Predictive impairment in autism: towards the emergence of phenotypes

自闭症的预测障碍：表型的出现

• 批准号: EP/X021947/1
• 负责人: Parvaneh Adibpour
• 金额: $ 24.26万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX021947%2F1
• 关键词: Predictive; impairment; autism; towards; emergence

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.

自闭症表型的特征是行为维度的广泛多样性。目前尚不清楚这些特征或其中的一部分是否共享因果神经机制。在成年期，非典型行为的复杂性在一定程度上是神经回路与环境相互作用的适应性的副产品。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，潜在的神经行为在婴儿期很早就出现了，然后逐渐发展成不同的行为。通过观察这个时间窗，我们可以在自闭症患者进化为更复杂的行为之前，以及在环境影响他们的发展之前，描述早期的非典型机制。最近的研究提出了一个自闭症表型共有的核心过程：当大脑不断产生关于传入感官输入的假设时，对环境刺激的预测能力受损。在这种观点中，自闭症表型的几个行为维度可能是预测能力潜在障碍的表现。受这些报道的启发，我调查了是否出现了自闭症家族史的新生儿的预测机制中的非典型行为的指导。通过使用神经成像技术，并将认知科学和神经科学的理论结合在一起，我追求两个目标：1）识别神经典型新生儿早期预测能力的神经机制，2）调查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，在他们导致后来的更多样化的行为之前。为此，我提出了一个实验范式，加上两种神经影像学方式，以调查早期预测能力的神经相关性。这将为大脑发育的早期典型和非典型机制提供戏剧性的新见解。