Weichen Huang

All Publications

• Electrophysiological Brain Connectivity and Subjective States Evoked by Electrical Stimulation of the Human Mid-Thalamus. The Journal of neuroscience : the official journal of the Society for Neuroscience Pantis, S., Togo, M., Lyu, D., Huang, W., Quabs, J., Jung, H., van Staalduinen, E., Liu Yang, L., Chan, A., Fedor, M., Fisher, R., Buch, V., Parvizi, J. 2026

  Abstract

  Recent developments in intracranial EEG (iEEG) allow direct recordings from the human thalamus, offering new insight into thalamocortical relationships in the human brain. In this study, we applied direct intracranial electrical stimulation (iES) to the mid-thalamus, within or close to the mediodorsal nucleus, to examine its impact on conscious experience and causal brain connectivity in 30 patients with focal epilepsy (10 females, 128 sites; 4±1 sites per patient). Applying 50Hz stimulations (iESHF) in the mid-thalamus region elicited changes in conscious experience in 11 of 12 patients (39 sites; 83 stimulations across 27 unique pairs), predominantly in the visceral, emotional, or somatosensory domains and often described as unpleasant without any seemingly obvious lateralization effect. Our connectivity analyses based on single pulse 0.5Hz stimulations (iESLF), at the individual brain level, revealed strong electrophysiological connectivity between the mid-thalamus and the insula, anterior- and mid-cingulate, as well as the other prefrontal cortices (PFC) and medial temporal lobe structures. Notably, inflow signals from some of the sites to the mid-thalamus were significantly stronger than those in the reverse direction, indicating clear asymmetry in connectivity. These findings demonstrate that stimulation of the human thalamus modulates conscious experience and reveal an asymmetric electrophysiological relationship between the thalamus and human cerebral cortex.Significance statement Our findings provide a functional and causal map of the mid-thalamus in the human brain. We provide direct evidence that stimulation of the human thalamus can modulate conscious experience. This study also holds clinical and translational value for identifying thalamic pathways involved in the propagation and generalization of seizures, especially seizures involving the medial temporal lobe, as well as for neuromodulation in epilepsy and other neuropsychiatric disorders.

  View details for DOI 10.1523/JNEUROSCI.2100-25.2026

  View details for PubMedID 42086322

• Functional Architecture of the Human Insula Revealed by Causal Intracranial Mapping. Research square Parvizi, J., Quabs, J., Pantis, S., Chen, G., Huang, W., Ma, E., Del Vecchio, M., Lyu, D., Wang, C., Avanzini, P., Buch, V., Ramayya, A., Caspers, S., Vogel, H. 2026

  Abstract

  The insular cortex plays a central role in pain, emotion, and cognition, yet its functional architecture and causal electrophysiological relationships among its subregions remain poorly understood. Here, we integrated intracranial electrical stimulation and task-based electroencephalography recordings with connectivity mapping within a cytoarchitectonic atlas of the human insula in 87 neurosurgical participants, identifying a quadripartite functional architecture comprising functionally distinct regions: (i) dorsal-posterior region encoding somatotopically organized nociceptive/thermoceptive and somatosensory signals; (ii) ventral-posterior region integrating somatic information across multiple body parts; (iii) mid-anterior region associated with visceral sensations and anxiety states; and (iv) anterior-polar region, largely silent to direct stimulation, yet showing robust activation during salience detection and change of action mode. Critically, this anterior region, with its strong connections with the prefrontal cortex including anterior cingulate cortex, exerts strong and direct influence over other insular regions, while receiving less strong indirect inputs from them, revealing an electrophysiological pathway for cognitive modulation of pain and bodily perception. Together, these findings define a functional architecture of the human insula that links cytoarchitecture to directed and asymmetric electrophysiological interactions with mechanistic implications for cognitive modulation of pain and interoceptive experience.

