Neuropsychology Laboratory, Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico,
Neuropsychology Laboratory, Department of Physiology, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
Neurodegener Dis. 2022;22(1):24-28. doi: 10.1159/000526778. Epub 2022 Sep 6.
Recent resting-state functional magnetic resonance imaging studies have reported abnormal functional connectivity (FC) in the prefrontal cortex (PFC)-striatum circuit in patients with premanifest Huntington's disease (HD). However, there is a lack of evidence showing persistence of abnormal frontostriatal FC and its relation to cognitive flexibility performance in patients with clinically manifest HD.
The aim of this study was to evaluate the resting-state FC integrity of the frontostriatal circuit and its relation to cognitive flexibility in HD patients and healthy controls (HCs).
Eighteen patients with early clinical HD manifestation and 18 HCs matched for age, sex, and education participated in this study. Both groups performed the Cambridge Neuropsychological Test Automated Battery (CANTAB) Intra-Extra Dimensional (IED) set-shift task, which measures cognitive flexibility. Resting-state functional magnetic resonance images were also acquired to examine the FC in specific frontostriatal circuits. Eight regions of interest were preselected based on regions previously associated with extradimensional (ED) shifting in patients with premanifest HD.
Significant negative correlations between the number of attentional set-shifting errors and the ventral striatum-ventrolateral PFC FC were found in the HD group. This group also showed negative FC correlations between the total errors and the FC between right ventral striatum-right ventrolateral PFC, left ventral striatum-left ventrolateral PFC, and right ventral striatum-left ventrolateral PFC. Negative correlations between the ED errors and left ventral striatum-left ventrolateral PFC and right ventral striatum-right ventrolateral PFC FC were also found. Finally, a positive correlation between the number of stages completed and left ventral striatum-left ventrolateral PFC FC was found.
Manifest HD patients show significant cognitive flexibility deficits in attentional set-shifting that are associated with FC alterations in the frontostriatal circuit. These results show that FC abnormalities found in the prodromal stage of the disease can also be associated with cognitive flexibility deficits at a later clinical stage, making them good candidates to be explored in longitudinal studies.
最近的静息态功能磁共振成像研究报告称，在有临床前期亨廷顿病（HD）的患者中，前额叶皮层（PFC）-纹状体回路存在异常功能连接（FC）。然而，缺乏证据表明在有临床症状的 HD 患者中，异常的额纹状体 FC 持续存在及其与认知灵活性表现的关系。
本研究旨在评估额纹状体回路的静息态 FC 完整性及其与 HD 患者和健康对照（HC）认知灵活性的关系。
18 例早期临床 HD 表现的患者和 18 例年龄、性别和教育程度相匹配的 HC 参加了这项研究。两组均完成剑桥神经心理学测试自动化电池（CANTAB）内外维度（IED）转换任务，该任务用于测量认知灵活性。还采集了静息态功能磁共振图像以检查特定的额纹状体回路的 FC。根据先前与有临床前期 HD 的患者的外维度（ED）转换相关的区域，预先选择了 8 个感兴趣区。
在 HD 组中，注意力集转换错误的数量与腹侧纹状体-腹外侧 PFC FC 之间存在显著的负相关。该组还显示出总错误与右侧腹侧纹状体-右侧腹外侧 PFC、左侧腹侧纹状体-左侧腹外侧 PFC 和右侧腹侧纹状体-左侧腹外侧 PFC 之间的 FC 之间的负相关。ED 错误与左侧腹侧纹状体-左侧腹外侧 PFC 和右侧腹侧纹状体-右侧腹外侧 PFC FC 之间也存在负相关。最后，还发现 ED 错误与左侧腹侧纹状体-左侧腹外侧 PFC FC 之间存在正相关。
有临床症状的 HD 患者在注意力集转换中表现出明显的认知灵活性缺陷，这与额纹状体回路的 FC 改变有关。这些结果表明，在疾病的前驱期发现的 FC 异常也可能与以后的临床阶段的认知灵活性缺陷相关，这使它们成为在纵向研究中进行探索的良好候选者。
