White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study

Diffusion tensor imaging was used to evaluate cerebral white matter in eight patients (ages 10-17), with myotonic dystrophy type 1 (3 congenital-onset, 5 juvenile-onset) compared to eight controls matched for age and sex. Four regions of interest were examined: inferior frontal, superior frontal, supracallosal, and occipital. The myotonic dystrophy group showed white matter abnormalities compared to controls in all regions. All indices of white matter integrity were abnormal: fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. With no evidence of regional variation, correlations between whole cerebrum white matter fractional anisotropy and neurocognitive functioning were examined in the patients. Strong correlations were observed between whole cerebrum fractional anisotropy and full-scale intelligence and a measure of executive functioning. Results indicate that significant white matter abnormality is characteristic of young patients with myotonic dystrophy type 1 and that the white matter abnormality seen with neuroimaging has implications for cognitive functioning.     

Transcranial direct current stimulation and constraint-induced therapy in cerebral palsy: A randomized,blinded, sham-controlled clinical trial

We investigated the safety, feasibility, and efficacy of transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) in children and young adults with unilateral cerebral palsy. Twenty participants were randomized to receive active or sham tDCS. The intervention consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers, and interventionists were blinded to group assignment. The primary safety outcome investigated adverse events. The primary behavioral outcome was the Assisting Hand Assessment. All 20 participants (mean age = 12.7 yrs, range = 7.4–21.6 years) were evaluated for the primary outcomes. No serious adverse events occurred, and the most commonly reported minor adverse events were headache and itchiness. Both groups demonstrated a significant improvement in hand function after the intervention, although no significant effect of tDCS was observed (between-group difference = ?2.18, 95% CI = [?6.48, 2.12], p = 0.30). Although hand function improved overall, no significant differences between intervention groups were found. Children with preserved corticospinal tract circuitry from the lesioned hemisphere, compared to those without, showed greater improvement in hand function (mean difference = 3.04, 95% CI = [?0.64, 6.72], p = 0.099). Our study demonstrates the safety and feasibility of serial sessions of tDCS, and presents preliminary evidence for the effect of CST circuitry on outcomes following tDCS/CIMT. Future work in children with unilateral cerebral palsy should focus on the optimal dosing and consider individual brain circuitry when describing response to combined interventions.

Molecular epidemiology of eastern equine encephalitis virus, New York

Perpetuation, overwintering, and extinction of eastern equine encephalitis virus (EEEV) in northern foci are poorly understood. We therefore sought to describe the molecular epidemiology of EEEV in New York State during current and past epizootics. To determine whether EEEV overwinters, is periodically reintroduced, or both, we sequenced the E2 and partial NSP3 coding regions of 42 EEEV isolates from New York State and the Eastern Seaboard of the United States. Our phylogenetic analyses indicated that derived subclades tended to contain southern strains that had been isolated before genetically similar northern strains, suggesting southern to northern migration of EEEV along the Eastern Seaboard. Strong clustering among strains isolated during epizootics in New York from 2003-2005, as well as from 1974-1975, demonstrates that EEEV has overwintered in this focus. This study provides molecular evidence for the introduction of southern EEEV strains to New York, followed by local amplification, perpetuation, and overwintering.     

Design considerations for a study to evaluate the impact of smoking cessation treatment on stimulant use outcomes in stimulant-dependent individuals

Cigarette smoking is prevalent in cocaine/methamphetamine-dependent patients and associated with significant morbidity and mortality, yet, the provision of smoking cessation treatment in conjunction with substance use disorder (SUD) treatment is not standard practice. This is due, in part, to clinician concern that combining smoking cessation treatment with SUD treatment could lead to poorer SUD outcomes. The NIDA Clinical Trials Network is conducting a 10-week, two-group, randomized trial to evaluate the impact of providing smoking cessation treatment (SCT) with SUD treatment as usual (TAU), compared to TAU alone, in smokers who are in outpatient treatment for cocaine or methamphetamine dependence. Approximately 528 participants, recruited from 12 community treatment programs, will be randomized into the trial. The present paper describes key design decisions made during protocol development. The trial is designed to evaluate the relationship between cigarette smoking and stimulant use, which prior research suggests is linked, and should contribute to our understanding of how best to address the co-occurring problems of nicotine dependence and cocaine/methamphetamine-dependence. Unique aspects of the trial include the primary question of interest, which concerns the impact of providing SCT on SUD outcomes rather than on smoking outcomes, and the intensity of the SCT chosen, which includes bupropion, nicotine replacement, and two psychosocial interventions.     

