People with schizophrenia have documented evidence of abnormal prefrontal cortex (PFC) mediated cognitive control. A group of healthy people exist who manifest neither signs nor symptoms of schizophrenia but who nevertheless show impaired cognitive control. In this healthy group, both task performance and brain activities are like those observed in people schizophrenia. Yet, schizophrenia is a unique disorder that must be caused by neural deviations differentiable from those solely associated with manifestations of poor PFC-mediated cognitive control. This project will demonstrate that nonspecific neural noise (as a function of cognitive control requirements) accentuates and characterizes the behavioral and neural manifestations of poor cognitive control in schizophrenia. Long-term Goals: This work will show that cognitive control abnormalities resulting in similar behavioral manifestations have different neural etiologies. It will link seemingly disparate behavioral and brain activity deviations for a unified theory of schizophrenia, thus providing a template for translational studies of the illness.
Specific Aims : This project will address 4 critical issues for understanding associations between neural noise, cognitive control, regulation of sensory systems, and behavioral performance in schizophrenia: (i) excess (nonspecific) neural noise as a primary neurophysiological deviation; (ii) PFC activation and PFC-mediated modulation of sensory processing as a function of cognitive control requirements; (iii) regulation of sensory input to support visual attention and perceptual target detection as a function of stimulus density; and (iv) specificity of deviations in (i)-(iii) to schizophrenia. Methods: During visual tasks, eye movements will be recorded using EOG and neural activity data will be collected with combined MEG (143 channel) / EEG (64 sensor) equipment designed for simultaneous measurements. Combining EEG/MEG yields the best spatial accuracy and temporal certainty for solving source localization problems given their shared and unique sensitivities to brain activities because they act synergistically to improve source localizations. The advantages of combining imaging technologies like EEG/MEG to solve source localization problems has been known for some time but it is still an uncommon practice, although we have demonstrated our ability to perform combined EEG/MEG source localizations using saccade tasks (McDowell et al., 2005). This research will have important implications for understanding the neural bases of cognitive control problems inherent to schizophrenia and how those differ from comparison populations. We also aim to develop a more coherent understanding of the role of PFC problems in schizophrenia, which would guide translational research and inform strategies for developing rehabilitation and treatment techniques.

Public Health Relevance

The research focuses on the behavioral and brain activity patterns associated with poor cognitive control observed among people with schizophrenia, and how that differs from healthy people who have poor cognitive control, without the signs and symptoms of the illness. It is hypothesized that an increase in baseline neural noise (analogous to the static heard in the background of a radio) is responsible for these problems in schizophrenia and that we will be able to measure and manipulate these levels by presenting visual stimuli and recording the resulting brain responses. Provision of evidence for the effect of increased neural noise in schizophrenia that is specific to the illness would provide a template for translational research on schizophrenia and facilitate research on rehabilitation and treatment of this disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH094172-05
Application #
8795615
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Meinecke, Douglas L
Project Start
2011-02-08
Project End
2016-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
5
Fiscal Year
2015
Total Cost
$371,250
Indirect Cost
$121,250
Name
University of Georgia
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
004315578
City
Athens
State
GA
Country
United States
Zip Code
30602
Hudgens-Haney, Matthew E; Ethridge, Lauren E; McDowell, Jennifer E et al. (2018) Psychosis subgroups differ in intrinsic neural activity but not task-specific processing. Schizophr Res 195:222-230
Rodrigue, Amanda L; Schaeffer, David J; Pierce, Jordan E et al. (2018) Evaluating the Specificity of Cognitive Control Deficits in Schizophrenia Using Antisaccades, Functional Magnetic Resonance Imaging, and Healthy Individuals With Poor Cognitive Control. Front Psychiatry 9:107
Hamm, Jordan P; Bobilev, Anastasia M; Hayrynen, Lauren K et al. (2015) Stimulus train duration but not attention moderates ?-band entrainment abnormalities in schizophrenia. Schizophr Res 165:97-102
Schaeffer, David J; Rodrigue, Amanda L; Burton, Courtney R et al. (2015) White matter structural integrity differs between people with schizophrenia and healthy groups as a function of cognitive control. Schizophr Res 169:62-68
Hamm, Jordan P; Ethridge, Lauren E; Shapiro, John R et al. (2013) Family history of psychosis moderates early auditory cortical response abnormalities in non-psychotic bipolar disorder. Bipolar Disord 15:774-86
Hamm, Jordan P; Dyckman, Kara A; McDowell, Jennifer E et al. (2012) Pre-cue fronto-occipital alpha phase and distributed cortical oscillations predict failures of cognitive control. J Neurosci 32:7034-41