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1.
Background
Schizophrenia is associated with impairments of the perception of objects, but how this affects higher cognitive functions, whether this impairment is already present after recent onset of psychosis, and whether it is specific for schizophrenia related psychosis, is not clear. We therefore tested the hypothesis that because schizophrenia is associated with impaired object perception, schizophrenia patients should differ in shifting attention between objects compared to healthy controls. To test this hypothesis, a task was used that allowed us to separately observe space-based and object-based covert orienting of attention. To examine whether impairment of object-based visual attention is related to higher order cognitive functions, standard neuropsychological tests were also administered.Method
Patients with recent onset psychosis and normal controls performed the attention task, in which space- and object-based attention shifts were induced by cue-target sequences that required reorienting of attention within an object, or reorienting attention between objects.Results
Patients with and without schizophrenia showed slower than normal spatial attention shifts, but the object-based component of attention shifts in patients was smaller than normal. Schizophrenia was specifically associated with slowed right-to-left attention shifts. Reorienting speed was significantly correlated with verbal memory scores in controls, and with visual attention scores in patients, but not with speed-of-processing scores in either group.Conclusions
deficits of object-perception and spatial attention shifting are not only associated with schizophrenia, but are common to all psychosis patients. Schizophrenia patients only differed by having abnormally slow right-to-left visual field reorienting. Deficits of object-perception and spatial attention shifting are already present after recent onset of psychosis. Studies investigating visual spatial attention should take into account the separable effects of space-based and object-based shifting of attention. Impaired reorienting in patients was related to impaired visual attention, but not to deficits of processing speed and verbal memory. 相似文献2.
Sander Martens Stefan M. Wierda Mathijs Dun Michal de Vries Henderikus G. O. M. Smid 《PloS one》2015,10(2)
BackgroundFormal musical training is known to have positive effects on attentional and executive functioning, processing speed, and working memory. Consequently, one may expect to find differences in the dynamics of temporal attention between musicians and non-musicians. Here we address the question whether that is indeed the case, and whether any beneficial effects of musical training on temporal attention are modality specific or generalize across sensory modalities.Conclusion/SignificanceAB magnitude within one modality can generalize to another modality, but this turns out not to be the case for every individual. Formal musical training seems to have a domain-general, but modality-specific beneficial effect on selective attention. The results fit with the idea that a major source of attentional restriction as reflected in the AB lies in modality-specific, independent sensory systems rather than a central amodal system. The findings demonstrate that individual differences in AB magnitude can provide important information about the modular structure of human cognition. 相似文献
3.
Background
Most people show a remarkable deficit to report the second of two targets when presented in close temporal succession, reflecting an attentional restriction known as the ‘attentional blink’ (AB). However, there are large individual differences in the magnitude of the effect, with some people showing no such attentional restrictions.Methodology/Principal Findings
Here we present behavioral and electrophysiological evidence suggesting that these ‘non-blinkers’ can use alphanumeric category information to select targets at an early processing stage. When such information was unavailable and target selection could only be based on information that is processed relatively late (rotation), even non-blinkers show a substantial AB. Electrophysiologically, in non-blinkers this resulted in enhanced distractor-related prefrontal brain activity, as well as delayed target-related occipito-parietal activity (P3).Conclusion/Significance
These findings shed new light on possible strategic mechanisms that may underlie individual differences in AB magnitude and provide intriguing clues as to how temporal restrictions as reflected in the AB can be overcome. 相似文献4.
Kemperman RF Veurink M van der Wal T Knegtering H Bruggeman R Fokkema MR Kema IP Korf J Muskiet FA 《Prostaglandins, leukotrienes, and essential fatty acids》2006,74(2):75-85
We assessed essential fatty acid (EFA) and B-vitamin status, together with their determinants, in 61 patients with schizophrenia and established whether those with poor status responded biochemically to the appropriate dietary supplements. As a group, the patients had high erythrocyte saturated fatty acids (FAs), monounsaturated FA and low polyunsaturated FA of the omega3 and omega6 series. Patients reporting not to take vitamin supplements had low vitamin B12 and high homocysteine. Homocysteine variance proved best explained by folate in both the total group and male patients, and by vitamins B12 and B6 in females. Alcohol consumption and duration of illness are risk factors for low polyunsaturated FA status (< P2.5 of reference range), while male gender and absence of fish consumption predict hyperhomocysteinemia (> P97.5 of reference range). Two patients exhibited biochemical EFA deficiency and seven showed biochemical signs of omega3/docosahexaenoic acid (DHA) marginality. Four patients exhibited moderate hyperhomocysteinemia with plasma values ranging from 57.5 to 74.8 micromol/L. None of the five patients with either moderate hyperhomocysteinemia, biochemical EFA deficiency, or both, was predicted by their clinicians to have poor diets. That diet was nevertheless at the basis of these abnormalities became confirmed after supplementing 4 of them with B vitamins and with soybean and fish oils. We conclude that a subgroup of patients with schizophrenia has biochemical EFA deficiency, omega3/DHA marginality, moderate hyperhomocysteinemia, or combinations. Correction seems indicated in view of the possible relation of poor EFA and B-vitamin status with some of their psychiatric symptoms, but notably to reduce their high risk of cardiovascular disease. 相似文献
5.
Peter J. M. van Haastert Ineke Keizer-Gunnink Henderikus Pots Claudia Ortiz-Mateos Douwe Veltman Wouter van Egmond Arjan Kortholt 《Molecular biology of the cell》2021,32(20)
In Dictyostelium, chemoattractants induce a fast cGMP response that mediates myosin filament formation in the rear of the cell. The major cGMP signaling pathway consists of a soluble guanylyl cyclase sGC, a cGMP-stimulated cGMP-specific phosphodiesterase, and the cGMP-target protein GbpC. Here we combine published experiments with many unpublished experiments performed in the past 45 years on the regulation and function of the cGMP signaling pathway. The chemoattractants stimulate heterotrimeric Gαβγ and monomeric Ras proteins. A fraction of the soluble guanylyl cyclase sGC binds with high affinity to a limited number of membrane binding sites, which is essential for sGC to become activated by Ras and Gα proteins. sGC can also bind to F-actin; binding to branched F-actin in pseudopods enhances basal sGC activity, whereas binding to parallel F-actin in the cortex reduces sGC activity. The cGMP pathway mediates cell polarity by inhibiting the rear: in unstimulated cells by sGC activity in the branched F-actin of pseudopods, in a shallow gradient by stimulated cGMP formation in pseudopods at the leading edge, and during cAMP oscillation to erase the previous polarity and establish a new polarity axis that aligns with the direction of the passing cAMP wave. 相似文献
6.
Edith J. Liemburg Stynke Castelein Frank van Es Anne Neeltje Scholte-Stalenhoef Gerard van de Willige Henderikus Smid Ellen Visser Henderikus Knegtering Richard Bruggeman 《PloS one》2014,9(11)
Psychotic disorders are among the most complex medical conditions. Longitudinal cohort studies may offer further insight into determinants of functional outcome after a psychotic episode. This paper describes the Psychosis Recent Onset in GRoningen Survey (PROGR-S) that currently contains data on 1076 early-episode patients with psychosis, including symptoms, personality, cognition, life events and other outcome determinants. Our goal in this report is to give an overview of PROGR-S, as a point of reference for future publications on the effect of cognition, personality and psychosocial functioning on outcomes. PROGR-S contains an extensive, diagnostic battery including anamnesis, biography, socio-demographic characteristics, clinical status, drug use, neuropsychological assessment, personality questionnaires, and physical status tests. Extensive follow-up data is available on psychopathology, physical condition, medication use, and care consumption. Sample characteristics were determined and related to existing literature. PROGR-S (period 1997–2009, n = 718) included the majority of the expected referrals in the catchment area. The average age was 27 (SD = 8.6) and two-thirds were male. The average IQ was lower than that in the healthy control group. The majority had been diagnosed with a psychotic spectrum disorder. A substantial number of the patients had depressive symptoms (479/718, 78%) and current cannabis or alcohol use (465/718, 75%). The level of community functioning was moderate, i.e. most patients were not in a relationship and were unemployed. The PROGR-S database contains a valuable cohort to study a range of aspects related to symptomatic and functional outcomes of recent onset psychosis, which may play a role in the treatment of this complex and disabling disorder. Results reported here show interesting starting points for future research. Thus, we aim to investigate long-term outcomes on the basis of cognition, personality, negative symptoms and physical health. Ultimately, we hope that this paper will contribute improving the health of patients with psychotic disorders. 相似文献
7.
EJ Liemburg L van der Meer M Swart B Curcic-Blake R Bruggeman H Knegtering A Aleman 《PloS one》2012,7(8):e42707
Lack of insight (unawareness of illness) is a common and clinically relevant feature of schizophrenia. Reduced levels of self-referential processing have been proposed as a mechanism underlying poor insight. The default mode network (DMN) has been implicated as a key node in the circuit for self-referential processing. We hypothesized that during resting state the DMN network would show decreased connectivity in schizophrenia patients with poor insight compared to patients with good insight. Patients with schizophrenia were recruited from mental health care centers in the north of the Netherlands and categorized in groups having good insight (n = 25) or poor insight (n = 19). All subjects underwent a resting state fMRI scan. A healthy control group (n = 30) was used as a reference. Functional connectivity of the anterior and posterior part of the DMN, identified using Independent Component Analysis, was compared between groups. Patients with poor insight showed lower connectivity of the ACC within the anterior DMN component and precuneus within the posterior DMN component compared to patients with good insight. Connectivity between the anterior and posterior part of the DMN was lower in patients than controls, and qualitatively different between the good and poor insight patient groups. As predicted, subjects with poor insight in psychosis showed decreased connectivity in DMN regions implicated in self-referential processing, although this concerned only part of the network. This finding is compatible with theories implying a role of reduced self-referential processing as a mechanism contributing to poor insight. 相似文献
8.
