José M. Maisog

The functional organization of human extrastriate cortex: a PET-rCBF study of selective attention to faces and locations

The functional dissociation of human extrastriate cortical processing streams for the perception of face identity and location was investigated in healthy men by measuring visual task-related changes in regional cerebral blood flow (rCBF) with positron emission tomography (PET) and H2(15)O. Separate scans were obtained while subjects performed face matching, location matching, or sensorimotor control tasks. The matching tasks used identical stimuli for some scans and stimuli of equivalent visual complexity for others. Face matching was associated with selective rCBF increases in the fusiform gyrus in occipital and occipitotemporal cortex bilaterally and in a right prefrontal area in the inferior frontal gyrus. Location matching was associated with selective rCBF increases in dorsal occipital, superior parietal, and intraparietal sulcus cortex bilaterally and in dorsal right premotor cortex. Decreases in rCBF, relative to the sensorimotor control task, were observed for both matching tasks in auditory, auditory association, somatosensory, and midcingulate cortex. These results suggest that, within a sensory modality, selective attention is associated with increased activity in those cortical areas that process the attended information but is not associated with decreased activity in areas that process unattended visual information. Selective attention to one sensory modality, on the other hand, is associated with decreased activity in cortical areas dedicated to processing input from other sensory modalities. Direct comparison of our results with those from other PET-rCBF studies of extrastriate cortex demonstrates agreement in the localization of cortical areas mediating face and location perception and dissociations between these areas and those mediating the perception of color and motion.

A functional lesion in developmental dyslexia : Left angular gyral blood flow predicts severity

Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p <.01), but with worse reading skill in dyslexia (p <.01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia.

Persistent Environmental Pollutants and Couple Fecundity: The LIFE Study

Background: Evidence suggesting that persistent environmental pollutants may be reproductive toxicants underscores the need for prospective studies of couples for whom exposures are measured. Objectives: We examined the relationship between selected persistent pollutants and couple fecundity as measured by time to pregnancy. Methods: A cohort of 501 couples who discontinued contraception to become pregnant was prospectively followed for 12 months of trying to conceive or until a human chorionic gonadotrophin (hCG) test confirmed pregnancy. Couples completed daily journals on lifestyle and provided biospecimens for the quantification of 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, 36 polychlorinated biphenyls (PCBs), and 7 perfluorochemicals (PFCs) in serum. Using Cox models for discrete time, we estimated fecundability odds ratios (FORs) and 95% CIs separately for each partner’s concentrations adjusting for age, body mass index, serum cotinine, serum lipids (except for PFCs), and study site (Michigan or Texas); sensitivity models were further adjusted for left truncation or time off of contraception (≤ 2 months) before enrollment. Results: The adjusted reduction in fecundability associated with standard deviation increases in log-transformed serum concentrations ranged between 18% and 21% for PCB congeners 118, 167, 209, and perfluorooctane sulfonamide in females; and between 17% and 29% for p,p´-DDE and PCB congeners 138, 156, 157, 167, 170, 172, and 209 in males. The strongest associations were observed for PCB 167 (FOR 0.79; 95% CI: 0.64, 0.97) in females and PCB 138 (FOR = 0.71; 95% CI: 0.52, 0.98) in males. Conclusions: In this couple-based prospective cohort study with preconception enrollment and quantification of exposures in both female and male partners, we observed that a subset of persistent environmental chemicals were associated with reduced fecundity.

Selective attention to face identity and color studied with f MRI.

Cortical areas associated with selective attention to the color and identity of faces were located using functional magnetic resonance imaging (fMRI). Six subjects performed tasks which required selective attention to face identity or color similarity using the same color‐washed face stimuli. Performance of the color attention task but not the face attention task was associated with a region of activity in the collateral sulcus and nearby regions of the lingual and fusiform gyri. Performance of both tasks was associated with a region of activity in ventral occipitotemporal cortex that was lateral to the color responsive area and had a greater spatial extent. These fMRI results converge with results obtained from PET and ERP studies to demonstrate similar anatomical locations of functional areas for face and color processing across studies. Hum. Brain Mapping5:293–297, 1997. Published 1997 Wiley‐Liss, Inc.

