Previous Institutionalization Is Followed by Broader Amygdala-Hippocampal-PFC Network Connectivity during Aversive Learning in Human Development.
Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala-hippocampal-prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7-16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7-16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS-). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS- trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal-subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience.



Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive learning. Among youth who experienced prior institutionalization, individual differences in aversive learning were associated with worse current anxiety. However, connectivity between the hippocampus and prefrontal cortex prospectively predicted significant improvements in anxiety 2 years following scanning for previously institutionalized youth. Among youth who experienced prior institutionalization, age-atypical engagement of a distributed set of brain regions during aversive learning may serve a protective function.
Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095, silvers@ucla.edu nlt7@columbia.edu.
Jennifer A
0000-0002-6615-5473
JA
Silvers
Department of Psychology, University of Denver, Denver, Colorado 80208.
Daniel S
0000-0002-4480-9931
DS
Lumian
Department of Psychology, Columbia University, New York, New York 10027.
Laurel
L
Gabard-Durnam
Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, New York 10065.
Dylan G
0000-0002-3685-2710
DG
Gee
Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095.
Bonnie
0000-0002-3126-6579
B
Goff
Department of Psychology, University of Oregon, Eugene, Oregon 97403.
Dominic S
DS
Fareri
Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095.
Christina
0000-0002-6205-5918
C
Caldera
Gordon F. Derner Institute of Advanced Psychological Studies, Adelphi University, Garden City, New York 11530.
Jessica
0000-0003-0710-2512
J
Flannery
Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, Illinois 61820, and.
Eva H
EH
Telzer
Department of Psychology, Stanford University, Stanford, California 94305.
Kathryn L
0000-0002-5715-6597
KL
Humphreys
Department of Psychology, Columbia University, New York, New York 10027, silvers@ucla.edu nlt7@columbia.edu.
Nim
0000-0002-9574-4197
N
Tottenham
D000293:Adolescent; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001007:Anxiety / Q000503:physiopathology*; D001362:Avoidance Learning / Q000502:physiology*; D001931:Brain Mapping; D002648:Child; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D065886:Neurodevelopmental Disorders / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology
D010100:Oxygen
early life stress; fMRI; learning; neurodevelopment; threat