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Dissertation Defense: Causal mapping of pain and autonomic function in the anterior midcingulate cortex

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Andrew Strohman
Dissertation Defense

Causal mapping of pain and autonomic function in the anterior midcingulate cortex

Andrew Strohman

Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, Legon Lab, Fralin Biomedical Research Institute at VTC 
June 23, at 1 p.m.
Room G101 A/B, 4 Riverside Circle
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About this Dissertation

The anterior midcingulate cortex (aMCC) is a deep brain region involved in pain and regulating the autonomic nervous system, the part of the nervous system that automatically controls bodily functions like heart rate, breathing, sweating, and blood pressure. Although prior work has linked the aMCC to pain and autonomic function, its depth from the scalp has made it difficult to test its causal role in healthy people. In this thesis, we leveraged low-intensity focused ultrasound (LIFU), a noninvasive brain stimulation technique that can safely and precisely target deep brain regions in humans. We used LIFU to ask how the aMCC processes pain signals and regulates autonomic responses to pain.

In the first study, we delivered brief pulses of heat pain while applying LIFU to the aMCC and measuring pain ratings, autonomic responses, and a brain response called the contact heat-evoked potential (CHEP). Compared with sham stimulation, LIFU to the aMCC reduced pain perception, autonomic responses, and the amplitude of the CHEP. These findings demonstrate LIFU can manipulate pain and autonomic processing in the aMCC while revealing its causal role during brief painful stimuli.

In the second study, we performed two separate experiments. First, we delivered LIFU to the aMCC, posterior insular cortex, or sham between trials of the cold pressor test, a longer-lasting pain stimulus that produces strong blood pressure and heart rate responses. While continuously recording blood pressure and heart rate, we found that LIFU to the aMCC, but not insular or sham stimulation, caused real-time increases in blood pressure and reduced later blood pressure responses to the cold pressor with no change in pain ratings. These blood pressure effects were associated with connections between the aMCC and the insula and hypothalamus, two other key autonomic brain regions, measured using resting-state functional connectivity.

Finally, we asked whether certain autonomic measures tracked pain perception better than others. Participants completed the cold pressor test at three intensities while we recorded continuous blood pressure, heart rate, respiration rate, and sweat responses. We found that only systolic blood pressure specifically tracked reported pain perception compared to a vibration task designed to control for nonpainful sensation and a motor task designed to control for attention without sensation.

Together, the work in this thesis reveals a causal role of the aMCC in pain and autonomic processing during both brief and sustained pain in healthy people. Next steps include translating these findings into clinical trials to test whether LIFU can target the autonomic nervous system to improve the lives of people living with chronic pain.

More About the Candidate and Project

Education

Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate

Virginia Commonwealth University, Masters of Public Health


University of Virginia, B.S., Biology

Training

Graduate Research Assistant, Legon Lab, Fralin Biomedical Research Institute at VTC 

Mentors

Wynn Legon, Ph.D., Assistant Professor, School of Neuroscience; Fralin Biomedical Research Institute at VTC

Committee Members

  • Anthony-Samuel LaMantia, Ph.D., Professor, Fralin Biomedical Research Insittute at VTC; Director, Center for Neurobiology Research
  • Mark Witcher, MD, Ph.D., Vice Chair of Research and Education, Neurosurgery at VTC School of Medicine; Functional Neurosurgery, Carilion Clinic
  • Shan Siddiqi, MD, Assistant Professor, Harvard Medical School; Neuropsychiatrist, Center for Brain Cirtuit Therapeutics at Brighman and Women's Hospital
  • Bruce Scarpa-Friedman, Ph.D., Associate Professor, Department of Psychology

Publications

  • Legon, J., Strohman, A., Ni, Y., Isaac, G., Kapoor, A., Painchaud, K., ... & Legon, W. (2026). Anterior insula and mid-cingulate cortex differentially regulate anxiety and fear brain/body responses. medRxiv. DOI: 10.1101/2025.10.08.25337596. (Under review).


  • Webler, R., Neudorfer, C., …. Strohman, A., Legon, W., … Siddiqi, S. Focal brain stimulation sites that modify autonomic arousal map to a convergent brain circuit and potential therapeutic target. DOI: 10.64898/2026.01.08.698446. (Under review).
  • Kapoor, A., Strohman, A., Ni, Y., Isaac, G., Raymond, J., Legon, W. (2026). Acoustic Coupling for Double-Blind Human Low-Intensity Focused Ultrasound Neuromodulation. bioRxiv. DOI: 10.1101/2025.10.02.680055 (in press, Ultrasound for Medicine and Biology)
  • Legon, W., Isaac, G., Kappor, A., Strohman, A. Modulation of Posterior Insula Selectively Enhances Nociceptive Sensory Gating in Humans. Neurobiology of Pain. DOI: 10.1016/j.ynpai.2026.100220





  • Philip, N., Arulpragasm, A., Curtin, D., Strohman, A., Fouragnan, E., & Legon, W. A standardized framework for reporting participant-experienced events in low intensity focused ultrasound neuromodulation. Brain Stimulation (2026). DOI: 10.1016/j.brs.2026.103104.
  • Strohman, A. & Legon, W. Neuromodulation of the cingulate cortex for pain. The Neuroscientist (2025). DOI: 10.1177/10738584251337652.



  • Olaitan, G., Ganesana, M., Strohman, A., Lynch, W., Legon, W, & Venton, J. Focused Ultrasound Modulates Dopamine in a Mesolimbic Reward Circuit. Journal of Neurochemistry (2025). DOI: doi.org/10.1111/jnc.70001.


  • In, A., Strohman, A., Payne, B., & Legon, Low-intensity focused ultrasound to the posterior insula reduces temporal summation of pain. Brain Stimulation (2024). DOI: 10.1016/j.brs.2024.07.020.


  • Ennasr, A.♰, Isaac, G.♰, Strohman, A., & Legon, W. Examination of the interaction of parameters for low-intensity focused ultrasound of the human motor cortex. Brain Stimulation (2024). DOI: 10.1016/j.brs.2024.11.005.


  • Legon, W., Strohman, A., In, A., & Payne, B. Non-invasive neuromodulation of sub-regions of the human insula differentially affect pain processing and heart-rate variability. PAIN (2024) DOI: 10.1097/j.pain.0000000000003171.
  • Strohman, A., Isaac, G., Payne, B., Verdonk, C., Khalsa, S., & Legon, W. Low-intensity focused ultrasound to the insula differentially modulates the heartbeat-evoked potential: A proof-of-concept study. Clinical Neurophysiology (2024). DOI: 10.1016/j.clinph.2024.09.006.
  • Legon, W. & Strohman, A. Low-intensity focused ultrasound for human neuromodulation. Nature Reviews Methods Primers (2024). DOI: 10.1038/s43586-024-00368-6.
  • Strohman, A., Payne, B., In, A., Stebbins, K. & Legon, W. Low-intensity focused ultrasound to the human dorsal anterior cingulate attenuates acute pain perception and autonomic responses. Journal of Neuroscience (2024). DOI: 10.1523/JNEUROSCI.1011-23.2023.
  • Strohman, A., In, A., Stebbins, K. & Legon, W. Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. Ultrasound in Medicine & Biology (2023) DOI: 10.1016/j.ultrasmedbio.2023.02.003.