Biology subjects

Hipp, J. F.

Publications and source records attributed to Hipp, J. F..

7 recordsLinked to original sources

bioRxiv2026

Linking human brain functional connectivity to underlying neurotransmission

The human brain is organized into interacting functional systems. Their underlying neurobiological mechanisms remain difficult to study in vivo. Here, we adopt a topological framework to quantify the association between neurobiology and brain functional connectivity derived from both resting-state fMRI and MEG. Across six healthy adult cohorts (n = 19-112), regional variation in fMRI connectivity robustly aligns with the distribution of neurotransmitter receptors and transporters. These patterns are present in every single subject, replicate across all cohorts, and are mirrored in MEG. Most prominently, noradrenergic modulation of connectivity in a sensorimotor-insular network is consistently detected across individuals and linked to autonomic arousal. In pharmacological and clinical samples, associations are sensitive to neurotransmitter system manipulation and are altered in early psychosis, aligning with clinical symptomatology. These findings provide biological insight into typical and atypical functional organization of the human brain using a framework linking underlying neurobiology to the functional connectome (NEOFC).

neuroscience↗

bioRxiv2024

Qualitative EEG abnormalities signal a shift towards inhibition-dominated brain networks. Results from the EU-AIMS LEAP studies

Qualitative EEG abnormalities are common in Autism Spectrum Disorder (ASD) and hypothesized to reflect disrupted excitation/inhibition balance. To test this, we recently introduced a functional measure of network-level E/I ratio (fE/I). Here, we applied fE/I and other EEG measures to alpha oscillations from source-reconstructed data in the EU-AIMS dataset (267 ASD, 209 controls). We analyzed these measures alongside qualitative EEG abnormalities ranging from slowing of activity to epileptiform patterns, aiming to replicate the findings from the SPACE-BAMBI study. EEG abnormalities were rare in adults and could not be statistically assessed. ASD children-adolescents with EEG abnormalities exhibited lower relative alpha power and fE/I compared to those without. However, EEG-abnormality scoring did not stratify the behavioral heterogeneity of ASD using clinical measures. Surprisingly, several controls also exhibited qualitative EEG abnormalities with a strikingly similar anatomical distribution of reduced fE/I, suggesting a shift towards inhibition-dominated network dynamics in sensory processing regions. The robustness of this association between EEG abnormalities and reduced fE/I was further supported by re-analysis of the SPACE-BAMBI study in source space. Stratification by the presence of EEG abnormalities and their effects on network activity may help understand neurodevelopmental physiological heterogeneity and the difficulties in implementing E/I targeting treatments in unselected cohorts.

neuroscience↗

bioRxiv2024

GREEN: a lightweight architecture using learnable wavelets and Riemannian geometry for biomarker exploration

Spectral analysis using wavelets is widely used for identifying biomarkers in EEG signals. At the same time, Riemannian geometry enabled theoretically grounded machine learning models with high performance for predicting biomedical outcomes from multichannel EEG recordings. However, these methods often rely on handcrafted rules and sequential optimization. In contrast, deep learning (DL) offers end-to-end trainable models that achieve state-of-the-art performance on various prediction tasks but lack interpretability and interoperability with established neuroscience concepts. We introduce GREEN (Gabor Riemann EEGNet), a lightweight neural network that integrates wavelet transforms and Riemannian geometry for processing raw EEG data. Benchmarking on five prediction tasks (age, sex, eyes-closed detection, dementia diagnosis, EEG pathology) across three datasets (TUAB, CAUEEG, TDBRAIN) with over 5000 participants, GREEN outperformed non-deep state-of-the-art models and performed favorably against large DL models on the CAU benchmark using orders of magnitude fewer parameters. Computational experiments showed that GREEN facilitates learning sparse representations without compromising performance. The modularity of GREEN allows for the computation of classical measures of phase synchrony, such as pairwise phase-locking values, which are found to convey information for dementia diagnosis. The learned wavelets can be interpreted as bandpass filters, enhancing explainability. We illustrate this with the Berger effect, demonstrating the modulation of 8-10 Hz power when closing the eyes. By integrating domain knowledge, GREEN achieves a desirable complexity-performance trade-off and learns interpretable EEG representations. The source code is publicly available.

