The Translational Neuroscience of Post-Anesthetic Recovery

Connor Brenna, MD

Perioperative neurocognitive disorders are among the most common complications after anesthesia and surgery, and are expected to become even more prevalent in our aging surgical population. At the same time, these disorders offer a unique window into translational neuroscience by illustrating how anesthetic drugs, surgical insult, and medical illness can converge on sustained deficits in brain function. This was the focus of the session “Clearing the Fog: Emerging Strategies to Improve Post-Anesthetic Cognitive Recovery,” held Friday, May 1, and cosponsored by the Early-Stage Anesthesiology Scholars (eSAS), during the 2026 Annual Meeting, presented by IARS and SOCCA. Three talks moved deliberately across the translational spectrum of postanesthetic cognitive recovery, from clinical observations to mechanistic studies aimed at identifying future therapeutic targets. The session was moderated by Mitra Heshmati, MD, PhD, an assistant professor of anesthesiology and pain medicine and neurobiology and biophysics, and an affiliate faculty of the Center for Neurobiology of Addiction Pain and Emotion at University of Washington.

The opening presentation, “Clinical Strategies to Support Cognitive Recovery Post Surgery,” was delivered by Stacie Deiner, MD, MS, a neurosurgical anesthesiologist and professor of anesthesiology, Geisel School of Medicine at Dartmouth Health, chair of the American Society of Anesthesiology Brain Health Initiative and a director for the American Board of Anesthesiology, who framed the modern clinical understanding of perioperative neurocognitive disorders. Historically, postoperative cognitive dysfunction (POCD) served as a broad and poorly defined umbrella term for cognitive changes after surgery. In 2018, however, consensus recommendations for a new nomenclature aligned perioperative neurocognitive disorders with DSM-5 terminology for cognitive change, enabling clinicians and researchers to distinguish between postoperative delirium (POD), delayed neurocognitive recovery (dNCR), and longer-term postoperative neurocognitive disorders (pNCDs). Dr. Deiner highlighted some of the diagnostic challenges that remain: subjective cognitive complaints are sensitive but nonspecific markers of these disorders, and longitudinal studies need to be cautious to distinguish changes at late postoperative timepoints from normal cognitive decline that occurs with aging. There are currently no targeted therapies to treat perioperative neurocognitive disorders, but several important risk factors have emerged, with preexisting cognitive impairment and clinical frailty chief among them. Current best practices emphasize prevention and early recognition, for example, through preoperative cognitive screening and high-risk medication review, consideration of dexmedetomidine and regional anesthetic techniques when appropriate in perioperative care, and early postoperative delirium screening and pain control paired with nonpharmacological best practices such as early mobilization, hydration, and sleep.

In the second session, “Through the Fog and Into the Night: Harnessing Sleep to Prevent Delirium and Maintain Attention,” Michael Devinney, MD, PhD, a critical care anesthesiologist in his fifth year on faculty in the Department of Anesthesiology at Duke University, remarked on the relationship between sleep, attention, and POD. Preoperative sleep disorders have been associated with increased POD risk, while sleep deprivation itself is closely linked to impaired attention (a hallmark feature of POD). Dr. Devinney presented a secondary analysis of the REPOSE Trial, comprising cognitive assessments, measurements of attention using the psychomotor vigilance test, and sleep data derived from electroencephalogram (EEG) recordings in a sample of postoperative patients. Unexpectedly, patients who developed POD demonstrated increased sleep duration and fewer sleep disruptions over the first two postoperative days compared with their nondelirious counterparts. Automated EEG staging suggested that this increase was predominantly in N2-stage sleep, with possible contributions of REM sleep as well. These findings suggest that sleep may not play an intuitively protective or restorative role to safeguard against POD. Instead, it is possible that altered arousal pathways contribute to POD vulnerability, and that these pathways may contain promising therapeutic targets for perioperative intervention.

The final talk, “Circuit-Based Approaches to Cognitive Recovery: Insights from Animal Models,” was presented by Kathleen Vincent, PhD, an assistant professor in the Department of Anesthesia, Critical Care, and Pain Medicine at Massachusetts General Hospital and Harvard Medical School. Dr. Vincent described how rodent models can provide mechanistic insight into cognitive recovery after anesthesia. These models offer several advantages: for example, investigators can isolate the effects of anesthesia from surgery, study transgenic animals that reflect at-risk patient populations, and probe specific neural circuits underlying attention and arousal. Dr. Vincent’s work has shown that transgenic mouse models of Alzheimer’s disease recover more slowly from anesthesia, and exhibit both specific deficits in attention-based cognitive tasks as well as broader behavioral hypoactivity. These findings led her team to investigate whether impaired arousal circuitry contributes to delayed emergence. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADD) chemogenetic tools, Dr. Vincent selectively activated dopaminergic neurons within the ventral tegmental area of the brain, accelerating recovery even in cognitively vulnerable mice. Similar effects were achieved by pharmacologically activating these neurons with methylphenidate. Together, these experiments suggest that dopamine arousal circuits may be a clinically relevant therapeutic target to speed up emergence from anesthesia.

These three presentations illustrated a compelling translational arc that has become familiar in perioperative neuroscience: characterizing behavioral and physiologic markers of vulnerability, and working backwards to identify the tractable neural circuits that regulate them. In this way we can find potential biologic targets for new therapies, like drugs that deliberately modulate the brain’s arousal systems, to be translated back to the bedside in service of perioperative brain health.