Theis Nicholas, Bahuguna Jyotika, Rubin Jonathan E, Banerjee Shubha Sankar, Muldoon Brendan, Prasad Konasale M
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Neuroscience, Laboratoire de Neurosciences Cognitive et Adaptive, University of Strasbourg, France.
bioRxiv. 2024 Oct 15:2023.11.06.565753. doi: 10.1101/2023.11.06.565753.
Adolescent-onset schizophrenia (AOS) is rare, under-studied, and associated with more severe cognitive impairments and poorer outcomes than adult-onset schizophrenia. Neuroimaging has shown altered regional activations (first-order effects) and functional connectivity (second-order effects) in AOS compared to controls. The pairwise maximum entropy model (MEM) integrates first- and second-order factors into a single quantity called energy, which is inversely related to probability of occurrence of brain activity patterns. We take a combinatorial approach to study multiple brain-wide MEMs of task-associated components; hundreds of independent MEMs for various sub-systems are fit to 7 Tesla functional MRI scans. Acquisitions were collected from 23 AOS individuals and 53 healthy controls while performing the Penn Conditional Exclusion Test (PCET) for executive function, which is known to be impaired in AOS. Accuracy of PCET performance was significantly reduced among AOS compared to controls. A majority of the models showed significant negative correlation between PCET scores and the total energy attained over the fMRI. Across all instantiations, the AOS group was associated with significantly more frequent occurrence of states of higher energy, assessed with a mixed effects model. An example MEM instance was investigated further using energy landscapes, which visualize high and low energy states on a low-dimensional plane, and trajectory analysis, which quantify the evolution of brain states throughout this landscape. Both supported patient-control differences in the energy profiles. Severity of psychopathology was correlated positively with energy. The MEM's integrated representation of energy in task-associated systems can help characterize pathophysiology of AOS, cognitive impairments, and psychopathology.
青少年起病的精神分裂症（AOS）较为罕见，研究不足，且与成人起病的精神分裂症相比，伴有更严重的认知障碍和更差的预后。神经影像学研究表明，与对照组相比，AOS患者存在区域激活改变（一阶效应）和功能连接改变（二阶效应）。成对最大熵模型（MEM）将一阶和二阶因素整合为一个称为能量的单一量，该能量与大脑活动模式出现的概率呈负相关。我们采用组合方法研究与任务相关组件的多个全脑MEM；将数百个针对各个子系统的独立MEM拟合到7特斯拉功能磁共振成像扫描数据中。在23名AOS患者和53名健康对照者执行用于执行功能的宾夕法尼亚条件排除测试（PCET）时收集了数据，已知AOS患者的执行功能受损。与对照组相比，AOS患者的PCET表现准确性显著降低。大多数模型显示PCET分数与功能磁共振成像获得的总能量之间存在显著负相关。在所有实例中，使用混合效应模型评估发现，AOS组与更高能量状态的更频繁出现相关。使用能量景观进一步研究了一个MEM实例，能量景观在低维平面上可视化高能量和低能量状态，以及轨迹分析，轨迹分析量化了整个景观中大脑状态的演变。两者都支持患者与对照在能量分布上的差异。精神病理学的严重程度与能量呈正相关。MEM在与任务相关系统中对能量的综合表示有助于表征AOS的病理生理学、认知障碍和精神病理学。
