Developmental trajectories in social reward and salience brain networks: A combined behavioral and structural MRI study in infant rhesus macaques 公开
Saavedra, Sara (Spring 2020)
Abstract
Non-human primate (NHP) translational models are critical for understanding social deficits in neurodevelopmental disorders, such as Autism Spectrum Disorder (ASD). The goal of this study was to map developmental trajectories of social reward and salience neurocircuits that support the maturation of early prosocial behaviors in infant rhesus macaques.
Longitudinal structural MRI scans were acquired at 2, 4, 8, 12, 24wks from 25 infant male macaques living with their mothers in social groups; 21 of 25 subjects were also scanned at 16, 20wks, and 4 were scanned at 6wks. T1- and T2-weighted images were acquired using a 3T MRI scanner and analyzed for volumetric changes in social reward and salience neurocircuits, which include the amygdala (AMY), nucleus accumbens (NAcc), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), ventromedial PFC (vmPFC) and insula (INS). Measures of social development were collected from a subset of subjects (n = 9), using: (1) focal observations and a rhesus ethogram, (2) rating scales of atypical social behaviors (adapted from the Social Responsiveness Scale (SRS) used for ASD diagnosis in humans). Associations between brain and social behavior developmental measures were examined in a subset of 4 animals with both sMRI and behavioral data.
Region-specific developmental trajectories were identified in these social salience and reward brain networks, although rapid growth was shown by most regions between 8-12 and 16-20 weeks. These changes were paralleled by a decline in frequency and duration of mother-infant affiliative, contact, and proximity behaviors by 8 weeks, when infants increase independence-seeking behaviors and social play. Finally, our preliminary analysis identified the ACC and subgenual cingulate (a subregion of the mPFC) developmental volume changes as significant predictors of changes in social behaviors.
Our findings suggest that during the first 24 weeks of life (equivalent to 2 years in humans), social salience and reward brain networks undergo robust structural changes that parallel the infant’s maturation to independence and increased emotional awareness of appropriate social interaction. Understanding normative development of social behavior and the underlying social brain networks in an NHP model can help elucidate the roots of brain-behavior pathogenesis of human social deficits.
Table of Contents
Introduction................................................................................................................... 1
Methods....................................................................................................................... 12
Subjects...................................................................................................................... 12
Structural MRI............................................................................................................. 13
Image Acquisition................................................................................................ 13
Image Processing and Analysis............................................................................. 14
Behavior..................................................................................................................... 17
Infant Socioemotional Behaviors ......................................................................... 17
Juvenile Social Responsiveness Scale.................................................................... 19
Statistical Analysis....................................................................................................... 20
sMRI................................................................................................................... 20
Infant Socioemotional Behaviors.......................................................................... 21
jmSRS ................................................................................................................ 21
Exploratory Analysis ........................................................................................... 21
Results.......................................................................................................................... 22
sMRI Results............................................................................................................... 22
Behavioral Results....................................................................................................... 31
Infant Socioemotional Behaviors Data.................................................................. 31
jmSRS Data......................................................................................................... 34
Exploratory Analysis Results......................................................................................... 34
Discussion..................................................................................................................... 36
Figures.......................................................................................................................... 58
Tables........................................................................................................................... 75
References.................................................................................................................... 76
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