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Papers by paul picton

Frontiers in Human Neuroscience

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major p... more The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, upon recovery of consciousness (ROC), and at half-hour intervals up to 3 h following ROC. EEG networks were derived using the strength of functional connectivity measured through the weighted phase lag inde...

Journal of Clinical Monitoring and Computing

Understanding how consciousness and cognitive function return after a major perturbation is impor... more Understanding how consciousness and cognitive function return after a major perturbation is important clinically and neurobiologically. To address this question, we conducted a three-center study of 30 healthy humans receiving general anesthesia at clinically relevant doses for three hours. We administered a pre- and post-anesthetic battery of neurocognitive tests, recorded continuous electroencephalography to assess cortical dynamics, and monitored sleep-wake activity before and following anesthetic exposure. We hypothesized that cognitive reconstitution would be a process that evolved over time in the following sequence: attention, complex scanning and tracking, working memory, and executive function. Contrary to our hypothesis, executive function returned first and electroencephalographic analyses revealed that frontal cortical dynamics recovered faster than posterior cortical dynamics. Furthermore, actigraphy indicated normal sleep-wake patterns in the post-anesthetic period. Th...

Motifs are patterns of inter-connections between nodes of a network, and have been investigated a... more Motifs are patterns of inter-connections between nodes of a network, and have been investigated as building blocks of directed networks. This study explored the re-organization of 3-node motifs during loss and recovery of consciousness. Nine healthy subjects underwent a 3-hour anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8–13 Hz) band, five-minute epochs of EEG were extracted for: baseline; induction; unconsciousness; 30-, 10- and 5-minutes pre-recovery of consciousness; 30- and 180-minutes post-recovery of consciousness. We constructed a functional brain network using both the weighted and the directed phase lag index, on which we calculated graph theoretical network properties, and the frequency and topography of 3-node motifs. Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p<0.05). While graph theoretical properties varied inconsistently across uncon...

BMC Anesthesiology

Background Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide int... more Background Perioperative hyperglycemia is associated with poor outcomes yet evidence to guide intraoperative goals and treatment modalities during non-cardiac surgery are lacking. End-stage liver disease is associated with altered glucose homeostasis; patients undergoing liver transplantation display huge fluctuations in blood glucose (BG) and represent a population of great interest. Here, we conduct a randomized trial to compare the effects of strict versus conventional glycemic control during orthotopic liver transplant (OLT). Methods Following approval by the Institutional Review Board of the University of Michigan Medical School and informed consent, 100 adult patients undergoing OLT were recruited. Patients were randomized to either strict (target BG 80–120 mg/dL) or conventional (target BG 180–200 mg/dL) BG control with block randomization for diabetic and nondiabetic patients. The primary outcomes measured were 1-year patient and graft survival assessed on an intention to tr...

Frontiers in Neurology

Background: Stroke is a devastating perioperative complication without effective methods for prev... more Background: Stroke is a devastating perioperative complication without effective methods for prevention or diagnosis. The objective of this study was to analyze evidence-based strategies for detecting cerebrovascular vulnerability and injury in a high-risk cohort of non-cardiac surgery patients. Methods: This was a single-center, prospective cohort study. Fifty patients undergoing non-cardiac surgery were recruited −25 with known cerebrovascular disease and 25 matched controls. Neurologic vulnerability was measured with intraoperative cerebral oximetry as the primary outcome. Perioperative neurocognitive testing and serum biomarker analysis (S-100β, neuron specific enolase, glial fibrillary acid protein, and matrix metalloproteinase-9) were measured as secondary outcomes. Results: Cerebral desaturation events (an oximetry decrease ≥20% from baseline or <50% absolute value for ≥3 min) occurred in 7/24 (29%) cerebrovascular disease patients and 2/24 (8.3%) controls (relative risk 3.5, 95% CI 0.81-15.2; P = 0.094). Cognitive function trends were similar in both groups, though overall scores (range: 1,500-7,197) were ∼1 standard deviation lower in cerebrovascular patients across the entire perioperative period (−1,049 [95% CI −1,662, −436], P < 0.001). No significant serum biomarker differences were found between groups over time. One control patient experienced intraoperative hypoxic-ischemic injury, but no robust biomarker or oximetry changes were observed. Conclusions: Cerebrovascular disease patients did not demonstrate dramatic differences in cerebral oximetry, cognitive trajectory, or molecular biomarkers compared to controls. Moreover, a catastrophic hypoxic-ischemic event was neither predicted nor detected by any strategy tested. These findings support the need for novel research into cerebrovascular risk and vulnerability.

Anesthesiology

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New... more Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Recent studies of anesthetic-induced unconsciousness in healthy volunteers have focused on functional brain connectivity patterns, but the protocols rarely parallel the depth and duration of surgical anesthesia. Furthermore, it is unknown whether there is a single functional connectivity pattern that correlates with general anesthesia for the duration of prolonged anesthetic exposure. Methods The authors analyzed electroencephalographic data in 30 healthy participants who underwent induction of anesthesia with propofol followed by 3 h of isoflurane anesthesia at age-adjusted 1.3 minimum alveolar concentration. Functional connectivity was assessed by frequency-resolved weighted phase lag index between frontal and parietal channels and between prefrontal and frontal channels, which were classified into a discrete set of states through k-means cluster analysis. Temporal dynamics...

Scientific reports, Jan 4, 2018

Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great... more Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert consciousness. Using noninvasive neuroimaging in healthy volunteers, we identified a healthy study participant who was able to exhibit the specific fMRI signatures of volitional mental imagery while behaviorally unresponsive due to sedation with propofol. Our findings reveal a novel model that may accelerate the development of new approaches to reproducibly detect covert consciousness, which is difficult to achieve in patients with heterogeneous and sometimes clinically unstable neuropathology.

