Biology subjects

Audrain, S.

Publications and source records attributed to Audrain, S..

8 recordsLinked to original sources

bioRxiv2026

HippoGenes: A robust workflow for subregional transcriptomic profiling of the human hippocampus

The human hippocampus is a unique cortical structure central to brain function, plasticity, and disease. Unravelling its complex organization requires the integration of multiscale data, linking molecular features to mesoscale anatomy and macroscale functional patterns. Gene expression is a fundamental microscale phenotype, and its profiling can provide a reference description of how molecular features are distributed across the brain. Capitalizing on recent imaging-transcriptomic analyses, we introduce HippoGenes, a repository of fine-grained gene expression patterns across human hippocampal subregions. We leveraged spatial statistical models and hippocampal surface mapping to reconstruct dense transcriptomic maps from sparse post-mortem tissue samples of the Allen Human Brain Atlas, generating continuous expression estimates for thousands of genes aligned to a common surface-based coordinate system. We illustrate the utility of HippoGenes to (i) map medial-lateral and anterior-posterior transcriptomic gradients that align with subfield and tripartite subdivisions of the hippocampal formation, (ii) examine associations between gene expression and canonical microstructural and functional features of the hippocampus, and (iii) perform a molecular decoding of subregional alterations in neurological patients with hippocampal pathology. HippoGenes provides a framework for exploring the molecular organization of the hippocampus, opening avenues for multiscale integration in health and disease, and is openly available on https://hippogenes.readthedocs.io/.

neuroscience↗

bioRxiv2026

Fiber-tract development contributes to functional specialization in the human hippocampus

Fiber-tracts exhibit distinct projection patterns along the anterior-posterior axis of the hippocampus, promoting a specialization in function. This specialization becomes increasingly pronounced throughout child development, with important implications for neurocognitive outcomes. Developmental changes in fiber-tract properties, including intra-axonal cross-sectional area and myelin content, may contribute to this anterior-posterior functional specialization. To test this, we developed a diffusion-MRI tractography pipeline to identify hippocampal fiber-tracts in single subjects, then examined whether age-related differences in total intra-axonal cross-sectional area and myelin content (T1w/T2w) could predict functional specialization in a large cross-sectional sample (N=539, aged 5-21 years). With age, we found that the cross-sectional area of short-range medial-temporal tracts, which primarily target the anterior/body of the hippocampus, exhibited rapid growth. Concomitantly, the cross-sectional area of long-range occipito-parietal tracts, which primarily target the posterior hippocampus, exhibited a modest pruning. Increases in myelin content were relatively homogenous across fiber-tracts. In support of our hypothesis, we found that the cross-sectional area of fiber-tracts significantly predicts the surface-area of an fMRI-defined posterior system; a sensitive marker of functional specialization in the hippocampus. Tracts targeting early visual cortex (V2, V3, V4) showed the strongest association, with statistical modeling indicating a mediating effect of early-visual tract development on the relation between age and functional specialization. These findings provide evidence consistent with a mechanism whereby anatomical neurodevelopment contributes to functional specialization in the human hippocampus.

neuroscience↗

bioRxiv2026

Connectome-wide mega-analysis identifies a reproducible functional network signature of temporal lobe epilepsy

Resting-state functional magnetic resonance imaging (MRI) studies have reported abnormal intrinsic functional connectivity (FC) across distributed circuits in patients with temporal lobe epilepsy (TLE), indicating a system-level impact of the disorder. However, findings remain inconsistent due to limited sample sizes and methodological heterogeneity, leaving the structural determinants and clinical relevance of FC alterations unresolved. To identify a robust and reproducible FC signature, we conducted a data-driven, connectome-wide mega-analysis in a large multicentre cohort of 652 participants (297 TLE, 73 disease controls, and 282 healthy controls) with multimodal 3T MRI and deep clinical phenotyping. We identified convergent FC reconfigurations at both group and individual levels that preferentially involved densely connected hubs, manifesting as hyperconnectivity in frontoparietal association systems and hypoconnectivity in temporal and paralimbic systems. Integrating structural cortical wiring features further revealed that these extensive alterations were constrained by corticocortical proximity, microstructural similarity, and white matter connectivity. Clinically, the FC phenotype tracked symptom burden and disease progression, informed postsurgical seizure outcome, and distinguished TLE from other focal epilepsies. Collectively, these findings systematically delineate a neurobiologically grounded, hub-centric pattern of intrinsic network disruption in TLE, anchored in temporolimbic and adjacent transmodal systems, with potential utility for individualized phenotypic stratification and outcome prognostication.

neuroscience↗

bioRxiv2025

Personalized Biomarkers of Multiscale Functional Alterations in Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) presents with substantial inter-patient variability in clinical and neuroimaging manifestations. This multicenter study examined inter-individual differences in spatial patterns of intrinsic brain function in TLE using normative modeling at multiple spatial scales and evaluated the effectiveness of individual functional deviations for clinical diagnosis and postsurgical outcome prediction. We analyzed multimodal MRI data on 298 healthy controls, 282 TLE patients, and 45 disease controls with extratemporal epilepsy. Cortical function was profiled at local, regional, and global scales using brain signal variability, regional homogeneity, and node strength. We estimated patient-specific W-score maps to index deviations from normative metrics. Compared to healthy controls, patients with TLE showed considerable variations in patterns of functional alterations across the cortex, with the highest overlap in the ipsilateral mesiotemporal regions. Connectome-based simulation revealed the paralimbic and medial default mode regions as key disease epicenters. Functional changes were primarily underpinned by superficial white matter anomalies. Supervised pattern learning achieved classification AUCs of 0.76 for TLE versus disease controls, 0.74 for left versus right TLE, and 0.63 for seizure-free versus non-seizure-free TLE, with greater contralateral temporal functional deviations correlating with unfavorable postsurgical seizure outcome. Our findings reveal the heterogeneous impact of TLE on intrinsic cortical function. These biomarkers hold promise for clinical translation, guiding precision therapeutics and enhancing presurgical decision-making in TLE.

