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.
Key Words
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References
- Executive function, neural circuitry, and genetic mechanisms in schizophrenia.Neuropsychopharmacology. 2010; 35: 258-277
- Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia.Arch Gen Psychiatry. 2005; 62: 1071-1080
- Re-evaluating dorsolateral prefrontal cortex activation during working memory in schizophrenia.Schizophr Res. 2009; 108: 143-150
- Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis.Am J Psychiatry. 2005; 162: 475-484
- Prefrontal function in schizophrenia: Confounds and controversies.Philos Trans R Soc Lond B Biol Sci. 1996; 351: 1495-1503
- Impairment of working memory maintenance and response in schizophrenia: Functional magnetic resonance imaging evidence.Biol Psychiatry. 2008; 64: 1026-1034
- Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia.Arch Gen Psychiatry. 2009; 66: 811-822
- Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited.Cereb Cortex. 2000; 10: 1078-1092
- Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance.Biol Psychiatry. 2000; 48: 99-109
- Beyond hypofrontality: A quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia.Hum Brain Mapp. 2005; 25: 60-69
- Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down.Am J Psychiatry. 2003; 160: 2209-2215
- Prefrontal cortex dysfunction during working memory performance in schizophrenia: Reconciling discrepant findings.Schizophr Res. 2003; 60: 285-298
- Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia.Cereb Cortex. 2007; 17: i171-i181
- Dysfunctional prefrontal regional specialization and compensation in schizophrenia.Am J Psychiatry. 2006; 163: 1969-1977
- Excessive recruitment of neural systems subserving logical reasoning in schizophrenia.Brain. 2002; 125: 1793-1807
- Ageing and early-stage Parkinson's disease affect separable neural mechanisms of mesolimbic reward processing.Brain. 2007; 130: 2412-2424
- Prefrontal function and activation in bipolar disorder and schizophrenia.Am J Psychiatry. 2008; 165: 378-384
- Altered brain activity in healthy seniors: What does it mean?.Prog Brain Res. 2006; 157: 45-56
- The missing link: A failure of fronto-hippocampal integration in schizophrenia.Nat Neurosci. 1998; 1: 266-267
- Impaired recruitment of the hippocampus during conscious recollection in schizophrenia [see comments].Nat Neurosci. 1998; 1: 318-323
- Hemispheric asymmetry reduction in older adults: The HAROLD model.Psychol Aging. 2002; 17: 85-100
- Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia.Proc Natl Acad Sci U S A. 2009; 106: 1279-1284
- Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia.Arch Gen Psychiatry. 2005; 62: 379-386
- Failure to deactivate in the prefrontal cortex in schizophrenia: Dysfunction of the default mode network?.Psychol Med. 2008; 38: 1185-1193
- Brain imaging of human memory systems: Between-systems similarities and within-system differences.Brain Res Cogn Brain Res. 2002; 13: 281-292
- Functional dissociation among components of remembering: Control, perceived oldness, and content.J Neurosci. 2003; 23: 3869-3880
- Damage to the fronto-polar cortex is associated with impaired multitasking.PLoS One. 2008; 3: e3227
- Organization of cognitive control within the lateral prefrontal cortex in schizophrenia.Arch Gen Psychiatry. 2009; 66: 377-386
- Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.Biol Psychiatry. 2003; 53: 376-384
- Interindividual differences in functional interactions among prefrontal, parietal and parahippocampal regions during working memory.Cereb Cortex. 2003; 13: 1352-1361
- Prefrontal neurons and the genetics of schizophrenia.Biol Psychiatry. 2001; 50: 825-844
- Is the mechanism of prefrontal hypofunction in depression the same as in schizophrenia?.Br J Psychiatry. 1993; 162: 183-192
- Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET.J Cogn Neurosci. 2000; 12: 174-187
- The adaptive brain: Aging and neurocognitive scaffolding.Annu Rev Psychol. 2009; 60: 173-196
- Context-dependent, neural system-specific neurophysiological concomitants of ageing: Mapping PET correlates during cognitive activation.Brain. 1999; 122: 963-979
- Anatomical organization of the parahippocampal-hippocampal network.Ann N Y Acad Sci. 2000; 911: 1-24
- Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI.Proc Natl Acad Sci U S A. 2004; 101: 4637-4642
- Functional deactivations: change with age and dementia of the Alzheimer type.Proc Natl Acad Sci U S A. 2003; 100: 14504-14509
- Age differences in deactivation: A link to cognitive control?.J Cogn Neurosci. 2007; 19: 1021-1032
- Evidence for abnormal cortical functional connectivity during working memory in schizophrenia.Am J Psychiatry. 2001; 158: 1809-1817
- Task-independent and task-specific age effects on brain activity during working memory, visual attention and episodic retrieval.Cereb Cortex. 2004; 14: 364-375
- A pathophysiological framework of hippocampal dysfunction in ageing and disease.Nat Rev Neurosci. 2011; 12: 585-601
- The correlative triad among aging, dopamine, and cognition: Current status and future prospects.Neurosci Biobehav Rev. 2006; 30: 791-807
- Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.Proc Natl Acad Sci U S A. 1996; 93: 9235-9240
- The hippocampal-VTA loop: Controlling the entry of information into long-term memory.Neuron. 2005; 46: 703-713
- Age-related changes in midbrain dopaminergic regulation of the human reward system.Proc Natl Acad Sci U S A. 2008; 105: 15106-15111
Article info
Publication history
Published online: February 20, 2012
Accepted:
January 6,
2012
Received in revised form:
January 6,
2012
Received:
June 1,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
