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 (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE 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 MP2RAGE 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.
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Contributors All authors contributed to the concept and design of the study, as well as data acquisition and interpretation of results. JA and AELW obtained funding. AELW carried out the statistical analysis and wrote the first draft of the manuscript. KJB performed the surgical implantations. JA was the main supervisor of the study. All authors critically reviewed the manuscript and approved the final version before submission.
Funding This study was supported by a project grant from the National Health and Medical Research Council of Australia (grant number 1108881) and a seed grant (grant number 2634) from the Rare Disease Foundation (www.rarediseasefoundation.org) and the British Columbia Children's Hospital Foundation (www.bcchf.ca). AELW was supported by a Postdoctoral Fellowship from the LGS Foundation (www.lgsfoundation.org).
Competing interests WT has received honoraria from Medtronic and Boston Scientific.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data are available upon reasonable request.