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Dev Neurosci 2009;31:293–299
(DOI:10.1159/000216540)

Prefrontal Plasticity and Stress Inoculation-Induced Resilience

Katz M.a · Liu C.b · Schaer M.c, d · Parker K.J.a · Ottet M.-C.c · Epps A.a · Buckmaster C.L.a · Bammer R.b · Moseley M.E.b · Schatzberg A.F.a · Eliez S.c · Lyons D.M.a
Departments of aPsychiatry and bRadiology, Stanford University, Stanford, Calif., USA; cDivision of Child and Adolescent Psychiatry, Geneva University, Geneva, and dSignal Processing Institute, Swiss Federal Institute of Technology, Lausanne, Switzerland
email Corresponding Author


 goto top of outline Key Words

  • Emotion regulation
  • Cognitive control
  • Fear
  • Curiosity
  • Cortisol

 goto top of outline Abstract

Coping with mild early life stress tends to make subsequent coping efforts more effective and therefore more likely to be used as a means of arousal regulation and resilience. Here we show that this developmental learning-like process of stress inoculation increases ventromedial prefrontal cortical volumes in peripubertal monkeys. Larger volumes do not reflect increased cortical thickness but instead represent surface area expansion of ventromedial prefrontal cortex. Expansion of ventromedial prefrontal cortex coincides with increased white matter myelination inferred from diffusion tensor magnetic resonance imaging. These findings suggest that the process of coping with early life stress increases prefrontal myelination and expands a region of cortex that broadly controls arousal regulation and resilience.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Khoshaba DM, Maddi SR: Early experiences in hardiness development. Consult Psychol J 1999;51:106–116.

    External Resources

  2. Mortimer JT, Staff J: Early work as a source of developmental discontinuity during the transition to adulthood. Dev Psychopathol 2004;16:1047–1070.
  3. Boyce WT, Ellis BJ: Biological sensitivity to context. I. An evolutionary-developmental theory of the origins and functions of stress reactivity. Dev Psychopathol 2005;17:271–301.
  4. Gunnar MR, Frenn K, Wewerka SS, Van Ryzin MJ: Moderate versus severe early life stress: associations with stress reactivity and regulation in 10–12-year-old children. Psychoneuroendocrinology 2009;34:62–75.
  5. Garmezy N, Masten AS, Tellegen A: The study of stress and competence in children: a building block for developmental psychopathology. Child Dev 1984;55:97–111.
  6. Rutter M: Implications of resilience concepts for scientific understanding. Ann NY Acad Sci 2006;1094:1–12.
  7. Meichenbaum D: Stress inoculation training: a preventative and treatment approach; in Lehrer PM, Woolfolk RL, Sime WE (eds): Principles and Practice of Stress Management. New York, Guildford Press, 2007, pp 497–518.
  8. Fergus S, Zimmerman MA: Adolescent resilience: a framework for understanding healthy development in the face of risk. Annu Rev Publ Health 2005;26:399–419.
  9. Boinski S, Fragaszy DM: The ontogeny of foraging in squirrel monkeys, Saimiri oerstedi. Anim Behav 1989;37:415–428.
  10. Lyons DM, Kim S, Schatzberg AF, Levine S: Postnatal foraging demands alter adrenocortical activity and psychosocial development. Dev Psychobiol 1998;32:285–291.
  11. Hennessy MB: Multiple, brief maternal separations in the squirrel monkey: changes in hormonal and behavioral responsiveness. Physiol Behav 1986;36:245–250.
  12. Coe CL, Glass JC, Wiener SG, Levine S: Behavioral, but not physiological, adaptation to repeated separation in mother and infant primates. Psychoneuroendocrinology 1983;8:401–409.
  13. Lyons DM, Martel FL, Levine S, Risch NJ, Schatzberg AF: Postnatal experiences and genetic effects on squirrel monkey social affinities and emotional distress. Horm Behav 1999;36:266–275.
  14. Levine S, Mody T: The long-term psychobiological consequences of intermittent postnatal separation in the squirrel monkey. Neurosci Biobehav Rev 2003;27:83–89.
  15. Parker KJ, Buckmaster CL, Schatzberg AF, Lyons DM: Prospective investigation of stress inoculation in young monkeys. Arch Gen Psychiatry 2004;61:933–941.
  16. Lyons DM, Parker KJ: Stress inoculation-induced indications of resilience in monkeys. J Trauma Stress 2007;20:423–433.
  17. Parker KJ, Rainwater KL, Buckmaster CL, Schatzberg AF, Lindley SE, Lyons DM: Early life stress and novelty seeking behavior in adolescent monkeys. Psychoneuroendocrinology 2007;32:785–792.
  18. Parker KJ, Buckmaster CL, Justus KR, Schatzberg AF, Lyons DM: Mild early life stress enhances prefrontal-dependent response inhibition in monkeys. Biol Psychiatry 2005;57:848–855.
  19. Lyons DM: Stress, depression, and inherited variation in primate hippocampal and prefrontal brain development. Psychopharmacol Bull 2002;36:27–43.

