Biology subjects

Arafat, T.

Publications and source records attributed to Arafat, T..

14 recordsLinked to original sources

bioRxiv2026

Assessing the Functional-Structural Reorganization of Connector Hubs in Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is associated with altered functional connectivity, yet its effects on connector hubs, regions supporting long-range and inter-network communication, remain poorly understood. We used SParsity-based Analysis of Reliable k-hubness to characterize connector hub reorganization in unilateral TLE compared with healthy controls. Patients exhibited significant widespread reductions in k-hubness involving the occipital, cingulate, and precuneus regions, ipsilateral hippocampus, and the bilateral pallidum. Compared to the distribution of k-hubness in healthy controls, the hub disruption index revealed rapid loss of k-hubness alongside emergence of new hubs in contralateral homologous regions. To investigate microstructural substrates of these functional changes, apparent diffusion coefficient and fractional anisotropy from diffusion magnetic resonance imaging were examined. The strongest associations with k-hubness were observed in subcortical structures and the hippocampus. These findings demonstrate that TLE is characterized by widespread, asymmetric connector hub reorganization extending beyond the epileptogenic temporal lobe, revealing distinct patterns of network disruption and reorganization across the brain.

neuroscience↗

bioRxiv2026

HIPPOCAMPAL TAU RELATED SIGNAL INDEXES HYPEREXCITABILITY AND NREM SLEEP MEMORY DYSFUNCTION IN TEMPORAL LOBE EPILEPSY

Background Sleep and memory disturbances are common in temporal lobe epilepsy (TLE), yet their relationship with tau-targeted neuroimaging measures remains unclear. We investigated whether in-vivo temporal 18F-MK6240 tracer retention relates to seizure burden, non-rapid eye movement (NREM) sleep microstructure, and memory performance in TLE. Methods This cross-sectional study was conducted from 2019 to 2024 at the Montreal Neurological Institute-Hospital. Eligible patients had unilateral TLE diagnosed according to International League Against Epilepsy criteria and underwent overnight electroencephalography (EEG) recordings, research-protocol 3T magnetic resonance imaging, and 18F-MK6240 positron emission tomography. Regional 18F-MK6240 standardized uptake value ratios (SUVRs), using the cerebellum as the reference region, were quantified in the ipsilateral hippocampus (defined a priori as the primary region of interest), as well as in peri-hippocampal and lateral temporal regions. Electroclinical and neuropsychological measures, including seizure burden (high vs low), N2 interictal epileptiform discharge frequency (frequent vs non-frequent), and memory performance (impaired vs intact), were classified according to predefined clinical criteria. N2 spindle rate and N3 slow-wave rate were quantified from overnight EEG recordings. Findings Of 70 eligible patients, 25 were included (eight [32%] females; mean age 35.2 years [SD 12.1]). Higher ipsilateral hippocampal 18F-MK6240 uptake was observed in participants with greater focal seizure burden (median [IQR] 0.70 [0.67-0.78] vs 0.64 [0.58-0.65], rank-biserial correlation=-0.58, 95% CI -0.82 to -0.19; p=0.02), was associated with lower N2 spindle rate (r=-0.42, 95% CI -0.70 to -0.03; p=0.04) and higher N3 slow-wave rate (r=0.47; 95% CI 0.09 to 0.73; p=0.02), and was also higher in participants with impaired than intact memory performance (n=21; mean [SD] 0.80 [0.12] vs 0.68 [0.10], Cohen's d=1.15, 95% CI 0.07 to 2.21; p=0.04). Associations outside the hippocampus were generally less consistent and less precise, with the largest non-hippocampal estimate observed in peri-hippocampal regions. Interpretation Higher hippocampal 18F-MK6240 uptake was associated with greater focal seizure burden, altered NREM sleep microstructure, and impaired memory performance in TLE. These findings suggest that hippocampal 18F-MK6240 uptake may represent a candidate marker of circuit vulnerability associated with NREM sleep-memory dysfunction in TLE, warranting validation in larger longitudinal studies.

