PROF. TALMA HENDLER (MD, PhD)

Talma Hendler (MD PhD) is a professor of Psychiatry and Neuroscience at Tel Aviv University, and the founding director of the Sagol Brain Institute Tel-Aviv. Professor Hendler holds an MD from Tel Aviv University and a PhD from SUNY at Stony Brook, NY. and is a licensed psychiatrist in Israel. 

Prof. Hendler leads the #Neuropsychiatry & Neuromodulation research team and an associated investigator of all the other 6 research teams at the Sagol Brain Institute.

Neurobehavioral Moderators of Post-Traumatic Stress Disorder (PTSD) Trajectories

2015 – 2020, Sagol Brain Institute, Tel Aviv, Israel 

This work was supported by award number R01-MH-103287 from the National Institute of Mental Health (NIMH), in collaboration with Prof. Arieh Y. Shalev (NYU) and Prof. Israel Liberzon (Texas A&M).

Background: 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, often incomplete, remission. Symptom trajectories provide an observable dimension of how PTSD develops, or remits. To better understand the underlying neurobiology these trajectories must be linked with pertinent brain alterations, present initially, or developing simultaneously. To date, large scale, prospective longitudinal studies of PTSD symptom trajectories that involve repeated functional and structural neuroimaging assessment, had not been performed.

 

Research Goal: To uncover the neurocognitive moderators underlying PTSD symptom trajectories. To do so, we repeatedly and simultaneously evaluated trauma survivors’ clinical symptoms, cognitive functioning, brain structure and function, at 1-, 6-, and 14-months following trauma exposure (for more details, see study protocol: Ben-Zion et al., 2019). 

Results: 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, 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 which 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 (i.e., hippocampus and cavum septum pellucidum volumes) (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)

Conclusion: By linking observed symptoms with cognitive functioning and neural alternations, findings from this 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 life of trauma survivors and increasing cost-effectiveness of personalized interventions.

Key Publications

Cognitive Flexibility Predicts PTSD Symptoms: Observational and Interventional Studies

Neuroanatomical Risk Factors for Posttraumatic Stress Disorder in Recent Trauma Survivors

Neurobehavioral moderators of post-traumatic stress disorder (PTSD) trajectories: study protocol of a prospective MRI study of recent trauma survivors

Multi-domain potential biomarkers for post-traumatic stress disorder (PTSD) severity in recent trauma survivors