功能MRI观察左旋甲状腺素对亚临床甲状腺功能减退空间工作记忆损伤的影响

摘要

目的：采用血氧依赖水平功能磁共振成像（BOLD-fMRI）探讨左旋甲状腺素（LT4）替代治疗对亚临床甲状腺功能减退（SCH）患者空间工作记忆的影响。资料与方法16例SCH患者进行LT4治疗6个月前后与对照组16例甲状腺功能正常志愿者分别进行n-back任务负载下fMRI扫描，以AFNI软件对fMRI数据进行定位定量分析。结果在n-back任务负载下，所有受试者共同激活的脑区包括双侧背外侧前额叶（DLPFC）、双侧前运动区（PreMA）、双侧顶叶（PA）、前扣带皮层/辅助运动区及右侧尾状核/丘脑，且表现为右侧大脑半球优势。定量分析发现，对照组以上脑区均表现出与记忆负载相关的负载效应（P<0.001），而SCH组治疗前仅在左侧DLPFC、左侧PA、双侧PreMA及右侧尾状核/丘脑发现了这种负载效应。经LT4替代治疗6个月后，包括右侧DLPFC、右侧PA及前扣带回/辅助运动区在内的脑感兴趣区均出现与记忆负载相关的BOLD信号变化（P<0.001）。在n-back任务负载下，SCH组大部分工作记忆相关脑区的激活强度均比对照组小。结论 SCH患者存在空间工作记忆损伤，可能与右侧背外侧前额-右顶叶后部网络功能减退有关；LT4替代治疗对SCH患者记忆功能的恢复尤为重要。%Purpose To explore the effect of Levothyroxine on spatial working memory in patients with subclinical hypothyroidism (SCH) using blood oxygenation level dependent-functional MRI (BOLD-fMRI). Materials and Methods Sixteen patients with SCH before and after 6 months levothyroxine (LT4) treatment and 16 matched euthyroid volunteers underwent n-back task fMRI scanning. AFNI software was used for localization and quantification. Results All the subjects demonstrated activated areas including bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal area (PA) and right caudate nucleus/thalamus, with right hemisphere dominance. Quantitative analysis of regions of interests showed that all these regions had load effect related to memory load in the control group (P<0.001), whereas only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in SCH group. After 6-month treatment with LT4, BOLD signal change was observed in SCH patients within the right DLPFC, right PA and anterior cingulate/supplementary motor cortex (P<0.001). The activation intensity of working memory related brain regions was lower in SCH group compared with that of the control group. Conclusion Spatial working memory impairments in SCH patients are likely related to decreased right DLPFC and right posterior parietal function. LT4 replacement therapy is important to improve and reverse the memory impairment.