Biology subjects

Auer, H.

Publications and source records attributed to Auer, H..

7 recordsLinked to original sources

bioRxiv2024

From histology to macroscale function in the human amygdala

The amygdala is a subcortical region in the mesiotemporal lobe that plays a key role in emotional and sensory functions. Conventional neuroimaging experiments treat this structure as a single, uniform entity, but there is ample histological evidence for subregional heterogeneity in microstructure and function. The current study characterized subregional structure-function coupling in the human amygdala, integrating post mortem histology and in vivo MRI at ultrahigh fields. Core to our work was a novel neuroinformatics approach that leveraged multiscale texture analysis as well as non-linear dimensionality reduction techniques to identify salient dimensions of microstructural variation in a 3D post mortem histological reconstruction of the human amygdala. We observed two axes of subregional variation in this region, describing inferior-superior as well as medio-lateral trends in microstructural differentiation that in part recapitulated established atlases of amygdala subnuclei. Translating our approach to in vivo MRI data acquired at 7 Tesla, we could demonstrate generalizability of these spatial trends across 10 healthy adults. We then cross-referenced microstructural axes with functional blood-oxygen-level dependent (BOLD) signal analysis obtained during task-free conditions, and revealed a close association of structural axes with macroscale functional network embedding, notably the temporo-limbic, default mode, and sensory-motor networks. Our novel multiscale approach consolidates descriptions of amygdala anatomy and function obtained from histological and in vivo imaging techniques.

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

MULTIMODAL GRADIENTS UNIFY LOCAL AND GLOBAL CORTICAL ORGANIZATION

AO_SCPLOWBSTRACTC_SCPLOWSpecialization of brain areas and subregions, as well as their integration into large-scale networks are key principles in neuroscience. Consolidating both local and global cortical organization, however, remains challenging. Our study developed a new approach to map global cortex-wise similarities of microstructure, structural connectivity, and functional interactions, and integrate these patterns with maps of cortical arealization. Our analysis combined repeated high-field in-vivo 7 tesla (7T) Magnetic Resonance Imaging (MRI) data collected in 10 healthy adults with a recently introduced probabilistic post-mortem atlas of cortical cytoarchitecture. We obtained multimodal eigenvectors describing cortex-wide gradients at the level of microstructural covariance, structural connectivity, and intrinsic functional interactions, and then assessed inter- and intra-area differences in cortex-wide embedding based on these multimodal eigenvectors. Inter-area similarities followed a canonical sensory-fugal gradient, with primary sensorimotor cortex being the most distinctive from all other areas, while paralimbic regions were least distinctive. This pattern largely corresponded to functional connectivity variations across different tasks collected in the same participants, suggesting that the degree of global cortical integration mirrors the functional diversity of brain areas across contexts. When studying heterogeneity within areas, we did not observe a similar relationship, despite overall higher heterogeneity in association cortices relative to paralimbic and idiotypic cortices. The results were replicated in a different dataset. Our findings highlight a close coupling between cortical arealization and global cortical motifs in shaping specialized versus integrative human brain function. SO_SCPLOWIGNIFICANCEC_SCPLOWOur work situates cytoarchitecture-derived cortical areas within multimodal gradients of cortical microstructure, connectivity, and function derived from high-definition multimodal neuroimaging. We demonstrated that primary sensory and motor areas show most distinctive gradient profiles while paralimbic areas were least distinctive, overall recapitulating a sensory-fugal axis. This axis was shown to relate to the diversity of cortical areas across different functional contexts, and findings could be replicated across an independent dataset. Overall, our work shows how frameworks of cortical arealization and macroscale gradients converge in shaping functional specialization versus integration in the human brain.

neuroscience↗

bioRxiv2023

Cerebral perfusion alterations in temporal lobe epilepsy: Structural underpinnings and network disruptions

