Abstract
Background
Processing negatively and positively valenced stimuli involves multiple brain regions
including the amygdala and ventral striatum (VS). Posttraumatic stress disorder (PTSD)
is often associated with hyperresponsivity to negatively valenced stimuli, yet recent
evidence also points to deficient positive valence functioning. It is yet unclear
what the relative contribution is of such opposing valence processing shortly after
trauma to the development of chronic PTSD.
Methods
Neurobehavioral indicators of motivational positive versus negative valence sensitivities
were longitudinally assessed in 171 adults (87 females, age = 34.19 ± 11.47 years)
at 1, 6, and 14 months following trauma exposure (time point 1 [TP1], TP2, and TP3,
respectively). Using a gambling functional magnetic resonance imaging paradigm, amygdala
and VS functionality (activity and functional connectivity with the prefrontal cortex)
in response to rewards versus punishments were assessed with relation to PTSD severity
at different time points. The effect of valence processing was depicted behaviorally
by the amount of risk taken to maximize reward.
Results
PTSD severity at TP1 was associated with greater neural functionality in the amygdala
(but not in the VS) toward punishments versus rewards, and with fewer risky choices.
PTSD severity at TP3 was associated with decreased neural functionality in both the
VS and the amygdala toward rewards versus punishments at TP1 (but not with risky behavior).
Explainable machine learning revealed the primacy of VS-biased processing, over the
amygdala, in predicting PTSD severity at TP3.
Conclusions
These results highlight the importance of biased neural responsivity to positive relative
to negative motivational outcomes in PTSD development. Novel therapeutic strategies
early after trauma may thus target both valence fronts.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological Psychiatry: Cognitive Neuroscience and NeuroimagingAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Neural circuit motifs in valence processing.Neuron. 2018; 100: 436-452
- Research Domain Criteria (RDoC): Toward a new classification framework for research on mental disorders.Am J Psychiatry. 2010; 167: 748-751
- Toward the future of psychiatric diagnosis: The seven pillars of RDoC.BMC Med. 2013; 11: 126
- Emotional environments retune the valence of appetitive versus fearful functions in nucleus accumbens.Nat Neurosci. 2008; 11: 423-425
- Stress transforms lateral habenula reward responses into punishment signals.Proc Natl Acad Sci U S A. 2019; 116: 12488-12493
- A behavioral and neural evaluation of prospective decision-making under risk.J Neurosci. 2010; 30: 14380-14389
- Neural computations of threat.Trends Cogn Sci. 2021; 25: 151-171
- The effects of acute stress on core executive functions: A meta-analysis and comparison with cortisol.Neurosci Biobehav Rev. 2016; 68: 651-668
- How positive affect modulates cognitive control: Reduced perseveration at the cost of increased distractibility.J Exp Psychol Learn Mem Cogn. 2004; 30: 343-353
- Voluntary action and cognitive control from a cognitive neuroscience perspective.in: Maasen S. Prinz W. Roth G. Voluntary Action: Brains, Minds, and Sociality. Oxford University Press, London2003: 49-85
- Chapter two - Between persistence and flexibility: The yin and yang of action control.in: Elliot A.J. Advances in Motivation Science, vol 2. Elsevier, New York2015: 33-67
- Reminiscing about positive memories buffers acute stress responses.Nat Hum Behav. 2017; 10093
- Resilient individuals use positive emotions to bounce back from negative emotional experiences.J Pers So Psychol. 2004; 86: 320-333
- Cognitive flexibility predicts PTSD symptoms: Observational and interventional studies.Front Psychiatry. 2018; 9: 477
- The neuropsychology of fear and anxiety: A foundation for reinforcement sensitivity theory.in: Corr P.J. The Reinforcement Sensitivity Theory of Personality. Cambridge University Press, Cambridge, United Kingdom2008: 44-94
- Imbalance of approach and avoidance: The yin and yang of anxiety disorders.Biol Psychiatry. 2009; 66: 1072-1074
- Sacrificing reward to avoid threat: Characterizing PTSD in the context of a trauma-related approach-avoidance conflict task.J Abnorm Psychol. 2020; 129: 457-468
