PLoS Computational Biology
August 18, 2021
Indie C. Garwood, S. Chakravarty, Jacob Donoghue et al.
32 citations
Ketamine, an anesthetic that blocks NMDA receptors, produces alternating bursts of gamma (25-50 Hz) and slow-delta (0.1-4 Hz) brain oscillations. A hidden Markov model fitted to local field potentials from two non-human primates and electroencephalograms from nine humans quantified these dynamics. Gamma activity lasted on average 2.2 seconds in one primate, 1.2 in the other, and 2.5 in humans; slow-delta lasted 1.6, 1.0, and 1.8 seconds respectively. Five sub-states with regular sequential transitions were identified. These findings provide quantitative constraints for models of rhythm generation underlying ketamine-induced altered arousal.
bioRxiv Preprint Server
April 3, 2024
Elie Adam, Marek Kowalski, Oluwaseun Akeju et al.
5 citations
preprint
Ketamine, an NMDA-receptor antagonist, produces sedation, analgesia, and dissociation at low doses and unconsciousness at high doses, generating gamma oscillations (>25 Hz) in the EEG at both doses, with slow-delta oscillations (0.1-4 Hz) interrupting gamma at high doses. Using a biophysical model of cortical circuits, the authors show how NMDA-receptor antagonism by ketamine leads to disinhibition in neuronal circuits, and how the disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition generates gamma oscillations at both doses and slow-delta oscillations at high doses. This work reveals general mechanisms for oscillatory brain dynamics distinct from previous reports and offers insights into ketamine's action as an anesthetic and therapy for treatment-resistant depression.
bioRxiv Preprint Server
May 2, 2022
Fangyun Tian, Laura D. Lewis, David W. Zhou et al.
preprint
A subanesthetic dose of ketamine increases gamma oscillations in the prefrontal cortex and hippocampus, brain areas linked to its rapid antidepressant effects, and produces a 3 Hz oscillation in the posteromedial cortex that may underlie its dissociative effects. By adding propofol, which blocks NMDA-mediated disinhibition and shares HCN1 inhibition with ketamine, the study distinguished brain dynamics caused by NMDA-mediated disinhibition from those caused by HCN1 inhibition. The results suggest ketamine engages distinct neural circuits in frequency-dependent patterns to produce antidepressant and dissociative effects, potentially guiding development of new depression therapies with fewer side effects.
medRxiv Preprint Server
November 12, 2020
Indie C. Garwood, Sourish Chakravarty, Jacob Donoghue et al.
preprint
Ketamine, an anesthetic and psychoactive drug, produces alternating patterns of brain activity: bursts of gamma oscillations (30-50 Hz) and slow oscillations (0.1-10 Hz). A hidden Markov model (HMM) was applied to brainwave data from two non-human primates and nine human subjects receiving anesthetic doses of ketamine. The model revealed distinct states corresponding to gamma bursts and slow oscillations, with intermediate states. Mean gamma burst durations were 2.5 seconds (non-human primate 1), 1.2 seconds (non-human primate 2), and 2.7 seconds (humans). Mean slow oscillation durations were 1.6 seconds, 0.7 seconds, and 2.8 seconds, respectively. This framework provides quantitative constraints for understanding how ketamine alters states of consciousness.
bioRxiv Preprint Server
July 13, 2023
Brian L. Edlow, Mark Olchanyi, Holly J. Freeman et al.
preprint
Consciousness depends on both arousal (wakefulness) and awareness. While cortical networks for awareness are well studied, the subcortical networks supporting arousal are less understood. By combining ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI in three human brain specimens, the authors identified a default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. They mapped connections within the dAAN and between the dAAN and the cortical default mode network (DMN), suggesting a structural basis for integrating arousal and awareness. The data and methods are released to aid further mapping of human consciousness.