Biology subjects

Arena, A.

Publications and source records attributed to Arena, A..

5 recordsLinked to original sources

bioRxiv2026

Nyx: a flexible framework for sleep scoring across species, lifespan and modalities

Sleep is a key factor in almost every physiological process, yet scoring tools lag behind innovations in basic to clinical research. New automated algorithms are trained on narrow datasets, typically healthy adult mouse or human, and fail to generalise, leaving labs to fall back on slow, laborious, and often poorly reproducible manual scoring. Here we introduce Nyx, an unsupervised framework built on principal component analysis that flexibly clusters epochs into sleep states, akin to how spike-sorting algorithms cluster single-neuron activity. Validated on about 8,000 hours spanning 19 independent datasets, it generalises across species, lifespan, recording modalities, and altered sleep architectures, matching human inter-scorer agreement. Beyond this, Nyx opens new ground for modern sleep research: classifying NREM subtypes in rodents, revealing states that cut across canonical boundaries in non-mammalian species, and enabling real-time, closed-loop manipulation. Distributed as an open-source package with a graphical user interface, Nyx offers an accessible, explainable framework built to scale with the pace of innovation itself.

neuroscience↗

bioRxiv2022

The activity of deep cortical layers characterizes thecomplexity of brain responses during wakefulnessfollowing electrical stimulation

It has been suggested that the complexity of the brain is closely related to its state of consciousness. The perturbational complexity index (PCI) has been used in humans and rodents to distinguish conscious from unconscious states based on the global cortical responses (recorded by electroencephalography; EEG) to local cortical stimulation (CS). However, it has been unclear how different cortical layers respond to CS and contribute to the resulting intra- and inter-areal cortical communication and PCI. A detailed investigation of these local dynamics is needed to understand the basis for PCI. We hypothesized that the complexity level of global cortical responses (PCI) corresponds to variations in layer-specific activity and connectivity patterns. We investigated global cortical dynamics and layer specific activity in mice, combining cortical electrical stimulation, global EEG, and local multi-electrode, laminar recordings from layers 1-6 in somatosensory cortex, during wakefulness and general anesthesia (sevoflurane). We found that transition from wake to sevoflurane anesthesia correlated with a drop in global and local PCI values (complexity). This was accompanied by a local decrease in neural firing rate, spike-field coherence, and long-range functional connectivity specific to deep layers (L5, L6). Our results suggest that deep cortical layers are mechanistically important for changes in PCI, and thereby for variations in the states of consciousness. HighlightsO_LIAnesthesia caused a reduction in the perturbational complexity index (PCIST) at both global (inter-areal) and local (intra-areal, across layers) cortical scales. C_LIO_LIDeep cortical layers (L6 and L5), exhibited strong connectivity with remote cortical areas during wakefulness but not during anesthesia. C_LIO_LILayer 6 showed the strongest modulation of spike firing and spike field coherence compared to more superficial layers during wakefulness. C_LI

neuroscience↗

bioRxiv2022

Novel feature selection methods for construction of accurate epigenetic clocks

Epigenetic clocks allow the accurate prediction of age based on the methylation status of specific CpG sites in a variety of tissues. These predictive models can be used to distinguish the biological age of an organism from its chronological age, and are a powerful tool to measure the effectiveness of aging interventions. There is a growing need for methods to efficiently construct epigenetic clocks. The most common approach is to create clocks using elastic net regression modelling of all measured CpG sites, without first identifying specific features or CpGs of interest. The addition of feature selection approaches provides the opportunity to reduce the cost and time of clock development by decreasing the number of CpG sites included in clocks. Here, we apply both classic feature selection methods and novel combinatorial methods to the development of epigenetic clocks. We perform feature selection on the human whole blood methylation dataset of [~]470,000 CpG features published by Hannum and colleagues (2015). We develop clocks to predict age, using a variety of feature selection approaches, and all clocks have R2 correlation scores of greater than 0.73. The most predictive clock uses 35 CpG sites for a R2 correlation score of 0.87. The five most frequent sites across all clocks are also modelled to build a clock with a R2 correlation score of 0.83. These two clocks are validated on two external datasets where they maintain excellent predictive accuracy and outperform Hannum et als model in accuracy of age prediction despite using significantly less CpGs. We also identify the associated gene regulatory regions of these CpG sites, which may be possible targets for future aging studies. These novel feature selection algorithms will lower the number of sites needed to be sequenced to build clocks and allow conventionally expensive aging epigenetic studies to cost a fraction of what it would normally.

bioinformatics↗

bioRxiv2021

Does the posteromedial cortex play a primary role for the capacity for consciousness in rats?

It remains unclear how specific cortical regions contribute to the brains overall capacity for consciousness. Clarifying this could help distinguish between theories of consciousness. Here, we investigate the association between markers of regionally specific (de)activation and the brains overall capacity for consciousness. We recorded electroencephalographic (EEG) responses to cortical electrical stimulation in 6 rats, and computed Perturbational Complexity Index state-transition (PCIST), which has been extensively validated as an index of the capacity for consciousness in humans. We also estimated the balance between activation and inhibition of specific cortical areas with the ratio between high and low frequency power (HF/LF) from spontaneous EEG activity at each electrode. We repeated these measurements during wakefulness, and under the influence of ketamine anaesthesia at two doses: the minimal dose needed to induce behavioural unresponsiveness and twice this dose. We found that PCIST was only slightly reduced from wakefulness to light ketamine anaesthesia, but dropped significantly down with deeper anaesthesia. The high-dose effect was selectively associated with reduced HF/LF ratio in the posteromedial cortex, which strongly correlated with PCIST. Conversely, behavioural unresponsiveness induced by light ketamine anaesthesia, was associated with similar spectral changes in frontal, but not posterior cortical regions. These findings seem to support the claim that the posteromedial cortex may play a primary role for the capacity for consciousness. Such region-specific associations between cortical activation and the overall capacity for consciousness must be accounted for by theories of consciousness.

neuroscience↗

bioRxiv2020

General anaesthesia disrupts complex cortical dynamics in response to intracranial electrical stimulation in rats

The capacity of the human brain to sustain complex dynamics consistently drops when consciousness fades. Several recent studies in humans found a remarkable reduction of the complexity of cortical responses to local stimulation during dreamless sleep, general anaesthesia, and coma. So far, this perturbational complexity has never been estimated in non-human animals in vivo. Here, we quantify the complexity of electroencephalographic responses to intracranial electrical stimulation in rats, comparing wakefulness to propofol, sevoflurane, and ketamine anaesthesia. We confirm the changes previously observed in humans: from highly complex evoked activity during wakefulness, to simpler responses, suppression of high frequencies, and reduced phase-locking with propofol and sevoflurane. We then deepen our mechanistic understanding by analyzing functional connectivity, and by showing how these parameters dissociate with ketamine, and depend on intensity and site of stimulation. This approach opens the way for further direct investigations of the mechanisms underlying brain complexity and consciousness.

neuroscience↗