Faculty Bibliography

OBJECTIVES/OBJECTIVE:We examined whether past-year suicidality among sexual-minority adolescents was more common in neighborhoods with a higher prevalence of hate crimes targeting lesbian, gay, bisexual, and transgender (LGBT) individuals. METHODS:Participants' data came from a racially/ethnically diverse population-based sample of 9th- through 12th-grade public school students in Boston, Massachusetts (n = 1292). Of these, 108 (8.36%) reported a minority sexual orientation. We obtained data on LGBT hate crimes involving assaults or assaults with battery between 2005 and 2008 from the Boston Police Department and linked the data to the adolescent's residential address. RESULTS:Sexual-minority youths residing in neighborhoods with higher rates of LGBT assault hate crimes were significantly more likely to report suicidal ideation (P = .013) and suicide attempts (P = .006), than were those residing in neighborhoods with lower LGBT assault hate crime rates. We observed no relationships between overall neighborhood-level violent and property crimes and suicidality among sexual-minority adolescents (P > .05), providing evidence for specificity of the results to LGBT assault hate crimes. CONCLUSIONS:Neighborhood context (i.e., LGBT hate crimes) may contribute to sexual-orientation disparities in adolescent suicidality, highlighting potential targets for community-level suicide-prevention programs.

The uncinate fasciculus is a major white matter tract that provides a crucial link between areas of the human brain that underlie emotion processing and regulation. Specifically, the uncinate fasciculus is the major direct fiber tract that connects the prefrontal cortex and the amygdala. The aim of the present study was to use a multi-modal imaging approach in order to simultaneously examine the relation between structural connectivity of the uncinate fasciculus and functional activation of the amygdala in a youth sample (children and adolescents). Participants were 9 to 19years old and underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). Results indicate that greater structural connectivity of the uncinate fasciculus predicts reduced amygdala activation to sad and happy faces. This effect is moderated by age, with younger participants exhibiting a stronger relation. Further, decreased amygdala activation to sad faces predicts lower internalizing symptoms. These results provide important insights into brain structure-function relationships during adolescence, and suggest that greater structural connectivity of the uncinate fasciculus may facilitate regulation of the amygdala, particularly during early adolescence. These findings also have implications for understanding the relation between brain structure, function, and the development of emotion regulation difficulties, such as internalizing symptoms.

This paper presents a method for intensity inhomogeniety removal in fMRI studies of a moving subject. In such studies, subtle changes in signal as the subject moves in the presence of a bias field can be a significant confound for BOLD signal analysis. The proposed method avoids the need for a specific tissue model or assumptions about tissue homogeneity by making use of the multiple views of the underlying bias field provided by the subject's motion. A parametric bias field model is assumed and a regression model is used to estimate the basis function weights of this model. Quantitative evaluation of the effects of motion and noise in motion estimates are performed using simulated data. Results demonstrate the strength and robustness of the new method compared to the state of the art 4D nonparametric bias estimator (N4ITK). We also qualitatively demonstrate the impact of the method on resting state neuroimage analysis of a moving adult brain with simulated motion and bias fields, as well as on in vivo moving fetal fMRI.

BACKGROUND:Previous research suggests that testosterone (T) plays a key role in shaping competitive and aggressive behavior in humans, possibly by modulating threat-related neural circuitry. However, this research has been limited by the use of T augmentation that fails to account for baseline differences and has been conducted exclusively in women. Thus, the extent to which normal physiologic concentrations of T affect threat-related brain function in men remains unknown. METHODS:In the current study, we use a novel two-step pharmacologic challenge protocol to overcome these limitations and to evaluate causal modulation of threat- and aggression-related neural circuits by T in healthy young men (n = 16). First, we controlled for baseline differences in T through administration of a gonadotropin releasing hormone antagonist. Once a common baseline was established across participants, we then administered T to within the normal physiologic range. During this second step of the protocol we acquired functional neuroimaging data to examine the impact of T augmentation on neural circuitry supporting threat and aggression. RESULTS:Gonadotropin releasing hormone antagonism successfully reduced circulating concentrations of T and brought subjects to a common baseline. Administration of T rapidly increased circulating T concentrations and was associated with heightened reactivity of the amygdala, hypothalamus, and periaqueductal grey to angry facial expressions. CONCLUSIONS:These findings provide novel causal evidence that T rapidly potentiates the response of neural circuits mediating threat processing and aggressive behavior in men.

The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

OBJECTIVE:Cerebrovascular reactivity is impaired in patients suffering from obstructive sleep apnea syndrome (OSAS) as demonstrated by transcranial Doppler studies. We use magnetic resonance imaging techniques to investigate the anatomical distribution of cerebrovascular reactivity changes in patients with OSAS, as well as their evolution after therapeutic and sham continuous positive airway pressure (CPAP) treatment. METHODS:Twenty-three men with moderate or severe obstructive sleep apnea were compared to a healthy control group (n=7) using a breath-holding functional magnetic resonance imaging task and the flow-sensitive alternating inversion recovery (FAIR) imaging before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment. RESULTS:Significantly higher cerebrovascular reactivity was found in healthy controls as compared to patients in bilateral cortical and subcortical brain regions. Cerebrovascular reactivity increased with therapeutic CPAP in the thalamus and decreased with sham CPAP in medial frontal regions in OSAS patients. Duration of nocturnal hypoxemia and body mass index negatively correlated with cerebrovascular reactivity, particularly in the medial temporal lobe structures, suggesting a possible pathophysiological mechanism for hippocampal injury. There was no difference in perfusion between patients and control group, and no effect of CPAP or sham-CPAP treatment on perfusion in patients. CONCLUSIONS:Observed cerebrovascular reactivity changes were neither homogeneous throughout the brain nor followed vascular territories, but rather corresponded to underlying neuronal networks, establishing a relationship between cerebrovascular reactivity and surrounding neuronal activity.

