Neurometabolic and functional connectivity basis of prosocial behavior in early adolescence

Human prosocial behavior (PB) emerges in childhood and matures during adolescence. Previous task-related functional magnetic resonance imaging (fMRI) studies have reported involvement of the medial prefrontal cortex including the anterior cingulate cortex (ACC) in social cognition in adolescence. However, neurometabolic and functional connectivity (FC) basis of PB in early adolescence remains unclear. Here, we measured GABA levels in the ACC and FC in a subsample (aged 10.5–13.4 years) of a large-scale population-based cohort with MR spectroscopy (MEGA-PRESS) and resting-state fMRI. PB was negatively correlated with GABA levels in the ACC (N = 221), and positively correlated with right ACC-seeded FC with the right precentral gyrus and the bilateral middle and posterior cingulate gyrus (N = 187). Furthermore, GABA concentrations and this FC were negatively correlated, and the FC mediated the association between GABA levels and PB (N = 171). Our results from a minimally biased, large-scale sample provide new insights into the neurometabolic and neurofunctional correlates of prosocial development during early adolescence.

[1]  R. Viner,et al.  Pubertal transitions in health , 2007, The Lancet.

[2]  Stewart H Mostofsky,et al.  Reduced GABA concentration in attention-deficit/hyperactivity disorder. , 2012, Archives of general psychiatry.

[3]  D. Margulies,et al.  Development of anterior cingulate functional connectivity from late childhood to early adulthood. , 2009, Cerebral cortex.

[4]  Samuel E. Ehrenreich,et al.  Prosocial Behavior: Long-Term Trajectories and Psychosocial Outcomes. , 2015, Social development.

[5]  M. Garwood,et al.  Simultaneous in vivo spectral editing and water suppression , 1998, NMR in biomedicine.

[6]  D. Lewis,et al.  Cortical inhibitory neurons and schizophrenia , 2005, Nature Reviews Neuroscience.

[7]  Colin F Camerer,et al.  Insensitivity to social reputation in autism , 2011, Proceedings of the National Academy of Sciences.

[8]  D. Laible,et al.  Early Adolescence and Prosocial/Moral Behavior I: , 1999 .

[9]  Chandan J. Vaidya,et al.  Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children , 2015, NeuroImage: Clinical.

[10]  Danielle Z. Bolling,et al.  Development of neural systems for processing social exclusion from childhood to adolescence. , 2011, Developmental science.

[11]  Dimitrios Kapogiannis,et al.  Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network , 2013, NeuroImage.

[12]  Michael J. Kofler,et al.  Developmental trajectories of aggression, prosocial behavior, and social-cognitive problem solving in emerging adolescents with clinically elevated attention-deficit/hyperactivity disorder symptoms. , 2015, Journal of abnormal psychology.

[13]  J. Krystal,et al.  Cortical γ-Aminobutyric Acid Levels Across the Menstrual Cycle in Healthy Women and Those With Premenstrual Dysphoric Disorder: A Proton Magnetic Resonance Spectroscopy Study , 2002 .

[14]  F. Lin,et al.  Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI , 2015, PloS one.

[15]  Michael D. Greicius,et al.  Development of functional and structural connectivity within the default mode network in young children , 2010, NeuroImage.

[16]  Kuei Yuan Tseng,et al.  Mechanisms contributing to prefrontal cortex maturation during adolescence , 2016, Neuroscience & Biobehavioral Reviews.

[17]  G. Caprara,et al.  The development of prosociality from adolescence to early adulthood: the role of effortful control. , 2013, Journal of personality.

[18]  G. Caprara,et al.  Prosocial development from childhood to adolescence: a multi-informant perspective with Canadian and Italian longitudinal studies. , 2009, Journal of child psychology and psychiatry, and allied disciplines.

[19]  Aad van der Lugt,et al.  Pediatric population-based neuroimaging and the Generation R Study: the intersection of developmental neuroscience and epidemiology , 2013, European Journal of Epidemiology.

[20]  Peter B Barker,et al.  Spatial effects in the detection of γ‐aminobutyric acid: Improved sensitivity at high fields using inner volume saturation , 2007, Magnetic resonance in medicine.

[21]  P. Brambilla,et al.  GABAergic dysfunction in mood disorders , 2003, Molecular Psychiatry.

[22]  S. Provencher.  Automatic quantitation of localized in vivo 1H spectra with LCModel , 2001, NMR in biomedicine.

