Cognitive impairments associated with formal thought disorder in people with schizophrenia

Formal thought disorder (FTD), or disorganized speech, is one of the central signs of schizophrenia. Despite extensive research, the cognitive processes associated with FTD are still unclear. However, the authors' review of FTD theories and research indicates that considerable progress has been made in identifying possible cognitive impairments associated with FTD. Specifically, FTD is strongly associated with impaired executive functioning and with impaired processing of semantic information. Their review indicates that previous research has not yet supported an association between FTD and either an increase in spreading activation or an impairment within the language production system.     

Verbal Declarative Memory Dysfunction in Schizophrenia: From Clinical Assessment to Genetics and Brain Mechanisms

The recent literature on the neuropsychology of schizophrenia has emphasized memory deficits as a key area of impairment. Abnormalities in the medial temporal lobe, a brain region crucial for long-term memory formation, have also consistently been reported. We conducted a comprehensive review of verbal declarative memory (VDM) in schizophrenia with the aim of systematically addressing the nature of this impairment. We conclude that verbal declarative memory is significantly impaired in schizophrenia and is largely accounted for by deficits in the encoding stage. Subtle impairments in increased rates of forgetting are present, but are mild compared with those in amnestic disorders. Impairment in other cognitive domains studied thus far (e.g., attention), medication effects, or fluctuations in symptoms do not completely account for the deficit. VDM is among the most impaired neurocognitive domains in schizophrenia (along with attention and executive functions). Milder encoding deficits are present in high-risk subjects and non-psychotic relatives of individuals with schizophrenia suggesting that components of the deficit are associated with a genetic vulnerability to the illness, and are independent of the frank psychotic illness. Furthermore, VDM is observed in individuals experiencing their first-psychotic episode and it remains fairly consistent over time. Preliminary imaging studies and other work suggest abnormalities in prefrontal-hippocampal processing networks. Future work should emphasize delineating specific information processing components contributing to the deficit. This would allow imaging studies to determine which brain regions contribute to specific information processing deficits in schizophrenia.     

The importance of impaired physical health and age in normal cognitive aging

The objective of this study was to investigate the importance of impaired physical health and age in normal cognitive aging. In our cross-sectional, clinical and explorative study, medical and neuropsychological data from 118 voluntary healthy controls aged 26-91 years were collected from five recruitment occasions. Health was assessed according to a criterion reflecting clinical and subclinical severity. The examinations included a clinical investigation, brain neuroimaging, and a comprehensive neuropsychological assessment. Regression analyses showed a significant incidence of clinical and subclinical medical disorders that explained 10.8% of the variation in cognitive performance, while age-related impairment explained 5.6%. Findings of the central nervous system were important but various other medical findings explained about half of the health-related variation. Cognitively demanding tasks were more susceptible to impaired physical health while tasks comprising salient motor- and visual spatial elements were more prone to be impaired by age. Our findings suggest (1) that impaired physical health is more important than chronological age in accounting for cognitive impairment across the adult lifespan, (2) that age and health dissociate with regard to cognitive functions affected, and (3) that selection for so-called "super healthy" elderly people might be justified in cognitive research. Because the prevalent diseases in normal aging are potentially preventable, the present findings promise good prospect for prevention of future cognitive disability among elderly people.     

Effects of early sensorimotor disorder on contextual learning in autism

Cognitive explanations of autism often involve higher order cognitive functions developing late in childhood, such as theory of mind, executive functions or central coherence. In home videos of infants later diagnosed with autism, children display early signs of developmental disorders, for example impaired sensorimotor functions, attention to social and non-social stimuli and a lack of circadian regulation. We propose that these early signs need to be understood using a framework of context learning. It is also important to understand the role for context understanding in guiding the maturation of behavior. The role for inhibition in context learning as understood within learning theory provides us with helpful tools for this analysis. Our research aim is not to identify and explain early markers for autism, but to understand the cognitive developmental pathway set into rolling by an early impairment. This will help us understand the seemingly unrelated symptoms that define the complex syndrome of autism.     

