The role of the motor thalamus in deep brain stimulation for essential tremor.

The advent of next-generation technology has significantly advanced the implementation and delivery of Deep Brain Stimulation (DBS) for Essential Tremor (ET), yet controversies persist regarding optimal targets and networks responsible for tremor genesis and suppression. This review consolidates key insights from anatomy, neurology, electrophysiology, and radiology to summarize the current state-of-the-art in DBS for ET. We explore the role of the thalamus in motor function and describe how differences in parcellations and nomenclature have shaped our understanding of the neuroanatomical substrates associated with optimal outcomes. Subsequently, we discuss how seminal studies have propagated the ventral intermediate nucleus (Vim)-centric view of DBS effects and shaped the ongoing debate over thalamic DBS versus stimulation in the posterior subthalamic area (PSA) in ET. We then describe probabilistic- and network-mapping studies instrumental in identifying the local and network substrates subserving tremor control, which suggest that the PSA is the optimal DBS target for tremor suppression in ET. Taken together, DBS offers promising outcomes for ET, with the PSA emerging as a better target for suppression of tremor symptoms. While advanced imaging techniques have substantially improved the identification of anatomical targets within this region, uncertainties persist regarding the distinct anatomical substrates involved in optimal tremor control. Inconsistent subdivisions and nomenclature of motor areas and other subdivisions in the thalamus further obfuscate the interpretation of stimulation results. While loss of benefit and habituation to DBS remain challenging in some patients, refined DBS techniques and closed-loop paradigms may eventually overcome these limitations.

Human Motor Thalamus Reconstructed in 3D from Continuous Sagittal Sections with Identified Subcortical Afferent Territories.

Classification and delineation of the motor-related nuclei in the human thalamus have been the focus of numerous discussions for a long time. Difficulties in finding consensus have for the most part been caused by paucity of direct experimental data on connections of individual nuclear entities. Kultas-Ilinsky et al. (2011) showed that distribution of glutamic acid decarboxylase isoform 65 (GAD65), the enzyme that synthesizes inhibitory neurotransmitter γ-aminobutyric acid, is a reliable marker that allows to delineate connectionally distinct nuclei in the human motor thalamus, namely the territories innervated by nigral, pallidal, and cerebellar afferents. We compared those immunocytochemical staining patterns with underlying cytoarchitecture and used the latter to outline the three afferent territories in a continuous series of sagittal Nissl-stained sections of the human thalamus. The 3D volume reconstructed from the outlines was placed in the Talairach stereotactic coordinate system relative to the intercommissural line and sectioned in three stereotactic planes to produce color-coded nuclear maps. This 3D coordinate-based atlas was coregistered to the Montreal Neurological Institute (MNI-152) space. The current report proposes a simplified nomenclature of the motor-related thalamic nuclei, presents images of selected histological sections and stereotactic maps illustrating topographic relationships of these nuclei as well as their relationship with adjacent somatosensory afferent region. The data are useful in different applications such as functional MRI and diffusion tractography. The 3D dataset is publicly available under an open license and can also be applicable in clinical interventions in the thalamus.