Early Linguistic Markers of Trauma-Specific Processing Predict Post-trauma Adjustment

Identifying early predictors for psychiatric disorders, such as post-traumatic stress disorder (PTSD), is crucial for effective treatment and prevention efforts. Obtaining such predictors is challenging and methodologically limited, for example by individuals' distress, arousal, and reduced introspective ability. We investigated the predictive power of language-based, implicit markers of psychological processes (N = 163) derived from computerized text-analysis of trauma and control narratives provided within 18 days post-trauma. Trauma narratives with fewer cognitive processing words (indicating less cognitive elaboration), more death-related words (indicating perceived threat to life), and more first-person singular pronouns (indicating self-immersed processing) predicted greater PTSD symptoms at 6 months. These effects were specific to trauma narratives and held after controlling for early PTSD symptom severity and verbal intelligence. When self-report questionnaires of related processes were considered together with the trauma narrative linguistic predictors, use of more first-person singular pronouns remained a significant predictor alongside self-reported mental defeat. Language-based processing markers may complement questionnaire measures in early forecasting of post-trauma adjustment

Effect of the Matrix Metalloproteinase Inhibitor Doxycycline on Human Trace Fear Memory

Learning to predict threat is of adaptive importance, but aversive memory can also become disadvantageous and burdensome in clinical conditions such as posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a laboratory model of aversive memory and thought to rely on structural synaptic reconfiguration involving matrix metalloproteinase (MMP)9 signaling. It has recently been suggested that the MMP9-inhibiting antibiotic doxycycline, applied before acquisition training in humans, reduces fear memory retention after one week. This previous study used cued delay fear conditioning, in which predictors and outcomes overlap in time. However, temporal separation of predictors and outcomes is common in clinical conditions. Learning the association of temporally separated events requires a partly different neural circuitry, for which the role of MMP9 signaling is not yet known. Here, we investigate the impact of doxycycline on long-interval (15 s) trace fear conditioning in a randomized controlled trial with 101 (50 females) human participants. We find no impact of the drug in our preregistered analyses. Exploratorypost hocanalyses of memory retention suggested a serum level-dependent effect of doxycycline on trace fear memory retention. However, effect size to distinguish CS+/CS− in the placebo group turned out to be smaller than in previously used delay fear conditioning protocols, which limits the power of statistical tests. Our results suggest that doxycycline effect on trace fear conditioning in healthy individuals is smaller and less robust than anticipated, potentially limiting its clinical application potential

Appreciating methodological complexity and integrating neurobiological perspectives to advance the science of resilience

Kalisch and colleagues identify several routes to a better understanding of mechanisms underlying resilience and highlight the need to integrate findings from neuroscience and animal learning. We argue that appreciating methodological complexity and integrating neurobiological perspectives will advance the science of resilience and ultimately help improve the lives of those exposed to stress and adversit

Erasing Sensorimotor Memories via PKMζ Inhibition

Sensorimotor cortex has a role in procedural learning. Previous studies suggested that this learning is subserved by long-term potentiation (LTP), which is in turn maintained by the persistently active kinase, protein kinase Mzeta (PKMζ). Whereas the role of PKMζ in animal models of declarative knowledge is established, its effect on procedural knowledge is not well understood. Here we show that PKMζ inhibition, via injection of zeta inhibitory peptide (ZIP) into the rat sensorimotor cortex, disrupts sensorimotor memories for a skilled reaching task even after several weeks of training. The rate of relearning the task after the memory disruption by ZIP was indistinguishable from the rate of initial learning, suggesting no significant savings after the memory loss. These results indicate a shared molecular mechanism of storage for declarative and procedural forms of memory

The Vermicelli and Capellini Handling Tests: Simple quantitative measures of dexterous forepaw function in rats and mice