Memory-Prediction Errors and Their Consequences in Schizophrenia

Cognitive deficits play a central role in the onset of schizophrenia. Cognitive impairment precedes the onset of psychosis in at least a subgroup of patients, and accounts for considerable dysfunction. Yet cognitive deficits as currently measured are not significantly related to hallucinations and delusions. Part of this counterintuitive absence of a relationship may be caused by the lack of an organizing principle of cognitive impairment in schizophrenia research. We review literature suggesting that a system of memory-based prediction is central to human perception, thought and action , and forward the notion that many of the symptoms of schizophrenia are a result of a failure of this system.     

Social cognition and its neural correlates in schizophrenia and autism

The study of social cognition in psychiatric disorders has become increasingly popular in recent years. This is due to the its proposed link to social functioning and the inability of general neurocognitive skills to explain the spectrum of impairments observed in patients. This article reviews research into two of the processes thought to underlie social cognition (emotion perception and theory of mind) in schizophrenia and autism. This is followed by a look at neuroimaging studies and their efforts to localize the neural correlates of emotion perception and theory of mind in the two disorders. We concluded that while a specific impairment in emotion perception and theory of mind skills cannot be generalized to all individuals with autism and schizophrenia, there are subpopulations that have lingering deficits of social cognition tasks. Neuroimaging work consistently points to the involvement of the fusiform gyrus and amygdala in emotion processing, while the medial prefrontal and frontal cortex are implicated in tasks invoking theory of mind. We propose that deficits of social cognition may benefit from cognitive remediation therapy and pharmacological cognitive enhancers.     

Neuropsychological profile in patients with schizotypal personality disorder or schizophrenia

Neuropsychological impairments have been consistently reported in patients with schizophrenia. As little is known whether subjects with schizotypal personality disorder exhibit neurocognitive dysfunction similar to that in schizophrenia, we assessed the neuropsychological profile of 15 subjects with schizotypal personality disorder and compared it with that for 15 patients with schizophrenia and for 15 psychiatrically normal volunteers. All participants were administered a standard neuropsychological battery assessing language ability, spatial ability, visuomotor function, verbal memory, visual memory, auditory attention, visual attention, and executive function. Performance on most of the cognitive domains was impaired in patients with schizotypal personality disorder but less than patients with schizophrenia. Specifically, impairment in verbal memory and visuomotor ability in patients with schizotypal personality disorder and patients with schizophrenia were comparable, while patients with schizophrenia performed worse on the test of executive function than did patients with schizotypal personality disorder. As a whole, cognitive deficits in patients with schizotypal personality disorder were qualitatively similar to, but quantitatively milder than, those for patients with schizophrenia. The results suggest that cognitive abilities related to frontotemporal lobe function are disturbed across these schizophrenia-spectrum disorders.     

EEG theta phase coupling during executive control of visual working memory investigated in individuals with schizophrenia and in healthy controls

In healthy humans, it has been shown that executive functions are associated with increased frontal-midline EEG theta activity and theta phase coupling between frontal and posterior brain regions. In individuals with schizophrenia, central executive functions are supposed to be heavily impaired. Given that theta phase coupling is causally involved in central executive functions, one would expect that patients with an executive function deficit should display abnormal EEG theta synchronization. We therefore investigated executive functioning in 21 healthy controls and 21 individuals with schizophrenia while they performed a visuospatial delayed match to sample task. The task required either high executive demands (manipulation of content in working memory [WM]) or low executive demands (retention of WM content). In addition, WM load (one vs. three items) was varied. Results indicated higher frontal theta activity for manipulation processes than for retention processes in patients with schizophrenia, as compared with healthy controls, independently of WM load. Furthermore, individuals with schizophrenia revealed a reduction in theta phase coupling during early stages of the delay period for retention, as well as for manipulation processes at high-WM loads. Deviations in theta phase coupling in individuals with schizophrenia were mainly characterized by aberrant fronto-posterior connections, but also by attenuated posterior connections during manipulation of high-WM load. To conclude, fronto-parietal theta coupling seems to be substantially involved in executive control, whereas frontal theta activity seems to reflect general task demands, such as deployment of attentional resources during WM.     

