Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder.
Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder.
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DOI：
10.1093/brain/awac430
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发表时间：
2023-06-01
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特发性快速眼动睡眠行为障碍（iRBD）现已被确定为帕金森病和相关突触核蛋白病前驱期的重要标志物。然而，尽管多巴胺转运蛋白单光子发射计算机断层扫描（SPECT）已被用来证明iRBD中黑质纹状体缺陷的存在，但目前缺乏可量化的相关性。在一些帕金森病患者中，对奖励刺激的敏感性降低，可能导致这些个体的神经精神表型。此外，多巴胺能药物可以改善奖赏不敏感性，这一事实表明多巴胺能变性的作用。iRBD患者提供了一个独特的机会来研究奖励敏感性和未用药状态下早期多巴胺能缺陷之间的关系。在这里，我们调查是否是一个非侵入性的，客观的措施奖励敏感性可能是一个标志物多巴胺能状态在前驱帕金森氏病通过比较SPECT/CT测量多巴胺能损失在基底神经节。iRBD患者的纹状体多巴胺能缺陷与进展为帕金森病相关因此，确定这种退行性过程的临床可测量相关性可能为开发新的风险分层工具提供基础。使用最近开发的激励眼动追踪任务，我们量化了41名iRBD患者的奖励敏感性，并将其与40名帕金森病患者和41名健康对照的数据进行了比较。iRBD患者还接受了多巴胺转运蛋白SPECT/CT神经成像。总的来说，奖励敏感性，指数瞳孔反应的货币激励，减少iRBD的情况下，与对照组相比，并没有显着不同的帕金森病患者。然而，在多巴胺转运蛋白SPECT/CT成像正常的iRBD患者中，奖赏敏感性与健康对照组无显著差异。在所有iRBD病例中，观察到奖励敏感性与壳核中多巴胺能SPECT/CT信号之间存在正相关。这些发现表明iRBD患者的多巴胺能缺陷和奖赏敏感性之间存在直接关系，并表明瞳孔反应的测量在这些个体的风险分层和疾病进展模型中可能具有价值。快速眼动睡眠行为障碍是帕金森病前驱期的重要标志。Barber等人证明，具有确定的多巴胺能缺陷的RBD患者对奖赏的瞳孔反应迟钝。因此，瞳孔奖赏敏感性可能是前驱期多巴胺能下降的标志。
Idiopathic rapid eye movement sleep behaviour disorder (iRBD) has now been established as an important marker of the prodromal stage of Parkinson’s disease and related synucleinopathies. However, although dopamine transporter single photon emission computed tomography (SPECT) has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson’s disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals. Furthermore, a role for dopaminergic degeneration is suggested by the fact that reward insensitivity can be improved by dopaminergic medications. Patients with iRBD present a unique opportunity to study the relationship between reward sensitivity and early dopaminergic deficit in the unmedicated state. Here, we investigate whether a non-invasive, objective measure of reward sensitivity might be a marker of dopaminergic status in prodromal Parkinson’s disease by comparing with SPECT/CT measurement of dopaminergic loss in the basal ganglia. Striatal dopaminergic deficits in iRBD are associated with progression to Parkinsonian disorders. Therefore, identification of a clinically measurable correlate of this degenerative process might provide a basis for the development of novel risk stratification tools. Using a recently developed incentivized eye-tracking task, we quantified reward sensitivity in a cohort of 41 patients with iRBD and compared this with data from 40 patients with Parkinson’s disease and 41 healthy controls. Patients with iRBD also underwent neuroimaging with dopamine transporter SPECT/CT. Overall, reward sensitivity, indexed by pupillary response to monetary incentives, was reduced in iRBD cases compared with controls and was not significantly different to that in patients with Parkinson’s disease. However, in iRBD patients with normal dopamine transporter SPECT/CT imaging, reward sensitivity was not significantly different from healthy controls. Across all iRBD cases, a positive association was observed between reward sensitivity and dopaminergic SPECT/CT signal in the putamen. These findings demonstrate a direct relationship between dopaminergic deficit and reward sensitivity in patients with iRBD and suggest that measurement of pupillary responses could be of value in models of risk stratification and disease progression in these individuals. REM sleep behaviour disorder is an important marker of the prodromal phase of Parkinsonian disorders. Barber et al. demonstrate that RBD patients with established dopaminergic deficits have blunted pupillary responses to reward. Pupillary reward sensitivity may therefore be a marker of prodromal dopaminergic decline.