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Neural mechanisms of mood-induced modulation of reality monitoring in schizophrenia.

ABSTRACT: Reality monitoring is the ability to accurately distinguish the source of self-generated information from externally-presented information. Although people with schizophrenia (SZ) show impaired reality monitoring, nothing is known about how mood state influences this higher-order cognitive process. Accordingly, we induced positive, neutral and negative mood states to test how different mood states modulate subsequent reality monitoring performance. Our findings indicate that mood affected reality monitoring performance in HC and SZ participants in both similar and dissociable ways. Only a positive mood facilitated task performance in Healthy Control (HC) subjects, whereas a negative mood facilitated task performance in SZ subjects. Yet, when both HC and SZ participants were in a positive mood, they recruited medial prefrontal cortex (mPFC) to bias better subsequent self-generated item identification, despite the fact that mPFC signal was reduced in SZ participants. Additionally, in SZ subjects, negative mood states also modulated left and right dorsal mPFC signal to bias better externally-presented item identification. Together our findings reveal that although the mPFC is hypoactive in SZ participants, mPFC signal plays a functional role in mood-cognition interactions during both positive and negative mood states to facilitate subsequent reality monitoring decision-making.

SUBMITTER: Subramaniam K

PROVIDER: S-EPMC5749425 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Neural mechanisms of mood-induced modulation of reality monitoring in schizophrenia.

Subramaniam Karuna K Ranasinghe Kamalini G KG Mathalon Daniel D Nagarajan Srikantan S Vinogradov Sophia S

Cortex; a journal devoted to the study of the nervous system and behavior 20170112

Reality monitoring is the ability to accurately distinguish the source of self-generated information from externally-presented information. Although people with schizophrenia (SZ) show impaired reality monitoring, nothing is known about how mood state influences this higher-order cognitive process. Accordingly, we induced positive, neutral and negative mood states to test how different mood states modulate subsequent reality monitoring performance. Our findings indicate that mood affected realit ...[more]

PMID: 28162778

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Project description:BACKGROUND:Mood disorders are expressed in many heterogeneous forms, varying from anxiety to severe major clinical depression. The disorders are expressed in individual variety through manifestations governed by co-morbidities, symptom frequency, severity, and duration, and the effects of genes on phenotypes. The underlying etiologies of mood disorders consist of complex interactive operations of genetic and environmental factors. The notion of endophenotypes, which encompasses the markers of several underlying liabilities to the disorders, may facilitate efforts to detect and define, through staging, the genetic risks inherent to the extreme complexity of disease state. AIMS:This review evaluates the role of genetic biomarkers in assisting clinical diagnosis, identification of risk factors, and treatment of mood disorders. METHODS:Through a systematic assessment of studies investigating the epigenetic basis for mood disorders, the present review examines the interaction of genes and environment underlying the pathophysiology of these disorders. RESULTS:The majority of research findings suggest that the notion of endophenotypes, which encompasses the markers of several underlying liabilities to the disorders, may facilitate efforts to detect and define, through staging, the genetic risks inherent to the extreme complexity of the disease states. Several strategies under development and refinement show the propensity for derivation of essential elements in the etiopathogenesis of the disorders affecting drug-efficacy, drug metabolism, and drug adverse effects, e.g., with regard to selective serotonin reuptake inhibitors. These include: transporter gene expression and genes encoding receptor systems, hypothalamic-pituitary-adrenal axis factors, neurotrophic factors, and inflammatory factors affecting neuroimmune function. Nevertheless, procedural considerations of pharmacogenetics presume the parallel investment of policies and regulations to withstand eventual attempts at misuse, thereby ensuring patient integrity. CONCLUSIONS:Identification of genetic biomarkers facilitates choice of treatment, prediction of response, and prognosis of outcome over a wide spectrum of symptoms associated with affective states, thereby optimizing clinical practice procedures. Epigenetic regulation of primary brain signaling, e.g., serotonin and hypothalamic-pituitary-adrenal function, and factors governing their metabolism are necessary considerations. The participation of neurotrophic factors remains indispensable for neurogenesis, survival, and functional maintenance of brain systems.

Project description:BackgroundThe significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients.MethodsIn the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups.ResultsPatients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate.ConclusionTRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism - a glutamatergic mechanism would be a possible candidate.

Project description:Unusual language use is a core feature of psychosis, but the nature and significance of this are not understood. In particular, thought disorder in schizophrenia (SZ) is characterized by markedly bizarre speech, but the cognitive components that contribute to this and the brain correlates of these components are unknown. A number of studies have demonstrated language abnormalities in single word processing, but few have examined speech in SZ at the discourse level. This has been at least partly due to the difficulty in quantifying content of discourse. Recently, methods in computational linguistics have been found to be useful for detecting differences in semantic coherence during discourse between different clinical groups. We build on this work by demonstrating how these methods can be combined with funtional magnetic resonance imaging (fMRI) in order to tease apart factors that underlie free discourse and its deviations, and how they relate to brain activity. Eleven volunteers with SZ and eleven controls participated in an interview during which they were asked to talk as much as they could about 'religious belief'. These same participants underwent fMRI during a word monitoring task, during which modality of monitoring was manipulated by varying the congruence of auditory and visual stimuli. Semantic coherence scores, measured from free discourse, were examined for their relationship to brain activations during fMRI. In healthy controls, regions associated with executive function were related to coherence. In persons with SZ, coherence was mainly related to auditory and visual regions, depending on the modality of monitoring, but superior/middle temporal cortex related to coherence regardless of task. These findings are consistent with existing evidence for a role of superior temporal cortex in thought disorder, and demonstrate that computational measures of semantic content capture objective measures of coherence in speech that can be usefully related to underlying neurophysiological processes.

Dataset Information

Neural mechanisms of mood-induced modulation of reality monitoring in schizophrenia.

Publications

Neural mechanisms of mood-induced modulation of reality monitoring in schizophrenia.

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