What causes aberrant salience in schizophrenia? A role for impaired short-term habituation and the GRIA1 (GluA1) AMPA receptor subunit.

The GRIA1 locus, encoding the GluA1 (also known as GluRA or GluR1) AMPA glutamate receptor subunit, shows genome-wide association to schizophrenia. As well as extending the evidence that glutamatergic abnormalities have a key role in the disorder, this finding draws attention to the behavioural phenotype of Gria1 knockout mice. These mice show deficits in short-term habituation. Importantly, under some conditions the attention being paid to a recently presented neutral stimulus can actually increase rather than decrease (sensitization). We propose that this mouse phenotype represents a cause of aberrant salience and, in turn, that aberrant salience (and the resulting positive symptoms) in schizophrenia may arise, at least in part, from a glutamatergic genetic predisposition and a deficit in short-term habituation. This proposal links an established risk gene with a psychological process central to psychosis and is supported by findings of comparable deficits in short-term habituation in mice lacking the NMDAR receptor subunit Grin2a (which also shows association to schizophrenia). As aberrant salience is primarily a dopaminergic phenomenon, the model supports the view that the dopaminergic abnormalities can be downstream of a glutamatergic aetiology. Finally, we suggest that, as illustrated here, the real value of genetically modified mice is not as ‘models of schizophrenia’ but as experimental tools that can link genomic discoveries with psychological processes and help elucidate the underlying neural mechanisms

Aspect-Oriented Programming

Aspect-oriented programming is a promising idea that can improve the quality of software by reduce the problem of code tangling and improving the separation of concerns. At ECOOP'97, the first AOP workshop brought together a number of researchers interested in aspect-orientation. At ECOOP'98, during the second AOP workshop the participants reported on progress in some research topics and raised more issues that were further discussed. \ud \ud This year, the ideas and concepts of AOP have been spread and adopted more widely, and, accordingly, the workshop received many submissions covering areas from design and application of aspects to design and implementation of aspect languages

Neural correlates of visuospatial working memory in the ‘at-risk mental state’

Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 agematched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object–location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis

The *subjectivity* of subjective experience - A representationalist analysis of the first-person perspective

This is a brief and accessible English summary of the "Self-model Theory of Subjectivity" (SMT), which is only available as German book in this archive. It introduces two new theoretical entities, the "phenomenal self-model" (PSM) and the "phenomenal model of the intentionality-relation" PMIR. A representationalist analysis of the phenomenal first-person persepctive is offered. This is a revised version, including two pictures

Reflective Composition: the declarative composition of roles to unify objects, roles, and aspects [poster session]

As bases for object-orientation, both class-based and prototype-based organization have limitations. We argue that roles have significant benefits as a foundation for organizing objects. We further argue that these benefits can be realised most flexibly using logic meta-programming. Additional benefits from this approach are to reduce redundancy and subsume aspects

Involuntary social cue integration in patients with obsessive compulsive disorder

Objective Patients with obsessive compulsive disorder (OCD) have inferior social functioning compared to healthy controls, but the exact nature of these social deficits, and the underpinning mechanisms, are unknown. We sought to investigate social functioning in patients with OCD by measuring their involuntary/spontaneous processing of social cues using a specifically designed test, which might reveal deficits in these patients that explicit voluntary tasks do not detect. Methods The sample of the study consisted of an OCD group (n = 25) and a control group (n = 26). Both groups performed an adaptation of the Social Distance Judgment Task (SDJT; Jellema et al., 2009), in which participants have to judge the geometrical distance between two human cartoon figures presented on a computer screen. Head/gaze direction and body direction were manipulated to be either compatible, i.e. both directed to the left or to the right (Compatible condition) or incompatible, i.e. body directed toward the observer (frontal view) and head/gaze directed to the left or right (Incompatible condition). Results In the Compatible condition, controls nor OCD patients were influenced by the social cues in their judgments of the geometrical distances. However, in the Incompatible condition, where the attentional cue was more conspicuous, both groups were influenced by the cues, but the controls to a significantly larger extent than the OCD patients. Conclusions This study showed that patients with OCD are less likely, compared to controls, to automatically/spontaneously integrate the other’s direction of attention into their visual percept. This may have resulted in their judgments of the geometrical distances between the agents to be more accurate than those of controls. The suggested impairment in automatically integrating social cues may have important repercussions for the social functioning of OCD patients

Facial emotion processing in schizophrenia : a non-specific neuropsychological deficit?

Original article can be found at : http://journals.cambridge.org/ Copyright Cambridge University PressBackground: Identification of facial emotions has been found to be impaired in schizophrenia but there are uncertainties about the neuropsychological specificity of the finding. Method: Twenty-two patients with schizophrenia and 20 healthy controls were given tests requiring identification of facial emotion, judgement of the intensity of emotional expressions without identification, familiar face recognition and the Benton Facial Recognition Test (BFRT). The schizophrenia patients were selected to be relatively intellectually preserved. Results: The patients with schizophrenia showed no deficit in identifying facial emotion, although they were slower than the controls. They were, however, impaired on judging the intensity of emotional expression without identification. They showed impairment in recognizing familiar faces but not on the BFRT. Conclusions: When steps are taken to reduce the effects of general intellectual impairment, there is no deficit in identifying facial emotions in schizophrenia. There may, however, be a deficit in judging emotional intensity. The impairment found in naming familiar faces is consistent with other evidence of semantic memory impairment in the disorder.Peer reviewe