Journal of Cardiothoracic and Vascular Anesthesia

Anesthesiology, Jul 1, 2017

Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although di... more Previous studies have demonstrated inconsistent neurophysiologic effects of ketamine, although discrepant findings might relate to differences in doses studied, brain regions analyzed, coadministration of other anesthetic medications, and resolution of the electroencephalograph. The objective of this study was to characterize the dose-dependent effects of ketamine on cortical oscillations and functional connectivity. Ten healthy human volunteers were recruited for study participation. The data were recorded using a 128-channel electroencephalograph during baseline consciousness, subanesthetic dosing (0.5 mg/kg over 40 min), anesthetic dosing (1.5 mg/kg bolus), and recovery. No other sedative or anesthetic medications were administered. Spectrograms, topomaps, and functional connectivity (weighted and directed phase lag index) were computed and analyzed. Frontal theta bandwidth power increased most dramatically during ketamine anesthesia (mean power ± SD, 4.25 ± 1.90 dB) compared to ...

Anesthesiology, 2015

Background: Beach chair positioning during general anesthesia is associated with cerebral oxygen ... more Background: Beach chair positioning during general anesthesia is associated with cerebral oxygen desaturation. Changes in cerebral oxygenation resulting from the interaction of inspired oxygen fraction (Fio2), end-tidal carbon dioxide (PETco2), and anesthetic choice have not been fully evaluated in anesthetized patients in the beach chair position. Methods: This is a prospective interventional within-group study of patients undergoing shoulder surgery in the beach chair position that incorporated a randomized comparison between two anesthetics. Fifty-six patients were randomized to receive desflurane or total intravenous anesthesia with propofol. Following induction of anesthesia and positioning, Fio2 and minute ventilation were sequentially adjusted for all patients. Regional cerebral oxygenation (rSo2) was the primary outcome and was recorded at each of five set points. Results: While maintaining Fio2 at 0.3 and PETco2 at 30 mmHg, there was a decrease in rSo2 from 68% (SD, 12) to ...

Anesthesiology, Jan 14, 2015

Hyperglycemia, defined as blood glucose (BG) levels above 200 mg/dl (11.1 mM), is associated with... more Hyperglycemia, defined as blood glucose (BG) levels above 200 mg/dl (11.1 mM), is associated with increased postoperative morbidity. Yet, the treatment standard for intraoperative glycemic control is poorly defined for noncardiac surgery. Little is known of the interindividual treatment variability or methods to modify intraoperative glycemic management behaviors. AlertWatch (AlertWatch, USA) is a novel audiovisual alert system that serves as a secondary patient monitor for use in operating rooms. The authors evaluated the influence of use of AlertWatch on intraoperative glycemic management behavior. AlertWatch displays historical patient data (risk factors and laboratory results) from multiple networked information systems, combined with the patient's live physiologic data. The authors extracted intraoperative data for 19 months to evaluate the relationship between AlertWatch usage and initiation of insulin treatment for hyperglycemia. Outcome associations were adjusted for phy...

Case Studies in Neuroanesthesia and Neurocritical Care, 2011

Liver Anesthesiology and Critical Care Medicine, 2012

Pediatric Anesthesia, 2002

Journal of Clinical Monitoring and Computing, 2010

The influence of basic ventilation strategies on cerebral oxygenation in anesthetized patients wi... more The influence of basic ventilation strategies on cerebral oxygenation in anesthetized patients without vascular disease.

BMC Anesthesiology, 2012

Background: Beach chair positioning during general anesthesia is associated with a high incidence... more Background: Beach chair positioning during general anesthesia is associated with a high incidence of cerebral desaturation; poor neurological outcome is a growing concern. There are no published data pertaining to changes in cerebral oxygenation seen with increases in the inspired oxygen fraction or end-tidal carbon dioxide in patients anesthetized in the beach chair position. Furthermore, the effect anesthetic agents have has not been thoroughly investigated in this context. We plan to test the hypothesis that changes in inspired oxygen fraction or end-tidal carbon dioxide correlate to a significant change in regional cerebral oxygenation in anesthetized patients in beach chair position. We will also compare the effects that inhaled and intravenous anesthetics have on this process. Methods/design: This is a prospective within-group study of patients undergoing shoulder arthroscopy in the beach chair position which incorporates a randomized comparison between two anesthetics, approved by the Institutional Review Board of the University of Michigan, Ann Arbor. The primary outcome measure is the change in regional cerebral oxygenation due to sequential changes in oxygenation and ventilation. A sample size of 48 will have greater than 80% power to detect an absolute 4-5% difference in regional cerebral oxygenation caused by changes in ventilation strategy. The secondary outcome is the effect of anesthetic choice on cerebral desaturation in the beach chair position or response to changes in ventilation strategy. Fifty-four patients will be recruited, allowing for drop out, targeting 24 patients in each group randomized to an anesthetic. Regional cerebral oxygenation will be measured using the INVOS 5100C monitor (Covidien, Boulder, CO). Following induction of anesthesia, intubation and positioning, inspired oxygen fraction and minute ventilation will be sequentially adjusted. At each set point, regional cerebral oxygenation will be recorded and venous blood gas analysis performed. The overall statistical analysis will use a repeated measures analysis of variance with Tukey's HSD procedure for post hoc contrasts. Discussion: If simple maneuvers of ventilation or anesthetic technique can prevent cerebral hypoxia, patient outcome may be improved. This is the first study to investigate the effects of ventilation strategies on cerebral oxygenation in patients anesthetized in beach chair position.