Preconception stress increases the risk of infertility: results from a couple-based prospective cohort study—the LIFE study

STUDY QUESTION Are womens stress levels prospectively associated with fecundity and infertility? SUMMARY ANSWER Higher levels of stress as measured by salivary alpha-amylase are associated with a longer time-to-pregnancy (TTP) and an increased risk of infertility. WHAT IS KNOWN ALREADY Data suggest that stress and reproduction are interrelated; however, the directionality of that association is unclear. STUDY DESIGN, SIZE, DURATION In 2005-2009, we enrolled 501 couples in a prospective cohort study with preconception enrollment at two research sites (Michigan and Texas, USA). Couples were followed for up to 12 months as they tried to conceive and through pregnancy if it occurred. A total of 401 (80%) couples completed the study protocol and 373 (93%) had complete data available for this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS Enrolled women collected saliva the morning following enrollment and then the morning following their first observed study menses for the measurement of cortisol and alpha-amylase, which are biomarkers of stress. TTP was measured in cycles. Covariate data were captured on both a baseline questionnaire and daily journals. MAIN RESULTS AND THE ROLE OF CHANCE Among the 401 (80%) women who completed the protocol, 347 (87%) became pregnant and 54 (13%) did not. After adjustment for female age, race, income, and use of alcohol, caffeine and cigarettes while trying to conceive, women in the highest tertile of alpha-amylase exhibited a 29% reduction in fecundity (longer TTP) compared with women in the lowest tertile [fecundability odds ratios (FORs) = 0.71; 95% confidence interval (CI) = (0.51, 1.00); P < 0.05]. This reduction in fecundity translated into a >2-fold increased risk of infertility among these women [relative risk (RR) = 2.07; 95% CI = (1.04, 4.11)]. In contrast, we found no association between salivary cortisol and fecundability. LIMITATIONS, REASONS FOR CAUTION Due to fiscal and logistical concerns, we were unable to collect repeated saliva samples and perceived stress questionnaire data throughout the duration of follow-up. Therefore, we were unable to examine whether stress levels increased as women continued to fail to get pregnant. Our ability to control for potential confounders using time-varying data from the daily journals, however, minimizes residual confounding. WIDER IMPLICATIONS OF THE FINDINGS This is the first US study to demonstrate a prospective association between salivary stress biomarkers and TTP, and the first in the world to observe an association with infertility. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable.

Preconception Maternal and Paternal Exposure to Persistent Organic Pollutants and Birth Size: The LIFE Study

Background: Persistent organic pollutants (POPs) are developmental toxicants, but the impact of both maternal and paternal exposures on offspring birth size is largely unexplored. Objective: We examined associations between maternal and paternal serum concentrations of 63 POPs, comprising five major classes of pollutants, with birth size measures. Methods: Parental serum concentrations of 9 organochlorine pesticides, 1 polybrominated biphenyl (PBB), 7 perfluoroalkyl chemicals (PFCs), 10 polybrominated diphenyl ethers (PBDEs), and 36 polychlorinated biphenyls (PCBs) were measured before conception for 234 couples. Differences in birth weight, length, head circumference, and ponderal index were estimated using multiple linear regression per 1-SD increase in natural log-transformed (ln-transformed) chemicals. Models were estimated separately for each parent and adjusted for maternal age, maternal prepregnancy body mass index (kilograms per meter squared) and other confounders, and all models included an interaction term between infant sex and each chemical. Results: Among girls (n = 117), birth weight was significantly lower (range, 84–195 g) in association with a 1-SD increase in ln-transformed maternal serum concentrations of DDT, PBDE congeners 28 and 183, and paternal serum concentrations of PBDE-183 and PCB-167. Among boys (n = 113), maternal (PCBs 138, 153, 167, 170, 195, and 209 and perfluorooctane sulfonamide) and paternal (PCBs 172 and 195) serum concentrations of several POPs were statistically associated with lower birth weight (range, 98–170 g), whereas paternal concentrations of PBDEs (66, 99) were associated with higher birth weight. Differences in offspring head circumference, length, and ponderal index were also associated with parental exposures. Conclusions: Preconceptional maternal and paternal concentrations of several POPs were associated with statistically significant differences in birth size among offspring. Citation: Robledo CA, Yeung E, Mendola P, Sundaram R, Maisog J, Sweeney AM, Barr DB, Buck Louis GM. 2015. Preconception maternal and paternal exposure to persistent organic pollutants and birth size: the LIFE Study. Environ Health Perspect 123:88–94; http://dx.doi.org/10.1289/ehp.1308016

A prospective study of prepregnancy serum concentrations of perfluorochemicals and the risk of gestational diabetes

OBJECTIVE To examine preconception serum concentrations of perfluorooctanoic acid (PFOA) and six other PFCs in relation to gestational diabetes (GDM) risk. DESIGN Prospective cohort with longitudinal follow-up. SETTING Not applicable. PATIENT(S) Among 501 women recruited upon discontinuing contraception for the purpose of becoming pregnant, 258 (51%) became pregnant and were eligible for the study, of which 28 (11%) reported having physician-diagnosed GDM during follow-up. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The odds ratios (ORs) and 95% confidence intervals (CIs) of GDM associated with each standard deviation (SD) increment of preconception serum PFOA concentration (ng/mL, log-transformed) and six other PFCs were estimated with the use of logistic regression after adjusting for age, prepregnancy body mass index, smoking, and parity conditional on gravidity. RESULT(S) Preconception geometric mean (95% CI) PFOA concentrations (in ng/mL) were higher for women with than without GDM (3.94 [3.15-4.93] vs. 3.07 [2.83-3.12], respectively). Each SD increment in PFOA was associated with a 1.87-fold increased GDM risk (adjusted OR 1.86 [95% CI 1.14-3.02]). A slightly increased risk associated with each SD increment for the six other PFCs was observed as well (all ORs >1.0, range 1.06-1.27), although the associations were not statistically significant. CONCLUSION(S) Our findings suggested that higher environmentally relevant concentrations of PFOA were significantly associated with an increased risk of GDM. If corroborated, these findings may be suggestive of a possible environmental etiology for GDM.

Persistent organic pollutants and pregnancy complications.

We sought to investigate the relationship between maternal preconception exposures to persistent organic pollutants (POPs) and pregnancy complications, gestational diabetes (GDM) and gestational hypertension. Data from 258 (51%) women with human chorionic gonadotropin (hCG) confirmed pregnancies reaching ≥24weeks gestation, from a prospective cohort of 501 couples who discontinued contraception to attempt pregnancy, were analyzed. Preconception concentrations of 9 organochlorine pesticides (OCPs) and 10 polybrominated diphenyl ethers (PBDEs) were quantified in serum. In separate multiple logistic regression models of self-reported physician diagnosed outcomes: GDM (11%) and gestational hypertension (10%), chemicals were natural log-transformed and rescaled by their standard deviation (SD). Models were adjusted for serum lipids, and then adjusted for age, body mass index, race, and smoking. Models were additionally adjusted for the sum of the remaining POPs in each chemical class. Womens serum concentration of PBDE congener 153 (PBDE-153) was positively associated with an increased odds of GDM per SD increase in log-transformed concentration, for unadjusted (OR=1.36, 95%CI: 1.02-1.81), a priori adjusted (OR=1.38, 95% CI: 1.03-1.86) and with the sum of remaining PBDEs (OR=1.79, 95% CI: 1.18, 2.74) models. Our findings suggest that at environmentally relevant concentrations, maternal exposure to POPs prior to conception may contribute to increased chance of developing GDM.

Birth outcomes and background exposures to select elements, the Longitudinal Investigation of Fertility and the Environment (LIFE).

