Language dysfunction in schizophrenia is believed to be an important component of schizophrenic psychopathology and a contributing factor to formal thought disorder. The features commonly observed in schizophrenic language include poverty of speech, derailment, loose associations, loss of goal, perseveration, tangentiality, and distractibility. In this application, we will focus on semantic aspects of language dysfunction in schizophrenia, more specifically the processes and structure of semantic memory in schizophrenia. There are two major hypotheses in the field regarding abnormal processes in semantic memory in schizophrenia. One holds that schizophrenia patients suffer from overactivation within semantic networks whereby activation spreads faster and/or more broadly, thus reaching semantic associates that would not be activated in the normal individuals. The other view holds that it is the late, controlled processes rather than early processes of automatic activation, which are abnormal in schizophrenia. Both theories can account for peculiar characteristics of schizophrenic language. In fact, almost all of the evidence in support of one or the other view comes from priming studies using either behavioral, or event related potential (ERP) measures. However, there are no published studies that explore brain activation in a priming paradigm in schizophrenia that map functional abnormalities onto the brain areas in a direct way. A major goal of this application is to contrast word priming using short and long stimulus onset asynchronies (SOAs) in order to evaluate differences in brain activation as a function of SOA in both normal and schizophrenic individuals. An additional goal of this application is to test whether categorical and associative priming paradigms are associated with unique patterns of activation and thus can inform our understanding of memory structure in both normal and schizophrenic individuals. In the case of schizophrenia, the question is whether persons suffering from this disorder have a structure of semantic memory similar to non-afflicted individuals, or whether that structure is different, given the fact that schizophrenia is partially genetically mediated and with a major developmental component. It is thus possible that abnormal links might develop within semantic memory and these may, in turn, contribute, at least in part, to some aspects of abnormal language observed in schizophrenia. Accordingly, a further goal of this application will be to explore brain activation patterns associated with processing of word- pairs that are related by either category membership or associative strength in both normal and schizophrenic individuals. Again, there are no published fMRI studies of semantic memory structure in schizophrenia, and only one fMRI study in normal individuals. Schizophrenia sufferers often use disordered language which makes successful social interactions difficult. However, understanding of underlying causes of language disorder in schizophrenia is far from complete, with most evidence coming from behavioral or event related potential studies. Thus, in this application we propose to use fMRI to describe possible abnormalities in semantic memory structure in schizophrenia and identify which brain structures are involved in mediating these abnormalities. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
1R03MH078036-01A1
Application #
7251770
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
2007-08-21
Project End
2009-07-31
Budget Start
2007-08-21
Budget End
2008-07-31
Support Year
1
Fiscal Year
2007
Total Cost
$64,350
Indirect Cost
Name
Harvard University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Pinheiro, Ana P; Del Re, Elisabetta; Nestor, Paul G et al. (2015) Abnormal interactions between context, memory structure, and mood in schizophrenia: an ERP investigation. Psychophysiology 52:20-31
Pinheiro, Ana P; Rezaii, Neguine; Rauber, Andréia et al. (2014) Abnormalities in the processing of emotional prosody from single words in schizophrenia. Schizophr Res 152:235-41
Pinheiro, Ana P; del Re, Elisabetta; Nestor, Paul G et al. (2013) Interactions between mood and the structure of semantic memory: event-related potentials evidence. Soc Cogn Affect Neurosci 8:579-94
Pinheiro, Ana P; Liu, Taosheng; Nestor, Paul G et al. (2013) Visual emotional information processing in male schizophrenia patients: combining ERP, clinical and behavioral evidence. Neurosci Lett 550:75-80
Pinheiro, A P; Del Re, E; Mezin, J et al. (2013) Sensory-based and higher-order operations contribute to abnormal emotional prosody processing in schizophrenia: an electrophysiological investigation. Psychol Med 43:603-18
Liu, Taosheng; Pinheiro, Ana; Zhao, Zhongxin et al. (2012) Emotional cues during simultaneous face and voice processing: electrophysiological insights. PLoS One 7:e31001
Liu, Taosheng; Pinheiro, Ana P; Deng, Guanghui et al. (2012) Electrophysiological insights into processing nonverbal emotional vocalizations. Neuroreport 23:108-12
Ungar, Lida; Nestor, Paul G; Niznikiewicz, Margaret A et al. (2010) Color Stroop and negative priming in schizophrenia: an fMRI study. Psychiatry Res 181:24-9
Niznikiewicz, M; Mittal, M Singh; Nestor, P G et al. (2010) Abnormal inhibitory processes in semantic networks in schizophrenia. Int J Psychophysiol 75:133-40
Yoshida, Takeshi; McCarley, Robert W; Nakamura, Motoaki et al. (2009) A prospective longitudinal volumetric MRI study of superior temporal gyrus gray matter and amygdala-hippocampal complex in chronic schizophrenia. Schizophr Res 113:84-94

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