Functional magnetic resource imaging assessment of altered brain function in hypothyroidism during working memory processing.

CONTEXT: Hypothyroidism is related to multiple cognitive deficits including working memory dysfunction, of which the underlying neural correlates were rarely studied. In this study, the impact of hypothyroidism on neural circuits involved in working memory processing was explored by functional magnetic resource imaging (fMRI). DESIGN: Using fMRI, we conducted a longitudinal study investigating alterations of brain function during a working memory task, the four-digit backward recall (BR) and forward recall (FR), in hypothyroid patients and controls. METHODS: fMRI scan was used in 13 female patients at two time points: before and after having been treated with levothyroxine (L-T(4)) for ∼6 months, and 12 matched euthyroid controls were also scanned. Wechsler Memory Scale-Chinese Revision was used to assess the memory states of each participant. RESULTS: The hypothyroid patients showed poorer memory states than that in controls. Furthermore, significant differences of task-induced deactivation (TID, task-dependent decreases in neural activity relative to rest) between patients and controls were found in the bilateral medial prefrontal cortices, posterior cingulate cortices, and left inferior partial lobule (P<0.05). These regions were considered as parts of a task-negative network, namely the default mode network (DMN). Concretely, relative to controls, patients showed diminished TID during BR in contrast to FR. After the L-T(4) treatment, neither the poor memory states nor the alteration of TID was detectable in patients. CONCLUSION: Hypothyroidism is related to alterations of TID within DMN regions during working memory processing. These exploratory findings may imply potential neural correlates in hypothyroidism-related cognitive deficits and their recoveries.

fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism.

Cognitive impairments have been found in thyroid hormone-related diseases (e.g. hyperthyroidism and hypothyroidism) for a long time. However, whether and how subclinical hypothyroidism (SCH) causes any deficits in brain functions, and whether a hormone-replacement treatment is necessary for SCH patients, still remain controversial subjects. In the present study, functional MRI (fMRI) was used to measure brain functions by asking euthyroid subjects, hyperthyroid patients and SCH patients to perform the widely used digit n-back working memory task. After having been treated with l-thyroxine for approximately 6 months, the SCH patients were asked to do the same fMRI experiment. The hypothyroid and SCH patients scored significantly lower in the 2-back task than either the hyperthyroid patients or the euthyroid subjects (P < 0.012). The fMRI showed that a common frontoparietal network, including bilateral middle/inferior frontal gyri (M/IFG), bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor areas (PreMA), the supplementary motor area/anterior cingulate cortex (SMA/ACC) and bilateral parietal areas (PA), was activated by the n-back task in all the subjects. Further quantitative analysis showed that the load effect of blood oxygen level-dependent (BOLD) response appeared in all the five regions of interest (ROIs) in the euthyroid and hyperthyroid subjects. In the pre-treatment SCH patients, however, the load effect of BOLD response was only found in the PA and PreMA, but not in other frontal cortex ROIs [general linear model (GLM), F < 2.6, P > 0.1]. After an approximately 6 month treatment with LT4, the SCH patients exhibited the same load effects in all five ROIs as the euthyroid subjects (GLM, F > 6, P < 0.05) along with an improvement of performance in n-back task. These results suggest that working memory (but not other memory functions) is impaired in SCH patients, mainly as far as disorders of the frontoparietal network were concerned. Both the memory performance and frontal executive functions were improved after an l-thyroxine-replacement treatment.