Predictive impairment in autism: towards the emergence of phenotypes

自闭症表型在行为维度上具有广泛的多样性。目前尚不清楚这些特征或其中的一部分是否有共同的因果神经机制。在成年期，非典型行为的复杂性在一定程度上是神经回路在与环境相互作用中适应的副产品。这使得将行为结果映射到神经机制非常具有挑战性。至关重要的是，潜在的神经非典型性在婴儿期出现得更早，然后逐渐发展成不同的行为。通过观察这个时间窗口，我们可以描述早期的非典型机制，在它们进化成更复杂的行为之前，在环境影响它们的发展之前。最近的研究提出了自闭症表型共有的一个核心过程：当大脑不断地对传入的感觉输入产生假设时，对环境刺激的预测能力受损。在这种观点下，自闭症表型的几个行为维度可能是预测能力潜在损伤的表现。在这些报告的激励下，我研究了具有自闭症家族史的新生儿的非典型预测机制的出现是否会指导后来的非典型行为。通过使用神经成像技术并结合认知科学和神经科学的理论，我追求两个目标：1)确定神经正常新生儿早期预测能力的神经机制，2)研究这些神经机制的早期偏差是否可以在具有高遗传可能性的新生儿中检测到，然后诊断为自闭症，在它们导致后来更多样化的行为之前。为此，我提出了一个结合两种神经成像模式的实验范式来研究早期预测能力的神经相关性。这将为早期典型和非典型大脑发育机制提供戏剧性的新见解。

Autism phenotypes are characterized by wide diversity across behavioral dimensions. It is unknown whether these traits or a subset of them share a causal neural mechanism. In adulthood, the complexity of atypical behaviors is in part the by-product of adaptation at the level of the neural circuitry in interaction with environment. This makes the mapping of behavioral outcomes to neural mechanisms very challenging. Crucially, the underlying neural atypicalities emerge much earlier in infancy and then gradually unfold into different behaviors. By looking at this time window, we can characterize early atypical mechanisms at play prior to their evolution into more complex behaviors and before the environment influences their development.Recent research has proposed a core process that is shared among autism phenotypes: an impairment in predictive skills in response to environmental stimuli, when the brain is continuously generating hypotheses about incoming sensory inputs. In this view, several behavioral dimensions of autism phenotypes may be manifestations of an underlying impairment in predictive abilities. Motivated by these reports, I investigate whether the emergence of atypicalities in predictive mechanisms in neonates with a family history of autism guide later atypical behaviors. By using neuroimaging techniques and bringing theories from cognitive science and neuroscience together, I pursue two goals: 1) identifying neural mechanisms underlying early predictive abilities in neurotypical neonates, 2) investigating whether early deviations in these neural mechanisms can be detected in neonates with a high-genetic likelihood of later autism diagnosis, before they lead to later, more diverse behaviors. To this end, I propose an experimental paradigm coupled with two neuroimaging modalities to investigate the neural correlates of early predictive abilities. This will provide dramatic new insights into the early typical and atypical mechanisms of brain development.