Ziv Ben-Zion, PhD
Research & Publications
I'm interested in the field of affective neuroscience, the study of neural mechanisms of emotions and emotional disorders. My goal is to conduct research that will allow us to better understand the complex interactions between human behavior, emotions, and our brain structure and function. Specifically, I wish to focus on stress- and anxiety-related disorders, having a personal motivation to improve treatments for individuals suffering from these debilitating disorders.
Extensive Research Description
Neurobiological processes that take place during the year that follows a traumatic event critically determine who will develop post-traumatic stress disorder (PTSD) and who will not. Among survivors of single traumatic incidents, the chronic disorder frequently follows a failure to recover from early PTSD symptoms. Longitudinal studies further describe diverging early symptom trajectories of non-remission, rapid remission, and delayed remission from early post-traumatic normative responses. To better understand the underlying neurobiology, these observable symptom trajectories must be linked with cognitive deficits and pertinent brain alterations (either present initially or developing simultaneously). To date, however, large-scale, prospective longitudinal studies of PTSD symptom trajectories that involve repeated cognitive and neuroimaging assessment are critically missing.
My doctoral research was designed as an observational prospective study of consecutive trauma survivors admitted to a general hospital’s emergency department (ED) following traumatic incidents. The overarching goal was to uncover the neurocognitive moderators underlying PTSD symptom trajectories. To achieve this goal, we repeatedly and simultaneously evaluated trauma survivors’ clinical symptoms, cognitive functioning, brain structure and function, at 1-, 6-, and 14-months following trauma exposure. Results can be organized into three objectives.
First, we utilized advanced computational methodology to characterize and classify individuals within 1-month following trauma, based on the collected multi-parametric measurements. We successfully identified subgroups of individuals (significantly related to PTSD clinical diagnosis, but not identical to it), with a unique set of potential mechanism-related cognitive and neural biomarkers differentiating between them, in line with previously documented PTSD literature (Ben-Zion et al., 2020). Second, we investigated which objective multi-parametric indices, collected shortly after trauma exposure, could be of value in predicting individuals’ long-term clinical PTSD symptoms. We found both a cognitive construct that emerged as a significant predictor of PTSD development (i.e., cognitive flexibility; Ben-Zion et al., 2018), as well as neuroanatomical risk factors for PTSD severity (Ben-Zion et al., 2019), both of which could guide early management and objective long-term monitoring. Finally, we elucidated the neurobehavioral mechanisms underlying motivational processing in PTSD development. During a competitive decision-making paradigm, we found that increased behavioral risk-aversion and imbalanced neural responsivity to punishments vs. rewards, early after trauma, were predictive of PTSD symptoms 13-months later on (Ben-Zion et al., 2021).
In summary, by linking observed symptoms with cognitive functioning and neural alternations, findings from this thesis work enhanced our understating of the nature of traumatic stress responses and its aftermath, informing both the pathogenesis of PTSD and the science of resilience and recovery from trauma. Lower cognitive flexibility in PTSD might be manifested as imbalanced neural responsivity to positive vs. negative valance stimuli, potentially involving key brain structures such as the hippocampus and the amygdala. Future studies using similar integrative, mechanism-oriented, exploratory approaches, may lead to improved early treatment and prevention of PTSD, thus improving the life of trauma survivors and increasing the cost-effectiveness of personalized interventions.
During my postdoctoral training at Yale, I’ve continued to work on this unique dataset with the additional expertise of my mentors and lab members. First, I conducted a conceptual replication of a recent promising study that identified distinct brain-based biotypes associated with different longitudinal patterns of post-traumatic symptoms (Stevens et al., 2021). Results did not replicate in our sample, suggesting that caution is warranted when attempting to define subtypes of psychiatric vulnerability using neural indices before treatment implications can be fully realized (Ben-Zion et al., In Press). As one of the first replications attempts in the fields of neuroimaging and psychiatry, I believe that this work will critically push the fields toward future replication studies to identify more stable and generalizable brain-based biotypes of psychopathology. Second, I’ve explored the longitudinal association between structural brain changes and PTSD symptom trajectories during the first critical year following trauma exposure. Utilizing a novel longitudinal segmentation pipeline assessing hippocampus and amygdala subregions volume, together with an advanced Bayesian multilevel modeling approach, we found that lower initial volumes of the hippocampus (specifically, the subiculum and CA1 subregions), and larger amygdala volumes, are associated with non-remitting PTSD, thus supporting the idea volumetric abnormalities serve as predisposing vulnerability factors for PTSD development (Ben-Zion et al., 2022). Moreover, no time-dependent volumetric changes were observed (from 1- to 14-months post-trauma) across all individuals or between those who developed PTSD and those who did not, thus not supporting the idea of progressive, stress-related atrophy of hippocampal or amygdala subregions. Third, collaborations with experts in computer and data sciences demonstrated the use of deep-learning models (Sheynin et al., 2021) and advanced statistical learning methods (Schultebraucks*, Ben-Zion* et al., 2022) to predict the risk to develop chronic PTSD from early cognitive and neural measures. Future work could further delineate the mechanisms that underlie such prediction models, and potentially improve single-patient characterization and preventive treatment.