In search of common foundations for cortical computation

It is worthwhile to search for forms of coding, processing, and learning common to various cortical regions and cognitive functions. Local cortical processors may coordinate their activity by maximizing the transmission of information coherently related to the context in which it occurs, thus forming synchronized population codes. This coordination involves contextual field (CF) connections that link processors within and between cortical regions. The effects of CF connections are distinguished from those mediating receptive field (RF) input; it is shown how CFs can guide both learning and processing without becoming confused with the transmission of RF information. Simulations explore the capabilities of networks built from local processors with both RF and CF connections. Physiological evidence for synchronization, CFs, and plasticity of the RF and CF connections is described. Coordination via CFs is related to perceptual grouping, the effects of context on contrast sensitivity, amblyopia, implicit influences of color in achromotopsia, object and word perception, and the discovery of distal environmental variables and their interactions through self-organization. Cortical computation could thus involve the flexible evaluation of relations between input signals by locally specialized but adaptive processors whose activity is dynamically associated and coordinated within and between regions through specialized contextual connections.     

Working memory deficits, increased anxiety-like traits, and seizure susceptibility in BDNF overexpressing mice

BDNF regulates components of cognitive processes and has been implicated in psychiatric disorders. Here we report that genetic overexpression of the BDNF mature isoform (BDNF-tg) in female mice impaired working memory functions while sparing components of fear conditioning. BDNF-tg mice also displayed reduced breeding efficiency, higher anxiety-like scores, high self-grooming, impaired prepulse inhibition, and higher susceptibility to seizures when placed in a new empty cage, as compared with wild-type (WT) littermate controls. Control measures of general health, locomotor activity, motor coordination, depression-related behaviors, and sociability did not differ between genotypes. The present findings, indicating detrimental effects of life-long increased BDNF in mice, may inform human studies evaluating the role of BDNF functional genetic variations on cognitive abilities and vulnerability to psychiatric disorders.     

Identification of tone duration, line length, and letter position: an experimental approach to timing and working memory deficits in schizophrenia

Patients with schizophrenia display numerous cognitive deficits, including problems in working memory, time estimation, and absolute identification of stimuli. Research in these fields has traditionally been conducted independently. We examined these cognitive processes using tasks that are structurally similar and that yield rich error data. Relative to healthy control participants (n = 20), patients with schizophrenia (n = 20) were impaired on a duration identification task and a probed-recall memory task but not on a line-length identification task. These findings do not support the notion of a global impairment in absolute identification in schizophrenia. However, the authors suggest that some aspect of temporal information processing is indeed disturbed in schizophrenia.     

Emotion processing deficits in the different dimensions of psychometric schizotypy

Schizotypy refers to a personality structure indicating “proneness” to schizophrenia. Around 10% of the general population has increased schizotypal traits, they also share other core features with schizophrenia and are thus at heightened risk for developing schizophrenia and spectrum disorders. A key aspect in schizophrenia‐spectrum pathology is the impairment observed in emotion‐related processes. This review summarizes findings on impairments related to central aspects of emotional processes, such as emotional disposition, alexithymia, facial affect recognition and speech prosody, in high schizotypal individuals in the general population. Although the studies in the field are not numerous, the current findings indicate that all these aspects of emotional processing are deficient in psychometric schizotypy, in accordance to the schizophrenia‐spectrum literature. A disturbed frontotemporal neural network seems to be the critical link between these impairments, schizotypy and schizophrenia. The limitations of the current studies and suggestions for future research are discussed.     

Emotion-cognition interaction in people at familial high risk for schizophrenia: the impact of sex differences

Cognitive deficits are fundamental to schizophrenia, and research suggests that negative emotion abnormally interferes with certain cognitive processes in those with the illness. To a lesser extent, cognitive impairment is found in persons at risk for schizophrenia, but there is limited research on the impact of emotion on cognitive processing in at-risk groups. It is unknown whether interference of negative emotion precedes illness and contributes to vulnerability for the disorder. We studied the extent to which negative emotional information interferes with working memory in 21 adolescent and young adult first-degree relatives of people with schizophrenia and 22 community controls. Groups were comparable in age, sex, education, ethnicity, and socioeconomic status. Primary measures were n-back tasks varying in cognitive load (1-back, 2-back, 3-back) with emotional faces (neutral, happy, fearful) as stimuli. The control group's response times (RTs) and the women's RTs, regardless of group, differed depending on the emotion condition. In contrast, the RTs of the relatives and of the men, regardless of group, did not differ by emotion. This study is the first to examine emotion-cognition interactions in relatives of individuals with schizophrenia. Reduced efficiency in processing emotional information may contribute to a greater vulnerability for schizophrenia that may be heightened in men. Additional research with larger samples of men and women is needed to test these preliminary findings.     

Dichotic listening,executive functions and grey matter cortical volume in patients with schizophrenia and healthy controls

Schizophrenia is characterized by cognitive impairment, especially in relation to executive functions. Brain structural abnormalities are also often seen in schizophrenia although little is known of the relationship between cognitive impairment and structural brain changes. Our aim was therefore to investigate this relationship further using MRI and a dichotic listening (DL) task with simple speech sounds and with instructions to focus attention and report only from the left or right ear stimulus. When instructed to focus attention on the left ear syllable a cognitive conflict is induced requiring the allocation of executive resources to be resolved. Grey matter (GM) volume was measured with MRI from four volumes of interests (VOIs), left and right frontal and temporal cortex, respectively, and correlated with DL performance. The results showed significant differences between the groups in their ability to focus attention on and report the left ear stimulus, which was accompanied by reduced GM volume in the left frontal and right temporal lobe VOIs. There was also a significant positive correlation between left frontal GM volume and performance on the DL task, for the groups combined. The results did not support a conclusion that an impairment in cognitive function in schizophrenia was driven by an corresponding impairment in brain structure, since there were no significant correlations when the groups were analyzed separately. It is however concluded that patients with schizophrenia are impaired in executive functions and that they also show reduced GM volumes in left frontal and right temporal lobe areas, compared to healthy controls.     

Un déficit de mémoire de la source spécifique chez les patients schizophrènes comparés à des volontaires sains et des patients présentant un épisode dépressif majeur

One of the main cognitive models of positive symptoms in schizophrenia proposes that they arise through impaired self-monitoring. The most replicated findings is that, compared to healthy volunteers, schizophrenics patients have impairment in source monitoring tasks required to distinguish between memories of their self-generated material and externally generated events, generally words, as a consequence of a malfunction in either a central monitor or in a reality discrimination process. However, only few studies have investigated the specificity of those tasks. The aim of this study was to compare performances in 2 source monitoring tasks of 3 groups: 30 schizophrenic patients with positive symptoms, 22 patients presenting a major depressive disorder and 24 healthy volunteers. Tasks were built using current French words extracted from a verbal fluency task. We reported a specific significant deficit in source monitoring task in patients with schizophrenia, no difference was observed between healthy volunteers and major depressive disorder patients.     

Motor fluency deficits in the sequencing of actions in schizophrenia

Many everyday activities depend on the capacity to organize and smoothly execute motor sequences. The authors tested the hypothesis that a sequencing deficit is associated with schizophrenia. They used a new method to distinguish between lower and higher order mechanisms for the impairment. The 1st task involved triggered sequences in which sensory information from 1 movement was the cue for initiation of the following movement. Results showed that the motor sequences were performed as fluently in patients as in controls. The 2nd and 3rd tasks involved sequences in which the entire movement sequence could be preplanned. Patients executed the sequences less fluently than controls but only under the condition where action sequences were required. Furthermore, the patients' fluency deficit increased with sequence complexity. The high discrimination power of Task 3 gave the authors a means to control for a potential psychometric confound involving differential discriminating power and to argue in favor of a specific higher order motor fluency deficit in patients with schizophrenia. It is suggested that basic lower order mechanisms that integrate sensory information with outgoing motor commands are preserved in schizophrenia, whereas higher order integrative mechanisms that are required for the smooth coordination of motor sequences are impaired.     

