Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Cell Rep Methods. 2024 Jan 22;4(1):100691. doi: 10.1016/j.crmeth.2023.100691. Epub 2024 Jan 11.
Therapeutic development for mental disorders has been slow despite the high worldwide prevalence of illness. Unfortunately, cellular and circuit insights into disease etiology have largely failed to generalize across individuals that carry the same diagnosis, reflecting an unmet need to identify convergent mechanisms that would facilitate optimal treatment. Here, we discuss how mesoscale networks can encode affect and other cognitive processes. These networks can be discovered through electrical functional connectome (electome) analysis, a method built upon explainable machine learning models for analyzing and interpreting mesoscale brain-wide signals in a behavioral context. We also outline best practices for identifying these generalizable, interpretable, and biologically relevant networks. Looking forward, translational electome analysis can span species and various moods, cognitive processes, or other brain states, supporting translational medicine. Thus, we argue that electome analysis provides potential translational biomarkers for developing next-generation therapeutics that exhibit high efficacy across heterogeneous disorders.
尽管精神障碍在全球范围内普遍存在,但治疗方法的发展却一直很缓慢。不幸的是,对于疾病病因的细胞和回路的深入了解在很大程度上未能在具有相同诊断的个体之间推广,这反映出需要确定能够促进最佳治疗的趋同机制。在这里,我们讨论了中尺度网络如何编码情感和其他认知过程。这些网络可以通过电功能连接组(electome)分析来发现,这是一种建立在可解释机器学习模型基础上的方法,用于在行为背景下分析和解释中尺度全脑信号。我们还概述了识别这些可推广、可解释和具有生物学相关性的网络的最佳实践。展望未来,转化型 electome 分析可以跨越物种和各种情绪、认知过程或其他大脑状态,为转化医学提供支持。因此,我们认为 electome 分析为开发新一代治疗药物提供了潜在的转化生物标志物,这些药物在异质障碍中表现出高效性。