Evidence suggests that trace exposures to select elements may increase the risk for adverse birth outcomes. To investigate further, we used multiple regression to assess associations between preconception parental exposures to Pb, Cd, and total Hg in blood, and 21 elements in urine, with n=235 singleton birth outcomes, adjusted for confounders and partners exposure. Earlier gestational age at delivery (GA) was associated with higher tertiles of urine maternal W (-1.22 days) and paternal U (-1.07 days), but GA was later for higher tertiles of maternal (+1.11 days) and paternal (+1.30 days) blood Hg. Additional analysis indicated shorter GA associated with higher paternal urine Ba, W, and U, and with higher maternal blood Pb for boys, but GA was longer in association with higher maternal urine Cr. Birth weight (BW) was lower for higher tertiles of paternal urine Cs (-237.85g), U (-187.34g), and Zn (-209.08g), and for higher continuous Cr (P=0.021). In contrast, BW was higher for higher tertiles of paternal urine As (+194.71g) and counterintuitively for maternal blood Cd (+178.52g). Birth length (BL) was shorter for higher tertiles of urine maternal W (-1.22cm) and paternal U (-1.10cm). Yet, higher tertiles of maternal (+1.11cm) and paternal (+1.30) blood Hg were associated with longer BL. Head circumference at delivery was lower for higher tertiles of paternal urine U (-0.83cm), and for higher continuous Mo in boys (-0.57cm). Overall, associations were most consistently indicated for GA and measures of birth size with urine W and U, and paternal exposures were more frequently associated than maternal. Though limited by several factors, ours is the largest multi-element investigation of prospective couple-level trace exposures and birth outcomes to date; the novel observations for W and U merit further investigation.

Successive time to pregnancy among women experiencing pregnancy loss

STUDY QUESTION Is time to pregnancy (TTP) similar across successive pregnancy attempts among women experiencing pregnancy loss? SUMMARY ANSWER TTP after a loss may be longer compared with TTP before a loss. WHAT IS KNOWN ALREADY Two pregnancy cohort studies have reported that TTP is similar across pregnancy attempts in fertile women. However, this has not been investigated among women experiencing pregnancy losses. STUDY DESIGN, SIZE, DURATION Data for this analysis come from the Longitudinal Investigation of Fertility and the Environment Study, a population-based, preconception cohort of couples attempting pregnancy. During 2005-2009, recruitment was targeted to 16 counties in Michigan and Texas with reported exposures to persistent environmental chemicals. A total of 501 couples were recruited and followed for up to 12 months of pregnancy attempts allowing for continued participation of women with pregnancy losses until censoring. PARTICIPANTS, SETTING, METHODS We assessed TTP among 70 couples recruited upon discontinuing contraception for purposes of becoming pregnant and experiencing ≥1 prospectively observed pregnancy losses during 12 months of trying. There were 61 couples who contributed two pregnancy attempts and 9 who contributed three. Women were instructed in the use of urine-based home fertility monitors to time intercourse relative to ovulation and recorded their bleeding patterns in daily journals. TTP was defined as the number of menstrual cycles taken to achieve pregnancy. Women were also instructed in the use of home digital pregnancy tests and asked to begin pregnancy testing on the day of expected menses. Women recorded the results of their pregnancy tests in a daily journal with a single positive pregnancy test result indicating an hCG-confirmed pregnancy. Pregnancy losses were ascertained from a subsequent recorded negative pregnancy test or clinically confirmed loss. We estimated fecundability odds ratios (FORs) comparing subsequent to first TTP using discrete Cox models with robust standard errors, accounting for cycles off contraception before study entry and adjusting for maternal age, body mass index, reproductive history and time-varying cigarette, alcohol and caffeine usage while trying. MAIN RESULTS AND THE ROLE OF CHANCE The mean female age was 30.3 ± 4.3 years; 21% had a prior pregnancy loss before study entry. Of the second and third attempts, 59 and 43%, respectively, were longer compared with the first attempt. FORs <1 suggest reduced fecundability or a longer TTP when comparing the second with the first attempt (0.42, 95% confidence interval (CI): 0.28, 0.65), and similarly for the third relative to the first attempt (0.64, 95% CI: 0.18, 2.36). TTP in the second attempt was a median of 1 cycle longer (interquartile range: 0, 3 cycles) compared with TTP in the first attempt. LIMITATIONS, REASONS FOR CAUTION As this is the first study to investigate successive TTP exclusively among women experiencing pregnancy loss, our findings await corroboration since most losses occurred early in gestation. As such, the generalizability of our findings for all pregnancy losses awaits further research. We also had limited power to detect a reduction in fecundability for the third compared with first pregnancy attempt. WIDER IMPLICATIONS OF THE FINDINGS Unlike fertile women, TTP in women experiencing early pregnancy losses may trend towards longer subsequent attempts. If the findings are corroborated, women experiencing losses may benefit from counselling regarding trying times. STUDY FUNDING/COMPETING INTERESTS This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358). K.J.S. was supported by an Intramural Research Training Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Intramural Population Health Research. The authors have no conflicts of interest to declare.