Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Castillo A

PROVIDER: S-EPMC10356754 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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

Castillo Adelaida A Dubois Julien J Field Ryan M RM Fishburn Frank F Gundran Andrew A Ho Wilson C WC Jawhar Sami S Kates-Harbeck Julian J M Aghajan Zahra Z Miller Naomi N Perdue Katherine L KL Phillips Jake J Ryan Wesley C WC Shafiei Mahdi M Scholkmann Felix F Taylor Moriah M

Scientific reports 20230719 1

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 spec ...[more]

PMID: 37468572

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Project description:BackgroundDespite controversies, epinephrine remains a mainstay of cardiopulmonary resuscitation (CPR). Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. The primary objectives of this study were to determine if (1) epinephrine doses have a significant acute effect on CBF and cerebral tissue oxygenation during CPR and (2) if the effect of each subsequent dose of epinephrine differs significantly from that of the first.MethodsOne-month-old piglets (n = 20) underwent asphyxia for 7 min, ventricular fibrillation, and CPR for 10-20 min. Epinephrine (20 mcg/kg) was administered at 2, 6, 10, 14, and 18 min of CPR. Invasive (laser Doppler, brain tissue oxygen tension [PbtO2]) and noninvasive (diffuse correlation spectroscopy and diffuse optical spectroscopy) measurements of CBF and cerebral tissue oxygenation were simultaneously recorded. Effects of subsequent epinephrine doses were compared to the first.ResultsWith the first epinephrine dose during CPR, CBF and cerebral tissue oxygenation increased by > 10%, as measured by each of the invasive and noninvasive measures (p < 0.001). The effects of epinephrine on CBF and cerebral tissue oxygenation decreased with subsequent doses. By the fifth dose of epinephrine, there were no demonstrable increases in CBF of cerebral tissue oxygenation. Invasive and noninvasive CBF measurements were highly correlated during asphyxia (slope effect 1.3, p < 0.001) and CPR (slope effect 0.20, p < 0.001).ConclusionsThis model suggests that epinephrine increases CBF and cerebral tissue oxygenation, but that effects wane following the third dose. Noninvasive measurements of neurological health parameters hold promise for developing and directing resuscitation strategies.

Project description:We studied the capability of a Hybrid functional neuroimaging technique to quantify human mental workload (MWL). We have used electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) as imaging modalities with 17 healthy subjects performing the letter n-back task, a standard experimental paradigm related to working memory (WM). The level of MWL was parametrically changed by variation of n from 0 to 3. Nineteen EEG channels were covering the whole-head and 19 fNIRS channels were located on the forehead to cover the most dominant brain region involved in WM. Grand block averaging of recorded signals revealed specific behaviors of oxygenated-hemoglobin level during changes in the level of MWL. A machine learning approach has been utilized for detection of the level of MWL. We extracted different features from EEG, fNIRS, and EEG+fNIRS signals as the biomarkers of MWL and fed them to a linear support vector machine (SVM) as train and test sets. These features were selected based on their sensitivity to the changes in the level of MWL according to the literature. We introduced a new category of features within fNIRS and EEG+fNIRS systems. In addition, the performance level of each feature category was systematically assessed. We also assessed the effect of number of features and window size in classification performance. SVM classifier used in order to discriminate between different combinations of cognitive states from binary- and multi-class states. In addition to the cross-validated performance level of the classifier other metrics such as sensitivity, specificity, and predictive values were calculated for a comprehensive assessment of the classification system. The Hybrid (EEG+fNIRS) system had an accuracy that was significantly higher than that of either EEG or fNIRS. Our results suggest that EEG+fNIRS features combined with a classifier are capable of robustly discriminating among various levels of MWL. Results suggest that EEG+fNIRS should be preferred to only EEG or fNIRS, in developing passive BCIs and other applications which need to monitor users' MWL.

Project description:RationaleSubanesthetic ketamine (KET) elicits rapid, robust, but transient antidepressant effects. KET's antidepressant actions can be augmented and maintained for a longer duration when repeatedly delivered. However, KET is recreationally abused, raising long-term treatment safety concerns. Women are more likely than men to seek treatment for depression, escalate from casual to compulsive drug use, and are more sensitive to antidepressants. Similarly, female rodents are more sensitive than males to KET's rapid antidepressant-like behavioral effects; dose-response thresholds in these assays equal 2.5 and 5.0mg/kg (i.p.), respectively. This suggests the utility of preclinical rodent models in optimizing sex-differential KET therapy protocols and minimizing adverse drug reactions.ObjectivesHere, we assessed behavioral and biochemical correlates of abuse liability following six serial KET treatments on alternating days at three subanesthetic, antidepressant-like doses (2.5, 5.0, or 10mg/kg, i.p.) in adult male and female rats. A potential role for ΔFosB-mediated transcription in the nucleus accumbens is outlined in the context of KET-mediated locomotor sensitization.ResultsAntidepressant-like threshold doses (2.5, 5.0mg/kg KET) failed to evoke a conditioned place preference in all animals, but only males positively responded to a higher dose (10mg/kg). Behavioral sensitization to 5.0 or 10mg/kg KET's locomotor-activating effects was established in both sexes, and females' sensitized response to 5.0mg/kg was greater than males'. KET-induced hyperlocomotion positively correlated with ΔFosB protein expression in the nucleus accumbens. rAAV-ΔJunD inhibition of ΔFosB-mediated transcription in the accumbens failed to block locomotor sensitization to 10mg/kg KET.ConclusionsThese data suggest that in rats, six alternating-day treatments with 2.5mg/kg KET do not induce apparent behavioral signatures of abuse liability despite accumulation of ΔFosB protein in the accumbens. Additionally, females are more sensitive than males to KET's locomotor-stimulant properties, both acutely and after repeated treatments. More studies are needed to determine brain regions and neural mechanisms responsible for KET-induced behavioral adaptations and to extrapolate these data to inform sex-dependent strategies for long-term KET therapy protocols for depression.

Dataset Information

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

Publications

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

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