title: Abnormal neural integration related to cognition in schizophrenia.
abstract: A striking feature of schizophrenia is the diversity of the phenomenology both within and between patients. This diversity can be contrasted with the well-circumscribed and stable deficits seen in classic neuropsychological syndromes. The argument will be advanced that the classic lesion model, based on the notion of a segregated deficit, is inappropriate in schizophrenia. Instead the idea will be developed that a more appropriate model is one derived from concepts of neural integration across large-scale brain networks. Empirical data derived from positron emission tomography (PET) within our laboratory that provide support for this suggestion will be presented. One critical observation from these data is a disruption of prefrontal-temporal interactions, under a variety of cognitive activation paradigms, in both chronic medicated and acute unmedicated schizophrenic patients. Furthermore, these data indicate that both regional and interregional neuronal function, including prefrontal-temporal interactions, can be significantly modulated by a neurochemical perturbation of ascending dopaminergic systems. The latter observations suggest that the deficit of abnormal cortico-cortical interactions are to some extent modifiable by neuromodulatory neurotransmitter systems.
authors.affiliation: Wellcome Department of Cognitive Neurology, Institute of Neurology, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Dolan
authors.forename: P C
authors.initials: PC
authors.lastname: Fletcher
authors.forename: P
authors.initials: P
authors.lastname: McKenna
authors.forename: K J
authors.initials: KJ
authors.lastname: Friston
authors.forename: C D
authors.initials: CD
authors.lastname: Frith
mesh_terms: D000208:Acute Disease; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000503:physiopathology*; D002908:Chronic Disease; D003072:Cognition Disorders / Q000503:physiopathology*; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D012559:Schizophrenia / Q000145:classification / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents; D004298:Dopamine