Spatial Working Memory Impairment in Subclinical Hypothyroidism: An fMRI Study

<b><i>Objective:</i></b> Using a block-designed BOLD-fMRI to explore the neural basis of spatial working memory impairment in patients with subclinical hypothyroidism (SCH) performing an n-back task. <b><i>Methods:</i></b> Sixteen patients with SCH before and after being treated with levothyroxine (LT₄) for 6 months and 16 matched euthyroid subjects were scanned by fMRI under the n-back task. <b><i>Results:</i></b> The fMRI scan found that a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal lobe (PA) and right caudate nucleus/thalamus was activated, with right hemisphere dominance. In euthyroid subjects, all these regions of interest (ROIs) showed load effect; however, only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in Pre-SCH patients. Furthermore, activation intensities of most ROIs (especially DLPFC and right PA) for Pre-SCH patients were lower than those in the euthyroid subjects (F <3.046, p > 0.062). Importantly, after a 6-month treatment with LT₄, the load effect in SCH patients appeared the same as in the euthyroid subjects in all the ROIs (F >13.176, p < 0.0001). <b><i>Conclusion:</i></b> Our previous study shows that verbal working memory of SCH patients is impaired with abnormal activity in bilateral frontal areas. In this study, the results indicated that SCH patients may also have spatial working memory impairments, and the altered activities of right DLPFC and right posterior parietal lobe may be one of the underlying neural mechanisms. Most importantly, this study shows that LT₄ replacement therapy can improve the memory impairment and reverse the altered neural activity network.