Stanford Advisors


All Publications


  • Mapping the Effects of Intracranial Electrical Stimulation of the Human Orbitofrontal Cortex. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society Pantis, S., Lyu, D., Huang, W., Kwon, A., Cheng, C., Duong, A., Ma, E., Fox, K. C., Parvizi, J. 2025

    Abstract

    INTRODUCTION: Prior findings on direct intracranial electrical stimulation (iES) of the human orbitofrontal cortex (OFC), which includes the orbital and ventromedial prefrontal regions, have been mixed, with several reports lacking replication. We aimed to clarify the effects of iES in the OFC.METHODS: We analyzed data from 608 stimulations across 277 OFC site pairs (352 sites total) in 49 patients collected over 17 years of our practice.RESULTS: We found 24.4% of sites as responsive to iES, with subjects reporting visual and olfactory sensations. However, post hoc analysis revealed that these responses largely originated from the stimulation of nearby non-OFC optic and olfactory structures. After applying quality controls, stimulation of only 0.6% of OFC sites (2 sites, 2 patients) produced changes in subjective domain, while 99.4% had no reportable effects. Contrary to earlier studies, we found no evidence of valence lateralization or functional organization within the OFC.CONCLUSIONS: Our findings suggest that the electrical perturbation of OFC is largely silent and does not lead to reportable change in the subjective state of the individual.SIGNIFICANCE: Orbitofrontal cortex is a higher transmodal cortical area. The variability and limited replicability of reported effects from prior publications and the inconsistencies in the extant literature about OFC stimulations can be attributed to methodological shortcomings.

    View details for DOI 10.1097/WNP.0000000000001184

    View details for PubMedID 40637402

  • Naturalistic acute pain states decoded from neural and facial dynamics. Nature communications Huang, Y., Gopal, J., Kakusa, B., Li, A. H., Huang, W., Wang, J. B., Persad, A., Ramayya, A., Parvizi, J., Buch, V. P., Keller, C. J. 2025; 16 (1): 4371

    Abstract

    Pain remains poorly understood in task-free contexts, limiting our understanding of its neurobehavioral basis in naturalistic settings. Here, we use a multimodal, data-driven approach with intracranial electroencephalography, pain self-reports, and facial expression analysis to study acute pain in twelve epilepsy patients under continuous neural and audiovisual monitoring. Using machine learning, we successfully decode individual participants' high versus low pain states from distributed neural activity, involving mesolimbic regions, striatum, and temporoparietal cortex. Neural representation of pain remains stable for hours and is modulated by pain onset and relief. Objective facial expressions also classify pain states, concordant with neural findings. Importantly, we identify transient periods of momentary pain as a distinct naturalistic acute pain measure, which can be reliably discriminated from affect-neutral periods using neural and facial features. These findings reveal reliable neurobehavioral markers of acute pain across naturalistic contexts, underscoring the potential for monitoring and personalizing pain interventions in real-world settings.

    View details for DOI 10.1038/s41467-025-59756-5

    View details for PubMedID 40350488

    View details for PubMedCentralID 6146950

  • Naturalistic acute pain states decoded from neural and facial dynamics. bioRxiv : the preprint server for biology Huang, Y., Gopal, J., Kakusa, B., Li, A. H., Huang, W., Wang, J. B., Persad, A., Ramayya, A., Parvizi, J., Buch, V. P., Keller, C. 2024

    Abstract

    Pain is a complex experience that remains largely unexplored in naturalistic contexts, hindering our understanding of its neurobehavioral representation in ecologically valid settings. To address this, we employed a multimodal, data-driven approach integrating intracranial electroencephalography, pain self-reports, and facial expression quantification to characterize the neural and behavioral correlates of naturalistic acute pain in twelve epilepsy patients undergoing continuous monitoring with neural and audiovisual recordings. High self-reported pain states were associated with elevated blood pressure, increased pain medication use, and distinct facial muscle activations. Using machine learning, we successfully decoded individual participants' high versus low self-reported pain states from distributed neural activity patterns (mean AUC = 0.70), involving mesolimbic regions, striatum, and temporoparietal cortex. High self-reported pain states exhibited increased low-frequency activity in temporoparietal areas and decreased high-frequency activity in mesolimbic regions (hippocampus, cingulate, and orbitofrontal cortex) compared to low pain states. This neural pain representation remained stable for hours and was modulated by pain onset and relief. Objective facial expression changes also classified self-reported pain states, with results concordant with electrophysiological predictions. Importantly, we identified transient periods of momentary pain as a distinct naturalistic acute pain measure, which could be reliably differentiated from affect-neutral periods using intracranial and facial features, albeit with neural and facial patterns distinct from self-reported pain. These findings reveal reliable neurobehavioral markers of naturalistic acute pain across contexts and timescales, underscoring the potential for developing personalized pain interventions in real-world settings.

    View details for DOI 10.1101/2024.05.10.593652

    View details for PubMedID 38766098

    View details for PubMedCentralID PMC11100805