    External Resources

  20. Lyons DM, Afarian H, Schatzberg AF, Sawyer-Glover A, Moseley ME: Experience-dependent asymmetric variation in primate prefrontal morphology. Behav Brain Res 2002;136:51–59.
  21. Matsuo K, Nicoletti M, Nemoto K, Hatch JP, Peluso MA, Nery FG, Soares JC: A voxel-based morphometry study of frontal gray matter correlates of impulsivity. Hum Brain Mapp 2009;30:1188–1195.
  22. Yamasue H, Abe O, Suga M, Yamada H, Inoue H, Tochigi M, Rogers M, Aoki S, Kato N, Kasai K: Gender-common and -specific neuroanatomical basis of human anxiety-related personality traits. Cereb Cortex 2008;18:46–52.
  23. Milad MR, Quinn BT, Pitman RK, Orr SP, Fischl B, Rauch SL: Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory. Proc Natl Acad Sci USA 2005;102:10706–10711.
  24. Delgado MR, Nearing KI, Ledoux JE, Phelps EA: Neural circuitry underlying the regulation of conditioned fear and its relation to extinction. Neuron 2008;59:829–838.
  25. Quirk GJ, Mueller D: Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 2008;33:56–72.
  26. Bishop SJ: Neurocognitive mechanisms of anxiety: an integrative account. Trends Cogn Sci 2007;11:307–316.
  27. Drabant EM, McRae K, Manuck SB, Hariri AR, Gross JJ: Individual differences in typical reappraisal use predict amygdala and prefrontal responses. Biol Psychiatry 2009;65:367–373.
  28. Moseley M: Diffusion tensor imaging and aging: a review. NMR Biomed 2002;15:553–560.
  29. Fields RD: White matter in learning, cognition and psychiatric disorders. Trends Neurosci 2008;31:361–370.
  30. Barnea-Goraly N, Menon V, Eckert M, Tamm L, Bammer R, Karchemskiy A, Dant CC, Reiss AL: White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. Cereb Cortex 2005;15:1848–1854.
  31. Casey BJ, Epstein JN, Buhle J, Liston C, Davidson MC, Tonev ST, Spicer J, Niogi S, Millner AJ, Reiss A, Garrett A, Hinshaw SP, Greenhill LL, Shafritz KM, Vitolo A, Kotler LA, Jarrett MA, Glover G: Frontostriatal connectivity and its role in cognitive control in parent-child dyads with ADHD. Am J Psychiatry 2007;164:1729–1736.
  32. Lyons DM, Yang C, Eliez S, Reiss AL, Schatzberg AF: Cognitive correlates of white matter growth and stress hormones in female squirrel monkey adults. J Neurosci 2004;24:3655–3662.
  33. Liu C, Bammer R, Kim DH, Moseley ME: Self-navigated interleaved spiral (SNAILS): application to high-resolution diffusion tensor imaging. Magn Reson Med 2004;52:1388–1396.
  34. Dale AM, Fischl B, Sereno MI: Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 1999;9:179–194.
  35. Fischl B, Sereno MI, Dale AM: Cortical surface-based analysis. II. Inflation, flattening, and a surface-based coordinate system. Neuroimage 1999;9:195–207.
  36. Fischl B, Dale AM: Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci USA 2000;97:11050–11055.
  37. Fischl B, Sereno MI, Tootell RB, Dale AM: High-resolution intersubject averaging and a coordinate system for the cortical surface. Hum Brain Mapp 1999;8:272–284.
  38. Rakic P: The development of the frontal lobe: a view from the rear of the brain. Adv Neurol 1995;66:1–6.
  39. Huttenlocher PR, Dabholkar AS: Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol 1997;387:167–178.
  40. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL: Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 1999;2:861–863.
  41. Markham JA, Morris JR, Juraska JM: Neuron number decreases in the rat ventral, but not dorsal, medial prefrontal cortex between adolescence and adulthood. Neuroscience 2007;144:961–968.
  42. Bock J, Murmu RP, Ferdman N, Leshem M, Braun K: Refinement of dendritic and synaptic networks in the rodent anterior cingulate and orbitofrontal cortex: critical impact of early and late social experience. Dev Neurobiol 2008;68:685–695.
  43. Malkova L, Heuer E, Saunders RC: Longitudinal magnetic resonance imaging study of rhesus monkey brain development. Eur J Neurosci 2006;24:3204–3212.
