NEURAL AND MOLECULAR CORRELATES OF IMPULSIVE TRAITS FROM INTEGRATING RESTING-STATE FMRI AND GENE EXPRESSION

Impulsivity is a behaviourally and genetically heterogeneous trait linked to psychiatric and neurological disorders, yet the circuit-level mechanisms governing the impulsive decision-making remain understudied. Here, we employed an integrative neuroimaging and transcriptomic approach to map the functional and molecular architecture of trait impulsivity. First, we stratified mice with high and low impulsivity phenotypes using the Go/No-go task, a well-validated assay of impulse control in both humans and rodents. Subsequently, resting-state functional magnetic resonance imaging (rs-fMRI) was performed to assess intrinsic functional connectivity patterns in both groups. To probe pharmacological modulators of impulsive circuits, animals received acute administration of amphetamine (dopaminergic agonist) or atomoxetine (noradrenergic reuptake inhibitor) prior to neuroimaging. Functional connectivity analysis revealed phenotype-dependent network organization, with distinct alterations in inter-regional correlations between high and low impulsive animals. Moreover, amphetamine and atomoxetine induced divergent effects on network topology, suggesting dissociable neurochemical contributions to impulsivity regulation. Interestingly, different subregions were activated at the interaction of trait impulsivity and pharmacology. To mechanistically link functional connectivity patterns with molecular substrates, gene enrichment analyses were performed on brain regions exhibiting significant connectivity differences between phenotypes using publicly available transcriptomic data. This approach identified candidate pathways and molecular processes potentially underlying individual variation in impulse control. A hotspot detection strategy further nominated specific brain regions as putative network hubs modulating not only impulsive behaviour but also potential pharmacological targets. By bridging functional neuroimaging with genome-level insights, this work provides a multimodal perspective on impulsivity neurobiology with implications for understanding disease vulnerability and therapeutic target discovery.