Brett A Clementz
University Of Georgia (uga)
Project start date: 2011-02-08
Project end date: 2016-01-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Brett A Clementz
PHYCHOPHYSIOLOGY AND LIABILITY FOR SCHIZOPHRENIA
Brett A Clementz, Professor
University Of California San Diego 9500 Gilman Dr, Dept 0934 La Jolla, Ca 920930934
Grant 5R03MH049906-02 from National Institute Of Mental Health IRG: EPI
Abstract: Schizophrenia is a genetic disorder, but being psychiatrically normal is consistent with being a gene carrier for this illness. This suggests that the clinical diagnosis of affection alone may be an inefficient means of defining the phenotype for subtle genetic analyses. The main purpose of this project is to evaluate the efficacy of variables other than interview and questionnaire which might more adequately identify "clinically nonpenetrant" gene carriers. Perhaps the three most promising measures for such an enterprise are ocular motor functioning, deficient sensory gating of the first positive-going wave in an auditory evoked potential paradigm (P50), and challenging tasks of sustained attention (CPT d ). These measures will be obtained from probands with schizophrenia and their first-degree biological relatives. It will first be determined whether these variables are related to syndromal and subsyndromal manifestations of schizophrenia among the relatives (specifically, if they are related to social-interpersonal schizophrenia-related characteristics). Second, we will determine what mode of genetic transmission is most likely for these variables within the families of schizophrenic probands. Third, we will determine whether these variables seem to be segregating in different families or whether they seem to be pleiotropic manifestations of the same predisposing factor. If these variables demonstrate interesting patterns of results in such analyses, then they may be more useful for linkage and segregation analyses than the clinical diagnosis of schizophrenia (and spectrum disorders). Research projects such as this may be necessary if the genetic factors predisposing to this clinical phenotype are to be understood.
Keywords: disease proneness /risk, family genetics, psychophysiology, schizophrenia, attention, auditory stimulus, evoked potential, eye movement, genetic mapping, mental disorder diagnosis, mental health epidemiology, human subject
Project start date: 1992-09-01
Project end date: 1995-08-31
5R03MH049906-02 (1993): $69407
OCULAR MOTOR AND NEUROANATOMIC STUDIES OF SCHIZOPHRENIA
Brett A Clementz, Professor
Psychologyuniversity Of California San Diego
9500 Gilman Dr, Dept 0934
la Jolla, Ca 920930934
Grant 5R01MH051129-09 from National Institute Of Mental Health IRG: CPP
Abstract: Ocular motor performance provides a powerful behavioral means for studying what is specifically different about the functioning of schizophrenia subjects´ brains, and for evaluating functional deviations that are correlated with predisposition for developing this illness. Identifying and refining schizophrenia-specific ocular motor abnormalities will serve at least two important functions. First, the ocular motor system is well understood both functionally and neuroanatomically. Dysfunction in particular parts of its neural control system result in characteristic patterns of ocular motor response. By presenting subjects with the appropriate set of tasks and monitoring their performance, hypotheses about the location of neuropathology can be tested. Ocular motor measurement, therefore, can aid the investigation of schizophrenia´s neuropathology. Second, schizophrenia patients´ clinically normal biological relatives seem to have the same pattern of ocular motor abnormalities as the patients themselves. These findings suggest that some aspect of ocular motor system dysfunction is assessing a component of brain functioning closely associated with a neurobiological predisposition for this illness. Further research on this phenomenon, therefore, could lead to the development of highly sensitive indicators of clinically unaffected gene carriers. A research programme appropriate for these undertakings requires collecting data on ocular motor performance across a range of tasks, a strategy we have used with considerable success. It is remarkable to think that studies of schizophrenia subjects´ behavioral performance can provide consistent and theoretically meaningful neurologically localizing information. This is exactly the conclusion that could be drawn with data from some additional clarifying studies. Research