[23]  T. Blumensath,et al.  Reduced Default Mode Connectivity in Adolescents With Conduct Disorder. , 2016, Journal of the American Academy of Child and Adolescent Psychiatry.

[24]  Jin Fan,et al.  Abnormal autonomic and associated brain activities during rest in autism spectrum disorder. , 2014, Brain : a journal of neurology.

[25]  Marco F. H. Schmidt,et al.  The emergence of human prosociality: aligning with others through feelings, concerns, and norms , 2014, Front. Psychol..

[26]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[27]  C. Frith,et al.  Social Cognition in Humans , 2007, Current Biology.

[28]  Yasuyuki Taki,et al.  Association between resting-state functional connectivity and empathizing/systemizing , 2014, NeuroImage.

[29]  Maarten Mennes,et al.  Resting state FMRI research in child psychiatric disorders , 2013, European Child & Adolescent Psychiatry.

[30]  Nancy Eisenberg,et al.  Prosocial Development in Adolescence: A Longitudinal Study , 1991 .

[31]  Margot J. Taylor,et al.  The developing human brain: age‐related changes in cortical, subcortical, and cerebellar anatomy , 2016, Brain and behavior.

[32]  T. Ohnishi,et al.  Changes of brain activity in the neural substrates for theory of mind during childhood and adolescence , 2007, Psychiatry and clinical neurosciences.

[33]  Peter de Jonge,et al.  The Reciprocity of Prosocial Behavior and Positive Affect in Daily Life. , 2018, Journal of personality.

[34]  R. Buckner,et al.  Functional-Anatomic Fractionation of the Brain's Default Network , 2010, Neuron.

[35]  S. Israel,et al.  Genetic and environmental influences on prosocial behavior. , 2010 .

[36]  Alan C. Evans,et al.  Atypical functional brain connectivity during rest in autism spectrum disorders , 2015, Annals of neurology.

[37]  K. Hugdahl,et al.  “Brain MR spectroscopy in autism spectrum disorder—the GABA excitatory/inhibitory imbalance theory revisited” , 2015, Front. Hum. Neurosci..

[38]  Donald C. Rojas,et al.  Decreased left perisylvian GABA concentration in children with autism and unaffected siblings , 2014, NeuroImage.

[39]  J. O'Doherty,et al.  Neural Mechanisms Underlying Human Consensus Decision-Making , 2015, Neuron.

[40]  R. Goodman.  The Strengths and Difficulties Questionnaire: a research note. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[41]  Tomáš Paus,et al.  Population neuroscience: Why and how , 2010, Human brain mapping.

[42]  Ines Blazevic.  Family, Peer and School Influence on Children's Social Development. , 2016 .

[43]  Mary Beth Nebel,et al.  Reduction of motion-related artifacts in resting state fMRI using aCompCor , 2014, NeuroImage.

[44]  S. Petersen,et al.  The maturing architecture of the brain's default network , 2008, Proceedings of the National Academy of Sciences.

[45]  Yufeng Zang,et al.  DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging , 2016, Neuroinformatics.

[46]  J. Golding,et al.  Social and behavioural outcomes in children diagnosed with autism spectrum disorders: a longitudinal cohort study. , 2012, Journal of child psychology and psychiatry, and allied disciplines.

[47]  Amene Shahrokhi,et al.  Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring , 2014, Science.

[48]  Mirella Dapretto,et al.  Developmental changes in the neural basis of interpreting communicative intent. , 2006, Social cognitive and affective neuroscience.

[49]  Eveline A. Crone,et al.  Sharing and giving across adolescence: an experimental study examining the development of prosocial behavior , 2014, Front. Psychol..

[50]  D. Hay,et al.  Prosocial development. , 1994, Journal of child psychology and psychiatry, and allied disciplines.

[51]  P. Boesiger,et al.  GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI , 2007, Nature Neuroscience.

[52]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[53]  Sarah-Jayne Blakemore,et al.  Functional connectivity during a social emotion task in adolescents and in adults , 2009, The European journal of neuroscience.

[54]  L. Spear,et al.  Adolescent neurodevelopment. , 2013, The Journal of adolescent health : official publication of the Society for Adolescent Medicine.

[55]  Qinglin Zhang,et al.  Synchronous activation within the default mode network correlates with perceived social support , 2014, Neuropsychologia.

