Tricia Z. King

White Matter Integrity in Highly Traumatized Adults With and Without Post-Traumatic Stress Disorder

Prior structural imaging studies of post-traumatic stress disorder (PTSD) have observed smaller volumes of the hippocampus and cingulate cortex, yet little is known about the integrity of white matter connections between these structures in PTSD samples. The few published studies using diffusion tensor imaging (DTI) to measure white matter integrity in PTSD have described individuals with focal trauma rather than chronically stressed individuals, which limits generalization of findings to this population; in addition, these studies have lacked traumatized comparison groups without PTSD. The present DTI study examined microstructural integrity of white matter tracts in a sample of highly traumatized African-American women with (n=25) and without (n=26) PTSD using a tract-based spatial statistical approach, with threshold-free cluster enhancement. Our findings indicated that, relative to comparably traumatized controls, decreased integrity (measured by fractional anisotropy) of the posterior cingulum was observed in participants with PTSD (p<0.05). These findings indicate that reduced microarchitectural integrity of the cingulum, a white matter fiber that connects the entorhinal and cingulate cortices, appears to be associated with PTSD symptomatology. The role of this pathway in problems that characterize PTSD, such as inadequate extinction of learned fear, as well as attention and explicit memory functions, are discussed.

Parental Distress, Parenting Practices, and Child Adaptive Outcomes Following Traumatic Brain Injury

Moderate and severe pediatric traumatic brain injuries (TBI) are associated with significant familial distress and child adaptive sequelae. Our aim was to examine the relationship between parental psychological distress, parenting practices (authoritarian, permissive, authoritative), and child adaptive functioning 12-36 months following TBI or orthopedic injury (OI). Injury type was hypothesized to moderate the relationship between parental distress and child adaptive functioning, demonstrating a significantly stronger relationship in the TBI relative to OI group. Authoritarian parenting practices were hypothesized to mediate relationship between parental distress and child adaptive functioning across groups. Groups (TBI n = 21, OI n = 23) did not differ significantly on age at injury, time since injury, sex, race, or SES. Parents completed the Brief Symptom Inventory, Parenting Practices Questionnaire, and Vineland-II. Moderation and mediation hypotheses were tested using hierarchical multiple regression and a bootstrapping approach, respectively. Results supported moderation and revealed that higher parental psychological distress was associated with lower child adaptive functioning in the TBI group only. Mediation results indicated that higher parental distress was associated with authoritarian parenting practices and lower adaptive functioning across groups. Results suggest that parenting practices are an important area of focus for studies attempting to elucidate the relationship between parent and child functioning following TBI.

FKBP5 Genotype and Structural Integrity of the Posterior Cingulum

Alterations in the microarchitecture of the posterior cingulum (PC), a white matter tract proximal to the hippocampus that facilitates communication between the entorhinal and cingulate cortices, have been observed in individuals with psychiatric disorders, such as depression and post-traumatic stress disorder (PTSD). PC decrements may be a heritable source of vulnerability for the development of affective disorders; however, genetic substrates for these white matter abnormalities have not been identified. The FKBP5 gene product modulates glucocorticoid receptor function and has been previously associated with differential hippocampal structure, function, and affect disorder risk. Thus, FKBP5 is an attractive genetic target for investigations of PC integrity. We examined associations between PC integrity, measured through diffusion tensor imaging (DTI) and fractional anisotropy (FA; an index of white matter integrity), and polymorphisms in the FKBP5 SNP rs1360780 in a sample of 82 traumatized female civilians. Findings indicated that, compared with individuals without this allele, individuals who carried two ‘risk’ alleles for this FKBP5 SNP (T allele; previously associated with mood and anxiety disorder risk) demonstrated significantly lower FA in the left PC, even after statistically controlling for variance associated with age, trauma exposure, and PTSD symptoms. These data suggest that specific allelic variants for an FKBP5 polymorphism are associated with decrements in the left PC microarchitecture. These white matter abnormalities may be a heritable biological marker that indicates increased vulnerability for the development of psychiatric disorders, such as PTSD.

Verbal Memory Abilities of Children With Brain Tumors

Several critical neuroanatomical structures and pathways for memory performance are located in the third ventricle region. This led us to predict that verbal memory abilities would be more impaired in children treated for third ventricle tumors compared to those treated for cerebellar tumors. Archival data was obtained from 24 pediatric patients with third ventricle region tumors and 18 pediatric patients with cerebellar tumors. Neuroradiological verifications of tumor involvement and hydrocephalus severity (i.e., Evans Index) on preoperative scans and MRIs proximal to the time of the neuropsychological evaluation were conducted. The potential confounds of hydrocephalus severity, seizure medication, age, radiation treatment, and chemotherapy were addressed. Verbal IQ was comparable between tumor groups and in the Average range. The third ventricle region group performed significantly worse on list learning and delayed list recall compared to the cerebellar group. Their mean performance was in the clinically impaired range on both trials. The third ventricle region tumor group performed better than the cerebellar tumor group on Digit Span, a basic repetition, attention span task. These findings support the hypothesis that pediatric patients with third ventricle region brain tumors are more likely to be impaired on verbal recall tasks compared to pediatric patients with cerebellar brain tumors. In contrast, patients who were treated for cerebellar tumors were more impaired on the basic repetition, attention span task compared to patients who were treated for third ventricle tumors. Future studies should examine the specific neuroanatomical structures and pathways that are damaged and may influence differential cognitive impairments in children.

