RESEARCH



The Anesthesiology Neuroscience Research program at the University of Pittsburgh focuses on answering fundamental questions about aspects of cognition central to the practice of anesthesiology and pain medicine. Using state of the art human cognitive neuroscience techniques, we aim to better understand the intertwined mechanisms of the conscious experience, with a focus on memory formation and experiencing pain.



Systems-neuroscience of anesthetic effects in human subjects

One important thread of Dr. Vogt’s work involves a cross-sectional study of commonly-used sedative-hypnotic and analgesic drugs, funded by the NIH's National Institute of General Medical Sciences (R35GM146822). Using functional MRI and behavioral measures, we aim to characterize the systems-level brain changes that are responsible for impairment of memory encoding, fear learning, and pain processing. The puzzle image depicts how such agents can fit together in modern anesthesia practice, but this image also represents a map of previous and ongoing ANR investigations.

A previous study, funded by The Foundation for Anesthesia Education and Research (MRTG 2-2017), explored low doses of midazolam and ketamine (light blue puzzle pieces). Using a memory-encoding task with periodic painful electric nerve stimulation, this study found that hippocampal and amygdalar activity was diminished under both of these – very different – anesthetic medications. This was accompanied by more prominent decreases in memory performance under midazolam (but not ketamine) and significant pain relief under ketamine (but not midazolam). The underlying changes in brain functional connectivity, during this period of intermittent pain, were different between the two drugs in several features. First, the direction of connectivity change, using a seed-to-voxel analysis, was predominantly decreased with ketamine and almost exclusively increased under midazolam. Further analysis using a network-level ROI-to-ROI methodology revealed consistent connectivity changes under midazolam, with bilateral differences and posterior predominance. Results differed, however, under ketamine, with few network-level connectivity changes detected. The key mechanisms underpinning these differences, depending on analysis methodology is the subject of ongoing investigation.

Recently completed work, highlighted by the sand-colored puzzle pieces in the figure, compares propofol, dexmedetomidine, and fentanyl in a similar paradigm. In partnering with the 7TRF Bioengineering research program here at Pitt, we have greatly expanded our imaging capabilities and are able to characterize, under steady-state drug conditions, brain activity in memory, fear, and pain centers, and functional connectivity changes with and without pain. This represents a powerful paradigm for understanding brain changes under the influence of these three distinct drugs.

Lidocaine is a commonly-used non-opiod analgesic, often used as an anesthetic ajunct (as in the gray puzzle piece). We recently completed a study showing changes in pain response and functional connectivity during intravenous lidocaine infusion, with surprisingly widespread changes seen.

An current ongoing study (NCT06044740) focused on Sevoflurane, represents the final red puzzle piece. We are actively seeking volunteer particpants (see the Opportunities page) to participate in this investigation of how brain activity and connectivity are affected by escalating doses of this commonly-used inhaled anesthetic.

Peri-operative neurocognitive disorders

The core thread of Dr. Ibinson's research interest is leveraging neuroimaging to better understand the devleopment of perioperative neurocognitive disorders. This spans the spectrum of acute delirium to the less common phenomenon of persistent postoperative cognitive dysfunction. A variety of structural and functional imaging can help elucidate the mechanisms of these disorders, and our group is employing advanced acquisition and analysis techniques in ongoing investigations.

Collaborations

The ANR team welcomes scientific collaborations with investigators that have overlapping clinical or basic research interests. Faculty and trainees interested in the intersection of neuroscience and anesthesiology, perioperative and pain medicine practice are invited to attend the Perioperative Neuro-outcomes Group meetings, held monthly. For more information, contact Dr. Vogt.

One important collaboration, with Caroline Oppenheimer, PhD from the department of Psychiatry, is funded by the American Federation for Suicide Prevention. This study uses seeks to understand the overlap between social rejection and physical pain in adolescents with suicidal ideation and a history of self-injury. Functional MRI is being employed to determine the overlap between processing acute painful stimulation and the experience of social rejection from peers in a novel experimental paradigm.  

Another study, spearheaded by Dr. Jacques Chelly, is focused on understanding the neural correlates of auriculotherapy. This pilot study is comparing functional connectivity before and after treatment with this complimentary therapy in patients with chronic low back pain, to understand the brain changes that accompany pain relief.

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