Department de Psiquiatria i Psicobiologia Clinica, Universitat de Barcelona, Barcelona, Catalonia, Spain.
PLoS One. 2012;7(12):e51833. doi: 10.1371/journal.pone.0051833. Epub 2012 Dec 19.
Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS.Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.
脑损伤的行为后果代表了损伤与大脑其余部分适应损伤的能力之间的相互作用。我们为这样一种观点提供了实验支持，即遗传因素在这种适应中起着关键作用。我们使用重复经颅磁刺激(rTMS)诱导了一种可控的脑损伤，并表明 APOE 状态决定了其对功能磁共振成像(fMRI)评估的分布式脑网络的影响。20 名表现出轻度记忆功能障碍的非痴呆老年人在进行面孔-名字编码任务时接受了两次 fMRI 研究（在 rTMS 之前和之后）。基线任务表现与前额叶、顶叶、内侧颞叶和视觉联想区域的脑网络激活有关。APOE ε4 携带者在两个独立的成分中表现出这种模式，而 ε4-非携带者则表现出一个部分重叠的网络。在 rTMS 之后，所有受试者的记忆表现都略有改善，无论 APOE 状态如何。然而，在 rTMS 之后，APOE ε4 携带者的脑网络激活发生了显著变化，表现出与非携带者组在刺激前观察到的相似的空间配置。同样，在默认模式网络(DMN)的活动在 ε4-非携带者的一个单一成分中被发现，而在携带者中，它表现为三个不同的时空成分离散化，在 rTMS 后变为一个集成的单一成分。我们的发现表明，遗传背景在大脑对局部损伤的反应中起着根本作用，决定了不同脑网络的表达，以维持相似的认知表现。
