The role of awareness in delay and trace fear conditioning in humans

Expression of conditional fear without awareness has been previously demonstrated during delay conditioning, a procedure in which the conditioned stimulus (CS) and unconditioned stimulus (UCS) overlap. However, less is known about the role of awareness in trace fear conditioning, where an interval of time separates the CS and UCS. The present study assessed skin conductance response (SCR) and UCS expectancy during delay and trace conditioning. UCS predictability was varied on a trial-bytrial basis by presenting perithreshold auditory CSs. Differential UCS expectancies were demonstrated only on perceived delay and trace trials. Learning-related SCRs were observed during both perceived and unperceived delay CSs. In contrast, differential SCRs were demonstrated only for perceived trace CSs. These data suggest that awareness is necessary for conditional responding during trace, but not delay, fear conditioning.     

Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?

Antidepressants, in particular newer agents, are among the most widely prescribed medications worldwide with annual sales of billions of dollars. The introduction of these agents in the market has passed through seemingly strict regulatory control. Over a thousand randomized trials have been conducted with antidepressants. Statistically significant benefits have been repeatedly demonstrated and the medical literature is flooded with several hundreds of "positive" trials (both pre-approval and post-approval). However, two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits. A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness. These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied. I discuss how the use of many small randomized trials with clinically non-relevant outcomes, improper interpretation of statistical significance, manipulated study design, biased selection of study populations, short follow-up, and selective and distorted reporting of results has built and nourished a seemingly evidence-based myth on antidepressant effectiveness and how higher evidence standards, with very large long-term trials and careful prospective meta-analyses of individual-level data may reach closer to the truth and clinically useful evidence.     

The 9th annual INDUS-EM 2013 Emergency Medicine Summit, “Principles,Practices, and Patients,” a level one international meeting,Kerala University of Health Sciences and Jubilee Mission Medical College and Research Institute,Thrissur, Kerala,India, October 23–27, 2013

INDUS-EM is India’s only level one conference imparting and exchanging quality knowledge in acute care. Specifically, in general and specialized emergency care and training in trauma, burns, cardiac, stroke, environmental and disaster medicine. It provides a series of exchanges regarding academic development and implementation of training tools related to developing future academic faculty and residents in Emergency Medicine in India. The INDUS-EM leadership and board of directors invited scholars from multiple institutions to participate in this advanced educational symposium that was held in Thrissur, Kerala in October 2013.     

Aberrant neural mediation of verbal fluency in autism spectrum disorders

Objective

Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD).

Method

We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n = 17, mean verbal IQ = 117) and neurotypical (NT; n = 20, mean verbal IQ = 112) adolescent and young adult males (12–23 years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency.

Results

Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in cortico-striatal circuits previously linked to repetitive behaviors (Langen, Durston, Kas, van Engeland, & Staal, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand.

Conclusions

These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses.