Norbury Agnes, Kurth-Nelson Zeb, Winston Joel S, Roiser Jonathan P, Husain Masud
Institute of Cognitive Neuroscience (Ms Norbury and Drs Winston and Roiser), Wellcome Trust Centre for Neuroimaging (Drs Kurth-Nelson and Winston), Max Plank-UCL Centre for Computational Psychiatry and Ageing (Dr Kurth-Nelson), University College London, London, United Kingdom; Department of Experimental Psychology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (Professor Husain).
Int J Neuropsychopharmacol. 2015 Apr 9;18(10):pyv041. doi: 10.1093/ijnp/pyv041.
Sensation-seeking is a trait that constitutes an important vulnerability factor for a variety of psychopathologies with high social cost. However, little is understood either about the mechanisms underlying motivation for intense sensory experiences or their neuropharmacological modulation in humans.
Here, we first evaluate a novel paradigm to investigate sensation-seeking in humans. This test probes the extent to which participants choose either to avoid or self-administer an intense tactile stimulus (mild electric stimulation) orthogonal to performance on a simple economic decision-making task. Next we investigate in a different set of participants whether this behavior is sensitive to manipulation of dopamine D2 receptors using a within-subjects, placebo-controlled, double-blind design.
In both samples, individuals with higher self-reported sensation-seeking chose a greater proportion of mild electric stimulation-associated stimuli, even when this involved sacrifice of monetary gain. Computational modelling analysis determined that people who assigned an additional positive economic value to mild electric stimulation-associated stimuli exhibited speeding of responses when choosing these stimuli. In contrast, those who assigned a negative value exhibited slowed responses. These findings are consistent with involvement of low-level, approach-avoidance processes. Furthermore, the D2 antagonist haloperidol selectively decreased the additional economic value assigned to mild electric stimulation-associated stimuli in individuals who showed approach reactions to these stimuli under normal conditions (behavioral high-sensation seekers).
These findings provide the first direct evidence of sensation-seeking behavior being driven by an approach-avoidance-like mechanism, modulated by dopamine, in humans. They provide a framework for investigation of psychopathologies for which extreme sensation-seeking constitutes a vulnerability factor.
寻求刺激是一种特质,是多种社会成本高昂的精神病理学的重要易感性因素。然而,对于强烈感官体验的动机背后的机制或其在人类中的神经药理学调节知之甚少。
在这里,我们首先评估一种用于研究人类寻求刺激的新范式。该测试探究参与者在简单经济决策任务的表现不受影响的情况下,选择避免或自我施加强烈触觉刺激(轻度电刺激)的程度。接下来,我们在另一组参与者中研究这种行为是否对使用受试者内、安慰剂对照、双盲设计的多巴胺D2受体操纵敏感。
在两个样本中,自我报告寻求刺激程度较高的个体选择与轻度电刺激相关的刺激的比例更高,即使这涉及到金钱收益的牺牲。计算模型分析确定,那些给与轻度电刺激相关的刺激赋予额外正经济价值的人在选择这些刺激时反应速度加快。相反,那些赋予负价值的人反应速度减慢。这些发现与低水平的趋近-回避过程的参与一致。此外,D2拮抗剂氟哌啶醇选择性降低了在正常条件下对这些刺激表现出趋近反应的个体(行为上的高寻求刺激者)赋予与轻度电刺激相关的刺激的额外经济价值。
这些发现提供了首个直接证据,证明在人类中,寻求刺激行为是由一种类似趋近-回避的机制驱动,并受多巴胺调节。它们为研究极端寻求刺激构成易感性因素的精神病理学提供了一个框架。