Biology subjects

Pana, R.

Publications and source records attributed to Pana, R..

4 recordsLinked to original sources

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↗

bioRxiv2024

HippoMaps: Multiscale cartography of the human hippocampal formation

The hippocampus has a unique microarchitecture, is situated at the nexus of multiple macroscale functional networks, contributes to numerous cognitive as well as affective processes, and is highly susceptible to brain pathology across common disorders. These features make the hippocampus a model to understand how brain structure covaries with function, in both health and disease. Here, we introduce HippoMaps, an open access toolbox and online data warehouse for the mapping and contextualization of subregional hippocampal data in the human brain (http://hippomaps.readthedocs.io). HippoMaps capitalizes on a unified hippocampal unfolding approach as well as shape intrinsic registration capabilities to allow for cross-subject and cross-modal data aggregation. We initialize this repository with an unprecedented combination of hippocampal data spanning 3D ex-vivo histology, ex-vivo 9.4 Tesla MRI, as well as in-vivo structural MRI and resting-state functional MRI (rsfMRI) obtained at 3 and 7 Tesla, together with intracranial encephalography (iEEG) recordings in epilepsy patients. HippoMaps also contains validated tools for spatial map association analysis in the hippocampus that correct for autocorrelation. All code and data are compliant with community standards, and comprehensive online tutorials facilitate broad adoption. Applications of this work span methodologies and modalities, spatial scales, as well as clinical and basic research contexts, and we encourage community feedback and contributions in the spirit of open and iterative scientific resource development.

neuroscience↗

bioRxiv2023

Differential reorganization of episodic and semantic memory systems in epilepsy-related mesiotemporal pathology

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE), as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE as well as 60 age and sex-matched healthy controls and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. In the neocortex, alterations were characterized by reduced functional differentiation in patients in lateral temporal and midline parietal cortices in both hemispheres. In the MTL, on the other hand, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, while hippocampal functional topographies were unaffected. Leveraging MRI proxies of MTL pathology, we furthermore observed alterations in hippocampal microstructure and morphology are associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic, but again not semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, while episodic processes are supported by a network involving both the hippocampus and neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE.

neuroscience↗