Project 3: The neurobiology of adverse early care in rhesus infants....

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Project 3 uses a nonhuman primate model of early life stress (ELS) in the form of adverse early care to provide information on its neurodevelopmental impact using methods that cannot be used with the very young children studied in the Center's human projects (1 & 2). By nesting our rhesus project in the context of comparable work on young children exposed to ELS, and by using comparable measures of behavior and physiology across species, we are in a unique position to use the neurodevelopmental findings to understand the neural systems impacted by ELS in young primates. We have chosen a nonhuman model of adverse early care, maternal maltreatment, with striking resemblance to human maltreatment. The targeted developmental period in Project 3 is birth through 18 mos, which corresponds to the birth to 6-7 yr period targeted in our human projects. In both species this developmental period is one of rapid brain development believed to be vulnerable to ELS impact. Project 3 will assess all Center aims: (1) to test the hypothesis that ELS sensitizes developing stress- and threat-response systems and alters the development of prefrontal circuits involved in emotion- and attention-regulation; and (2) to examine the dimensions of caregiving associatedwith this sensitization of stress- and threat-response systems. Project 3 shares aims and methods with Projects 1 (foster care) and 2 (post-institutionalization). In Aim 1 stress system activity is assessed using plasma cortisol and ACTH and CSF measures of neuropeptides (CRF, AVP) and moncaminergic function; alterations in emotional behavior (fear, anxiety) are assessed from observations in the social groups and laboratory challenges; prefrontal attention- and behavior-regulatory function is assessed using tasks of attention regulation (ID/ED shift), impulsivity (Object Retrieval/Detour) and inhibitory control of behavior (Reinforcer Devaluation); effects of ELS on neurodevelopment are assessed by structural MRI, DTI and MRS. In Aim 2, caregiving behavior is assessedfocusing on the sensitivity and rejection dimensions from observations in the social groups and from videotapes using qualitative ratings. This project draws all five cores of the Center.