Schizophrenia affects ~1% of all people. It is characterized by delusions and hallucinations resulting in high morbidity and mortality. These symptoms may be underpinned by misperceptions and misinterpretations of sensations that result from a basic inability to predict sensations and adapt to deviations from the expected. If predictive coding mechanisms are dysfunctional, sensations that should have been predicted, but were not, may take on inappropriate salience and lead to the construction of delusional schema to explain aberrant experience. These errors of prediction are costly to society and the patient. Predictive coding models posit that higher order brain areas develop and maintain representations of predictable sensory stimuli, increasing efficiency of neural activity by reducing sensory cortical responses to these stimuli and increasing sensory responses to stimuli that violate the predicted pattern. In such models, the role of primary sensory cortices is to encode and transmit sensory "prediction errors," that is, to respond mainly to those stimuli that deviate from the brain's representations of expected stimuli. In context-based predictive coding, the brain acquires and remembers the context of regular temporal and spatial patterns of sensory input. In action-based predictive coding, the predictability of sensory events derives from the fact that sensory events are a predictable consequence of one's own actions, and do not need to be learned or remembered. Conceptually, action-based predictive coding models subsume efference-copy/corollary discharge forward model systems described across the animal kingdom in which an "efference copy" of an impending motor plan is transmitted from motor to sensory cortex where it generates a "corollary discharge" representation of the expected sensory consequences of the imminent motor act. Building on our prior work, we propose to ask how predictability and performance monitoring affect action-based predictive coding and how they affect sensory/perceptual processing in schizophrenia. We will use EEG and fMRI, acquired separately and simultaneously, to interrogate details of efference copy and corollary discharge components of action-based predictive coding. Using EEG, we can assess the split-second activity preceding a motor act, or the efference copy. Using fMRI, we can assess the spatial precision of the suppressive action of the corollary discharge mechanism. By integrating EEG and fMRI, we can understand the functional neuroanatomical basis of predictive coding and its abnormalities in schizophrenia. Finally, we are adopting a paradigm and using methods that are translatable to animal models of SZ and that can ultimately be used to identify specific elements of circuits involved in predictive coding, transmitters involved in te neural mechanisms responsible for predictive coding, and even genes that underlie psychotic experiences and behavior.

Public Health Relevance

Predictive coding abnormalities characterize schizophrenia. By using paradigms and methods to study predictive coding that are used in lab animals, we can identify specific elements of the circuit, transmitters involved in the neural mechanisms, and even genes that underlie psychotic experiences and behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH058262-13
Application #
8632792
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
1998-08-01
Project End
2018-11-30
Budget Start
2013-12-11
Budget End
2014-11-30
Support Year
13
Fiscal Year
2014
Total Cost
$638,750
Indirect Cost
$218,259
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Wang, Jun; Mathalon, Daniel H; Roach, Brian J et al. (2014) Action planning and predictive coding when speaking. Neuroimage 91:91-8
Ford, Judith M; Morris, Sarah E; Hoffman, Ralph E et al. (2014) Studying hallucinations within the NIMH RDoC framework. Schizophr Bull 40 Suppl 4:S295-304
Whitford, Thomas J; Ford, Judith M; Mathalon, Daniel H et al. (2012) Schizophrenia, myelination, and delayed corollary discharges: a hypothesis. Schizophr Bull 38:486-94
Mathews, Carol A; Perez, Veronica B; Delucchi, Kevin L et al. (2012) Error-related negativity in individuals with obsessive-compulsive symptoms: toward an understanding of hoarding behaviors. Biol Psychol 89:487-94
Perez, Veronica B; Ford, Judith M; Roach, Brian J et al. (2012) Error monitoring dysfunction across the illness course of schizophrenia. J Abnorm Psychol 121:372-87
Reinhart, Robert M G; Mathalon, Daniel H; Roach, Brian J et al. (2011) Relationships between pre-stimulus ýý power and subsequent P300 and reaction time breakdown in schizophrenia. Int J Psychophysiol 79:16-24
Whitford, T J; Mathalon, D H; Shenton, M E et al. (2011) Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia. Psychol Med 41:959-69
Ford, Judith M; Roach, Brian J; Faustman, William O et al. (2008) Out-of-synch and out-of-sorts: dysfunction of motor-sensory communication in schizophrenia. Biol Psychiatry 63:736-43