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      Kamin Blocking Is Associated with Reduced Medial-Frontal Gyrus Activation: Implications for Prediction Error Abnormality in Schizophrenia

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          Abstract

          The following study used 3-T functional magnetic resonance imaging (fMRI) to investigate the neural signature of Kamin blocking. Kamin blocking is an associative learning phenomenon seen where prior association of a stimulus (A) with an outcome blocks subsequent learning to an added stimulus (B) when both stimuli are later presented together (AB) with the same outcome. While there are a number of theoretical explanations of Kamin blocking, it is widely considered to exemplify the use of prediction error in learning, where learning occurs in proportion to the difference between expectation and outcome. In Kamin blocking as stimulus A fully predicts the outcome no prediction error is generated by the addition of stimulus B to form the compound stimulus AB, hence learning about it is “blocked”. Kamin blocking is disrupted in people with schizophrenia, their relatives and healthy individuals with high psychometrically-defined schizotypy. This disruption supports suggestions that abnormal prediction error is a core deficit that can help to explain the symptoms of schizophrenia. The present study tested 9 healthy volunteers on an f-MRI adaptation of Oades' “mouse in the house task”, the only task measuring Kamin blocking that shows disruption in schizophrenia patients that has been independently replicated. Participant's Kamin blocking scores were found to inversely correlate with Kamin-blocking-related activation within the prefrontal cortex, specifically the medial frontal gyrus. The medial frontal gyrus has been associated with the psychological construct of uncertainty, which we suggest is consistent with disrupted Kamin blocking and demonstrated in people with schizophrenia. These data suggest that the medial frontal gyrus merits further investigation as a potential locus of reduced Kamin blocking and abnormal prediction error in schizophrenia.

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          Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia.

          The clinical hallmark of schizophrenia is psychosis. The objective of this overview is to link the neurobiology (brain), the phenomenological experience (mind), and pharmacological aspects of psychosis-in-schizophrenia into a unitary framework. Current ideas regarding the neurobiology and phenomenology of psychosis and schizophrenia, the role of dopamine, and the mechanism of action of antipsychotic medication were integrated to develop this framework. A central role of dopamine is to mediate the "salience" of environmental events and internal representations. It is proposed that a dysregulated, hyperdopaminergic state, at a "brain" level of description and analysis, leads to an aberrant assignment of salience to the elements of one's experience, at a "mind" level. Delusions are a cognitive effort by the patient to make sense of these aberrantly salient experiences, whereas hallucinations reflect a direct experience of the aberrant salience of internal representations. Antipsychotics "dampen the salience" of these abnormal experiences and by doing so permit the resolution of symptoms. The antipsychotics do not erase the symptoms but provide the platform for a process of psychological resolution. However, if antipsychotic treatment is stopped, the dysregulated neurochemistry returns, the dormant ideas and experiences become reinvested with aberrant salience, and a relapse occurs. The article provides a heuristic framework for linking the psychological and biological in psychosis. Predictions of this hypothesis, particularly regarding the possibility of synergy between psychological and pharmacological therapies, are presented. The author describes how the hypothesis is complementary to other ideas about psychosis and also discusses its limitations.
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            Neuronal correlates of theory of mind and empathy: a functional magnetic resonance imaging study in a nonverbal task.

            Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from Sarfati et al. (1997) [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25, 199-209.]with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy.
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              From prediction error to psychosis: ketamine as a pharmacological model of delusions.

              Recent cognitive neuropsychiatric models of psychosis emphasize the role of attentional disturbances and inappropriate incentive learning in the development of delusions. These models highlight a pre-psychotic period in which the patient experiences perceptual and attentional disruptions. Irrelevant details and numerous associations between stimuli, thoughts and percepts are imbued with inappropriate significance and the attempt to rationalize and account for these bizarre experiences results in the formation of delusions. The present paper discusses delusion formation in terms of basic associative learning processes. Such processes are driven by prediction error signals. Prediction error refers to mismatches between an organism's expectation in a given environment and what actually happens and it is signalled by both dopaminergic and glutamatergic mechanisms. Disruption of these neurobiological systems may underlie delusion formation. We review similarities between acute psychosis and the psychotic state induced by the NMDA receptor antagonist drug ketamine, which impacts upon both dopaminergic and glutamatergic function. We conclude by suggesting that ketamine may provide an appropriate model to investigate the formative stages of symptom evolution in schizophrenia, and thereby provide a window into the earliest and otherwise inaccessible aspects of the disease process.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                31 August 2012
                : 7
                : 8
                : e43905
                Affiliations
                [1 ]School of Psychology, University of Nottingham, Nottingham, United Kingdom
                [2 ]Division of Psychiatry, School of Community Health Sciences, University of Nottingham, Nottingham, United Kingdom
                Utrecht University, The Netherlands
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PMM JLR RC MS. Performed the experiments: JLR BC MS PMM. Analyzed the data: MS JLR BC PMM. Contributed reagents/materials/analysis tools: MS. Wrote the paper: PMM MS JLR RC.

                Article
                PONE-D-12-15775
                10.1371/journal.pone.0043905
                3432033
                23028415
                6da5c2f4-540c-4fde-9172-4015492363da
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 May 2012
                : 27 July 2012
                Page count
                Pages: 7
                Funding
                JLR was supported by a University of Nottingham School of Psychology studentship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Molecular Cell Biology
                Signal Transduction
                Signaling in Selected Disciplines
                Neurological Signaling
                Neuroscience
                Cognitive Neuroscience
                Cognition
                Neurochemistry
                Neurochemicals
                Neurotransmitters
                Neuroimaging
                Fmri
                Neurotransmitters
                Medicine
                Mental Health
                Psychiatry
                Schizophrenia
                Psychology
                Neuropsychology

                Uncategorized
                Uncategorized

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