1987 — 2000 |
Barbas, Helen |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Anatomy of Limbic Prefrontal Cortex @ Boston University Medical Campus
The objective of this research program is to investigate the anatomic pattern of communication of the prefrontal cortex with other cortical and subcortical brain regions. The specific purpose is to examine the connectional organization of those prefrontal cortices which are considered limbic. The rationale is based on the importance of the prefrontal cortex, in general, and the limbic system, in particular, for memory, cognition and emotion. The choice of a primate is predicated by the unique set of connections between the phylogenetically older limbic system and the more recently evolved isocortex in primates. Damage to the limbic system in primates disrupts a series of higher order functions previously associated exclusively with the neocortices. Our previous work suggests that the degree of cortical architectonic differentiation is central to the pattern of connections between prefrontal and sensory association cortices, and seems to be also associated with several other cortical organizational features. This hypothesis will be tested further by: investigating the sources of cortical and subcortical projections to the largely unexplored medial and orbital frontal limbic regions; comparing the sources of afferent projections to medial and orbital limbic regions; and studying the regional distribution of acetylcholinesterase, cytochrome oxidase, and myelin to determine the chemical composition of the projection zones. Connections will be studied using both horseradish peroxidase and fluorescent dyes to label the neurons of origin. Limbic cortices have widespread cortical and subcortical connections, suggesting that they may exercise a tonic influence on the entire brain. These studies may have important implications for the processes underlying the disruption of higher order functions following traumatic or degenerative insult to the limbic cortices, and for the development of the cortex in phylogeny.
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2001 — 2021 |
Barbas, Helen |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Prefrontal Anatomic Pathways in Executive Control @ Boston University (Charles River Campus)
Goal-directed behavior requires selection of signals from the external and internal emotional environments based on memory and prior experience for action. Processes that rely on emotions and memory engage the network of medial frontal area 25 and medial temporal lobe (MTL) cortices, which are affected in psychiatric diseases. The goal of the proposed studies is to investigate specific circuits of the medial frontal (subgenual area 25) and MTL regions in rhesus monkeys. Pathways will be studied in the context of the excitatory and inhibitory neuronal composition in both monkeys and humans, which critically affects function and disruption in brain diseases. Our overarching hypothesis is that the Structural Model, which predicts the patterns and strength of cortical connections studied in non-human primates, apply for study of pathology in brain diseases in humans. Subgenual area 25 and MTL areas are affected in depression, which often manifests early in chronic traumatic encephalopathy (CTE). Medial frontal and temporal areas show distinct types of pathology in CTE by unknown circuit mechanisms. The goal of the proposed studies is to use high resolution connections in monkeys to investigate the circuit mechanisms of the distinct pathology in medial frontal and MTL areas in CTE through study of: (1) The synaptic targets of frontal area 25 to MTL area 28 in monkeys, and the excitatory- inhibitory neuronal composition of the respective areas in both monkeys and humans; (2) Laminar connections within MTL in monkeys, to compare with laminar-specific tau pathology in CTE; (3) The normal excitatory and inhibitory neuronal and glial make-up of frontal area 25 in monkeys and humans to compare with CTE, based on evidence that hyperactivity in area 25 perturbs normal function in depression; and (4) The density and integrity of axons below area 25 in human control and CTE brains, which give rise to bidirectional pathways that link with nearby prefrontal and distant cortices. Hypotheses about pathway relationships are based on the theoretical and data based Structural Model, in the context of principles of excitatory and inhibitory control in primates. Pathways in rhesus monkeys will be labeled with distinct neural tracers, combined with multiple labeling for inhibitory neurons and receptors. High-resolution data from monkeys will be compared with CTE cortex to identify distinct pathology in MTL and medial frontal regions. Quantitative data will be obtained using correlated light, confocal and electron microscopy, analyzed using advanced statistical methods and synthesized through modeling. Findings will establish the still unknown circuit basis for distinct pathology in MTL and medial frontal areas in CTE, which perturbs the excitation-inhibition balance in depression and the processes of interoception, emotion and memory.
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