Spectral and Functional Connectivity Features of the Anterior and Centromedian Thalamic Nuclei in Patients with Epilepsy
Subeikshanan Venkatesan, Giridhar Kalamangalam, John Whalen and Yue Wang
American Epilepsy Society
December 8, 2025
Abstract
Rationale:
Thalamic DBS is increasingly used for epilepsy, but stimulation paradigms remain largely empirical, with numerous adjustable parameters – amplitude, pulse width, frequency, and electrode configuration1. Since treatment response is typically assessed using video-scalp EEG, understanding thalamo-cortical interactions is crucial for optimizing therapy and identifying biomarkers of efficacy.
Methods:
Two patients, one (60/M) with ANT DBS for bitemporal epilepsy (L >R) and one (35/M) with CM DBS for LGS, were evaluated in the epilepsy monitoring unit. Simultaneous scalp EEG and DBS recordings were obtained during eyes open (EO), eyes closed (EC), hyperventilation (HV), and photic stimulation (Ph). Data analyzed for spectral power and band-wise functional connectivity (coherence and wPLI) between thalami and between each thalamus and scalp electrodes.
Results:
ANT patient (94.5 min): Normalized power was significantly higher in the left thalamus across all bands (δ: 0.65 vs 0.46, θ: 0.26 vs 0.30, α: 0.16 vs 0.27, β: 0.12 vs 0.20; p < 0.0001). Alpha power was higher during EO than EC (p < 0.0001). Inter-thalamic coherence peaked in the alpha band (0.63), followed by β > θ > δ (p < 0.0001), with coherence highest during HV (HV > EO > EC ≈ Ph). wPLI peaked in the delta band (0.60), followed by θ > α > β, also highest during HV (p < 0.0001). Thalamus-to-scalp coupling was strongest in the delta band: C4 > C3 > Cz (coherence) and C4 > Cz > Fz (wPLI) for both hemispheres.
CM patient (57 min): Right thalamus showed higher power in δ, θ, α bands; left had higher β (δ: 0.23 vs 0.25, θ: 0.32 vs 0.33, α: 0.34 vs 0.35, β: 0.35 vs 0.34; p < 0.001). Alpha power was higher during EO than EC (p < 0.0001). Inter-thalamic coherence was highest in the delta band (0.33) across EO, EC, HV; theta (0.34) during Ph (p < 0.001). wPLI followed δ > θ > α > β, with delta (0.30) highest during EO, EC, Ph and theta (0.36) during HV (p < 0.001). Thalamus-to-scalp coupling was strongest posteriorly and centrally: P8 > F4 > C3 (coherence) and P3 > P8 > Pz (wPLI) for left; C3 > P8 > O1 (coherence) and P4 > F4 > C4 (wPLI) for right.
Conclusions:
Spectral and connectivity analyses of ANT showed dominant delta power bilaterally (L > R), with strongest inter-thalamic coherence and wPLI in alpha and delta bands respectively. Thalamus-to-scalp coupling peaked in the delta band over central, and frontal regions, especially during HV.
CM exhibited symmetric power distribution across bands, with enhanced inter-thalamic connectivity in delta and theta bands. Thalamus-to-scalp coupling was strongest in the delta range over posterior, central, and frontal areas, notably during HV and Ph.
Alpha power was significantly higher during EO versus EC in both nuclei, in contrast with cortical alpha suppression with EO. These results highlight distinct spectral and connectivity profiles for ANT and CM, reflecting their differential roles in subcortical–cortical interaction in epilepsy.
1.Fasano A, Eliashiv D, Herman ST, Lundstrom BN, Polnerow D, Henderson JM, Fisher RS. Experience and consensus on stimulation of the anterior nucleus of thalamus for epilepsy. Epilepsia. 2021 Dec;62(12):2883-98.