Furthermore, I’ve contributed to several research projects led by fellow postdocs in my labs, while also learning from them and improving my scientific skills and knowledge. First, using robust Bayesian statistics and two independent samples of veterans, we showed that the amygdala’s response to pain is lower in PTSD individuals, and is associated with greater emotional numbing symptoms (Korem et al., 2022). Second, we demonstrated that machine-learning models, based on routinely collected nursing data in an acute care setting, can reliably predict patients at risk for delirium (Spiller et al., 2022). Finally, I’ve co-led a pre-registered scoping review aiming to map the availability of translated and evaluated screening questionnaires for PTSD. Overall, we screened 866 studies, of which 126 were included, with a total of 128 translations of 12 different PTSD questionnaires (Hoffman*, Ben-Zion* et al., 2022). Results showed very large heterogeneity in the translation and validation processes, making a quality assessment impractical. This highlights both the need for more transparency in translation processes and the need for more rigorous evaluation methods. Furthermore, translations into languages spoken in middle- or low-income countries were underrepresented, emphasizing that more investment is needed in those neglected countries and language groups. Finally, as the majority of existing translations (73%) were not accessible, we developed an online open repository for translated & validated PTSD screening questionnaires (tobiasrspiller.github.io/PTSD-Screener-Repo/).
Currently, I’m learning the field of computational decision-making neuroscience (Prof. Levy) and expanding my clinical knowledge to anxiety- and stress-related disorders (Prof. Harpaz-Rotem). My main research aims to characterize neural computations of value (how good or bad something is), uncertainty (how precise these value estimations can be), and prediction error (the discrepancy between expected and observed information) across different processes (learning, decision-making, memory) and domains (positive vs. negative valance). My hypothesis is that estimations of this basic set of computations in different processes and domains rely on both shared and distinct neural mechanisms; and that different psychopathology symptoms are associated with the type and magnitude of alterations in these computations. To test these computations within individuals, I’ve developed a naturalistic computer-game task of a new virtual world, in which participants learn the associations between different stimuli and outcomes; choose between different stimuli; and update their learning when circumstances change based on previous memory. In the short term, we aim to conduct a large online behavioral study (N=1000) and an fMRI study (N=100) testing our ecological task within individuals from the general population. Using computational modeling and advanced classification techniques, we will characterize individuals based on their behavioral and neural patterns, and explore this objective classification in relation to stress- and anxiety-related symptoms. In the long term, we hope to use this task to study various mental health symptoms (beyond stress and anxiety) based on objective neurobehavioral individual profiles of value, uncertainty, and prediction error in different processes and domains. This approach could inform mechanism-based objective diagnoses and individually tailored effective interventions.
Anxiety Disorders; Biology; Decision Making; Emotions; Motivation; Psychiatry; Psychology; Punishment; Reward; Stress Disorders, Post-Traumatic; Stress, Psychological; Neuroimaging; Functional Neuroimaging
- Evaluating the Evidence for Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of TraumaBen-Zion Z, Spiller T, Keynan J, Admon R, Levy I, Liberzon I, Shalev A, Hendler T, Harpaz-Rotem I. Evaluating the Evidence for Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma American Journal Of Psychiatry 2023, 180: 146-154. PMID: 36628514, PMCID: PMC9898083, DOI: 10.1176/appi.ajp.20220271.
- Mapping the availability of translated versions of posttraumatic stress disorder screening questionnaires for adults: A scoping reviewHoffman J, Ben-Zion Z, Arévalo A, Duek O, Greene T, Hall B, Harpaz-Rotem I, Liddell B, Locher C, Morina N, Nickerson A, Pfaltz M, Schick M, Schnyder U, Seedat S, Shatri F, Sit H, von Känel R, Spiller T. Mapping the availability of translated versions of posttraumatic stress disorder screening questionnaires for adults: A scoping review European Journal Of Psychotraumatology 2022, 13: 2143019. PMCID: PMC9724641, DOI: 10.1080/20008066.2022.2143019.
- Longitudinal volumetric evaluation of hippocampus and amygdala subregions in recent trauma survivorsBen-Zion Z, Korem N, Spiller TR, Duek O, Keynan JN, Admon R, Harpaz-Rotem I, Liberzon I, Shalev AY, Hendler T. Longitudinal volumetric evaluation of hippocampus and amygdala subregions in recent trauma survivors Molecular Psychiatry 2022, 28: 657-667. PMID: 36280750, PMCID: PMC9918676, DOI: 10.1038/s41380-022-01842-x.
