Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls.

BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.

DWI and complex brain network analysis predicts vascular cognitive impairment in spontaneous hypertensive rats undergoing executive function tests

The identification of biomarkers of vascular cognitive impairment is urgent for its early diagnosis. The aim of this study was to detect and monitor changes in brain structure and connectivity, and to correlate them with the decline in executive function. We examined the feasibility of early diagnostic magnetic resonance imaging (MRI) to predict cognitive impairment before onset in an animal model of chronic hypertension: Spontaneously Hypertensive Rats. Cognitive performance was tested in an operant conditioning paradigm that evaluated learning, memory, and behavioral flexibility skills. Behavioral tests were coupled with longitudinal diffusion weighted imaging acquired with 126 diffusion gradient directions and 0.3 mm(3) isometric resolution at 10, 14, 18, 22, 26, and 40 weeks after birth. Diffusion weighted imaging was analyzed in two different ways, by regional characterization of diffusion tensor imaging (DTI) indices, and by assessing changes in structural brain network organization based on Q-Ball tractography. Already at the first evaluated times, DTI scalar maps revealed significant differences in many regions, suggesting loss of integrity in white and gray matter of spontaneously hypertensive rats when compared to normotensive control rats. In addition, graph theory analysis of the structural brain network demonstrated a significant decrease of hierarchical modularity, global and local efficacy, with predictive value as shown by regional three-fold cross validation study. Moreover, these decreases were significantly correlated with the behavioral performance deficits observed at subsequent time points, suggesting that the diffusion weighted imaging and connectivity studies can unravel neuroimaging alterations even overt signs of cognitive impairment become apparent.

Mild Cognitive Impairment and Early Detection of Alzheimer`s Disease. A Positron Emission Tomography Study

Alzheimer`s disease (AD) is characterised neuropathologically by the presence of extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and cerebral neuronal loss. The pathological changes in AD are believed to start even decades before clinical symptoms are detectable. AD gradually affects episodic memory, cognition, behaviour and the ability to perform everyday activities. Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially AD. The predictive accuracy of the current and commonly used MCI criteria devide this disorder into amnestic (aMCI) and non-amnestic (naMCI) MCI. It seems that many individuals with aMCI tend to convert to AD. However many MCI individuals will remain stable and some may even recover. At present, the principal drugs for the treatment of AD provide only symptomatic and palliative benefits. Safe and effective mechanism-based therapies are needed for this devastating neurodegenerative disease of later life. In conjunction with the development of new therapeutic drugs, tools for early detection of AD would be important. In future one of the challenges will be to detect at an early stage these MCI individuals who will convert to AD. Methods which can predict which MCI subjects will convert to AD will be much more important if the new drug candidates prove to have disease-arresting or even disease–slowing effects. These types of drugs are likely to have the best efficacy if administered in the early or even in the presymptomatic phase of the disease when the synaptic and neuronal loss has not become too widespread. There is no clinical method to determine with certainly which MCI individuals will progress to AD. However there are several methods which have been suggested as predictors of conversion to AD, e.g. increased [11C] PIB uptake, hippocampal atrophy in MRI, low CSF A beta 42 level, high CSF tau-protein level, apolipoprotein E (APOE) ε4 allele and impairment in episodic memory and executive functions. In the present study subjects with MCI appear to have significantly higher [¹¹C] PIB uptake vs healthy elderly in several brain areas including frontal cortex, the posterior cingulate, the parietal and lateral temporal cortices, putamen and caudate. Also results from this PET study indicate that over time, MCI subjects who display increased [¹¹C] PIB uptake appear to be significantly more likely to convert to AD than MCI subjects with negative [¹¹C] PIB retention. Also hippocampal atrophy seems to increase in MCI individuals clearly during the conversion to AD. In this study [¹¹C] PIB uptake increases early and changes relatively little during the AD process whereas there is progressive hippocampal atrophy during the disease. In addition to increased [¹¹C] PIB retention and hippocampal atrophy, the status of APOE ε4 allele might contribute to the conversion from MCI to AD.

