Faculty Bibliography

We examined the risk and protective factors and mental health problems of 105 low SES, urban adolescents whose mothers were coping with alcohol abuse and other drug problems. Approximately half of the mothers were also HIV-infected. As hypothesized, there were few differences between adolescents of HIV-infected and HIV-uninfected mothers in background characteristics, mental health issues and current substance use risk behaviors. In addition to maternal substance abuse, youth in both groups experienced similar risk factors including early foster care placement and high levels of maltreatment. Current patterns of emerging risk behaviors were evident among youth in both groups as well as signs of resiliency including high levels of school attendance. These results underscore the importance of interventions for youth of substance abusing mothers, particularly those living in urban poverty.

Increasing numbers of youth are presenting for psychiatric evaluation with markedly irritable mood plus "hyperarousal" symptoms. Diagnostically homeless in current nosology, the syndrome (as well as its underlying neurobiology) is little understood. To address this problem, we conducted an exploratory proton magnetic resonance spectroscopy (MRS) study in a large sample of youth with chronic, functionally disabling irritability accompanied by hyperarousal, a clinical syndrome known as "severe mood dysregulation" (SMD), which may represent a broad phenotype of pediatric bipolar disorder. Medication-free SMD youth (N=36) and controls (N=48) underwent 1.5 Tesla MRS in four regions of interest. The following three neurometabolites, relative to creatine (Cr), were quantified with LCModel Software: (a) myo-inositol (mI), a marker of intra-cellular second messengers linked to the neurobiology of bipolar disorder; (b) glutamate/glutamine (GLX), a marker of the major excitatory neurotransmitter glutamate; and (c) N-acetyl aspartate (NAA), a marker of neuronal energetics. SMD subjects had significantly lower temporal mI/Cr versus controls. However, this difference did not survive correction for multiple comparisons. Given studies implicating mI in lithium's action in BD adults and youth, further work is necessary to determine potential therapeutic implications of our present finding and how SMD youth differ pathophysiologically from those with strictly defined BD.

Previous studies have shown that VEGF expression in forebrain increases after experimental manipulations that increase neuronal activity. One question is whether this also occurs in motor neurons. If so, it could be potentially advantageous from a therapeutic perspective, because VEGF prevents motor neuron degeneration. Therefore, we asked whether endogenous VEGF expression in motor neurons could be modulated. We also asked how VEGF exposure would influence motor neurons using electrophysiology. Immunocytochemistry showed that motor neuron VEGF expression increased after a stimulus that increases neuronal and motor activity, i.e., convulsive seizures. The increase in VEGF immunoreactivity occurred in all motor neuron populations that were examined 24h later. This effect was unlikely to be due to seizure-induced toxicity, because silver degeneration stain did not show the typical appearance of a dying or dead neuron. To address the effects of VEGF on motor neuron function, VEGF was applied directly to motor neurons while recording intracellularly, using a brainstem slice preparation. Exposure to exogenous VEGF (200 ng/ml) in normal conditions depressed stimulus-evoked depolarization of hypoglossal motor neurons. There was no detectable effect of VEGF on membrane properties or firing behavior. We suggest that VEGF is upregulated in neurons when they are strongly activated, and VEGF depresses neuronal excitation as a compensatory mechanism. Failure of this mechanism may contribute to diseases that involve a dysregulation of VEGF, excessive excitation of motor neurons, and motor neuron loss, such as amyotrophic lateral sclerosis (ALS)

Split-brain patients present a unique opportunity to address controversies regarding subcortical contributions to interhemispheric coordination. We characterized residual functional connectivity in a complete commissurotomy patient by examining patterns of low-frequency BOLD functional MRI signal. Using independent components analysis and region-of-interest-based functional connectivity analyses, we demonstrate bilateral resting state networks in a patient lacking all major cerebral commissures. Compared with a control group, the patient's interhemispheric correlation scores fell within the normal range for two out of three regions examined. Thus, we provide evidence for bilateral resting state networks in a patient with complete commissurotomy. Such continued interhemispheric interaction suggests that, at least in part, cortical networks in the brain can be coordinated by subcortical mechanisms

