Mary Ellen Lynch

A pilot study on voucher-based incentives to promote abstinence from cigarette smoking during pregnancy and postpartum

We report results from a pilot study examining the use of vouchers redeemable for retail items as incentives for smoking cessation during pregnancy and postpartum. Of 100 study-eligible women who were still smoking upon entering prenatal care, 58 were recruited from university-based and community obstetric practices to participate in a smoking cessation study. Participants were assigned to either contingent or noncontingent voucher conditions. Vouchers were available during pregnancy and for 12 weeks postpartum. In the contingent condition, vouchers were earned for biochemically verified smoking abstinence. In the noncontingent condition, vouchers were earned independent of smoking status. Abstinence monitoring and associated voucher delivery was conducted daily during the initial 5 days of the cessation effort, gradually decreased to every other week antepartum, increased to once weekly during the initial 4 weeks postpartum, and then decreased again to every other week for the remaining 8 weeks of the postpartum intervention period. Contingent vouchers increased 7-day point-prevalence abstinence at the end-of-pregnancy (37% vs. 9%) and 12-week postpartum (33% vs. 0%) assessments. That effect was sustained through the 24-week postpartum assessment (27% vs. 0%), which was 12 weeks after discontinuation of the voucher program. Total mean voucher earnings across antepartum and postpartum were 397 US dollars (SD=414 US dollars) and 313 US dollars (SD=142 dollars) in the contingent and noncontingent conditions, respectively. The magnitude of these treatment effects exceed levels typically observed with pregnant and recently postpartum smokers, and the maintenance of effects through 24 weeks postpartum extends the duration beyond those reported previously.

Evaluation of Corpus Callosum Anisotropy in Young Adults With Fetal Alcohol Syndrome According to Diffusion Tensor Imaging

BACKGROUND Fetal alcohol syndrome (FAS) and associated disorders resulting from maternal alcohol use during gestation are among the most common developmental disorders. However, they are rarely diagnosed and not fully understood in terms of their behavioral and neurocognitive phenotype. Prenatal exposure leads to alterations in facial morphology, growth, and neurocognition. The nature and extent of teratogenic effects on the brain and the relationship between such effects and observed behaviors remain in debate because there are no established markers for the neurological effects of exposure. In this study, we examined the impact of prenatal alcohol exposure on white-matter integrity in the corpus callosum by using diffusion tensor imaging (DTI) and herein describe the relationship between such effects and observed physical and behavioral outcomes. METHODS DTI was used to evaluate diffusion anisotropy in the genu and splenium of corpus callosum in 16 low-income, primarily African-American volunteers. Volunteers were recruited from a cohort of young adults who had received neuropsychological evaluations during adolescence. Nine had been prenatally exposed to alcohol and had characteristics of FAS, and seven were nonexposed controls. RESULTS Significant difference in the means for diffusion fractional anisotropy (t = 2.26, df = 9, p <0.002) and apparent diffusion coefficient (t = 2.14, df = 14, p < 0.008) were observed in the corpus callosum of alcohol-exposed youth compared with nonexposed youth. No significant differences were found in intracranial volume between these groups. CONCLUSIONS Our results illustrate that DTI can be used in evaluating the integrity of corpus callosum in alcohol-exposed individuals. If future studies support these findings, diffusion anisotropy, represented by fractional anisotropy, has the potential to be used as a clinical marker in the diagnosis of FAS.

Voxelwise and skeleton‐based region of interest analysis of fetal alcohol syndrome and fetal alcohol spectrum disorders in young adults

Though fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders are among the most common developmental disorders, their understanding is incomplete. Diffusion tensor imaging (DTI), which is sensitive to microstructural organization in white matter, may provide a relevant measure in this population demonstrating incompletely characterized white matter pathology. In this study, tract‐based spatial statistics (TBSS) routine and a skeleton‐based region of interest analyses were employed to detect differences in DTI‐derived metrics between young adults who were alcohol exposed and an unexposed control group. Participants include 28 with dysmorphic features associated with FAS, 29 who were prenatally exposed but do not show physical effects, and 25 with the same low socioeconomic status but unexposed. The TBSS analysis revealed a statistically significant decrease in fractional anisotropy at the isthmus of the corpus callosum and its connected callosal fibers in dysmorphic individuals relative to controls (clusterwise PFWE < 0.05). This finding was consistent with that of the follow‐up skeleton‐based region of interest analysis (F(2,79) = 3.256, p = 0.044). In addition, the patterns in axial and radial diffusivity changes suggest that demyelination may be associated with the degraded white matter integrity observed in the dysmorphic group. Hum Brain Mapp, 2009.

Memory and Brain Volume in Adults Prenatally Exposed to Alcohol.

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.

