Studies aimed at investigating brain regions involved in arousal state control have been traditionally limited to subcortical structures. In the current study, we tested the hypothesis that inactivation of prefrontal cortex, but not two subregions within parietal cortex—somatosensory barrel field and medial/lateral parietal association cortex—would suppress arousal, as measured by an increase in anesthetic sensitivity. Male and female Sprague Dawley rats were surgically prepared for recording electroencephalogram and bilateral infusion into prefrontal cortex (N = 13), somatosensory barrel field (N = 10), or medial/lateral parietal association cortex (N = 9). After at least 10 days of post-surgical recovery, 156 μM tetrodotoxin or saline was microinjected into one of the cortical sites. Ninety minutes after injection, rats were anesthetized with 2.5% sevoflurane and the time to loss of righting reflex, a surrogate for loss of consciousness, was measured. Sevoflurane was stopped after 45 min and the time to return of righting reflex, a surrogate for return of consciousness, was measured. Tetrodotoxin-mediated inactivation of all three cortical sites decreased (p < 0.05) the time to loss of righting reflex. By contrast, only inactivation of prefrontal cortex, but not somatosensory barrel field or medial/lateral parietal association cortex, increased (p < 0.001) the time to return of righting reflex. Burst suppression ratio was not altered following inactivation of any of the cortical sites, suggesting that there was no global effect due to pharmacologic lesion. These findings demonstrate that prefrontal cortex plays a causal role in emergence from anesthesia and behavioral arousal.

BACKGROUND: Delirium is an acute syndrome characterized by inattention, disorganized thinking, and an altered level of consciousness. A reliable biomarker for tracking delirium does not exist, but oscillations in the electroencephalogram (EEG) could address this need. We evaluated whether the frequencies of EEG oscillations are associated with delirium onset, severity, and recovery in the postoperative period. METHODS: Twenty-six adults enrolled in the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES; ClinicalTrials.gov NCT02241655) study underwent major surgery requiring general anesthesia, and provided longitudinal postoperative EEG recordings for this prespecified substudy. The presence and severity of delirium were evaluated with the confusion assessment method (CAM) or the CAM-intensive care unit. EEG data obtained during awake eyes-open and eyes-closed states yielded relative power in the delta (1-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) bands. Discriminability for delirium presence was evaluated with c-statistics. To account for correlation among repeated measures within patients, mixedeffects models were generated to assess relationships between: (1) delirium severity and EEG relative power (ordinal), and (2) EEG relative power and time (linear). Slopes of ordinal and linear mixed-effects models are reported as the change in delirium severity score/change in EEG relative power, and the change in EEG relative power/time (days), respectively. Bonferroni correction was applied to confidence intervals (CIs) to account for multiple comparisons. RESULTS: Occipital alpha relative power during eyes-closed states offered moderate discriminability (c-statistic, 0.75; 98% CI, 0.58-0.87), varying inversely with delirium severity (slope, -0.67; 98% CI, -1.36 to -0.01; P = .01) and with severity of inattention (slope, -1.44; 98% CI, -2.30 to -0.58; P = .002). Occipital theta relative power during eyes-open states correlated directly with severity of delirium (slope, 1.28; 98% CI, 0.12-2.44; P = .007), inattention (slope, 2.00; 98% CI, 0.48-3.54; P = .01), and disorganized thinking (slope, 3.15; 98% CI, 0.66-5.65; P = .01). Corresponding frontal EEG measures recapitulated these relationships to varying degrees. Severity of altered level of consciousness correlated with frontal theta relative power during eyes-open states (slope, 11.52; 98% CI, 6.33-16.71; P < .001). Frontal theta relative power during eyes-open states correlated inversely with time (slope, -0.05; 98% CI, -0.12 to -0.04; P = .002). CONCLUSIONS: Presence, severity, and core features of postoperative delirium covary with spectral features of the EEG. The cost and accessibility of EEG facilitate the translation of these findings to future mechanistic and interventional trials. (Anesth Analg 2023;136:140-51) KEY POINTS• Question: Can a small array of electroencephalogram (EEG) electrodes track postoperative delirium presence, severity, and resolution over time? • Findings: Relative power in a sparse array of occipital...

