Disruption of corticocortical information transfer during ketamine anesthesia in the primate brain

Abstract

The neural mechanisms of anesthetic-induced unconsciousness have yet to be fully elucidated, in part because of the diverse molecular targets of anesthetic agents. We demonstrate, using intracortical recordings in macaque monkeys, that information transfer between structurally connected cortical regions is disrupted during ketamine anesthesia, despite preserved primary sensory representation. Furthermore, transfer entropy, an information-theoretic measure of directed connectivity, decreases significantly between neuronal units in the anesthetized state. This is the first direct demonstration of a general anesthetic disrupting corticocortical information transfer in the primate brain. Given past studies showing that more commonly used GABAergic drugs inhibit surrogate measures of cortical communication, this finding suggests the potential for a common network-level mechanism of anesthetic-induced unconsciousness.

Keywords: Anesthesia; Consciousness; Functional connectivity; Information integration; Ketamine; Sensorimotor.

Figure 1

(A) Electrode placement in three monkeys. A: anterior; P: posterior; CS: central sulcus; Sp: spur of the arcuate. (B) Experimental trial structure and digits stimulated on each animal – color legend same as (A). (C) Trial block structure for each day of experiments. Blue marker denotes block of stimulation trials. Inj: intramuscular ketamine injection.

Figure 2

Loss of sensory representation from motor cortex under ketamine. (A) Percent correct classification of stimulated finger across all monkeys and sessions. *p<.001 when compared to chance level (dashed line). Error bars denote S.E.M. (B) Example confusion matrices showing decoder performance for one session of Monkey P.

Figure 3

Multiunit behavior and power spectra. (A) Firing rates of sorted multiunits before and after ketamine (+10’ time point). (B) Example raster plot of all recorded multiunits during portions of one awake trial and one ketamine trial from monkey L. Grey bars: stimulator in contact with digit. (C) PSTHs of two example M1 units, aligned to first stimulus of trial. (D) Normalized mean power spectra for unit activity averaged across modulated units from monkeys P and L. Red vertical line emphasizes 2Hz, the frequency of stimulation.

Figure 4

Loss of corticocortical directed connectivity under ketamine. (A) Peak high order transfer entropy (HOTE) between multiunit pairs during one monkey L experiment. (B) Comparison of Peak HOTE including all sessions for monkeys P and L. *p<.001. (C) HOTE between multiunit pairs after shuffling S1 spikes; same dataset as (A).

Figure 5

S1 electrodes lose beta power, gain gamma under ketamine. (A) Band power modulations of two monkey P sessions and two monkey L sessions (shaded area: SD, red vertical bar: injection). (B) Spectrograms from representative electrodes in S1 and M1 during a single Monkey L session (red vertical bar: injection). (C) Raw beta and gamma power from representative electrodes in S1 and M1 during a single monkey L session.