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Schizophrenia is a devastating disease affecting one out of every one hundred people worldwide. It is characterized by symptoms that include disorganized thought, symptoms of psychosis such as delusions and hallucinations, and poverty of action. The underlying cause of this disorder is unknown and existing treatments have varying degrees of efficacy. Patients often have persistent symptoms despite medication, and frequently cannot function in day-to-day activities. The course of this disease is generally a downhill one, beginning in late adolescence/early adulthood with periodic exacerbations, usually requiring hospitalization. Various theories of the underlying etiology of schizophrenia have been proposed and include genetic defects, neurodevelopmental cytoarchitectonic abnormalities, and exposure to infectious agents in utero; however, none of these can fully explain the characteristics of this disorder. It is likely that neurochemical abnormalities are present because the administration of neuroleptic medication, which blocks dopamine (a brain neurotransmitter), often has some beneficial effect (although it can have debilitating side effects). Nevertheless, the brain abnormalities underlying schizophrenia are not well understood. Functional brain imaging techniques are uniquely suited to the task of helping to identify such abnormalities.

The FNL uses a symptom-oriented approach to study schizophrenia, and has focused upon identifying neural circuitry abnormalities underlying the positive symptoms of hallucinations and delusions, specifically paranoia.  In addition to using complementary neuropsychological paradigms to probe top-down and bottom-up mechanisms that may underlie symptom formation, in-depth examination of the role of language processing, and its interaction with emotional symptoms, is being examined.  Finally, in collaboration with Dr. Yulia Landa at Weill Cornell Medical Center, the FNL is also exploring mechanisms and predictors of treatment response to a novel cognitive behavioral treatment approach specifically developed by Dr. Landa to address the symptom of paranoia.

Perez DL, Pan H, Weisholtz DS, Root JC, Tuescher O, Fischer DB, Butler T, Vago DR, Isenberg N, Epstein J, Landa Y, Smith TE, Savitz AJ, Silbersweig DA, Stern E. Altered threat and safety neural processing linked to persecutory delusions in schizophrenia: a two-task fMRI study. Psychiatry Research: Neuroimaging 233(3): 352-366. doi: 10.1016/j.pscychresns.2015.06.002. Epub 2015 Jun 23. PMID: 26208746.

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Gu H, Engelien W, Feng H, Silbersweig DA, Stern E, Yang Y. Mapping transient, randomly occurring neuropsychological events using independent component analysis. Neuroimage, 14: 1432-1443, 2001

Yang Y, Engelien A, Engelien W, Xu S, Stern E, Silbersweig DA. A Silent Event-Related Functional MRI Technique for Brain Activation Studies without Interference of Scanner Acoustic Noise. Magnetic Resonance in Medicine, 43:185-90,2000.

Epstein J, Stern E, Silbersweig DA, Mesolimbic activity associated with psychosis in schizophrenia: symptom-specific PET studies, in Advancing from the ventral striatum to the extended amygdala: implications for neuropsychiatry and drug abuse, McGinty JF, ed. New York, Annals of the New York Academy of Sciences, 877:562-74,1999.

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Silbersweig DA and Stern E. Functional neuroimaging of hallucinations in schizophrenia: toward an integration of bottom-up and top-down approaches. Molecular Psychiatry, 1: 367-375, 1996.

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Silbersweig DA, Stern E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua SE, Schnorr L, Jones T, Frackowiak RSJ. A functional neuroanatomy of hallucinations in schizophrenia. Nature, 378: 176-179, 1995.

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