Department of Psychiatry, University of Cambridge, Cambridge, UK.
MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK.
Neuropsychopharmacology. 2019 Jun;44(7):1216-1223. doi: 10.1038/s41386-019-0343-6. Epub 2019 Feb 15.
Impulsivity has been suggested as a neurocognitive endophenotype conferring risk across a number of neuropsychiatric conditions, including substance and behavioural addictions, eating disorders, and attention deficit/hyperactivity disorder. We used a paradigm with interspecies translation validity (the four-choice serial reaction time task, 4CSRTT) to assess 'waiting' impulsivity in a youth sample (N = 99, aged 16-26 years). We collected magnetization prepared two rapid acquisition gradient echo (MP2RAGE) scans, which enabled us to measure R1, the longitudinal relaxation rate, a parameter closely related to tissue myelin content, as well as quantify grey matter volume. We also assessed inhibitory control (commission errors) on a Go/NoGo task and measured decisional impulsivity (delay discounting) using the Monetary Choice Questionnaire (MCQ). We found R1 of the bilateral ventral putamen was negatively correlated with premature responding, the index of waiting impulsivity on the 4CSRTT. Heightened impulsivity in youth was significantly and specifically associated with lower levels of myelination in the ventral putamen. Impulsivity was not associated with grey matter volume. The association with myelination was specific to waiting impulsivity: R1 was not associated with decisional impulsivity on the MCQ or inhibitory control on the Go/NoGo task. We report that heightened waiting impulsivity, measured as premature responding on the 4CSRTT, is specifically associated with lower levels of ventral putaminal myelination, measured using R1. This may represent a neural signature of vulnerability to diseases associated with excessive impulsivity and demonstrates the added explanatory power of quantifying the mesoscopic organization of the human brain, over and above macroscopic volumetric measurements.
冲动性被认为是一种神经认知内表型,它增加了多种神经精神疾病的风险,包括物质和行为成瘾、饮食失调和注意缺陷/多动障碍。我们使用了具有跨物种翻译有效性的范式(四选择序列反应时间任务,4CSRTT)来评估青年样本中的“等待”冲动性(N=99,年龄 16-26 岁)。我们收集了磁化准备双快速获取梯度回波(MP2RAGE)扫描,这使我们能够测量 R1,即纵向弛豫率,这是一个与组织髓鞘含量密切相关的参数,以及量化灰质体积。我们还在 Go/NoGo 任务中评估了抑制控制(冲动性错误),并使用货币选择问卷(MCQ)测量了决策冲动性(延迟折扣)。我们发现双侧腹侧纹状体的 R1 与过早反应呈负相关,过早反应是 4CSRTT 中等待冲动性的指标。年轻人的冲动性升高与腹侧纹状体的髓鞘化水平降低显著相关。冲动性与灰质体积无关。与髓鞘化的关联是特定于等待冲动性的:R1 与 MCQ 上的决策冲动性或 Go/NoGo 任务上的抑制控制无关。我们报告说,4CSRTT 上的过早反应测量的等待冲动性升高与腹侧纹状体的 R1 测量的髓鞘化水平降低密切相关。这可能代表了与过度冲动相关的疾病易感性的神经特征,并表明了量化人类大脑的中观组织的额外解释力,超过了宏观体积测量。