Psychedelics have been recognized as model interventions for studying altered states of consciousness. However, few empirical studies of the shamanic state of consciousness, which is anecdotally similar to the psychedelic state, exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 shamanic practitioners and 24 healthy controls during rest, shamanic drumming, and classical music listening, followed by an assessment of altered states of consciousness. EEG data were used to assess changes in absolute power, connectivity, signal diversity, and criticality, which were correlated with assessment measures. We also compared assessment scores to those of individuals in a previous study under the influence of psychedelics. Shamanic practitioners were significantly different from controls in several domains of altered states of consciousness, with scores comparable to or exceeding that of healthy volunteers under the influence of psychedelics. Practitioners also displayed increased gamma power during drumming that positively correlated with elementary visual alterations. Furthermore, shamanic practitioners had decreased low alpha and increased low beta connectivity during drumming and classical music and decreased neural signal diversity in the gamma band during drumming that inversely correlated with insightfulness. Finally, criticality in practitioners was increased during drumming in the low and high beta and gamma bands, with increases in the low beta band correlating with complex imagery and elementary visual alterations. These findings suggest that psychedelic drug-induced and non-pharmacologic alterations in consciousness have overlapping phenomenal traits but are distinct states of consciousness, as reflected by the unique brain-related changes during shamanic trance compared to previous literature investigating the psychedelic state.

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Electroconvulsive therapy (ECT) relies on the electrical induction of generalized seizures to treat major depressive disorder and other psychiatric illnesses. These planned procedures provide a clinically relevant model system for studying neurophysiologic characteristics of generalized seizures. We recently described novel central-positive complexes (CPCs), which were observed during ECT-induced seizures as generalized, high-amplitude waveforms with maximum positive voltage over the vertex. Here, we performed a systematic characterization of 6,928 CPC ictal waveforms recorded in 11 patients undergoing right unilateral (RUL) ECT. Analyses of high-density 65-electrode EEG recordings during these 50 seizures allowed evaluation of these CPCs across temporal, spatial, and spectral domains. Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. Total duration of CPCs positively correlated with the time required for return of responsiveness after ECT treatment (r = 0.39, p = 0.005). The rate of CPCs showed a frequency decline consistent with an exponential decay (median 0.032 (IQR 0.053) complexes/second). Gamma band (30-80 Hz) oscillations correlated with the peak amplitude of CPCs, which was also reproducible across seizures, with band power declining over time (r = -0.32, p < 10-7). The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Our findings demonstrated CPC characteristics that were invariant to participant, stimulus charge, time, and agent used to induce general anesthesia during the procedure. Consistent with ictal waveforms of other generalized epilepsy syndromes, CPCs showed topographic distribution over the fronto-central regions, predictable intra-seizure frequency decline, and correlation with gamma-range frequencies. Furthermore, source localization to the medial thalamus was consistent with underlying thalamocortical pathophysiology, as established in generalized epilepsy syndromes. The consistency and reproducibility of CPCs offers a new avenue for studying the dynamics of seizure activity and thalamocortical networks.

Despite the use of shamanism as a healing practice for several millennia, few empirical studies of the shamanic state of consciousness exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 shamanic practitioners and 24 healthy controls during rest, shamanic drumming, and classical music listening, followed by a validated assessment of altered states of consciousness. EEG data were used to assess changes in absolute power, connectivity, signal diversity, and criticality, which were correlated with assessment measures. We also compared assessment scores to those of individuals in a previous study under the influence of psychedelics. Shamanic practitioners were significantly different from controls in several domains of altered states of consciousness, with scores comparable to or exceeding that of healthy volunteers under the influence of psychedelics. Practitioners also displayed increased gamma power during drumming that positively correlated with elementary visual alterations. Furthermore, shamanic practitioners had decreased low alpha and increased low beta connectivity during drumming and classical music, and decreased neural signal diversity in the gamma band during drumming that inversely correlated with insightfulness. Finally, criticality in practitioners was increased during drumming in the low and high beta and gamma bands, with increases in the low beta band correlating with complex imagery and elementary visual alterations. These findings suggest that psychedelic drug-induced and non-pharmacologic alterations in consciousness have overlapping phenomenal traits but are distinct states of consciousness, as reflected by the unique brain-related changes during shamanic trance compared to previous literature investigating the psychedelic state.

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