Alcohol, flexible behavior, and the prefrontal cortex: Functional changes underlying impaired cognitive flexibility.

Cognitive flexibility enables individuals to alter their behavior in response to changing environmental demands, facilitating optimal behavior in a dynamic world. The inability to do this, called behavioral inflexibility, is a pervasive behavioral phenotype in alcohol use disorder (AUD), driven by disruptions in cognitive flexibility. Research has repeatedly shown that behavioral inflexibility not only results from alcohol exposure across species but can itself be predictive of future drinking. Like many high-level executive functions, flexible behavior requires healthy functioning of the prefrontal cortex (PFC). The scope of this review addresses two primary themes: first, we outline tasks that have been used to investigate flexibility in the context of AUD or AUD models. We characterize these based on the task features and underlying cognitive processes that differentiate them from one another. We highlight the neural basis of flexibility measures, focusing on the PFC, and how acute or chronic alcohol in humans and non-human animal models impacts flexibility. Second, we consolidate findings on the molecular, physiological and functional changes in the PFC elicited by alcohol, that may contribute to cognitive flexibility deficits seen in AUD. Collectively, this approach identifies several key avenues for future research that will facilitate effective treatments to promote flexible behavior in the context of AUD, to reduce the risk of alcohol related harm, and to improve outcomes following AUD.

Mixed Methods Study of Patient and Primary Care Provider Perceptions of Chronic Pain Treatment.

OBJECTIVE: A mixed-method study involving patient focus groups and survey of primary care providers (PCPs) sought to compare perspectives about chronic pain (CP) and its treatment. Our goal was to identify needs and barriers for facilitating patient-centered care. METHODS: Two focus groups of CP patients from a single academic medical center explored interactions with PCPs and their understandings, experiences, and expectations of CP treatment. They were also asked their opinions about self-assessment/communication tools. We compared themes with survey data from two PCP research networks. RESULTS: CP patients understand opioid risks and fear PCP judgement and condescension, while sensing PCP fear and avoidance of opioid prescribing. PCPs are dissatisfied with their ability to provide optimal CP care, despite feeling that patients are generally satisfied with their clinic visits. Evaluation tools, especially assessment of functional activities, are favorably viewed by all, but deemed time prohibitive. CONCLUSION: Patients' understanding of opioid risks, desire for attention on functional goals and behavioral treatment may be greater than PCPs perceive. Such gaps in understanding and attitudes, if recognized, could support high-quality communication and interventional strategies. PRACTICE IMPLICATIONS: These findings guide patient-PCP communication toward alignment of treatment goals and enhanced coordination of care.

Atypical audiovisual word processing in school-age children with a history of specific language impairment: an event-related potential study.

BACKGROUND: Visual speech cues influence different aspects of language acquisition. However, whether developmental language disorders may be associated with atypical processing of visual speech is unknown. In this study, we used behavioral and ERP measures to determine whether children with a history of SLI (H-SLI) differ from their age-matched typically developing (TD) peers in the ability to match auditory words with corresponding silent visual articulations. METHODS: Nineteen 7-13-year-old H-SLI children and 19 age-matched TD children participated in the study. Children first heard a word and then saw a speaker silently articulating a word. In half of trials, the articulated word matched the auditory word (congruent trials), while in another half, it did not (incongruent trials). Children specified whether the auditory and the articulated words matched. We examined ERPs elicited by the onset of visual stimuli (visual P1, N1, and P2) as well as ERPs elicited by the articulatory movements themselves-namely, N400 to incongruent articulations and late positive complex (LPC) to congruent articulations. We also examined whether ERP measures of visual speech processing could predict (1) children's linguistic skills and (2) the use of visual speech cues when listening to speech-in-noise (SIN). RESULTS: H-SLI children were less accurate in matching auditory words with visual articulations. They had a significantly reduced P1 to the talker's face and a smaller N400 to incongruent articulations. In contrast, congruent articulations elicited LPCs of similar amplitude in both groups of children. The P1 and N400 amplitude was significantly correlated with accuracy enhancement on the SIN task when seeing the talker's face. CONCLUSIONS: H-SLI children have poorly defined correspondences between speech sounds and visually observed articulatory movements that produce them.

Matching heard and seen speech: An ERP study of audiovisual word recognition.

