Nakuci Johan, Garcia Javier, Bansal Kanika
U.S. Army DEVCOM Army Research Laboratory, Aberdeen Proving Ground, Aberdeen, MD, 21005, USA.
Computer Science and Electrical Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
Netw Neurosci. 2025 Apr 30;9(2):522-548. doi: 10.1162/netn_a_00444. eCollection 2025.
Functional connectivity (FC) reflects brain-wide communication essential for cognition, yet the role of underlying biophysical factors in shaping FC remains unclear. We quantify the influence of physical factors-structural connectivity (SC) and Euclidean distance (DC), which capture anatomical wiring and regional distance-and molecular factors-gene expression similarity (GC), and neuroreceptor congruence (RC), representing neurobiological similarity-on resting-state FC. We assess how these factors impact graph-theoretic and gradient features, capturing pairwise and higher-order interactions. By generating after selectively removing connections tied to specific factors, we show that molecular factors, particularly RC, dominate graph-theoretic features, while gradient features are shaped by a mix of molecular and physical factors, especially GC and DC. SC has a surprisingly minor role. We also link FC alterations to biophysical factors in schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD), with physical factors differentiating these groups. These insights are key for understanding FC across various applications, including task performance, development, and clinical conditions.
功能连接性（FC）反映了大脑中对认知至关重要的广泛通信，但潜在生物物理因素在塑造FC中的作用仍不清楚。我们量化了物理因素——结构连接性（SC）和欧几里得距离（DC）（分别反映解剖布线和区域距离）以及分子因素——基因表达相似性（GC）和神经受体一致性（RC）（代表神经生物学相似性）对静息态FC的影响。我们评估这些因素如何影响图论和梯度特征，这些特征捕捉成对和高阶相互作用。通过在选择性去除与特定因素相关的连接后生成 ，我们表明分子因素，特别是RC，主导图论特征，而梯度特征由分子和物理因素的混合塑造，尤其是GC和DC。SC的作用出人意料地小。我们还将FC改变与精神分裂症、双相情感障碍和注意力缺陷多动障碍（ADHD）中的生物物理因素联系起来，物理因素区分了这些群体。这些见解对于理解FC在各种应用中的情况至关重要，包括任务表现、发育和临床状况。