neuroscience↗

bioRxiv2026

FUNCTIONAL FRAGMENTATION AND STRUCTURAL DRIVERS OF THALAMO-CORTICAL CIRCUITS IN TEMPORAL LOBE EPILEPSY

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSObjectiveC_ST_ABSIn temporal lobe epilepsy (TLE), the thalamus acts as a nexus in a pathophysiological network that implicates mesiotemporal, subcortical, and neocortical regions. Studying a large multimodal and multicentre dataset, we profiled thalamic, hippocampal, and neocortical functional connectivity (FC), assessed structural mediators, and examined clinical associations. MethodsWe studied resting-state FC alongside structural and diffusion MRI data in 250 unilateral TLE patients and 259 healthy controls, with measures aggregated across four independent datasets. Data were processed using open-access neuroinformatics workflows and analyzed at a subregional level to maximize anatomical precision. Statistical analysis and mediation models assessed between-group FC changes, structural contributors, and clinical correlations. ResultsCompared to controls, TLE patients presented with reduced thalamo-cortical FC, which was most marked in mesiotemporal, fronto-central, and occipital regions. Thalamo-hippocampal FC was also reduced, with effects seen in all CA subfields. In the thalamus, FC reductions peaked in the ventral posterior nucleus when considering neocortical target regions and in the mediodorsal nucleus when considering hippocampal target regions. While ipsilateral hippocampal volume and diffusion changes mediated thalamo-hippocampal FC, thalamo-cortical FC appeared decoupled from structural alterations. Findings were consistent in left and right TLE patients, in patients with short and long disease duration, and across imaging sites, suggesting that thalamo-cortical FC imbalances are a consistent signature of TLE. Conversely, thalamo-hippocampal FC was elevated in patients with focal-to-bilateral-tonic-clonic seizures and FC alterations were more marked in the subgroup of operated patients that became seizure-free after surgery. ConclusionOur multi-site findings demonstrate marked thalamic circuit fragmentation in TLE. Ipsilateral findings robustly showed subdivision-specific effects, which point to both mesiotemporal co-lateralization as well as broader system-level involvement. Mediation analyses furthermore confirmed a key role of hippocampal pathology in disrupted thalamo-hippocampal connectivity in TLE, while broader thalamo-cortical fragmentation becomes increasingly independent of mesiotemporal compromise. Critically, thalamic FC represents a network substrate for seizure generalization and can serve as a prognostic indicator for surgical outcome. These results underscore the contribution of the thalamus as a hub in macroscale dysfunction in TLE.

neuroscience↗

bioRxiv2026

The electro-MICA toolbox for integrating electrophysiology within multimodal imaging and connectomics workflows

AO_SCPLOWBSTRACTC_SCPLOWThe integration of electrophysiological recordings with multimodal neuroimaging data holds great promise for advancing our understanding of brain function and neurological disorders. To facilitate this endeavour, we present electro-MICA, an open-access Python toolbox designed to project electrophysiological features from scalp and intracranial electroencephalography (EEG) onto cortical and hippocampal surfaces generated by validated multimodal imaging ecosystems. The toolbox comprises two pipelines: one for intracranial EEG (iEEG) recorded with stereo-EEG depth electrodes, and one for scalp EEG source localization. Both pipelines are grounded in numerical solutions to the electromagnetic equations governing electric activity in the brain, solved using the Boundary Element Method. A key methodological contribution is the use of a current density double layer model for neural generators, which avoids the mathematical singularities introduced by conventional dipole-based models when electrodes are near the cortical surface, a situation that can arise in iEEG. Electrode contacts are additionally modeled with non-zero length, improving physical realism. Scalp EEG source localization is performed using eLORETA on a subject-specific three-layer head model derived from the anatomical input. Validation against empirical gamma-band iEEG data from 32 subjects demonstrates that the distributed generator model outperforms both distance-based and dipole-based alternatives. An illustrative clinical example demonstrates the toolboxs capacity to reveal associations between intracranial spike rates, cortical thickness, and anatomical connectivity in an epilepsy patient. Electro-MICA requires no parameter selection from the user, facilitating straightforward multimodal analyses in both research and clinical settings. The toolbox is available at github.com/MICA-MNI/electromica with extensive online documentation at electromica.readthedocs.io.

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↗

bioRxiv2026

Precision mapping and molecular contextualization of surgical outcome epicenters in temporal lobe epilepsy

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy is the most common drug-resistant epilepsy, with surgical resection offering the primary path to seizure freedom. Despite standardized approaches, a substantial proportion of patients experience seizure recurrence, and the neurobiological substrates underlying these divergent outcomes remain unclear. We applied an individualized normative modeling framework to multimodal preoperative MRI data in a group that subsequently underwent surgical resection, to characterize patient-specific structural deviations and identify disease epicenters. Patients who became seizure-free exhibited spatially coherent abnormalities localized to the hippocampus and ipsilateral association regions, anchored in agranular limbic territories and enriched for genes linked to calcium-dependent signaling. Non-seizure-free patients, on the other hand, showed a more heterogeneous and distributed pattern of deviations, consistent with a "temporal-plus" network organization, and broader neuromodulatory dysregulation. Crucially, overlap between resected tissue and network-defined epicenters was closely associated with seizure freedom, independent of total resection volume. These findings provide a multiscale framework for precision surgical planning, shifting the focus from standardized tissue removal to targeted disconnection of patient-specific pathological hubs.

neuroscience↗

bioRxiv2025

The Hemodynamic Response Function Varies Across Anatomical Location and Pathology in the Epileptic Brain

The hemodynamic response function (HRF) links neuronal activity to functional magnetic resonance imaging (fMRI) signals. While most fMRI studies use a "canonical" HRF, increasing evidence from studies of healthy subjects suggests that the HRF depends on anatomical location and disease states. Here, we investigate how HRF variability relates to anatomical location and pathology in the epileptic brain, using a large simultaneous electroencephalogram and fMRI dataset. Applying HRF deconvolution and temporal decomposition, we built the first whole-brain HRF library specific to epilepsy, identifying four distinct shape groups. We mapped HRF features across parcellations of two atlases using novel Bayesian hierarchical models. In non-epileptogenic regions, HRF shape and spatial distributions align with findings from healthy subjects. Within pathological regions, they vary significantly according to pathology. Our results indicate that HRF variability is associated with pathology, in addition to its dependence on anatomical location, motivating region- and pathology-based HRF modulation in epilepsy studies.

neuroscience↗

bioRxiv2025

Memory network activity flow failures in temporal and frontal lobe epilepsy

Declarative memory deficits represent considerable challenges to adequate functioning and wellbeing in temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE), two of the most common pharmaco-resistant epilepsies. TLE and FLE are impacted differently however, with TLE affecting primarily episodic, and mildly semantic memory, while FLE presenting with overall lesser declarative impairments and a greater involvement of language processes. Although functional magnetic resonance imaging (fMRI) studies are overall compatible with differential disruptions of medial temporal and fronto-limbic networks in both syndromes, direct comparisons of brain activity and connectivity remain scarce. The current study investigated how alterations in intrinsic functional brain organization, as mapped with resting-state connectivity (rsFC), shapes altered brain network activations in both episodic and semantic memory states. To this end, we acquired task- and rs-fMRI data in 28 TLE patients and 17 FLE patients and 87 age- and sex-matched healthy controls (HCs). We used activity flow mapping (AFM), a generative machine learning technique that derives plausible task activation patterns via individualized rsFC as well as normative task activation data. Previous studies in HC as well as patient populations have shown that this technique has been effective in identifying mechanisms contributing to atypical functional organization across different context. Overall, AFM reliably predicted task activations across HC, TLE, and FLE, but prediction accuracy was consistently reduced in both patient groups, indicating impaired propagation of task-relevant signals. These reductions co-occurred with abnormal episodic and semantic task activation patterns, atypical rsFC, and behavioral profiles marked by preserved semantic but impaired episodic memory performance in both patient groups. Importantly, although neither task-evoked abnormalities nor rsFC disruptions alone were associated with clinical variables, lower AFM accuracy in patients robustly tracked poorer episodic and semantic memory performance and longer disease duration. Prediction accuracy was driven more by intrinsic functional than structural network features, suggesting that altered network communication, rather than gross anatomy, constrains AFM in pharmaco-resistant epilepsy. Our work revealed syndrome-specific yet convergent disruptions in paralimbic and heteromodal association systems, linking intrinsic dysconnectivity to a shared episodic vulnerability and semantic resilience across TLE and FLE. By modelling how intrinsic connectivity shapes task-evoked responses, AFM provides a mechanistic account of imbalanced memory-state activations and isolates network-flow pathways as targets for intervention and rehabilitation.

