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Earl K. Miller

6 papers in the library · 107 citations · publishing 2020-2025

Papers

Propofol-mediated loss of consciousness disrupts predictive routing and local field phase modulation of neural activity.

Proceedings of the National Academy of Sciences of the United States of America October 15, 2024 Yihan Sophy Xiong, Jacob Donoghue, Mikael Lundqvist et al. 32 citations

Predictive coding in the cortex relies on predictions fed back from deep layers via alpha/beta oscillations (8–30 Hz) that inhibit gamma (40–100 Hz) and spiking carrying sensory input forward. Intracranial recordings in macaques during passive auditory oddball tasks showed that in the awake state alpha/beta oscillations inhibited processing of predictable sounds. Propofol-induced loss of consciousness eliminated this alpha/beta modulation in sensory cortex and reduced alpha/beta coherence between sensory and frontal areas. Consequently, oddball stimuli evoked enhanced gamma power, late spiking, and superficial layer sinks in auditory cortex, indicating a disinhibited state. However, differential spiking to oddballs in higher-order cortex was lost, likely due to disrupted spike-field coupling. These findings constrain theories of consciousness.

A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque local field potentials and human electroencephalograms

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.

Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors.

Proceedings of the National Academy of Sciences of the United States of America May 28, 2024 Elie Adam, Marek Kowalski, Oluwaseun Akeju et al. 30 citations

Ketamine, an NMDA-receptor antagonist, produces sedation and dissociation at low doses and unconsciousness at high doses, while generating gamma oscillations (>25 Hz) in the EEG that are interrupted by slow-delta oscillations (0.1–4 Hz) at high doses. Using a biophysical model of cortical circuits, the authors show how NMDA-receptor antagonism leads to disinhibition in neuronal circuits, and how disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition produces gamma oscillations at both doses and slow-delta oscillations at high doses. This work reveals general mechanisms for generating oscillatory brain dynamics and provides insights into ketamine's actions as an anesthetic and therapy for treatment-resistant depression.

Convergent effects of different anesthetics on changes in phase alignment of cortical oscillations.

Cell Reports May 27, 2025 Alexandra G Bardon, Jesus J Ballesteros, Scott L Brincat et al. 8 citations

Two anesthetics with different molecular actions, ketamine and dexmedetomidine, both increase phase locking of neural oscillations in the prefrontal cortex of nonhuman primates during loss of responsiveness. Within a hemisphere, neighboring prefrontal subregions become less phase-aligned, possibly due to large traveling waves. However, homologous areas across hemispheres become more aligned in phase. These distinct patterns of cortical phase alignment, markedly different from waking states, may represent a common mechanism by which diverse anesthetics produce loss of responsiveness.

Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors

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.

A hidden Markov model reliably characterizes ketamine-induced spectral dynamics in macaque LFP and human EEG

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.