Quantifying Pediatric Neuro-oncology Risk Factors: Development of the Neurological Predictor Scale

Pediatric neuro-oncology researchers face methodological challenges associated with quantifying the influence of tumor and treatment-related risk factors on child outcomes. The Neurological Predictor Scale was developed to serve as a cumulative index of a childs exposure to risk factors. The clinical utility of the Neurological Predictor Scale was explored in a sample of 25 children with heterogeneous brain tumors. Consistent with expectation, a series of regression analyses demonstrated that the Neurological Predictor Scale significantly predicted composite intellectual functioning (r 2 = 0.21, p < .05), short-term memory (r 2 = 0.16, p = .05), and abstract visual reasoning abilities (r 2 = 0.28, p < .05). With the exception of chemotherapy, the Neurological Predictor Scale accounted for a significant amount of the variance in child intellectual functioning above and beyond individually examined variables. The Neurological Predictor Scale can be used to quickly quantify the cumulative risk factors associated with pediatric brain tumor diagnoses.

Fear-potentiated Startle During Extinction is Associated with White Matter Microstructure and Functional Connectivity

BACKGROUND Extinction of conditioned fear is an associative learning process that involves communication among the hippocampus, medial prefrontal cortex, and amygdala. Strength of connectivity between the hippocampus and the anterior cingulate cortex (ACC), and between the amygdala and ventromedial prefrontal cortex (vmPFC), may influence fear-potentiated startle (FPS) responses during extinction. Specific white matter tracts, the cingulum and uncinate fasciculus (UF), serve as primary routes of communication for these areas. Our objective was to investigate associations between FPS during extinction and cingulum and UF connectivity. METHOD Diffusion tensor imaging (DTI) and probabilistic tractography analyses were used to examine cingulum and UF structural connectivity in 40 female African-Americans with psychological trauma exposure. FPS responses during fear conditioning and extinction were assessed via electromyography (EMG) of the right orbicularis oculi muscle. Secondarily, functional connectivity analyses were performed with the seed regions of interest (ROIs) used for tractography. RESULTS A significant negative association between cingulum microstructure and FPS during early extinction (r = -.42, p = .01) and late extinction (r = -.36, p = .03) was observed after accounting for the effects of age, trauma exposure, and psychopathology (post-traumatic stress disorder symptoms); this pattern was similar for early extinction and functional connectivity between these regions (p < .05(corrected)). No significant correlations were observed between FPS and UF microstructure. CONCLUSIONS These data indicate that structural integrity of the cingulum is directly associated with extinction learning and appears to influence functional connectivity between these regions. Decrements in cingulum microstructure may interfere with extinction learning, thereby increasing risk for the development of pathological anxiety.

Epilepsy stigma and stigma by association in the workplace

In the first experimental study of epilepsy-based discrimination in the workplace, we examined the influence of stigmatization on the workplace outcomes of hypothetical employees who were associated with epilepsy, but who did not have epilepsy themselves (stigma by association). Participants (40 women, 16 men), acting as employers, evaluated one of six randomly assigned employee work portfolios that were identical except that the employee was either male or female and had taken leave during the past year to care for a child with either epilepsy or asthma, or for whom no leave was mentioned. They then evaluated the employee and made recommendations concerning the employees workplace rewards (promotion, raise) and penalties (job termination). Work quality evaluation was similar across conditions. However, parents of a child with epilepsy received fewer workplace rewards and greater workplace penalties than did employees in the other conditions. Implications for mental health and antibias interventions are discussed.

Undifferentiated facial electromyography responses to dynamic, audio‐visual emotion displays in individuals with autism spectrum disorders

We examined facial electromyography (fEMG) activity to dynamic, audio-visual emotional displays in individuals with autism spectrum disorders (ASD) and typically developing (TD) individuals. Participants viewed clips of happy, angry, and fearful displays that contained both facial expression and affective prosody while surface electrodes measured corrugator supercilli and zygomaticus major facial muscle activity. Across measures of average and peak activity, the TD group demonstrated emotion-selective fEMG responding, with greater relative activation of the zygomatic to happy stimuli and greater relative activation of the corrugator to fearful stimuli. In contrast, the ASD group largely showed no significant differences between zygomatic and corrugator activity across these emotions. There were no group differences in the magnitude and timing of fEMG response in the muscle congruent to the stimuli. This evidence that fEMG responses in ASD are undifferentiated with respect to the valence of the stimulus is discussed in light of potential underlying neurobiological mechanisms.

Cognitive Predictors of Adaptive Functioning Vary According to Pediatric Brain Tumor Location

This archival study sought to determine if the relationship between cognitive and adaptive abilities varied according to brain tumor location. Participants were 36 children treated for brain tumors. The best cognitive predictors of adaptive functioning were hypothesized to be attention span within the cerebellar group and verbal memory within the third ventricle group. Auditory attention span significantly predicted communication skills for the cerebellar group, whereas verbal memory significantly predicted socialization skills for the third ventricle group. These findings suggest that cognitive predictors vary according to tumor location, and highlight the need for more research examining adaptive functioning and its correlates.

Parent Report of Attention Problems Predicts Later Adaptive Functioning in Children with Brain Tumors

Children with brain tumors are at risk for psychological and behavioral difficulties. This study examined the ability of parent report of attention problems, withdrawal, anxiety, and depression, as well as IQ, to predict later adaptive functioning in 42 children treated for brain tumors. Age at diagnosis, SES, gender, and scores on the Neurological Predictor Scale (NPS) also were examined as predictors. Parent report of attention problems, SES, and NPS were significant predictors of later adaptive functioning across domains. This finding highlights the ability of parent report of attention problems to predict later adaptive functioning in children treated for brain tumors.