neuroscience↗

bioRxiv2025

An open dataset of cerebral tau deposition in young healthy adults based on MK6240 positron emission tomography

Tauopathies are pathologies wherein phosphorylated insoluble tau aggregates in neurons, leading to dysfunction and degeneration. Positron emission tomography (PET) enables measurement of in vivo tau, with second-generation radiotracers such as [18F]MK6240 showing high tau affinity with minimal off-target binding. While tauopathies are commonly linked to age-related neurodegenerative diseases, notably Alzheimers disease (AD), evidence suggests pathophysiological cascades may begin long before clinical onset. Increasingly, tau is recognized in pathologies affecting younger individuals, including autosomal dominant AD, Niemann-Pick disease type C, chronic traumatic encephalopathy, and epilepsy, thus highlighting the importance of normative data in non-geriatric populations. Here, we present a dataset of 33 young to middle-age healthy adults (mean age 34.0{+/-}10.4 years, 12 female) with [18F]MK6240 PET data and T1w magnetic resonance imaging. Longitudinal data are also available in a subset of 9 participants with a minimum follow-up time of 1 year. Our dataset aims to support imaging biomarker studies on younger individuals potentially at risk for AD and to advance work in tauopathies affecting non-geriatric populations generally excluded from neurodegeneration studies.

neuroscience↗

bioRxiv2025

In-vivo evidence for increased tau deposition in temporal lobe epilepsy

Temporal lobe epilepsy (TLE), the most common pharmaco-resistant epilepsy in adults, has been linked to structural brain changes extending beyond the mesiotemporal areas. While not traditionally viewed as a neurodegenerative disorder, recent ex-vivo studies have shown elevated levels of misfolded tau protein in TLE. This study investigated tau deposition in TLE patients using the in-vivo PET tracer [18F]MK-6240. We studied 28 TLE patients and 28 healthy controls to assess tau uptake and its relationship with brain connectivity, clinical variables, and cognitive function alongside post-surgical tissue from a subset of patients. Compared to controls, TLE patients exhibited markedly increased [18F]MK-6240 uptake in bilateral superior and medial temporal regions and the parietal cortex, with tau accumulation following regional functional and structural connectivity and cognitive impairment. Immunohistochemistry analysis confirmed variable phosphorylated tau staining in 5/6 operated cases with available specimens. These findings suggest that tau accumulation contributes to cognitive decline observed in TLE, supporting a potential role of tau in epilepsy-related neurodegeneration.

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↗

bioRxiv2025

Human cortical dynamics reflect graded contributions of local geometry and network topography

The brain is a physically embedded and heavily interconnected system that expresses neural rhythms across multiple time scales. While these dynamics result from the complex interplay of local and inter-regional factors, the relative contribution of such mechanisms across the cortex remains unclear. Our study explores geometric, microstructural, and connectome-level constraints on cortex-wide neural activity. We leverage intracranial electroencephalography recordings to derive a coordinate system of human cortical dynamics. Using multimodal neuroimaging, we could then demonstrate that these patterns are largely explainable by geometric properties indexed by inter-regional distance. However, dynamics in transmodal association regions are additionally explainable by incorporation of inter-regional microstructural similarity and connectivity information. Our findings are generally consistent when cross-referencing electroencephalography and imaging data from large-scale atlases and when using data obtained in the same individuals, suggesting subject-specificity and population-level generalizability. Together, our results suggest that the relative contribution of local and macroscale constraints on cortical dynamics varies systematically across the cortical sheet, specifically highlighting the role of transmodal networks in inter-regional cortical coordination.

