Objective: To relate subject-specific pathway activation models of motor thalamic deep brain stimulation (DBS) to clinical outcomes in patients with Essential Tremor (ET).

Background: Computational modeling of DBS has been shown to be a promising approach for understanding pathway activation around the ventral intermediate nucleus (VIM) of thalamus [1]. Clinical testing of simulated DBS configurations can further provide information about which pathways are associated with tremor suppression and with stimulation-induced side effects. In this study, we leveraged an ongoing prospective clinical trial in subjects with medication-refractory ET to determine how parcellated tracts around implanted directional DBS leads contribute to clinical outcomes in VIM-DBS.

Method: Subject-specific pathway activation models were constructed for 12 directional DBS leads from 7 patients as part of a prospective clinical trial (NCT03984643). Pathways were generated from pre-operative ultra-high field (7T) MR and post-operative CT imaging with pathways that included the cortico-thalamo-cortical tracts, subdivided cerebellothalamic tract (CTT), zona incerta (ZI), medial lemniscus (ML), internal capsule (IC), thalamic fasciculus, and lenticular fasciculus. Clinical rating scales (TETRAS for tremor, BARS for ataxia) were collected during a monopolar review (10 electrode configurations per lead) to assess tremor and side effect (dysarthria, gait ataxia) severity at two current amplitudes between 0-5 mA. For any pathway with >20% activation, mixed effect models were used to determine which pathways significantly contributed to clinical outcomes.

Results: The lateral CTT had the highest activation at DBS settings causing maximal tremor suppression. Activation of the ML was significantly associated with increased dysarthria scores (p<0.01). Activation of the ML (p<0.01) and somatosensory cortex projections into the ventral posterolateral nucleus of thalamus (p<0.05) were significantly associated with increased gait ataxia scores.

Conclusion: Knowledge of the fiber pathways associated with tremor suppression and with stimulation-induced side effects in ET can help guide physicians towards better DBS optimization on a patient-specific basis through use of computational modeling-based algorithms.

References: [1] Brinda A, Slopsema JP, Butler RD, et al. Lateral cerebellothalamic tract activation underlies DBS therapy for Essential Tremor. Brain Stimul. 2023 Feb 4;16(2):445-55.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subject-specific-investigation-of-pathways-underlying-therapeutic-outcomes-of-deep-brain-stimulation-for-essential-tremor/