Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (233)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Callicott, J. H.
Right arrow Articles by Weinberger, D. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Callicott, J. H.
Right arrow Articles by Weinberger, D. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Cerebral Cortex, Vol. 10, No. 11, 1078-1092, November 2000
© 2000 Oxford University Press

Physiological Dysfunction of the Dorsolateral Prefrontal Cortex in Schizophrenia Revisited

Joseph H. Callicott, Alessandro Bertolino, Venkata S. Mattay, Frederick J.P. Langheim, Jeffrey Duyn1, Richard Coppola, Terry E. Goldberg and Daniel R. Weinberger

Clinical Brain Disorders Branch, IRP, NIMH, 1 Laboratory of Diagnostic Radiology Research, CC, NIH, Bethesda, MD, USA

Evidence implicates subtle neuronal pathology of the prefrontal cortex (PFC) in schizophrenia, but how this pathology is reflected in physiological neuroimaging experiments remains controversial. We investigated PFC function in schizophrenia using functional magnetic resonance imaging (fMRI) and a parametric version of the n-back working memory (WM) task. In a group of patients who performed relatively well on this task, there were three fundamental deviations from the ‘healthy’ pattern of PFC fMRI activation to varying WM difficulty. The first characteristic was a greater magnitude of PFC fMRI activation in the context of slightly impaired WM performance (i.e. physiological inefficiency). The second was that the significant correlations between behavioral WM performance and dorsal PFC fMRI activation were in opposite directions in the two groups. Third, the magnitude of the abnormal dorsal PFC fMRI response was predicted by an assay of N-acetylaspartate concentrations (NAA) in dorsal PFC, a measure of neuronal pathology obtained using proton magnetic resonance spectroscopy. Patients had significantly lower dorsal PFC NAA than controls and dorsal PFC NAA inversely predicted the fMRI response in dorsal PFC (areas 9, 46) to varying WM difficulty — supporting the assumption that abnormal PFC responses arose from abnormal PFC neurons. These data suggest that under certain conditions the physiological ramifications of dorsal PFC neuronal pathology in schizophrenia includes exaggerated and inefficient cortical activity, especially of dorsal PFC.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Schizophr BullHome page
N. C. Andreasen, C. A. Calage, and D. S. O'Leary
Theory of Mind and Schizophrenia: A Positron Emission Tomography Study of Medication-Free Patients
Schizophr Bull, July 1, 2008; 34(4): 708 - 719.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
G. D. Honey, P. R. Corlett, A. R. Absalom, M. Lee, E. Pomarol-Clotet, G. K. Murray, P. J. McKenna, E. T. Bullmore, D. K. Menon, and P. C. Fletcher
Individual Differences in Psychotic Effects of Ketamine Are Predicted by Brain Function Measured under Placebo
J. Neurosci., June 18, 2008; 28(25): 6295 - 6303.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
C. Haenschel, R. A. Bittner, F. Haertling, A. Rotarska-Jagiela, K. Maurer, W. Singer, and D. E. J. Linden
Contribution of Impaired Early-Stage Visual Processing to Working Memory Dysfunction in Adolescents With Schizophrenia: A Study With Event-Related Potentials and Functional Magnetic Resonance Imaging
Arch Gen Psychiatry, November 1, 2007; 64(11): 1229 - 1240.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
H.-Y. Tan, J. H. Callicott, and D. R. Weinberger
Dysfunctional and Compensatory Prefrontal Cortical Systems, Genes and the Pathogenesis of Schizophrenia
Cereb Cortex, September 1, 2007; 17(suppl_1): i171 - i181.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. H. Williams-Gray, A. Hampshire, T. W. Robbins, A. M. Owen, and R. A. Barker
Catechol O-Methyltransferase val158met Genotype Influences Frontoparietal Activity during Planning in Patients with Parkinson's Disease
J. Neurosci., May 2, 2007; 27(18): 4832 - 4838.
[Abstract] [Full Text] [PDF]

Home page
 Schizophr BullHome page
E. Granholm, S. P. Verney, D. Perivoliotis, and T. Miura
Effortful Cognitive Resource Allocation and Negative Symptom Severity in Chronic Schizophrenia
Schizophr Bull, May 1, 2007; 33(3): 831 - 842.
[Abstract] [Full Text] [PDF]