neuroscience↗

bioRxiv2024

Structural compromise in spiking cortex and connected networks

INTRODUCTIONEpilepsy is increasingly conceptualized as a network disorder, and advancing methods for its diagnosis and treatment requires characterizing both the epileptic generator and related networks. We combined multimodal magnetic resonance imaging (MRI) and high-density electroencephalography (HD-EEG) to interrogate alterations in cortical microstructure, morphology, and intrinsic local function within and beyond spiking tissue in focal epilepsy. METHODSWe studied 25 patients with focal epilepsy (12F, mean {+/-} SD age = 31.28 {+/-} 9.30 years) and 55 age- and sex-matched healthy controls, subdivided into a group of 30 for imaging feature normalization (15F, 31.40 {+/-} 8.74 years) and a group of 25 for replication (12F, 31.04 {+/-} 5.65 years). The 3T MRI acquisition included T1-weighted, diffusion, quantitative T1 relaxometry, and resting-state functional imaging. Open-access MRI processing tools derived cortex-wide maps of morphology and microstructure (cortical thickness, mean diffusivity, and quantitative T1 relaxometry) and intrinsic local function and connectivity (timescales, connectivity distance, and node strength) for all participants. Multivariate approaches generated structural and functional alteration scores for each cortical location. Using HD-EEG electrical source imaging, the most prominent spike type was localized and we quantified MRI alterations within spike sources, as well as in proximal and connected networks. RESULTSRegions harboring spike sources showed increased structural MRI alterations compared to the rest of the brain in patients. Structural compromise extended to all regions with close functional coupling to spike sources, but not to anatomical neighbors of spike sources. This finding was replicated using average control functional and anatomical matrices instead of patient-specific matrices. CONCLUSIONSpiking regions contain more marked alterations in microstructure and morphology than the remaining cortex, and combining imaging with neurophysiology techniques may ultimately help identify the epileptogenic zone non-invasively. There are nevertheless broader networks effects, which may relate to a cascading of structural changes to functionally connected cortices. These results underscore the utility of combining high-definition MRI and EEG approaches for characterizing epileptogenic tissue and assessing distributed network effects.

neuroscience↗

bioRxiv2024

Pharmaco-resistant temporal lobe epilepsy gradually perturbs the cortex-wide excitation-inhibition balance

AO_SCPLOWBSTRACTC_SCPLOWExcitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with a mounting body of previous research focusing on elucidating its cellular manifestations. However, there are limited studies into E/I imbalance at macroscale and its microcircuit-level mechanisms and clinical associations. In our current work, we computed the Hurst exponent--a previously validated index of the E/I ratio--from resting-state fMRI time series, and simulated microcircuit parameters using biophysical computational models. We found a broad reduction in the Hurst exponent in pharmaco-resistant temporal lobe epilepsy (TLE), indicative of a shift towards more excitable network dynamics. Connectome decoders pointed to temporolimbic and frontocentral areas as plausible network epicenters of E/I imbalance. Computational simulations further revealed that enhancing cortical excitability in patients likely reflected atypical increases in recurrent connection strength of local neuronal ensembles. Moreover, mixed cross-sectional and longitudinal analyses revealed heightened E/I elevation in patients with longer disease duration, more frequent electroclinical seizures and inter-ictal epileptic spikes, and worse cognitive functioning. Replicated in an independent dataset, our work provides compelling in-vivo evidence of a macroscale shift in E/I balance in TLE patients that undergoes progressive changes and underpins cognitive impairments, potentially informing treatment strategies targeting E/I mechanisms.

neuroscience↗