This revised application requests continuing support to evaluate characteristics of information processing deficits in schizophrenia. Central to this research is the dissociation of processing effort from informational utilization. We suggest that most schizophrenia patients are actively expending effort to attend to information, while cognitive deficits reflect disturbances in analysis, integration, and manipulation of information. We propose to assess changes in pupil diameter because the pupillary system is exquisitely sensitive to differential activation on the basis of processing effort and informational complexity. A key objective is to evaluate differential sympathetic and parasympathetic innervation of the pupil to quantify the extent of cognitive deficits, while providing evidence for intact effortful processing in the same schizophrenia patients. Psychophysiological assessment will be carried out as patients perform tasks varying in attentional and processing demands. In the current application, special emphasis has been placed on paradigms associated with the concept of working memory, which has strongly impacted current views of processing deficits in schizophrenia. A psychiatric control group of depressed individuals also will be studied. To delineate the pathways that contribute to the changes in the pupillary control system, two non-invasive methodologies are employed. 1) The contribution of the parasympathetic pathway will be enhanced through modulation of illumination. 2) In schizophrenia patients and healthy control subjects, the final sympathetic and parasympathetic pathways will be isolated at separate experimental sessions by temporary pharmacological blockade of the complementary neuromusculature junction of the pupil. Direct evaluation of the relationship of pupillary changes and activation of brain regions will be accomplished by a study of concurrent pupillary and neuroimaging data in schizophrenia patients and healthy controls. Elucidating the neurophysiological systems that are affected in patients provides a rationale for exploring etiological factors and treatment strategies. Differentiation of processing capacity from general mental effort, in particular, allows a clear examination of the types of cognitive deficits in schizophrenia. Findings will further pinpoint functional systems to be examined using current and future imaging technologies.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Meinecke, Douglas L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Schools of Medicine
United States
Zip Code
Mandell, Darcy; Siegle, Greg J; Shutt, Luann et al. (2014) Neural substrates of trait ruminations in depression. J Abnorm Psychol 123:35-48
Kang, Peter; Kloke, John; Jain, Samay (2012) Olfactory dysfunction and parasympathetic dysautonomia in Parkinson's disease. Clin Auton Res 22:161-6
Siegle, Greg J; Steinhauer, Stuart R; Friedman, Edward S et al. (2011) Remission prognosis for cognitive therapy for recurrent depression using the pupil: utility and neural correlates. Biol Psychiatry 69:726-33
Jain, Samay; Siegle, Greg J; Gu, Chen et al. (2011) Pupillary unrest correlates with arousal symptoms and motor signs in Parkinson disease. Mov Disord 26:1344-7
Jain, Samay; Siegle, Greg J; Gu, Chen et al. (2011) Autonomic insufficiency in pupillary and cardiovascular systems in Parkinson's disease. Parkinsonism Relat Disord 17:119-22
Condray, Ruth; Siegle, Greg J; Keshavan, Matcheri S et al. (2010) Effects of word frequency on semantic memory in schizophrenia: electrophysiological evidence for a deficit in linguistic access. Int J Psychophysiol 75:141-56
Steinhauer, Stuart R; Condray, Ruth (2010) Psychophysiology of language processes in psychopathology: an overview of the special issue. Int J Psychophysiol 75:63-5
Chakraborty, Beatrice H; Steinhauer, Stuart R (2010) Reporting of minority participation rates and racial differences in schizophrenia and psychophysiological research: improving but still not adequate. Schizophr Res 123:90-1
Siegle, Greg J; Condray, Ruth; Thase, Michael E et al. (2010) Sustained gamma-band EEG following negative words in depression and schizophrenia. Int J Psychophysiol 75:107-18
Condray, Ruth; Yao, Jeffrey K; Steinhauer, Stuart R et al. (2008) Semantic memory in schizophrenia: association with cell membrane essential fatty acids. Schizophr Res 106:13-28

Showing the most recent 10 out of 22 publications