Subanaesthetic ketamine and altered states of consciousness in humans

Abstract

Background: Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine.

Methods: High-density EEG was recorded in 15 human volunteers before, during, and after subanaesthetic ketamine infusion (0.5 mg kg^-1 over 40 min), with self-reported measures of altered states of consciousness obtained after ketamine exposure. Sensor- and source-level EEG changes were analysed with a focus on spectral power and regional changes.

Results: Ketamine-induced altered states were characterised predominantly by dissociative experiences such as disembodiment and ego transcendence; sensory disturbances were also common. Ketamine broadly decreased low-frequency power, with mean reductions largest at alpha (8-12 Hz) in parietal (-0.94 dB, P<0.001) and occipital (-1.8 dB, P<0.001) channel clusters. Significant decreases in alpha were identified in the precuneus and temporal-parietal junction.

Conclusions: Ketamine induces altered states of consciousness during periods of reduced alpha power in the precuneus and temporal-parietal junction. Modulation of these temporal-parietal loci are candidate mechanisms of the psychoactive effects of ketamine, given that this region is involved in multisensory integration, body representation, and consciousness.

Keywords: consciousness; dissociative anaesthetics; ketamine.

Fig 1

Schematic representation of the study protocol. The protocol began with a baseline, 5-min eyes-closed period, followed by a 40-min ketamine infusion (0.5 mg kg⁻¹ total dose). After completion of the infusion, ondansetron was given for nausea and vomiting prophylaxis. The altered states of consciousness questionnaire was then administered after a short rest period. EEG data were recorded throughout the entire protocol as outlined above. ASC, altered states of consciousness.

Fig 2

Grand average power spectrum, spectrograms, and topomaps (n=15). (A) The power spectrum values for baseline and subanaesthetic conditions (block 3). (B) Differences between baseline and subanaesthetic periods (block 3) at five frequency bands and four channel clusters. Negative values represent mean relative decreases in power from baseline, and positive values represent mean relative increases from baseline. Error bars represent standard deviation of these relative means. Lines with stars show significant post hoc comparisons between frequency bands across all channels. (C) Frontal and posterior channel-cluster spectrograms for baseline and subanaesthetic periods (blocks 1–3). (D) Frontal and posterior channel-cluster baselined spectrograms for subanaesthetic periods (blocks 1–3). (E) Topomaps for baseline (row 1) and subanaesthetic block 3 (row 2) periods.

Fig 3

Alpha-band source estimates of differences between subanaesthetic and baseline periods. (A) Consists of current source estimates, with significant voxels (P<0.05) in dark blue, kernel scaling=7. From left to right, (A) includes a right hemisphere lateral view, a posterior view, and an inflated posterior view of the right hemisphere. (B) Depicts the four source clusters. Black squares on smaller images are zoomed in within the larger black squares. The clusters are shown on the right hemisphere only. sLORETA, standardised Low Resolution Brain Electromagnetic Tomography.

Fig 4

Correlation coefficients (Spearman's rho) presented for exploratory EEG channel-altered states of consciousness correlation analysis. Only correlation values with magnitude ≥0.5 are presented. None of these correlations reached statistical significance when correcting for multiple comparisons (P=0.05/88 correlations=0.00057). Disemb, disembodiment; AVSyn, audiovisual synaesthesia; ICC, impaired control and cognition; CI, complex imagery; EI, elementary imagery; CMP, changed meaning of percepts; Insight, insightfulness; Bliss, blissful state; Unity, experiences of unity; TST, transcendence of time and space; Ineff, ineffability.

Fig 5

Spearman's rho correlations presented for exploratory EEG source-altered states of consciousness analyses. Correlation values with magnitude ≥0.5 are presented. None of these correlations reached statistical significance when correcting for multiple comparisons (P=0.05/44 correlations=0.0011). Disemb, disembodiment; AVSyn, audiovisual synaesthesia; ICC, impaired control and cognition; CI, complex imagery; EI, elementary imagery; CMP, changed meaning of percepts; Insight, insightfulness; Bliss, blissful state; Unity, experiences of unity; TST, transcendence of time and space; Ineff, Ineffability; MTG, medial temporal gyrus; PCUN, precuneus; SMG, supramarginal gyrus; IPL, inferior parietal lobe.

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