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Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring. [ABSTRACT FROM AUTHOR]

Dose-dependent effects of ketamine on processed electroencephalographic depth-of-hypnosis indices have been reported. Limited data are available for the NeuroSENSE WAVCNS index. Our aim was to establish the feasibility of closed-loop propofol-remifentanil anesthesia guided by the WAVCNS index in the presence of an analgesic dose of ketamine. Thirty ASA I-II adults, 18-54 years, requiring general anesthesia for anterior cruciate ligament surgery were randomized to receive: full-dose [ketamine, 0.5 mg kg-1 initial bolus, 10 mcg kg-1 min-1 infusion] (recommended dose for postoperative pain management); half-dose [ketamine, 0.25 mg kg-1 bolus, 5 mcg kg-1 min-1 infusion]; or control [no ketamine]. After the ketamine bolus, patients received 1.0 mcg kg-1 remifentanil over 30 s, then 1.5 mg kg-1 propofol over 30 s, followed by manually-adjusted propofol-remifentanil anesthesia. The WAVCNS was > 60 for 7/9 patients in the full-dose group at 7 min after starting the propofol infusion. This was inconsistent with clinical observations of depth-of-hypnosis and significantly higher than control (median difference [MD] 17.0, 95% confidence interval [CI] 11.4-26.8). WAVCNS was median [interquartile range] 49.3 [42.2-62.6] in the half-dose group, and not different to control (MD 5.1, 95% CI - 4.9 to 17.9). During maintenance of anesthesia, the WAVCNS was higher in the full-dose group compared to control (MD 14.7, 95% CI 10.2-19.2) and in the half-dose group compared to control (MD 11.4, 95% CI 4.7-20.4). The full-dose of ketamine recommended for postoperative pain management had a significant effect on the WAVCNS. This effect should be considered when using the WAVCNS to guide propofol-remifentanil dosing.Trial Registration ClinicalTrails.gov No. NCT02908945. [ABSTRACT FROM AUTHOR]

Objective: The goal of this paper was to optimize robust PID control for propofol anesthesia in children aged 5–10 years to improve performance, particularly to decrease the time of induction of anesthesia while maintaining robustness. Methods: We analyzed results of a previous study conducted by our group to identify opportunities for system improvement. Allometric scaling was introduced to reduce the interpatient variability and a new robust PID controller was designed using an optimization-based method. We evaluated this optimized design in a clinical study involving 16 new cases. Results: The optimized controller design achieved the performance predicted in simulation studies in the design stage. Time of induction of anesthesia was median [Q1, Q3] 3.7 [2.3, 4.1] min and the achieved global score was 13.4 [9.9, 16.8]. Conclusion: Allometric scaling reduces the interpatient variability in this age group and allows for improved closed-loop performance. The uncertainty described by the model set, the predicted closed-loop responses, and the predicted robustness margins are realistic. The system meets the design objectives of improved speed of induction of anesthesia while maintaining robustness and improving clinically relevant system behavior. Significance: Control system optimization and ongoing system improvements are essential to the development of a clinically relevant commercial device. This paper demonstrates the validity of our approach, including system modeling, controller optimization, and pre-clinical testing in simulation. [ABSTRACT FROM AUTHOR]

Sedation in the intensive care unit (ICU) is challenging, as both over- and under-sedation are detrimental. Current methods of assessment, such as the Richmond Agitation Sedation Scale (RASS), are measured intermittently and rely on patients' behavioral response to stimulation, which may interrupt sleep/rest. A non-stimulating method for continuous sedation monitoring may be beneficial and allow more frequent assessment. Processed electroencephalography (EEG) monitors have not been routinely adopted in the ICU. The aim of this observational study was to assess the feasibility of using the NeuroSENSE™ monitor for EEG-based continuous sedation assessment. With ethical approval, ICU patients on continuous propofol sedation were recruited. Depth-of-hypnosis index (WAVCNS) values were obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE, performed regular RASS assessments and maintained the sedation regimen as per standard of care. Participants were monitored throughout the duration of their propofol infusion, up to 24 h. Fifteen patients, with median [interquartile range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7-20.1] h. Valid WAVCNS values were obtained for 89% [66-99] of monitoring time and were widely distributed within and between individuals, with 6% [1-31] spent < 40 (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89 (40%) assessments. The WAVCNS variability, and incidence of EEG suppression, highlight the limitations of using RASS as a standalone sedation measure, and suggests potential benefit of adjunct continuous brain monitoring. [ABSTRACT FROM AUTHOR]

