Abstract
Obstructive sleep apnea syndrome (OSAS) leads to neurocognitive and autonomic deficits that are partially mediated by thalamic and putamen pathology. We examined the underlying neurochemistry of those structures using compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (JRESI), and quantified values with prior knowledge fitting. Bilaterally increased thalamic mI/Cr, putamen Glx/Cr, and Glu/Cr, and bilaterally decreased thalamic and putamen tCho/Cr and GABA/Cr occurred in OSAS vs healthy subjects (p < 0.05). Increased right thalamic Glx/Cr, Glu/Cr, Gln/Cr, Asc/Cr, and decreased GPC/Cr and decreased left thalamic tNAA/Cr, NAA/Cr were detected. The right putamen showed increased mI/Cr and decreased tCho/Cr, and the left, decreased PE/Cr ratio. ROC curve analyses demonstrated 60–100% sensitivity and specificity for the metabolite ratios in differentiating OSAS vs. controls. Positive correlations were found between: left thalamus mI/Cr and baseline oxygen saturation (SaO2); right putamen tCho/Cr and apnea hypopnea index; right putamen GABA/Cr and baseline SaO2; left putamen PE/Cr and baseline SaO2; and left putamen NAA/Cr and SaO2 nadir (all p < 0.05). Negative correlations were found between left putamen PE/Cr and SaO2 nadir. These findings suggest underlying inflammation or glial activation, with greater alterations accompanying lower oxygen saturation. These metabolite levels may provide biomarkers for future neurochemical interventions by pharmacologic or other means.
Highlights
The putamen serves essential roles in autonomic regulation, a major concern in Obstructive sleep apnea syndrome (OSAS) given the poor sympathetic control in the condition
Patients with OSAS showed altered neurochemical levels in the thalamus and putamen suggestive of substantially elevated glial responses to hypoxia and other stresses, and the presence of mild neurodegenerative processes
These results show cerebral metabolite changes associated with OSAS in the thalamus and putamen, areas with functions related to symptoms of this disorder, and which have been affected structurally in other neuroimaging studies
Summary
The putamen serves essential roles in autonomic regulation, a major concern in OSAS given the poor sympathetic control in the condition. The thalamus interacts with the extended prefrontal neural systems, integrating higher order brain actions with autonomic and inhibitory control functions; dysfunction in those systems could underlie the cognitive deficits found in OSAS8. Both structural and functional neuroimaging studies show brain injury in the putamen[9,15,16], and thalamus in OSAS patients[17,18], but information on metabolite levels in damaged areas is sparse[19,20]. Due to the combination of the speed advantage of EPSI readout and increased spectral dispersion offered by 2D JRESI, 4D EP-JRESI enables recording of better-resolved 2D spectra from multiple voxels in a single recording. A pilot validation for its application on human brain was performed on a small sample of OSAS subjects[21]
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