Effects of Threat Conditioning on the Negative Valanced Systems and Cognitive Systems

Rodrigo S. Fernández, Soledad Picco, Fernando Messore, María E. Pedreira
2018 Scientific Reports  
Threat conditioning is held as a model of anxiety disorders. However, this approach is focused on implicit responses evaluated in a single day. Here, we evaluated negative-valence, positive-valence and cognitive-systems in order to evaluate the extent to which threat conditioning models anxiety disorders. Subjects underwent threat conditioning and five-minutes (Short-term evaluation) or 48 hs (Long-term evaluation) later, both groups performed several tasks targeting cognitive-systems and
more » ... ed-systems. In the short-term evaluation, successful conditioning maintained state-anxiety and increased the aversiveness representation of the CS+ and the valuation for negative events. Reactiontimes for the CS+ were faster, reflecting an attentional bias toward threat. In the long-term evaluation, participants represented the CS+ as more aversive and generalized to all stimuli. Reaction-times showed a more restricted attentional bias. Threat conditioning alters the negative-valence systems and creates a cognitive bias, which is transformed by memory consolidation, suggesting that this protocol could be a useful resource to understand the deficits associated with anxiety disorders. Anxiety and fear-related disorders as a group are the most prevalent mental illness 1,2 . Individuals with anxiety disorders are excessively anxious, fearful and avoidant of a large range of internal or external threats. At the behavioral level, fear and anxiety frequently overlap; however, they can be differentiated by considering the level of uncertainty regarding the probability, timing or nature of future danger 3-5 . Fear refers to a defensive motivational response to an actual (acute) or immediate threat 6 . In contrast, anxiety is defined as a persistent and generalized defensive response to a potential, unpredictable or uncertain threat 3,7,8 . Typical anxiety symptoms are physiological (i.e., muscle tension, palpitations, dizziness, nausea), cognitive (i.e., fear of losing control, hypervigilance, worry), behavioral (i.e., avoidance, freezing) and emotional (i.e., arousal, fearfulness, impatience). From Pavlov's "experimental neurosis" 9 to the modern neuroscientific theories 10,11 , it is clear that learning, and more specifically, Pavlovian threat (fear) conditioning, plays a critical role in the pathogenesis and maintenance of anxiety disorders 11,12 . Ultimately, anxiety disorders are not acquired in an instant and actually develop gradually. However, threat conditioning in animals and healthy populations is held as a model of anxiety-and fear-related disorders. As a laboratory model, threat conditioning, conceptualized as an aversive-implicit memory, has allowed researchers to gain tremendous knowledge about the neurobiological basis of anxiety disorders and to develop novel treatments 13,14 . However, considering that anxiety disorders engage physiological, emotional and cognitive changes, this approach reduces the modeled disorder to an acquired associative response at physiological (i.e., heartbeat interval, electrodermal activity, etc.) and declarative (i.e., contingency awareness) levels. As a result, this research bias neglects fundamental aspects of threat processing and anxiety disorders such as valenced (positive/negative), cognitive or regulatory domains. On the other hand, the current diagnosis system is suffering a shift from a categorical classification (DSM V) to a dimensional one including a constellation of factors. Consequently, the Research Domain Criteria (RDoc) 15 proposed a framework to study mental illness using a dimensional matrix that considers different domains (positive, negative, cognitive, regulatory or social systems) and units of analysis (from genes to behavior). In this regard, highly anxious individuals could be thought as having alterations in negative-valence and cognitive system processing. Negative valence systems are involved in the anticipation, maintenance and processing of aversive Published: xx xx xxxx OPEN www.nature.com/scientificreports/
doi:10.1038/s41598-018-29603-3 pmid:30046052 pmcid:PMC6060145 fatcat:nsgo4vgxwzextb46po43e3o6wq