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Many individuals with TSC manifest neuropsychiatric symptoms, such as learning impairments, cognitive deficits and anxiety. Current pharmacological treatment for TSC is the use of mTOR inhibitors. However, they are not effective in treating neuropsychiatric symptoms. We previously used curcumin, a diet\u2010derived mTOR inhibitor, which possesses both anti\u2010inflammatory and antiproliferative properties, to improve learning and memory deficits in <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice. Diffusion tensor imaging (DTI) provides microstructural information in brain tissue and has been used to study the neuropathological changes in TSC. In this study, we confirmed that the impaired recognition memory and increased anxiety\u2010like behavior in <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice can be reversed by curcumin treatment. Second, we found altered fractional anisotropy and mean diffusivity in the anterior cingulate cortex and the hippocampus of the <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice, which may indicate altered circuitry. Finally, the mTOR complex 1 hyperactivity was found in the cortex and hippocampus, coinciding with abnormal cortical myelination and increased glial fibrillary acidic protein expression in the hippocampal CA1 of <jats:italic>Tsc2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice, both of which can be rescued with curcumin treatment. Overall, DTI is sensitive to the subtle alterations that cannot be detected by conventional imaging, suggesting that noninvasive DTI may be suitable for longitudinally monitoring the <jats:italic>in vivo<\/jats:italic> neuropathology associated with the neuropsychiatric symptoms in TSC, thereby facilitating future clinical trials of pharmacological treatments.<\/jats:p>","DOI":"10.1111\/bpa.12870","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T12:17:38Z","timestamp":1591964258000},"page":"4-19","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Detection of endophenotypes associated with neuropsychiatric deficiencies in a mouse model of tuberous sclerosis complex using diffusion tensor imaging"],"prefix":"10.1111","volume":"31","author":[{"given":"Christine Chin\u2010jung","family":"Hsieh","sequence":"first","affiliation":[{"name":"Taiwan International Graduate Program in 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