Focused Ultrasound Thalamotomy Sensory Side Effects Follow the Thalamic Structural Homunculus

Abstract

Objective: Focused ultrasound thalamotomy is an effective treatment for tremor; however, side effects may occur. The purpose of the present study was to investigate the spatial relationship between thalamotomies and specific sensory side effects and their functional connectivity with somatosensory cortex and relationship to the medial lemniscus (ML).

Methods: Sensory adverse effects were categorized into 4 groups based on the location of the disturbance: face/mouth/tongue numbness/paresthesia, hand-only paresthesia, hemibody/limb paresthesia, and dysgeusia. Then, areas of significant risk (ASRs) for each category were defined using voxel-wise mass univariate analysis and overlaid on corresponding odds ratio maps. The ASR associated with the maximum risk was used as a region of interest in a normative functional connectome to determine side effect-specific functional connectivity. Finally, each ASR was overlaid on the ML derived from normative template.

Results: Of 103 patients, 17 developed sensory side effects after thalamotomy persisting 3 months after the procedures. Lesions producing sensory side effects extended posteriorly into the principle sensory nucleus of the thalamus or below the thalamus in the ML. The topography of sensory adverse effects followed the known somatotopy of the ML and the sensory nucleus. Functional connectivity patterns between each sensory-specific thalamic seed and the primary somatosensory areas supported the role of the middle insula in processing of gustatory information and in multisensory integration.

Conclusions: Distinct regions in the sensory thalamus and its afferent connections rise to specific sensory disturbances. These findings demonstrate the relationship between the sensory thalamus, ML, and bilateral sensory cortical areas.

Figure 1. Location of Sensory Side Effects

Subtraction maps were created by subtracting each summed map of the lesions associated with each type of sensory side effect (n = 17) from the summed map of all the lesions associated with no sensory side effects (n = 86). Shown are areas covered by the thalamotomy lesions associated with all sensory side effects combined. The color bar indicates the number of subtraction maps that overlap at each voxel. (A) Sagittal and (B) axial T1-weighted MRI (Montreal Neurological Institute) of the brain demonstrates that the lesions associated with sensory side effects tended to extend more posteriorly from the ventral intermediate nucleus (green) into the ventral caudal nucleus (pink) (Hassler/Schaltenbrand and Wahren nomenclature).

Figure 2. Sensory Side Effect ASRs

Binary ASR maps overlaid on thalamic nuclei, indicating areas associated with a statistically significant risk of the sensory side effect (p < 0.05, FDR-corrected) on T1-weighted MRI (Montreal Neurological Institute) of the brain. (A) Coronal image of the sensory ASRs in relation to the ML (yellow), Vim (green), and Vc (pink). (B) Axial image of the sensory ASRs in relation to the ML, Vim, and Vc. (C) Coronal image of the sensory ASRs in relation to the VPM (blue) and VPL (red) thalamic nuclei. (D) Axial image of the sensory ASRs in relation to the VPM and VPL thalamic nuclei. Blue: dysgeusia; red: hand; turquoise: face; green: limb/hemibody, A and B: pink: Vc; light green: Vim, C and D: blue: VMP; red: VPL. ASR = area of significant risk; FDR = false discovery rate; ML = medial lemniscus; Vc = ventral caudal nucleus; Vim = ventral intermediate nucleus; VPL = ventral posterior lateral; VPM = ventral posterior medial.

Figure 3. Cortical Connectivity Maps of Thalamic Seed ROIs Associated With the Highest Risk of Sensory Side Effects

Primary somatosensory cortex (postcentral gyrus) and insular cortex ROIs were isolated from the Harvard-Oxford atlas. These ROIs were used to visualize the functional connectivity between each seed and the corresponding primary sensory areas. The strength of connectivity is expressed by t values. Note that although all thalamic seed ROIs demonstrated positive connectivity with portions of the insula, the strongest was with the dysgeusia seed ROI, which is reflected in this figure. Blue: dysgeusia; turquoise: face; red: hand; green: limb/hemibody. ROI = region of interest.

Figure 4. Somatotopy of the Medial Lemniscus

Streamlines of the ML touched by the ASRs overlaid on a T1-weighted MRI (Montreal Neurological Institute) of the brain. (A) Just inferior to the level of the thalamus and (B) at the level of the midbrain. ML fibers touched by the dysgeusia ASR are located medially, whereas fibers touched by the limb/hemibody ASR are located at the lateral margin of the ML. Blue: dysgeusia; turquoise: face; red: hand; green: limb/hemibody. ASR = area of significant risk; ML = medial lemniscus.