A companion to the preclinical common data elements on neurobehavioral comorbidities of epilepsy: a report of the TASK3 behavior working group of the ILAE/AES Joint Translational Task Force

Abstract

The provided companion has been developed by the Behavioral Working Group of the Joint Translational Task Force of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) with the purpose of assisting the implementation of Preclinical Common Data Elements (CDE) for studying and for reporting neurobehavioral comorbidities in rodent models of epilepsy. Case Report Forms (CRFs) are provided, which should be completed on a per animal/per test basis, whereas the CDEs are a compiled list of the elements that should be reported. This companion is not designed as a list of recommendations, or guidelines for how the tests should be run-rather, it describes the different types of assessments, and highlights the importance of rigorous data collection and transparency in this regard. The tests are divided into 7 categories for examining behavioral dysfunction on the syndrome level: deficits in learning and memory; depression; anxiety; autism; attention deficit/hyperactivity disorder; psychosis; and aggression. Correspondence and integration of these categories into the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) is introduced. Developmental aspects are addressed through the introduction of developmental milestones. Discussion includes complexities, limitations, and biases associated with neurobehavioral testing, especially when performed in animals with epilepsy, as well as the importance of rigorous data collection and of transparent reporting. This represents, to our knowledge, the first such resource dedicated to preclinical CDEs for behavioral testing of rodents.

Keywords: Animal models; Behavior; Comorbidities; Epilepsy.

Figure 1

Correspondence between disorders and RDoC constructs. The matrix shows comparison between the TASK3 elements and RDoC constructs as assessed by the degree of matching between the descriptors. Perfect matching is indicated in black; nonoverlapping descriptors are white. 1, dysregulated HPA axis enters as element of Physiology in this construct; 2, sexual dysfunction enters as communication and affiliation in Social Processes and as sex generically in Regulatory Systems; 3, serotonergic dysfunction enters as element of Molecule; 4, impulsive behaviors are included in the sub‐construct Response Selection; Inhibition/Suppression; 5, behavioral rigidity enters as the sub‐construct Flexible Updating; 6, Physical and Relational Aggression is included in this construct; 7, Dopaminergic/glutamatergic enters as elements of the unit Molecule in Reward Learning and Habits. (L.M. de la Prida).