Measuring acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans using TD-fNIRS.

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, 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 study demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine in humans, 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.

Change in brain asymmetry reflects level of acute alcohol intoxication and impacts on inhibitory control.

Alcohol is one of the most commonly used substances and frequently abused, yet little is known about the neural underpinnings driving variability in inhibitory control performance after ingesting alcohol. This study was a single-blind, placebo-controlled, randomized design with participants (N = 48 healthy, social drinkers) completing three study visits. At each visit participants received one of three alcohol doses; namely, a placebo dose [equivalent Blood Alcohol Concentration (BAC) = 0.00%], a low dose of alcohol (target BAC = 0.04%), or a moderate dose of alcohol (target BAC = 0.08%). To measure inhibitory control, participants completed a Go/No-go task paradigm twice during each study visit, once immediately before dosing and once after, while their brain activity was measured with time-domain functional near-infrared spectroscopy (TD-fNIRS). BAC and subjective effects of alcohol were also assessed. We report decreased behavioral performance for the moderate dose of alcohol, but not the low or placebo doses. We observed right lateralized inhibitory prefrontal activity during go-no-go blocks, consistent with prior literature. Using standard and novel metrics of lateralization, we were able to significantly differentiate between all doses. Lastly, we demonstrate that these metrics are not only related to behavioral performance during inhibitory control, but also provide complementary information to the legal gold standard of intoxication (i.e. BAC).