conducted with this grant will allow us to (1) rule out the possibility that schizophrenia subjects have a primary dysfunction of their smooth pursuit systems, (2) provide data inconsistent with the thesis that schizophrenia subjects have dysfunction of either posterior parietal cortex ocular motor-related regions or frontal eye fields, and (3) corroborate the hypothesis that the ocular motor abnormalities observed among schizophrenia subjects are a consequence of dysfunction in dorsolateral prefrontal cortex and/or its related subcortical circuitry. These data will be critically important for the success and efficiency of future functional neuroimaging and genetic linkage studies, because research with these important, but expensive, technologies will be suboptimal if they are based on the wrong behavioral measures. In this regard, it will be especially important to refine stimulus conditions to the point where measurement error is reduced as much as is practically feasible, a goal toward which we will aspire with our proposed research
Keywords: eye movement disorder, family genetics, neuroanatomy, neuropathology, schizophrenia behavioral genetics, bipolar depression, mental disorder diagnosis, motion perception, parietal lobe /cortex, prefrontal lobe /cortex, saccade, smooth pursuit eye movement, visual field, visual fixation, visual stimulus clinical research, human middle age (35-64), human subject, vision test, young adult human (21-34)
Project start date: 1993-09-01
Project end date: 2002-08-15
5R01MH051129-09 (2002): $120223
5R01MH051129-08 (2001): $153686
5R01MH051129-07 (2000): $119169
5R01MH051129-11 (2003): $159994
5R29MH051129-05 (1997): $95083
5R29MH051129-03 (1995): $89466
5R29MH051129-02 (1994): $78402
1R29MH051129-01 (1993): $59571
MEG Studies Of P50 Suppression In Schizophrenia
Brett A Clementz, Professor
University Of Georgia (uga) Office Of Sponsored Programs Athens, Ga 306027411
Grant 5R01MH057886-06 from National Institute Of Mental Health IRG: NPAS
Abstract: During auditory paired-stimulus paradigms, schizophrenia subjects have smaller differences between S1 and S2 amplitudes than normal. A series of reports indicate this effect results from smaller S1 amplitudes, not larger S2 amplitudes, among patients. These findings are consistent with reports from other studies of auditory information processing in schizophrenia, perhaps revealing a pattern that contains important clues about the neuropathological correlates of this illness. The proposed research will evaluate this possibility by studying the cognitive and sensory correlates of auditory evoked responses (AERs) using 143-channel MEG and dense array EEG. We will use steady-state stimulation and auditory oddball and paradigms to help clarify (1) The limits on cortical neuronal response rates and the associated ability to integrate information over time during auditory processing in schizophrenia, (2) whether group processing of simple auditory stimuli can be normalized among schizophrenia patients by entrainment of neuronal activity at a manageable rate (which will have implications for understanding the relationship between background brain states and auditory processing in schizophrenia), and (3) whether auditory processing abnormalities in schizophrenia is primarily associated with left hemisphere dysfunction and is a predictor of presence of auditory hallucinations, and (4) whether interhemispheric communication secondary to dysfunction of left auditory cortex is a cause of auditory recognition abnormalities among schizophrenia patients. Analyses will rely on current distributed source reconstructions, measures of spectral coherence in source and sensor space, measures of spectral power, and dipole modeling using realistic head models. It is hypothesized that schizophrenia patients have a limited ability to integrate information over time secondary to a low ceiling on neuronal response rates and that this effect is primarily due to left auditory cortex dysfunction. Indeed, right auditory cortex will be found to function normally among schizophrenia patients. Because of a low sampling rate on schizophrenia patients auditory information processing systems, they have difficulty recovering the initial stimulus information, an abnormality that could facilitate the development of hallucinatory phenomena. In addition, dysfunction of left auditory cortex impedes proper inter-hemispheric communication, which interferes with the ability to generate normal recognition-type responses measured during oddball-type paradigms.