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSOO_SCPLOWBJECTIVEC_SCPLOWC_ST_ABSNeuroimaging has been the prevailing method to study brain networks in temporal lobe epilepsy (TLE), showing widespread alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. MO_SCPLOWETHODSC_SCPLOWWe studied 24 individuals with pharmaco-resistant TLE and 38 healthy adults using multimodal 3T magnetic resonance imaging. We compared regional CBF changes in patients relative to controls and related our perfusion findings to morphological and microstructural metrics. We further probed inter-regional vascular networks in TLE, using graph theoretical CBF covariance analysis. Finally, we assessed the effects of disease duration to study progressive changes. RO_SCPLOWESULTSC_SCPLOWCompared to controls, individuals with TLE showed widespread CBF reductions, predominantly in fronto-temporal regions, with 83% of patients showing more marked decreases ipsilateral than contralateral to the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partly constrained by grey and white matter changes and topologically segregated from whole-brain perfusion networks. Negative effects of progressive disease duration further targeted regional CBF profiles in patients. Findings were confirmed in a subgroup of patients who remained seizure-free after surgery. IO_SCPLOWNTERPRETATIONC_SCPLOWOur multimodal findings provide insights into vascular contributions to TLE pathophysiology and highlight their clinical potential in seizure lateralization.

neuroscience↗

bioRxiv2023

Atypical connectome topography and signal flow in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is one of the most common pharmaco-resistant epilepsies in adults. While hippocampal pathology is the hallmark of this condition, emerging evidence indicates that brain alterations extend beyond the mesiotemporal epicenter and affect macroscale brain function and cognition. We studied macroscale functional reorganization in TLE, explored structural substrates, and examined cognitive associations. We investigated a multisite cohort of 95 patients with pharmaco-resistant TLE and 95 healthy controls using state-of-the-art multimodal 3T magnetic resonance imaging (MRI). We quantified macroscale functional topographic organization using connectome dimensionality reduction techniques and estimated directional functional flow using generative models of effective connectivity. We observed atypical functional topographies in patients with TLE relative to controls, manifesting as reduced functional differentiation between sensory/motor networks and transmodal systems such as the default mode network, with peak alterations in bilateral temporal and ventromedial prefrontal cortices. TLE-related topographic changes were consistent in all three included sites and reflected reductions in hierarchical flow patterns between cortical systems. Integration of parallel multimodal MRI data indicated that these findings were independent of TLE-related cortical grey matter atrophy, but mediated by microstructural alterations in the superficial white matter immediately beneath the cortex. The magnitude of functional perturbations was robustly associated with behavioral markers of memory function. Overall, this work provides converging evidence for macroscale functional imbalances, contributing microstructural alterations, and their associations with cognitive dysfunction in TLE.

neuroscience↗

bioRxiv2022

DIFFERENTIAL MEMORY IMPAIRMENT ACROSS RELATIONAL DOMAINS IN TEMPORAL LOBE EPILEPSY

BO_SCPLOWACKGROUNDC_SCPLOWTemporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory processes, including episodic, semantic, and spatial memory. While it is widely accepted that TLE-associated hippocampal alterations may underlie global deficits in memory, it remains poorly understood whether TLE may present with shared or unique impairment across distinct relational memory domains. MO_SCPLOWETHODSC_SCPLOWWe administered a recently validated behavioral paradigm to evaluate episodic, semantic, and spatial memory in 20 pharmacoresistant TLE patients and 53 age- and sex-matched healthy controls. We implemented linear mixed effects models to identify memory deficits in individuals with TLE relative to controls, and used partial least squares analysis to identify factors contributing to overall variations in relational memory performance across both cohorts. RO_SCPLOWESULTSC_SCPLOWTLE patients showed marked impairment in episodic memory compared to controls, while spatial and semantic memory remained relatively intact. Findings were robust, with slight decreases in effect sizes after controlling for performance on executive function tests. Via partial least squares analysis, we identified group, age, and bilateral hippocampal volumes as important variables relating to relational memory impairment. CO_SCPLOWONCLUSIONC_SCPLOWOur behavioral framework provides a granular approach for assessing relational memory deficits in people with TLE and may inform future prognostic strategies in patients with hippocampal pathology. Our work warrants further investigations into the underlying neural substrates of relational memory.

neuroscience↗

bioRxiv2022

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a contracted gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post mortem dataset, we observed that in vivo findings reflected topographical variations in cortical lamination patterns, confirming that TLE-related changes in the microstructural gradient reflected increased proximity of regions with more dissimilar laminar structure. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm, and correlated with inter-individual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a parsimonious explanation for functional network reorganization and cognitive dysfunction characteristic of TLE.

neuroscience↗