TY - JOUR
T1 - Neural Responsivity to Reward Versus Punishment Shortly After Trauma Predicts Long-Term Development of Posttraumatic Stress Symptoms
AU - Ben-Zion, Ziv
AU - Shany, Ofir
AU - Admon, Roee
AU - Keynan, Nimrod Jackob
AU - Avisdris, Netanell
AU - Balter, Shira Reznik
AU - Shalev, Arieh Y.
AU - Liberzon, Israel
AU - Hendler, Talma
N1 - Funding Information:
This work was supported by National Institute of Mental Health Grant No. R01-MH-103287 (to AS [principal investigator], IL [co-investigator, subcontractor], and TH [co-investigator, subcontractor]), U.S. Department of Defense Grant No. W81XWH-16-C-0198 , the Human Brain Project from the European Union Seventh Framework Program (FP7/2007-2013) under Grant No. 604102 , the European Union’s Horizon 2020 research and innovation programme under Grant Nos. 777084 (Dynamic Modelling of Resilience [DynaMORE]) and 945539 (Human Brain Project SGA3), and the Israel Science Foundation (Grant No. 2923/20 ), within the Israel Precision Medicine Partnership program. The Sagol School of Neuroscience at Tel Aviv University, Sagol Brain Institute at Tel Aviv Sourasky Medical Center, and the Human Brain Project also supported the authors’ fellowships.
Funding Information:
This work was supported by National Institute of Mental Health Grant No. R01-MH-103287 (to AS [principal investigator], IL [co-investigator, subcontractor], and TH [co-investigator, subcontractor]), U.S. Department of Defense Grant No. W81XWH-16-C-0198, the Human Brain Project from the European Union Seventh Framework Program (FP7/2007-2013) under Grant No. 604102, the European Union's Horizon 2020 research and innovation programme under Grant Nos. 777084 (Dynamic Modelling of Resilience [DynaMORE]) and 945539 (Human Brain Project SGA3), and the Israel Science Foundation (Grant No. 2923/20), within the Israel Precision Medicine Partnership program. The Sagol School of Neuroscience at Tel Aviv University, Sagol Brain Institute at Tel Aviv Sourasky Medical Center, and the Human Brain Project also supported the authors’ fellowships. We thank the research team at Tel Aviv Sourasky Medical Center—including Nili Green, Mor Halevi, Sheli Luvton, Yael Shavit, Olga Nevenchannaya, Iris Rashap, Efrat Routledge, and Ophir Leshets—for their major contribution in carrying out this research, including subjects’ recruitment and screening, and performing clinical and neural assessments. We also extend our gratitude to all the participants of this study for their contribution to science. A previous version of this work was published as a preprint on bioRxiv: https://www.biorxiv.org/content/10.1101/2021.03.08.434335v2. The authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Neurobehavioral Moderators of Post-traumatic Disease Trajectories; https://clinicaltrials.gov/ct2/show/NCT03756545; NCT03756545.
Publisher Copyright:
© 2021 Society of Biological Psychiatry
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Amygdala
KW - Functional MRI
KW - Negative valence system
KW - PTSD
KW - Positive valence system
KW - Posttraumatic stress disorder
KW - Ventral striatum
KW - fMRI
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U2 - 10.1016/j.bpsc.2021.09.001
DO - 10.1016/j.bpsc.2021.09.001
M3 - Article
C2 - 34534702
AN - SCOPUS:85120430931
VL - 7
SP - 150
EP - 161
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
SN - 2451-9022
IS - 2
ER -