Faculty Bibliography

Classical fear-conditioning is central to many etiologic accounts of panic disorder (PD), but few lab-based conditioning studies in PD have been conducted. One conditioning perspective proposes associative-learning deficits characterized by deficient safety learning among PD patients. The current study of PD assesses acquisition and retention of discriminative aversive conditioning using a fear-potentiated startle paradigm. This paradigm was chosen for its specific capacity to independently assess safety- and danger learning in the service of characterizing putative anomalies in each type of learning among those with PD. Though no group difference in fear-potentiated startle was found at retention, acquisition results demonstrate impaired discriminative learning among PD patients as indexed by measures of conditioned startle-potentiation to learned safety and danger cues. Importantly, this discrimination deficit was driven by enhanced startle-potentiation to the learned safety cue rather than aberrant reactivity to the danger cue. Consistent with this finding, PD patients relative to healthy individuals reported higher expectancies of dangerous outcomes in the presence of the safety cue, but equal danger expectancies during exposure to the danger cue. Such results link PD to impaired discrimination learning, reflecting elevated fear responding to learned safety cues.

OBJECTIVE: This study identified barriers and facilitators to the high-fidelity implementation of assertive community treatment. METHODS: As part of a multistate implementation project for evidence-based practices, training and consultation were provided to 13 newly implemented assertive community treatment teams in two states. Model fidelity was assessed at baseline and at six, 12, 18, and 24 months. Key informant interviews, surveys, and monthly on-site visits were used to monitor implementation processes related to barriers and facilitators. RESULTS: Licensing processes of the state mental health authority provided critical structural supports for implementation. These supports included a dedicated Medicaid billing structure, start-up funds, ongoing fidelity monitoring, training in the model, and technical assistance. Higher-fidelity sites had effective administrative and program leadership, low staff turnover, sound personnel practices, and skilled staff, and they allocated sufficient resources in terms of staffing, office space, and cars. Lower-fidelity sites were associated with insufficient resources, prioritization of fiscal concerns in implementation, lack of change culture, poor morale, conflict among staff, and high staff turnover. In cross-state comparisons, the specific nature of fiscal policies, licensing processes, and technical assistance appeared to influence implementation. CONCLUSIONS: State mental health authorities can play a critical role in assertive community treatment implementation but should carefully design billing mechanisms, promote technical assistance centers, link program requirements to fidelity models, and limit bureaucratic requirements. Successful implementation at the organizational level requires committed leadership, allocation of sufficient resources, and careful hiring procedures.

Standard particle filtering technique have previously been applied to the problem of fiber tracking by Brun et al. [Brun, A., Bjornemo, M., Kikinis, R., Westin, C.F., 2002. White matter tractography using sequential importance sampling. In: Proceedings of the ISMRM Annual Meeting, p. 1131] and Bjornemo et al. [Bjornemo, M., Brun, A., Kikinis, R., Westin, C.F., 2002. Regularized stochastic white matter tractography using diffusion tensor MRI, In: Proc. MICCAI, pp. 435-442]. However, these previous attempts have not utilised the full power of the technique, and as a result the fiber paths were tracked in a goal directed way. In this paper, we provide an advanced technique by presenting a fast and novel probabilistic method for white matter fiber tracking in diffusion weighted MRI (DWI), which takes advantage of the weighting and resampling mechanism of particle filtering. We formulate fiber tracking using a non-linear state space model which captures both smoothness regularity of the fibers and the uncertainties in the local fiber orientations due to noise and partial volume effects. Global fiber tracking is then posed as a problem of particle filtering. To model the posterior distribution, we classify voxels of the white matter as either prolate or oblate tensors. We then construct the orientation distributions for prolate and oblate tensors separately. Finally, the importance density function for particle filtering is modeled using the von Mises-Fisher distribution on a unit sphere. Fast and efficient sampling is achieved using Ulrich-Wood's simulation algorithm. Given a seed point, the method is able to rapidly locate the globally optimal fiber and also provides a probability map for potential connections. The proposed method is validated and compared to alternative methods both on synthetic data and real-world brain MRI datasets.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) has been widely used to investigate the development of white matter (WM). However, information about this development in healthy children younger than 2 years of age is lacking, and most previous studies have only measured fractional anisotropy (FA). This study used FA and radial and axonal diffusivities in children younger than 2 years of age, aiming to determine the temporal and spatial development of axonal maturation and myelination of WM in healthy children. MATERIALS AND METHODS: A total of 60 healthy pediatric subjects were imaged by using a 3T MR imaging scanner. They were divided into 3 groups: 20 at 3 weeks, 20 at 1 year of age, and 20 at 2 years of age. All subjects were imaged asleep without sedation. FA and axial and radial diffusivities were obtained. Eight regions of interest were defined, including both central and peripheral WM for measuring diffusion parameters. RESULTS: A significant elevation in FA (P < .0001) and a reduction in axial and radial diffusivities (P < .0001) were observed from 22 days to 1 year of age, whereas only radial diffusivity showed significant changes (P = .0014) from 1 to 2 years of age. The region-of-interest analysis revealed that FA alone may not depict the underlying biologic underpinnings of WM development, whereas directional diffusivities provide more insights into the development of WM. Finally, the spatial development of WM begins from the central to the peripheral WM and from the occipital to the frontal lobes. CONCLUSIONS: With both FA and directional diffusivities, our results demonstrate the temporal and spatial development of WM in healthy children younger than 2 years of age.

