Methamphetamine modulates functional connectivity signatures of sustained attention and arousal.

BACKGROUND: Between-subjects studies suggest that psychostimulants can shift whole-brain functional connectivity toward patterns linked to heightened sustained attention. In this study, we examined how a single dose of methamphetamine (MA, 20 mg) changes sustained attention and associated network-level functional organization in healthy adults. METHODS: We conducted a within-subject study in which 76 healthy participants completed two fMRI scanning sessions after taking MA or placebo. We tested whether MA selectively affects behavioral and fMRI connectivity signatures of sustained attention and arousal. RESULTS: Under MA, participants showed improved sustained attention task performance as well as functional connectivity signatures of higher sustained attention and arousal. These network changes emerged consistently across resting-state and task-based fMRI, indicating that MA influences attention- and arousal-related networks regardless of cognitive context. Furthermore, a support vector classifier distinguished functional connectivity patterns observed during the MA and placebo conditions, identifying connections overlapping with networks related to arousal. CONCLUSIONS: Together, these findings align with prior work on other psychostimulants like methylphenidate, showing that MA modulates sustained attention and related large-scale brain networks. By revealing how MA modulates attention-relevant brain connectivity patterns, our results highlight the utility of psychostimulants as causal tools for probing the robustness, generalizability, and interpretability of brain-based biomarkers of behavior.