Visuo-spatial processing is linked to cortical glutamate dynamics in Parkinson's disease - a 7-T functional magnetic resonance spectroscopy study

Background and purpose: Cognitive decline is a frequent and debilitating non-motor symptom for patients with Parkinson's disease (PD). Metabolic alterations in the occipital cortex during visual processing may serve as a biomarker for cognitive decline in patients with PD. Methods: Sixteen patients with PD (Unified Parkinson's Disease Rating Scale Part 3, OFF, 38.69 +/- 17.25) and 10 age-and sex-matched healthy controls (HC) underwent 7-T functional magnetic resonance spectroscopy (MRS) utilizing a visual checkerboard stimulation. Glutamate metabolite levels during rest versus stimulation were compared. Furthermore, correlates of the functional MRS response with performance in visuo-cognitive tests were investigated. Results: No differences in static MRS between patients with PD and HC were detected, but a dynamic glutamate response was observed in functional MRS in HC upon visual stimulation, which was blunted in patients with PD (F-1,F-22 = 7.13, p = 0.014; eta(2)(p) = 0.245). A diminished glutamate response correlated with poorer performance in the Benton Judgment of Line Orientation test in PD (r = -0.57, p = 0.020). Conclusions: Our results indicate that functional MRS captures even subtle differences in neural processing linked to the behavioral performance, which would have been missed by conventional, static MRS. Functional MRS thus represents a promising tool for studying molecular alterations at high sensitivity. Its prognostic potential should be evaluated in longitudinal studies, prospectively contributing to earlier diagnosis and individual treatment decisions.