What are the functional consequences of neurocognitive deficits in schizophrenia
TL;DR: Verbal memory and vigilance appear to be necessary for adequate functional outcome in schizophrenic patients and may prevent patients from attaining optimal adaptation and hence act as "neurocognitive rate-limiting factors."
Abstract: Objective : It has been well established that schizophrenic patients have neurocognitive deficits, but it is not known how these deficits influence the daily lives of patients. The goal of this review was to determine which, if any, neurocognitive deficits restrict the functioning of schizophrenic patients in the outside world. Method : The author reviewed studies that have evaluated neurocognitive measures as predictors and correlates of functional outcome for schizophrenic patients. The review included 1) studies that have prospectively evaluated specific aspects of neurocognition and community (e.g., social and vocational) functioning (six studies), 2) all known studies of neurocognitive correlates of social problem solving (five studies), and 3) all known studies of the neurocognitive correlates and predictors of psychosocial skill acquisition (six studies). Results : Despite wide variation among studies in the selection of neurocognitive measures, some consistencies emerged. The most consistent finding was that verbal memory was associated with all types of functional outcome. Vigilance was related to social problem solving and skill acquisition. Card sorting predicted community functioning but not social problem solving. Negative symptoms were associated with social problem solving but not skill acquisition. Notably, psychotic symptoms were not significantly associated with outcome measures in any of the studies reviewed. Conclusions : Verbal memory and vigilance appear to be necessary for adequate functional outcome. Deficiencies in these areas may prevent patients from attaining optimal adaptation and hence act as neurocognitive rate-limiting factors. On the basis of this review of the literature, a series of hypotheses are offered for follow-up studies.
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TL;DR: This paper will attempt to confirm the conclusions from a previous review that certain neurocognitive domains (secondary verbal memory, immediate memory, executive functioning as measured by card sorting, and vigilance) are associated with functional outcome.
Abstract: There has been a surge of interest in the functional consequences of neurocognitive deficits in schizophrenia. The published literature in this area has doubled in the last few years. In this paper, we will attempt to confirm the conclusions from a previous review that certain neurocognitive domains (secondary verbal memory, immediate memory, executive functioning as measured by card sorting, and vigilance) are associated with functional outcome. In addition to surveying the number of replicated findings and tallying box scores of results, we will approach the review of the studies in a more thorough and empirical manner by applying a meta-analysis. Lastly, we will discuss what we see as a key limitation of this literature, specifically, the relatively narrow selection of predictor measures. This limitation has constrained identification of mediating variables that may explain the mechanisms for these relationships.
2,911 citations
Cites background or result from "What are the functional consequence..."
...Overall, the meta-analyses convincingly demonstrate what was suggested in the previous review (Green 1996), that each of these four neurocognitive constructs have significant relationships with functional outcome....
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...In a previous review of the literature, we concluded that specific domains of neurocognition were significantly related to functional outcome (Green 1996)....
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...These three outcome domains are similar, but not identical, to the outcome domains used in our previous review of the literature (Green 1996)....
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TL;DR: Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia.
Abstract: Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (γ-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
2,153 citations
TL;DR: Evidence that certain brain disorders, such as schizophrenia, epilepsy, autism, Alzheimer's disease, and Parkinson's are associated with abnormal neural synchronization is reviewed to suggest close correlations between abnormalities in neuronal synchronization and cognitive dysfunctions.
1,956 citations
Cites background from "What are the functional consequence..."
...Cognitive dysfunctions are prominent throughout the course of schizophrenia and have been shown to be a better predictor for outcome than the overt symptoms, suggesting that cognitive deficits represent a core pathology of the disorder (Green, 1996)....
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TL;DR: Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (γ-aminobutyric acid) interneurons and in cortico-cortical connections.
Abstract: Converging evidence from electrophysiological, physiological and anatomical studies suggests that abnormalities in the synchronized oscillatory activity of neurons may have a central role in the pathophysiology of schizophrenia. Neural oscillations are a fundamental mechanism for the establishment of precise temporal relationships between neuronal responses that are in turn relevant for memory, perception and consciousness. In patients with schizophrenia, the synchronization of beta- and gamma-band activity is abnormal, suggesting a crucial role for dysfunctional oscillations in the generation of the cognitive deficits and other symptoms of the disorder. Dysfunctional oscillations may arise owing to anomalies in the brain's rhythm-generating networks of GABA (gamma-aminobutyric acid) interneurons and in cortico-cortical connections.
1,813 citations
TL;DR: A plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention, and implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
Abstract: Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
1,774 citations
Cites background or result from "What are the functional consequence..."
...Since strongly recurrent working memory circuits are particularly prone to fast oscillations, as we discussed in section VIE, abnormal gamma or beta rhythm observed in schizophrenia could be a sign of an impaired working memory circuitry (1033), in line with the well-documented working memory and selective attention deficits associated with schizophrenia (52, 258, 363, 379)....
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...Cognitive deficits are at the core of a wide range of mental pathologies in schizophrenia (379)....
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