Preoperative Cognitive Abnormality, Intraoperative Electroencephalogram Suppression, and Postoperative Delirium: A Mediation Analysis.

BACKGROUND: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. METHODS: This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. RESULTS: Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation). CONCLUSIONS: A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.

Central-Positive Complexes: A Novel Characterization of Ictal Markers Induced During Electroconvulsive Therapy.

OBJECTIVES: Electroencephalography (EEG) allows monitoring of generalized seizures induced during electroconvulsive therapy (ECT). Scalp EEG recordings show different phases of electroencephalographic ictal activity during ECT seizures, documenting a pattern of seizures that may vary within and across individuals. In this case series, we used 64-electrode high-density EEG recording to detect topographic electroencephalographic changes not typically evident with conventional limited montages commonly used during ECT. METHODS: The EEG recordings were acquired from 5 participants (24 ECT sessions) during index courses for treatment-resistant depression. Using previously proposed staging criteria, the ictal EEG and simultaneously acquired video were interpreted by an expert reviewer blinded to study treatment parameters. RESULTS: The EEG recordings of all seizures showed generalized, high-amplitude, central-positive complexes (CPCs), which emerged at the beginning of phase III (polyspike and slow wave activity), with median duration of 47 seconds (interquartile range, 77 seconds), ranging from 14 to 203 seconds. Although individuals showed variability in frequency and amplitude of CPCs, CPCs typically evolved from 4.0 to 1.5 Hz in frequency and decreased in amplitude as the seizure progressed. Elaborating on previously described phases of ECT-induced electrographic seizures, we describe variability in morphology at seizure termination. Initiation of CPCs typically corresponded with clonic movements, but often terminated after motor signs ceased. CONCLUSIONS: Generalized, high-amplitude, CPCs during ECT are a previously uncharacterized ictal waveform during ECT, which may have important scientific and clinical value. These complexes offer a specific marker for correlating clinical outcomes in ECT and greater understanding of generalized tonic-clonic seizures.

Individual differences in orthographic priming relate to phonological decoding skill in adults.

We examined relationships between individual differences in orthographic priming and a battery of measures assessing orthographic processing ability, reading history, current reading ability, and verbal intelligence in university students. Pronounceable and unpronounceable nonword primes preceded word and nonword targets. Individual differences in nonword reading skill and other measures of reading and spelling ability were associated with the degree of orthographic priming. Individuals with less phonological decoding skill benefited more from anagram primes for word targets preceded by unpronounceable primes and nonword targets preceded by pronounceable primes. Analyses of extreme groups revealed that the group with the lowest phonemic decoding efficiency scores showed a general benefit of orthographic relatedness, while the group with the highest phonemic decoding efficiency scores showed a benefit only under certain conditions. Thus, individuals with worse nonword reading skills may have less precise orthographic representations and therefore benefit more from overlapping coarse-grained orthographic information, regardless of the pronounceability of the prime or the lexical status of the target. These findings demonstrate that university students vary in their orthographic processing skill and the degree to which orthographic information is used during word recognition.

Cognitive and Neurophysiological Recovery Following Electroconvulsive Therapy: A Study Protocol.

Electroconvulsive therapy (ECT) employs the elective induction of generalizes seizures as a potent treatment for severe psychiatric illness. As such, ECT provides an opportunity to rigorously study the recovery of consciousness, reconstitution of cognition, and electroencephalographic (EEG) activity following seizures. Fifteen patients with major depressive disorder refractory to pharmacologic therapy will be enrolled (Clinicaltrials.gov, NCT02761330). Adequate seizure duration will be confirmed following right unilateral ECT under etomidate anesthesia. Patients will then undergo randomization for the order in which they will receive three sequential treatments: etomidate + ECT, ketamine + ECT, and ketamine + sham ECT. Sessions will be repeated in the same sequence for a total of six treatments. Before each session, sensorimotor speed, working memory, and executive function will be assessed through a standardized cognitive test battery. After each treatment, the return of purposeful responsiveness to verbal command will be determined. At this point, serial cognitive assessments will begin using the same standardized test battery. The presence of delirium and changes in depression severity will also be ascertained. Sixty-four channel EEG will be acquired throughout baseline, ictal, and postictal epochs. Mixed-effects models will correlate the trajectories of cognitive recovery, clinical outcomes, and EEG metrics over time. This innovative research design will answer whether: (1) time to return of responsiveness will be prolonged with ketamine + ECT compared with ketamine + sham ECT; (2) time of restoration to baseline function in each cognitive domain will take longer after ketamine + ECT than after ketamine + sham ECT; (3) postictal delirium is associated with delayed restoration of baseline function in all cognitive domains; and (4) the sequence of reconstitution of cognitive domains following the three treatments in this study is similar to that occurring after an isoflurane general anesthetic (NCT01911195). Sub-studies will assess the relationships of cognitive recovery to the EEG preceding, concurrent, and following individual ECT sessions. Overall, this study will lead the development of biomarkers for tailoring the cogno-affective recovery of patients undergoing ECT.