Attention disturbances have been described as core deficits underlying global cognitive dysfunction in schizophrenia. These deficits appear prior to illness onset, are observed in unaffected relatives, and are highly susceptible to emotional interference. This proposal has two broad aims that extend our previous studies on attention in schizophrenia: (1) To characterize the functional neuroanatomy of involuntary and voluntary attention processes in schizophrenia, and assess their disruption by affective interference and (2) To evaluate whether genetic high-risk individuals with prodromal symptoms (GHRP) show impairments in these domains of attention, thus exploring their potential significance as clinically relevant """"""""risk markers"""""""" in vulnerable populations. We will use functional magnetic resonance imaging (fMRI) to map the spatial localization of the neural activity associated with attention processes in the brain, electrophysiological recordings to gather temporal information as to whether these deficits occur at the sensory or cognitive stages of processing, and performance indicators of target discrimination and distractor interference. This project has three specific aims.
In Aim1, we will characterize the neural and hemodynamic correlates of VOLUNTARY attention in recent onset schizophrenia (roSCZ) and GHRP individuals. FMRI will probe the integrity of fronto-striate, fronto-temporal and fronto-parietal circuitry during a voluntary attention task, while ERP measures will assess N2/P3 component characteristics during the same task.
In Aim 2, we will characterize the neural and hemodynamic correlates of EMOTIONAL INTERFERENCE during the deployment of VOLUNTARY attention processes in roSCZ and GHRP individuals. FMRI measures will . assess fronto-limbic and fronto-striate activations and interactions, while ERP measures will characterize the novelty N2/P3 components elicited by the task-irrelevant emotional stimuli.
In Aim 3, we will evaluate the neural and hemodynamic correlates of INVOLUNTARY attention in roSCZ and GHRP individuals, and determine whether these deficits are independent of global attention limits by manipulating the complexity of the primary task. Secondary aims will evaluate diffusion tensor imaging (DTI) and time-frequency domain EEG measures to inform whether co-existing alterations in white matter properties or local cortical neural synchrony may lend support to the """"""""functional dysconnectivity"""""""" model of schizophrenia. The use of converging evidence from multiple methodologies as proposed in this project is highly innovative and can help us build a more complete model of the pathophysiological mechanisms underlying schizophrenia. Furthermore, this project is highly significant, as it aims to identify clinically relevant risk markers in vulnerable populations. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH058251-06A2
Application #
7320052
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2001-04-06
Project End
2012-05-31
Budget Start
2007-09-01
Budget End
2008-05-31
Support Year
6
Fiscal Year
2007
Total Cost
$444,156
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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