Targeting the centromedian thalamic nucleus for deep brain stimulation.

Objectives: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM's neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI).
Methods: 19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP 2 RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP 2 RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest.
Results: The CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex.
Conclusions: In the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP 2 RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.
Competing Interests: Competing interests: WT has received honoraria from Medtronic and Boston Scientific.
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