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

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

Kernel Flow:a high channel count scalable time-domain functional near-infrared spectroscopy system

Significance: Time-domain functional near-infrared spectroscopy (TD-fNIRS) has been considered as the gold standard of noninvasive optical brain imaging devices. However, due to the high cost, complexity, and large form factor, it has not been as widely adopted as continuous wave NIRS systems. Aim: Kernel Flow is a TD-fNIRS system that has been designed to break through these limitations by maintaining the performance of a research grade TD-fNIRS system while integrating all of the components into a small modular device. Approach: The Kernel Flow modules are built around miniaturized laser drivers, custom integrated circuits, and specialized detectors. The modules can be assembled into a system with dense channel coverage over the entire head. Results: We show performance similar to benchtop systems with our miniaturized device as characterized by standardized tissue and optical phantom protocols for TD-fNIRS and human neuroscience results. Conclusions: The miniaturized design of the Kernel Flow system allows for broader applications of TD-fNIRS.</p

Correction: fNIRS measurement of cortical activation and functional connectivity during a visuospatial working memory task.

[This corrects the article DOI: 10.1371/journal.pone.0201486.]

JND output example.

<p>Outcome of JND estimation task for a single participant. The light and dark circles and dotted lines represent JND trials for 3 and 5 dot conditions respectively. The size of each dot represents the number of trials experienced at that distance from the original position of the target dot location. Each staircase procedure began with a spatial deviation of 150 pixels. The JND was calculated as the average point along the x-axis at which both non-linear trend lines crossed the 50% correct response point along the y-axis. The JND is marked with a ‘*’.</p

Coherence within regions of interest.

<p>Inter-quartile ranges of channel-wise coherence within each region of interest. Because no significant difference in coherence was identified between the encoding/maintenance and retrieval portions of the task, the data shown here have been combined across conditions. Coherence was significantly greater within the parietal compared to prefrontal regions, as well as within same- as opposed to different regions.</p

Trial structure for JND and fNIRS task trials.

<p>A. Participants completed 200 JND estimation trials. Each trial began with a 5–7 second ITI, and was followed by a 3 or 5 dot array. Next, a visual mask was displayed for .5s, and was immediately followed by the single-dot presentation, at which point the participant could respond. The fNIRS task trails proceeded in a similar fashion, except the visual mask portion was extended to 6s and the screen simply remained blank except for a central cross; B. fNIRS task difficulty was modulated by the spatial difference between the original target dot location within its array and its location on the response screen. Spatial deviations were defined as “no difference”, “subtle difference” (JND x 0.1), and “obvious difference” (JND x 0.8). The updated location of the target dot was randomly selected from a vector of x- and y-axis values that constitute a circle, with a radius equal to the spatial deviation in pixels, that lay around the center of the original dot.</p

fNIRS task response time.

<p>Inter-quartile ranges of fNIRS task response times across each trial type. Similar to the task accuracy outcome, the predicted pattern of faster median trial response times for control trials was identified, followed by “obvious change”, “subtle change”, and “no change” trials in that order.</p

fNIRS measurement of cortical activation and functional connectivity during a visuospatial working memory task

<div><p>Demands on visuospatial working memory are a ubiquitous part of everyday life. As such, significant efforts have been made to understand how the brain responds to these demands in real-world environments. Multiple brain imaging studies have highlighted a fronto-parietal cortical network that underlies visuospatial working memory, is modulated by cognitive load, and that appears to respond uniquely to encoding versus retrieval components. Furthermore, multiple studies have identified functional connectivity in regions of the fronto-parietal network during working memory tasks. Together, these findings have helped outline important aspects of the neural architecture that underlies visuospatial working memory. Here, we provide results from the first fNIRS-based investigation of fronto-parietal signatures of cortical activation and functional connectivity during a computer-based visuospatial working memory task. Our results indicate that the local maxima of cortical activation and functional coherence do not necessarily overlap spatially, and that cortical activation is significantly more susceptible to task-specific demands compared to functional connectivity. These results highlight important and novel information regarding neurotypical signatures of cortical activation and functional connectivity during visuospatial working memory. Our findings also demonstrate the utility of fNIRS for interrogating these cognitive processes.</p></div