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Title: Targeting the centromedian thalamic nucleus for deep brain stimulation.
Austin Authors: Warren, Aaron E L;Dalic, Linda J ;Thevathasan, Wesley;Roten, Annie ;Bulluss, Kristian J ;Archer, John S 
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Surgery, The University of Melbourne, Parkville, Victoria, Australia
Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, Victoria, Australia
Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Murdoch Children's Research Institute, Parkville, Victoria, Australia
Department of Neurology, Austin Health, Heidelberg, Victoria, Australia
Bionics Institute, East Melbourne, Victoria, Australia
Department of Neurosurgery, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 24-Jan-2020 2020-01-24
Publication information: Journal of Neurology, Neurosurgery, and Psychiatry 2020; 91(4): 339-349
Abstract: 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). 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. 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. 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.
DOI: 10.1136/jnnp-2019-322030
ORCID: 0000-0001-6534-2800
PubMed URL: 31980515
Type: Journal Article
Appears in Collections:Journal articles

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