R1ρ dispersion in white matter correlates with quantitative metrics of cognitive impairment.

Much previous neuroimaging research in Alzheimer's disease has focused on the roles of amyloid and tau proteins, but recent studies have implicated microvascular changes in white matter as early indicators of damage related to later dementia. We used MRI to derive novel, non-invasive measurements of R1ρ dispersion using different locking fields to characterize variations of microvascular structure and integrity in brain tissues. We developed a non-invasive 3D R1ρ dispersion imaging technique using different locking fields at 3T. We acquired MR images and cognitive assessments of participants with mild cognitive impairment (MCI) and compared them to age-matched healthy controls in a cross-sectional study. After providing informed consent, 40 adults aged 62 to 82 years (n = 17 MCI) were included in this study. White matter ΔR1ρ-fraction measured by R1ρ dispersion imaging showed a strong correlation with the cognitive status of older adults (ßstd = -0.4, p-value < 0.01) independent of age, in contrast to other conventional MRI markers such as T2, R1ρ, and white matter hyperintense lesion volume (WMHs) measured with T2-FLAIR. The correlation of WMHs with cognitive status was no longer significant after adjusting for age and sex in linear regression analysis, and the size of the regression coefficient was substantially decreased (53% lower). This work establishes a new non-invasive method that potentially characterizes impairment of the microvascular structure of white matter in MCI patients compared to healthy controls. The application of this method in longitudinal studies would improve our fundamental understanding of the pathophysiologic changes that accompany abnormal cognitive decline with aging and help identify potential targets for treatment of Alzheimer's disease.

Contemporary Pharmacotherapeutics and the Management of Aggressive Behavior in an Adolescent Animal Model of Maladaptive Aggression.

OBJECTIVE: Antipsychotic and anticonvulsant medications are increasingly being used as pharmacotherapeutic treatments for maladaptive aggression in youth, yet no information is available regarding whether these drugs exhibit aggression- specific suppression in preclinical studies employing adolescent animal models of maladaptive aggression. This study examined whether the commonly used antipsychotics medications haloperidol and risperidone and the anticonvulsant medication valproate exert selective aggression-suppressing effects using a validated adolescent animal model of maladaptive aggression. METHODS: Twenty-seven-day old Syrian hamsters (Mesocricetus auratus) were administered testosterone for 30 consecutive days during the first 4 weeks of adolescent development. The following day (during late adolescence), experimental animals received a single dose of haloperidol (0.00, 0.025, 0.50, 1.0 mg/kg), risperidone (0.00, 0.01, 0.03, 1.0 mg/kg), or valproate (0.00, 1.0, 5.0, 10.0 mg/kg) and tested for offensive aggression using the Resident/Intruder Paradigm. As a baseline, non-aggressive behavioral control, a separate set of pubertal hamsters was treated with sesame oil vehicle during the first 4 weeks of adolescence and then tested for aggression during late adolescence in parallel with the haloperidol, risperidone or valproate-treated experimental animals. RESULTS: Risperidone and valproate selectively reduced the highly impulsive and intense maladaptive aggressive phenotype in a dose-dependent fashion. While haloperidol marginally reduced aggressive responding, its effects were non-specific as the decrease in aggression was concurrent with reductions in a several ancillary (non-aggressive) behaviors. CONCLUSION: These studies provide pre-clinical evidence that the contemporary pharmacotherapeutics risperidone and valproate exert specific aggression-suppressing effects in an adolescent animal model of maladaptive aggression.

Serotonin type-3 receptors differentially modulate anxiety and aggression during withdrawal from adolescent anabolic steroid exposure.

