The long-term goal of this project is to define the functional organization of the ventromedial frontal cortex and related structures such as the temporal and insular cortex, and the relation of these circuits to mood disorders. Previous work defined two distinct """"""""orbital"""""""" and """"""""medial"""""""" networks of interconnected areas within the orbital and medial prefrontal cortex (OMPFC). Differential connections to sensory and visceral control structures, and other observations, suggest that the orbital network is a sensory system related to food and reward, while the medial network is a viscero-motor system related to emotion. In humans, the OMPFC has been implicated in mood disorders and other psychiatric conditions but it is not known to what degree these differentially affect the two prefrontal networks. These neural circuits will be studied both in macaque monkeys and in humans. An ongoing neuroanatomical analysis in monkeys of the relation of the orbital and medial prefrontal networks with the temporal lobe with multiple anterograde and retrograde axonal tracers will be continued, and extended to include an analysis of the insula. In addition a new project is proposed to analyze pathways from the periaqueductal gray and the intralaminar nuclei of the thalamus to the OMPFC. In humans, a recently completed architectonic analysis of the OMPFC will be extended to an analysis of the temporal pole, temporal cortex and insula. The variability within the architectonic map of the OMPFC between different subjects or from side-to-side of the same brain will also be studied, using recently enhanced software to produce three-dimensional reconstructions and unfolded cortical maps. The role of OMPFC in mood disorders will be studied in two ways. First, previous observations of glial decreases in mood disorders will be extended to include additional brains obtained from the NIMH brain bank (in collaboration with Drs. Joel Kleineman and Wayne Drevets at NIMH), and to confirm recent data that oligodendrocytes are the major glial type affected. Second, activity patterns from functional imaging scans (PET and fMRI) from controls and mood disorder subjects will be analyzed in relation to the architectonic areas of the OMPFC (in collaboration with Dr. Drevets), to determine which specific areas and networks are affected in these disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH070941-37
Application #
7346940
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
1976-09-01
Project End
2010-01-31
Budget Start
2008-02-01
Budget End
2010-01-31
Support Year
37
Fiscal Year
2008
Total Cost
$440,504
Indirect Cost
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Saleem, Kadharbatcha S; Miller, Brad; Price, Joseph L (2014) Subdivisions and connectional networks of the lateral prefrontal cortex in the macaque monkey. J Comp Neurol 522:1641-90
Price, Joseph L; Drevets, Wayne C (2012) Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn Sci 16:61-71
Shear, M Katherine (2012) Grief and mourning gone awry: pathway and course of complicated grief. Dialogues Clin Neurosci 14:119-28
Price, Joseph L; Drevets, Wayne C (2010) Neurocircuitry of mood disorders. Neuropsychopharmacology 35:192-216
Hsu, David T; Price, Joseph L (2009) Paraventricular thalamic nucleus: subcortical connections and innervation by serotonin, orexin, and corticotropin-releasing hormone in macaque monkeys. J Comp Neurol 512:825-48
Saleem, Kadharbatcha S; Kondo, Hideki; Price, Joseph L (2008) Complementary circuits connecting the orbital and medial prefrontal networks with the temporal, insular, and opercular cortex in the macaque monkey. J Comp Neurol 506:659-93
Hsu, David T; Price, Joseph L (2007) Midline and intralaminar thalamic connections with the orbital and medial prefrontal networks in macaque monkeys. J Comp Neurol 504:89-111
Price, Joseph L (2007) Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions. Ann N Y Acad Sci 1121:54-71
Saleem, Kadharbatcha S; Price, Joseph L; Hashikawa, Tsutomu (2007) Cytoarchitectonic and chemoarchitectonic subdivisions of the perirhinal and parahippocampal cortices in macaque monkeys. J Comp Neurol 500:973-1006
Kondo, Hideki; Saleem, Kadharbatcha S; Price, Joseph L (2005) Differential connections of the perirhinal and parahippocampal cortex with the orbital and medial prefrontal networks in macaque monkeys. J Comp Neurol 493:479-509