Article

Effects of treatment with the atypical neuroleptic quetiapine on working memory function: A functional MRI follow-up investigation

Dept. of Psychiatry, Ludwig-Maximilians-University of Munich, Nussbaumstrasse 7, 80336, Munich, Germany.
European Archives of Psychiatry and Clinical Neuroscience (Impact Factor: 3.53). 01/2007; 256(8):522-31. DOI: 10.1007/s00406-006-0687-x
Source: PubMed

ABSTRACT

Working memory as a part of higher-order executive functions is defined by the parallel storage and processing of information. Recent functional fMRI studies have revealed a functional, interregional disintegration of a neuronal network connecting cortical, subcortical and cerebellar regions in schizophrenic patients (SZ). Cognitive impairment in working memory is a core psychopathological correlate of schizophrenic symptoms. Atypical neuroleptics such as quetiapine have shown good efficacy in treating positive and negative symptoms. The presented study evaluated the impact of a neuroleptic steady state treatment with quetiapine on the altered working memory activation patterns in schizophrenia.
Patients were examined by fMRI at baseline and after 12 weeks of steady state treatment with quetiapine. Matched healthy controls (HC) underwent baseline examination. In the scanner, stimuli were presented in a 2-back and 0-back condition of a working memory (wm) paradigm, whereby a degraded and a non-degraded version were used each time. Additionally, behavioural responses (reaction time to target stimuli and error ratio) were measured.
At baseline, healthy controls revealed increased activity in the frontal lobe, especially in regions of the prefrontal cortex. Compared to HC, SZ showed hypoactivation in the right dorsolateral prefrontal cortex (DLPFC) and the ventrolateral prefrontal cortex (VLPFC) bilaterally for the 2-back condition. In the 2-back degraded condition there was a hypoactivation in both, the right DLPFC and the VLPFC. Additionally, patients showed bilaterally decreased activation in the basalganglia in the 2-back and in the right caudatus in the 2-back degraded condition compared to healthy controls. After treatment with quetiapine, patients activations patterns were increased. The pre-post comparison of the 2-back condition revealed a significant increase of activation in the left VLPFC at a significance level of 0.001 (uncorrected). The 2-back degraded condition led to a significant activation pattern in the lingual gyrus and the right precuneus. In both wm conditions, at baseline there were no differences in reaction time but only a worse performance in SZ. After treatment, behavioural measurement of responses, including reaction time and performance, showed slight improvements in SZ, although these did not reach statistical significance.
The neuronal networks underlying working memory are clearly altered in schizophrenia. After 12 weeks of treatment with quetiapine monotherapy, patients showed significant clinical improvement and revealed increased BOLD activity in the VLPFC during a working memory task, although there was no improvement of cognitive performance.

0 Followers
 · 
29 Reads
    • "fMRI studies in schizophrenics before and after 12 weeks of quetiapine monotherapy showed that treated patients had a significant increase of activation in the ventrolateral prefrontal cortex, lingual gyrus, and right precuneus. Behavioral measurement of responses including reaction time and performance demonstrated slight improvements, but these did not reach statistical significance (Meisenzahl et al. 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.
    No preview · Article · Jan 2015 · Current Topics in Behavioral Neurosciences
  • Source
    • "It should also be noted that the performance-by-load and treatment-by-load interactions were observed only when considering individual ROIs but not at the voxelwise level. Previous studies have noted that antipsychotic effects at the level of BOLD may be of small to moderate effect size (Meisenzahl et al. 2006); therefore, replication using larger samples will be important. A further limitation is the fact that some patients were co-medicated with other compounds; these may influence cognition and brain function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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. 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. 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.
    Full-text · Article · Feb 2011 · Psychopharmacology
  • Source
    • "More recently, Meisenzhal et al. (2006) have demonstrated that medicating drug free patients with quetiapine for 12 weeks is associated with significant increase of activity in ventrolateral PFC during a WM task [110]. A few other studies [111-113] have focused on the effect of antipsychotic treatment on brain activity associated with emotion processing . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent evidence suggests that genetic variation is associated with individual variability in response to treatment with antipsychotics. Although numerous studies have been performed for identification of potential genetic variants affecting response to treatment, initial enthusiasm has been tempered by inconsistent results. Along with some specific methodological issues, another plausible explanation for such inconsistencies is lack of sensitivity of the phenotype (clinical measures) used to define response. In this paper, we review use of Imaging Genetics, a relatively new approach that combines genetic assessment with functional neuroimaging, to explore in vivo neurobiological effects of genetic variation. Moreover, we propose to use Imaging Genetics as a tool to evaluate and predict response to treatment with antipsychotics based on the individual genetic makeup.
    Full-text · Article · Feb 2009 · Current pharmaceutical design
Show more