Keywords: auditory cortex, auditory discrimination, brain electrical activity, brain imaging /visualization /scanning, neural information processing, neuropathology, psychopathology, schizophrenia, sound perception, computer simulation, dipole moment, evoked potential, hallucination, interhemispheric transfer, mental disorder diagnosis, behavioral /social science research tag, bioimaging /biomedical imaging, clinical research, electroencephalography, human subject, magnetic resonance imaging, magnetoencephalography, questionnaire
Project start date: 2000-03-15
Project end date: 2009-01-31
5R01MH057886-06 (2007): $237273
Sponsored Links Excellgen http://Excellgen.com
5R01MH057886-05 (2006): $244359
2R01MH057886-04A2 (2005): $250240
NEURAL MECHANISMS FOR ANTISACCADE ERRORS AMONG SCHIZOPHRENIA FAMILIES
Brett A Clementz, Prof Psych0l And Neurosci
University Of Georgia (uga), Office Of Sponsored Programs, Athens, Ga 30602-7411
Grant 5R01MH085485-02 from National Institute Of Mental Health
Abstract: Diagnostic systems in psychiatry have limitations resulting in classifications that are heterogeneous, lack clear boundaries, and inadequately match biological constructs. Clinical phenotypes such as schizophrenia (SZ)-spectrum diagnoses, when applied in genetic analyses, result in inconsistent findings, despite some interesting leads. Endophenotypes are specific deficits in brain anatomy and/or function interposed between overt clinical disease and aberrant genes. Such measures provide more direct clues to genetic underpinnings than do clinical syndromes because they are closer in the etiological chain to the primary constitutional deviations resulting in disease. The current application responds to the need for endophenotypes in two important ways. First, we will identify in SZ the critical deviation at the level of brain function accounting for their antisaccade abnormalities, a promising and replicated behavioral endophenotype for this illness. Second, we will determine whether biological relatives of SZ (SZREL) manifest the same deviations in brain functioning as the SZ. This project will address a major question about SZ with implications for models of pathophysiology, clinical diagnostic nosology, and genetics. A common anomaly in brain function in SZ is disruption of prefrontal cortex (PFC). An inability to inhibit behavioral responses is an important manifestation of PFC pathology, an abnormality that can be quantified by the inability to inhibit reflexive glances to peripheral targets during antisaccade tasks. SZ and SZREL have high antisaccade error rates suggesting that anti-performance indexes a constitutional abnormality of liability for this illness. Demonstrating a relationship between SZ and anti-performance is an important step toward understanding the essential neuropathology and genetics of this illness. Clarifying how SZ-related neuropathology causes increased anti-errors requires studying the neural correlates of sub- processes necessary to enact this behavior. The present project will address this specific issue, and the results will yield a precise measure of failed neural control accounting for poor anti-performance among SZ and SZREL. Animal research indicates that neural bias signals are crucial for enabling successful inhibition on an anti-trial. Whether reduced or atypical preparatory activities in sensory or motor areas account for SZ and SZREL behavioral regulation difficulties during anti-tasks is uncertain. The proposed work, therefore, will address a fundamentally important question in the clinical neuroscience of SZ. This research requires the use of a novel paradigm, the use of high temporal resolution brain measurement technology (multichannel EEG), access to large SZ and SZREL samples, and collaboration between investigators with complimentary knowledge of this research area. The present project meets these requirements. PUBLIC HEALTH RELEVANCE People with schizophrenia have problems with inhibition which can be predicted by changes in brain activity. The patterns of activity in healthy subjects involve a distinct balance between increased activity in regions that help prepare a correct response and decreased activity in regions supporting competing processes, a pattern will be probed using measurement of brain activity via EEG and a novel antisaccade paradigm. It is expected this pattern will be disrupted in people with schizophrenia and their relatives
