Subanaesthetic ketamine and altered states of consciousness in humans

Vlisides, Phillip E.; Bel-Bahar, Tarik; Nelson, Anna‐Gay D.; Chilton, K.; Smith, Ezra E.; Janke, Ellen; Tarnal, Vijay; Picton, Paul; Harris, R. L. N.; Mashour, George A.

doi:10.1016/j.bja.2018.03.011

Cited by 74 publications

(91 citation statements)

References 55 publications

(61 reference statements)

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“…generally, these were increases after ketamine (Figure 8m-q), apart from in the alpha band as found previously (Blain-Moraes, Lee, Ku, Noh, & Mashour, 2014;Vlisides et al, 2018), and decreases after midazolam (Figure 8m-q), also previously found (Ferrarelli et al, 2010), although a recent article found no change in overall functional connectivity using PLI (Numan et al, 2019). While the electrophysiological connectivity metric derived from the power envelope more closely resembled fMRI, this method results in a loss of some of the rich temporal information that electrophysiological methods can provide such as true zero-phase synchrony.…”

Section: Comparing Whole-brain Connectomes From Eeg and Fmrisupporting

confidence: 87%

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Forsyth

McMillan

Campbell

et al. 2019

Human Brain Mapping

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The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood‐oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo‐controlled, three‐way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting‐state networks. Independent components analysis (ICA)‐denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross‐modal comparisons of pharmacologically‐modulated functional connectivity.

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Section: Comparing Whole-brain Connectomes From Eeg and Fmrisupporting

confidence: 87%

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Forsyth

McMillan

Campbell

et al. 2019

Human Brain Mapping

View full text Add to dashboard Cite

show abstract

“…6D). Prior studies have reported global hyperconnectivity of fMRI signals in schizophrenic patients (34), as well as shared phenomenology between schizophrenic symptoms and ketamine's dissociative/ psychoactive effects (30,32). All participants receiving ketamine reported having dreams, and 8 of 12 participants in our study could recall their hallucinations (e.g., flying on a cloud, weird smells, taking an elevator, and thick mist) after recovery from anesthesia.…”

Section: Distinct Spatiotemporal Characteristics During Behavioral Unmentioning

confidence: 62%

“…We assessed whether the suppression of DMN+ and DAT+ is specific to the reduced level of responsiveness as opposed to disorders of cognitive function in general. Another motivation was to further understand the ketamine-specific alterations in the CAP occurrence rates, as altered states of consciousness induced by ketamine are often associated with psychoactive effects and unique brain dynamics (30)(31)(32). Using the same method applied in the task dataset (i.e., maximal similarity to the predefined CAP centroids from the main cohort), we identified eight comparable CAPs in the psychiatric cohort ( Fig.…”

Section: Stimulus Modulations Of Caps and Control Analysis In Psychiamentioning

confidence: 99%

Temporal circuit of macroscale dynamic brain activity supports human consciousness

et al. 2020

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The ongoing stream of human consciousness relies on two distinct cortical systems, the default mode network and the dorsal attention network, which alternate their activity in an anticorrelated manner. We examined how the two systems are regulated in the conscious brain and how they are disrupted when consciousness is diminished. We provide evidence for a “temporal circuit” characterized by a set of trajectories along which dynamic brain activity occurs. We demonstrate that the transitions between default mode and dorsal attention networks are embedded in this temporal circuit, in which a balanced reciprocal accessibility of brain states is characteristic of consciousness. Conversely, isolation of the default mode and dorsal attention networks from the temporal circuit is associated with unresponsiveness of diverse etiologies. These findings advance the foundational understanding of the functional role of anticorrelated systems in consciousness.

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“…Thus, at the molecular level, its impact on central glutamate signaling underlies the long-lasting effects of ketamine on pain behaviors and may also mediate its effect on high-gamma oscillations in the ACC. Previous studies have also found that ketamine can decrease the power in low-frequency bands [ 85 – 88 ], and changes in the low-gamma and beta region have in fact been associated with altered glutamatergic levels in the ACC [ 89 ]. Interestingly, we also observed decreases in the power of low-gamma and beta bands after ketamine administration in the current study.…”

Section: Discussionmentioning

confidence: 99%

Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model

et al. 2020

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Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood at the network level. In this study, we recorded local field potentials from the ACC of freely moving rats. Animals were injected with complete Freund’s adjuvant (CFA) to induce persistent inflammatory pain. Mechanical stimulations were administered to the hind paw before and after CFA administration. We found a significant increase in the high-gamma band (60–100 Hz) power in response to evoked pain after CFA treatment. Ketamine, however, reduced the high-gamma band power in response to evoked pain in CFA-treated rats. In addition, ketamine had a sustained effect on the high-gamma band power lasting up to five days after a single dose administration. These results demonstrate that ketamine has the potential to alter maladaptive neural responses in the ACC induced by chronic pain.

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Subanaesthetic ketamine and altered states of consciousness in humans

Cited by 74 publications

References 55 publications

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam

Temporal circuit of macroscale dynamic brain activity supports human consciousness

Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model

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