The overall objective of this research proposal is to determine the neurobiological basis of auditory hallucinations (AHs) of spoken speech. This syndrome produces high levels of distress and disability in patients with schizophrenia and other psychotic disorders. The research proposal is based on pilot studies using functional and structural MRI involving schizophrenic patients with AHs, nonhallucinating patients with schizophrenia, and normal control subjects. Functional MRI data suggest that coactivation of Broca's and Wernicke's area occurs during hallucination periods. A second fMRI study suggests that these two brain areas are excessively coupled in hallucinators compared to nonhallucinating patients and normal controls. Abnormal coupling between these two regions is hypothesized to arise from loss of intrinsic connectivity within Wernicke's region suggested by cortical thinning found in our pilot structural MRI study. Loss of intrinsic connectivity is predicted to increase salience of interactions between that region and Broca's area, which could produce hallucinated speech with percept-like characteristics. 40 patients with AHs, 20 patients without a recent history of AHs, and 20 normal control subjects will be studied.
Specific Aim #1 : Brain activation during hallucination periods will be shown to involve Broca's and Wernicke's regions in a neuroanatomic distribution that approximates but is distinct from activation associated with listening to external speech.
Specific Aim #2 : The neuroanatomic distribution of BOLD signal correlations referenced to Wernicke's region will be shown to converge with activation maps for hallucination periods.
Specific Aim #3 : Using BOLD signal correlations, Broca's area will be shown to be excessively coupled to Wernicke's area in patients with AHs when compared to nonhallucinating patients and normal controls.
Specific Aim #4 : Cortical thickness in superior temporal cortex will be shown to be decreased in hallucinators compared to the other two groups of subjects. In summary, the proposed research plan will establish new neuroimaging tools for delineating the neuroanatomic and physiological basis of AHs. These findings could advance our ability to develop more specific and efficacious treatments targeting this syndrome. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH067073-03
Application #
6902648
Study Section
Special Emphasis Panel (ZRG1-BBBP-5 (01))
Program Officer
Meinecke, Douglas L
Project Start
2003-07-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$328,230
Indirect Cost
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Powers, A R; Mathys, C; Corlett, P R (2017) Pavlovian conditioning-induced hallucinations result from overweighting of perceptual priors. Science 357:596-600
Fineberg, Sarah K; Stahl, Dylan; Corlett, Philip (2017) Computational Psychiatry in Borderline Personality Disorder. Curr Behav Neurosci Rep 4:31-40
Erickson, Molly A; Albrecht, Matthew; Ruffle, Abigail et al. (2017) No association between symptom severity and MMN impairment in schizophrenia: A meta-analytic approach. Schizophr Res Cogn 9:13-17
van Schalkwyk, Gerrit I; Volkmar, Fred R; Corlett, Philip R (2017) A Predictive Coding Account of Psychotic Symptoms in Autism Spectrum Disorder. J Autism Dev Disord 47:1323-1340
Corlett, Philip R; Honey, Garry D; Fletcher, Paul C (2016) Prediction error, ketamine and psychosis: An updated model. J Psychopharmacol 30:1145-1155
Powers III, Albert R; Kelley, Megan; Corlett, Philip R (2016) Hallucinations as top-down effects on perception. Biol Psychiatry Cogn Neurosci Neuroimaging 1:393-400
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
Hoffman, Ralph E; Wu, Kun; Pittman, Brian et al. (2013) Transcranial magnetic stimulation of Wernicke's and Right homologous sites to curtail ""voices"": a randomized trial. Biol Psychiatry 73:1008-14
Allen, Paul; Modinos, Gemma; Hubl, Daniela et al. (2012) Neuroimaging auditory hallucinations in schizophrenia: from neuroanatomy to neurochemistry and beyond. Schizophr Bull 38:695-703
Hoffman, Ralph E; Hampson, Michelle (2011) Functional connectivity studies of patients with auditory verbal hallucinations. Front Hum Neurosci 6:6

Showing the most recent 10 out of 22 publications