Long-term habituation (LTH) in the crab Chasmagnathus: a model for behavioral and mechanistic studies of memory

A decade of studies on long-term habituation (LTH) in the crab Chasmagnathus is reviewed. Upon sudden presentation of a passing object overhead, the crab reacts with an escape response that habituates promptly and for at least five days. LTH proved to be an instance of associative memory and showed context, stimulus frequency and circadian phase specificity. A strong training protocol (STP) (³15 trials, intertrial interval (ITI) of 171 s) invariably yielded LTH, while a weak training protocol (WTP) (£10 trials, ITI = 171 s) invariably failed. STP was used with a presumably amnestic agent and WTP with a presumably hypermnestic agent. Remarkably, systemic administration of low doses was effective, which is likely to be due to the lack of an endothelial blood-brain barrier. LTH was blocked by inhibitors of protein and RNA synthesis, enhanced by protein kinase A (PKA) activators and reduced by PKA inhibitors, facilitated by angiotensin II and IV and disrupted by saralasin. The presence of angiotensins and related compounds in the crab brain was demonstrated. Diverse results suggest that LTH includes two components: an initial memory produced by spaced training and mainly expressed at an initial phase of testing, and a retraining memory produced by massed training and expressed at a later phase of testing (retraining). The initial memory would be associative, context specific and sensitive to cycloheximide, while the retraining memory would be nonassociative, context independent and insensitive to cycloheximide

The brain decade in debate: I. Neurobiology of learning and memory

This article is a transcription of an electronic symposium in which some active researchers were invited by the Brazilian Society for Neuroscience and Behavior (SBNeC) to discuss the last decade's advances in neurobiology of learning and memory. The way different parts of the brain are recruited during the storage of different kinds of memory (e.g., short-term vs long-term memory, declarative vs procedural memory) and even the property of these divisions were discussed. It was pointed out that the brain does not really store memories, but stores traces of information that are later used to create memories, not always expressing a completely veridical picture of the past experienced reality. To perform this process different parts of the brain act as important nodes of the neural network that encode, store and retrieve the information that will be used to create memories. Some of the brain regions are recognizably active during the activation of short-term working memory (e.g., prefrontal cortex), or the storage of information retrieved as long-term explicit memories (e.g., hippocampus and related cortical areas) or the modulation of the storage of memories related to emotional events (e.g., amygdala). This does not mean that there is a separate neural structure completely supporting the storage of each kind of memory but means that these memories critically depend on the functioning of these neural structures. The current view is that there is no sense in talking about hippocampus-based or amygdala-based memory since this implies that there is a one-to-one correspondence. The present question to be solved is how systems interact in memory. The pertinence of attributing a critical role to cellular processes like synaptic tagging and protein kinase A activation to explain the memory storage processes at the cellular level was also discussed.

Neuropsychological rehabilitation of memory deficits and activities of daily living in patients with Alzheimer's disease: a pilot study

Patients with Alzheimer's disease (AD) gradually lose their cognitive competence, particularly memory, and the ability to perform daily life tasks. Neuropsychological rehabilitation is used to improve cognitive functions by facilitating memory performance through the use of external aids and internal strategies. The effect of neuropsychological rehabilitation through memory training - motor movements, verbal association, and categorization - and activities of daily living (ADL) training was tested in a sample of 5 elderly out-patients (mean age: 77.4 ± 2.88 years), with mild AD (Mini-Mental State Examination score: 22.20 ± 2.17) and their caregivers. All patients had been taking rivastigmine (6-12 mg/day) for at least 3 months before being assigned to the rehabilitation sessions, and they continued to take the medication during the whole program. Just before and after the 14-week neuropsychological rehabilitation program all patients were assessed by interviewers that did not participate in the cognitive training, using the Mini-Mental State Examination, Montgomery-Alsberg Depression Rating Scale, Hamilton Anxiety Scale, Interview to Determine Deterioration in Functioning in Dementia, Functional Test, Memory Questionnaire of Daily Living for patient and caregiver, Quality of Life Questionnaire for patient and caregiver, and a neuropsychological battery. The results showed a statistically significant improvement in ADL measured by Functional Test (P = 0.04), and only a small improvement in memory and psychiatric symptoms. Our results support the view that weekly stimulation of memory and training of ADL is believed to be of great value in AD treatment, not only delaying the progress of the disease, but also improving some cognitive functions and ADL, even though AD is a progressively degenerative disease.

Cognitive performance of young and elderly subjects on the free word recall memory test: effect of presentation order on recall order

The influence of aging on memory has been extensively studied, but the importance of short-term memory and recall sequence has not. The objective of the current study was to examine the recall order of words presented on lists and to determine if age affects recall sequence. Physically and psychologically healthy male subjects were divided into two groups according to age, i.e., 23 young subjects (20 to 30 years) and 50 elderly subjects (60 to 70 years) submitted to the Wechsler Adult Intelligence Scale-Revised and the free word recall test. The order of word presentation significantly affected the 3rd and 4th words recalled (P < 0.01; F = 14.6). In addition, there was interaction between the presentation order and the type of list presented (P < 0.05; F = 9.7). Also, both groups recalled the last words presented from each list (words 13-15) significantly more times 3rd and 4th than words presented in all remaining positions (P < 0.01). The order of word presentation also significantly affected the 5th and 6th words recalled (P = 0.05; F = 7.5) and there was a significant interaction between the order of presentation and the type of list presented (P < 0.01; F = 20.8). The more developed the cognitive functions, resulting mainly from formal education, the greater the cognitive reserve, helping to minimize the effects of aging on the long-term memory (episodic declarative).

Memory mixed with desire : a preliminary study of philosophy and literature in the works of Friedrich Nietzsche and Milan Kundera

Memory Mixed with Desire: A preliminary study of Philosophy and Literature in the works of Friedrich Nietzsche and Milan Kundera Robert Spinelli Brock University, Department of Philosophy This thesis studies intertextuality in the works of Friedrich Nietzsche and Milan Kundera through the primary themes of memory and forgetting. The thesis starts with two introductory chapters that delineate memory according to Nietzsche and Kundera respectively. From here, I move into a discussion of Nietzsche's Ubermensch as an example of the type of forgetting that Nietzsche sees as a cure for the overabundance of memory that has led to Christian morality. Next, I explore the Kunderan concept of kitsch as the polar opposite of what Nietzsche has sought in his philosophy, finishing the chapter by tying the two thinkers together in a Kunderan critique of Nietzsche. The thesis ends with a chapter devoted to the Eternal Return beginning with an exegesis of Nietzsche's idea and ending with a similar exegesis of Kundera's treatment of this thought. What I suggest in this chapter is that the Eternal Return might itself be a form of kitsch even in its attempt to revalue existence.

A social-cognitive model of monitoring and its relationship to behaviour in a naturalistic observation : development and individual differences

years 8 months) and 24 older (M == 7 years 4 months) children. A Monitoring Process Model (MPM) was developed and tested in order to ascertain at which component process ofthe MPM age differences would emerge. The MPM had four components: (1) assessment; (2) evaluation; (3) planning; and (4) behavioural control. The MPM was assessed directly using a referential communication task in which the children were asked to make a series of five Lego buildings (a baseline condition and one building for each MPM component). Children listened to instructions from one experimenter while a second experimenter in the room (a confederate) intetjected varying levels ofverbal feedback in order to assist the children and control the component ofthe MPM. This design allowed us to determine at which "stage" ofprocessing children would most likely have difficulty monitoring themselves in this social-cognitive task. Developmental differences were obselVed for the evaluation, planning and behavioural control components suggesting that older children were able to be more successful with the more explicit metacomponents. Interestingly, however, there was no age difference in terms ofLego task success in the baseline condition suggesting that without the intelVention ofthe confederate younger children monitored the task about as well as older children. This pattern ofresults indicates that the younger children were disrupted by the feedback rather than helped. On the other hand, the older children were able to incorporate the feedback offered by the confederate into a plan ofaction. Another aim ofthis study was to assess similar processing components to those investigated by the MPM Lego task in a more naturalistic observation. Together the use ofthe Lego Task ( a social cognitive task) and the naturalistic social interaction allowed for the appraisal of cross-domain continuities and discontinuities in monitoring behaviours. In this vein, analyses were undertaken in order to ascertain whether or not successful performance in the MPM Lego Task would predict cross-domain competence in the more naturalistic social interchange. Indeed, success in the two latter components ofthe MPM (planning and behavioural control) was related to overall competence in the naturalistic task. However, this cross-domain prediction was not evident for all levels ofthe naturalistic interchange suggesting that the nature ofthe feedback a child receives is an important determinant ofresponse competency. Individual difference measures reflecting the children's general cognitive capacity (Working Memory and Digit Span) and verbal ability (vocabulary) were also taken in an effort to account for more variance in the prediction oftask success. However, these individual difference measures did not serve to enhance the prediction oftask performance in either the Lego Task or the naturalistic task. Similarly, parental responses to questionnaires pertaining to their child's temperament and social experience also failed to increase prediction oftask performance. On-line measures ofthe children's engagement, positive affect and anxiety also failed to predict competence ratings.

