Prodromal Huntington Disease as a Model for Functional Compensation of Early Neurodegeneration
Prodromal Huntington Disease as a Model for Functional Compensation of Early Neurodegeneration
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DOI：
10.1371/journal.pone.0114569
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发表时间：
2014-12-26
期刊：
影响因子：
3.7
通讯作者：
Abler, Birgit
中科院分区：
文献类型：
--
作者：
Malejko, Kathrin;Weydt, Patrick;Abler, Birgit
功能性代偿被证明是抵消早期阿尔茨海默病中神经元损失的机制，也可能发生在其他成人发病的神经退行性疾病中，特别是亨廷顿病（HD），其遗传决定和结构完整性的逐渐变化。在HD中，神经变性通常起始于背侧纹状体，连续影响腹侧纹状体区域。研究HD突变携带者的背侧纹状体明显萎缩，但腹侧纹状体萎缩极小或无萎缩，我们期望找到腹侧纹状体功能补偿的证据。我们调查了14名导致HD的突变的前期或早期症状携带者和18名匹配的健康对照者。参与者在探索腹侧纹状体功能的奖励任务中接受了结构T1磁共振成像（MRI）和功能MRI。运动功能和注意力与反应时间（RT）任务进行了评估。结构图像证实了特定的背侧纹状体，但只有边缘腹侧纹状体体积HD相对于对照组，平行延长RT的运动反应任务。虽然在功能磁共振成像扫描的奖励任务的行为表现是不受损害的，奖励相关的功能磁共振成像信号在HD组的差异增强，在双侧腹侧纹状体和双侧眶额皮质/前额叶，作为另一个敏感的区域奖励处理。我们提供了证据的概念，功能性补偿在表现前HD，这可能表明在神经退行性疾病的防御机制。鉴于到目前为止不可避免的过程中，HD与其遗传决定的终点，这种疾病可能提供另一种模式来研究不同方面的概念的功能补偿。
Functional compensation demonstrated as mechanism to offset neuronal loss in early Alzheimer disease may also occur in other adult-onset neurodegenerative diseases, particularly Huntington disease (HD) with its genetic determination and gradual changes in structural integrity. In HD, neurodegeneration typically initiates in the dorsal striatum, successively affecting ventral striatal areas. Investigating carriers of the HD mutation with evident dorsal, but only minimal or no ventral striatal atrophy, we expected to find evidence for compensation of ventral striatal functioning. We investigated 14 pre-or early symptomatic carriers of the mutation leading to HD and 18 matched healthy controls. Participants underwent structural T1 magnetic resonance imaging (MRI) and functional MRI during a reward task that probes ventral striatal functioning. Motor functioning and attention were assessed with reaction time (RT) tasks. Structural images confirmed a specific decrease of dorsal striatal but only marginal ventral striatal volume in HD relative to control subjects, paralleling prolonged RT in the motor response tasks. While behavioral performance in the reward task during fMRI scanning was unimpaired, reward-related fMRI signaling in the HD group was differentially enhanced in the bilateral ventral striatum and in bilateral orbitofrontal cortex/anterior insula, as another region sensitive to reward processing. We provide evidence for the concept of functional compensation in premanifest HD which may suggest a defense mechanism in neurodegeneration. Given the so far inevitable course of HD with its genetically determined endpoint, this disease may provide another model to study the different aspects of the concept of functional compensation.