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.  

One important thread of Dr. Vogt’s work involves a cross-sectional study of commonly-used sedative-hypnotic and analgesic drugs. 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 future 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.

Ongoing work, highlighted by the sand-colored puzzle pieces in the figure above, compares propofol, dexmedetomidine, and fentanyl in a similar paradigm. This is funded by the NIH (K23GM132755) and registered with ClinicalTrials.gov (NCT04062123). 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, behavioral performance changes across cognitive domains, 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.

Additional work, anticipated to be supported by future extramural grant awards, will expand this body of knowledge. One avenue will include exploring other agents ubiquitously-used in everyday practice of anesthesia, such as lidocaine and sevoflurane, represented by the remaining puzzle pieces, above. Additionally, key questions of dose-response to individual agents across the spectrum of depth of anesthesia will be explored.  There is also a significant gap between research and clinical practice in the use of multiple agents (rare in research, universal in practice), which we hope to model in future experimental work.