[56]  Sonja Lyubomirsky,et al.  Do unto others or treat yourself? The effects of prosocial and self-focused behavior on psychological flourishing. , 2016, Emotion.

[57]  Michael Scharkow,et al.  The Relative Trustworthiness of Inferential Tests of the Indirect Effect in Statistical Mediation Analysis , 2013, Psychological science.

[58]  G. V. van Wingen,et al.  Perceived threat predicts the neural sequelae of combat stress , 2011, Molecular Psychiatry.

[59]  Irene Neuner,et al.  GABA Concentration in Posterior Cingulate Cortex Predicts Putamen Response during Resting State fMRI , 2014, PloS one.

[60]  Edgar Erdfelder,et al.  G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences , 2007, Behavior research methods.

[61]  G. Sideridis,et al.  On Social Achievement Goals: Their Relations With Peer Acceptance, Classroom Belongingness, and Perceptions of Loneliness , 2009 .

[62]  C. Frith,et al.  Adolescent development of the neural circuitry for thinking about intentions , 2007, Social cognitive and affective neuroscience.

[63]  Heidi Johansen-Berg,et al.  Local GABA concentration is related to network-level resting functional connectivity , 2014, eLife.

[64]  Lisanne L. Stone,et al.  Psychometric Properties of the Parent and Teacher Versions of the Strengths and Difficulties Questionnaire for 4- to 12-Year-Olds: A Review , 2010, Clinical child and family psychology review.

[65]  Francis Eustache,et al.  Neural Correlates of Self and Its Interaction With Memory in Healthy Adolescents. , 2015, Child development.

[66]  Isabelle M. Rosso,et al.  Frontal Lobe γ-Aminobutyric Acid Levels During Adolescence: Associations with Impulsivity and Response Inhibition , 2013, Biological Psychiatry.

[67]  Karl J. Friston,et al.  Movement‐Related effects in fMRI time‐series , 1996, Magnetic resonance in medicine.

[68]  S. Blakemore.  The social brain in adolescence , 2008, Nature Reviews Neuroscience.

[69]  T. Callaghan,et al.  Early prosocial development across cultures. , 2018, Current opinion in psychology.

[70]  Maolin Qiu,et al.  GABA, Resting-State Connectivity and the Developing Brain , 2014, Neonatology.

[71]  Cornelis J. Stam,et al.  Genetic control of functional brain network efficiency in children , 2013, European Neuropsychopharmacology.

[72]  B. Rockenbach,et al.  Egalitarianism in young children , 2008, Nature.

[73]  B. J. Casey,et al.  Anatomical MRI of the developing human brain: what have we learned? , 2001, Journal of the American Academy of Child and Adolescent Psychiatry.

[74]  Ellen Leibenluft,et al.  Adolescent immaturity in attention-related brain engagement to emotional facial expressions , 2003, NeuroImage.

[75]  S. Bölte,et al.  Alterations in resting state connectivity along the autism trait continuum: a twin study , 2018, Molecular Psychiatry.

[76]  G. Blatt,et al.  Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism , 2009, Autism research : official journal of the International Society for Autism Research.

[77]  Jonathan D. Power,et al.  Functional Brain Networks Develop from a “Local to Distributed” Organization , 2009, PLoS Comput. Biol..

[78]  Maarten Mennes,et al.  The executive control network and symptomatic improvement in attention-deficit/hyperactivity disorder , 2015, Cortex.

[79]  P. Brambilla,et al.  GABAergic dysfunction in mood disorders , 2003, Molecular Psychiatry.

[80]  W. Kilb.  Development of the GABAergic System from Birth to Adolescence , 2012, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[81]  Hans M Koot,et al.  Prosocial Behavior in Adolescence: Gender Differences in Development and Links with Empathy , 2018, Journal of youth and adolescence.

[82]  E. Ansell,et al.  Prosocial Behavior Mitigates the Negative Effects of Stress in Everyday Life , 2016, Clinical psychological science : a journal of the Association for Psychological Science.

[83]  Luke Bloy,et al.  GABA estimation in the brains of children on the autism spectrum: Measurement precision and regional cortical variation , 2014, NeuroImage.

[84]  Jonathan D. Power,et al.  The Development of Human Functional Brain Networks , 2010, Neuron.

[85]  N. Logothetis.  What we can do and what we cannot do with fMRI , 2008, Nature.