The misattribution of salience in delusional patients with schizophrenia

Holt, Daphne J.; Titone, Debra; Long, Louis; Goff, Donald C.; Cather, Corinne; Rauch, Scott L.; Judge, Abigail M.; Kuperberg, Gina R.

doi:10.1016/j.schres.2005.12.858

Cited by 67 publications

(64 citation statements)

References 42 publications

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“…As a result, stimuli that are neutral and innocuous among healthy controls may gain a status as motivationally salient among patients with schizophrenia. In line with this finding, a recent study using a word classification paradigm showed that deluded patients with schizophrenia displayed a bias towards classifying words as unpleasant, a misattribution of salience, compared to nondeluded patients and healthy controls (Holt et al, 2006b). It has been proposed that positive symptoms (such as delusions and hallucinations) are the product of abnormally reinforced thoughts and associations, and the current study could serve as a model of how context-inappropriate associations are reinforced (Kapur, 2003;King et al, 1984;Miller, 1984;Shaner, 1999).…”

Section: Discussionsupporting

confidence: 82%

The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence

Jensen

Willeit

Zipursky

et al. 2007

Neuropsychopharmacol

206

155

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It is hypothesized that due to an abnormal functioning of the reward system patients with schizophrenia form context-inappropriate associations. It has been shown that the dopamine target regions, especially the ventral striatum, are critical in the formation of reward associations. We wanted to examine how the ventral striatum responds as patients learn reward-related associations and how this neural response is linked to objective and subjective behavioral measures. Functional magnetic resonance imaging (fMRI) Blood oxygen level dependent (BOLD) responses were examined using aversive Pavlovian learning in 13 medicated patients with schizophrenia and 13 matched healthy controls. Colored circles served as conditioned stimulus (CS + ) while a loud, individually adjusted, noise served as the unconditioned stimulus. Circles of another color served as neutral comparators (CSÀ). Subjective indices were assessed by a post-scan self-report, and galvanic skin responses (GSR) were used as objective measures of associative learning. fMRI data were analyzed using a random effects model in SPM2. Patients showed inappropriately strong activations in the ventral striatum in response to the neutral stimulus (CSÀ) as compared to the healthy controls. Consistent with this neural evidence of aberrant learning, patients also showed evidence of abnormal learning by self-report and as indexed by GSR. The main finding here is that patients with schizophrenia, when exposed to neutral stimuli in a threatening situation, show an abnormal pattern of learning. The aberrant activations and response are consistent with the idea that patients aberrantly assign motivational salience to neutral stimuli, and this process may be one of the aberrations that predisposes them to psychosis.

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Section: Discussionsupporting

confidence: 82%

The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence

Jensen

Willeit

Zipursky

et al. 2007

Neuropsychopharmacol

206

155

View full text Add to dashboard Cite

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“…Furthermore, persecutory delusions in patients with schizophrenia have been associated with a tendency to classify neutral stimuli as unpleasant. 40 The current evidence indicates that an elevated amygdala response to neutral faces in the context of positive emotional stimuli may be characteristic of chronically violent men, regardless of their level of psychopathic features.…”

Section: Discussionmentioning

confidence: 65%

Neural responses to emotional and neutral facial expressions in chronically violent men

Pardini

Phillips

2010

J Psychiatry Neurosci

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Background: Abnormal neural responses to others' emotions, particularly cues of threat and distress, have been implicated in the development of chronic violence. We examined neural responses to several emotional cues within a prospectively identified group of chronically violent men. We also explored the association between neural responses to social emotions and psychopathic features. Methods:We compared neural responses to happy, sad, angry, fearful and neutral faces between chronically violent (n = 22) and nonviolent (n = 20) men using functional magnetic resonance imaging (fMRI). Participants were prospectively identified from a longitudinal study based on information collected from age 7 to 27 years. We assessed psychopathic features using a self-report measure administered in adulthood. Results: The chronically violent men exhibited significantly reduced neural responses in the dorsomedial prefrontal cortex to all faces, regardless of the emotional content, compared with nonviolent men. We also observed a hyperactive amygdala response to neutral faces in chronically violent men, but only within the context of viewing happy faces. Moreover, they exhibited a greater dorsomedial prefrontal cortex response to mildly fearful faces than nonviolent men. These abnormalities were not associated with psychopathic features in chronically violent men. Limitations: It remains unclear whether the observed neural abnormalities preceded or are a consequence of persistent violence, and these results may not generalize to chronically violent women. Conclusion: Chronically violent men exhibit a reduced neural response to facial cues regardless of emotional content. It appears that chronically violent men may view emotionally ambiguous facial cues as potentially threatening and implicitly reinterpret subtle cues of fear in others so they no longer elicit a negative response.

