Objective To test the existence of sex differences in cortical activation during verb generation when performance is controlled for. Methods 20 male and 20 female healthy adults underwent fMRI using a covert verb generation task (BD-VGT) and its event-related version (ER-VGT) that allowed for intra-scanner recordings of overt responses. Task-specific activations were determined using the following contrasts: BD-VGT covert generation>finger-tapping; ER-VGT overt generation>repetition; ER-VGT overt>covert generation. Lateral cortical regions activated during each contrast were used for calculating language lateralization index scores. Voxelwise regressions were used to determine sex differences in activation, with and without controlling for performance. Each brain region showing male/female activation differences for ER-VGT overt generation>repetition (isolating noun-verb association) was defined as a region of interest (ROI). For each subject, the signal change in each ROI was extracted, and the association between ER-VGT activation related to noun-verb association and performance was assessed separately for each sex. Results Males and females performed similarly on language assessments, had similar patterns of language lateralization, and exhibited similar activation patterns for each fMRI task contrast. Regression analysis controlling for overt intra-scanner performance either abolished (BD-VGT) or reduced (ER-VGT) the observed differences in activation between sexes. The main difference between sexes occurred during ER-VGT processing of noun-verb associations, where males showed greater activation than females in the right middle/superior frontal gyrus (MFG/SFG) and the right caudate/anterior cingulate gyrus (aCG) after controlling for performance. Better verb generation performance was associated with increased right caudate/aCG activation in males and with increased right MFG/SFG activation in females. Conclusions Males and females exhibit similar activation patterns during verb generation fMRI, and controlling for intra-scanner performance reduces or even abolishes sex differences in language-related activation. These results suggest that previous findings of sex differences in neuroimaging studies that did not control for task performance may reflect false positives.

Behavioral studies have shown that verbal information is better retained when it is self-generated rather than read (learned passively). We used fMRI and a paired associates task to examine brain networks underlying self-generated memory encoding. Subjects were 49 healthy English speakers ages 19–62 (30 female). In the fMRI task, related word pairs were presented in a “read” condition, where subjects viewed both words and read the second word aloud, or a “generate” condition, where the second word was presented with only the first letter and the subject was required to generate the word. Thirty word pairs were presented in each condition. After the fMRI scan, words that were read or generated were presented, each with two foils, in a forced-choice recognition task. On the recognition post-test, words from the “generate” condition were more correctly recognized than from the “read” condition (80.0% for generated words versus 72.0% for read words; t(48) = 5.17, p < 0.001). FMRI revealed increased activation for generate>read in inferior/middle frontal gyri bilaterally (L>R), anterior cingulate, and caudate nucleus and the temporo-parietal-occipital junction bilaterally. For the “read” condition, better subsequent memory performance across individual subjects was positively correlated with activation in the cuneus bilaterally. In the “generate” condition, better subsequent memory performance was positively correlated with activation in the left superior temporal gyrus. These results suggest that self-generation improves memory performance, that enhanced cortical activation accompanies self-generated encoding, and that recruitment of a specific brain network underlies self-generated encoding. The findings may have implications for the development of procedures to enhance memory performance.

Verbal information is better retained when it is self-generated rather than when it is received passively. The application of self-generation procedures has been found to improve memory in healthy elderly and in individuals with impaired cognition. Overall, the available studies support the notion that active participation in verbal encoding engages memory mechanisms that supplement those used during passive observation. Thus, the objective of this study was to investigate the age-related changes in the neural mechanisms involved in the encoding of paired-associates using a self-generation method that has been shown to improve memory performance across the lifespan. Subjects were 113 healthy right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18–76, native speakers of English with no history of neurological or psychiatric disorders. Subjects underwent fMRI at 3 T while performing didactic learning (“read”) or self-generation learning (“generate”) of 30 word pairs per condition. After fMRI, recognition memory for the second word in each pair was evaluated outside of the scanner. On the post-fMRI testing more “generate” words were correctly recognized than “read” words (p < 0.001) with older adults recognizing the “generated” words less accurately (p < 0.05). Independent component analysis of fMRI data identified task-related brain networks. Several components were positively correlated with the task reflecting multiple cognitive processes involved in self-generated encoding; other components correlated negatively with the task, including components of the default-mode network. Overall, memory performance on generated words decreased with age, but the benefit from self-generation remained consistently significant across ages. Independent component analysis of the neuroimaging data revealed an extensive set of components engaged in self-generation learning compared with didactic learning, and identified areas that were associated with age-related changes independent of performance.