neuroscience↗

bioRxiv2023

Single voxel autocorrelation reflects hippocampal function in temporal lobe epilepsy

We have previously shown that autocorrelation analyses of BOLD signal applied to single voxels in healthy controls can identify behaviorally-relevant gradients of temporal dynamics throughout the hippocampal long-axis. A question that remains is how changes in the brains functional and structural integrity affect single voxel autocorrelation. In this study we investigate how hippocampal autocorrelation is affected by hippocampal dysfunction by investigating a population of patients with unilateral temporal lobe epilepsy (TLE). Many patients with TLE have mesial temporal sclerosis (MTS), characterized by scarring and neuronal loss particularly in the anterior hippocampus. Here we compared patients with left and right TLE, some with and without MTS, to healthy controls. We applied our single voxel autocorrelation method and data-driven clustering approach to segment the hippocampus based on the autocorrelation of resting state fMRI. We found that patients with left TLE had longer intrinsic timescales (i.e., higher autocorrelation) compared to controls, particularly in the anterior-medial portion of the hippocampus. This was true for both the epileptogenic and non-epileptogenic hemispheres. We also evaluated the extent of cluster preservation (i.e., spatial overlap with controls) of patient autocorrelation clusters and the relationship to verbal and visuospatial memory. We found that patients with greater cluster preservation in the anterior-medial hippocampus had better memory performance. Surprisingly, we did not find any effect of MTS on single voxel autocorrelation, despite the structural changes associated with the condition. These results suggest that spatiotemporal dynamics of activity can be informative regarding the functional integrity of the hippocampus in TLE.

neuroscience↗

bioRxiv2022

Leveraging the resting brain to predict memory decline after temporal lobectomy

ObjectivesAnterior temporal lobectomy as a treatment for temporal lobe epilepsy is associated with a variable degree of postoperative memory decline, and estimating this decline for individual patients is a critical step of preoperative planning. Presently, predicting memory morbidity relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly understood as a network disorder, and memory a network phenomenon. We aimed to assess the utility of functional network measures to predict postoperative memory changes. MethodsPatients with left and right temporal lobe epilepsy (TLE) were recruited from an epilepsy clinic. Patients underwent preoperative resting-state fMRI (rs-fMRI) and pre- and postoperative neuropsychological assessment approximately one year after surgery. We compared functional connectivity throughout the memory network of each patient to a healthy control template based on 19 individuals to identify differences in global organization. A second metric indicated the degree of integration of the to-be-resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical and demographic variables as predictors of memory change after surgery. ResultsSeventy-two adults with TLE were included in this study (37 left/35 right). Left TLE patients with more abnormal memory networks, and with greater functional integration of the to-be-resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change (F(2,31)=12.01, p=0.0001), outperforming standard clinical and demographic variables. None of the variables examined in this study were associated with visuospatial memory change in patients with right TLE. ConclusionResting-state connectivity provides valuable information concerning both the integrity of to-be-resected tissue as well as functional reserve across memory-relevant regions outside of the to-be-resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision-making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE.

neuroscience↗

bioRxiv2022

A role for the anterior hippocampus in autobiographical memory construction regardless of temporal distance

Mounting evidence suggests distinct functional contributions of the anterior and posterior hippocampus to autobiographical memory retrieval, but how these subregions function under different retrieval demands as memories age is not yet understood. Specifically, autobiographical memory retrieval is not a homogenous process, rather, it is thought to consist of multiple stages: an early stage of memory construction and a later stage of detailed elaboration, which may differently engage the hippocampus over time. In the present study, we analyzed data from 40 participants who constructed and overtly elaborated upon recent and remote memories in response to picture cues in the fMRI scanner. We previously reported a temporal gradient in the posterior hippocampus during the elaboration period of autobiographical retrieval, with posterior hippocampal activation observed for recent but not remote timepoints. Here, we consider the previously unanalyzed construction stage of retrieval, where participants searched for and selected a memory. We found no evidence of a temporal gradient during memory construction, instead observing strong anterior hippocampus activity regardless of memory remoteness. Our findings suggest a unique contribution of the anterior hippocampus to the construction process of autobiographical retrieval over time. These findings highlight that retrieval processes, which have yet to be considered in current models of systems consolidation, offer novel insights to hippocampal subregion function over time.

neuroscience↗

bioRxiv2020

Schemas provide a scaffold for neocortical integration at the cost of memory specificity over time

Memory transformation is increasingly acknowledged in theoretical accounts of systems consolidation, yet how memory quality and neural representation change over time and how schemas influence this process remains unclear. In this fMRI study, participants encoded and retrieved schema-congruent and incongruent object-scene pairs using a paradigm that probed coarse and detailed memories over 10-minutes and 72-hours. When a congruent schema was available, details were lost over time as representations were integrated in the medial prefrontal cortex (mPFC), and enhanced post-encoding coupling between the anterior hippocampus and mPFC was associated with coarser memories. Over time, pattern similarity in the hippocampus changed such that the posterior hippocampus represented specific details and the anterior hippocampus represented the general context of specific memories, irrespective of congruency. Our findings suggest schemas are used as a scaffold for accelerated consolidation of congruent information, and illustrate change in hippocampal organization of detailed contextual memory over time.

neuroscience↗