Faculty Bibliography

The amygdala is composed of structurally and functionally distinct nuclei that contribute to the processing of emotion through interactions with other subcortical and cortical structures. While these circuits have been studied extensively in animals, human neuroimaging investigations of amygdala-based networks have typically considered the amygdala as a single structure, which likely masks contributions of individual amygdala subdivisions. The present study uses resting state functional magnetic resonance imaging (fMRI) to test whether distinct functional connectivity patterns, like those observed in animal studies, can be detected across three amygdala subdivisions: laterobasal, centromedial, and superficial. In a sample of 65 healthy adults, voxelwise regression analyses demonstrated positively-predicted ventral and negatively-predicted dorsal networks associated with the total amygdala, consistent with previous animal and human studies. Investigation of individual amygdala subdivisions revealed distinct differences in connectivity patterns within the amygdala and throughout the brain. Spontaneous activity in the laterobasal subdivision predicted activity in temporal and frontal regions, while activity in the centromedial nuclei predicted activity primarily in striatum. Activity in the superficial subdivision positively predicted activity throughout the limbic lobe. These findings suggest that resting state fMRI can be used to investigate human amygdala networks at a greater level of detail than previously appreciated, allowing for the further advancement of translational models.

We present a simple computational model of the dentate gyrus to evaluate the hypothesis that pattern separation, defined as the ability to transform a set of similar input patterns into a less-similar set of output patterns, is dynamically regulated by hilar neurons. Prior models of the dentate gyrus have generally fallen into two categories: simplified models that have focused on a single granule cell layer and its ability to perform pattern separation, and large-scale and biophysically realistic models of dentate gyrus, which include hilar cells, but which have not specifically addressed pattern separation. The present model begins to bridge this gap. The model includes two of the major subtypes of hilar cells: excitatory hilar mossy cells and inhibitory hilar interneurons that receive input from and project to the perforant path terminal zone (HIPP cells). In the model, mossy cells and HIPP cells provide a mechanism for dynamic regulation of pattern separation, allowing the system to upregulate and downregulate pattern separation in response to environmental and task demands. Specifically, pattern separation in the model can be strongly decreased by decreasing mossy cell function and/or by increasing HIPP cell function; pattern separation can be increased by the opposite manipulations. We propose that hilar cells may similarly mediate dynamic regulation of pattern separation in the dentate gyrus in vivo, not only because of their connectivity within the dentate gyrus, but also because of their modulation by brainstem inputs and by the axons that 'backproject' from area CA3 pyramidal cells. (c) 2008 Wiley-Liss, Inc

Although antidepressants are moderately effective in treating major depressive disorder (MDD), concerns have arisen that selective serotonin-reuptake inhibitors (SSRIs) are associated with suicidal thinking and behavior, especially in children, adolescents and young adults. Almost no experimental research in model systems has considered the mechanisms by which SSRIs might be associated with this potential side effect in some susceptible individuals. Suicide is a complex behavior and impossible to fully reproduce in an animal model. However, by investigating traits that show strong cross-species parallels in addition to associations with suicide in humans, animal models might elucidate the mechanisms by which SSRIs are associated with suicidal thinking and behavior. Traits linked with suicide in humans that can be successfully modeled in rodents include aggression, impulsivity, irritability and hopelessness/helplessness. Modeling these relevant traits in animals can help to clarify the impact of SSRIs on these traits, suggesting avenues for reducing suicide risk in this vulnerable population.