Purpose Although organic solvents are often used in agricultural operations, neurotoxic effects of solvent exposure have not been extensively studied among famers. The current analysis examined associations between questionnaire-based metrics of organic solvent exposure and depressive symptoms among farmers. Methods Results from 692 male Agricultural Health Study participants were analyzed. Solvent type and exposure duration were assessed by questionnaire. An “ever-use” variable and years of use categories were constructed for exposure to gasoline, paint/lacquer thinner, petroleum distillates, and any solvent. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression Scale (CES-D); scores were analyzed separately as continuous (0-60) and dichotomous (<16 versus ≥16) variables. Multivariate linear and logistic regression models were used to estimate crude and adjusted associations between measures of solvent exposure and CES-D score. Results Forty-one percent of the sample reported some solvent exposure. The mean CES-D score was 6.5 (SD=6.4; median=5; range=0 – 44); 92% of the sample had a score below 16. After adjusting for covariates, statistically significant associations were observed between ever-use of any solvent, long duration of any solvent exposure, ever-use of gasoline, ever-use of petroleum distillates, and short duration of petroleum distillate exposure and continuous CES-D score (p<0.05). Although nearly all associations were positive, fewer statistically significant associations were observed between metrics of solvent exposure and the dichotomized CES-D variable. Conclusions Solvent exposures were associated with depressive symptoms among farmers. Efforts to limit exposure to organic solvents may reduce the risk of depressive symptoms among farmers.

Previous studies have shown that self-generated information is better remembered than information that has been read passively. To further examine this subsequent memory effect, we investigated the effect of five different linguistic relationships on memory encoding. Ninety subjects were administered 60 paired associates during an encoding condition: 30 of the second words from each pair were to be read aloud and 30 were to be self-generated from clues as to the correct word. Word pairs were composed of five linguistic relationships: category, rhyme, opposite, synonym, and association. Subsequently, subjects were presented with the words that were read or generated in a forced recognition memory task. Overall, reading accuracy was higher than generation accuracy during the encoding phase (all P < 0.001). During the recognition phase, subjects' performance was better on the generate than on the read conditions for opposite, synonym, category, and association relationships (all P < 0.05), with no difference in the rhyme relationship. These results confirm previous findings that self-generated information is better remembered than read information and suggest that this advantage may be mediated by using opposite, synonym, category, and association relationships, while rhyme relationship may not extend such an advantage. These findings may have implications for future studies of memory interventions in healthy controls and subjects with cognitive impairments.

Wewish to thank A. Toblin of NUSfor his efforts,in the application of MEPASand his review comments on this report. We wish to acknowledge T. Longo of DOE's Office of Environmental Restoration for detailed review comments. We also wish to acknowledge the valuable insights on ranking parameter issues from the discussion at DOE's working group on risk characterization and External ReviewGroup (ERG). , , Special thanks go to R. J. Aiken of DOE's Office of Environment, Safety, and Health (DOE-ESH) for his comments, guidance, and support in the development of MEPAS.

Workers in various industries can be exposed to oil mists when oil-based fluids are aerosolized during work processes. Oil mists can be inhaled or deposited on the skin. Little research exists on the reproductive effects of oil mist exposure in pregnant workers. We aimed to investigate associations between occupational oil mist exposure in early pregnancy and a spectrum of birth defects using data from 22,011 case mothers and 8140 control mothers in the National Birth Defects Prevention Study. In total, 150 mothers were rated as exposed. Manufacturing jobs, particularly apparel manufacturing, comprised the largest groups of exposed mothers. Mothers of infants with septal heart defects (odds ratio (OR): 1.8, 95% confidence interval (CI): 1.0–3.3), and especially perimembranous ventricular septal defects (OR: 2.5, CI: 1.2–5.2), were more likely to be occupationally exposed to oil mists in early pregnancy than control mothers; and their rater-estimated cumulative exposure was more likely to be higher. This was the first U.S. study evaluating associations between oil mist exposure and a broad spectrum of birth defects. Our results are consistent with previous European studies, supporting a potential association between oil-based exposures and congenital heart defects. Further research is needed to evaluate the reproductive effects of occupational oil mist exposure.

ObjectiveNail technicians and hairdressers may be exposed to chemicals with potential reproductive effects. While studies have examined birth defects in children of hairdressers, those in children of nail technicians have not been evaluated. We investigated associations between selected birth defects and maternal occupation as a nail technician or hairdresser versus a non-cosmetology occupation during pregnancy.MethodsWe analysed population-based case–control data from the multisite National Birth Defects Prevention Study, 1997–2011. Cases were fetuses or infants with major structural birth defects; controls were live-born infants without major birth defects. Expert raters classified self-reported maternal jobs as nail technician, combination nail technician-hairdresser, hairdresser, other cosmetology work or non-cosmetology work. We used logistic regression to calculate adjusted ORs and 95% CIs for associations between occupation during pregnancy and birth defects, controlling for age, smoking, education and race/ethnicity.ResultsSixty-one mothers worked as nail technicians, 196 as hairdressers, 39 as combination nail technician-hairdressers and 42 810 as non-cosmetologists. The strongest associations among nail technicians included seven congenital heart defect (CHD) groups (ORs ranging from 2.7 to 3.5) and neural tube defects (OR=2.6, CI=0.8 to 8.4). Birth defects most strongly associated with hairdressing included anotia/microtia (OR=2.1, CI=0.6 to 6.9) and cleft lip with cleft palate (OR=2.0, CI=1.1 to 3.7). All oral cleft groups were associated with combination nail technician-hairdresser work (ORs ranging from 4.2 to 5.3).ConclusionsSmall samples resulted in wide CIs. Still, results suggest associations between maternal nail technician work during pregnancy and CHDs and between hairdressing work and oral clefts.