Lisa Yamada

All Publications

• Compression-Enabled Joint Entropy Estimation for Seizure Detection on Human Intracortical Electroencephalography IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Yamada, L., Oskotsky, T., Nuyujukian, P. 2025; 72 (12): 3440-3452

  Abstract

  Of the 1% of the world population with epilepsy, one-third have drug-resistant epilepsy and often turn to surgical intervention. Current epilepsy treatment relies on manual review by epileptologists and could benefit from reliable quantitative electroencephalography (qEEG) approaches to speed up evaluation, minimize inter-reviewer variance, and deliver higher quality and more equitable care.We present the inverse compression ratio (ICR), an estimate of an upper bound of joint entropy using common compression algorithms, as a potential qEEG method for seizure detection. This technique was tested on our repository of 10 kHz intracortical neurophysiological data across 30 participants (15 adults and 15 children, 240+ total seizures).Single-electrode ICR achieved a F1 score of 0.80 and an area under precision-recall curve of 0.69, outperforming conventional qEEG methods. Multielectrode ICR performed within the top 2% of individual electrodes, potentially eliminating the need for electrode selection.ICR may be useful for automated seizure detection; its integration into clinical systems may translate to broad clinical impact.We believe this clinical study analyzed the largest volume of continuous, multi-day intracortical neuroelectrophysiology for quantitative methods-with 2,900+ recording hours (420,000+ electrode-hours, amounting to 30+ TB of data). It is also the first demonstration of compression-based multidimensional estimation in a biological or clinical application. By computing an ensemble effect without linear assumptions or parametric modeling, ICR offers a model-free solution to the classically combinatorially intractable problem of high-dimensional joint entropy; its application likely extends beyond epilepsy to other domains of biomedical signal processing.

  View details for DOI 10.1109/TBME.2025.3563789

  View details for Web of Science ID 001617899100018

  View details for PubMedID 41231686

• Conserved brain-wide emergence of emotional response from sensory experience in humans and mice. Science (New York, N.Y.) Kauvar, I., Richman, E. B., Liu, T. X., Li, C., Vesuna, S., Chibukhchyan, A., Yamada, L., Fogarty, A., Solomon, E., Choi, E. Y., Mortazavi, L., Chau Loo Kung, G., Mukunda, P., Raja, C., Gil-Hernández, D., Patron, K., Zhang, X., Brawer, J., Wrobel, S., Lusk, Z., Lyu, D., Mitra, A., Hack, L., Luo, L., Grosenick, L., van Roessel, P., Williams, L. M., Heifets, B. D., Henderson, J. M., McNab, J. A., Rodríguez, C. I., Buch, V., Nuyujukian, P., Deisseroth, K. 2025; 388 (6750): eadt3971

  Abstract

  Emotional responses to sensory experience are central to the human condition in health and disease. We hypothesized that principles governing the emergence of emotion from sensation might be discoverable through their conservation across the mammalian lineage. We therefore designed a cross-species neural activity screen, applicable to humans and mice, combining precise affective behavioral measurements, clinical medication administration, and brain-wide intracranial electrophysiology. This screen revealed conserved biphasic dynamics in which emotionally salient sensory signals are swiftly broadcast throughout the brain and followed by a characteristic persistent activity pattern. Medication-based interventions that selectively blocked persistent dynamics while preserving fast broadcast selectively inhibited emotional responses in humans and mice. Mammalian emotion appears to emerge as a specifically distributed neural context, driven by persistent dynamics and shaped by a global intrinsic timescale.

  View details for DOI 10.1126/science.adt3971

  View details for PubMedID 40440375

• Ketamine Increases Theta Oscillations and Cortical Connectivity of the Human Hippocampus Solomon, E., Liu, T., Kauvar, I., Vesuna, S., Chibukhchyan, A., Yamada, L., Fogarty, A., Mukunda, P., Patron, K., Nuyujukian, P., Rodriguez, C., Buch, V., Deisseroth, K. ELSEVIER SCIENCE INC. 2025

  View details for Web of Science ID 001491697600080

• Classifying High-Frequency Oscillations by Morphologic Contrast to Background, With Surgical Outcome Correlates. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society Qing, K., Von Stein, E., Yamada, L., Fogarty, A., Nuyujukian, P. 2024

  Abstract

  Ictal high-frequency oscillations (HFOs) are a reliable indicator of a seizure onset zone for intracranial EEG recordings. Interictal HFOs often are also observed and may be a useful biomarker to supplement ictal data, but distinguishing pathologic from physiologic HFOs continues to be a challenging task. We present a method of classifying HFOs based on morphologic contrast to the background.We retrospectively screened 31 consecutive patients who underwent intracranial recordings for epilepsy at Stanford Medical Center during a 2-year period, and 13 patients met the criteria for inclusion. Interictal EEG data were analyzed using an automated event detector followed by morphologic feature extraction and k-means clustering. Instead of only using event features, the algorithm also incorporated features of the background adjacent to the events. High-frequency oscillations with higher morphologic contrast to the background were labeled as pathologic, and "hotspots" with the most active pathologic HFOs were identified and compared with clinically determined seizure onset zones.Clustering with contrast features produced groups with better separation and more consistent boundaries. Eleven of the 13 patients proceeded to surgery, and patients whose hotspots matched seizure onset zones had better outcomes, with 4 out of 5 "match" patients having no disabling seizures at 1+ year postoperatively (Engel I or International League Against Epilepsy Class 1-2), while all "mismatch" patients continued to have disabling seizures (Fisher exact test P-value = 0.015).High-frequency oscillations with higher contrast to background more likely represent paroxysmal bursts of pathologic activity. Patients with HFO hotspots outside of identified seizure onset zones may not respond as well to surgery.

  View details for DOI 10.1097/WNP.0000000000001121

  View details for PubMedID 39354667

• A scalable platform for acquisition of high-fidelity human intracranial EEG with minimal clinical burden. PloS one Yamada, L., Oskotsky, T., Nuyujukian, P. 2024; 19 (6): e0305009

  Abstract

  Human neuroscience research has been significantly advanced by neuroelectrophysiological studies from people with refractory epilepsy-the only routine clinical intervention that acquires multi-day, multi-electrode human intracranial electroencephalography (iEEG). While a sampling rate below 2 kHz is sufficient for manual iEEG review by epileptologists, computational methods and research studies may benefit from higher resolution, which requires significant technical development. At adult and pediatric Stanford hospitals, research ports of commercial clinical acquisition systems were configured to collect 10 kHz iEEG of up to 256 electrodes simultaneously with the clinical data. The research digital stream was designed to be acquired post-digitization, resulting in no loss in clinical signal quality. This novel framework implements a near-invisible research platform to facilitate the secure, routine collection of high-resolution iEEG that minimizes research hardware footprint and clinical workflow interference. The addition of a pocket-sized router in the patient room enabled an encrypted tunnel to securely transmit research-quality iEEG across hospital networks to a research computer within the hospital server room, where data was coded, de-identified, and uploaded to cloud storage. Every eligible patient undergoing iEEG clinical evaluation at both hospitals since September 2017 has been recruited; participant recruitment is ongoing. Over 350+ terabytes (representing 1000+ days) of neuroelectrophysiology were recorded across 200+ participants of diverse demographics. To our knowledge, this is the first report of such a research integration within a hospital setting. It is a promising approach to promoting equitable participant enrollment and building comprehensive data repositories with consistent, high-fidelity specifications towards new discoveries in human neuroscience.

  View details for DOI 10.1371/journal.pone.0305009

  View details for PubMedID 38870212