Home page
 J. Neuropsychiatry Clin. Neurosi.Home page
L. T. Eyler, R. K. Olsen, G. V. Nayak, H. Mirzakhanian, G. G. Brown, and D. V. Jeste
Brain Response Correlates of Decisional Capacity in Schizophrenia: A Preliminary fMRI Study
J Neuropsychiatry Clin Neurosci, May 1, 2007; 19(2): 137 - 144.
[Abstract] [Full Text] [PDF]

Home page
 Schizophr BullHome page
R. E. Gur, M. E. Calkins, R. C. Gur, W. P. Horan, K. H. Nuechterlein, L. J. Seidman, and W. S. Stone
The Consortium on the Genetics of Schizophrenia: Neurocognitive Endophenotypes
Schizophr Bull, January 1, 2007; 33(1): 49 - 68.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
G. Winterer, F. Musso, C. Beckmann, V. Mattay, M. F. Egan, D. W. Jones, J. H. Callicott, R. Coppola,, and D. R. Weinberger
Instability of Prefrontal Signal Processing in Schizophrenia
Am J Psychiatry, November 1, 2006; 163(11): 1960 - 1968.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
H.-Y. Tan, S. Sust, J. W. Buckholtz, V. S. Mattay, A. Meyer-Lindenberg, M. F. Egan, D. R. Weinberger, and J. H. Callicott
Dysfunctional Prefrontal Regional Specialization and Compensation in Schizophrenia
Am J Psychiatry, November 1, 2006; 163(11): 1969 - 1977.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
J. L. Reilly, M. S. H. Harris, M. S. Keshavan, and J. A. Sweeney
Adverse effects of risperidone on spatial working memory in first-episode schizophrenia.
Arch Gen Psychiatry, November 1, 2006; 63(11): 1189 - 1197.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
D.-F. Zhu, Z.-X. Wang, D.-R. Zhang, Z.-L. Pan, S. He, X.-P. Hu, X.-C. Chen, and J.-N. Zhou
fMRI revealed neural substrate for reversible working memory dysfunction in subclinical hypothyroidism
Brain, November 1, 2006; 129(11): 2923 - 2930.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
P. R. Corlett, G. D. Honey, M. R. F. Aitken, A. Dickinson, D. R. Shanks, A. R. Absalom, M. Lee, E. Pomarol-Clotet, G. K. Murray, P. J. McKenna, et al.
Frontal responses during learning predict vulnerability to the psychotogenic effects of ketamine: linking cognition, brain activity, and psychosis.
Arch Gen Psychiatry, June 1, 2006; 63(6): 611 - 621.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. Bertolino, G. Blasi, V. Latorre, V. Rubino, A. Rampino, L. Sinibaldi, G. Caforio, V. Petruzzella, A. Pizzuti, T. Scarabino, et al.
Additive Effects of Genetic Variation in Dopamine Regulating Genes on Working Memory Cortical Activity in Human Brain
J. Neurosci., April 12, 2006; 26(15): 3918 - 3922.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
H.-Y. Tan, W.-C. Choo, C. S.L. Fones, and M. W.L. Chee
fMRI Study of Maintenance and Manipulation Processes Within Working Memory in First-Episode Schizophrenia
Am J Psychiatry, October 1, 2005; 162(10): 1849 - 1858.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
T. D. Cannon, D. C. Glahn, J. Kim, T. G. M. Van Erp, K. Karlsgodt, M. S. Cohen, K. H. Nuechterlein, S. Bava, and D. Shirinyan
Dorsolateral Prefrontal Cortex Activity During Maintenance and Manipulation of Information in Working Memory in Patients With Schizophrenia
Arch Gen Psychiatry, October 1, 2005; 62(10): 1071 - 1080.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. PsychiatryHome page
M. S. KESHAVAN, G. BERGER, R. B. ZIPURSKY, S. J. WOOD, and C. PANTELIS
Neurobiology of early psychosis
The British Journal of Psychiatry, August 1, 2005; 187(48): s8 - s18.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. PsychiatryHome page
S. A. SPENCE, R. D. GREEN, I. D. WILKINSON, and M. D. HUNTER
Modafinil modulates anterior cingulate function in chronic schizophrenia
The British Journal of Psychiatry, July 1, 2005; 187(1): 55 - 61.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
S. Krieger, S. Lis, T. Cetin, B. Gallhofer, and A. Meyer-Lindenberg
Executive Function and Cognitive Subprocesses in First-Episode, Drug-Naive Schizophrenia: An Analysis of N-Back Performance
Am J Psychiatry, June 1, 2005; 162(6): 1206 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
G. Blasi, V. S. Mattay, A. Bertolino, B. Elvevag, J. H. Callicott, S. Das, B. S. Kolachana, M. F. Egan, T. E. Goldberg, and D. R. Weinberger
Effect of Catechol-O-Methyltransferase val158met Genotype on Attentional Control
J. Neurosci., May 18, 2005; 25(20): 5038 - 5045.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
C. H.Y. Fu, J. Suckling, S. C.R. Williams, C. M. Andrew, G. N. Vythelingum, and P. K. McGuire
Effects of Psychotic State and Task Demand on Prefrontal Function in Schizophrenia: An fMRI Study of Overt Verbal Fluency
Am J Psychiatry, March 1, 2005; 162(3): 485 - 494.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