  View details for DOI 10.21203/rs.3.rs-8912902/v1

  View details for PubMedID 41836516

• Electrophysiological connections linking medial pulvinar, anterior nuclei of the thalamus and the hippocampus. Brain : a journal of neurology Togo, M., Lyu, D., Huang, W., Pantis, S., Fisher, R., Matsumoto, R., Buch, V., Parvizi, J. 2025

  Abstract

  The Papez circuit traditionally highlights the anterior nuclei of the thalamus (ANT) as the main relay of hippocampal (HPC) output to the cortex, a view that has shaped neuromodulation strategies in temporal lobe epilepsy (TLE). However, recent studies suggest that the medial subregion of the pulvinar (mPLV)- a thalamic nucleus that has undergone significant evolutionary expansion throughout the mammalian brain evolution- also forms functional connections with medial temporal lobe (MTL) structures, including the hippocampus (HPC). To date, however, there is a lack of causal evidence directly comparing the connectivity between the HPC and the two thalamic nuclei (mPLV and ANT) and between the two thalamic structures within the same brains. In this study, we investigated 41 patients with medial (mTLE, N=22) and non-medial temporal lobe epilepsy (non-mTLE, N=19) implanted with simultaneous depth electrodes in the HPC, ANT, and mPLV. Repeated single-pulse electrical stimulations were applied to compare the causal electrophysiological connectivity of these regions within the same individuals. Our intra-subject analysis revealed that anterior HPC stimulation evoked strong responses in both ANT and mPLV, with mPLV responses occurring significantly later than those in the ANT [linear mixed-effect model (LMM), Mean: 10.19ms, 95% CI [1.78, 18.59], (FDR corrected P = 0.040)]. In contrast, stimulation of the posterior HPC resulted in stronger (and a trend for earlier) responses in mPLV compared to ANT [LMM: Mean: 0.117, 95% CI [0.033, 0.201] (FDR corrected P = 0.012)]. This finding suggests anterio-posterior gradient of HPC connectivity. Furthermore, we found robust bilateral and bidirectional connectivity between ANT and mPLV. Stimulation of either elicited responses in the other, including contralateral thalamus. This represents clear evidence for both intra-thalamic and inter-thalamic connectivity within the human brain. Our findings offer new insights about the connectivity of human HPC with the thalamus and strong intra-thalamic exchange of electrophysiological activity within the human brain.

  View details for DOI 10.1093/brain/awaf342

  View details for PubMedID 41048168

• Functionally diverse human insular architecture with memory-related hippocampal interactions NATURE NEUROSCIENCE Huang, W., Parvizi, J. 2025

  View details for DOI 10.1038/s41593-025-02035-9

  View details for Web of Science ID 001530804700001

  View details for PubMedID 40670686

  View details for PubMedCentralID 11044197

• Direct interactions between the human insula and hippocampus during memory encoding. Nature neuroscience Huang, W., Lyu, D., Stieger, J. R., Gotlib, I. H., Buch, V., Wagner, A. D., Parvizi, J. 2025

  Abstract

  The hippocampus is critical for encoding episodic memories, but how it interacts with cortical regions during this process remains unclear. In this study, 16 participants with implanted electrodes in the insula (217 sites) and hippocampus (131 sites) viewed emotionally valenced words and attempted to recall them. During encoding, one subset of insular neuronal populations showed changes in aperiodic activity that predicted successful recall. These insular changes followed hippocampal theta but preceded hippocampal ripples. Another subset of insular sites responded to word valence, unrelated to memory performance. Direct electrical stimulation of memory-related insular sites evoked early responses in the ipsilateral hippocampus, whereas stimulation of valence-related sites did not. Conversely, stimulating hippocampal sites produced slow, variable signals across all insular sites, suggesting asymmetric communication between the hippocampus and the insula. These findings provide a glimpse of mesoscale hippocampal interactions with functionally selective neuronal populations within a given cortical structure.

  View details for DOI 10.1038/s41593-025-02005-1

  View details for PubMedID 40659846

  View details for PubMedCentralID 3172893

• 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