAL MRI
HIGH FIELD MR
Memory
MRI
STRUCTURAL MRI
Sub-Cortical
Tractography
Other - Hippocampus; CA1; CA3; Subiculum
1|2Indicates the priority used for review
Provide references using author date format
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