Epilepsy is increasingly recognized as a disorder of distributed networks rather than isolated cortical foci, with the thalamus playing a central and heterogeneous role in seizure propagation and maintenance. Different thalamic nuclei are recruited at distinct times and frequencies during seizures, even within the same patient. Thalamic recruitment often does not align with predictions based solely on cortical seizure onset,reinforcing the need for direct, multisite thalamic recordings rather than anatomical assumptions.

Goals of Multinuclear Thalamic Sampling

·        Capture nucleus-specific seizure dynamics rather thantreating the thalamus as a unitary structure

·        Maximize coverage of functionally distinctthalamocortical networks (limbic, associative, posterior)

·        Inform therapeutic decisions, including DBS candidacy,target selection, and stimulation parameters

·        Achieve this coverage safely and efficiently, without excessive electrode burden

Importantly, the goal is not exhaustive thalamic coverage in every patient, but strategic sampling guided by suspected seizure networks.

Trajectory Strategies to Optimize Thalamic Sampling

Jamiolkowski et al. (2024) provides a practical anatomical framework for thalamic sampling. By using the Orthogonal transsylvian trajectories, it allows to perform sampling of ANT, MD, and pulvinar in a single electrode, and enable bilateral MD sampling.  

Regarding the Long-axis posterior-to-anteriort rajectories, it allows to sample with only one electrode the pulvinar → MD →ANT along the thalamic long axis.

Combining these strategies enables multinuclear, multidimensional thalamic coverage while limiting electrode count.
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Clinical Benefits: Deep Brain Stimulation (DBS) and Patient-Specific Network Mapping
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Clinical response to thalamic DBS is highly variable. Wu et al. provide physiological evidence that it is not always the anterior nucleus of the thalamus (ANT) involved first in seizure but that pulvinar, can be the 1^stthalamic nucleus involved.
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Multinuclear sEEG of the thalamus enables:

·        Identification of the dominant thalamic relay nucleus for seizure propagation

·        Differentiation between early driver nuclei and laterelay or synchronizing nuclei

·        Rational selection of DBS targets or multi-targetstrategies rather than empiric ANT stimulation

·        Directionality of seizure spread (cortex → thalamus vsbidirectional loops)

·        Variability between seizure types within the samepatient

Technical and Clinical Considerations

Key considerations are emphasized across both studies.The first one is that the specific trajectory planning has to based on thepatient seizure semiology and cortical hypotheses. Additionally, thalamicnuclei are functionally heterogeneous, even within the same nucleus, leading toa variability in the recordings. Regarding safety, Jamiolkowski et al. (2024) cohortdemonstrates that, with careful planning, multinuclear thalamic sEEG can beperformed without added morbidity.

Overall Significance

Together, these studies provide complementary anatomical and physiological evidence that multinuclear thalamic sEEG is essential for accurate seizure network characterization and precision neuromodulation. This integrated approach represents a critical step toward network-informed, patient-specific DBS and advanced epilepsy care.

References

1. Wu TQ, Kaboodvand N, McGinn RJ, Veit M, Davey Z, Datta A, et al. Multisite thalamic recordings to characterize seizure propagation in the human brain. Brain. 2023;146(7):2792–802.

2. Jamiolkowski RM, Datta A, Willsey MS, Parvizi J, Buch VP. Multinuclear thalamic targeting with human stereotactic electroencephalography: surgical technique and nuances.J Neurosurg. 2025; 142(4):936–44.

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