Neurometabolic Signatures of Alexithymia and Visuospatial Abilities in Parkinson’s Disease: An Exploratory 1H-MRS Study of the Substantia Nigra and Globus Pallidus

Background: Parkinson’s Disease (PD) is a multisystem neurodegenerative disorder associated with cognitive and emotional disturbances, including visuospatial deficits and alexithymia, which may substantially affect quality of life (QoL). The metabolic underpinnings of non-motor and emotional features within deep basal ganglia nuclei remain poorly understood. This exploratory proof-of-concept study aimed to examine 1H-MRS-derived metabolite ratios in the substantia nigra (SN) and globus pallidus (GP) and to explore their preliminary associations with visuospatial-attentional abilities and alexithymia. Methods: Fifteen individuals with PD and 15 healthy controls (HCs) underwent Proton Magnetic Resonance Spectroscopy (1H-MRS) targeting the SN and GP bilaterally. Metabolite ratios were quantified with LCModel and analyzed as left, right, and hemisphere-averaged measures. PD participants completed a multidisciplinary assessment including motor severity, cognition, visuospatial abilities, mood and alexithymia. Multiple testing was controlled using false discovery rate (FDR). Given the between-group imbalance in age and education, exploratory covariate-adjusted sensitivity analyses were also performed. Results: PD participants were older, less educated, and showed lower global cognition than HCs, including significantly reduced MoCA scores (20.9 ± 6.6 vs. 28.7 ± 1.8; FDR-corrected p < 0.001). In uncorrected analyses, between-group metabolite comparisons showed lower myo-inositol (Ins) in the SN (p = 0.04) and higher glutamatergic signal in the right GP in PD relative to HCs (p = 0.03); however, these differences were not robust after adjustment for age, education and multiple testing. Within the PD group, an uncorrected right–left asymmetry was observed for pallidal Ins. Exploratory correlations suggested uncorrected associations between SN metabolites and alexithymia dimensions related to emotional awareness and verbalization, whereas GP metabolites were more frequently associated with selected visuospatial, attentional, language-related, and broader cognitive measures. None of these associations survived FDR correction. Conclusions: This exploratory proof-of-concept study provides preliminary feasibility data and effect-size estimates for future 1H-MRS investigations of basal ganglia metabolites in PD. Given the small sample size, lack of cognitive matching, age and education imbalance, and absence of correction-surviving associations, the findings should not be interpreted as evidence of PD-specific neurometabolic markers. Larger, prospectively matched, and adequately powered studies are needed.