Effects of treatment with the atypical neuroleptic quetiapine on working memory function: A functional MRI follow-up investigation
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.
- SourceAvailable from: Fabio Sambataro
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- "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 . A few other studies [111-113] have focused on the effect of antipsychotic treatment on brain activity associated with emotion processing . "
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.Current pharmaceutical design 02/2009; 15(22):2560-72. DOI:10.2174/138161209788957483 · 3.29 Impact Factor
Article: ARCHIVESOF GENERAL PSYCHIATRY
Conference Paper: Pattern classification using teurons[Show abstract] [Hide abstract]
ABSTRACT: Neural networks consist of simple elements capable of summation and thresholding. The authors define a more general element, the task-oriented neuron or teuron, which can compute higher-order functions. They further define teuron networks and show two such networks that can be used as content addressable memories and as pattern classifiers. The first network is based on the Godel encoding scheme. It uses this scheme in order to memorize sequences of numbers. These sequences are then stored analogically. The second network uses binary encoding, i.e. a binary sequence is translated into its decimal equivalent and then stored analogically. The authors demonstrate the feasibility of implementing such networks. It is concluded that they can be implemented in such a way as to reduce cost, due to a reduction in the number of elements coupled with constancy of link values (synaptic weights)Pattern Recognition, 1990. Proceedings., 10th International Conference on; 07/1990