A translational research program will investigate the integrity of cerebellar-mediated timing functions in schizophrenia and identify mechanisms that may modulate synaptic properties of cerebellar timing networks. Mounting theoretical and empirical evidence indicates that schizophrenia is associated with a fundamental disturbance in the timing of neural processes and behavior. This deficit in the temporal coordination of information processing, sometimes referred to as cognitive dysmetria, may lead to poor temporal coordination of perceptual, cognitive, affective, and motor processes. Abnormalities in a cortico-cerebellar-thalamic-cortical (CCTC) brain circuit, which is responsible for fluid, temporal coordination of sequences of behavior, are a likely source of the timing anomalies in schizophrenia. The proposed research will examine the functional integrity of the cerebellar mode of this circuit. Parallel and complementary human and non-human studies will be conducted primarily using cerebellar-dependent eye-blink conditioning tasks. The overarching aims are to: (1) comprehensively characterize the nature of the eyeblink conditioning (EEC) acquisition and timing abnormalities in schizophrenia and use a rabbit model to identify cerebellar mechanisms that may be responsible for the observed deficits; (2) examine the contribution of primary sensory processes associated with stimulus modality and intensity to the observed EBC acquisition and timing abnormalities in schizophrenia and a rabbit model; (3) systematically explore the effect of stable, antipsychotic medication treatment on EBC and other cerebellar-dependent measures of timing; and (4) determine the clinical, behavioral, and structural neuroanatomical correlates of EBC deficits in schizophrenia. Taken together, the studies will determine the functional integrity of the cerebellar node of the cortico-cerebellar-thalamic-cortical circuit in schizophrenia and test models of impaired cerebellar functioning that may give rise to timing deficits in the disorder. This research will result in knowledge about neural mechanisms associated with an extraordinarily debilitating psychological disorder, schizophrenia. A better understanding of these mechanisms will advance knowledge about the pathophysiology of schizophrenia, and may lead to the identification of neurobiological targets of treatment. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH074983-01A1
Application #
7094419
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Meinecke, Douglas L
Project Start
2006-05-05
Project End
2011-04-30
Budget Start
2006-05-05
Budget End
2007-04-30
Support Year
1
Fiscal Year
2006
Total Cost
$338,043
Indirect Cost
Name
Indiana University Bloomington
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Lundin, Nancy B; Bartolomeo, Lisa A; O'Donnell, Brian F et al. (2017) Reduced electroencephalogram responses to standard and target auditory stimuli in bipolar disorder and the impact of psychotic features: Analysis of event-related potentials, spectral power, and inter-trial coherence. Bipolar Disord :
Seitzman, Benjamin A; Abell, Malene; Bartley, Samuel C et al. (2017) Cognitive manipulation of brain electric microstates. Neuroimage 146:533-543
Bolbecker, Amanda R; Petersen, Isaac T; Kent, Jerillyn S et al. (2016) New Insights into the Nature of Cerebellar-Dependent Eyeblink Conditioning Deficits in Schizophrenia: A Hierarchical Linear Modeling Approach. Front Psychiatry 7:4
Kim, Dae-Jin; Davis, Elysia Poggi; Sandman, Curt A et al. (2016) Children's intellectual ability is associated with structural network integrity. Neuroimage 124:550-556
Kent, Jerillyn S; Bolbecker, Amanda R; O'Donnell, Brian F et al. (2015) Eyeblink Conditioning in Schizophrenia: A Critical Review. Front Psychiatry 6:146
Cheng, Hu; Newman, Sharlene D; Kent, Jerillyn S et al. (2015) White matter abnormalities of microstructure and physiological noise in schizophrenia. Brain Imaging Behav 9:868-77
Cheng, Hu; Newman, Sharlene; Goñi, Joaquín et al. (2015) Nodal centrality of functional network in the differentiation of schizophrenia. Schizophr Res 168:345-52
Kim, Dae-Jin; Kent, Jerillyn S; Bolbecker, Amanda R et al. (2014) Disrupted modular architecture of cerebellum in schizophrenia: a graph theoretic analysis. Schizophr Bull 40:1216-26
Kim, Dae-Jin; Davis, Elysia Poggi; Sandman, Curt A et al. (2014) Longer gestation is associated with more efficient brain networks in preadolescent children. Neuroimage 100:619-27
Dominelli, Rachelle M; Boggs, Jennifer M; Bolbecker, Amanda R et al. (2014) Affect modulated startle in schizophrenia: subjective experience matters. Psychiatry Res 220:44-50

Showing the most recent 10 out of 43 publications