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“…Aleman and Kahn [75] hypothesized that affective flattening and emotion recognition deficits are produced by a compromised amygdala in combination with reduced connectivity with the prefrontal cortex, so that schizophrenic patients fail to coordinate the prefrontal monitoring of salient signals. On the other hand, other studies found elevated hippocampal and amygdaloid activity in schizophrenic patients during passive viewing [76] and emotional discrimination of faces [77,78] . This exaggerated amygdala activation during emotional intensity judgment is believed to reflect impaired gating of emotional sensory input.…”

Section: Interpretation Of Resultsmentioning

confidence: 81%

A Systems Approach to Prefrontal-Limbic Dysregulation in Schizophrenia

Rǎdulescu

Mujica‐Parodi²

2008

Neuropsychobiology

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Introduction: Using a prefrontal-limbic dysregulation model for schizophrenia, we tested whether a dynamic control systems approach in conjunction with neuroimaging might increase detection sensitivity in characterizing the illness. Our analyses were modeled upon diagnostic tests for other dysregulatory diseases, such as diabetes, in which trajectories for the excitatory and inhibitory components of the negative feedback loops that reestablish homeostasis are measured after system perturbation. We hypothesized that these components would show distinct coupling dynamics within the patient population, as compared to healthy controls, and that these coupling dynamics could be quantified statistically using cross-correlations between excitatory and inhibitory time series using fMRI. Methods: As our perturbation, we activated neural regions associated with the emotional arousal response, using affect-valent facial stimuli presented to 11 schizophrenic patients (all under psychotropic medication) and 65 healthy controls (including 11 individuals age- and sex-matched to the patients) during fMRI scanning. We first performed a random-effects analysis of the fMRI data to identify activated regions. Those regions were then analyzed for group differences, using both standard analyses with respect to the time series peaks, as well as a dynamic analysis that looked at cross-correlations between excitatory and inhibitory time series and group differences over the entire time series. Results: Patients and controls showed significant differences in signal dynamics between excitatory and inhibitory components of the negative feedback loop that controls emotional arousal, specifically between the right amygdala and Brodmann area 9 (BA9), when viewing angry facial expressions (p = 0.002). Further analyses were performed with respect to activation amplitudes for these areas in response to angry faces, both over the entire time series as well as for each time point along the time series. While the amygdala responses were not significantly different between groups, patients showed significantly lower BA9 activation during the beginning of the response (0.000 ≤ p ≤ 0.021) and significantly higher BA9 activation towards the end of the response (0.008 ≤ p ≤ 0.025), suggesting longer time-lags between patients’ excitatory responses and the inhibitory activation that modulates it. Conclusions: Our results capture a significant dysregulation between the excitatory (amygdala) and inhibitory (prefrontal) limbic regions in medicated schizophrenic patients versus healthy controls. They suggest that, analogously to diagnostic tests used in other physiological diseases, quantifying dysregulation using a control systems approach may provide an appropriate model to investigate further in developing presymptomatic neurobiological assessments of risk, or illness severity in symptomatic patients.

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The misattribution of salience in delusional patients with schizophrenia

Cited by 67 publications

References 42 publications

The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence

The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence

Neural responses to emotional and neutral facial expressions in chronically violent men

A Systems Approach to Prefrontal-Limbic Dysregulation in Schizophrenia

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