This proposal is designed to assess the presence and nature of the relationship between the prefrontal cortex and two medial temporal lobe areas (hippocampal formation and rhinal cortices) in subserving memory and executive function in the primate. In the rhesus monkey, we will use a crossed lesion / split brain technique to isolate and disconnect these two regions of the medial temporal lobe from the prefrontal cortex in order to assess whether there exists a functional interaction between these two brain regions in the performance of memory and executive functions. In order to assess the presence and nature of a functional interaction, it will be necessary to first assess the specific effect of bilateral lesions on each of these three regions. Hence, in the first phase of the study, a cognitive test battery,"""""""" in which executive function"""""""" and """"""""mnemonic"""""""" demands within and across tasks will be systematically varied, will be administered to monkeys with bilateral lesions of either the dorsal prefrontal cortex (BFF), the hippocampal formation (BHH), or the rhinal cortices (BRR). In the second phase (""""""""disconnections""""""""), using the same test battery as in the first phase, one experimental group (Group CFHS) will receive a unilateral lesion of the dorsal prefrontal cortex and a contralateral lesion of the hippocampal formation together with a transection of the forebrain commissures. This lesion will disconnect the intact hippocampal formation and prefrontal cortex of the opposite hemispheres. The second experimental group (CFRS) will be prepared with the same unilateral lesion of the dorsal prefrontal cortex but a contralateral lesion of the rhinal cortices with transection of the forebrain commissures. This lesion will disconnect the intact prefrontal cortex from the intact parahippocampal cortices of the opposite hemispheres. In order to assess the effect of these two """"""""disconnections"""""""", we will compare their performance to three control groups. The first will be an operated control group (OC) that will also serve as controls for the bilateral lesions in the first phase. The second group (IFHS) will have a unilateral hippocampal formation lesion, an ipsilateral dorsolateral prefrontal lesion, and a transection of the forebrain commissures. This will produce brain damage identical to that in group CFHS, controlling for the total brain damage, but will leave the hippocampal formation and prefrontal cortex on the same side intact and """"""""connected"""""""". The third group (IFRS) will have a unilateral lesion of the rhinal cortices along with a unilateral lesion of the dorsolateral prefrontal cortex and transection of the forebrain commissures. This will produce the same degree of brain damage to that in group CFRS, but leave the rhinal and prefrontal cortices on one side intact and """"""""connected"""""""".

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH069686-04
Application #
7152890
Study Section
Biobehavioral and Behavioral Processes 3 (BBBP)
Program Officer
Osborn, Bettina D
Project Start
2003-12-01
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2007-11-30
Support Year
4
Fiscal Year
2007
Total Cost
$526,606
Indirect Cost
Name
Boston University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118