- Neural systems underlying approach and avoidance in anxiety disorders.Dialogues Clin Neurosci. 2010; 12: 517-531
- Quantitative meta-analysis of neural activity in posttraumatic stress disorder.Biol Mood Anxiety Disord. 2012; 2: 9
- Emotion and cognition interactions in PTSD: A review of neurocognitive and neuroimaging studies.Front Integr Neurosci. 2012; 6: 89
- Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD.Psychoneuroendocrinology. 2016; 70: 1-9
- Altered emotional interference processing in the amygdala and insula in women with post-traumatic stress disorder.NeuroImage Clin. 2013; 2: 43-49
- Reduced hippocampal and amygdala activity predicts memory distortions for trauma reminders in combat-related PTSD.J Psychiatr Res. 2011; 45: 660-669
- Revisiting the role of the amygdala in posttraumatic stress disorder.in: Ferry B. The Amygdala - Where Emotions Shape Perception, Learning and Memories. InTechOpen, London2017: 67585
- The centrality of fear extinction in linking risk factors to PTSD: A narrative review.Neurosci Biobehav Rev. 2016; 69: 15-35
- Emotion circuits in the brain.Annu Rev Neurosci. 2000; 23: 155-184
- The study of fear extinction: Implications for anxiety disorders.Am J Psychiatry. 2011; 168: 1255-1265
- The neural consequences of combat stress: Long-term follow-up.Mol Psychiatry. 2012; 17: 116-118
- Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors.Transl Psychiatry. 2020; 10: 208
- Posttraumatic stress symptoms and aversion to ambiguous losses in combat veterans.Depress Anxiety. 2016; 33: 606-613
- Imbalanced neural responsivity to risk and reward indicates stress vulnerability in humans.Cereb Cortex. 2013; 23: 28-35
- Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.Hum Brain Mapp. 2016; 37: 1120-1135
- Exposure-based therapy changes amygdala and hippocampus resting-state functional connectivity in patients with posttraumatic stress disorder.Depress Anxiety. 2018; 35: 974-984
- Reward functioning in PTSD: A systematic review exploring the mechanisms underlying anhedonia.Neurosci Biobehav Rev. 2015; 51: 189-204
- The reward system and post-traumatic stress disorder: Does trauma affect the way we interact with positive stimuli?.Chronic Stress (Thousand Oaks). 2021; 5 (2470547021996006)
- Brain reward circuitry beyond the mesolimbic dopamine system: A neurobiological theory.Neurosci Biobehav Rev. 2010; 35: 129-150
- Ventral striatum reactivity to reward and recent life stress interact to predict positive affect.Biol Psychiatry. 2012; 72: 157-163
- Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder.Am J Psychiatry. 2009; 166: 702-710
- Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram.J Psychopharmacol. 2012; 26: 677-688
- Functional neuroimaging of reward circuitry responsivity to monetary gains and losses in posttraumatic stress disorder.Biol Psychiatry. 2009; 66: 1083-1090
- Altered reward processing in the nucleus accumbens and mesial prefrontal cortex of patients with posttraumatic stress disorder.Neuropsychologia. 2008; 46: 2836-2844
- Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.PLoS One. 2014; 9e103653
- Inflammation, reward circuitry and symptoms of anhedonia and PTSD in trauma-exposed women.Soc Cogn Affect Neurosci. 2020; 15: 1046-1055
- Altered resting state functional connectivity of fear and reward circuitry in comorbid PTSD and major depression.Depress Anxiety. 2017; 34: 641-650
- Diagnostic and Statistical Manual of Mental Disorders.5th ed. American Psychiatric Press, Washington, DC2013
- Parsing inter- and intra-individual variability in key nervous system mechanisms of stress responsivity and across functional domains.Neurosci Biobehav Rev. 2020; 120: 550-564
- 636,120 ways to have posttraumatic stress disorder.Perspect Psychol Sci. 2013; 8: 651-662
- One quintillion ways to have PTSD comorbidity: Recommendations for the disordered DSM-5.Psychol Inj Law. 2014; 7: 61-74
- Biological studies of post-traumatic stress disorder.Nat Rev Neurosci. 2012; 13: 769-787
- Current status on behavioral and biological markers of PTSD.Neurosci Biobehav Rev. 2013; 37: 860-895
- Anterior prefrontal brain activity during emotion control predicts resilience to post-traumatic stress symptoms.Nat Hum Behav. 2021; 5: 1055-1064
- Neurobehavioral moderators of post-traumatic stress disorder trajectories: Prospective fMRI study of recent trauma survivors.Eur J Psychotraumatol. 2019; 10: 1683941