Investigating the effects of arousal state on cognitive performance in individuals with and without mild head injury

We examined the cognitive and emotional sequelae following mild head injury (MHI; e.g., concussion) in high-functioning individuals and whether persons with MHI pre~ent, both physiologically and via self-report, in a manner different from (i.e., underaroused) that of persons who have no history of head injury. We also investigated the effect arousal state ~as on the cognitive performance of this population. Using a quasiexperimental research design (N = 91), we examined changes in attention, working memory, and cognitive flexibility (subtests ofthe WAIS-III, 1997,WMS-III, 1997, & DKEFS, 2002) as a function of manipulated arousal (i.e., induced psychosocial stress/activation; reduced activation/relaxation). In addition to self-reported arousal and state anxiety (State-Trait Anxiety Inventory; Speilberger, 1983a) measures, physiological indices of arousal state (i.e., electrodermal responsivity, heart rate, and respiration activity) were recorded (via Polygraph Professional Suite, 2008) across a 2.5 hour interval while completing various cognitive tasks. Students also completed the Post-concussive Symptom Checklist (Gouvier et aI., 1992). The results demonstrate that university students who report a history ofMHI (i.e., "altered state of consciousness") experience significantly lower levels of anxiety, were physiologically underaroused, and were less responsive to stressors in their environment, compared to their non-~HI cohorts. As expected, cognitive flexibility (but not other neuropsychological measures of cognition) was advantaged with increased stress, and disadvantaged with reduced stress, in persons with reported MHI, but not for those without reported MHI which provided limited support for our hypothesis. Further, university students who had no complaints related to their previous MHI endorsed a greater number of traditional post-concussive symptoms in terms of intensity, duration and frequency as compared to students who did not report a MHI. The underarousal in traumatic brain injury has been associated with (ventromedial prefrontal cortex) VMPFC disruption and may be implicated in MHI generally. Students who report sustaining a previous MHI may be less able to physiologically respond and/or cognitively appraise, stressful experiences as compared to their no-MHI cohort and experience persistent, long-lasting consequences despite the subtle nature of a history of head injury.

Cognitive consequences of expressive suppression : effects of sex and emotional valence

The present research was designed to examine whether sex and/or emotional valence pl aya role in the cognitive consequences (e.g., memory) of expressive suppression. Seventy-two (36 male and 36 female) undergraduates were randomly assigned to either a control or expressive suppression condition, and were asked to watch silent film clips intended to elicit amusement and disgust. While watching each film, participants listened to sixteen nonemotional words. After each film, participants were asked to answer questions about wha t they had seen in the film (visual memory), to recall as many words as they could (auditory recall memory), and to select from a list any words that they had heard during the previous film clip (auditory recognition memory). With regard to the effects of expressive suppression on visual memory, results indicated a 3-way interaction between condition, sex and film emotion: Men performed more poorly than women on the visual memory test after watching both the amusing and disgusting films in the control condition, and when watching the amusing film in the expressive suppression condition. However, men in the expressive suppression condition performed better than women after watching the disgusting film. In terms of the effects of expressive suppression on auditory memory (recognition and recall), a condition x film emotion interaction indicated that there was no difference in auditory memory for the expressive suppression and control conditions when watching the amusing film, but that the expressive suppression group showed poorer auditory memory than the control group for words presented during the disgusting film. Moreover, a ma in effect of sex on auditory memory suggested that men recalled and recognized more words than women across conditions. Taken together, these findings suggest that both sex and the emotional valence of films may influence the effects of expressive suppression on memory. Results will be discussed in the context of previous literature concerning the effects of expressive suppression on cognition.

Disambiguating the Effects of Social Instability Stress in Adolescence on Learning and Memory Tasks that Involve the Medial Prefrontal Cortex and Hippocampus

Exposure to chronic stress can alter the structure and function of brain regions involved in learning and memory, and these effects are typically long-lasting if the stress occurs during sensitive periods of development. Until recently, adolescence has received relatively little attention as a sensitive period of development, despite marked changes in behaviour, heightened reactivity to stressors, and cognitive and neural maturation. Therefore, the purpose of the present study was to investigate the long-term effects of chronic stress in adolescence on two spatial learning and memory tasks (Morris water maze and Spatial Object Location test) and on a working memory task (Delayed Alternation task). Male rats were randomly assigned to chronic social instability stress (SS; daily 1 hour isolation and subsequent change of cage partner between postnatal days 30 and 45) or to a no-stress control group (CTL). During acquisition learning in the Morris water maze task, SS rats demonstrated impaired long-term memory for the location of the hidden escape platform compared to CTL rats, although the impairment was only seen after the first day of training. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 minutes), but not after shorter delays (15 or 60 minutes) compared to CTL rats. On the Delayed Alternation task, which assessed working memory across delays ranging from 5 to 90 seconds, no group differences were observed. These results are partially in line with previous research that revealed adult impairment on spatial learning and memory tasks after exposure to chronic social instability stress in adolescence. The observed deficits, however, appear to be limited to long-term memory as no group differences were observed during brief periods of retention.