- Delirium screening in an acute care setting with a machine learning classifier based on routinely collected nursing data: A model development studySpiller TR, Tufan E, Petry H, Böttger S, Fuchs S, Duek O, Ben-Zion Z, Korem N, Harpaz-Rotem I, von Känel R, Ernst J. Delirium screening in an acute care setting with a machine learning classifier based on routinely collected nursing data: A model development study Journal Of Psychiatric Research 2022, 156: 194-199. PMID: 36252349, DOI: 10.1016/j.jpsychires.2022.10.018.
- Emotional numbing in PTSD is associated with lower amygdala reactivity to painKorem N, Duek O, Ben-Zion Z, Kaczkurkin AN, Lissek S, Orederu T, Schiller D, Harpaz-Rotem I, Levy I. Emotional numbing in PTSD is associated with lower amygdala reactivity to pain Neuropsychopharmacology 2022, 47: 1913-1921. PMID: 35945274, PMCID: PMC9485255, DOI: 10.1038/s41386-022-01405-2.
- P658. Longitudinal Evaluation of Hippocampal Volume in Recent Trauma SurvivorsBen-Zion Z, Keynan N, Admon R, Liberzon I, Shalev A, Hendler T. P658. Longitudinal Evaluation of Hippocampal Volume in Recent Trauma Survivors Biological Psychiatry 2022, 91: s356-s357. DOI: 10.1016/j.biopsych.2022.02.895.
- Social Robots for Supporting Post-traumatic Stress Disorder Diagnosis and TreatmentLaban G, Ben-Zion Z, Cross ES. Social Robots for Supporting Post-traumatic Stress Disorder Diagnosis and Treatment Frontiers In Psychiatry 2022, 12: 752874. PMID: 35185629, PMCID: PMC8854768, DOI: 10.3389/fpsyt.2021.752874.
- Assessment of early neurocognitive functioning increases the accuracy of predicting chronic PTSD riskSchultebraucks K, Ben-Zion Z, Admon R, Keynan JN, Liberzon I, Hendler T, Shalev AY. Assessment of early neurocognitive functioning increases the accuracy of predicting chronic PTSD risk Molecular Psychiatry 2022, 27: 2247-2254. PMID: 35082440, DOI: 10.1038/s41380-022-01445-6.
- COVID-19 epidemic-induced changes in mood and anxiety mediate the relationship between resilience and symptoms of depression and generalized anxiety in sexual assault survivorsArmon DB, Fine NB, Seligman Z, Ginzburg K, Ben-Zion Z. COVID-19 epidemic-induced changes in mood and anxiety mediate the relationship between resilience and symptoms of depression and generalized anxiety in sexual assault survivors Journal Of Affective Disorders Reports 2021, 6: 100252. PMID: 35036985, PMCID: PMC8743166, DOI: 10.1016/j.jadr.2021.100252.
- Neural Responsivity to Reward Versus Punishment Shortly After Trauma Predicts Long-Term Development of Posttraumatic Stress SymptomsBen-Zion Z, Shany O, Admon R, Keynan NJ, Avisdris N, Balter SR, Shalev AY, Liberzon I, Hendler T. Neural Responsivity to Reward Versus Punishment Shortly After Trauma Predicts Long-Term Development of Posttraumatic Stress Symptoms Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2021, 7: 150-161. PMID: 34534702, DOI: 10.1016/j.bpsc.2021.09.001.
- Deep learning model of fMRI connectivity predicts PTSD symptom trajectories in recent trauma survivorsSheynin S, Wolf L, Ben-Zion Z, Sheynin J, Reznik S, Keynan JN, Admon R, Shalev A, Hendler T, Liberzon I. Deep learning model of fMRI connectivity predicts PTSD symptom trajectories in recent trauma survivors NeuroImage 2021, 238: 118242. PMID: 34098066, PMCID: PMC8350148, DOI: 10.1016/j.neuroimage.2021.118242.
- Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivorsBen-Zion Z, Zeevi Y, Keynan NJ, Admon R, Kozlovski T, Sharon H, Halpern P, Liberzon I, Shalev AY, Benjamini Y, Hendler T. Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors Translational Psychiatry 2020, 10: 208. PMID: 32594097, PMCID: PMC7320966, DOI: 10.1038/s41398-020-00898-z.