Otten HG de Gast GC Vooijs WC van der Gouw AP de Boer M Ossevoort MA Jonker M 《Cancer immunology, immunotherapy : CII》2003,52(9):569-575
CD86 and CD80 costimulatory antigens are highly overexpressed on Hodgkin/Reed-Sternberg cells in patients with Hodgkin's disease (HD) and are candidate target antigens for immunotoxins in order to eliminate minimal residual disease. In this study we have evaluated the pharmacokinetics (and immunological) toxicity in rhesus monkeys of immunotoxins consisting of gelonin conjugated to anti-CD86 (alphaCD86-IT). Both alphaCD86-IT and alphaCD80-IT inhibited protein synthesis in B cell lines from rhesus monkeys and inhibited the mixed leukocyte reaction. Reactivity of the alphaCD86 antibody with rhesus monkey CD86 (RhCD86) was shown by cloning and transfecting RhCD86, which conferred reactivity of the alphaCD86 antibody used in this study. alphaCD86-IT was administered as single intravenous bolus injection in four rhesus monkeys, and achieved plasma concentration in 50-fold excess able to eliminate cultured Hodgkin/Reed-Sternberg cells up to 6 h. The animals were capable of generating primary immune responses to both gelonin and murine IgG within 9 days after infusion with alphaCD86-IT. No evidence could be found of significant (immunological) toxicity. The results of this study show that alphaCD86-IT can be applied safely in an effective dose. 相似文献
9.
Impairment of sustained attention is assumed to be a core cognitive abnormality in schizophrenia. However, this seems inconsistent with a recent hypothesis that in schizophrenia the implementation of selection (i.e., sustained attention) is intact but the control of selection (i.e., switching the focus of attention) is impaired. Mounting evidence supports this hypothesis, indicating that switching of attention is a bigger problem in schizophrenia than maintaining the focus of attention. To shed more light on this hypothesis, we tested whether schizophrenia patients are impaired relative to controls in sustaining attention, switching attention, or both. Fifteen patients with recent-onset schizophrenia and fifteen healthy volunteers, matched on age and intelligence, performed sustained attention and attention switching tasks, while performance and brain potential measures of selective attention were recorded. In the sustained attention task, patients did not differ from the controls on these measures. In the attention switching task, however, patients showed worse performance than the controls, and early selective attention related brain potentials were absent in the patients while clearly present in the controls. These findings support the hypothesis that schizophrenia is associated with an impairment of the mechanisms that control the direction of attention (attention switching), while the mechanisms that implement a direction of attention (sustained attention) are intact. 相似文献
10.
Katharina Rudi Franz?Y. Ho Bernd?K. Gilsbach Henderikus Pots Alfred Wittinghofer Arjan Kortholt Johann?P. Klare 《Bioscience reports》2015,35(5)
Ras of complex proteins (Roc) is a Ras-like GTP-binding domain that always occurs in tandem with the C-terminal of Roc (COR) domain and is found in bacteria, plants and animals. Recently, it has been shown that Roco proteins belong to the family of G-proteins activated by nucleotide (nt)-dependent dimerization (GADs). We investigated the RocCOR tandem from the bacteria Chlorobium tepidum with site-directed spin labelling and pulse EPR distance measurements to follow conformational changes during the Roco G-protein cycle. Our results confirm that the COR domains are a stable dimerization device serving as a scaffold for the Roc domains that, in contrast, are structurally heterogeneous and dynamic entities. Contrary to other GAD proteins, we observed only minor structural alterations upon binding and hydrolysis of GTP, indicating significant mechanistic variations within this protein class. Mutations in the most prominent member of the Roco family of proteins, leucine-rich repeat (LRR) kinase 2 (LRRK2), are the most frequent cause of late-onset Parkinson''s disease (PD). Using a stable recombinant LRRK2 Roc-COR-kinase fragment we obtained detailed kinetic data for the G-protein cycle. Our data confirmed that dimerization is essential for efficient GTP hydrolysis and PD mutations in the Roc domain result in decreased GTPase activity. Previous data have shown that these LRRK2 PD-mutations are located in the interface between Roc and COR. Importantly, analogous mutations in the conserved C. tepidum Roc/COR interface significantly influence the structure and nt-induced conformational changes of the Roc domains. 相似文献