Community Research and Development Information Service - CORDIS

FP7

ERBT Report Summary

Project ID: 618534
Funded under: FP7-PEOPLE
Country: Israel

Periodic Report Summary 1 - ERBT (Fear Conditioning and Extinction in Anxious Youth: Identifying Neuro-cognitive Abnormalities and Their Relation to Pediatric Anxiety Treatment Outcomes)

Anxiety disorders are the most common form of pediatric psychopathology, affecting 5 – 20% of children and adolescents. Despite therapeutic advances, treatment-resistance remains high, and progress towards early detection of at-risk populations and more effective treatments has stalled. The proposed research objective is to target information-processing functions, specifically fear learning and extinction, in an effort to link pediatric anxiety to dysfunction in cognitive mechanisms and in underlying fear circuits.

Two specific objectives guide the proposal: Objective 1: To examine differences in fear learning, extinction and extinction recall in anxious and non-anxious children, using a novel fear conditioning paradigm. This research will extend previous work to a younger age group. Objective 2: To demonstrate the therapeutic relevance of dysfunction in fear learning and extinction for treatment. Exposure Therapy is one of the most effective interventions for anxiety disorders. This intervention relies heavily on extinction learning principles and may produce beneficial effects by altering brain function. The proposed study was designed to assess fear conditioning and extinction and brain function in anxious children pre and post exposure therapy.

Since receiving the CIG grant I was able to publish a manuscript that described the novel fear conditioning paradigm (the bell paradigm) that was designed to be used with children. This paradigm was described in the grant proposal. The paper titled “Fear conditioning and extinction in anxious and non-anxious youth and adults: Examining a novel developmentally-appropriate fear conditioning task” was published in Depression and Anxiety (impact factor 4.4). The paradigm was tested in a study that examined differences in fear conditioning and extinction in anxious and non-anxious youth –directly following the first objective of this grant. Since its publication, two additional studies were published using this novel task (related but not directly linked to the CIG grant proposal):

McLaughlin, K.A., Sheridan, A.S., Gold, A.L., Duys, A., Lambert,H.K., Perverill, M., Heleniak, C., Shechner, T., & Pine D. S. (2016). Trauma exposure, brain structure, and fear conditioning in children. Neuropsychopharmacology.

Michalska, K. J., Shechner, T., Britton, J. C., Pine D. S.,& Fox, N. A. (2016). A developmental analysis of fear learning and generalization in childhood. Journal of Experimental Child Psychology, 46, 95-105.

Following IRB approval from the University of Haifa (093/15) my team began to run the behavioral and physiological aspects of the study that could be conducted in our lab. The major tool that I was planning to use for brain imaging was functional magnetic resonance imaging (fMRI). This past month (June, 2016) we received Helsinki approval from Haemek hospital (EMC 97-15) and the Israeli Ministry of Health (20161710), which will allow us to be able to begin the scanning of anxious and non-anxious youth. The study has also been registered in the NIH’s clinical trials database (NCT02631785).

In the interim, however, while waiting for the final Helsinki approval we began testing anxious and non-anxious children using event related potential (ERP). For this study - the IRB from the University of Haifa was sufficient. Specifically, following objective 1 and objective 2 of the proposal, we examine differences in fear conditioning, extinction and extinction recall while recording ERPs of anxious and non-anxious youth using the bell task. To the best of our knowledge, this is the first ERP study examining differences in brain activation during fear learning in anxious and non-anxious youth. ERPs provide a unique and highly informative perspective on brain processing. The greatest advantage of ERPs is their ability to achieve excellent temporal precision and resolution and to measure electrical differences in an inexpensive way. In addition, because ERP measurement is noninvasive, it can be easily used to examine brain-emotional-behavior association in young children.
Our current sample is comprised of 31 non-anxious children and 10 anxious children. During visit 1, participants and their parents sign consent and ascent forms followed by a comprehensive clinical interview. Participants then undergo a fear learning task (the bell paradigm) that includes both a fear conditioning and extinction phase. Psychophysiology measurements (skin conductance, fear potentiated startle and heart rate) and participant’s self-reported ratings of fear are acquired. One week after completing visit 1, participants return to the laboratory to perform an extinction recall task while their brain activation is measured by EEG/ERP. Morphed images of the colored bells are presented, forming a continuum of similarity between the CS- and CS+, and participant’s ERP waves and components are assessed.

Results thus far are very exciting. Fear conditioning and extinction was obtained as indexed by self-report and psychophysiological measures (n = 34). In addition, ERP results from extinction recall indicate varied brain activation in response to different stimuli (CS) one week following extinction as seen in the late positive potential component (LPP). We hope that these results will soon be published in a paper that is currently in preparation, which will set the stage for the next imaging phase of the study.

To complete objective 2 – a clinical psychologist was hired for the project and currently 2 anxious children have completed 12 treatment sessions (cognitive behavioral therapy - CBT) and 6 are currently in different stages of treatment. All of these children completed the ERP extinction recall task before and after treatment. In line with objective 2 of the proposal, clinical benefits will be examined in light of behavioral, cognitive and brain functioning during fear learning pre-treatment.

In sum, the experiments conducted thus far further our understanding regarding differences in fear learning among anxious and non-anxious children. The findings highlight the importance of using multi-level analyses to measure such differences particularly in a pediatric clinical study. In addition, we established a task to measure fear conditioning and extinction across development and adapted it to ERP setting. The current findings and paradigms set the stage for the next phase of the study, which will involve fMRI scans of these tasks.

Related information

Contact

Tsvia Beker, (Head of European desk)
Tel.: +972 4 8288485
E-mail

Subjects

Life Sciences
Record Number: 187692 / Last updated on: 2016-08-23
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