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Emery N Brown

The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02139, USA.

5 papers in the library · 83 citations · publishing 2024-2025

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 A 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.

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.

Anesthetics as Treatments for Depression: Clinical Insights and Underlying Mechanisms.

Annual review of neuroscience February 19, 2025 Macauley Smith Breault, Sirma Orguc, Ohyoon Kwon et al. 13 citations

Several anesthetic agents beyond ketamine show antidepressant effects, including nitrous oxide, propofol, isoflurane, sevoflurane, dexmedetomidine, and xenon. This review examines clinical and basic science studies on these anesthetics for treating depression. The authors propose that anesthetics may alleviate depression by modulating brain dynamics that alter arousal states, linking anesthetic mechanisms to depression pathophysiology and findings from other treatments. The work suggests that repurposing anesthetics could offer new options for major depressive disorder and 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.

REcovery from DEXmedetomidine-Induced Unresponsiveness (REDEX): A Study Protocol for a Single Center, Parallel Arm, Non-Randomized, Controlled Pilot Trial in Healthy Volunteers.

Nature and science of sleep January 1, 2025 David R Schreier, Matteo Fecchio, Christian S Guay et al.

Dexmedetomidine (DEX) is a sedative that produces a sleep-like state and offers a way to study shifts in consciousness using behavior, EEG, and TMS-evoked EEG responses. Little is known about how repeated DEX exposure affects recovery. This pilot trial plans to sedate 12 healthy volunteers twice, one week apart, monitoring responsiveness with an auditory click task. It will compare time to return of responsiveness between visits, explore sex differences, and assess state transitions via EEG signatures, TMS-evoked complexity, and cognitive tests. The study also evaluates the feasibility of TMS-EEG during DEX sedation and reports on sleep quality and experiences.