Quantitative evidence for distinct cognitive impairment in anorexia nervosa and bulimia nervosa

It is generally agreed that at least some aspects of abnormal eating behaviour is indeed due in part to disordered cognition. The accumulated literature illustrates cognitive impairment in patients with anorexia nervosa (AN) and bulimia nervosa (BN). Yet beyond being inconsistent, these independent studies also do not reveal the magnitude of impairment within and across studies and fail to give due consideration to the magnitude of impairment so as to understand the severity and breadth of impairment and/or differences in cognitive profiles between patients with AN and BN. Hence, the present review on the subject sought to articulate the magnitude of cognitive impairment in patients with AN and BN by quantitatively synthesizing the existing literature using meta-analytic methodology. The results demonstrate modest evidence of cognitive impairment specific to AN and BN that is related to body mass index in AN in terms of its severity, and is differentially impaired between disorders. Together, these results suggest that disturbed cognition is figural in the presentation of eating disorders and may serve to play an integral role in its cause and maintenance. Implications of these findings with respects to future research are discussed.     

Development of eye-movement control

Cognitive control of behavior continues to improve through adolescence in parallel with important brain maturational processes including synaptic pruning and myelination, which allow for efficient neuronal computations and the functional integration of widely distributed circuitries supporting top-down control of behavior. This is also a time when psychiatric disorders, such as schizophrenia and mood disorders, emerge reflecting a particularly vulnerability to impairments in development during adolescence. Oculomotor studies provide a unique neuroscientific approach to make precise associations between cognitive control and brain circuitry during development that can inform us of impaired systems in psychopathology. In this review, we first describe the development of pursuit, fixation, and visually-guided saccadic eye movements, which collectively indicate early maturation of basic sensorimotor processes supporting reflexive, exogenously-driven eye movements. We then describe the literature on the development of the cognitive control of eye movements as reflected in the ability to inhibit a prepotent eye movement in the antisaccade task, as well as making an eye movement guided by on-line spatial information in working memory in the oculomotor delayed response task. Results indicate that the ability to make eye movements in a voluntary fashion driven by endogenous plans shows a protracted development into adolescence. Characterizing the transition through adolescence to adult-level cognitive control of behavior can inform models aimed at understanding the neurodevelopmental basis of psychiatric disorders.     

Conflict and Cognitive Control in the Brain

ABSTRACT— Recent research from cognitive psychology and cognitive neuroscience has suggested that the control mechanisms by which people are able to regulate task performance can be dissociated into evaluative and executive components. One process, implemented in the anterior cingulate cortex of the brain, monitors the amount of conflict that occurs during information processing; another process, implemented in the dorsolateral prefrontal cortex, is involved with maintaining the requirements of the task at hand and with biasing information processing in favor of appropriate responses. In the current article, we review this theory and some of the research that has supported it, including its implication for understanding cognitive disturbances in clinical disorders such as schizophrenia and obsessive-compulsive disorder. We conclude by addressing several interesting possibilities for future research.     

Role of individual neurons and neural networks in cognitive functioning of the brain: a new insight

The prevailing concept in modern neuroscience is that neuron networks play a dominant role in the functioning of the nervous system, whereas the role of individual neurons is rather insignificant. This concept suggests that "individuality" of single neurons is primarily determined by their place in a network rather than their intrinsic properties. Here I argue that individual neurons may play an important, if not decisive, role in performing cognitive functions of the brain. This tentative viewpoint is supported by experimental and clinical insights into disorders of cognitive functions and by genetic studies of cognitive abilities and disabilities. The results obtained in these studies indicate that many specific cognitive functions are carried out by groups of highly specialized neurons whose roles in performing these functions are genetically predetermined and their activity could not be substituted by the activity of other neurons. In this context, the main role of neural networks and intercellular interactions is to form dynamic ensembles of neurons involved in performing a given cognitive function.