  44. Kern S, Oakes TR, Stone CK, McAuliff EM, Kirschbaum C, Davidson RJ: Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor. Psychoneuroendocrinology 2008;33:517–529.
  45. Davidson RJ, Jackson DC, Kalin NH: Emotion, plasticity, context, and regulation: perspectives from affective neuroscience. Psychol Bull 2000;126:890–909.
  46. Cicchetti D, Blender JA: A multiple-levels-of-analysis perspective on resilience: implications for the developing brain, neural plasticity, and preventive interventions. Ann NY Acad Sci 2006;1094:248–258.
  47. Charney DS: Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 2004;161:195–216.
  48. Rosabal F: Cytoarchitecture of the frontal lobe of the squirrel monkey. J Comp Neurol 1967;130:87–108.
  49. Sanides F: The architecture of the cortical taste nerve areas in squirrel monkey (Saimiri sciureus) and their relationships to insular, sensorimotor and prefrontal regions. Brain Res 1968;8:97–124.
  50. Goldman-Rakic PS: The ‘psychic cell’ of Ramon y Cajal. Prog Brain Res 2002;136:427–434.
  51. Fuster JM: The prefrontal cortex – an update: time is of the essence. Neuron 2001;30:319–333.
  52. Price JL: Free will versus survival: brain systems that underlie intrinsic constraints on behavior. J Comp Neurol 2005;493:132–139.
  53. Barbas H, Zikopoulos B: The prefrontal cortex and flexible behavior. Neuroscientist 2007;13:532–545.
  54. Kozorovitskiy Y, Gross CG, Kopil C, Battaglia L, McBreen M, Stranahan AM, Gould E: Experience induces structural and biochemical changes in the adult primate brain. Proc Natl Acad Sci USA 2005;102:17478–17482.
  55. Rosenzweig MR: Effects of differential experience on the brain and behavior. Dev Neuropsychol 2003;24:523–540.
  56. Dong WK, Greenough WT: Plasticity of nonneuronal brain tissue: roles in developmental disorders. Ment Retard Dev Disabil Res Rev 2004;10:85–90.
  57. Fox C, Merali Z, Harrison C: Therapeutic and protective effect of environmental enrichment against psychogenic and neurogenic stress. Behav Brain Res 2006;175:1–8.
  58. Moncek F, Duncko R, Johansson BB, Jezova D: Effect of environmental enrichment on stress related systems in rats. J Neuroendocrinol 2004;16:423–431.
  59. Schrijver NC, Pallier PN, Brown VJ, Wurbel H: Double dissociation of social and environmental stimulation on spatial learning and reversal learning in rats. Behav Brain Res 2004;152:307–314.
  60. Stetz MC, Thomas ML, Russo MB, Stetz TA, Wildzunas RM, McDonald JJ, Wiederhold BK, Romano JA Jr: Stress, mental health, and cognition: a brief review of relationships and countermeasures. Aviat Space Environ Med 2007;78:B252–B260.
  61. Foa EB, Kozak MJ: Emotional processing of fear: exposure to corrective information. Psychol Bull 1986;99:20–35.
  62. De Raedt R: Does neuroscience hold promise for the further development of behavior therapy? The case of emotional change after exposure in anxiety and depression. Scand J Psychol 2006;47:225–236.
  63. Epstein S: Natural healing processes of the mind: graded stress inoculation as an inherent coping mechanism; in Meichenbaum D, Jaremko ME (eds): Stress Reduction and Prevention. New York, Plenum Press, 1983, pp 39–66.

 goto top of outline Author Contacts

David M. Lyons
1201 Welch Rd
MSLS P104
Stanford, CA 94305-5485 (USA)
Tel. +1 650 725 5931, Fax +1 650 498 7761, E-Mail dmlyons@stanford.edu


 goto top of outline Article Information

Received: January 9, 2009
Accepted: January 9, 2009
Published online: June 17, 2009
Number of Print Pages : 7
Number of Figures : 3, Number of Tables : 1, Number of References : 63


 goto top of outline Publication Details

Developmental Neuroscience

Vol. 31, No. 4, Year 2009 (Cover Date: June 2009)

Journal Editor: Levison S.W. (Newark, N.J.)
ISSN: 0378-5866 (Print), eISSN: 1421-9859 (Online)

For additional information: http://www.karger.com/DNE


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