BACKGROUND: Dysfunction of the dorsolateral prefrontal cortex (DLPFC) and parahippocampal region along with poor working memory are common neurophysiological and behavioral features associated with schizophrenia and normal aging. It is, however, unknown whether the associated patterns of neural activation differ between these two groups when their cognitive performance is closely matched in a pairwise manner. The authors sought to pinpoint common and differential pathophysiological features that accompany comparable working memory impairments in schizophrenia and healthy aging. METHODS: Fifty-three subjects were scanned with oxygen-15 water positron emission tomography regional cerebral blood flow measurements during working memory. Seventeen medication-free patients with schizophrenia were individually matched for working memory performance with 17 healthy aging subjects. Brain activation of the two index groups were compared with each other and with 19 young healthy individuals. RESULTS: Patients with schizophrenia showed right DLPFC hypoactivation, both when compared with age-matched control subjects and after direct comparison with working memory performance-matched elderly subjects. Moreover, both groups with working memory deficits shared an inability to suppress parahippocampal and anterior medial prefrontal cortex activation. CONCLUSIONS: These results provide new insights into the mechanisms by which impaired working memory performance can arise by showing that both common (parahippocampal/anterior medial PFC) and differential (DLPFC) pathophysiological features accompany similar cognitive impairments. The aging data also demonstrate that poor performance is not necessarily accompanied by the DLPFC hypofunction that was seen in schizophrenia. Finally, these results more closely link the DLPFC functional abnormalities in schizophrenia to the pathophysiology of the disorder rather than to poor performance per se.
BACKGROUND: Dysfunction of the dorsolateral prefrontal cortex (DLPFC) and parahippocampal region along with poor working memory are common neurophysiological and behavioral features associated with schizophrenia and normal aging. It is, however, unknown whether the associated patterns of neural activation differ between these two groups when their cognitive performance is closely matched in a pairwise manner. The authors sought to pinpoint common and differential pathophysiological features that accompany comparable working memory impairments in schizophrenia and healthy aging. METHODS: Fifty-three subjects were scanned with oxygen-15water positron emission tomography regional cerebral blood flow measurements during working memory. Seventeen medication-free patients with schizophrenia were individually matched for working memory performance with 17 healthy aging subjects. Brain activation of the two index groups were compared with each other and with 19 young healthy individuals. RESULTS:Patients with schizophrenia showed right DLPFC hypoactivation, both when compared with age-matched control subjects and after direct comparison with working memory performance-matched elderly subjects. Moreover, both groups with working memory deficits shared an inability to suppress parahippocampal and anterior medial prefrontal cortex activation. CONCLUSIONS: These results provide new insights into the mechanisms by which impaired working memory performance can arise by showing that both common (parahippocampal/anterior medial PFC) and differential (DLPFC) pathophysiological features accompany similar cognitive impairments. The aging data also demonstrate that poor performance is not necessarily accompanied by the DLPFC hypofunction that was seen in schizophrenia. Finally, these results more closely link the DLPFC functional abnormalities in schizophrenia to the pathophysiology of the disorder rather than to poor performance per se.
Authors: D R Weinberger; M F Egan; A Bertolino; J H Callicott; V S Mattay; B K Lipska; K F Berman; T E Goldberg Journal: Biol Psychiatry Date: 2001-12-01 Impact factor: 13.382
Authors: Angus W MacDonald; Cameron S Carter; John G Kerns; Stefan Ursu; Deanna M Barch; Avram J Holmes; V Andrew Stenger; Jonathan D Cohen Journal: Am J Psychiatry Date: 2005-03 Impact factor: 18.112
Authors: Katherine H Karlsgodt; Jacqueline Sanz; Theo G M van Erp; Carrie E Bearden; Keith H Nuechterlein; Tyrone D Cannon Journal: Schizophr Res Date: 2009-02-03 Impact factor: 4.939
Authors: Alan Anticevic; Michael W Cole; John D Murray; Philip R Corlett; Xiao-Jing Wang; John H Krystal Journal: Trends Cogn Sci Date: 2012-11-08 Impact factor: 20.229
Authors: Britta Hahn; Alexander N Harvey; James M Gold; Bernard A Fischer; William R Keller; Thomas J Ross; Elliot A Stein Journal: Schizophr Bull Date: 2016-02-28 Impact factor: 9.306
Authors: Francesca Managò; Maddalena Mereu; Surjeet Mastwal; Rosa Mastrogiacomo; Diego Scheggia; Marco Emanuele; Maria A De Luca; Daniel R Weinberger; Kuan Hong Wang; Francesco Papaleo Journal: Cell Rep Date: 2016-08-11 Impact factor: 9.423
Authors: Arash Nazeri; M Mallar Chakravarty; Daniel Felsky; Nancy J Lobaugh; Tarek K Rajji; Benoit H Mulsant; Aristotle N Voineskos Journal: Neuropsychopharmacology Date: 2013-04-16 Impact factor: 7.853
Authors: Jennifer S Yokoyama; Virginia E Sturm; Luke W Bonham; Eric Klein; Konstantinos Arfanakis; Lei Yu; Giovanni Coppola; Joel H Kramer; David A Bennett; Bruce L Miller; Dena B Dubal Journal: Ann Clin Transl Neurol Date: 2015-01-26 Impact factor: 5.430
Authors: Jessica L Reed; Enrico D'Ambrosio; Stefano Marenco; Gianluca Ursini; Amanda B Zheutlin; Giuseppe Blasi; Barbara E Spencer; Raffaella Romano; Jesse Hochheiser; Ann Reifman; Justin Sturm; Karen F Berman; Alessandro Bertolino; Daniel R Weinberger; Joseph H Callicott Journal: PLoS One Date: 2018-04-10 Impact factor: 3.240