Functional connectivity targeting for deep brain stimulation in essential tremor

Abstract

Background and purpose: Deep brain stimulation of the thalamus has become a valuable treatment for medication-refractory essential tremor, but current targeting provides only a limited ability to account for individual anatomic variability. We examined whether functional connectivity measurements among the motor cortex, superior cerebellum, and thalamus would allow discrimination of precise targets useful for image guidance of neurostimulator placement.

Materials and methods: Resting BOLD images (8 minutes) were obtained in 58 healthy adolescent and adult volunteers. Regions of interest were identified from an anatomic atlas and a finger movement task in each subject in the primary motor cortex and motor activation region of the bilateral superior cerebellum. Correlation was measured in the time series of each thalamic voxel with the 4 seeds. An analogous procedure was performed on a single subject imaged for 10 hours to constrain the time needed for single-subject optimization of thalamic targets.

Results: Mean connectivity images from 58 subjects showed precisely localized targets within the expected location of the ventral intermediate nucleus of the thalamus, within a single voxel of currently used deep brain stimulation anatomic targets. These targets could be mapped with single-voxel accuracy in a single subject with 3 hours of imaging time, though targets were reproduced in different locations for the individual than for the group averages.

Conclusions: Interindividual variability likely exists in optimal placement for thalamic deep brain stimulation targeting of the cerebellar thalamus for essential tremor. Individualized thalamic targets can be precisely estimated for image guidance with sufficient imaging time.

Fig 1.

Seed regions of interest used for calculating thalamic motor functional connectivity in 58 subjects. Analogous regions of interest were derived from the finger movement task for the individual subject.

Fig 2.

Thalamic motor functional connectivity averaged from 58 subjects. The red cross identifies the anatomic coordinates of the voxel used for deep brain stimulation. Images are in radiologic format. Section locations are MNI: z = −2, 0, 2, 4 (top left to bottom right).

Fig 3.

Single-subject thalamic motor functional connectivity. Voxels within the top 50% of peak z scores are shown in the thalamus. The red cross indicates the voxel that would be targeted by using anatomic positioning for thalamic deep brain stimulation. The left column shows mean connectivity scores from 50 five-minute scans obtained during 5 sessions with the subject in a resting state, and the right column, from 50 five-minute scans obtained during 5 different sessions with the subject watching cartoons. Images are in radiologic format.

Fig 4.

Variability in the target by using only 3 sessions. Ten different sets of 3 scanning sessions were randomly selected from the 10 scanning sessions. The optimal target (peak connectivity) was selected for the average of each group of 3 scans and was compared with the target by using all 10 scans. Distance from the target is shown for the left and right thalami for each of the 10 sets of 3 sessions.