Abstract Maternal addiction remains a significant public health concern, impacting the health and well-being of mothers as well as their developing child. Crucially, addiction disrupts early maternal care, increasing the vulnerability of the child to later substance use, abuse, and dependence1,2. Therefore, work in this area of parenting and addiction resonates with Goal 1 of NIDA’s strategic plan in understanding causes and consequences of drug use and addiction across the lifespan, and will inform Goal 2 in the identification of new and improved strategies to prevent drug use and its consequences. Recent efforts to advance our understanding of the impact of addiction on caregiving have employed neurobiological methods to examine how mothers respond to salient infant affective cues (infant face and cry stimuli). Such an approach has yielded convergent EEG/ERP and fMRI findings of delayed and decreased neural responses to infant cues in mothers with addiction, relative to mothers not engaged in substance use3-5. Building on this research, theoretical models have posited that addiction’s co-optation of reward neural circuits decrease the salience of infant cues and leads to the diminishment of the pleasure and reward of caregiving6-8. However, there is no empirical data that indicates the attenuated neural responses to infant affective cues measured in mothers with addiction translate to measures of caregiving behavior. This represents a significant challenge to the validity of neurobiological studies of parenting and addiction in the identification of mechanisms that may inform intervention efforts to decrease substance use and enhance caregiving and mother-child well-being. Therefore, this R21 application seeks to explore whether addiction impacts neural processing of infant affective cues and affiliated caregiving in recent mothers. Neural processing of infant cues will be accomplished through EEG/ERP methodology and caregiving in this context will incorporate self-report and observed behavior. The project will be actualized within the context of tobacco-smoking and nicotine addiction, allowing for the extension of this work to other substance use disorders.