The neurophysiological mechanism of interhemispheric inhibition (IHI) between the human primary sensory cortices (S1s) is poorly understood. Here we used a paired median nerve somatosensory evoked potential protocol to observe S1-S1 IHI from the dominant to the nondominant hemisphere with electroencephalography. In 10 healthy, right-handed individuals, we compared mean peak-to-peak amplitudes of five somatosensory evoked potential components (P14/N20, N20/P25, P25/N30, N30/P40, and P40/N60) recorded over the right S1 after synchronous versus asynchronous stimulation of the right and left median nerves. Asynchronous conditioning + test stimuli (CS+TS) were delivered at interstimulus intervals of 15, 20, 25, 30, and 35 ms. We found that, in relation to synchronous stimulation, when a CS to the left S1 preceded a TS to the right S1 at the short intervals (15 and 20 ms) the amplitude of the cortical N20/P25 complex was significantly depressed, whereas at the longer intervals (25, 30, and 35 ms) significant inhibition was observed for the thalamocortical P14/N20 as well as the cortical N20/P25 components. We conclude that the magnitude of S1 IHI appears to depend on the temporal asynchrony of bilateral inputs and the specific timing is likely reflective of a direct transcallosal mechanism. Employing a method that enables direct S1 IHI to be reliably quantified may provide a novel tool to assess potential IHI imbalances in individuals with neurological damage, such as stroke. [ABSTRACT FROM AUTHOR]

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri -central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15–30 Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke. [ABSTRACT FROM AUTHOR]

Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10−4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10−7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10−7). This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication. • This study examined the role of genetics in the cardiac safety of ondansetron. • 1.2% of patients experienced unsafe ondansetron-induced QT prolongation. • 24.1% of patients experienced a shift in QTc after ondansetron treatment. • The biggest shift in QTc occurred at five minutes post-ondansetron administration. • Genome-wide analyses provided new insights into the genetics of this adverse event. [ABSTRACT FROM AUTHOR]

Closed-loop control of anesthesia based on continuous feedback from processed electroencephalography adjusts drug dosing to target a desired depth of hypnosis during dynamic clinical circumstances, freeing the anesthesiologist to focus on more complex tasks. We describe a case of closed-loop control of total intravenous anesthesia in which a sudden loss of blood required immediate intervention. This case illustrates that closed-loop control of drug delivery maintained an appropriate depth of hypnosis during a rapidly changing surgical situation, and that processed electroencephalography may be a useful adjunct indicator for cerebral hypoperfusion.

Background: Brain injury after intracerebral hemorrhage (ICH) arises from numerous contributors, of which some also play essential roles. Notably, thrombin production, needed to stop bleeding, also causes acute cell death and edema. In some rodent models of ICH, peri-hematoma neurons die over weeks. Hence we evaluated whether thrombin is responsible for this chronic degeneration. Functional impairments after ICH also result from sub-lethal damage to neurons, especially the loss of dendrites. Thus, we evaluated whether thrombin infusion alone, a reductionist model of ICH, causes similar injury., Methods: Adult rats had a modest intra-striatal infusion of thrombin (1 U) or saline followed by a behavioral test, to verify impairment, 7 days later. After this they were euthanized and tissue stained with Golgi-Cox solution to allow the assessment of dendritic morphology in striatal neurons. In a second experiment, rats survived 7 or 60 days after thrombin infusion in order to histologically determine lesion volume., Results: Thrombin caused early cell death and considerable atrophy in surviving peri-lesion neurons, which had less than half of their usual numbers of branches. However, total tissue loss was comparable at 7 (24.1 mm3) and 60 days (25.6 mm3)., Conclusion: Thrombin infusion causes early cell death and neuronal atrophy in nearby surviving striatal neurons but thrombin does not cause chronic tissue loss. Thus, the chronic degeneration found after ICH in rats is not simply and solely due to acute thrombin production. Nonetheless, thrombin is an important contributor to behavioral dysfunction because it causes cell death and substantial dendritic injury.

Sensory feedback is critical for motor learning, and thus to neurorehabilitation after stroke. Whether enhancing sensory feedback by applying excitatory repetitive transcranial magnetic stimulation (rTMS) over the ipsilesional primary sensory cortex (IL-S1) might enhance motor learning in chronic stroke has yet to be investigated. The present study investigated the effects of 5 Hz rTMS over IL-S1 paired with skilled motor practice on motor learning, hemiparetic cutaneous somatosensation, and motor function. Individuals with unilateral chronic stroke were pseudo-randomly divided into either Active or Sham 5 Hz rTMS groups (n = 11/group). Following stimulation, both groups practiced a Serial Tracking Task (STT) with the hemiparetic arm; this was repeated for 5 days. Performance on the STT was quantified by response time, peak velocity, and cumulative distance tracked at baseline, during the 5 days of practice, and at a no-rTMS retention test. Cutaneous somatosensation was measured using two-point discrimination. Standardized sensorimotor tests were performed to assess whether the effects might generalize to impact hemiparetic arm function. The active 5 Hz rTMS + training group demonstrated significantly greater improvements in STT performance {response time [F (1, 286.04) = 13.016, p < 0.0005], peak velocity [F (1, 285.95) = 4.111, p = 0.044], and cumulative distance [F (1, 285.92) = 4.076, p = 0.044]} and cutaneous somatosensation [F (1, 21.15) = 8.793, p = 0.007] across all sessions compared to the sham rTMS + training group. Measures of upper extremity motor function were not significantly different for either group. Our preliminary results suggest that, when paired with motor practice, 5 Hz rTMS over IL-S1 enhances motor learning related change in individuals with chronic stroke, potentially as a consequence of improved cutaneous somatosensation, however no improvement in general upper extremity function was observed.