Thalamic neuromodulation in epilepsy: A primer for emerging circuit-based therapies

ABSTRACT

Introduction

Epilepsy is a common, often debilitating disease of hyperexcitable neural networks. While medically intractable cases may benefit from surgery, there may be no single, well-localized focus for resection or ablation. In such cases, approaching the disease from a network-based perspective may be beneficial.

Areas covered

Herein, the authors provide a narrative review of normal thalamic anatomy and physiology and propose general strategies for preventing and/or aborting seizures by modulating this structure. Additionally, they make specific recommendations for targeting the thalamus within different contexts, motivated by a more detailed discussion of its distinct nuclei and their respective connectivity. By describing important principles governing thalamic function and its involvement in seizure networks, the authors aim to provide a primer for those now entering this fast-growing field of thalamic neuromodulation for epilepsy.

Expert opinion

The thalamus is critically involved with the function of many cortical and subcortical areas, suggesting it may serve as a compelling node for preventing or aborting seizures, and so it has increasingly been targeted for the surgical treatment of epilepsy. As various thalamic neuromodulation strategies for seizure control are developed, there is a need to ground such interventions in a mechanistic, circuit-based framework.

KEYWORDS:

• thalamus
• neuromodulation
• seizures
• epilepsy
• anterior nucleus
• centromedian nucleus
• pulvinar nucleus
• microcircuits
• neurosurgery

Article highlights

• Epilepsy affects more than 45 million people worldwide and is conservatively estimated to cost over 10 billion dollars each year in the United States alone.

• The thalamus acts as a control point for brain-wide information processing, neural synchronization, and cortical state via thalamocortical microcircuits.

• There is extensive evidence that the thalamus is involved, both as a passive node and active participant, in seizure onset and propagation in animal models of epilepsy.

• Clinical trials have thus far highlighted stimulation of the anterior and centromedian nuclei of the thalamus as compelling therapies for temporal lobe and generalized epilepsies, respectively.

• The thalamus is likely to become a critical and routinely utilized target for network-based seizure treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.