- Estimating the risk of PTSD in recent trauma survivors: Results of the International Consortium to Predict PTSD (ICPP).World Psychiatry. 2019; 18: 77-87
- Prevention of posttraumatic stress disorder by early treatment: Results from the Jerusalem trauma outreach and prevention study.Arch Gen Psychiatry. 2012; 69: 166-176
- Human vulnerability to stress depends on amygdala’s predisposition and hippocampal plasticity.Proc Natl Acad Sci U S A. 2009; 106: 14120-14125
- Psychometric properties of the PTSD checklist (PCL).Behav Res Ther. 1996; 34: 669-673
- The Clinician-Administered PTSD Scale for DSM–5 (CAPS-5): Development and initial psychometric evaluation in military veterans.Psychol Assess. 2018; 30: 383-395
- The role of the amygdala in signaling prospective outcome of choice.Neuron. 2002; 33: 983-994
- Brain activity dissociates mentalization from motivation during an interpersonal competitive game.Brain Imaging Behav. 2009; 3: 24-37
- Altered reward-related neural responses in non-manifesting carriers of the Parkinson disease related LRRK2 mutation.Brain Imaging Behav. 2019; 13: 1009-1020
- Reward-related dorsal striatal activity differences between former and current cocaine dependent individuals during an interactive competitive game.PLoS One. 2012; 7e34917
- From animal model to human brain networking: Dynamic causal modeling of motivational systems.J Neurosci. 2012; 32: 7218-7224
- fMRIPrep: A robust preprocessing pipeline for functional MRI.Nat Methods. 2019; 16: 111-116
- Nipype: A flexible, lightweight and extensible neuroimaging data processing framework in Python.Front Neuroinform. 2011; 5: 13
- The Human Brainnetome Atlas: A new brain atlas based on connectional architecture.Cereb Cortex. 2016; 26: 3508-3526
- Data Descriptor: A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei.Sci Data. 2018; 5: 180063
- Region of interest analysis using an SPM toolbox.Neuroimage. 2003; 19: 1303-1316
- A generalized form of context-dependent psychophysiological interactions (gPPI): A comparison to standard approaches.Neuroimage. 2012; 61: 1277-1286
- Conn: A functional connectivity toolbox for correlated and anticorrelated brain networks.Brain Connect. 2012; 2: 125-141
- Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression.Brain. 2016; 139: 3296-3309
- Individual differences in sensitivity to reward and punishment and neural activity during reward and avoidance learning.Soc Cogn Affect Neurosci. 2014; 10: 1219-1227
- Dissociable systems for gain- and loss-related value predictions and errors of prediction in the human brain.J Neurosci. 2006; 26: 9530-9537
- The AURORA Study: A longitudinal, multimodal library of brain biology and function after traumatic stress exposure.Mol Psychiatry. 2020; 25: 283-296
- Abstract reward and punishment representations in the human orbitofrontal cortex.Nat Neurosci. 2001; 4: 95-102
- Controlling the false discovery rate: A practical and powerful approach to multiple testing.J R Stat Soc Ser B. 1995; 57: 289-300
- A unified approach to interpreting model predictions.In: Adv Neural Inf Process Syst. 2017; 30: 4766-4775
- From local explanations to global understanding with explainable AI for trees.Nat Mach Intell. 2020; 2: 56-67
- The functional neuroanatomy of PTSD: A critical review.Prog Brain Res. 2007; 167: 151-169
- The neurocircuitry of fear, stress and anxiety disorders.Neuropsychopharmacology. 2010; 35: 169-191
- Amygdala reactivity and anterior cingulate habituation predict posttraumatic stress disorder symptom maintenance after acute civilian trauma.Biol Psychiatry. 2017; 81: 1023-1029
- Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo.J Neurosci. 2002; 22: 324-337
- Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons.J Neurosci. 2003; 23: 8800-8807
- The amygdala modulates prefrontal cortex activity relative to conditioned fear.Nature. 1999; 402: 294-296
- Neural substrates for voluntary suppression of negative affect: A functional magnetic resonance imaging study.Biol Psychiatry. 2005; 57: 210-219
- Dissociable functions in the medial and lateral orbitofrontal cortex: Evidence from human neuroimaging studies.Cereb Cortex. 2000; 10: 308-317
- A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.Arch Gen Psychiatry. 2005; 62: 273-281
- Trauma modulates amygdala and medial prefrontal responses to consciously attended fear.Neuroimage. 2006; 29: 347-357
- Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder.Neuroimage. 2011; 56: 881-889
- Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder.Arch Gen Psychiatry. 2008; 65: 568-576
- Functional connectivity bias of the orbitofrontal cortex in drug-free patients with major depression.Biol Psychiatry. 2010; 67: 161-167
- Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression.Brain Struct Funct. 2008; 213: 93-118
- Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: State versus trait vulnerability markers of depression in bipolar disorder.Biol Psychiatry. 2010; 67: 422-431
- A causal model of post-traumatic stress disorder: Disentangling predisposed from acquired neural abnormalities.Trends Cogn Sci. 2013; 17: 337-347
- Regional specialization within the human striatum for diverse psychological functions.Proc Natl Acad Sci U S A. 2016; 113: 1907-1912
- Informatic parcellation of the network involved in the computation of subjective value.Soc Cogn Affect Neurosci. 2013; 9: 1289-1302
- Functional connectivity and coactivation of the nucleus accumbens: A combined functional connectivity and structure-based meta-analysis.J Cogn Neurosci. 2011; 23: 2864-2877
- The organization of the human striatum estimated by intrinsic functional connectivity.J Neurophysiol. 2012; 108: 2242-2263
- Putting a spin on the dorsal-ventral divide of the striatum.Trends Neurosci. 2004; 27: 468-474
- Prefrontal cortex in the rat: Projections to subcortical autonomic, motor, and limbic centers.J Comp Neurol. 2005; 492: 145-177
- Prefrontal cortex mediates extinction of responding by two distinct neural mechanisms in accumbens shell.J Neurosci. 2012; 32: 726-737
- Ventromedial prefrontal cortex damage is associated with decreased ventral striatum volume and response to reward.J Neurosci. 2016; 36: 5047-5054
- Corticostriatal pathways contribute to the natural time course of positive mood.Nat Commun. 2015; 6: 10065
- Multimodal frontostriatal connectivity underlies individual differences in self-esteem.Soc Cogn Affect Neurosci. 2015; 10: 364-370
- What good are positive emotions?.Rev Gen Psychol. 1998; 2: 300-319
- What good are positive emotions in crisis?.J Pers Soc Psychol. 2003; 84: 365-376
- Post-traumatic stress disorder in serious accidental injury: 3-Year follow-up study.Br J Psychiatry. 2008; 192: 376-383
- Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event.Biol Psychiatry. 1998; 44: 1305-1313
- Long term course of chronic posttraumatic stress disorder in traffic accident victims: A three-year prospective follow-up study.Behav Res Ther. 2001; 39: 1449-1458
- Longitudinal course of posttraumatic stress disorder and posttraumatic stress disorder symptoms in a community sample of adolescents and young adults.Am J Psychiatry. 2005; 162: 1320-1327
- PTSD following terrorist attacks: A prospective evaluation.Am J Psychiatry. 2005; 162: 1188-1191
- Posttraumatic stress disorder in the national comorbidity survey.Arch Gen Psychiatry. 1995; 52: 1048-1060
- Neuroanatomical risk factors for post traumatic stress disorder (PTSD) in recent trauma survivors.Biol Psychiatry Cogn Neurosci Neuroimaging. 2020; 5: 311-319
- A shift from value- to saliency- neural encoding of subjective value in combat veterans with PTSD during decision making under uncertainty.bioRxiv. 2020; https://doi.org/10.1101/2020.04.14.041467
- Affective valence in the brain: Modules or modes?.Nat Rev Neurosci. 2019; 20: 225-234
- The amygdala and reward.Nat Rev Neurosci. 2002; 3: 563-573
- Deep learning model of fMRI connectivity predicts PTSD symptom trajectories in recent trauma survivors.NeuroImage. 2021; 28: 118242
- Dissociable responses to punishment in distinct striatal regions during reversal learning.Neuroimage. 2010; 51: 1459-1467
- Trauma affects prospective relationships between reward-related ventral striatal and amygdala activation and 1-year future hypo/mania trajectories.Biol Psychiatry. 2021; 89: 868-877
- The amygdala, reward and emotion.Trends Cogn Sci. 2007; 11: 489-497
- The role of brain reward pathways in stress resilience and health.Neurosci Biobehav Rev. 2018; 95: 559-967
Article Info
Publication History
Published online: September 14, 2021
Accepted:
September 1,
2021
Received in revised form:
August 11,
2021
Received:
April 1,
2021
Identification
Copyright
© 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
