Dynamics of Propofol-Induced Loss of Consciousness Across Primate Neocortex

Abstract

The precise neural mechanisms underlying transitions between consciousness and anesthetic-induced unconsciousness remain unclear. Here, we studied intracortical neuronal dynamics leading to propofol-induced unconsciousness by recording single-neuron activity and local field potentials directly in the functionally interconnecting somatosensory (S1) and frontal ventral premotor (PMv) network during a gradual behavioral transition from full alertness to loss of consciousness (LOC) and on through a deeper anesthetic level. Macaque monkeys were trained for a behavioral task designed to determine the trial-by-trial alertness and neuronal response to tactile and auditory stimulation. We show that disruption of coherent beta oscillations between S1 and PMv preceded, but did not coincide with, the LOC. LOC appeared to correspond to pronounced but brief gamma-/high-beta-band oscillations (lasting ϳ3 min) in PMv, followed by a gamma peak in S1. We also demonstrate that the slow oscillations appeared after LOC in S1 and then in PMv after a delay, together suggesting that neuronal dynamics are very different across S1 versus PMv during LOC. Finally, neurons in both S1 and PMv transition from responding to bimodal (tactile and auditory) stimulation before LOC to only tactile modality during unconsciousness, consistent with an inhibition of multisensory integration in this network. Our results show that propofol-induced LOC is accompanied by spatiotemporally distinct oscillatory neuronal dynamics across the somatosensory and premotor network and suggest that a transitional state from wakefulness to unconsciousness is not a continuous process, but rather a series of discrete neural changes.

Reduced repertoire of cortical microstates and neuronal ensembles in medically-induced loss of consciousness

“…Consistent with previous studies, neural firing dropped promptly during mLOC (Ishizawa et al, 2016;Lewis et al, 2012), with total neuronal activity during surgical anesthesia falling below 10% of baseline ( Fig. 2B).…”

Leveraging Nonhuman Primate Multisensory Neurons and Circuits in Assessing Consciousness Theory

“…Characterizing multisensory neurons in S1 and vPM The data, drawn as a subset of a previously published dataset (Ishizawa et al, 2016), comprise neural responses recorded from 293 single units in S1 (228 from…”

“…To probe these predictions we simultaneously record single units from the primary somatosensory cortex (S1) and ventral premotor cortex (vPM) of nonhuman primates as they were presented with audio, tactile, or audio-tactile stimuli. The monkeys were trained to report the presence of a stimulus (regardless of sensory modality) via button press to determine their trial-to-trial alertness during propofol-induced loss of consciousness (Ishizawa et al, 2016). We first characterize both the central (e.g., mean) and dispersion (e.g., variance) tendencies of multisensory responses in S1 and vPM neurons under normal wakefulness, and based on these responses, divide neurons into integrative or convergent categories.…”

“…Parametric inferential statistics are used when assumptions of these tests are met, and nonparametric are used if not (specific test indicated when introducing the result). This dataset has been used previously in another publication (Ishizawa et al, 2016) focusing on the local field potentials. Complementing the current analyses focused on single units and targeting specific theoretical arguments, Ishizawa et al, (2016) detail the network-level disruption of coherent beta oscillations between S1 and vPM preceding loss of consciousness, a transient increase in gamma/beta band oscillations coincident with loss of consciousness, and the gradual ramp up of slow oscillations, first in S1 and then vPM, during and after loss of consciousness.…”

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex

“…Given that anesthetics act at diverse molecular and cellular targets (7,9), their effects on consciousness and sensory perception are best studied at the level of common brain circuits and systems (2,9,10). Indeed, recent studies focusing on the systems level effects of anesthesia proposed that LOC may involve sleep pathways (9,11), thalamocortical circuits (12), specific brainstem regions (2,13,14), or unbinding of fronto-parietal cortical activities (15,16).…”