White Matter Hyperintensities and Mild TBI in Post-9/11 Veterans and Service Members.

INTRODUCTION: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. MATERIALS AND METHODS: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median postinjury interval of 8 years) or negative mTBI history (n = 198), were examined. RESULTS: White matter hyperintensities were present in both mTBI and comparison groups at similar rates (39% and 37%, respectively). There was an age-by-diagnostic group interaction, such that older Veterans and Service Members with a history of mTBI demonstrated a significant increase in the number of WMHs present compared to those without a history of mTBI. Additional associations between an increase in the number of WMHs and service-connected disability, insulin-like growth factor-1 levels, and worse performance on tests of episodic memory and executive functioning-processing speed were found. CONCLUSIONS: Subtle but important clinical relationships are identified when larger samples of mTBI participants are used to examine the relationship between history of head injury and radiological findings. Future studies should use follow-up magnetic resonance imaging and longitudinal neurobehavioral assessments to evaluate the long-term implications of WMHs following mTBI.

Executive control network resting state fMRI functional and effective connectivity and delay discounting in cocaine dependent subjects compared to healthy controls.

Resting state functional magnetic resonance imaging (fMRI) has been used to study functional connectivity of brain networks in addictions. However, most studies to-date have focused on the default mode network (DMN) with fewer studies assessing the executive control network (ECN) and salience network (SN), despite well-documented cognitive executive behavioral deficits in addictions. The present study assessed the functional and effective connectivity of the ECN, DMN, and SN in cocaine dependent subjects (CD) (n = 22) compared to healthy control subjects (HC) (n = 22) matched on age and education. This study also investigated the relationship between impulsivity measured by delay discounting and functional and effective connectivity of the ECN, DMN, and SN. The Left ECN (LECN), Right ECN (RECN), DMN, and SN functional networks were identified using FSL MELODIC independent component analysis. Functional connectivity differences between CD and HC were assessed using FSL Dual Regression analysis and FSLNets. Effective connectivity differences between CD and HC were measured using the Parametric Empirical Bayes module of Dynamic Causal Modeling. The relationship between delay discounting and functional and effective connectivity were examined using regression analyses. Dynamic causal modeling (DCM) analysis showed strong evidence (posterior probability > 0.95) for CD to have greater effective connectivity than HC in the RECN to LECN pathway when tobacco use was included as a factor in the model. DCM analysis showed strong evidence for a positive association between delay discounting and effective connectivity for the RECN to LECN pathway and for the DMN to DMN self-connection. There was strong evidence for a negative association between delay discounting and effective connectivity for the DMN to RECN pathway and for the SN to DMN pathway. Results also showed strong evidence for a negative association between delay discounting and effective connectivity for the RECN to SN pathway in CD but a positive association in HC. These novel findings provide preliminary support that RECN effective connectivity may differ between CD and HC after controlling for tobacco use. RECN effective connectivity may also relate to tobacco use and impulsivity as measured by delay discounting.

Public attitudes to water fluoridation in the North East of England.

Introduction Local authorities in the North East of England plan to conduct a public consultation on community water fluoridation. Monitoring public opinion is an important consideration.Aims To measure public attitudes in five areas in the North East of England, to determine respondents' sources of information and their awareness of the current fluoridation status of their local water supply.Methods A face-to-face quota sample with quotas set for age, gender and district using six closed questions plus demographics. The questions and sample size were based on earlier similar studies.Results Just over one-third of respondents (283/761, 37%) had read or heard about fluoridation over the previous 12 months. Their main sources of information were local newspapers followed by dental practices. A substantial minority believed, incorrectly, that their water supply was already fluoridated. Sixty percent of respondents were in favour of adding fluoride to the water supply to prevent dental decay while 16% were opposed.Conclusion and recommendation Public opinion in the North East of England remains favourable to community water fluoridation. Monitoring public opinion should be conducted on a regular basis.

Preliminary Findings of Weaker Executive Control Network Resting State fMRI Functional Connectivity in Opioid Use Disorder compared to Healthy Controls.

Objective: Resting state functional magnetic resonance imaging (fMRI) functional connectivity has been used as a tool to study brain mechanisms associated with addictions. Recent research in substance use disorders has focused on three brain networks termed the default mode network (DMN), salience network (SN), and executive control network (ECN). The purpose of this study was to examine the functional connectivity of those three networks in opioid use disorder (OUD) subjects compared to healthy control subjects (HC). Methods: The present study investigated functional connectivity differences between OUD subjects compared to HC using independent component analysis. This study also examined the relationship between functional connectivity and negative urgency scores, as well as compared the functional connectivity of severe OUD to mild or moderate OUD. Results: In OUD subjects (n=25) compared to HC (n=25), a cluster in the left dorsolateral prefrontal cortex within the left ECN had significantly weaker functional connectivity. No significant differences were found between groups for the functional connectivity of the DMN, SN, or right ECN. No significant associations were found between functional connectivity and negative urgency, and no differences were found between severe OUD and mild or moderate OUD. Conclusion: These novel preliminary results suggest that ECN functional connectivity may differ between OUD and HC. This finding is consistent with previous research showing altered executive function in OUD and supports further examination of ECN functional connectivity in association with treatment response in OUD. Given our relatively small sample size (50 subjects total; 25 subjects per group), our results should be treated as preliminary for hypothesis generation, and replication will be needed in future studies.

Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder.

Individuals with opioid use disorder (OUD) often relapse when exposed to opioid-related cues. Previous functional magnetic resonance imaging (fMRI) studies have identified neuronal corticolimbic changes related to drug cue reactivity in OUD. However, the corresponding manner in which brain regions interact is still unclear. Effective (directional) connectivity was analyzed using dynamic causal modeling of fMRI data acquired from 27 OUD participants (13 with OUD and 14 with OUD and cocaine use disorder [OUD+CUD]), while performing an opioid-word Stroop task. Participants were shown opioid and neutral words presented in different colors and were instructed to indicate word color but ignore word meaning. The effects of opioid words relative to neutral words on effective connectivity and on behavioral reaction time were defined as modulatory change and attentional bias, respectively. For all the 27 participants, left anterior cingulate cortex (ACC) to right hippocampus effective connectivity exhibited the largest modulatory change, which was positively correlated with attentional bias. The findings for the ACC to hippocampus EC were consistent across OUD and CUD found in a previous study.

Brain Training with Video Games in Covert Hepatic Encephalopathy.

Despite the associated adverse outcomes, pharmacologic intervention for covert hepatic encephalopathy (CHE) is not the standard of care. We hypothesized that a video game-based rehabilitation program would improve white matter integrity and brain connectivity in the visuospatial network on brain magnetic resonance imaging (MRI), resulting in improved cognitive function in CHE subjects on measures consistent with the cognitive skill set emphasized by the two video games (e.g., IQ Boost-visual working memory, and Aim and Fire Challenge-psychomotor speed), but also generalize to thinking skills beyond the focus of the cognitive training (Hopkins verbal learning test (HVLT)-verbal learning/memory) and improve their health-related quality of life (HRQOL). The trial included three phases over 8 weeks; during the learning phase (cognitive tests administered twice over 2 weeks without intervening intervention), training phase (daily video game training for 4 weeks), and post-training phase (testing 2 weeks after the video game training ended). Thirty CHE patients completed all visits with significant daily achievement on the video games. In a subset of 13 subjects that underwent brain MRI, there was a significant decrease in fractional anisotropy, and increased radial diffusivity (suggesting axonal sprouting or increased cross-fiber formation) involving similar brain regions (i.e., corpus callosum, internal capsule, and sections of the corticospinal tract) and improvement in the visuospatial resting-state connectivity corresponding to the video game training domains. No significant corresponding improvement in HRQOL or HVLT performance was noted, but cognitive performance did transiently improve on cognitive tests similar to the video games during training. Although multimodal brain imaging changes suggest reductions in tract edema and improved neural network connectivity, this trial of video game brain training did not improve the HRQOL or produce lasting improvement in cognitive function in patients with CHE.

Supervised learning technique for the automated identification of white matter hyperintensities in traumatic brain injury.

BACKGROUND: White matter hyperintensities (WMHs) are foci of abnormal signal intensity in white matter regions seen with magnetic resonance imaging (MRI). WMHs are associated with normal ageing and have shown prognostic value in neurological conditions such as traumatic brain injury (TBI). The impracticality of manually quantifying these lesions limits their clinical utility and motivates the utilization of machine learning techniques for automated segmentation workflows. METHODS: This study develops a concatenated random forest framework with image features for segmenting WMHs in a TBI cohort. The framework is built upon the Advanced Normalization Tools (ANTs) and ANTsR toolkits. MR (3D FLAIR, T2- and T1-weighted) images from 24 service members and veterans scanned in the Chronic Effects of Neurotrauma Consortium's (CENC) observational study were acquired. Manual annotations were employed for both training and evaluation using a leave-one-out strategy. Performance measures include sensitivity, positive predictive value, [Formula: see text] score and relative volume difference. RESULTS: Final average results were: sensitivity = 0.68 ± 0.38, positive predictive value = 0.51 ± 0.40, [Formula: see text] = 0.52 ± 0.36, relative volume difference = 43 ± 26%. In addition, three lesion size ranges are selected to illustrate the variation in performance with lesion size. CONCLUSION: Paired with correlative outcome data, supervised learning methods may allow for identification of imaging features predictive of diagnosis and prognosis in individual TBI patients.

Valedictory Editorial: The past six years.

Fifty years ago this month I graduated from the University of Liverpool. A few months earlier, along with three friends, I had driven overland to attend the International Dental Students Congress held that year in Israel. On the way we drove the spectacular road from Beirut up to Damascus, visited Petra in the Southern Jordanian desert, at that time devoid of tourists, viewed the Chagall windows in the synagogue on the Hadassah University Medical campus, and listened to the world cup final with a group of German students in a youth hostel overlooking the Mandelbaum Gate. Little did we know that within twelve months these beautiful countries and their kind people would be plunged into war and that this conflict and chaos would continue to haunt this region, almost unabated, for the next fifty years.

