Functional brain activation during arithmetic processing in females with fragile X Syndrome is related to FMR1 protein expression

Arithmetic processing deficits in persons with fragile X Syndrome (fraX), the most common heritable cause of mental retardation, are well known. In this study, we characterize the neural underpinnings of these performance deficits using functional MRI. Given that a single gene defect (FMR1) is known to be responsible for this disorder, we also assess whether brain activation in arithmetic processing areas is related to amount of FMR1 protein expression (FMRP). Subjects included 16 females with fraX, and 16 female age-matched controls. Subjects viewed arithmetic equations with two (1 + 3 = 4) or three (2 + 3 - 1 = 5) operands, and were asked to judge whether the results were correct or not. Subjects with fraX showed significant impairment in behavioral performance on the 3-operand but not the 2-operand arithmetic equations. Significant brain activation was observed bilaterally in the prefrontal and parietal cortices for unaffected subjects, and bilateral prefrontal and left angular gyrus for subjects with fraX, for both trial types. Subjects with fraX exhibited less overall activation than did unaffected subjects in both types of trials; and, unlike the unaffected group, did not show increased extent of activation in association with greater task difficulty. During the 3-operand trials, activation in bilateral prefrontal and motor/premotor, and left supramarginal and angular gyri were positively correlated with FMRP, suggesting that decreased FMR1 protein expression underlies deficits in math performance in persons with fraX. More broadly, this investigation demonstrates a unique bridging of cognitive and molecular neuroscience and represents a useful approach for the study of brain development and function.     

Relating semantic and episodic memory systems

Episodic and semantic memory are two forms of declarative memory which appear to function in distinct yet interdependent ways. Here we provide direct evidence for a functional relationship between these two memory systems by showing that left lateral temporal lobe regions involved in semantic memory play an important role in accurate episodic memory retrieval.     

Amygdalar activation associated with positive and negative facial expressions

Most theories of amygdalar function have underscored its role in fear. One broader theory suggests that neuronal activation of the amygdala in response to fear-related stimuli represents only a portion of its more widespread role in modulating an organism's vigilance level. To further explore this theory, the amygdalar response to happy, sad, angry, fearful, and neutral faces in 17 subjects was characterized using 3 T fMRI. Utilizing a random effects model and hypothesis-driven analytic strategy, it was observed that each of the four emotional faces was associated with reliable bilateral activation of the amygdala compared with neutral. These findings suggest a broader role for the amygdala in modulating the vigilance level during the perception of several negative and positive facial emotions.     

An ecological risk assessment for triclosan in lotic systems following discharge from wastewater treatment plants in the United States

A modeling study was conducted to examine the distribution of concentrations of the antimicrobial triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) in rivers following discharge from wastewater treatment plants (WWTPs). Most uses of triclosan are disposed of down residential drains and ultimately reach WWTPs. A modeling analysis was conducted to simulate the discharge of triclosan in WWTP effluents to rivers and calculate the expected concentrations based on characteristics of the reach where the discharge occurred, the estimated concentration of triclosan in the WWTP effluent, and the physicochemical properties of triclosan. A probabilistic exposure assessment was conducted based on data on the characteristics of U.S. reaches receiving wastewater discharges and the physicochemical characteristics of triclosan. A risk assessment was conducted by comparing the estimated concentrations with toxicity endpoint concentrations for species representative of key ecological groups. For fish and invertebrates, neither acute nor chronic risks are of concern, and no concerns exist for vascular aquatic plants. However, certain types of algae are the most sensitive species to triclosan by more than an order of magnitude than other algal or aquatic plant species. For these algae, the potential exists for some risk from triclosan exposure near the WWTP discharge location during low-flow-rate periods for some WWTPs with small dilutions. The risks downstream are lower because of dissipation of triclosan.     

