Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline

Learning to predict threat is a fundamental ability of many biological organisms, and a laboratory model for anxiety disorders. Interfering with such memories in humans would be of high clinical relevance. On the basis of studies in cell cultures and slice preparations, it is hypothesised that synaptic remodelling required for threat learning involves the extracellular enzyme matrix metalloproteinase (MMP) 9. However, in vivo evidence for this proposal is lacking. Here we investigate human Pavlovian fear conditioning under the blood-brain barrier crossing MMP inhibitor doxycyline in a pre-registered, randomised, double-blind, placebo-controlled trial. We find that recall of threat memory, measured with fear-potentiated startle 7 days after acquisition, is attenuated by ~60% in individuals who were under doxycycline during acquisition. This threat memory impairment is also reflected in increased behavioural surprise signals to the conditioned stimulus during subsequent re-learning, and already late during initial acquisition. Our findings support an emerging view that extracellular signalling pathways are crucially required for threat memory formation. Furthermore, they suggest novel pharmacological methods for primary prevention and treatment of posttraumatic stress disorder.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.65

Application of Double-Difference Seismic Tomography to Carbon Sequestration Monitoring at the Aneth Oil Field, Utah

Double difference seismic tomography was performed using travel time data from a carbon sequestration site at the Aneth oil field in southeast Utah as part of a Department of Energy initiative on monitoring, verification, and accounting (MVA) of sequestered CO2. A total of 1211 seismic events were recorded from a borehole array consisting of 23 geophones. Artificial velocity models were created to determine the likelihood of detecting a CO2 plume with an unfavorable event and receiver arrangement. In tests involving artificially modeled ray paths through a velocity model, ideal event and receiver arrangements clearly show velocity reductions. When incorporating the unfavorable event and station locations from the Aneth Unit into synthetic models, the ability to detect velocity reductions is greatly diminished. Using the actual, recorded travel times, the Aneth Unit results show differences between a synthetic baseline model and the travel times obtained in the field, but the differences do not clearly indicate a region of injected CO2. MVA accuracy and precision may be improved through the use of a receiver array that provides more comprehensive ray path coverage, and a more detailed baseline velocity model

Court Review: Volume 44, Issue 1/2 – Children and Procedural Justice

The American Judges Association’s White Paper that forms the centerpiece of this issue begins with the recognition that even first graders have an understanding of procedural fairness. Developmental research has indeed established that young children are able to evaluate the fairness of activities and that they have a more positive perception of activities they deem to be more fair. Until recently, however, there has been little concern in the U.S. regarding children’s experiences of legal processes and procedures. In fact, children were not generally expected or encouraged to directly participate in most legal processes, even those where they were a main party to the proceedings, such as cases involving abuse/neglect and foster care. In the last several years in the U.S., there have been arguments made to increase children’s participation in legal processes that affect them and to increase children’s knowledge of legal processes. These arguments for increased participation are generally couched in the language of procedural justice—children desire and deserve a voice in legal proceedings that affect them. For example, a recent publication for and by foster youth, provided by the nonpartisan Pew Commission on Children in Foster Care, is titled My Voice, My Life, My Future. Similarly, efforts at increasing children’s knowledge of legal processes are attempts to empower them in their dealings with the legal system by increasing their understanding of the players and the process

CAUGHT IN THE NET PERINEURONAL NETS AND COCAINE MEMORY

Perineuronal nets (PNNs) are aggregations of extracellular matrix molecules that form net-like structures around the perimeter of a subset of neurons within the central nervous system. PNNs appear during development in an experience-dependent manner, and their appearance coincides with the closure of critical periods during which neuronal systems are highly malleable and influenced by external stimuli. During adulthood, PNNs regulate plasticity and are continually modulated by experience. Within this body of work, the relationship between PNNs, drugs of abuse, and memory was investigated in rats. The central hypothesis was that PNNs within the prefrontal cortex (PFC) dynamically change in response to drug exposure and are integral for the formation and persistence of drug-associated memories that underlie relapse. The PFC is involved in drug-seeking behavior, memory, and drug-associated memories. To test this hypothesis, PNNs within the PFC were removed to target different stages of drug-associated memory. Removal of PNNs disrupted both initial formation and reconsolidation of drug-associated memories. Next, a method of PNN staining intensity quantification was developed to assess the dynamic nature of PNNs. Several studies suggest that PNN staining is inversely related to plasticity; for example, as PNN staining decreases, the potential for plasticity increases. Our novel method of PNN staining intensity analysis allows for standardization and automation. Using this method of PNN staining intensity quantification, we examined PNNs after several behavioral manipulations. Following sucrose self-administration and exposure to environmental enrichment (EE), PNN staining intensity increased within several regions of the PFC, suggesting that EE decreased the potential for plasticity. Following acute novel EE exposure in rats without a history of sucrose self-administration, PNNs were altered in a region-dependent manner. Finally, PNNs within the PFC dynamically respond to cocaine exposure in a time- and region-dependent manner. Taken together these studies indicate that PNNs are dynamic structures that respond to environmental manipulations and are necessary for drug-associated memory formation and maintenance. These findings have implications for understanding of how drug-induced plasticity and cocaine-associated memories may be manipulated to diminish relapse

REPAIRING AT THE APP CLINIC: A CASE STUDY OF AN ONLINE WELLNESS APPLICATION

Presented is a brief account of a six-month ethnographic case study of an Internet-communications technology startup. This company has designed an online application for the purpose of increasing wellness of individuals in the workplace. By way of curated prompts of self- and group-reflection and self-tracking, the company seeks to transport workers through an architected experience that leads to greater production through holistic awareness. The methods used for this study include in-depth, unstructured interviews, participant-observation of the employees, and platform study. The company, which has a core group of four employees, includes a CEO, a product manager, a developer, and a designer. Following, is a summary of my observations in which I attempt to describe how the employees of this startup imagine the body in need of care. I then conclude with a description of how I see the discussion expanding to include their online platform and how it can be framed as a clinic for care