IDH1突变对额叶胶质瘤患者数字归纳推理能力的影响及其脑网络机制的研究

Patients with glioma often experience neurocognitive impairment. Isocitrate dehydrogenase 1 (IDH1) gene mutation has a clear relationship with the molecular typing and clinical prognosis of gliomas, which can improve the current treatment of gliomas. Patients with IDH1 wild type showed reduced neurocognitive function compared with patients with IDH1 mutant tumors. However, the neural correlates and information-processing mechanisms are still unknown. Our previous studies on functional magnetic resonance imaging (fMRI) showed that mutation of the IDH1 gene affected cerebral hemispheric functional connectivity in frontal lobe glioma patients. On basis of the above findings, the present study aimed to employ number series completion task combined with fMRI analyses and neurocognitive function tests to explore the effect and functional brain network mechanism of IDH1 mutation on numerical inductive reasoning in glioma patients. The project plans to collect task-fMRI, resting-state fMRI and neurocognitive function testing data from patients with IDH1 wild type and patients with IDH1 mutant glioma before and after surgery and healthy controls. And the intra- and cross-group statistical calculations will be compared. The expected results will reflect the genetic influence on brain network and neurocognitive characteristics in patients with glioma pre- and post-surgery. The comparison between the IDH1 wild type and the IDH1 mutant cognitive status gives evidence for the individual treatment, which considerably increases the probability of complete recovery and improves the quality of daily life.

脑胶质瘤患者常出现神经认知功能障碍的症状。异柠檬酸脱氢酶1（IDH1）基因突变与脑胶质瘤的分子分型、临床预后有明确的关系，对改善脑胶质瘤治疗现状有重要意义。研究提示，IDH1野生型脑胶质瘤患者比IDH1突变型患者表现出更严重的神经认知功能障碍，但具体的神经机制尚不明确。本课题前期在额叶胶质瘤患者功能磁共振成像（fMRI）研究中发现，IDH1突变状态影响患者大脑脑区功能连接。因此，本课题拟针对IDH1野生型脑胶质瘤患者、IDH1突变型脑胶质瘤患者和健康对照三组被试，采用任务态fMRI、静息态fMRI和神经认知量表评估相结合的方法，以数字归纳推理为神经认知任务，研究术前及短期术后IDH1突变对脑胶质瘤患者神经认知功能影响的脑网络机制。本课题基于脑功能网络分析不同基因型脑胶质瘤患者术前及术后的认知特性，有助于预判患者大脑认知功能重塑，为保护患者的认知功能提供个性化指导，最终提高患者的日常生活质量。

已有研究提示，IDH1野生型脑胶质瘤患者比IDH1突变型患者表现出更严重的神经认知功能障碍，但具体的神经机制尚不明确。本课题采用任务态fMRI、静息态fMRI和神经认知量表评估相结合的方法，以数字归纳推理为神经认知任务，研究IDH1突变对脑胶质瘤患者神经认知功能影响的脑网络机制。本研究发现，与健康对照相比，额叶胶质瘤患者完成数字归纳推理任务时额叶和皮层下脑区激活减弱，顶叶代偿性激活增强；与IDH1突变型额叶胶质瘤患者相比，IDH1野生型额叶胶质瘤患者在额中回和岛叶的激活减弱。推理有效任务的反应时在健康对照、IDH1突变型和IDH1野生型额叶胶质瘤患者中依次递增，而且被试推理有效任务反应时的增加与岛叶激活增强存在显著负相关。在健侧的默认网络和额顶网络内部的功能连接方面，与健康对照相比，IDH1突变型和IDH1野生型额叶胶质瘤患者均表现出功能连接的增强；在健侧的额顶网络和默认网络之间的功能连接方面，与健康对照和IDH1野生型额叶胶质瘤患者相比，IDH1突变型额叶胶质瘤患者表现出功能连接增强，与健康对照和IDH1突变型额叶胶质瘤患者相比，IDH1野生型额叶胶质瘤患者表现出功能连接减弱。综上，无论是在数字归纳推理任务完成需要调用的脑功能区，还是在与数字归纳推理密切相关的默认和额顶网络，IDH1野生型较IDH1突变型胶质瘤患者均表现更严重的受损。本研究通过基于脑功能网络分析不同基因型脑胶质瘤患者的认知特性，将有助于全面掌握患者的认知损伤情况，有助于为患者日常生活质量的提高提供个性化的指导，具有重要的临床应用价值。