A randomized controlled trial of outreach placement's effect on dental students' clinical confidence.

This randomized controlled trial compared the effects of outreach placement with traditional, exclusively dental school-based clinical experience on students' confidence in providing treatment for patients presenting with common dental problems. Senior dental students (n=49) were allocated at random to existing dental school-based clinics or placement in primary care clinics to work supervised by local dentists. At baseline, students self-rated their global confidence on a five-point scale. These measures were repeated at follow-up, augmented by a transition judgment and a then-test of confidence (asking students to look back and re-rate their pre-placement confidence). Groups were comparable at baseline. Follow-up scores for global confidence were similar between groups. The outreach group scored higher in the transition judgment (mean 3.7, SD 0.9) than the control group (mean 3.1, SD 1.1, P=0.05). In the then-test, on reflection, the outreach group considered their baseline ratings of confidence were overoptimistic (mean then-test scores 3.2, SD 0.9 and baseline 3.7, SD 0.5) while the control group thought theirs were accurate (mean then-test scores 3.8, SD 0.7 and baseline 3.6, SD 0.8, P=0.01). The findings suggest dental outreach training in primary care settings is more effective than dental school training alone in improving students' confidence in tackling clinical situations. The measurement of change in confidence is complicated by shifts in students' internal scales arising from insights gained on outreach.

The effective use of fluorides in public health.

Dental caries remain a public health problem for many developing countries and for underprivileged populations in developed countries. This paper outlines the historical development of public health approaches to the use of fluoride and comments on their effectiveness. Early research and development was concerned with waterborne fluorides, both naturally occurring and added, and their effects on the prevalence and incidence of dental caries and dental fluorosis. In the latter half of the 20th century, the focus of research was on fluoride toothpastes and mouth rinses. More recently, systematic reviews summarizing these extensive databases have indicated that water fluoridation and fluoride toothpastes both substantially reduce the prevalence and incidence of dental caries. We present four case studies that illustrate the use of fluoride in modern public health practice, focusing on: recent water fluoridation schemes in California, USA; salt fluoridation in Jamaica; milk fluoridation in Chile; and the development of "affordable" fluoride toothpastes in Indonesia. Common themes are the concern to reduce demands for compliance with fluoride regimes that rely upon action by individuals and their families, and the issue of cost. We recommend that a community should use no more than one systemic fluoride (i.e. water or salt or milk fluoridation) combined with the use of fluoride toothpastes, and that the prevalence of dental fluorosis should be monitored in order to detect increases in or higher-than-acceptable levels.

Effective use of fluorides for the prevention of dental caries in the 21st century: the WHO approach.

Despite great improvements in the oral health of populations across the world, problems still persist particularly among poor and disadvantaged groups in both developed and developing countries. According to the World Oral Health Report 2003, dental caries remains a major public health problem in most industrialized countries, affecting 60-90% of schoolchildren and the vast majority of adults. Although it appears that dental caries is less common and less severe in developing countries of Africa, it is anticipated that the incidence of caries will increase in several countries of that continent, due to changing living conditions and dietary habits, and inadequate exposure to fluorides. Research on the oral health effects of fluoride started around 100 years ago; the focus has been on the link between water and fluorides and dental caries and fluorosis, topical fluoride applications, fluoride toothpastes, and salt and milk fluoridation. Most recently, efforts have been made to summarize the extensive database through systematic reviews. Such reviews concluded that water fluoridation and use of fluoride toothpastes and mouthrinses significantly reduce the prevalence of dental caries. WHO recommends for public health that every effort must be made to develop affordable fluoridated toothpastes for use in developing countries. Water fluoridation, where technically feasible and culturally acceptable, has substantial advantages in public health; alternatively, fluoridation of salt and milk fluoridation schemes may be considered for prevention of dental caries.

Parental perception of fluorosis among 8-year-old children living in three communities in Iceland, Ireland and England.

OBJECTIVES: To assess the impact of enamel fluorosis in three of the communities examined in 'Project FLINT', it was decided to conduct a structured telephone interview with the parents of some of the children who took part in the study. METHODS: Three communities involved in this project were able to conduct this investigation: Reykjavik (Iceland), Cork (Ireland) and Knowsley (England). The aim was to interview the parents of children with a range of Thylstrup and Fejerskov (TF) index grades selected from each participating centre with respect to the appearance of their child's permanent maxillary central incisors. Interviewers were blinded as to the TF grade of the subject. RESULTS: Interviews were conducted with parents of 215 children: 69 with TF grade 0; 70 with TF grade 1; 60 with TF grade 2 and 16 with TF grade 3 or greater. There was a trend towards more parents being unhappy with the appearance of their child's teeth with increasing TF grade. However, the main reasons given by parents for being unhappy with the appearance of their child's teeth was tooth alignment followed by the more yellow colour of permanent compared with primary teeth. Only with a TF grade of 3 was any appreciable concern expressed about fluorosis. CONCLUSION: It would appear that there is a public awareness of both developmental defects and enamel fluorosis although this is not always expressed as dissatisfaction. Further research is required into the clinical impact of both fluorosis and other developmental defects of enamel.