PURPOSE/OBJECTIVE:To evaluate the feasibility of performing fetal brain magnetic resonance venography using susceptibility weighted imaging (SWI). MATERIALS AND METHODS/METHODS:After obtaining informed consent, pregnant women in the second and third trimester were imaged using a modified SWI sequence. Fetal SWI acquisition was repeated when fetal or maternal motion was encountered. The median and maximum number of times an SWI sequence was repeated was four and six respectively. All SWI image data were systematically evaluated by a pediatric neuroradiologist for image quality using an ordinal scoring scheme: 1. diagnostic; 2. diagnostic with artifacts; and 3. nondiagnostic. The best score in an individual fetus was used for further statistical analysis. Visibility of venous vasculature was also scored using a dichotomous variable. A subset of SWI data was re-evaluated by the first and independently by a second pediatric neuroradiologist. Kappa coefficients were computed to assess intra-rater and inter-rater reliability. RESULTS:SWI image data from a total of 22 fetuses were analyzed. Median gestational age and interquartile range of the fetuses imaged were 32 (29.9-34.9) weeks. In 68.2% of the cases (n = 15), there was no artifact; 22.7% (n = 5) had minor artifacts and 9.1% (n = 2) of the data was of nondiagnostic quality. Cerebral venous vasculature was visible in 86.4% (n = 19) of the cases. Substantial agreement (Kappa = 0.73; 95% confidence interval 0.44-1.00)) was observed for intra-rater reliability and moderate agreement (Kappa = 0.48; 95% confidence interval 0.19-0.77) was observed for inter-rater reliability. CONCLUSION/CONCLUSIONS:It is feasible to perform fetal brain venography in humans using SWI.

PURPOSE/OBJECTIVE:To evaluate fetal cerebral venous blood oxygenation, Yv, using principles of MR susceptometry. MATERIALS AND METHODS/METHODS:A cohort of 19 pregnant subjects, with a mean gestational age of 31.6 ± 4.7 weeks were imaged using a modified susceptibility-weighted imaging (SWI) sequence. Data quality was first assessed for feasibility of oxygen saturation measurement, and data from five subjects (mean ± std gestational age of 33.7 ± 3.6 weeks) were then chosen for further quantitative analysis. SWI phase in the superior sagittal sinus was used to evaluate oxygen saturation using the principles of MR susceptometry. Systematic error in the measured Y(v) values was studied through simulations. RESULTS:Simulations showed that the systematic error in Yv depended upon the assumed angle of the vessel, θ, relative to the main magnetic field and the error in that vessel angle δθ. For the typical vessel angle of θ = 30° encountered in the fetal data analyzed, a δθ as large as ±20° led to an absolute error, δYv, of less than 11%. The measured mean oxygen saturation across the five fetuses was 66% ± 9.4%. This average cerebral venous blood oxygenation value is in close agreement with values in the published literature. CONCLUSION/CONCLUSIONS:We have reported the first in vivo measurement of human fetal cerebral venous oxygen saturation using MRI.

OBJECTIVE:The objective of this study was to assess the ability of a dentifrice containing 8% arginine and calcium carbonate (Pro-Argin' Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP) to prevent enamel loss from an erosive acid challenge in comparison to a silica-based dentifrice with 1450 ppm fluoride as MFP using an intra-oral erosion model. METHODS:The intra-oral clinical study used a double blind, two-treatment, crossover design. A palatal retainer was used to expose the enamel specimens to the oral environment during the five-day treatment period. The retainer was designed to house three partially demineralized bovine enamel samples. The study population was composed of 24 adults, ages 18 to 70 years. The study consisted of two treatment periods, with a washout period lasting seven (+/- three) days preceding each treatment phase. A silica-based dentifrice without fluoride was used during the washout period. The Test Dentifrice used in this study contained 8% arginine and calcium carbonate (Pro-Argin Technology), and 1450 ppm fluoride as sodium monofluorophosphate (MFP). The Control Dentifrice was silica-based and contained 1450 ppm fluoride as MFP. The treatment period lasted five days, during which the panelists wore the retainer 24 hours a day (except during meals and the ex vivo acid challenges) and brushed with their assigned product while wearing the retainer. The panelists brushed once in the morning and once in the evening each day for one minute, followed by a one-minute swish with the slurry and a rinse with 15 ml of water. The panelists brushed only their teeth and not the specimens directly. There were four ex vivo challenges with 1% citric acid dispersed throughout the day: two in the morning, one in the afternoon, and one in the evening. Mineral loss was monitored by a quantitative light fluorescence (QLF) technique. RESULTS:Twenty-three of 24 subjects successfully completed the study. The one subject who did not complete the study did so for reasons unrelated to the study or products used. The average percent mineral loss for the Test Dentifrice and Control Dentifrice was 9.74 +/- 13.23 and 18.36 +/- 14.14, respectively. The statistical analysis showed that the observed product differences were statistically significant (p < 0.001). CONCLUSION/CONCLUSIONS:The Test Dentifrice with 8% arginine, calcium carbonate, and 1450 ppm fluoride as MFP provided significantly better protection against erosive challenges in comparison to the Control Dentifrice with 1450 ppm fluoride as MFP.