Altered resting state complexity in schizophrenia

The complexity of the human brain's activity and connectivity varies over temporal scales and is altered in disease states such as schizophrenia. Using a multi-level analysis of spontaneous low-frequency fMRI data stretching from the activity of individual brain regions to the coordinated connectivity pattern of the whole brain, we investigate the role of brain signal complexity in schizophrenia. Specifically, we quantitatively characterize the univariate wavelet entropy of regional activity, the bivariate pairwise functional connectivity between regions, and the multivariate network organization of connectivity patterns. Our results indicate that univariate measures of complexity are less sensitive to disease state than higher level bivariate and multivariate measures. While wavelet entropy is unaffected by disease state, the magnitude of pairwise functional connectivity is significantly decreased in schizophrenia and the variance is increased. Furthermore, by considering the network structure as a function of correlation strength, we find that network organization specifically of weak connections is strongly correlated with attention, memory, and negative symptom scores and displays potential as a clinical biomarker, providing up to 75% classification accuracy and 85% sensitivity. We also develop a general statistical framework for the testing of group differences in network properties, which is broadly applicable to studies where changes in network organization are crucial to the understanding of brain function.     

MRI assessment of cerebral oxygen metabolism in cocaine‐addicted individuals: hypoactivity and dose dependence

Long‐term cocaine use is known to negatively impact neural and cerebrovascular systems. However, the use of imaging markers to separately assess these parameters remains challenging. The primary reason is that most functional imaging markers, such as cerebral blood flow, functional connectivity, and task‐evoked functional MRI, are known to reflect a complex interplay between neural and vascular components, thus the interpretation of the results is not straightforward. The goal of the present study is to examine neural‐activity‐specific changes in cocaine addiction, using cerebral metabolic rate of oxygen (CMRO2) as a surrogate marker of aggregated neural activity. We applied a recently developed CMRO2 technique in 13 cocaine‐addicted subjects and 13 age‐ and gender‐matched control subjects, and examined the impact of long‐term cocaine use on CMRO2. Our results showed that CMRO2 in cocaine‐addicted subjects (152 ± 16 µmol/100 g/min) is significantly lower (p = 0.031) than that in controls (169 ± 20 µmol/100 g/min). Furthermore, the severity of this decreased metabolism is associated with lifetime cocaine use (p = 0.05). Additionally, the CMRO2 reduction was accompanied by a trend of decrease in cerebral blood flow (p = 0.058), but venous oxygenation was unaffected (p = 0.96), which suggested that the CMRO2 change may be attributed to a vascular deficiency in chronic cocaine users. To our knowledge, this is the first study to measure CMRO2 in cocaine‐addicted individuals. Our findings suggest that CMRO2 may be a promising approach for assessing the long‐term effects of cocaine use on the brain. Copyright © 2014 John Wiley & Sons, Ltd.     

Addictive‐like behaviours to ultraviolet light among frequent indoor tanners

Background. Frequent, purposeful exposure to ultraviolet (UV) light may induce a compulsive desire to tan despite the negative consequences being known, suggesting a behavioural complex similar to addictive disorders. Aim. To assess the presence of addictive‐like behaviours in subjects using indoor tanning salons. Methods. Subjects (n = 100) were surveyed by two questionnaires: a modified CAGE questionnaire to assess behaviours consistent with problem tanning and a modified Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM‐IV) (‘substance dependence’ criteria) to assess behaviours consistent with a dependence‐like disorder. Results. In total, 41% of subjects met criteria consistent with a ‘tanning addictive disorder’, and an additional 33% met criteria for problematic tanning behaviour based on the modified CAGE criteria or subthreshold criteria on the modified DSM‐IV criteria. Female gender and early age of onset were associated with meeting tanning addiction criteria. Conclusion. A high percentage of subjects who tan frequently in indoor salons experience behaviours and consequences to their tanning consistent with other identified addictive disorders.