Keywords: Accounting; Address; Anatomic; Anatomical Sciences; Anatomy; Animal Experimental Use; Animal Experimentation; Animal Research; Anterior Quadrigeminal Body; Appearance; Area; Attention; Behavior; Behavioral; Biological; Brain; Candidate Disease Gene; Candidate Gene; Causality; Cell Communication and Signaling; Cell Signaling; Cells; Chicago; Classification; Clinical; Cognition; Collaborations; Constitutional; Corpora quadrigemina, superior colliculus; Development; Diagnosis; Diagnostic; Dimensions; Disease; Disorder; Down-Regulation; Down-Regulation (Physiology); Downregulation; Dysfunction; EEG; Electroencephalography; Encephalon; Encephalons; Equilibrium; Etiology; Evoked Potentials, Visual; Family; Fixation; Functional disorder; Funding; Generations; Genes; Genetic; Genetic Risk; Genetic analyses; Goals; Heritability; Heterogeneity; History; Human Genome Project; Illinois; Intracellular Communication and Signaling; Investigators; Knowledge; Learning; Linkage Analysis; Location; Measurement; Measures; Method LOINC Axis 6; Methodology; Methods; Modeling; Motor; Motor Cell; Motor Neurons; Nervous; Nervous System, Brain; Neurobiology; Neurosciences; Optic Tectum; Parietal Lobe; Parietal Lobe of the Brain; Pathology; Patients; Pattern; Performance; Peripheral; Persons; Phenotype; Physiopathology; Predisposition gene; Prefrontal Cortex; Probability; Process; Psychiatry; Pursuit, Saccadic; Recording of previous events; Recruitment Activity; Regulation; Relative; Relative (related person); Research; Research Personnel; Research Resources; Researchers; Resolution; Resources; SUBGP; Saccades; Saccadic Eye Movements; Sampling; Schizophrenia; Schizophrenic Disorders; Science of Anatomy; Science of neurophysiology; Sensory; Sensory Process; Signal Transduction; Signal Transduction Systems; Signaling; Site; Source; Speed; Speed (motion); Stimulus; Subgroup; Superior Colliculus; Susceptibility Gene; Symptoms; Syndrome; System; System, LOINC Axis 4; Systematics; Task Performances; Technology; Tectums, Optic; Universities; Visual; Visual Cortex; Visual Evoked Response; Visual evoked cortical potential; Work; anatomy; austin; balance; balance function; base; biological signal transduction; clinical phenotype; cost; dementia praecox; disease causation; disease classification; disease etiology; disease/disorder; disease/disorder classification; disease/disorder etiology; disorder classification; disorder etiology; effective therapy; endophenotype; family based linkage study; frontal cortex; frontal eye fields; frontal lobe; genetic analysis; genetic linkage analyses; genetic linkage analysis; indexing; interest; linkage analyses; meetings; motoneuron; multimodality; neural; neural control; neural mechanism; neural regulation; neurobiological; neuroimaging; neuromechanism; neuropathology; neurophysiology; neuroregulation; new approaches; non-human primate; nonhuman primate; nosology; novel; novel approaches; novel strategies; novel strategy; parietal cortex; pathophysiology; predisposing gene; prevent; preventing; public health relevance; recruit; relating to nervous system; response; sample fixation; schizophrenic; sensory system; superior colliculus Corpora quadrigemina; trial comparing; visual cortical; visual motor; visual process; visual processing; visual tectum; visuomotor
Relevance: People with schizophrenia have problems with inhibition which can be predicted by changes in brain activity. The patterns of activity in healthy subjects involve a distinct balance between increased activity in regions that help prepare a correct response and decreased activity in regions supporting competing processes, a pattern will be probed using measurement of brain activity via EEG and a novel antisaccade paradigm. It is expected this pattern will be disrupted in people with schizophrenia and their relatives
Project start date: 2009-08-13
Project end date: 2014-04-30
Budget start date: 10-MAY-2010
Budget end date: 30-APR-2011
PFA/PA: PA-07-070
5R01MH085485-02 (2010): $290627
1R01MH085485-01A1 (2009): $306884
Brett A Clementz
University Of Georgia (uga)
Project start date: 2009-08-13
Project end date: 2014-02-28
MEG STUDIES OF P50 SUPPRESSION IN SCHIZOPHRENIA
Brett A Clementz, Professor
Psychologyuniversity Of California San Diego
9500 Gilman Dr, Dept 0934
la Jolla, Ca 920930934
Grant 5R01MH057886-02 from National Institute Of Mental Health IRG: ZRG1
Project start date: 2000-03-15
Project end date: 2002-08-14
5R01MH057886-02 (2001): $165627
1R01MH057886-01A2 (2000): $212750
OCULAR MOTOR AND NEUROANATOMIC STUDIES OF SCHIZOPHRENIA
Brett A Clementz, Professor
University Of California San Diego 9500 Gilman Dr, Dept 0934 La Jolla, Ca 920930934
Grant 5R29MH051129-04 from National Institute Of Mental Health IRG: BPP
Project start date: 1993-09-01
Project end date: 1998-05-31
5R29MH051129-04 (1996): $88968