Discussion
MDD, depressive, depressed, seeWhole head TD-fNIRS
CORTEX
In the current study, we report on behavioral, systemic physiological, and cerebrovascular measurements from participants who underwent neuroimaging using TD-fNIRS while experiencing altered states of consciousness as a result of subanesthetic ketamine injection in a clinical environment. We compared the acute effects of intramuscular bolus ketamine administration against a placebo (saline administration) condition. We demonstrate reliable physiological measurements of PR and PRV extracted from TD-fNIRS recordings that match those obtained from commercial PPG sensors, thus rendering the use of external sensors to measure cardiac activity unnecessary in future experiments. We also find robust differences between ketamine and saline conditions: (1) physiological measures: increased PR, decreased PRV, increased absolute HbO and decreased HbR, and elevated EDA (measured by an external sensor) during ketamine dosing, and (2) neural measures: decrease in fALFF and in the global brain functional connectivity of the prefrontal cortex following ketamine administration. These results are generally consistent with findings reported by previous studies (apart from the global functional connectivity result)By using a combination of systemic physiological (i.e. PR) and neural (i.e. fALFF) features, we were able to predict participants’ reported RMEQ scores. Further, we found that when the trained model was evaluated throughout the ketamine session, the predicted peak of mystical experience occurred at different times for different individuals. The predicted time-series approximate the expected pharmacokinetics after such an intramuscular bolus and may reflect the time course of the psychoactive effects of ketamine in each participant; to corroborate this, future studies could include continuous measurements of plasma concentration of the psychoactive substance as a proxy for continuous subjective experienceAlthough we observed a decrease in whole-brain fALFF following ketamine administration, this effect may be region- or network-specific. It has been suggested that fALFF within the default mode network (DMN) is of particular functional importanceOur result of acutely decreased global functional connectivity in the prefrontal cortex after ketamine administration appears to be at odds with extant literatureThe current study, due to its small sample size and limitations of only measuring cortical connectivity, was not designed to adjudicate conflicts in the existing literature. It was intended as a proof-of-principle for using a novel TD-fNIRS system in clinical settings. The simplicity of using TD-fNIRS in the clinic, and its ability to measure cortical function (fALFF, functional connectivity) in longitudinal and large-scale studies, may unlock insights on functional brain reorganization, acutely and chronically, following pharmacological interventions. These new insights may be particularly valuable for tailoring KAP or extended to tailoring PAP, more generally.This study has several further limitations. Our study population was not only small, it was also a sample of healthy volunteers rather than a patient population. If the intent is to understand the mechanism of action of RAADs in clinically depressed patients, a MDD patient sample would be most appropriate. Thus, the results that we report in this work may not apply directly to ketamine treatment of depressed patients. Another limitation is that, while we measured subjective depressive symptomatology one week after ketamine dosing, we did not include brain measurements post-dosing which is when many studies have noted neural changes and psychological effects are measurable (seeWhole head TD-fNIRS neuroimaging offers an ecologically valid methodology to measure the acute and delayed physiological and neural changes following pharmacological interventions, such as ketamine administration. This scalable technology that captures high-quality cerebrovascular signals and can be deployed widely in clinics may be the solution to the current lack of consistency in neuroimaging investigations of the effects of ketamine administration. But why prefer cerebrovascular measurements to electrophysiological measurements, such as those that can be captured with EEG? While EEG suffers from inherent limitations such as its sensitivity to artifacts (muscle, motion, ambient electromagnetic fields) and lack of spatial specificity, hemodynamic estimates of neural activity are themselves plagued with contamination from systemic physiology