A. Bertolino, G. Caforio, G. Blasi, M. De Candia, V. Latorre, V. Petruzzella, M. Altamura, G. Nappi, S. Papa, J. H. Callicott, et al.
Interaction of COMT Val108/158 Met Genotype and Olanzapine Treatment on Prefrontal Cortical Function in Patients With Schizophrenia
Am J Psychiatry, October 1, 2004; 161(10): 1798 - 1805.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. PsychiatryHome page
A. Mendrek, K. R. Laurens, K. A. Kiehl, E. T. C. Ngan, E. Stip, and P. F. Liddle
Changes in distributed neural circuitry function in patients with first-episode schizophrenia
The British Journal of Psychiatry, September 1, 2004; 185(3): 205 - 214.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. F. Egan, R. E. Straub, T. E. Goldberg, I. Yakub, J. H. Callicott, A. R. Hariri, V. S. Mattay, A. Bertolino, T. M. Hyde, C. Shannon-Weickert, et al.
Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia
PNAS, August 24, 2004; 101(34): 12604 - 12609.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
G. Winterer, R. Coppola, T. E. Goldberg, M. F. Egan, D. W. Jones, C. E. Sanchez, and D. R. Weinberger
Prefrontal Broadband Noise, Working Memory, and Genetic Risk for Schizophrenia
Am J Psychiatry, March 1, 2004; 161(3): 490 - 500.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
K. Hugdahl, B. R. Rund, A. Lund, A. Asbjornsen, J. Egeland, L. Ersland, N. I. Landro, A. Roness, K. I. Stordal, K. Sundet, et al.
Brain Activation Measured With fMRI During a Mental Arithmetic Task in Schizophrenia and Major Depression
Am J Psychiatry, February 1, 2004; 161(2): 286 - 293.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
J. H. Callicott, V. S. Mattay, B. A. Verchinski, S. Marenco, M. F. Egan, and D. R. Weinberger
Complexity of Prefrontal Cortical Dysfunction in Schizophrenia: More Than Up or Down
Am J Psychiatry, December 1, 2003; 160(12): 2209 - 2215.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
M. F. Glabus, B. Horwitz, J. L. Holt, P. D. Kohn, B. K. Gerton, J. H. Callicott, A. Meyer-Lindenberg, and K. F. Berman
Interindividual Differences in Functional Interactions among Prefrontal, Parietal and Parahippocampal Regions during Working Memory
Cereb Cortex, December 1, 2003; 13(12): 1352 - 1361.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
G. R. Kuperberg, M. R. Broome, P. K. McGuire, A. S. David, M. Eddy, F. Ozawa, D. Goff, W. C. West, S. C. R. Williams, A. J. W. van der Kouwe, et al.
Regionally Localized Thinning of the Cerebral Cortex in Schizophrenia
Arch Gen Psychiatry, September 1, 2003; 60(9): 878 - 888.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
T. E. Goldberg, M. F. Egan, T. Gscheidle, R. Coppola, T. Weickert, B. S. Kolachana, D. Goldman, and D. R. Weinberger
Executive Subprocesses in Working Memory: Relationship to Catechol-O-methyltransferase Val158Met Genotype and Schizophrenia
Arch Gen Psychiatry, September 1, 2003; 60(9): 889 - 896.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. PsychiatryHome page
E. BULLMORE and P. FLETCHER
The eye's mind: brain mapping and psychiatry
The British Journal of Psychiatry, May 1, 2003; 182(5): 381 - 384.
[Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
I. I. Gottesman and T. D. Gould
The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
Am J Psychiatry, April 1, 2003; 160(4): 636 - 645.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
J. H. Callicott, M. F. Egan, V. S. Mattay, A. Bertolino, A. D. Bone, B. Verchinksi, and D. R. Weinberger
Abnormal fMRI Response of the Dorsolateral Prefrontal Cortex in Cognitively Intact Siblings of Patients With Schizophrenia
Am J Psychiatry, April 1, 2003; 160(4): 709 - 719.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Akil, B. S. Kolachana, D. A. Rothmond, T. M. Hyde, D. R. Weinberger, and J. E. Kleinman
Catechol-O-Methyltransferase Genotype and Dopamine Regulation in the Human Brain
J. Neurosci., March 15, 2003; 23(6): 2008 - 2013.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
A. Bertolino, D. Sciota, F. Brudaglio, M. Altamura, G. Blasi, A. Bellomo, N. Antonucci, J. H. Callicott, T. E. Goldberg, T. Scarabino, et al.
Working Memory Deficits and Levels of N-Acetylaspartate in Patients With Schizophreniform Disorder
Am J Psychiatry, March 1, 2003; 160(3): 483 - 489.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
L. D. Selemon, J. Mrzljak, J. E. Kleinman, M. M. Herman, and P. S. Goldman-Rakic
Regional Specificity in the Neuropathologic Substrates of Schizophrenia: A Morphometric Analysis of Broca's Area 44 and Area 9
Arch Gen Psychiatry, January 1, 2003; 60(1): 69 - 77.
[Abstract] [Full Text] [PDF]