- Neuroanatomical Risk Factors for Post-Traumatic Stress Disorder (PTSD) in Recent Trauma SurvivorsBen-Zion Z, Artzi M, Niry D, Kenyan N, Zeevi Y, Admon R, Sharon H, Halpern P, Liberzon I, Shalev A, Hendler T. Neuroanatomical Risk Factors for Post-Traumatic Stress Disorder (PTSD) in Recent Trauma Survivors Biological Psychiatry 2020, 87: s422. DOI: 10.1016/j.biopsych.2020.02.1077.
- Hippocampal-Amygdala Resting State Functional Connectivity Serves as Resilience Factor for Short- and Long-Term Stress ExposureBen-Zion Z, Keynan N, Admon R, Sharon H, Halpern P, Liberzon I, Shalev A, Henlder T. Hippocampal-Amygdala Resting State Functional Connectivity Serves as Resilience Factor for Short- and Long-Term Stress Exposure Biological Psychiatry 2020, 87: s88-s89. DOI: 10.1016/j.biopsych.2020.02.248.
- Neuroanatomical Risk Factors for Posttraumatic Stress Disorder in Recent Trauma SurvivorsBen-Zion Z, Artzi M, Niry D, Keynan NJ, Zeevi Y, Admon R, Sharon H, Halpern P, Liberzon I, Shalev AY, Hendler T. Neuroanatomical Risk Factors for Posttraumatic Stress Disorder in Recent Trauma Survivors Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2019, 5: 311-319. PMID: 31973980, PMCID: PMC7064406, DOI: 10.1016/j.bpsc.2019.11.003.
- Neurobehavioral moderators of post-traumatic stress disorder (PTSD) trajectories: study protocol of a prospective MRI study of recent trauma survivorsBen-Zion Z, Fine NB, Keynan NJ, Admon R, Halpern P, Liberzon I, Hendler T, Shalev AY. Neurobehavioral moderators of post-traumatic stress disorder (PTSD) trajectories: study protocol of a prospective MRI study of recent trauma survivors European Journal Of Psychotraumatology 2019, 10: 1683941. PMID: 31762950, PMCID: PMC6853209, DOI: 10.1080/20008198.2019.1683941.
- F30. Neural Activation During Emotion Modulation Associated With Early PTSD Symptoms SeveritySheynin J, Duval E, Lokshina Y, Angstadt M, Ben-Zion Z, Keynan N, Halevy M, Green N, Admon R, Hendler T, Shalev A, Liberzon I. F30. Neural Activation During Emotion Modulation Associated With Early PTSD Symptoms Severity Biological Psychiatry 2019, 85: s223-s224. DOI: 10.1016/j.biopsych.2019.03.567.
- The Anger-Infused Ultimatum Game: A Reliable and Valid Paradigm to Induce and Assess AngerGilam G, Abend R, Shani H, Ben-Zion Z, Hendler T. The Anger-Infused Ultimatum Game: A Reliable and Valid Paradigm to Induce and Assess Anger Emotion 2019, 19: 84-96. PMID: 29565609, DOI: 10.1037/emo0000435.
- Cognitive Flexibility Predicts PTSD Symptoms: Observational and Interventional StudiesBen-Zion Z, Fine NB, Keynan NJ, Admon R, Green N, Halevi M, Fonzo GA, Achituv M, Merin O, Sharon H, Halpern P, Liberzon I, Etkin A, Hendler T, Shalev AY. Cognitive Flexibility Predicts PTSD Symptoms: Observational and Interventional Studies Frontiers In Psychiatry 2018, 9: 477. PMID: 30337890, PMCID: PMC6180246, DOI: 10.3389/fpsyt.2018.00477.
- Attenuating anger and aggression with neuromodulation of the vmPFC: A simultaneous tDCS-fMRI studyGilam G, Abend R, Gurevitch G, Erdman A, Baker H, Ben-Zion Z, Hendler T. Attenuating anger and aggression with neuromodulation of the vmPFC: A simultaneous tDCS-fMRI study Cortex 2018, 109: 156-170. PMID: 30343211, DOI: 10.1016/j.cortex.2018.09.010.
- Free viewing of sad and happy faces in depression: A potential target for attention bias modificationLazarov A, Ben-Zion Z, Shamai D, Pine DS, Bar-Haim Y. Free viewing of sad and happy faces in depression: A potential target for attention bias modification Journal Of Affective Disorders 2018, 238: 94-100. PMID: 29870821, PMCID: PMC6310000, DOI: 10.1016/j.jad.2018.05.047.
- Transcranial electrical stimulation targeting vmPFC leads to increased acceptance rates in an anger-infused Ultimatum GameGilam G, Abend R, Gurevitch G, Erdman A, Baker H, Ben-Zion Z, Hendler T. Transcranial electrical stimulation targeting vmPFC leads to increased acceptance rates in an anger-infused Ultimatum Game Brain Stimulation 2017, 10: e34. DOI: 10.1016/j.brs.2017.04.053.