Recursive Cluster Elimination Based Support Vector Machine for Disease State Prediction Using Resting State Functional and Effective Brain Connectivity

Background Brain state classification has been accomplished using features such as voxel intensities, derived from functional magnetic resonance imaging (fMRI) data, as inputs to efficient classifiers such as support vector machines (SVM) and is based on the spatial localization model of brain function. With the advent of the connectionist model of brain function, features from brain networks may provide increased discriminatory power for brain state classification. Methodology/Principal Findings In this study, we introduce a novel framework where in both functional connectivity (FC) based on instantaneous temporal correlation and effective connectivity (EC) based on causal influence in brain networks are used as features in an SVM classifier. In order to derive those features, we adopt a novel approach recently introduced by us called correlation-purged Granger causality (CPGC) in order to obtain both FC and EC from fMRI data simultaneously without the instantaneous correlation contaminating Granger causality. In addition, statistical learning is accelerated and performance accuracy is enhanced by combining recursive cluster elimination (RCE) algorithm with the SVM classifier. We demonstrate the efficacy of the CPGC-based RCE-SVM approach using a specific instance of brain state classification exemplified by disease state prediction. Accordingly, we show that this approach is capable of predicting with 90.3% accuracy whether any given human subject was prenatally exposed to cocaine or not, even when no significant behavioral differences were found between exposed and healthy subjects. Conclusions/Significance The framework adopted in this work is quite general in nature with prenatal cocaine exposure being only an illustrative example of the power of this approach. In any brain state classification approach using neuroimaging data, including the directional connectivity information may prove to be a performance enhancer. When brain state classification is used for disease state prediction, our approach may aid the clinicians in performing more accurate diagnosis of diseases in situations where in non-neuroimaging biomarkers may be unable to perform differential diagnosis with certainty.

Effects of Prenatal Alcohol Exposure on Brain Activation During an Arithmetic Task: An fMRI Study

BACKGROUND While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task. METHODS Participants were young adults from a low socio-economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n = 17) and PAE who were subdivided based on the presence (n = 19) or absence of physical dysmorphic signs (n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter-matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol-exposed population. RESULTS An exposure-dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task-related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation. CONCLUSIONS Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.

Verbal and nonverbal memory in adults prenatally exposed to alcohol.

BACKGROUND Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. METHODS In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. RESULTS Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. CONCLUSION These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

Increased “default mode” activity in adolescents prenatally exposed to cocaine

Prenatal cocaine exposure (PCE) is associated with attention/arousal dysregulation and possible inefficiencies in some cognitive functions. However, the neurobiological bases of these teratogenic effects have not been well characterized. Because activities in the default mode network (DMN) reflect intrinsic brain functions that are closely associated with arousal regulation and cognition, alterations in the DMN could underlie cognitive effects related to PCE. With resting‐state and task activation functional magnetic resonance imaging (fMRI), this study investigated the possible PCE related changes in functional brain connectivity and brain activation in the DMN. In the resting state, the PCE group was found to have stronger functional connectivity in the DMN, as compared to the nonexposed controls. During a working memory task with emotional distracters, the PCE group exhibited less deactivation in the DMN and their fMRI signal was more increased by emotional arousal. These data revealed additional neural effects related to PCE, and consistent with previous findings, indicate that PCE may affect behavior and functioning by increasing baseline arousal and altering the excitatory/inhibitory balancing mechanisms involved in cognitive resource allocation. Hum Brain Mapp, 2011.

The impact of maternal smoking on fast auditory brainstem responses.

Deficits in auditory processing have been posited as one of the underlying neurodevelopmental consequences of maternal smoking during pregnancy that leads to later language and reading deficits. Fast auditory brainstem responses were used to assess differences in the sensory processing of auditory stimuli among infants with varying degrees of prenatal cigarette exposure. Maternal report of consumption of cigarettes and blood samples were collected in the hospital to assess exposure levels and participants were then seen at 6-months. To participate in the study, all infants had to pass the newborn hearing exam or a clinically administered ABR and have no known health problems. After controlling for participant age, maternal smoking during pregnancy was negatively related to latency of auditory brainstem responses. Of several potential covariates, only perinatal complications and maternal alcohol use were also related to latency of the ABR responses and maternal smoking level accounted for significant unique variance after controlling for these factors. These results suggest that the relationship between maternal smoking may lead to disruption in the sensory encoding of auditory stimuli.

Connectomics signatures of prenatal cocaine exposure affected adolescent brains.

Recent in vivo neuroimaging studies revealed that several brain networks are altered in prenatal cocaine exposure (PCE) affected adolescent brains. However, due to a lack of dense and corresponding cortical landmarks across individuals, the systematical alterations of functional connectivities in large‐scale brain networks and the alteration of structural brain architecture in PCE affected brain are largely unknown. In this article, we adopted a newly developed data‐driven strategy to build a large set of cortical landmarks that are consistent and corresponding across PCE adolescents and their matched controls. Based on these landmarks, we constructed large‐scale functional connectomes and applied the well‐established approaches of deriving genomics signatures in genome‐wide gene expression studies to discover functional connectomics signatures for the characterization of PCE adolescent brains. Results derived from experimental data demonstrated that 10 structurally disrupted landmarks were identified in PCE, and more importantly, the discovered informative functional connectomics signatures among consistent landmarks distinctively differentiate PCE brains from their matched controls. Hum Brain Mapp 34:2494–2510, 2013.