Antiepileptics in Electroconvulsive Therapy: A Mechanism-Based Review of Recent Literature.

ABSTRACT: Although prior conventional wisdom strongly recommended complete discontinuation of medications increasing the seizure threshold before electroconvulsive therapy (ECT), more recent literature suggests that anticonvulsants should be considered a relative rather than an absolute contraindication to proceeding with therapy. Most literature regarding the use of use antiepileptic drugs in ECT focuses on antiepileptic mood stabilizers with which most psychiatrists are familiar. However, there is considerably less information available about the use of newer antiepileptics in conjunction with ECT, which may be prescribed to a patient with epilepsy or off-label for psychiatric reasons.In this article, we provide a mechanism-based review of recent available literature concerning the use of antiepileptics during ECT and discuss which medications have the most robust evidence supporting their continued use in select patients. Finally, we highlight important considerations for psychiatrists when deciding how to proceed with patients on antiepileptics who require ECT.

Differential recruitment of brain circuits during fear extinction in non-stressed compared to stress resilient animals.

Dysfunctional fear responses in post-traumatic stress disorder (PTSD) may be partly explained by an inability to effectively extinguish fear responses elicited by trauma-related cues. However, only a subset of individuals exposed to traumatic stress develop PTSD. Therefore, studying fear extinction deficits in animal models of individual differences could help identify neural substrates underlying vulnerability or resilience to the effects of stress. We used a rat model of social defeat in which rats segregate into passively and actively coping rats. In previous work, we showed that passively coping rats exhibit disruptions in social interaction whereas actively coping rats do not display behaviors differently from controls, indicating their resilience. Here, adult male rats exposed to 7 days of social defeat were tested for fear extinction, retention of extinction, and persistence of retention using contextual fear and ethologically-relevant fear tests. Passively coping rats exhibited elevated freezing in response to the previously extinguished context. Analyses of cFos expressing cells across select brain regions showed high correlations within dorsal hippocampal subregions, while passively coping rats had high correlations between the dorsal hippocampus CA1 and the central and basolateral subregions of the amygdala. Importantly, although control and actively coping rats showed similar levels of behavioral extinction, there was little similarity between activated structures, suggesting stress resilience in response to chronic social defeat involves an adaptive differential recruitment of brain circuits to successfully extinguish fear memories.

Analyses of turbulent flow fields and aerosol dynamics of diesel engine exhaust inside two dilution sampling tunnels using the CTAG model.

Experimental results from laboratory emission testing have indicated that particulate emission measurements are sensitive to the dilution process of exhaust using fabricated dilution systems. In this paper, we first categorize the dilution parameters into two groups: (1) aerodynamics (e.g., mixing types, mixing enhancers, dilution ratios, residence time); and (2) mixture properties (e.g., temperature, relative humidity, particle size distributions of both raw exhaust and dilution gas). Then we employ the Comprehensive Turbulent Aerosol Dynamics and Gas Chemistry (CTAG) model to investigate the effects of those parameters on a set of particulate emission measurements comparing two dilution tunnels, i.e., a T-mixing lab dilution tunnel and a portable field dilution tunnel with a type of coaxial mixing. The turbulent flow fields and aerosol dynamics of particles are simulated inside two dilution tunnels. Particle size distributions under various dilution conditions predicted by CTAG are evaluated against the experimental data. It is found that in the area adjacent to the injection of exhaust, turbulence plays a crucial role in mixing the exhaust with the dilution air, and the strength of nucleation dominates the level of particle number concentrations. Further downstream, nucleation terminates and the growth of particles by condensation and coagulation continues. Sensitivity studies reveal that a potential unifying parameter for aerodynamics, i.e., the dilution rate of exhaust, plays an important role in new particle formation. The T-mixing lab tunnel tends to favor the nucleation due to a larger dilution rate of the exhaust than the coaxial mixing field tunnel. Our study indicates that numerical simulation tools can be potentially utilized to develop strategies to reduce the uncertainties associated with dilution samplings of emission sources.

Modeling spatial variations of black carbon particles in an urban highway-building environment.

Highway-building environments are prevalent in metropolitan areas. This paper presents our findings in investigating pollutant transport in a highway-building environment by combing field measurement and numerical simulations. We employ and improve the Comprehensive Turbulent Aerosol Dynamics and Gas Chemistry (CTAG) model to simulate the spatial variations of black carbon (BC) concentrations near highway I-87 and an urban school in the South Bronx, New York. The results of CTAG simulations are evaluated against and agree adequately with the measurements of wind speed, wind directions, and BC concentrations. Our analysis suggests that the BC concentration at the measurement point of the urban school could decrease by 43-54% if roadside buildings were absent. Furthermore, we characterize two generalized conditions in a highway-building environment, i.e., highway-building canyon and highway viaduct-building. The former refers to the canyon between solid highway embankment and roadside buildings, where the spatial profiles of BC depend on the equivalent canyon aspect ratio and flow recirculation. The latter refers to the area between a highway viaduct (i.e., elevated highway with open space underneath) and roadside buildings, where strong flow recirculation is absent and the spatial profiles of BC are determined by the relative heights of the highway and buildings. The two configurations may occur at different locations or in the same location with different wind directions when highway geometry is complex. Our study demonstrates the importance of incorporating highway-building interaction into the assessment of human exposure to near-road air pollution. It also calls for active roles of building and highway designs in mitigating near-road exposure of urban population.

Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress.

BACKGROUND: Habituation to repeated stress refers to a progressive reduction in the stress response following multiple exposures to the same, predictable stressor. We previously demonstrated that the posterior division of the paraventricular thalamic nucleus (pPVT) nucleus regulates habituation to 5 days of repeated restraint stress in male rats. Compared to males, female rats display impaired habituation to 5 days of restraint. To better understand how activity of pPVT neurons is differentially impacted in stressed males and females, we examined the electrophysiological properties of pPVT neurons under baseline conditions or following restraint. METHODS: Adult male and female rats were exposed to no stress (handling only), a single period of 30 min restraint or 5 daily exposures to 30 min restraint. 24 h later, pPVT tissue was prepared for recordings. RESULTS: We report here that spontaneous excitatory post-synaptic current (sEPSC) amplitude was increased in males, but not females, following restraint. Furthermore, resting membrane potential of pPVT neurons was more depolarized in males. This may be partially due to reduced potassium leakage in restrained males as input resistance was increased in male, but not female, rats 24 h following 1 or 5 days of 30-min restraint. Reduced potassium efflux during action potential firing also occurred in males following a single restraint as action potential half-width was increased following a single restraint. Restraint had limited effects on electrophysiological properties in females, although the mRNA for 10 voltage-gated ion channel subunits was altered in the pPVT of female rats. CONCLUSIONS: The results suggest that restraint-induced changes in pPVT activation promote habituation in males. These findings are the first to describe a sexual dimorphism in stress-induced electrophysiological properties and voltage-gated ion channel expression in the pPVT. These results may explain, at least in part, why habituation to 5 days of restraint is disrupted in female rats.

Cerebral microbleeds in adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation.

Cranial radiation therapy is associated with white matter-specific brain injury, cortical volume loss, mineralization, microangiopathy and neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia. In this retrospective cross-sectional analysis, neurocognitive testing and 3 T brain MRI's were obtained in 101 survivors treated with cranial radiation. Small focal intracerebral hemorrhages only visible on exquisitely sensitive MRI sequences were identified and localized using susceptibility weighted imaging. Modified Poisson regression was used to assess the effect of cranial radiation on cumulative number and location of microbleeds in each brain region, and multiple linear regression was used to evaluate microbleeds on neurocognitive outcomes, adjusting for age at diagnosis and sex. At least one microbleed was present in 85% of survivors, occurring more frequently in frontal lobes. Radiation dose of 24 Gy conveyed a 5-fold greater risk (95% CI 2.57-10.32) of having multiple microbleeds compared to a dose of 18 Gy. No significant difference was found in neurocognitive scores with either the absence or presence of microbleeds or their location. Greater prevalence of microbleeds in our study compared to prior reports is likely related to longer time since treatment, better sensitivity of SWI for detection of microbleeds and the use of a 3 T MRI platform.

T-condylar fractures of the distal humerus in children: report on three cases.

T-condylar fractures of the distal humerus are very rare in children. Because of their rarity, there is a lack of evidence in the literature on the best method to treat such fractures. We report the cases of three paediatric patients with T-condylar fracture of the distal humerus. A high degree of attention is needed in order not to miss the presence of intra-articular fracture, especially in the case of a low supracondylar fracture and in those with a history of high-energy trauma. Anatomic intra-articular fracture reduction is the key to success in managing this rare injury.

Modeling multi-scale aerosol dynamics and micro-environmental air quality near a large highway intersection using the CTAG model.

A new methodology, referred to as the multi-scale structure, integrates "tailpipe-to-road" (i.e., on-road domain) and "road-to-ambient" (i.e., near-road domain) simulations to elucidate the environmental impacts of particulate emissions from traffic sources. The multi-scale structure is implemented in the CTAG model to 1) generate process-based on-road emission rates of ultrafine particles (UFPs) by explicitly simulating the effects of exhaust properties, traffic conditions, and meteorological conditions and 2) to characterize the impacts of traffic-related emissions on micro-environmental air quality near a highway intersection in Rochester, NY. The performance of CTAG, evaluated against with the field measurements, shows adequate agreement in capturing the dispersion of carbon monoxide (CO) and the number concentrations of UFPs in the near road micro-environment. As a proof-of-concept case study, we also apply CTAG to separate the relative impacts of the shutdown of a large coal-fired power plant (CFPP) and the adoption of the ultra-low-sulfur diesel (ULSD) on UFP concentrations in the intersection micro-environment. Although CTAG is still computationally expensive compared to the widely-used parameterized dispersion models, it has the potential to advance our capability to predict the impacts of UFP emissions and spatial/temporal variations of air pollutants in complex environments. Furthermore, for the on-road simulations, CTAG can serve as a process-based emission model; Combining the on-road and near-road simulations, CTAG becomes a "plume-in-grid" model for mobile emissions. The processed emission profiles can potentially improve regional air quality and climate predictions accordingly.