Reduced GABA levels in the medial prefrontal cortex are associated with cognitive impairment in patients with NMOSD

Cognitive impairment is a symptom present in part of patients with neuromyelitis optica spectrum disorder (NMOSD) and its pathophysiology is unknown. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters have been implicated in several neurological disorders. This study aimed to investigate the changes in inhibitory gamma-aminobutyric acid (GABA) and excitatory glutamate and glutamine (Glx) neurotransmitter levels and their correlations with cognitive functions in patients with NMOSD.A total of 29 patients with NMOSD and 28 sex-, age-, and education-matched healthy controls (HCs) were included in the study. All participants underwent clinical and cognitive assessments and proton magnetic resonance spectroscopy scanning. Meshcher-Garwood point-resolved spectroscopy was used to measure GABA and Glx levels in the medial prefrontal cortex (mPFC) and left thalamus. Total creatine (tCr) was applied as an internal reference. The GABA and Glx levels in the patient group were compared with those in HCs and correlated with cognitive scores and clinical variables.Patients with NMOSD showed lower GABA+/tCr levels in the mPFC compared with HCs (P = 0.028). The GABA+/tCr levels in the mPFC were significantly associated with verbal memory performance (r = 0.462, P = 0.027) and overall cognition (r = 0.440, P = 0.035) in the NMOSD group. The GABA+/tCr levels in the left thalamus or Glx/tCr levels in both regions were not significantly different between groups, nor were they related to any cognitive domain in patients with NMOSD (all P values > 0.05).The GABA+ levels in the mPFC decreased and correlated with cognitive dysfunction in patients with NMOSD, suggesting that the changes in regional GABA+ levels might be a potential metabolic feature of cognitive decline in patients with NMOSD.