Glucocorticoids are required for extinction of predator stress-induced hyperarousal

Background

The role of glucocorticoids in extinction of traumatic memories has not been fully characterized despite its potential as a therapeutic target for acquired posttraumatic stress disorder (PTSD). The predator stress paradigm allows us to determine whether glucocorticoids mediate the extinction of both context-dependent and context-independent fear memories.

Methods

Male C57BL/6J mice were exposed to a predator (cat) then repeatedly exposed to the predator stress context in the absence of the cat. Context-dependent (associative) fear memory was assessed as suppression of activity during re-exposure to the predator stress context without the cat (extinction trials). Context-independent fear (non-associative) was assessed seven days after extinction trials using measures of hyperarousal and anxiety-like behaviours in environments unlike the predator stress context. To assess the role of glucocorticoids, mice were injected with metyrapone (50 mg/kg) 90 min prior to extinction trials in predator stressed mice and context-dependent and context-independent fear memories were assessed. Finally, metyrapone-treated predator stressed mice were injected with corticosterone (5 or 10 mg/kg) immediately following extinction trials and context-dependent and context-independent fear memories were assessed.

Results

Repeated re-exposure to the predator stress context without the cat present extinguished context-dependent fear memory, and also reduced hyperarousal, a generalized, chronic PTSD-like symptom. We show that extinction of context-independent predator stress-induced hyperarousal is dependent on endogenous glucocorticoids during the extinction trials. Furthermore, the inhibition of extinction by metyrapone on startle amplitude was reduced by exogenous administration of corticosterone following extinction trials. Overall, these data implicate glucocorticoids in the extinction of hyperarousal, a core symptom of PTSD.     

Comparing observational software with paper and pencil for time-sampled data: A field test of Interval Manager (INTMAN)

In this article, we describe the Interval Manager (INTMAN) software system for collecting timesampled observational data and present a preliminary application comparing the program with a traditional paper-and-pencil method. INTMAN is a computer-assisted alternative to traditional paper-and-pencil methods for collecting fixed interval time-sampled observational data. The INTMAN data collection software runs on Pocket PC handheld computers and includes a desktop application for Microsoft Windows that is used for data analysis. Standard analysis options include modified frequencies, percent of intervals, conditional probabilities, and kappa agreement matrices and values. INTMAN and a standardized paper-and-pencil method were compared under identical conditions on five dimensions: setup time, duration of data entry, duration of interobserver agreement calculations, accuracy, and cost. Overall, the computer-assisted program was a more efficient and accurate data collection system for time-sampled data than the traditional method.     

“Editing” Genes: A Case Study About How Language Matters in Bioethics

Metaphors used to describe new technologies mediate public understanding of the innovations. Analyzing the linguistic, rhetorical, and affective aspects of these metaphors opens the range of issues available for bioethical scrutiny and increases public accountability. This article shows how such a multidisciplinary approach can be useful by looking at a set of texts about one issue, the use of a newly developed technique for genetic modification, CRISPRcas9.     

Luminance affects age-related deficits in object detection: implications for computerized psychological assessments

As psychological instruments are converted for administration on computers, differences in luminance and contrast of these displays may affect performance. Specifically, high-luminance assessments may mask age-group differences that are apparent under lower luminance conditions. We examined the effects of luminance and contrast on object detection using computerized and naturalistic assessments. Younger and older adults displayed more differences in performance across differing contrast levels in conditions that were matched for luminance, despite the conditions appearing perceptually different. These findings indicate that computerized assessments should be created with luminance levels that are similar to those of the tasks they purport to simulate in order to enhance their validity.     

Using Corticomuscular and Intermuscular Coherence to Assess Cortical Contribution to Ankle Plantar Flexor Activity During Gait

The present study used coherence and directionality analyses to explore whether the motor cortex contributes to plantar flexor muscle activity during the stance phase and push-off phase during gait. Subjects walked on a treadmill, while EEG over the leg motorcortex area and EMG from the medial gastrocnemius and soleus muscles was recorded. Corticomuscular and intermuscular coherence were calculated from pair-wise recordings. Significant EEG–EMG and EMG–EMG coherence in the beta and gamma frequency bands was found throughout the stance phase with the largest coherence towards push-off. Analysis of directionality revealed that EEG activity preceded EMG activity throughout the stance phase until the time of push-off. These findings suggest that the motor cortex contributes to ankle plantar flexor muscle activity and forward propulsion during gait.     

Amnesia, traumatic brain injury, and posttraumatic stress disorder: a methodological inquiry

This study explored the relationship between mild traumatic brain injury (MTBI), amnesia, and posttraumatic stress disorder (PTSD). MTBI status and amnesia for the event were assessed in 307 consecutive admissions to a Level 1 Trauma Center. Amnesia did not always occur concurrently with MTBI: 18% of those with MTBI had full recall and over half had partial recall of the event. Just over 10% of participants developed PTSD by 12 months post-injury, with prevalence comparable across MTBI and non-MTBI groups. Non-significant differences in incidence of PTSD were apparent between those with full recall (9%), partial recall (14%) and no recall (7%). These data highlight the fact that PTSD may develop following trauma despite amnesia for the event, and illustrate the importance in both clinical and research settings of carefully examining the extent of amnesia.     

The Effects of Practice on Children's Ability to Apply Ground Rules in a Narrative Interview

Despite the widespread use of ground rules in forensic interview guidelines, it is unknown whether children retain and apply these rules throughout narrative interviews. We evaluated the capacity of 260 five- to nine-year-olds to utilize three ground rules. At the beginning of the interview all children heard the rules; half also practiced them. Children then responded to open-ended prompts about a repeated laboratory event and were assessed for their application of the rules. Logistic regressions revealed that practice only benefitted the use of the “don't know” rule. Although the children accurately answered “don't understand” and “correct me” practice questions, practice appeared to give no greater benefit than just hearing the rules. Results suggest that the current format of ground rule practice in interview guidelines is appropriate for the “don't know” rule, but the other rules may require more extensive practice with this age group. Copyright © 2015 John Wiley & Sons, Ltd.     

Maternal Uniparental Isodisomy Causing Autosomal Recessive GM1 Gangliosidosis: A Clinical Report

Uniparental disomy is a genetic cause of disease that may result in the inheritance of an autosomal recessive condition. A child with developmental delay and hypotonia was seen and found to have severely abnormal myelination. Lysosomal enzyme testing identified an isolated deficiency of beta-galactosidase. Subsequently, homozygous missense mutations in the galactosidase, beta 1 (GLB1) gene on chromosome 3 were found. Parental testing confirmed inheritance of two copies of the same mutated maternal GLB1 gene, and no paternal copy. SNP analysis was also done to confirm paternity. The patient was ultimately diagnosed with autosomal recessive GM1 gangliosidosis caused by maternal uniparental isodisomy. We provide a review of this patient and others in which uniparental disomy (UPD) of a non-imprinted chromosome unexpectedly caused an autosomal recessive condition. This is the first case of GM1 gangliosidosis reported in the literature to have been caused by UPD. It is important for genetic counselors and other health care providers to be aware of the possibility of autosomal recessive disease caused by UPD. UPD as a cause of autosomal recessive disease drastically changes the recurrence risk for families, and discussions surrounding UPD can be complex. Working with families to understand UPD when it occurs requires a secure and trusting counselor-family relationship.