Objective: To investigate alterations of glutamate metabolism in the occipital cortex during visual processing in patients with Parkinson’s disease (PD).

Background: Cognitive decline is a frequent and debilitating non-motor symptom for patients with PD. Imaging studies showed a cortical hypometabolism associated with cognitive deterioration, especially in occipital areas, differentiating, e.g., PD-dementia from Alzheimer’s dementia. These changes have also been shown to predict cognitive decline and incipient PD-dementia. Visual stimulation has been shown to trigger heterogeneous glutamatergic responses in young adults. Glutamatergic alterations in the occipital cortex during visual processing may indicate cognitive decline in patients with PD.

Method: Sixteen patients with PD (UPDRS-III-OFF: 38.69±17.25) and ten age- and sex-matched healthy controls (HC) underwent functional magnetic resonance spectroscopy (MRS) at 7 Tesla. A T1-weighted mp2rage sequence was used for anatomical imaging to position the MRS voxel in the visual cortex. 120 spectra were acquired utilizing a stimulated echo acquisition mode (STEAM) sequence during the functional MRS paradigm. Spectral quantification was performed using LCModel (6.3-0I). During the REST condition of the MRS paradigm, a black fixation cross on a grey background was presented. During the stimulation (STIM) condition, a 3.3Hz alternating checkerboard was presented. Each condition lasted 5 minutes (block design) and participants were instructed to focus on the cross or the flickering checkerboard. Glutamate metabolite levels during REST versus STIM were compared and the functional MRS response was correlated to performance in visuo-cognitive tests.

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(1,22)=7.13, p=.014; h_p²=0.245]. A diminished glutamate response correlated with poorer performance in the Benton Judgment of Line Orientation test in patients with PD (r=-0.57, p=.020).

Conclusion: Our results indicate that functional MRS captures even subtle differences in neural processing linked to behavioral performance, which static MRS would have missed. Functional MRS, thus, represents a promising tool for studying molecular alterations with high sensitivity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/visuo-spatial-processing-is-linked-to-cortical-glutamate-dynamics-in-parkinsons-disease-a-7-tesla-functional-mrs-study/