Multitarget neurostimulation of the deep brain: clinical opportunities, challenges, and emerging technologies
Michael J Del Sesto*, Serban Negoita, Maria Bruzzone Giraldez, Zachary LaJoie, Khaleda Akhter Sathi, Joshua K Wong, Alik S Widge, Michael S Okun and Adam Khalifa
Published 29 October 2025 • © 2025 The Author(s). Published by IOP Publishing Ltd
Journal of Neural Engineering, Volume 22, Number 5
Abstract
Recent computational, pre-clinical, and clinical studies have demonstrated the potential for using neuromodulation through simultaneous targeting of multiple deep brain regions. This approach has already been used for therapeutic and systems neuroscience applications. However, the broad clinical adoption of invasive distributed deep brain interfaces remains in its early stages. This review explores the barriers to implementation by addressing three key questions: do the benefits of implanting multiple electrodes justify the associated risks for specific applications? What is the risk-benefit ratio, and what technological advancements will be necessary to encourage clinical adoption? We also examine next-generation technologies that could enable multi-target brain interfaces, including system-on-chip micro-stimulators as well as nanoparticles. We highlight the role of novel machine learning algorithms in the optimization of stimulation parameters and for the guidance of device placement. Emerging hardware accelerators equipped with on-chip AI have demonstrated functionality that can be used to decode and to classify distributed neuronal data. This advance in hardware accelerators has also contributed to the potential for enhanced closed-loop stimulation control of devices. Despite these advances, significant technological and translational barriers persist, limiting the widespread clinical application of multi-target brain interfaces. This review provides a critical analysis of recent prototypes and novel hardware for use in multi-target systems. We will discuss both clinical and research applications. We will focus on the utilization of multi-site technologies to meet the needs of neurological diseases. We conclude that there exists a critical need for further innovation and integration of multi-site technologies into clinical practice.
Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury
Joshua K. Wong, Günther Deuschl, Robin Wolke, Hagai Bergman, Muthuraman Muthurama, Sergiu Groppa, Sameer A. Sheth, Helen M. Bronte-Stewart, Kevin B. Wilkins, Matthew N. Petrucci, Emilia Lambert, Yasmine Kehnemouyi, Philip A. Starr, Simon Little, Juan Anso, Ro’ee Gilron, Lawrence Poree, Giridhar P. Kalamangalam, Gregory A. Worrell, Kai J. Miller, Nicholas D. Schiff, Christopher R. Butson, Jaimie M. Henderson, Jack W. Judy, Adolfo Ramirez-Zamora, Kelly D. Foote, Peter A. Silburn, Luming Li, Genko Oyama, Hikaru Kamo, Satoko Sekimoto, Nobutaka Hattori, James J. Giordano, Diane DiEuliis, John R. Shook, Darin D. Doughtery, Alik S. Widge, Helen S. Mayberg, Jungho Cha, Kisueng Choi, Stephen Heisig, Mosadolu Obatusin, Enrico Opri, Scott B. Kaufman, Prasad Shirvalkar, Christopher J. Rozell, Sankaraleengam Alagapan, Robert S. Raike, Hemant Bokil, David Green, Michael S. Okun
Front. Hum. Neurosci., 03 March 2022
Sec. Brain Imaging and Stimulation
Volume 16 – 2022 | https://doi.org/10.3389/fnhum.2022.813387
Introduction
The DBS Think Tank IX presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. It was estimated that globally more than 230,000 deep brain stimulation (DBS) devices have been implanted for neurological and neuropsychiatric disorders. The DBS Think Tank was founded in 2012 and it provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The emphasis of the DBS Think Tank is on cutting edge research and collaboration with the potential to advance the DBS field. The DBS Think Tank IX was held on August 25–27 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury. The DBS Think Tank discussed Maslow’s theories and a path to transcendence both for patients as well as for DBS practitioners. The attendees also participated in a DBS Think Tank survey, which documented the expansion of DBS into several indications such as movement disorders, psychiatric disorders, and pain disorders. This proceeding summarizes the advances discussed at the DBS Think Tank IX.