The challenge in understanding cognitive impairment in schizophrenia is that people with this illness have deficits in an array of domains. Here, we briefly review evidence regarding the pattern of ...deficits within three domains: context processing, working memory and episodic memory. We suggest that there may be a common mechanism driving deficits in these domains – an impairment in the ability to actively represent goal information in working memory to guide behavior, a function we refer to as proactive control. We suggest that such deficits in proactive control reflect impairments in dorsolateral prefrontal cortex, its interactions with other brain regions, such as parietal cortex, thalamus and striatum, and the influence of neurotransmitter systems, such as dopamine, GABA and glutamate.
Individuals with disorders that include psychotic symptoms (i.e. psychotic disorders) experience broad cognitive impairments in the chronic state, indicating a dimension of abnormality associated ...with the experience of psychosis. These impairments negatively impact functional outcome, contributing to the disabling nature of schizophrenia, bipolar disorder, and psychotic depression. The robust and reliable nature of cognitive deficits has led researchers to explore the timing and profile of impairments, as this may elucidate different neurodevelopmental patterns in individuals who experience psychosis. Here, we review the literature on cognitive deficits across the life span of individuals with psychotic disorder and psychotic-like experiences, highlighting the dimensional nature of both psychosis and cognitive ability. We identify premorbid generalized cognitive impairment in schizophrenia that worsens throughout development, and stabilizes by the first-episode of psychosis, suggesting a neurodevelopmental course. Research in affective psychosis is less clear, with mixed evidence regarding premorbid deficits, but a fairly reliable generalized deficit at first-episode, which appears to worsen into the chronic state. In general, cognitive impairments are most severe in schizophrenia, intermediate in bipolar disorder, and the least severe in psychotic depression. In all groups, cognitive deficits are associated with poorer functional outcome. Finally, while the generalized deficit is the clearest and most reliable signal, data suggests specific deficits in verbal memory across all groups, specific processing speed impairments in schizophrenia and executive functioning impairments in bipolar disorder. Cognitive deficits are a core feature of psychotic disorders that provide a window into understanding developmental course and risk for psychosis.
Abstract A range of emotional and motivation impairments have long been clinically documented in people with schizophrenia, and there has been a resurgence of interest in understanding the ...psychological and neural mechanisms of the so-called “negative symptoms” in schizophrenia, given their lack of treatment responsiveness and their role in constraining function and life satisfaction in this illness. Negative symptoms comprise two domains, with the first covering diminished motivation and pleasure across a range of life domains and the second covering diminished verbal and non-verbal expression and communicative output. In this review, we focus on four aspects of the motivation/pleasure domain, providing a brief review of the behavioral and neural underpinnings of this domain. First, we cover liking or in-the-moment pleasure: immediate responses to pleasurable stimuli. Second, we cover anticipatory pleasure or wanting, which involves prediction of a forthcoming enjoyable outcome (reward) and feeling pleasure in anticipation of that outcome. Third, we address motivation, which comprises effort computation, which involves figuring out how much effort is needed to achieve a desired outcome, planning, and behavioral response. Finally, we cover the maintenance emotional states and behavioral responses. Throughout, we consider the behavioral manifestations and brain representations of these four aspects of motivation/pleasure deficits in schizophrenia. We conclude with directions for future research as well as implications for treatment.
We investigated the relationship between individual subjects' functional connectomes and 280 behavioral and demographic measures in a single holistic multivariate analysis relating imaging to ...non-imaging data from 461 subjects in the Human Connectome Project. We identified one strong mode of population co-variation: subjects were predominantly spread along a single 'positive-negative' axis linking lifestyle, demographic and psychometric measures to each other and to a specific pattern of brain connectivity.
Following in the footsteps of other large "population neuroscience" studies, the Adolescent Brain Cognitive Development℠ (ABCD) study is the largest in the U.S. assessing brain development. The study ...is examining approximately 11,875 youth from 21 sites from age 9 to 10 for approximately ten years into young adulthood. The ABCD Study® has completed recruitment for the baseline sample generally using a multi-stage probability sample including a stratified random sample of schools. The dataset has a wealth of measured attributes of youths and their environment, including neuroimaging, cognitive, biospecimen, behavioral, youth self-report and parent self-report metrics, and environmental measures. The initial goal of the ABCD Study was to examine risk and resiliency factors associated with the development of substance use, but the project has expanded far beyond this initial set of questions and will also greatly inform our understanding of the contributions of biospecimens (e.g., pubertal hormones), neural alterations, and environmental factors to the development of both healthy behavior and brain function as well as risk for poor mental and physical outcomes. This review outlines how the ABCD Study was designed to elucidate factors associated with the development of negative mental and physical health outcomes and will provide a selective overview of results emerging from the ABCD Study. Such emerging data includes initial validation of new instruments, important new information about the prevalence and correlates of mental health challenges in middle childhood, and promising data regarding neural correlates of both healthy and disordered behavior. In addition, we will discuss the challenges and opportunities to understanding both healthy development and the emergence of risk from ABCD Study data. Finally, we will overview the future directions of this large undertaking and the ways in which it will shape our understanding of the development of risk for poor mental and physical health outcomes.
Individuals with schizophrenia consistently display deficits in a multitude of cognitive domains, but the neurobiological source of these cognitive impairments remains unclear. By analyzing the ...functional connectivity of resting-state functional magnetic resonance imaging (rs-fcMRI) data in clinical populations like schizophrenia, research groups have begun elucidating abnormalities in the intrinsic communication between specific brain regions, and assessing relationships between these abnormalities and cognitive performance in schizophrenia. Here we review studies that have reported analysis of these brain-behavior relationships. Through this systematic review we found that patients with schizophrenia display abnormalities within and between regions comprising (1) the cortico-cerebellar-striatal-thalamic loop and (2) task-positive and task-negative cortical networks. Importantly, we did not observe unique relationships between specific functional connectivity abnormalities and distinct cognitive domains, suggesting that the observed functional systems may underlie mechanisms that are shared across cognitive abilities, the disturbance of which could contribute to the "generalized" cognitive deficit found in schizophrenia. We also note several areas of methodological change that we believe will strengthen this literature.
The Human Connectome Project consortium led by Washington University, University of Minnesota, and Oxford University is undertaking a systematic effort to map macroscopic human brain circuits and ...their relationship to behavior in a large population of healthy adults. This overview article focuses on progress made during the first half of the 5-year project in refining the methods for data acquisition and analysis. Preliminary analyses based on a finalized set of acquisition and preprocessing protocols demonstrate the exceptionally high quality of the data from each modality. The first quarterly release of imaging and behavioral data via the ConnectomeDB database demonstrates the commitment to making HCP datasets freely accessible. Altogether, the progress to date provides grounds for optimism that the HCP datasets and associated methods and software will become increasingly valuable resources for characterizing human brain connectivity and function, their relationship to behavior, and their heritability and genetic underpinnings.
•The Human Connectome Project (HCP) will study brain connectivity in healthy adults.•Data acquisition: multiple imaging modalities, plus behavioral, and genetic data.•Imaging modalities: diffusion MRI, resting-fMRI, task-fMRI, and MEG/EEG.•Extensive refinement and optimization efforts are currently underway.•Data will be made freely available and will enable flexible data mining.
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