Seeing articulatory gestures while listening to speech-in-noise (SIN) significantly improves speech understanding. However, the degree of this improvement varies greatly among individuals. We examined a relationship between two distinct stages of visual articulatory processing and the SIN accuracy by combining a cross-modal repetition priming task with ERP recordings. Participants first heard a word referring to a common object (e.g., pumpkin) and then decided whether the subsequently presented visual silent articulation matched the word they had just heard. Incongruent articulations elicited a significantly enhanced N400, indicative of a mismatch detection at the pre-lexical level. Congruent articulations elicited a significantly larger LPC, indexing articulatory word recognition. Only the N400 difference between incongruent and congruent trials was significantly correlated with individuals' SIN accuracy improvement in the presence of the talker's face.

Are encephaloceles neural tube defects?

OBJECTIVE: Encephalocele is classified as a neural tube defect, but questions have been raised regarding whether its epidemiological characteristics are similar to those of other neural tube defects. DESIGN: We compared characteristics of temporal trends in, and the impact of folic acid grain fortification on, the prevalence of encephalocele, spina bifida, and anencephaly using data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system. Prevalences of encephalocele, spina bifida, and anencephaly were compared by maternal age, gender, race, birth weight, ascertainment period (1968-1981, 1982-1993, or 1994-2002), and fortification period (1994-1996 [prefortification] and 1998-2002 [postfortification]) using prevalence ratios with 95% confidence intervals. Temporal trends were assessed using Poisson and negative binomial regression models. RESULTS: Prevalence rates of encephalocele (n = 167), spina bifida (n = 650), and anencephaly (n = 431) were 1.4, 5.5, and 3.7 per 10 000 live births, respectively. Encephalocele was similar to anencephaly in showing an increased prevalence among girls and multiple gestation pregnancies and to spina bifida and anencephaly in an annual prevalence decrease between 1968 and 2002 (-1.2% for encephalocele, -4.2% for spina bifida, and -3.6% for anencephaly). With fortification, prevalence decreased for spina bifida but not significantly for encephalocele or anencephaly. CONCLUSIONS: Encephalocele shows more similarities to spina bifida or anencephaly than it shows differences with respect to characteristics, temporal trend, and impact of fortification. Additional studies should be done to explore the etiologic heterogeneity of encephalocele using better markers of folate status and a wider range of risk factors.

Preconception care and treatment with assisted reproductive technologies.

Couples with fertility problems seeking treatment with assisted reproductive technologies (ART) such as in vitro fertilization should receive preconception counseling on all factors that are provided when counseling patients without fertility problems. Additional counseling should address success rates and possible risks from ART therapies. Success rates from ART are improving, with the highest live birth rates averaging about 40% per cycle among women less than 35 years old. A woman's age lowers the chance of achieving a live birth, as do smoking, obesity, and infertility diagnoses such as hydrosalpinx, uterine leiomyoma, or male factor infertility. Singletons conceived with ART may have lower birth weights. Animal studies suggest that genetic imprinting disorders may be induced by certain embryo culture conditions. The major risk from ovarian stimulation is multiple gestation. About one-third of live-birth deliveries from ART have more than one infant, and twins represent 85% of these multiple-birth children. There are more complications in multiple gestation pregnancies, infants are more likely to be born preterm and with other health problems, and families caring for multiples experience more stress. Transferring fewer embryos per cycle reduces the multiple birth rate from ART, but the patient may have to pay for additional cycles of ART because of a lower likelihood of pregnancy.

Transmission of lymphocytic choriomeningitis virus by organ transplantation.

BACKGROUND: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. METHODS: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause. Epidemiologic investigations, including interviews, environmental assessments, and medical-record reviews, were performed to characterize clinical courses and to determine the cause of the illnesses. RESULTS: Laboratory testing revealed lymphocytic choriomeningitis virus (LCMV) in all the recipients, with a single, unique strain of LCMV identified in each cluster. In both investigations, LCMV could not be detected in the organ donor. In the 2005 cluster, the donor had had contact in her home with a pet hamster infected with an LCMV strain identical to that detected in the organ recipients; no source of LCMV infection was found in the 2003 cluster. The transplant recipients had abdominal pain, altered mental status, thrombocytopenia, elevated aminotransferase levels, coagulopathy, graft dysfunction, and either fever or leukocytosis within three weeks after transplantation. Diarrhea, peri-incisional rash, renal failure, and seizures were variably present. Seven of the eight recipients died, 9 to 76 days after transplantation. One recipient, who received ribavirin and reduced levels of immunosuppressive therapy, survived. CONCLUSIONS: We document two clusters of LCMV infection transmitted through organ transplantation.