title: Aberrant development of intrinsic brain activity in a rat model of caregiver maltreatment of offspring.
abstract: Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI). Rat pups were reared by mothers provided with insufficient or abundant bedding for nest building from postnatal (PN) days 8 to 12 and underwent behavioral assessments of affect-related behaviors (forced swim, sucrose preference and social interaction) in adolescence (PN45) and early adulthood (PN60). R-fMRI sessions were conducted under light anesthesia at both ages. Offspring reared with insufficient bedding (that is, maltreated) displayed enduring negative affective behaviors. Amygdala-prefrontal cortex (PFC) functional connectivity increased significantly from adolescence to adulthood in controls, but not in maltreated animals. We computed the fractional amplitude of low-frequency fluctuations (fALFF), an index of intrinsic brain activity, and found that fALFF in medial prefrontal cortex and anterior cingulate cortex (MPFC/ACC) increased significantly with age in controls but remained unchanged in maltreated animals during adolescence and adulthood. We used a seed-based analysis to explore changes in functional connectivity between this region and the whole brain. Compared with controls, maltreated animals demonstrated reduced functional connectivity between MPFC/ACC and left caudate/putamen across both ages. Functional connectivity between MPFC/ACC and right caudate/putamen showed a group by age interaction: decreased in controls but increased in maltreated animals. These data suggest that maltreatment induces vulnerability to psychopathology and is associated with differential developmental trajectories of prefrontal and subcortical circuits underlying affect regulation.
authors.affiliation: CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing, China.|Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.|Department of Child and Adolescent Psychiatry, NYU Langone Medical Center School of Medicine, New York, NY, USA.|Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: C-G
authors.initials: CG
authors.lastname: Yan
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU Langone Medical Center School of Medicine, New York, NY, USA.|The Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rincón-Cortés
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU Langone Medical Center School of Medicine, New York, NY, USA.|The Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Raineki
authors.affiliation: The Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Sarro
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Colcombe
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Guilfoyle
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.|Center for the Developing Brain, Child Mind Institute, New York, NY, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gerum
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.|Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, USA.
authors.forename: B B
authors.initials: BB
authors.lastname: Biswal
authors.affiliation: Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.|Center for the Developing Brain, Child Mind Institute, New York, NY, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Milham
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU Langone Medical Center School of Medicine, New York, NY, USA.|The Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Sullivan
authors.affiliation: Department of Child and Adolescent Psychiatry, NYU Langone Medical Center School of Medicine, New York, NY, USA.|Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
authors.forename: F X
authors.initials: FX
authors.lastname: Castellanos
mesh_terms: D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001921:Brain / Q000503:physiopathology*; D002648:Child; D002649:Child Abuse; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008425:Maternal Behavior; D009434:Neural Pathways / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans