Scholkmann, F. | bioRxiv Science

bioRxiv2023

Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 {+/-} 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations (fALFF), and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our studies demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.

neuroscience↗

bioRxiv2018

Systematic analysis of mouse genome reveals distinct evolutionary and functional properties among circadian and ultradian genes

In living organisms, biological clocks regulate 24 h (circadian) molecular, physiological, and behavioral rhythms to maintain homeostasis and synchrony with predictable environmental changes. Harmonics of these circadian rhythms having periods of 8 hours and 12 hours (ultradian) have been documented in several species. In mouse liver, harmonics of the 24-hour period of gene transcription hallmarked genes oscillating with a frequency two or three times faster than the circadian circuitry. Many of these harmonic transcripts enriched pathways regulating responses to environmental stress and coinciding preferentially with subjective dawn and dusk. We hypothesized that these stress anticipatory genes would be more evolutionarily conserved than background circadian and non-circadian genes. To investigate this issue, we performed broad computational analyses of genes/proteins oscillating at different frequency ranges across several species and showed that ultradian genes/proteins, especially those oscillating with a 12-hour periodicity, are more likely to be of ancient origin and essential in mice. In summary, our results show that genes with ultradian transcriptional patterns are more likely to be phylogenetically conserved and associated with the primeval and inevitable dawn/dusk transitions.

bioinformatics↗