Exercise participation after diagnosis of breast cancer: trends and effects on mood and quality of life

Individuals treated for cancer often experience higher levels of emotional distress than the general population. Previous research has shown that exercise can have an ameliorating effect on these problems. This 12-month prospective longitudinal study investigated mood, quality of life, cancer-related symptoms, and exercise behavior of 69 women who had completed treatment for Stage 0-2 breast cancer. We studied the natural progression of exercise participation after cancer treatment. Effects on mood, quality of life, and cancer-related symptoms were assessed after controlling for demographic variables, disease variables, social support, and baseline values to test the hypothesis that women who exercised were more likely to report better mood, higher quality of life, and fewer cancer-related symptoms. Results indicated that women did not increase their exercise participation over time and that overall mean minutes of exercise participation were below recommended levels. Baseline demographic predictors of exercise participation included younger age, having a spouse or partner, increased time since diagnosis, higher social support, and higher depression. Exercise participation was associated with improved physical functioning, but not overall mood or cancer-related symptoms. We discuss implications of these findings towards the well-being of breast cancer survivors.     

How to get paid for a new diabetes product

Manufacturers of diabetes devices and supplies ("Products") should consider developing information during the Products' clinical trials that will assist in the later marketing of their Products. Manufacturers should engage in the clinical trials of their Products physicians who may be able to provide future assistance in obtaining appropriate reimbursement codes for the Products. Manufacturers should develop during the clinical trial process cost-effectiveness information that can be used to pursue coverage and reimbursement decisions from third-party payors in the future. Different Product reimbursement codes are developed by the American Medical Association and by the Centers for Medicare and Medicaid Services. For both these organizations there is a long time frame to get any code established. Manufacturers can develop information in a way that will make these time periods shorter if the appropriate strategy is developed early in the Product development process.     

Functional brain activation during cognition is related to FMR1 gene expression

Fragile X syndrome, the most common known cause of inherited mental retardation, is caused by alterations of the FMR1 gene encoding the FMRP protein. We investigated the relation between FMRP protein levels and functional brain activation during a working memory task. Our study provides the first evidence for a relation between FMR1 gene expression and neural activity during higher-order cognition. More broadly, our findings provide the first demonstration of how gene-brain-behavior investigations can help to bridge the gap between molecular and systems neuroscience.     

Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia?

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.     

Cortisol and social stressors in children with fragile X: a pilot study

Evidence of neuroendocrine dysfunction, behavioral features of social anxiety and avoidance, and neuroanatomical abnormalities suggest that abnormal hypothalamic-pituitary-adrenal (HPA) function may be a component of the fragile X (fra X) syndrome. In this preliminary study, salivary cortisol levels of males (n = 8, mean age = 13.5 yr) and females (n = 7, mean age = 13.9 yr) with the fra X full mutation were studied for 3 days. Day 1 was an experimental day, during which subjects experienced a Social Stressor task midmorning. Days 2 and 3 were routine days, during which the subjects were engaged in their typical activities. Saliva samples were collected before breakfast, lunch, dinner, and bedtime. On the experimental day, the prelunch sample collection occurred 30 and 90 minutes after the Social Stressor task. Compared with children's norms, the combined group of males and females with fra X had significantly higher cortisol levels in the prelunch and the prebedtime samples for the routine days. Comparisons between the two fra X groups for the experimental day revealed similar diurnal patterns for cortisol level. However, compared with females with fra X, males with fra X had significantly higher cortisol levels at two points during the day: 30 minutes after the social stressor and at bedtime. These preliminary data suggest that individuals with fra X have abnormal HPA function. Understanding the relations among HPA dysfunction, abnormalities in brain structure and/or function, and maladaptive behavior and cognition in fra X could inform the design of early interventions using pharmacological or environmental measures designed to normalize neuroendocrine function.     

Morphological alteration of temporal lobe gray matter in dyslexia: an MRI study

Functional imaging studies of developmental dyslexia have reported reduced task-related neural activity in the temporal and inferior parietal cortices. To examine the possible contribution of subtle anatomic deviations to these reductions, volumes were measured for the major lobes of the brain, the subcortical nuclei, cerebellum, and lateral ventricles on magnetic resonance imaging (MRI) scans from 16 right-handed dyslexic men, ages 18 to 40, and 14 matched controls, most of whom had previously undergone PET imaging. A specific decrease in tissue volume was localized to the temporal lobes and was particularly prominent on the left (p < .01). An analysis of tissue composition revealed that this reduction was primarily attributable to decreased gray matter within the left temporal lobe (p < .002). Further segmentation of the temporal lobe showed that this reduction was not confined to the superior temporal gyrus, the primary location of primary auditory cortex. Reductions of temporal lobe gray matter may reflect a regional decrease in neuronal number or neuropil, which in turn may result in reading impairment.