This paper examines factors associated with adherence to antiretroviral medications (ARVs) in an HIV-infected population at high risk for non-adherence: individuals living with psychiatric and substance abuse disorders. Data were examined from baseline interviews of a multisite cohort intervention study of 1138 HIV-infected adults with both a psychiatric and substance abuse disorder (based on a structured psychiatric research interview using DSM-IV criteria). The baseline interview documented mental illness and substance use in the past year, mental illness and substance abuse severity, demographics, service utilization in the past three months, general health and HIV-related conditions, self-reported spirituality and self-reported ARV medication use. Among the participants, 62% were prescribed ARVs at baseline (n = 542) and 45% of those on ARVs reported skipping medications in the past three days. Reports of non-adherence were significantly associated with having a detectable viral load (p<.01). The factors associated with non-adherence were current drug and alcohol abuse, increased psychological distress, less attendance at medical appointments, non-adherence to psychiatric medications and lower self-reported spirituality. Increased psychological distress was significantly associated with non-adherence, independent of substance abuse (p<.05). The data suggest that both mental illness and substance use must be addressed in HIV-infected adults living with these co-morbid illnesses to improve adherence to ARVs

We examined the differences in conflict interaction between depressed mothers and their toddler and non-depressed dyads and whether these differences mediated the association of maternal depression with compromised child socioemotional development. Mother/ child interaction was videotaped during a teaching task and during a free play task as part of a home visit when the target child was between 16 and 18 months old. Each turn of every conflict was coded for behavior and affect of each member of the dyad. Interaction data were summarized to calculate the number of conflict turns, the rate of conflict, and the proportion of mother-initiated versus child-initiated conflicts per dyad. Sequential analysis was used to estimate the probability of specific maternal responses to specific child behaviors. Bivariate comparisons indicated that depressed dyads experienced higher rates of conflict, especially during the teaching task, and that depressed mothers were more likely to respond destructively to child oppositional behavior. Results of multivariate linear regression indicated that the higher probability of destructive response mediated the association of maternal depression with lower quality of mother-child attachment. These findings have implications for the development of interventions to support mothers in dealing with the conflicts that are so common during the second year of a child's life.

Child maltreatment has been associated with different psychiatric disorders. Studies on both animals and humans have suggested that some brain areas would be directly affected by severe psychological trauma. The pathophysiology of post-traumatic stress disorder (PTSD) appears to be related to a complex interaction involving genetic and environmental factors. Advanced neuroimaging techniques have been used to investigate neurofunctional and neurostructural abnormalities in children, adolescents, and adults with PTSD. This review examined structural brain imaging studies that were performed in abused and traumatized children, and discusses the possible biological mechanisms involved in the pathophysiology of PTSD, the implications and future directions for magnetic resonance imaging (MRI) studies. Published reports in refereed journals were reviewed by searching Medline and examining references of the articles related to structural neuroimaging of PTSD. Structural MRI studies have been performed in adults and children to evaluate the volumetric brain alterations in the PTSD population. In contrast with studies involving adults, in which hippocampus volumetric reduction was the most consistent finding, studies involving children and adolescents with PTSD have demonstrated smaller medial and posterior portions of the corpus callosum

This study explores relationships among childhood sexual abuse (CSA), age of substance use initiation, additional traumatic events, and posttraumatic stress disorder (PTSD) in a sample of adolescents. A history of CSA that preceded substance use was not related to an earlier age of substance use initiation. Early initiation of substance use predicted exposure to additional traumatic experiences. This relationship was partially mediated by engagement in risky behavior while under the influence of substances. Posttraumatic stress disorder was related to CSA, additional traumatic experiences and engagement in risky behavior while under the influence of substances

A core aspect of working memory (WM) is the capacity to maintain goal-relevant information in mind, but little is known about how this capacity develops in the human brain. We compared brain activation, via fMRI, between children (ages 7-12 years) and adults (ages 20-29 years) performing tests of verbal and spatial WM with varying amounts (loads) of information to be maintained in WM. Children made disproportionately more errors than adults as WM load increased. Children and adults exhibited similar hemispheric asymmetry in activation, greater on the right for spatial WM and on the left for verbal WM. Children, however, failed to exhibit the same degree of increasing activation across WM loads as was exhibited by adults in multiple frontal and parietal cortical regions. Thus, children exhibited adult-like hemispheric specialization, but appeared immature in their ability to marshal the neural resources necessary to maintain large amounts of verbal or spatial information in WM.

The way in which sex hormones influence cognitive and affective brain development is poorly understood. Despite increasing knowledge in the area of pediatric mood disorders, little is known about the influence of sex hormones on the regulation of emotion. Animal studies and preliminary human studies suggest a strong impact of testosterone on limbic structures such as the hippocampus and amygdala. We used functional magnetic resonance imaging (fMRI) to examine emotional processing in familial male-precocious puberty (FMPP), an extremely rare gonadotropin-independent form of precocious puberty characterized by early excess testosterone secretion. We compared this group (n = 7, mean age = 13 +/- 3.3 years) to healthy age and sex-matched controls (n = 14, mean age = 13 +/- 2.3 years). Participants were presented with emotional and neutral face stimuli and were required either to judge the hostility of the presented face, their subjective level of anxiety, or the width of the nose of the presented faces (nonemotional condition). In a fourth, passive viewing condition, no responses were required. Boys with FMPP responded faster to fearful faces during perception of threat compared to unaffected controls. Concurrently, fMRI data revealed significant differences in hippocampus activation in response to fearful faces relative to baseline whereas controls showed no differences. In contrast, no significant activation of the amygdala was found. These data are consistent with previous studies of the effects of sex hormones on brain function and support the role of testosterone on emotional development.