Abstract
INTRODUCTION: Methamphetamine use disorder (MUD) has substantial societal and individual implications, necessitating a comprehensive understanding of its neural underpinnings for effective intervention. Key to addiction is the amygdala, implicated in emotion processing and reward systems, which interacts with the prefrontal cortex in addictive behaviors. METHODS: We conducted a study involving 54 male individuals with MUD (age range: 22-44 years) to examine amygdala-cortical connectivity during methamphetamine cue reactivity, aiming to uncover effective neural pathways. We combined generalized psychophysiological interaction (gPPI) analysis and dynamic causal modeling (DCM) to elucidate connectivity dynamics and effective neural pathways. We delved deeper into neuro-behavioral connections using the Pearson correlation and group factor analysis (GFA). RESULTS: Our findings revealed increased functional connectivity within the amygdala-posterior cingulate cortex (PCC) and amygdala-dorsolateral prefrontal cortex (dlPFC) networks during methamphetamine cue reactivity. DCM revealed a neural network characterized by positive bidirectional connections among the amygdala, dlPFC, and PCC, along with negative intrinsic connections. Interestingly, we observed that the intrinsic self-inhibition of the dlPFC was negatively correlated with post-task positive affect, suggesting its role in emotional regulation. Nonetheless, utilizing GFA, we did not discover any noteworthy cross-unit latent factors between the neural group and variables related to behavior, psychology, or demographics. CONCLUSION: These discoveries enrich our comprehension of the neural mechanisms at play in methamphetamine cue reactivity and addiction-related processes. The increased amygdala-cortical connectivity underscores the role of these networks in drug cue processing, potentially contributing to craving and relapse. Effective connectivity analysis highlights the interconnectedness of the amygdala, dlPFC, and PCC, revealing potential pathways for neural signaling during cue reactivity. Our results contribute to the growing body of knowledge about addiction's neurobiological basis, offering insights that may inform targeted interventions to mitigate the impact of methamphetamine cue reactivity on addiction progression.