Thought disorder is a cardinal symptom of schizophrenia, and is inferred through abnormal language. Disordered thought has a high genetic penetrance, and is detected in relatives of schizophrenia patients at a high rate, even when these relatives do not exhibit overt psychosis. Thus, examination of thinking problems may be especially insightful for understanding schizophrenia. The broad aim of this proposal is to combine behavioral measures and brain activity measures to further understand the underlying abnormalities of semantic conceptual memory neural networks and of verbal working memory systems that allow adaptive and flexible human behavior in the face of unique current situations. More specifically, the aims are to understand automatic semantic activation versus controlled verbal working memory inhibition and to relate these dysfunctions to underlying brain systems, so as to understand the neurophysiology of psychosis. First, automatic memory processes and related brain activity will be contrasted with controlled contextual inhibitory processes and related brain activity during language processing tasks using lexical ambiguities (homographs like box;to box, the box). Second, the effects of expectations on language processing will be examined. Third, high frequency brain activity (gamma waves) during lexical access will be examined to assess the integrity of semantic memory neural network structure. Memories are stored in distributed networks, and gamma activity likely allows distributed brain areas to work in concert. Lastly, the effects of recent memory traces and recent response outcome traces on the current behavior of patients will be examined, to assess how the recent past benefits or detracts from current performance in patients. The studies will help determine where in the information processing stream most blame can be laid for thought disorder, early in the automatic semantic memory system, or later in the controlled working memory system, and how behavior relates to underlying brain systems. Together the data will help clarify the nature of thought disorder and cognitive abnormalities in schizophrenia with respect to actual brain structure and function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH058704-09
Application #
7797594
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2001-07-20
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2012-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$351,745
Indirect Cost
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Lee, Sang-Hyuk; Niznikiewicz, Margaret; Asami, Takeshi et al. (2016) Initial and Progressive Gray Matter Abnormalities in Insular Gyrus and Temporal Pole in First-Episode Schizophrenia Contrasted With First-Episode Affective Psychosis. Schizophr Bull 42:790-801
Gurrera, Ronald J; McCarley, Robert W; Salisbury, Dean (2014) Cognitive task performance and symptoms contribute to personality abnormalities in first hospitalized schizophrenia. J Psychiatr Res 55:68-76
Taylor, Grantley W; McCarley, Robert W; Salisbury, Dean F (2013) Early auditory gamma band response abnormalities in first hospitalized schizophrenia. Suppl Clin Neurophysiol 62:131-45
Mulert, Christoph; Kirsch, Valerie; Whitford, Thomas J et al. (2012) Hearing voices: a role of interhemispheric auditory connectivity? World J Biol Psychiatry 13:153-8
Salisbury, Dean F; Taylor, Grantley (2012) Semantic priming increases left hemisphere theta power and intertrial phase synchrony. Psychophysiology 49:305-11
Salisbury, Dean F (2012) Finding the missing stimulus mismatch negativity (MMN): emitted MMN to violations of an auditory gestalt. Psychophysiology 49:544-8
Hall, Mei-Hua; Smoller, Jordan W; Cook, Nancy R et al. (2012) Patterns of deficits in brain function in bipolar disorder and schizophrenia: a cluster analytic study. Psychiatry Res 200:272-80
Asami, Takeshi; Bouix, Sylvain; Whitford, Thomas J et al. (2012) Longitudinal loss of gray matter volume in patients with first-episode schizophrenia: DARTEL automated analysis and ROI validation. Neuroimage 59:986-96
Salisbury, Dean F (2010) Abnormal N400 Responses But Intact Differential Hemispheric Processing of Ambiguity in Schizophrenia. J Neurolinguistics 23:240
Salisbury, Dean (2010) N400 to lexical ambiguity and semantic incongruity in schizophrenia. Int J Psychophysiol 75:127-32

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