Biology subjects

Roth, V.

Publications and source records attributed to Roth, V..

4 recordsLinked to original sources

bioRxiv2023

A common flanking variant is associated with enhanced meiotic stability of the FGF14-SCA27B locus

The factors driving initiation of pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14-SCA27B (GAA)*(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a 5-flanking 17-bp deletion-insertion in 70.34% of alleles (3,463/4,923). This common sequence variation was present nearly exclusively on alleles with fewer than 30 GAA-pure repeats and was associated with enhanced meiotic stability of the repeat locus.

genetics↗

bioRxiv2022

The effect of lysergic acid diethylamide (LSD) on whole-brain functional and effective connectivity

Psychedelics have emerged as promising candidate treatments for various psychiatric conditions, and given their clinical potential, there is a need to identify biomarkers that underlie their effects. Here, we investigate the neural mechanisms of lysergic acid diethylamide (LSD) using regression dynamic causal modelling (rDCM), a novel technique that assesses whole-brain effective connectivity (EC) during resting-state functional magnetic resonance imaging (fMRI). We modelled data from two randomized, placebo-controlled, double-blind, cross-over trials, in which 45 participants were administered 100g LSD and placebo in two resting-state fMRI sessions. We compared EC against whole-brain functional connectivity (FC) using classical statistics and machine learning methods. Multivariate analyses of EC parameters revealed widespread increases in interregional connectivity and reduced self-inhibition under LSD compared to placebo, with the notable exception of primarily decreased interregional connectivity and increased self-inhibition in occipital brain regions. This finding suggests that LSD perturbs the Excitation/Inhibition balance of the brain. Moreover, random forests classified LSD vs. placebo states based on FC and EC with comparably high accuracy (FC: 85.56%, EC: 91.11%) suggesting that both EC and FC are promising candidates for clinically-relevant biomarkers of LSD effects.

neuroscience↗

bioRxiv2020

Enhancing mitochondrial activity in neurons protects against neurodegeneration in CNS inflammation

Central nervous system (CNS) inflammation in multiple sclerosis (MS) drives neuro-axonal loss resulting in irreversible disability. While transcripts of mitochondrial genes are strongly suppressed in neurons during CNS inflammation, it is unknown whether this results in mitochondrial dysfunction and whether interventions that increase mitochondrial function can rescue neurodegeneration. Here we show that suppression of mitochondrial gene transcripts in inflamed neurons was predominantly affecting genes of the electron transport chain resulting in impaired mitochondrial complex IV activity. This was associated with posttranslational inactivation of the transcriptional co-regulator peroxisome proliferator-activated receptor gamma co-activator 1- (PGC-1). Neuronal overexpression of Pgc-1 led to increased numbers of mitochondria, complex IV activity and elevated maximum respiratory capacity. Moreover, Pgc-1- overexpressing neurons showed a higher mitochondrial membrane potential that related to an improved calcium buffering capacity. Accordingly, neuronal deletion of Pgc-1 aggravated neurodegeneration during experimental autoimmune encephalomyelitis (EAE), while neuronal overexpression of Pgc-1 ameliorated EAE disease course and preserved neurons. Our study provides systemic insights into mitochondrial dysfunction in neurons during inflammation and commends elevation of mitochondrial activity as a promising neuroprotective strategy.

neuroscience↗

bioRxiv2020

Minimizing biosignal recording sites for hybrid noninvasive brain/neural robot control

Noninvasive brain/neural controlled robots are promising tools to improve autonomy and quality of life in severe paralysis, but require biosignal recordings, such as electroencephalography (EEG) and electrooculography (EOG), from various sites distributed over the users head. This limits the applicability and practicality of noninvasive brain/neural robot control on an everyday basis. It would thus be very desirable to minimize the number of necessary recording sites paving the way for miniaturized, headset-like EEG/EOG systems that users with hemiplegia can mount by themselves. Here, we introduce a novel EEG/EOG brain/neural robot control strategy using only scalp electrodes placed near cortical sensorimotor areas. The strategy was tested across 16 healthy volunteers engaging in an EEG/EOG brain/neural control task. Classification accuracies were compared using scalp electrodes only vs. the conventional electrode placements across the scalp and face. To evaluate whether cranial muscle artifacts impede classification accuracy, participants were asked to chew during the task. We found that brain/neural classification accuracy was comparable and that chewing did not impact classification accuracies when using scalp electrodes only. Our results suggest that the proposed new strategy allows for reliable EEG/EOG-based brain/neural robot control, a critical prerequisite to broaden the use of noninvasive brain/neural assistive and rehabilitative technologies.

neuroscience↗