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

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.

Specific and nonspecific thalamocortical connectivity in the auditory and somatosensory thalamocortical slices.

Two classes of thalamic nuclei project to either middle layers or upper layers, including layer 1, of the neocortex, and are referred to as 'specific' and 'nonspecific' nuclei, respectively. The electrophysiological properties of the nonspecific nuclei have not been investigated, largely because of the paucity of in vitro slice preparations containing intact nonspecific pathways. In this study, we used flavoprotein autofluorescence imaging to show intact thalamocortical connectivity of nonspecific nuclei in slice preparations of the somatosensory and auditory systems. These preparations will enable the elucidation of electrophysiological properties of nonspecific pathways.

The corticothalamocortical circuit drives higher-order cortex in the mouse.

An unresolved question in neuroscience relates to the extent to which corticothalamocortical circuits emanating from layer 5B are involved in information transfer through the cortical hierarchy. Using a new form of optical imaging in a brain slice preparation, we found that the corticothalamocortical pathway drove robust activity in higher-order somatosensory cortex. When the direct corticocortical pathway was interrupted, secondary somatosensory cortex showed robust activity in response to stimulation of the barrel field in primary somatosensory cortex (S1BF), which was eliminated after subsequently cutting the somatosensory thalamus, suggesting a highly efficacious corticothalamocortical circuit. Furthermore, after chemically inhibiting the thalamus, activation in secondary somatosensory cortex was eliminated, with a subsequent return after washout. Finally, stimulation of layer 5B in S1BF, and not layer 6, drove corticothalamocortical activation. These findings suggest that the corticothalamocortical circuit is a physiologically viable candidate for information transfer to higher-order cortical areas.