Previous characterizations of rodent eating behavior have revealed that they use coordinated forepaw movements to manipulate food pieces. We have extended upon this work to develop a simple quantitative measure of forepaw dexterity that is sensitive to lateralized impairments and age-dependent changes. Rodents learn skillful forepaw and digit movements to manage thin pasta pieces, which they eagerly consume. We have previously described methods for quantifying vermicelli handling in rats and showed that the measures are very sensitive to forelimb impairments resulting from unilateral ischemic lesions, middle cerebral artery occlusions and unilateral striatal dopamine depletion [Allred, R.P., Adkins, D.L., Woodlee, M.T., Husbands, L.C., Maldonado M.A., Kane, J.R., Schallert, T. & Jones, T.A. The Vermicelli Handling Test: a simple quantitative measure of dexterous forepaw function in rats. J. Neurosci. Methods 170, 229-244 (2008)]. Here we present a more detailed protocol for this test in rats and compare it with a newly developed version for mice, the Capellini Handling Test. Rats and mice are videotaped while handling short lengths of uncooked vermicelli or capellini pasta, respectively, with a camera positioned to optimize the view of paw movements. Slow motion video playback allows for the identification of forepaw adjustments, defined as any distinct removal and replacement of the paw, or of any number of digits, on the pasta piece after eating commences. Forepaw adjustments per piece are averaged over trials per each testing session. Repeated testing permits sensitive quantitative analysis of changes in forepaw dexterity over time. Protocols for pre-testing habituation and handling practice, as well as procedures for characterizing atypical handling patterns, are described. Because rats and mice perform the pasta handling tests slightly differently, species-specific differences in administration and scoring of these tests are highlighted. All animal use was in accordance with protocols approved by the University of Texas at Austin Animal Care and Use Committee

The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland

The authors sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype 5. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis it has been estimated that the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic

Effective psychological therapy for PTSD changes the dynamics of specific large-scale brain networks

In posttraumatic stress disorder (PTSD), re-experiencing of the trauma is a hallmark symptom proposed to emerge from a de-contextualised trauma memory. Cognitive therapy for PTSD (CT-PTSD) addresses this de-contextualisation through different strategies. At the brain level, recent research suggests that the dynamics of specific large-scale brain networks play an essential role in both the healthy response to a threatening situation and the development of PTSD. However, very little is known about how these dynamics are altered in the disorder and rebalanced after treatment and successful recovery. Using a data-driven approach and fMRI, we detected recurring large-scale brain functional states with high temporal precision in a population of healthy trauma-exposed and PTSD participants before and after successful CT-PTSD. We estimated the total amount of time that each participant spent on each of the states while being exposed to trauma-related and neutral pictures. We found that PTSD participants spent less time on two default mode subnetworks involved in different forms of self-referential processing in contrast to PTSD participants after CT-PTSD (mtDMN+ and dmDMN+) and healthy trauma-exposed controls (only mtDMN+). Furthermore, re-experiencing severity was related to decreased time spent on the default mode subnetwork involved in contextualised retrieval of autobiographical memories, and increased time spent on the salience and visual networks. Overall, our results support the hypothesis that PTSD involves an imbalance in the dynamics of specific large-scale brain network states involved in self-referential processes and threat detection, and suggest that successful CT-PTSD might rebalance this dynamic aspect of brain function

Constraint-induced Aphasia Therapy versus Intensive Semantic Treatment in Fluent Aphasia

Objective: To compare the effectiveness of two intensive therapy methods: Constraint- 4 Induced Aphasia Therapy (CIAT) and semantic therapy (BOX). Method: Nine patients with chronic fluent aphasia participated in a therapy programme 6 to establish behavioral treatment outcomes. Participants were randomly assigned to one of two groups (CIAT or BOX). Results: Intensive therapy significantly improved verbal communication. However, BOX 9 treatment showed a more pronounced improvement on two communication measures, namely on a standardized assessment for verbal communication, the Amsterdam Nijmegen Everyday Language Test (Blomert, Koster, & Kean, 1995) and on a subjective rating scale, the Communicative Effectiveness Index (Lomas et al., 1989). All 13 participants significantly improved on one (or more) subtests of the Aachen Aphasia Test (Graetz et al., 1992), an impairment-focused assessment. There was a treatment-specific effect. Therapy with BOX had a significant effect on language comprehension and on semantics, while of CIAT affected language production and phonology. Conclusion: The findings indicate that in patients with fluent aphasia (1) intensive treatment has a significant effect on language and verbal communication, (2) intensive therapy results in selective treatment effects and (3) an intensive semantic treatment shows a more striking mean improvement on verbal communication in comparison to communication-based CIAT-treatment