Home page
 Learn. Mem.Home page
T. W. Weickert, A. Terrazas, L. B. Bigelow, J. D. Malley, T. Hyde, M. F. Egan, D. R. Weinberger, and T. E. Goldberg
Habit and Skill Learning in Schizophrenia: Evidence of Normal Striatal Processing With Abnormal Cortical Input
Learn. Mem., November 1, 2002; 9(6): 430 - 442.
[Abstract] [Full Text] [PDF]

Home page
 Cereb CortexHome page
A. Bertolino, J. L. Roffman, B. K. Lipska, P. van Gelderen, A. Olson, and D. R. Weinberger
Reduced N-Acetylaspartate in Prefrontal Cortex of Adult Rats with Neonatal Hippocampal Damage
Cereb Cortex, September 1, 2002; 12(9): 983 - 990.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
N. F. Ramsey, H. A. M. Koning, P. Welles, W. Cahn, J. A. van der Linden, and R. S. Kahn
Excessive recruitment of neural systems subserving logical reasoning in schizophrenia
Brain, August 1, 2002; 125(8): 1793 - 1807.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. Abi-Dargham, O. Mawlawi, I. Lombardo, R. Gil, D. Martinez, Y. Huang, D.-R. Hwang, J. Keilp, L. Kochan, R. Van Heertum, et al.
Prefrontal Dopamine D1 Receptors and Working Memory in Schizophrenia
J. Neurosci., May 1, 2002; 22(9): 3708 - 3719.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurol. Neurosurg. PsychiatryHome page
G D Honey, P C Fletcher, and E T Bullmore
Functional brain mapping of psychopathology
J. Neurol. Neurosurg. Psychiatry, April 1, 2002; 72(4): 432 - 439.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. D. Cannon, P. M. Thompson, T. G. M. van Erp, A. W. Toga, V.-P. Poutanen, M. Huttunen, J. Lonnqvist, C.-G. Standerskjold-Nordenstam, K. L. Narr, M. Khaledy, et al.
Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia
PNAS, February 20, 2002; (2002) 52023499.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. F. Egan, T. E. Goldberg, B. S. Kolachana, J. H. Callicott, C. M. Mazzanti, R. E. Straub, D. Goldman, and D. R. Weinberger
Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia
PNAS, May 24, 2001; (2001) 111134598.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. D. Cannon, P. M. Thompson, T. G. M. van Erp, A. W. Toga, V.-P. Poutanen, M. Huttunen, J. Lonnqvist, C.-G. Standerskjold-Nordenstam, K. L. Narr, M. Khaledy, et al.
Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia
PNAS, March 5, 2002; 99(5): 3228 - 3233.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. F. Egan, T. E. Goldberg, B. S. Kolachana, J. H. Callicott, C. M. Mazzanti, R. E. Straub, D. Goldman, and D. R. Weinberger
Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia
PNAS, June 5, 2001; 98(12): 6917 - 6922.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.