neuroscience↗

bioRxiv2023

Machine learning of brain-specific biomarkers from EEG

Electroencephalography (EEG) has a long history as a clinical tool to study brain function, and its potential to derive biomarkers for various applications is far from exhausted. Machine learning (ML) can guide future innovation by harnessing the wealth of complex EEG signals to isolate relevant brain activity. Yet, ML studies in EEG tend to ignore physiological artifacts, which may cause problems for deriving biomarkers specific to the central nervous system (CNS). We present a framework for conceptualizing machine learning from CNS versus peripheral signals measured with EEG. A common signal representation across the frequency spectrum based on Morlet wavelets allowed us to define traditional brain activity features (e.g. log power) and alternative inputs used by state-of-the-art ML approaches (covariance matrices). Using more than 2600 EEG recordings from large public databases (TUAB, TDBRAIN), we studied the impact of peripheral signals and artifact removal techniques on ML models in exemplary age and sex prediction analyses. Across benchmarks, basic artifact rejection improved model performance whereas further removal of peripheral signals using ICA decreased performance. Our analyses revealed that peripheral signals enable age and sex prediction. However, they explained only a fraction of the performance provided by brain signals. We show that brain signals and body signals, both reflected in the EEG, allow for prediction of personal characteristics. While these results may depend on specific prediction problems, our work suggests that great care is needed to separate these signals when the goal is to develop CNS-specific biomarkers using ML.

neuroscience↗

bioRxiv2019

Motion Coherence and Luminance Contrast Interact in Driving Visual Gamma-Band Activity

Synchronized neuronal population activity in the gamma-frequency range (> 30 Hz) correlates with the bottom-up drive of various visual features. It has been hypothesized that gamma-band synchronization enhances the gain of neuronal representations, yet evidence remains sparse. We tested a critical prediction of the gain hypothesis, which is that features that drive synchronized gamma-band activity interact super-linearly. To test this prediction, we employed whole-head magnetencephalography (MEG) in human subjects and investigated if the strength of visual motion (motion coherence) and luminance contrast interact in driving gamma-band activity in visual cortex. We found that gamma-band activity (64 to 128 Hz) monotonically increased with coherence and contrast while lower frequency activity (8 to 32 Hz) decreased with both features. Furthermore, as predicted for a gain mechanism, we found a multiplicative interaction between motion coherence and contrast in their joint drive of gamma-band activity. The lower frequency activity did not show such an interaction. Our findings provide evidence, that gamma-band activity acts as a cortical gain mechanism that nonlinearly combines the bottom-up drive of different visual features in support of visually guided behavior.

neuroscience↗

bioRxiv2019

Emergence of consciousness and complexity amidst diffuse delta rhythms: the paradox of Angelman syndrome

Numerous theories link consciousness to informationally rich, complex neural dynamics. This idea is challenged by the observation that children with Angelman syndrome (AS), while fully conscious, display a hypersynchronous electroencephalogram (EEG) phenotype typical of information-poor dynamics associated with unconsciousness. If informational complexity theories are correct, then sufficiently complex dynamics must still exist during wakefulness and exceed that observed in sleep despite pathological delta (1 - 4 Hz) rhythms in children with AS. As characterized by multiscale metrics, EEGs from 35 children with AS feature significantly greater complexity during wakefulness compared with sleep, even when comparing the most pathological segments of wakeful EEG to the segments of sleep EEG least likely to contain conscious experiences, and when factoring out delta power differences across states. These findings support theories linking consciousness with complexity and warn against reverse inferring an absence of consciousness solely on the basis of clinical readings of EEG.

neuroscience↗

bioRxiv2018

Reproducible functional connectivity alterations are associated with autism spectrum disorder

Despite the high clinical burden little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here we address these questions in the most comprehensive, large-scale effort to date comprising evaluation of four large ASD cohorts. We followed a strict exploration and replication procedure to identify core rs-fMRI functional connectivity (degree centrality) alterations associated with ASD as compared to typically developing (TD) controls (ASD: N=841, TD: N=984). We then tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status and clinical symptom severity. We find reproducible patterns of ASD-associated functional hyper- and hypo-connectivity with hypo-connectivity being primarily restricted to sensory-motor regions and hyper-connectivity hubs being predominately located in prefrontal and parietal cortices. We establish shifts in between-network connectivity from outside to within the identified regions as a key driver of these abnormalities. The magnitude of these alterations is linked to core ASD symptoms related to communication and social interaction and is not affected by age, sex or medication status. The identified brain functional alterations provide a reproducible pathophysiological phenotype underlying the diagnosis of ASD reconciling previous divergent findings. The large effect sizes in standardized cohorts and the link to clinical symptoms emphasize the importance of the identified imaging alterations as potential treatment and stratification biomarkers for ASD.

neuroscience↗