Targeting the centromedian thalamic nucleus for deep brain stimulation

ObjectivesDeep 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).Methods19 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.ResultsThe 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.ConclusionsIn 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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Targeting the centromedian thalamic nucleus for deep brain stimulation

10.1101/19008136 ◽

2019 ◽

Author(s):

Aaron E.L Warren ◽

Linda J. Dalic ◽

Wesley Thevathasan ◽

Annie Roten ◽

Kristian J. Bulluss ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Background Noise ◽

Thalamic Nucleus ◽

3 Tesla ◽

Brain Diseases ◽

Limbic Cortex ◽

Therapeutic Effects ◽

Spike Firing ◽

Deep Brain

ABSTRACTObjectivesDeep 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 (i) developing a structural MRI approach for CM visualisation, (ii) identifying the CM’s neurophysiological characteristics, and (iii) mapping connectivity from CM-DBS sites using functional MRI (fMRI).MethodsNineteen patients with LGS (mean age=28 years) underwent pre-surgical 3 tesla MRI using magnetisation-prepared 2 rapid acquisition gradient echoes (MP2RAGE) and fMRI sequences; 16 proceeded to bilateral CM-DBS implantation and intraoperative microelectrode recordings (MERs) from the thalamus. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge-detection. Mixed-effects analysis compared two MER features (spike firing rate, background noise) between ventrolateral, CM, and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions-of-interest.ResultsThe 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.ConclusionsIn the largest clinical trial cohort of LGS patients undergoing CM-DBS reported to date, we show that accurate targeting of the CM is achievable using 3 tesla MP2RAGE MRI. MERs may provide additional localising features in some cases, however their utility is limited by inter-patient 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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Analysis of Gene Expression Changes in the Rat Hippocampus After Deep Brain Stimulation of the Anterior Thalamic Nucleus

Journal of Visualized Experiments ◽

10.3791/52457 ◽

2015 ◽

Cited By ~ 3

Author(s):

Tharakeswari Selvakumar ◽

Kambiz N. Alavian ◽

Travis Tierney

Keyword(s):

Gene Expression ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Thalamic Nucleus ◽

Rat Hippocampus ◽

Anterior Thalamic Nucleus ◽

Deep Brain ◽

Stimulation Of

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Long-Term Migration of a Deep Brain Stimulation (DBS) Lead in the Third Ventricle Caused by Cerebral Atrophy in a Patient with Anterior Thalamic Nucleus DBS

Journal of Epilepsy Research ◽

10.14581/jer.15016 ◽

2015 ◽

Vol 5 (2) ◽

pp. 96-100 ◽

Cited By ~ 2

Author(s):

Jin-gyu Choi ◽

Si-hoon Lee ◽

Young-Min Shon ◽

Byung-chul Son

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Thalamic Nucleus ◽

Third Ventricle ◽

Cerebral Atrophy ◽

Anterior Thalamic Nucleus ◽

The Third ◽

Deep Brain

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Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.590251 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lila H. Levinson ◽

David J. Caldwell ◽

Jeneva A. Cronin ◽

Brady Houston ◽

Steve I. Perlmutter ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Evoked Potentials ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

High Frequency ◽

Therapeutic Effects ◽

Stn Dbs ◽

Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

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