Specific relationship between prefrontal neuronal N-acetylaspartate and activation of the working memory cortical network in schizophrenia.
ABSTRACT Abnormal activation of the dorsolateral prefrontal cortex and a related cortical network during working memory tasks has been demonstrated in patients with schizophrenia, but the responsible mechanism has not been identified. The present study was performed to determine whether neuronal pathology of the dorsolateral prefrontal cortex is linked to the activation of the working memory cortical network in patients with schizophrenia.
The brains of 13 patients with schizophrenia and 13 comparison subjects were studied with proton magnetic resonance spectroscopic ((1)H-MRS) imaging (to measure N-acetylaspartate as a marker of neuronal pathology) and with [(15)O]water positron emission tomography (PET) during performance of the Wisconsin Card Sorting Test (to measure activation of the working memory cortical network). An independent cohort of patients (N=7) was also studied in a post hoc experiment with (1)H-MRS imaging and with the same PET technique during performance of another working memory task (the "N-back" task).
Measures of N-acetylaspartate in the dorsolateral prefrontal cortex strongly correlated with activation of the distributed working memory network, including the dorsolateral prefrontal, temporal, and inferior parietal cortices, during both working memory tasks in the two independent groups of patients with schizophrenia. In contrast, N-acetylaspartate in other cortical regions and in comparison subjects did not show these relationships.
These findings directly implicate a population of dorsolateral prefrontal cortex neurons as selectively accounting for the activity of the distributed working memory cortical network in schizophrenia and complement other evidence that dorsolateral prefrontal cortex connectivity is fundamental to the pathophysiology of the disorder.
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ABSTRACT: Although working memory is known to be impaired in schizophrenia the anatomical and functional relationships underlying this deficit remain to be elucidated. A combined imaging approach involving functional and structural magnetic resonance techniques was used, applying independent component analysis and surface-based morphometry to 14 patients with schizophrenia and 14 healthy controls. Neurocognitive functioning was assessed by a neuropsychological test battery that measured executive function. It was hypothesized that working memory dysfunctional connectivity in schizophrenia is related to underlying anatomical abnormalities. Patients with schizophrenia showed cortical thinning in the left inferior frontal gyrus and insula, which explained 57% of blood oxygenation level-dependent signal magnitude in functional magnetic resonance imaging in the central executive network (lateral prefrontal and parietal cortex) over-activation and default mode network (anterior and posterior cingulate) deactivation. No structure-function relationship emerged in the healthy control group. The study provides evidence to suggest that dysfunctional activation/deactivation patterns in schizophrenia may be explained in terms of underlying gray matter deficits.Psychiatry research. 08/2013;
- European Neuropsychopharmacology 01/2006; 16. · 5.40 Impact Factor
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ABSTRACT: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics.Neuropsychiatric Disease and Treatment 01/2014; 10:1243-53. · 2.00 Impact Factor