Department of
Psychological and Brain Sciences

• Clinical Science
• Neural Science

• Grant Support (2005 to present)Cognitive and neurobiological disturbances in schizophrenia and bipolar disorder
• Role of neural synchrony and oscillations in normal and perturbed brain function
• Rodent models of human behavioral disorders
• Behavioral and pharmacological treatment of behavioral disorders
• Cognitive electrophysiology

1. Neural synchrony and oscillations in schizophrenia spectrum disorders. Neural synchrony and oscillations may be required for efficient signaling within the nervous system. Persons with schizophrenia show poorer synchrony and altered oscillatory activity to auditory and visual stimulation, which may particularly affect cognitive processes requiring timing and integration. Electrophysiological measures of these phenomena are being studied in schizophrenia, Schizotypal Personality Disorder, relatives of persons with schizophrenia, and healthy individuals. This human data will test whether these deficits in synchronization meet key criteria for an endophenotype in the disorder, or are state indicators for clinical psychosis.
2. Rodent models of electrophysiological disturbance in schizophrenias. In the ketamine rodent model, we will test the sensitivity of these measures to acute and chronic administration of ketamine, a potent NMDA antagonist, and determine whether these are reversed by treatment with an atypical antipsychotic medication, olanzapine, or a glycine site agonist. The animal studies will therefore yield in-vivo evidence of the sensitivity of time-frequency measures to a well-validated rodent model of schizophrenia, and whether these deficits are ameliorated by anti-psychotic medications.
3. Human Connectivity Analysis: Application to Clinical Populationss. A fundamental goal in human neuroscience is to generate a three dimensional map which represents the organization of gray and white matter connectivity in the brain. This project will employ MRI tractography to map the connection architecture of the brain in healthy adults and individuals with disorders which appear to affect connectivity (schizophrenia and autism). New graph analytic computational methods developed by Olaf Sporns will be used to mathematically analyze network structure.
4. Cognitive remediation as a treatment for schizophrenias. Impairment of cognitive function is a key feature of schizophrenia which predates onset of psychotic symptoms, and persists after pharmacological treatment. Cognitive impairment contributes to the broad psychosocial disabilities observed in schizophrenia and has often been characterized as an illness trait that is refractory to pharmacological treatment. The purpose of this collaborative study is to test the effects of cognitive remediation (CR) on clinical, neurocognitive and psychosocial outcomes in schizophrenia. Primary outcome measures include tests of cognitive function and event-related potential (ERP) measures of brain function.

2005-2010 Principal Investigator, "Visual processing in schizophrenia and SPD," NIMH 2 RO1 MH62150-04A1.

2005 -2007 Investigator, "Sensory processing deficits in cannabis use." NIDA 1 R03 DA019630-0, (PI: Patrick D. Skosnik)

2005-2007 Mentor, "Visual System Neural Synchronization in Schizotypy and Cannabis Use," National Alliance for Research on Schizophrenia and Depression Young Investigator Award (PI: Patrick Skosnik)

2006-2011 Investigator, "Cerebellar timing dysfunction in schizophrenia," NIMH R01 MH074983-01, (PI: William P. Hetrick)

2007-2009 Mentor, NARSAD Young Investigator Award, "An Association Study with Psychophysiological Endophenotypes in Schizophrenia" (PI: Colleen Brenner)

2007-2009 Investigator, "The Effect of Cannabis use on Human Cerebellar Function," NIDA R21 DA 023097-01 (PI: Patrick D. Skosnik)

2008-2013 Core Faculty, "Integrative Predoctoral Training in Drug Abuse," 1 T32 DA024628-01 (PI: George Rebec). This project supports integrative predoctoral training in the neuroscience of drug abuse at Indiana University.

2009-2010 Principal Investigator, "Cognitive Remediation of Neurobehavioral Abnormalities in Schizophrenia," Collaboration in Biomedical/Translational Research Pilot Program, NIH CTSA UL1RR025761-01 (Shekhar, Center PI).

2010-2011 Principal Investigator, "Human Brain Connectivity Analysis: Application to Clinical Populations," Faculty Research Support Program, Office of the Vice Provost for Research, Indiana University.

2010-2012 Principal Investigator (Morzorati, Co-PI), "Neural Oscillations in Schizophrenia and a Rat Model," 1 R21 MH091774-01

2007 Giri Krishnan Indiana University College of Arts and Sciences Dissertation year Fellowship

2008 Jenifer Vohs Clinical Translational Sciences Institute Predoctoral Fellowship

2010 Woo Young Ahn Indiana University College of Arts and Science's Dissertation Fellowship

2010 Olga Rass NIDA 1 T32 DA024628-01 Predoctoral Fellowship (Rebec, Director)

O'Donnell, B.F., Bismark, A., Hetrick, W.P., Bodkins M., Vohs, J.L., Shekhar, A. (2006). Early stage vision in schizophrenia and schizotypal personality disorder. Schizophrenia Research, 86:89-98.

Skosnik PD, Krishnan GP, O'Donnell BF. (2007). The Effect of Selective Attention on the Gamma-Band Auditory Steady-State Response. Neuroscience Letters, 420, 223-228.

Vohs JL, Hetrick WP, Kieffaber PD, Bodkins M, Bismark A, Shekhar A. , O'Donnell B.F. (2008). Visual Event-Related Potentials in Schizotypal Personality Disorder and Schizophrenia. Journal of Abnormal Psychology, 117, 119-131.

Vohs JL, R. Chambers AR, Krishnan GP, O'Donnell BF, Hetrick WP, Kaiser ST, Berg S, Morzorati SL. (2009). Auditory Sensory Gating in the Neonatal Ventral Hippocampal Lesion Model of Schizophrenia. Neuropsychobiology, 60, 12-22.

Krishnan GP, Hetrick WP, Brenner CA, Shekhar A, Steffen AN, O'Donnell BF. (2009). Steady state and induced auditory gamma deficits in schizophrenia. Neuroimage, 47, 1711-1719.

Brenner CA, Kieffaber PD, Clementz BA, Johannesen JK, Shekhar A, O'Donnell BF, Herick WP. Event-related Potential Abnormalities in Schizophrenia: A Failure to "Gate In" Salient Information? Schizophrenia Research 2009;113:332-338.

Vohs JL, Chambers AR, Krishnan GP, O'Donnell BF, Berg S, Morzorati SL. (2009). GABAergic modulation of the 40 Hz auditory steady state response in a rat model of schizophrenia. International Journal of Neuropsychopharmacology, 23, 1-11.

Fridberg, D. J., Hetrick, W.P., Brenner, C.A., Shekhar, A., Steffen, A.N., Malloy, F. W., & O'Donnell, B. F. (2009). Relationships between auditory event-related potentials and mood state, medication, and comorbid psychiatric illness in patients with bipolar disorder. Bipolar Disorder, 35, 857-866.

Brenner CA, Krishnan GP, Vohs JL, Ahn WY, Hetrick WP, Morzorati SL, O'Donnell BF. (2009). Steady State Responses: Electrophysiological Assessment of Sensory Function in Schizophrenia. Schizophrenia Bulletin, 35, 1065-1077.

Krishnan G.P., Vohs J.L., Carroll C.A., Hetrick W.P., Shekhar A., Bockbrader M.A., O'Donnell B.F. (2005). Steady state visual evoked potential abnormalities in schizophrenia. Clinical Neurophysiology, 116, 614-624.

Krishnan GP, Skosnik PD, Vohs JL, Busey TA, O'Donnell BF. (2005). Relationship between steady state and induced gamma activity to motion. Neuroreport, 16, 625-630.