Introduction: Hypothyroidism leads to impaired white matter (WM) integrity, associated with cognitive/neuropsychiatric dysfunction. However, the specific segmental abnormalities of the fibers remain unexplored. Therefore, this study aimed to investigate whether the damage of the WM is limited to a specific segment or the entire bundle via diffusion metrics using automated fiber quantification. Methods: A cross-sectional study was conducted on 31 hypothyroid patients and 28 healthy controls. Thyroid-related hormone levels, cognitive/neuropsychiatric function, and diffusion tensor image data were collected and analyzed. Correlation and random forest analyses were also performed. Results: The mean fractional anisotropy (FA) values were reduced at the fiber tract level. The mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were increased in several fiber tracts, i.e., cingulum cingulate (CC), anterior forceps of corpus callosum (CCF_A). Significant correlations were found between cognitive function and diffusion indicators such as the FA value of the left corticospinal tract and arcuate fasciculus (AF), the MD value of left CC, the RD value of left AF, the AD value of left CC, and CCF_A. The widespread microstructure disruption was spread on multiple specific segments of different tracts at the point-wise level. The random forest revealed that the accuracy of recognizing hypothyroid patients was 82.5%, with the anterior component of CCF_A having the most significant contribution. Conclusion: WM microstructural integrity impairments were found in multi-segments of the multiple fiber bundles in hypothyroidism, which might be a potential mechanism of the underlying neurocognitive decline and cerebral impairment. The CCF_A might serve as a neuro biomarker for early warning of cerebral impairment in hypothyroidism.

Introduction: Type 2 diabetes mellitus (T2DM) patients with depression have a higher risk of complications and mortality than T2DM without depression. However, the exact neuropathophysiological mechanism remains unclear. Consequently, the current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in T2DM patients with and without depression. Methods: The demographic data, clinical variables, neuropsychological tests, and functional and anatomical magnetic resonance imaging of depressed T2DM (n=47) of non-depressed T2DM (n=59) and healthy controls (n=41) were collected and evaluated. The correlation analysis, stepwise multiple linear regression, and receiver operating characteristic curve were performed for further analysis. Results: Abnormal neural activities in the bilateral posterior cingulate cortex (PCC) and hippocampus were observed in depressed and non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore, the cortical amplitude of low-frequency fluctuation (ALFF) in PCC, subcortical DC in the putamen of depressed T2DM, and hippocampus of non-depressed T2DM was correlated with cognitive scores. In contrast, the cortical fractional ALFF in PCC of non-depressed T2DM was correlated with depression scores. Conclusions: The abnormalities of spontaneous cortical activity in PCC and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2DM. Notably, the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2DM, which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2DM.

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Purpose Abnormal spontaneous neuronal activities associated with cognitive deficits and emotional dysfunction were found in hypothyroidism. However, routine method employs a relatively broader range of spontaneous fluctuations and would mingle physiological fluctuations contained in specific frequency. In current study we explored how frequency-specific changes of fractional amplitude of low-frequency fluctuations (fALFF) in hypothyroidism. Methods Fifty-three hypothyroid patients and thirty-nine healthy controls (HCs) underwent clinical variables, neuropsychological assessment, and MRI scans. The fALFF in the routine band, slow-4, and slow-5 bands were analyzed. Additionally, Pearson correlation analysis was performed between fALFF and clinical variables and neuropsychological scores in hypothyroid patients. Results Compared to HCs, within the routine band, patients showed significantly decreased fALFF in left lingual gyrus, middle temporal gyrus (MTG), calcarine cortex, precentral gyrus, and right inferior occipital gyrus; within the slow-5 band, the patients exhibited decreased fALFF in left lingual gyrus, MTG, superior temporal gyrus, postcentral gyrus, and paracentral lobule, and increased fALFF in right middle frontal gyrus and supplementary motor area; Additionally, fALFF in the left lingual gyrus within the routine and slow-5 bands were negatively correlated with thyroid stimulating hormone level. Conclusions We found that fALFF in left lingual gyrus and MTG decreased both in routine and slow-5 bands in hypothyroid patients. These might be potential neuroimaging biomarkers of cerebral impairment in hypothyroid patients. Trial registration ClinicalTials. No:ChiCTR2000028966. Registered 9 January, 2020, https://www.chictr.org.cn

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