This study evaluated a calibration technique for scaling the fMRI-BOLD response during a simple motor task. A novel scaling parameter, resting state physiological fluctuation amplitude (RSFA), was tested using previously established scaling factors such as breath hold or 5% CO(2). RSFA was hypothesized to contain vascular reactivity information present in the resting state fMRI signal. Subjects were scanned under various stimulus conditions: (a) rest while breathing room air, (b) bilateral fingertapping, (c) breath holding and (d) moderate hypercapnia (breathing 5% CO(2)+air). In all subjects who breathed 5% CO(2), RSFA correlated highly with the BOLD response amplitude during 5% CO(2) inhalation. Also, RSFA correlated highly with the amplitude of the BOLD response elicited by breath hold. RSFA was therefore used as a hemodynamic scaling factor to calibrate both the amplitude and spatial extent of the fMRI-BOLD response during the motor task (fingertapping). Results revealed that amplitude scaling using RSFA was similar to that using breath hold or 5% CO(2), where the spatial extent of activation diminished by 20-37% over all subjects. Spatial extent of activation changed significantly after scaling and only 30-40% of the activated area overlapped with the unscaled activation. RSFA-scaled task-induced fMRI-BOLD response in both amplitude and spatial extent was comparable to that obtained using breath hold or 5% CO(2). We conclude that RSFA may be used to hemodynamically scale the fMRI-BOLD response and does not require the use of a hypercapnic challenge (which may not be purely non-neural), which can be difficult to implement in special populations

We studied the spatio-temporal characteristics of the resting state low-frequency fluctuations in fMRI-BOLD signal in isoflurane-anesthetized rats. fMRI-BOLD measurements at 9.4 T were made during normal and exsanguinated condition previously known to alter cerebral blood flow (CBF) fluctuations in anesthetized rats. fMRI signal time series were low pass filtered and studied by spectral analysis. During normal conditions, baseline mean arterial pressure (MAP) was 110+/-10 mm Hg and low-frequency fluctuations in BOLD signal were observed in the frequency range of 0.01 to 0.125 Hz. Following blood withdrawal (exsanguination), MAP decreased to 68+/-7 mm Hg, resulting in an increase in the amplitude of the low-frequency fluctuations in BOLD signal time series and an increase in power at several frequencies between 0.01 and 0.125 Hz. Spatially, the BOLD fluctuations were confined to the cortex and thalamus spanning both hemispheres with sparse presence in the caudate putamen and hippocampus during both normal and exsanguinated states. Spatial distribution of the low-frequency fluctuations in BOLD signal, from cross-correlation analysis, indicates substantial inter-hemispheric synchrony similar to that observed in the conscious human brain. The behavior of the resting state BOLD signal fluctuations similar to CBF fluctuations during exsanguination indicates a myogenic dependence. Also, a high inter-hemispheric synchrony combined with different phase characteristics of the low-frequency BOLD fluctuations particularly in the hippocampus relative to the cortex emphasizes distinct functional networks

The purpose of this paper is to examine the impact of parental mental health and types of racial socialization. The sample consisted of 169 African-American parents and their children (ages 9-11) who participated in a federally funded research project, "Knowledge about the African American Research Experience" (KAARE). Bivariate analyses revealed significant positive relationships between parent mental health status and two forms of racial socialization: spiritual/religious coping, and racial awareness teaching, while multivariate analyses supported the positive association between parental mental health and spiritual/religious coping. These results suggest that parental characteristics may influence the use of specific types of racial socialization to assist youth in coping with discriminatory societal messages.

Racial socialization is receiving research attention because of growing evidence that it can be a protective developmental process in African American families. The present study was an exploration of the relationship of parental mental health, discipline effectiveness, monitoring and racial socialization strategies on child externalizing behaviors in a sample of 140 African American parent/caregivers. Findings indicated that certain types of racial socialization-particularly, spirituality and religious coping-in conjunction with discipline effectiveness was related to child behavior problems. Specifically, among parents who felt they used more effective discipline strategies, moderate to high rates of spiritual and religious coping were associated with a reduction of child behavior problems. These findings support the hypothesis that racial socialization is an important aspect of parenting in African American families that can be associated with the effective management of children's behavior. Implications for parenting interventions and future research are discussed.

CONTEXT: Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly presented threats in GAD or in pediatric anxiety. OBJECTIVE: To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis. MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces. RESULTS: When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects. CONCLUSIONS: Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.