Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome
Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndrome
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DOI：
10.1002/hbm.20406
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Reiss, Allan L.
中科院分区：
文献类型：
--
作者：
Hoeft, Fumiko;Hernandez, Arvel;Reiss, Allan L.
反应抑制是执行功能的一个重要方面。脆性 X 综合征 (FraX) 具有已知的遗传病因（脆性 X 智力迟钝-1 (FMR1) 突变）和反应抑制缺陷，可能是阐明基因-大脑-行为关系之间相互作用的理想条件。功能磁共振成像 (fMRI) 研究显示，当 FraX 患者执行执行功能任务时，存在异常神经活动的证据，尽管这种改变的活动或可能的补偿过程的具体性质尚未阐明。为了解决这个问题，我们使用 fMRI 检查了患有 FraX 的青少年男性和对照组在执行 go/nogo 任务期间的大脑激活模式。在 FraX 个体与年龄、性别和智商 (IQ) 匹配的发育迟缓对照之间进行了关键比较；除了年龄和性别匹配的典型发育个体的对照组之外。与两个对照组相比，FraX 组的右腹外侧前额叶皮层 (VLPFC) 和右尾状核的激活减少，而对侧（左）VLPFC 的激活增加。患有 FraX 的个体（而非对照组）表现出任务表现与左侧 VLPFC 激活之间存在显着的正相关性。这种潜在的代偿性激活是通过 FMR1 蛋白 (FMRP) 水平与右侧纹状体功能障碍之间的相互作用来预测的。这些结果表明，右侧额纹状体功能障碍可能是 FraX 的一个可识别的神经表型特征，并且在成功的反应抑制过程中左侧 VLPFC 的激活可能反映了代偿过程。我们进一步表明，这些假定的补偿过程可以通过遗传风险和神经功能之间的复杂相互作用来预测。
Response inhibition is an important facet of executive function. Fragile X syndrome (FraX), with a known genetic etiology (fragile X mental retardation-1 (FMR1) mutation) and deficits in response inhibition, may be an ideal condition for elucidating interactions among gene-brain-behavior relationships. Functional magnetic resonance imaging (fMRI) studies have shown evidence of aberrant neural activity when individuals with FraX perform executive function tasks, though the specific nature of this altered activity or possible compensatory processes has yet to be elucidated. To address this question, we examined brain activation patterns using fMRI during a go/nogo task in adolescent males with FraX and in controls. The critical comparison was made between FraX individuals and age, gender, and intelligent quotient (IQ)-matched developmentally delayed controls; in addition to a control group of age and gender-matched typically developing individuals. The FraX group showed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) and right caudate head, and increased contralateral (left) VLPFC activation compared with both control groups. Individuals with FraX, but not controls, showed a significant positive correlation between task performance and activation in the left VLPFC. This potential compensatory activation was predicted by the interaction between FMR1 protein (FMRP) levels and right striatal dysfunction. These results suggest that right fronto-striatal dysfunction is likely an identifiable neuro-phenotypic feature of FraX and that activation of the left VLPFC during successful response inhibition may reflect compensatory processes. We further show that these putative compensatory processes can be predicted by a complex interaction between genetic risk and neural function.