Thalamic Metabolite Changes After Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: An Exploratory Magnetic Resonance Spectroscopy Study

Nathanael Göransson¹Sofie Tapper²Peter Lundberg³Peter Zsigmond^4*Anders Tisell⁵

• ¹Department of Biomedical Engineering, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
• ²Department of Biomedical Engineering, Linköping University, Linköping, Sweden
• ³Department of Medical Radiation Physics, Center for Medical Image Science and Visualization, Department of Radiology and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden
• ⁴Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
• ⁵Department of Medical Radiation Physics, Center for Medical Image Science and Visualization and department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden

Introduction: The mechanisms underlying the clinical effect of Deep Brain Stimulation (DBS) for Parkinson’s disease (PD) remain debated. Proton magnetic resonance spectroscopy (¹H-MRS) provides a biochemical non-invasive in vivo insight. This article aims to increase the understanding of advanced PD pathophysiology and DBS using MRS before and after surgery. Methods: Eleven PD patients and seven healthy controls were included. Preoperatively and approximately seven months postoperatively, single-voxel MRS using a PRESS sequence was performed on a 1.5 T (tesla) system. Voxels were placed bilaterally in the thalamus (14 x 13 x 13 mm3) and the lentiform nucleus (15 x 13 x 12 mm3). Metabolite concentrations of total N-acetylaspartate + N-acetyl-aspartyl-glutamate (tNA), total creatine + phosphocreatine (tCr), total choline + phosphocholine + glycerophosphocholine (tCho), and total glutamate and glutamine, which together constitute Glx were quantified. To assess treatment outcomes following surgery, medications were converted to levodopa equivalent doses (LED) using a standardized conversion formula, both pre- and post-DBS. Results: A total of 11 patients, with a mean PD duration of 9.4 years, were implanted with bilateral implantation (22 leads). All patients self-reported relief of symptoms and significantly reduced their medication (p < 0.001), with a calculated preoperative LED of 925 ± 272 and a postoperative LED of 611 ± 210 (mean ± SD), representing a 32% reduction after surgery. The patients, prior to surgery, compared to a healthy control group, showed no differences in the resulting metabolite concentrations (tCr, tNA, tCho, Glx) in voxels placed in the thalamus and lentiform nucleus. However, thalamic tNA concentrations differed significantly following DBS targeting the subthalamic nucleus, both in comparison to healthy controls (p = 0.02) and relative to preoperative concentrations within the patient group (p = 0.03). No furher resulting concentrations differed. Conclusion We present novel metabolite observations obtained through MRS in this exploratory study.. Thalamic tNA concentrations in PD patients were comparable to those of healthy controls prior to surgery, but were significantly reduced following DBS implantation targeting the subthalamic nucleus (STN). These findings suggests the presence of a metabolite thalamic effect associated with DBS treatment.