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Neural substrates underlying delusions in schizophrenia.

ABSTRACT: Delusions are cardinal positive symptoms in schizophrenia; however, the neural substrates of delusions remain unknown. In the present study, we investigated the neural correlates of delusions in schizophrenia using multi-modal magnetic resonance imaging (MRI) techniques. Diffusion, structural and perfusion MRIs were performed in 19 schizophrenia patients with severe delusions, 30 patients without delusions and 30 healthy controls. Fractional anisotropy (FA), gray matter volume (GMV) and cerebral blood flow (CBF) were voxel-wisely compared among the three groups. Although patients without delusions exhibited decreased FA in white matter regions and decreased GMV in gray matter regions relative to controls, patients with severe delusions demonstrated comparable FA in all of these white matter regions and similar GMV in most of these gray matter regions. Both patient subgroups had less GMV in the amygdala and anterior cingulate cortex than controls. Although two patient subgroups showed consistent CBF changes relative to controls, only CBF in the anterior cingulate cortex was lower in patients with severe delusions than in patients without delusions. These findings suggest that schizophrenia patients with severe delusions have relatively normal structural integrity. Importantly, the excessively reduced perfusion in the anterior cingulate cortex may be associated with the development of delusions in schizophrenia.

SUBMITTER: Zhu J

PROVIDER: S-EPMC5030611 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Neural substrates underlying delusions in schizophrenia.

Zhu Jiajia J Zhuo Chuanjun C Liu Feng F Xu Lixue L Yu Chunshui C

Scientific reports 20160921

Delusions are cardinal positive symptoms in schizophrenia; however, the neural substrates of delusions remain unknown. In the present study, we investigated the neural correlates of delusions in schizophrenia using multi-modal magnetic resonance imaging (MRI) techniques. Diffusion, structural and perfusion MRIs were performed in 19 schizophrenia patients with severe delusions, 30 patients without delusions and 30 healthy controls. Fractional anisotropy (FA), gray matter volume (GMV) and cerebral ...[more]

PMID: 27651212

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Project description:IntroductionThe neural substrates associated with the development of micrographia remain unknown. We aimed to elucidate the neural substrates underlying micrographia in Parkinson's disease (PD) patients.MethodsForty PD patients and 20 healthy controls underwent handwriting tests that involved free writing and copying. We measured the size of each letter and the resting cerebral glucose metabolic rate of the PD patients and another group of age- and sex-matched 14 healthy controls (HCs), who had not participated in the writing tests, using resting-state 18F-fluorodeoxyglucose positron emission tomography.ResultsIn the PD patients, the prevalence of consistent micrographia (CM) associated with free writing was 2.5% for both tasks. Alternatively, the prevalence of progressive micrographia (PM) was 15% for free writing and 17.5% for copying. In the PD patients, there was no significant difference in the letter sizes between these tasks, whereas the variability of the letter sizes for copying was significantly different from that for free writing. The means and decrements in letter sizes in either task were not significantly correlated with the severity of brady/hypokinesia in the PD patients. For free writing, the PD patients with PM showed glucose hypometabolism in the anterior part of the right middle cingulate cortex, including the rostral cingulate motor area, compared with those without PM. For copying, the PD patients with PM showed glucose hypometabolism in the right superior occipital gyrus, including V3A, compared with those without PM.ConclusionsThese findings suggest that PM in free writing in PD patients is caused by the difficulty of monitoring whether the actual handwriting movements are desirable for maintaining letter size during self-paced handwriting. By contrast, PM in copying in PD patients is evoked by a lack of visual information about the personal handwriting and hand motions that are used as cues for maintaining letter sizes.

Project description:Delusions, a core symptom of psychosis, are false beliefs that are rigidly held with strong conviction despite contradictory evidence. Alterations in inferential processes have long been proposed to underlie delusional pathology, but previous attempts to show this have failed to yield compelling evidence for a specific relationship between inferential abnormalities and delusional severity in schizophrenia. Using a novel, incentivized information-sampling task (a modified version of the beads task), alongside well-characterized decision-making tasks, we sought a mechanistic understanding of delusions in a sample of medicated and unmedicated patients with schizophrenia who exhibited a wide range of delusion severity. In this novel task, participants chose whether to draw beads from one of two hidden jars or to guess the identity of the hidden jar, in order to minimize financial loss from a monetary endowment, and concurrently reported their probability estimates for the hidden jar. We found that patients with higher delusion severity exhibited increased information seeking (i.e. increased draws-to-decision behaviour). This increase was highly specific to delusion severity as compared to the severity of other psychotic symptoms, working-memory capacity, and other clinical and socio-demographic characteristics. Delusion-related increases in information seeking were present in unmedicated patients, indicating that they were unlikely due to antipsychotic medication. In addition, after adjusting for delusion severity, patients as a whole exhibited decreased information seeking relative to healthy individuals, a decrease that correlated with lower socioeconomic status. Computational analyses of reported probability estimates further showed that more delusional patients exhibited abnormal belief updating characterized by stronger reliance on prior beliefs formed early in the inferential process, a feature that correlated with increased information seeking in patients. Other decision-making parameters that could have theoretically explained the delusion effects, such as those related to subjective valuation, were uncorrelated with both delusional severity and information seeking among the patients. In turn, we found some preliminary evidence that subjective valuation (rather than belief updating) may explain group differences in information seeking unrelated to delusions. Together, these results suggest that abnormalities in belief updating, characterized by stronger reliance on prior beliefs formed by incorporating information presented earlier in the inferential process, may be a core computational mechanism of delusional ideation in psychosis. Our results thus provide direct empirical support for an inferential mechanism that naturally captures the characteristic rigidity associated with delusional beliefs.

Project description:Motor skill learning is critical in post-stroke motor recovery, but little is known about its underlying neural substrates. Recently, using a new visuomotor skill learning paradigm involving a speed/accuracy trade-off in healthy individuals we identified three subpopulations based on their behavioral trajectories: fitters (in whom improvement in speed or accuracy coincided with deterioration in the other parameter), shifters (in whom speed and/or accuracy improved without degradation of the other parameter), and non-learners. We aimed to identify the neural substrates underlying the first stages of motor skill learning in chronic hemiparetic stroke patients and to determine whether specific neural substrates were recruited in shifters versus fitters. During functional magnetic resonance imaging (fMRI), 23 patients learned the visuomotor skill with their paretic upper limb. In the whole-group analysis, correlation between activation and motor skill learning was restricted to the dorsal prefrontal cortex of the damaged hemisphere (DLPFCdamh: r = -0.82) and the dorsal premotor cortex (PMddamh: r = 0.70); the correlations was much lesser (-0.16 < r > 0.25) in the other regions of interest. In a subgroup analysis, significant activation was restricted to bilateral posterior parietal cortices of the fitters and did not correlate with motor skill learning. Conversely, in shifters significant activation occurred in the primary sensorimotor cortexdamh and supplementary motor areadamh and in bilateral PMd where activation changes correlated significantly with motor skill learning (r = 0.91). Finally, resting-state activity acquired before learning showed a higher functional connectivity in the salience network of shifters compared with fitters (qFDR < 0.05). These data suggest a neuroplastic compensatory reorganization of brain activity underlying the first stages of motor skill learning with the paretic upper limb in chronic hemiparetic stroke patients, with a key role of bilateral PMd.

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Neural substrates underlying delusions in schizophrenia.

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Neural substrates underlying delusions in schizophrenia.

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