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

Abstract

RationaleWorking 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.ObjectivesWe 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.MethodWe 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.ResultsPerformance 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.ConclusionsTogether, 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-011-2214-7) contains supplementary material, which is available to authorized users.

Neuropsychopharmacology of auditory hallucinations: insights from pharmacological functional MRI and perspectives for future research

“…Nevertheless, most converging results appear to be stemming from studies that have reported effects on haloperidol, expressed as a reduction of BOLD signal amplitude (potentially due to higher affinity for the dopamine D 2 receptors), in contrast to studies that have used quetiapine where there is a tendency for an increase of the BOLD signal in the frontal lobe. In agreement with this, differences between FGAs and SGAs were shown by Ettinger et al [93]. However, caution should be made in the interpretation of these findings, as the majority of studies are small and unreplicated, and the results may be vulnerable to confounders such as other symptoms and side effects.…”

Cortical morphology changes in women with borderline personality disorder: a multimodal approach

“…[33][34][35] Longitudinal studies utilizing structural neuroimaging techniques comparing drug-naïve patients before and after psychotropic treatment have observed positive effects 33,34,36 or no brain structure modification 35 after psychotropic treatment, while functional neuroimaging studies have observed enhancements in neuroplasticity and in brain connectivity. [37][38][39][40] The findings reported herein should be interpreted in the context of a number of limitations. The relatively small number of patients enrolled may preclude wider conclusions.…”

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis

“…Earlier EEG and fMRI studies also revealed hyperfrontality combined with increased parietal activity in patients with first-episode psychosis during working memory tasks. 10,[51][52][53][54] It is thus likely that the early activation of parietal generators in attentional tasks observed in our study may represent a compensatory mechan ism 55 to facilitate the maintenance of executive performances in patients with first-episode psychosis.…”