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Functional magnetic resonance imaging of a parametric working memory task in schizophrenia: relationship with performance and effects of antipsychotic treatment.

Ettinger U, Williams SC, Fannon D, Premkumar P, Kuipers E, Möller HJ, Kumari V - Psychopharmacology (Berl.) (2011)

Bottom Line: The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls.Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load.This difference increased with increasing working memory load in the prefrontal areas.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Munich, Nussbaumstr. 7, 80336, Munich, Germany. ulrich.ettinger@med.uni-muenchen.de

ABSTRACT

Rationale: Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls.

Objectives: We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group.

Method: We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task.

Results: Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area.

Conclusions: Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics.

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Related in: MedlinePlus

Group-by-load interactions in BOLD response. The upper part of the figure depicts in red the areas that show a significant main effect of load and in blue the two prefrontal areas that show a significant group-by-load interaction. The selection of the two coronal slices corresponds to the Talairach y coordinates of the peak voxel for the right (y  = 18) and left (y  = 17) PFC clusters, respectively. The lower parts of the figure depict the nature of the interaction effects separately for left and right PFC
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Fig2: Group-by-load interactions in BOLD response. The upper part of the figure depicts in red the areas that show a significant main effect of load and in blue the two prefrontal areas that show a significant group-by-load interaction. The selection of the two coronal slices corresponds to the Talairach y coordinates of the peak voxel for the right (y  = 18) and left (y  = 17) PFC clusters, respectively. The lower parts of the figure depict the nature of the interaction effects separately for left and right PFC

Mentions: The group-by-load interaction (Fig. 2) revealed two significant clusters (p  <  0.05 corrected cluster level): (1) left middle frontal gyrus (BA9; x  =  −46, y  =  17, z  =  36; 2,032 voxels; Z  =  4.43) and (2) right inferior frontal gyrus (BA45/47; x  =  46, y  =  18, z  =  18; 749 voxels; Z  =  3.94) extending into right middle frontal gyrus. A third cluster with a peak in the occipital cortex (BA17; x  = −22, y  =  −86, z  =  −11; 535 voxels; Z  =  4.10) showed the same pattern but narrowly missed the level of statistical significance (p  =  0.054, corrected cluster level). These clusters showed stronger increases across load in patients than in controls. On the other hand, there were no significant clusters showing stronger increases across load in controls than in patients at the corrected or uncorrected cluster level, and there were no significant voxels at the chosen height threshold (p  <  0.001).Fig. 2


Functional magnetic resonance imaging of a parametric working memory task in schizophrenia: relationship with performance and effects of antipsychotic treatment.

Ettinger U, Williams SC, Fannon D, Premkumar P, Kuipers E, Möller HJ, Kumari V - Psychopharmacology (Berl.) (2011)

Group-by-load interactions in BOLD response. The upper part of the figure depicts in red the areas that show a significant main effect of load and in blue the two prefrontal areas that show a significant group-by-load interaction. The selection of the two coronal slices corresponds to the Talairach y coordinates of the peak voxel for the right (y  = 18) and left (y  = 17) PFC clusters, respectively. The lower parts of the figure depict the nature of the interaction effects separately for left and right PFC
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111549&req=5

Fig2: Group-by-load interactions in BOLD response. The upper part of the figure depicts in red the areas that show a significant main effect of load and in blue the two prefrontal areas that show a significant group-by-load interaction. The selection of the two coronal slices corresponds to the Talairach y coordinates of the peak voxel for the right (y  = 18) and left (y  = 17) PFC clusters, respectively. The lower parts of the figure depict the nature of the interaction effects separately for left and right PFC
Mentions: The group-by-load interaction (Fig. 2) revealed two significant clusters (p  <  0.05 corrected cluster level): (1) left middle frontal gyrus (BA9; x  =  −46, y  =  17, z  =  36; 2,032 voxels; Z  =  4.43) and (2) right inferior frontal gyrus (BA45/47; x  =  46, y  =  18, z  =  18; 749 voxels; Z  =  3.94) extending into right middle frontal gyrus. A third cluster with a peak in the occipital cortex (BA17; x  = −22, y  =  −86, z  =  −11; 535 voxels; Z  =  4.10) showed the same pattern but narrowly missed the level of statistical significance (p  =  0.054, corrected cluster level). These clusters showed stronger increases across load in patients than in controls. On the other hand, there were no significant clusters showing stronger increases across load in controls than in patients at the corrected or uncorrected cluster level, and there were no significant voxels at the chosen height threshold (p  <  0.001).Fig. 2

Bottom Line: The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls.Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load.This difference increased with increasing working memory load in the prefrontal areas.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Munich, Nussbaumstr. 7, 80336, Munich, Germany. ulrich.ettinger@med.uni-muenchen.de

ABSTRACT

Rationale: Working memory dysfunction is frequently observed in schizophrenia. The neural mechanisms underlying this dysfunction remain unclear, with functional neuroimaging studies reporting increased, decreased or unchanged activation compared to controls.

Objectives: We investigated the neural correlates of spatial working memory in schizophrenia with particular consideration of effects of antipsychotic treatment and relation to performance levels in the patient group.

Method: We used functional magnetic resonance imaging and studied the blood-oxygen-level-dependent (BOLD) response of 45 schizophrenia outpatients and 19 healthy controls during a parametric spatial n-back task.

Results: Performance in both groups deteriorated with increasing memory load (0-back, 1-back, 2-back), but the two groups did not significantly differ in performance overall or as a function of load. Patients produced stronger BOLD signal in occipital and lateral prefrontal cortex during task performance than controls. This difference increased with increasing working memory load in the prefrontal areas. We also found that in patients with good task performance, the BOLD response in left prefrontal cortex showed a stronger parametric increase with working memory load than in patients with poor performance. Second-generation antipsychotics were independently associated with left prefrontal BOLD increase in response to working memory load, whereas first-generation antipsychotics were associated with BOLD decrease with increasing load in this area.

Conclusions: Together, these findings suggest that in schizophrenia patients, normal working memory task performance may be achieved through compensatory neural activity, especially in well-performing patients and in those treated with second-generation antipsychotics.

Show MeSH
Related in: MedlinePlus