OBJECTIVE: The 2003 Medicare Modernization Act shifted medication coverage from Medicaid to Medicare for persons dually eligible for both programs. This study examined the extent to which access to psychiatric and concomitant medications was reduced for dually eligible individuals in New York State. It also examined the extent to which consumer copayments and state costs were changed when the act was implemented in 2006. METHODS: Data were from psychiatric medication Medicaid claims in 2002 for the 36,842 dually eligible adults with severe mental illness and from the 2006 formulary data of New York State's 15 prescription drug plans available after the Medicare Modernization Act was implemented. The study simulated how dually eligible persons in New York State would fare under the plans' random and best-fit enrollment scenarios, taking into account the additional coverage provided by New York State's 2006 safety net policy. RESULTS: Implementation of the Medication Modernization Act reduced drug availability and increased usage restrictions. A study-defined generosity measure estimated a 51%+/-19% reduction in access. Dually eligible individuals with depression experienced the largest treatment gap. Cost changes to the state were essentially budget neutral, primarily because of the required claw-back payment. Consumer copayments increased percentage-wise, but actual dollar amounts remained small; increases were higher under best-fit enrollment compared with random enrollment. CONCLUSIONS: Without a generous safety net policy, dually eligible beneficiaries, especially those with depression, are likely to experience large gaps in their medication coverage and somewhat higher out-of-pocket costs. Treatment gaps were somewhat reduced by placement in best-fit plans, and such placement resulted in no added financial burden to the state. However, this resulted in higher consumer copayments--payments that are small in the actual dollar amount but that might have an impact on spending and on medication access for a largely poor consumer group

Predictors of attrition from individual parent-child interaction therapy were examined for 99 families of preschoolers with disruptive behavior disorders. Seventy-one percent of treatment dropouts were identified by lower SES, more maternal negative talk, and less maternal total praise at pretreatment. Following PCIT, families were randomly assigned to an Assessment-Only or Maintenance Treatment condition. Higher maternal distress predicted 63% of dropouts in the Assessment-Only condition. Lower maternal intellectual functioning predicted 83% of dropouts from Maintenance Treatment. Findings highlight a continuing need for evidence-based retention strategies at various phases of engagement in PCIT

Obtaining validation data and comparison metrics for segmentation of magnetic resonance images (MRI) are difficult tasks due to the lack of reliable ground truth. This problem is even more evident for images presenting pathology, which can both alter tissue appearance through infiltration and cause geometric distortions. Systems for generating synthetic images with user-defined degradation by noise and intensity inhomogeneity offer the possibility for testing and comparison of segmentation methods. Such systems do not yet offer simulation of sufficiently realistic looking pathology. This paper presents a system that combines physical and statistical modeling to generate synthetic multi-modal 3D brain MRI with tumor and edema, along with the underlying anatomical ground truth, Main emphasis is placed on simulation of the major effects known for tumor MRI, such as contrast enhancement, local distortion of healthy tissue, infiltrating edema adjacent to tumors, destruction and deformation of fiber tracts, and multi-modal MRI contrast of healthy tissue and pathology. The new method synthesizes pathology in multi-modal MRI and diffusion tensor imaging (DTI) by simulating mass effect, warping and destruction of white matter fibers, and infiltration of brain tissues by tumor cells. We generate synthetic contrast enhanced MR images by simulating the accumulation of contrast agent within the brain. The appearance of the the brain tissue and tumor in MRI is simulated by synthesizing texture images from real MR images. The proposed method is able to generate synthetic ground truth and synthesized MR images with tumor and edema that exhibit comparable segmentation challenges to real tumor MRI. Such image data sets will find use in segmentation reliability studies, comparison and validation of different segmentation methods, training and teaching, or even in evaluating standards for tumor size like the RECIST criteria (response evaluation criteria in solid tumors).

Although it is known that schizophrenia is associated with social class, controversy exists as to the nature of this association. The authors studied the incidence of schizophrenia in relation to social class at birth in a population-based cohort of 88,829 offspring born in Jerusalem in 1964-1976. They constructed a six-point scale to index social class, based on paternal occupation at the time of birth, with each of 108 occupations being ranked by mean education. Cox proportional hazards methods were used in adjusting for sex, parents' ages, duration of marriage and birth order. Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. There was no gradient of risk for schizophrenia associated with social class at birth; however, offspring of fathers in the lowest social class showed a modest increase in risk (adjusted Relative Risk = 1.4; 95% Confidence interval = 1.1-1.8, P = 0.002). These data suggest that in contrast to many other health outcomes, there is not a continuous gradient for increasing schizophrenia with decreasing social class of origin. Instead, a modest increase in risk for schizophrenia was observed only for those born at the bottom of the social ladder