Cognition sociale et traitement du contexte dans la schizophrénie : effets des stéréotypes

Un déficit de la cognition sociale incluant l’attribution d’états mentaux, la perception sociale et la perception des émotions est l’une des caractéristiques les plus handicapantes de la schizophrénie. Les résultats d’une étude par Hardy-Baylé et al. (2003) suggèrent que les difficultés des schizophrènes (SZ) à attribuer des intentions aux autres seraient dues à l’incapacité à utiliser l’information contextuelle. Certaines études (Ivanko & Pexman, 2003; Pexman & Olineck, 2002b) démontrent que des facteurs comme le degré d’incongruité entre le contexte et l’énoncé, l’intonation de la voix et les caractéristiques des personnages peuvent influencer la compréhension de l’intention ironique chez les sujets sains (CT). L’objectif de cette étude est de manipuler des informations contextuelles afin de déterminer si le type de métier du locuteur est un indice social facilitant la compréhension de l’intention du locuteur (théorie de l’esprit ; TdE) et de la perception sociale chez les patients SZ. Trente participants SZ appariés avec trente participants CT ont été recrutés. Ils ont été évalués sur la compréhension de l’ironie et sur la mémoire de travail. Les histoires étaient développées selon deux conditions de métier: un métier favorisant la compréhension de l’ironie (e.g. comédien) et un métier ne favorisant pas la compréhension de l’ironie (e.g. prêtre). Les résultats montrent que les patients SZ ont un trouble de TdE et ils ne semblent pas sensibles aux stéréotypes contrairement aux participants CT. Toutefois, les résultats indiquent que les participants SZ n’ont pas de déficit concernant la perception sociale.

Encountering the suffering other in illness narratives : between the memory of suffering and the suffering memory

Cette étude porte sur la dimension intersubjective de la souffrance qui affecte le rapport du souffrant à son corps, au temps et à l’espace vécus de même que son identité narrative et sa mémoire narrative. Mon argument principal est que la voix narrative constitue le rapport intersubjectif dans les récits de maladie que les proches écrivent sur leurs partenaires souffrant de cancer de cerveau ou de la maladie d’Alzheimer. Ma discussion est basée sur l’éthique, la phénoménologie, les théories de l’incorporation, les études des récits de vie, la sociologie et l’anthropologie médicales et la narratologie. L’objet de mon étude est l’expérience incorporée de la souffrance dans les récits de maladie et je me concentre sur la souffrance comme perte de la mémoire et du soi narratif. J’analyse le journal How Linda Died de Frank Davey et les mémoires de John Bayley, Iris: A Memoir of Iris Murdoch et Iris and Her Friends: A Memoir of Memory and Desire. J’explore comment les récits de maladie constituent le rapport éthique à l’Autre souffrant de la rupture de la mémoire. La discussion de la voix est située dans le contexte des récits de vie et se propose de dépasser les limites des approches sociologiques et anthropologiques de la voix dans les récits de maladie. Dans ce sens, dans un premier temps je porte mon attention sur des études narratologiques de la voix en indiquant leurs limites. Ma propre définition de la voix narrative est basée sur l’éthique dans la perspective d’Emmanuel Levinas et de Paul Ricœur, sur l’interprétation du temps, de la mémoire et de l’oubli chez St-Augustin et la discussion levinasienne de la constitution intersubjective du temps. J’avance l’idée que la “spontanéité bienveillante” (Ricœur, Soi-même comme un autre 222) articule la voix narrative et l’attention envers l’Autre souffrant qui ne peut plus se rappeler, ni raconter sa mémoire. En reformulant la définition augustinienne du temps qui met en corrélation les modes temporels avec la voix qui récite, j’avance l’idée que la voix est distendue entre la voix présente de la voix présente, la voix présente de la voix passée, la voix présente de la voix future. Je montre comment la voix du soignant est inscrite par et s’inscrit dans les interstices d’une voix interrompue, souffrante. Je définis les récits de vies comme des interfaces textuelles entre le soi et l’Autre, entre la voix du soi et la voix du souffrant, comme un mode de restaurer l’intégrité narrative de l’Autre.