Schilling Louisa, Singleton S Parker, Tozlu Ceren, Hédo Marie, Zhao Qingyu, Pohl Kilian M, Jamison Keith, Kuceyeski Amy
Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA.
bioRxiv. 2024 Sep 4:2024.09.03.610959. doi: 10.1101/2024.09.03.610959.
An individual's risk of substance use disorder (SUD) is shaped by a complex interplay of potent biosocial factors. Current neurodevelopmental models posit vulnerability to SUD in youth is due to an overreactive reward system and reduced inhibitory control. Having a family history of SUD is a particularly strong risk factor, yet few studies have explored its impact on brain function and structure prior to substance exposure. Herein, we utilized a network control theory approach to quantify sex-specific differences in brain activity dynamics in youth with and without a family history of SUD, drawn from a large cohort of substance-naïve youth from the Adolescent Brain Cognitive Development Study. We summarize brain dynamics by calculating transition energy, which probes the ease with which a whole brain, region or network drives the brain towards a specific spatial pattern of activation (i.e., brain state). Our findings reveal that a family history of SUD is associated with alterations in the brain's dynamics wherein: i) independent of sex, certain regions' transition energies are higher in those with a family history of SUD and ii) there exist sex-specific differences in SUD family history groups at multiple levels of transition energy (global, network, and regional). Family history-by-sex effects reveal that energetic demand is increased in females with a family history of SUD and decreased in males with a family history of SUD, compared to their same-sex counterparts with no SUD family history. Specifically, we localize these effects to higher energetic demands of the default mode network in females with a family history of SUD and lower energetic demands of attention networks in males with a family history of SUD. These results suggest a family history of SUD may increase reward saliency in males and decrease efficiency of top-down inhibitory control in females. This work could be used to inform personalized intervention strategies that may target differing cognitive mechanisms that predispose individuals to the development of SUD.
个体患物质使用障碍（SUD）的风险是由强大的生物社会因素之间复杂的相互作用所塑造的。当前的神经发育模型认为，青少年易患SUD是由于奖励系统反应过度和抑制控制能力下降。有SUD家族史是一个特别强的风险因素，但很少有研究探讨其在接触物质之前对脑功能和结构的影响。在此，我们采用网络控制理论方法，从青少年大脑认知发展研究的大量未接触过物质的青少年队列中，量化有无SUD家族史的青少年大脑活动动力学中的性别特异性差异。我们通过计算转换能量来总结大脑动力学，转换能量探测的是整个大脑、区域或网络将大脑驱动至特定激活空间模式（即脑状态）的难易程度。我们的研究结果表明，SUD家族史与大脑动力学的改变有关，其中：i）与性别无关，有SUD家族史者某些区域的转换能量较高；ii）在多个转换能量水平（全局、网络和区域）上，SUD家族史组存在性别特异性差异。家族史与性别的交互作用表明，与无SUD家族史的同性个体相比，有SUD家族史的女性能量需求增加，有SUD家族史的男性能量需求减少。具体而言，我们将这些影响定位到有SUD家族史的女性默认模式网络的较高能量需求以及有SUD家族史的男性注意力网络的较低能量需求。这些结果表明，SUD家族史可能会增加男性的奖励显著性，并降低女性自上而下抑制控制的效率。这项工作可用于为个性化干预策略提供信息，这些策略可能针对使个体易患SUD的不同认知机制。
