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Focke, N. K.

Publications and source records attributed to Focke, N. K..

9 recordsLinked to original sources

Correlations of neural predictability and information transfer in cortex and their relation to predictive coding

Predictive-coding like theories agree in describing top-down communication through the cortical hierarchy as a transmission of predictions generated by internal models of the inputs. With respect to the bottom-up connections, however, these theories differ in the neural processing strategies suggested for updating the internal model. Some theories suggest a coding strategy where unpredictable inputs, i.e., those not captured by the internal model, are passed on through the cortical hierarchy, whereas others claim that the predictable part of the inputs is passed on. Here, we addressed which neural coding strategy is employed in cortico-cortical connections using an information-theoretic approach. Our framework allows for quantifying two core aspects of both strategies, namely, predictability of inputs and information transfer, through local active information storage and local transfer entropy, respectively. A previous study on the neural processing of retinal ganglion cells connected to the lateral geniculate nucleus showed a coding for predictable information, captured by an increase in the information transfer with the predictability of inputs. Here, we further investigate predictive coding strategies at the cortical level. In particular, we analyzed LFP activity obtained from intracranial EEG recordings in humans and spike recordings from mouse cortex. We detected cortico-cortical connections with increasing information transfer with the predictability of inputs in recorded channels from frontal, parietal and temporal areas in human cortex. In the mouse visual system, we detected connections exhibiting both an increase and decrease in the information transfer with input predictability, although the former was predominant. Our evidence supports the presence of both predictive coding strategies at the cortical level, with a potential predominance of encoding for predictable information. SummaryThe ability of the brain to infer the hidden causes of sensory experiences has been conceptualized within the computational framework of predictive coding. This framework explains perceptual inference and learning as a process of constantly updating an internal model of the world. Predictive coding describes cortical activity as a communication of sensory evidence and predictions generated from prior expectations. While different views of predictive coding agree on the communication of prior expectations throughout cortex, they differ in how internal expectations are updated. One view states that, to update the internal model, the cortex propagates the mismatch between the expected neural activity and the actual neural response to sensory stimuli. In contrast, another view suggests that the cortex propagates the match between the expected neural activity and the actual neural response. In this work, we were able to tease apart these two views, both in human cortex and the mouse visual system, using information theory. We observed that the brain predominantly propagates expected information, i.e., the match between prior expectations and incoming sensory inputs.

neuroscience↗

Associations between epilepsy-related polygenic risk and brain morphology in childhood

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is associated with a complex genetic architecture, but the translation from genetic risk factors to brain vulnerability remains unclear. Here, we examined associations between epilepsy-related polygenic risk scores for HS (PRS-HS) and brain structure in a large sample of neurotypical children, and correlated these signatures with case-control findings in in multicentric cohorts of patients with TLE-HS. Imaging-genetic analyses revealed PRS-related cortical thinning in temporo-parietal and fronto-central regions, strongly anchored to distinct functional and structural network epicentres. Compared to disease-related effects derived from epilepsy case-control cohorts, structural correlates of PRS-HS mirrored atrophy and epicentre patterns in patients with TLE-HS. By identifying a potential pathway between genetic vulnerability and disease mechanisms, our findings provide new insights into the genetic underpinnings of structural alterations in TLE-HS and highlight potential imaging-genetic biomarkers for early risk stratification and personalized interventions.

neuroscience↗

Extensive MEG time-series phenotyping unveils neural markers predictive of age

Understanding the evolving dynamics of the brain throughout life is pivotal for anticipating and evaluating individual health. While previous research has described age effects on spectral properties of neural signals, it remains unclear which ones are most indicative of age-related processes. This study addresses this gap by analyzing resting-state data obtained from magnetoencephalography in 350 adults (18-88 years). We employed advanced time-series analysis at the brain region level and machine learning to predict age. While traditional spectral features achieved low to moderate accuracy, over a hundred novel time-series features proved superior. Notably, temporal autocorrelation emerged as the most robust predictor of age. Distinct patterns of autocorrelation within the visual and temporal cortex were most informative, offering a versatile measure of age-related signal changes for comprehensive health assessments based on brain activity.

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A worldwide ENIGMA study on epilepsy-related gray and white matter compromise across the adult lifespan

ObjectivesTemporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. MethodsWe studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. ResultsIn TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. ConclusionsThis study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

neuroscience↗

Adult lifespan trajectories of neuromagnetic signals and interrelations with cortical thickness

Oscillatory power and phase synchronization map neuronal dynamics and are commonly studied to differentiate the healthy and diseased brain. Yet, little is known about the course and spatial variability of these features from early adulthood into old age. Leveraging magnetoencephalography (MEG) resting-state data in a cross-sectional adult sample (n = 350), we probed lifespan differences (18-88 years) in connectivity and power and interaction effects with sex. Building upon recent attempts to link brain structure and function, we tested the spatial correspondence between age effects on cortical thickness and those on functional networks. We further probed a direct structure-function relationship at the level of the study sample. We found MEG frequency-specific patterns with age and divergence between sexes in low frequencies. Connectivity and power exhibited distinct linear trajectories or turning points at midlife that might reflect different physiological processes. In the delta and beta bands, these age effects corresponded to those on cortical thickness, pointing to co-variation between the modalities across the lifespan. Structure-function coupling was frequency-dependent and observed in unimodal or multimodal regions. Altogether, we provide a comprehensive overview of the topographic functional profile of adulthood that can form a basis for neurocognitive and clinical investigations. This study further sheds new light on how the brains structural architecture relates to fast oscillatory activity.

neuroscience↗

Linking neuronal and hemodynamic network signatures in the resting human brain

Despite several studies investigating the relationship between blood-oxygen-level-dependent functional MRI (BOLD-fMRI) and neuroelectric activity, our understanding is rather incomplete. For instance, the canonical hemodynamic response function (HRF) is commonly used, regardless of brain region, frequency of electric activity and functional networks. We studied this relationship between BOLD-fMRI and electroencephalography (EEG) signal of the human brain in detail using simultaneous fMRI and EEG in healthy awake human subjects at rest. Signals from EEG sensors were filtered into different frequency bands and reconstructed it in the three-dimensional source space. The correlation of the time courses of the two modalities were quantified on a voxel-by-voxel basis on full-brain level as well as separately for each resting state network, with different temporal shifts and EEG frequency bands. We found highly significant correlations between the BOLD-fMRI signal and simultaneously measured EEG, yet with varying time-lags for different frequency bands and different resting state networks. Additionally, we found significant negative correlations with a much longer delay in the fMRI BOLD signal. The positive correlations were mostly around 6-8 seconds delayed in the BOLD time course while the negative correlations were noticed with a BOLD delay of around 20 to 26 seconds. These positive and negative correlation patterns included the commonly reported alpha and gamma bands but also extend in other frequency bands giving characteristic profiles for different resting state networks. Our results confirm recent works that suggest that the relationship between the two modalities is rather brain region / network-specific than a global function and suggest that applying a global canonical HRF for electrophysiological data is probably insufficient to account for the different spatial and temporal dynamics of different brain networks. Moreover, our results suggest that the HRF also varies in different frequency bands giving way to further studies investigating cross-frequency coupling and its interplay with resting state networks.

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Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

neuroscience↗

Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide enigma study

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

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Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies.

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