Graves’ disease-associated dopaminergic system dysfunction and its effects on striatocortical functional connectivity and cognitive function

Background: Cognitive deficits in various psychiatric disorders could be linked to attenuated striatal dopaminergic tone and disrupted striatocortical functional connectivity (FC). Hyperthyroidism's associated decrease in striatal dopaminergic tone and its effects on striatocortical FC may also be the underlying cause of cognitive deficits in Graves' disease (GD). This study investigated striatal dopamine transporter (DAT) availability, its effect on striatal seed-based (six seeds) whole-brain FC and IQ as an index of global cognitive function in GD. Methods: We recruited 34 GD patients and 24 healthy controls (HCs). DAT availability by single-photon emission tomography, FC by resting-state functional MRI, and Full-scale IQ (FIQ) were measured. Results: Left striatal DAT availability was significantly lower and strongly associated with FC between left ventral rostral putamen (VRP)-left insula, left VRP-left supramarginal gyrus, and left dorsal caudate (DC)-left superior parietal gyrus in the GD patients as compared with the HCs. Right striatal DAT availability was also significantly lower and strongly associated with FC between the right VRP-left insula. FIQ was significantly lower and weakly associated with FC between right dorsal caudal putamen (DCP)-left temporal pole, left DCP-left middle frontal gyrus, and left DCP-left superior parietal gyrus. Conclusions: Cognitive deficits in GD could be the result of dysfunction in the striatal dopaminergic system and altered striatocortical FC. Notably, the FC between the parietal gyrus (an area known to be associated with IQ) and striatum exhibited deviated associations with DAT availability and FIQ scores, suggesting the role of dopamine-associated disrupted parieto-striatal connectivity in compromising IQ.