Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness

Abstract

Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

Keywords: Fractional amplitude of low-frequency fluctuation (fALFF); Loss of consciousness; Propofol sedation; Resting-state fMRI; Spontaneous neural activity.

Fig. 1

Group average of fALFF index presented on the brain surface (fsaverage in FreeSurfer) in the four states of consciousness in wakefulness (A), light sedation (B), deep sedation (C), and recovery (D), respectively.

Fig. 2

Two-sided one-sample paired t-tests of fALFF between wakefulness and light sedation (A), between wakefulness and deep sedation (B), between light sedation and deep sedation (C), and between recovery and deep sedation (D). Warm colors indicate higher fALFF in the first state of each paired comparison. The significance of results is reported at P = 0.01, corrected for multiple comparisons.

Fig. 3

Region-specific changes in the sum of fALFF across the four states of consciousness in wakefulness (W), light sedation (L), deep sedation (D), and recovery (R). Paired t-test comparisons that show a main effect of difference are marked by an asterisk. Error bars represent the standard error of measurement. (* denotes p<=0.05; ** p<=0.01; and *** p<=0.001. PFC: prefrontal cortex; IC: insular cortex; Hipp: hippocampus; Parahipp: parahippocampal gyrus)