Male Syrian hamsters (Mesocricetus auratus) administered anabolic/androgenic steroids during adolescent development display increased aggression and decreased anxious behavior during the adolescent exposure period. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts and hamsters exhibit decreased aggression and increased anxious behavior. This study investigated the hypothesis that alterations in anterior hypothalamic signaling through serotonin type-3 receptors modulate the behavioral shift between adolescent anabolic/androgenic steroid-induced aggressive and anxious behaviors during the withdrawal period. To test this, hamsters were administered anabolic/androgenic steroids during adolescence then withdrawn from drug exposure for 21 days and tested for aggressive and anxious behaviors following direct pharmacological manipulation of serotonin type-3 receptor signaling within the latero-anterior hypothalamus. Blockade of latero-anterior hypothalamic serotonin type-3 receptors both increased aggression and decreased anxious behavior in steroid-treated hamsters, effectively reversing the pattern of behavioral responding normally observed during anabolic/androgenic steroid withdrawal. These findings suggest that the state of serotonin neural signaling within the latero-anterior hypothalamus plays an important role in behavioral shifting between aggressive and anxious behaviors following adolescent exposure to anabolic/androgenic steroids.

Assessing the relevance, efficiency, and sustainability of HIV/AIDS in-service training in Nigeria.

More than three million people in Nigeria are living with HIV/AIDS. In order to reduce the HIV/AIDS burden in Nigeria, the US Government (USG) has dedicated significant resources to combating the epidemic through the President's Emergency Plan for AIDS Relief (PEPFAR). In-service training (IST) of health workers is one of the most commonly used strategies to improve the quality and coverage of HIV/AIDS services. At USAID/Nigeria's request, the USAID-funded CapacityPlus project conducted an assessment of PEPFAR-funded IST for all cadres of health workers in Nigeria. Using the IST Improvement Framework, developed by the USAID Applying Sciences to Strengthen and Improve Systems Project (ASSIST), as a guide, the authors developed a survey tool to assess the efficiency, effectiveness and sustainability of IST provided between January 2007 and July 2012 by PEPFAR-funded implementing partners in Nigeria. The instrument was adapted to the Nigerian context and refined through a stakeholder engagement process. It was then distributed via an online platform to more than 50 PEPFAR-funded implementing partners who provided IST in Nigeria. A total of 39 implementing partners completed the survey. Our survey found that PEPFAR implementing partners have been providing a wide range of IST to a diverse group of health workers in Nigeria since 2007. Most trainings are developed using national curricula, manuals and/or other standard operating procedures. Many of the partners are conducting Training Needs Assessments to inform the planning, design and development of their training programs. However, the assessment also pointed to a number of recommendations to increase the efficiency, effectiveness and sustainability of PEPFAR-funded IST. These actions are as follows: improve collaboration and coordination among implementing partners; apply a more diverse and cost-effective set of training modalities; allocate funding specifically for the evaluation of the effectiveness of training; improve links between IST and both continuing professional development and pre-service education; require implementing partners to create sustainability plans to transition training from PEPFAR funding to other funding sources; and develop a training information management system to track key aspects of IST, such as the number and types of providers, courses, and participants of PEPFAR-funded IST.

Plasticity in the rat posterior auditory field following nucleus basalis stimulation.

Classical conditioning paradigms have been shown to cause frequency-specific plasticity in both primary and secondary cortical areas. Previous research demonstrated that repeated pairing of nucleus basalis (NB) stimulation with a tone results in plasticity in primary auditory cortex (A1), mimicking the changes observed after classical conditioning. However, few studies have documented the effects of similar paradigms in secondary cortical areas. The purpose of this study was to quantify plasticity in the posterior auditory field (PAF) of the rat after NB stimulation paired with a high-frequency tone. NB-tone pairing increased the frequency selectivity of PAF sites activated by the paired tone. This frequency-specific receptive field size narrowing led to a reorganization of PAF such that responses to low- and mid-frequency tones were reduced by 40%. Plasticity in A1 was consistent with previous studies -- pairing a high-frequency tone with NB stimulation expanded the high-frequency region of the frequency map. Receptive field sizes did not change, but characteristic frequencies in A1 were shifted after NB-tone pairing. These results demonstrate that experience-dependent plasticity can take different forms in both A1 and secondary auditory cortex.