Neuroimaging studies have found evidence of altered brain structure and function in schizophrenia, but have had complex findings regarding the localization of abnormality. We applied multimodal ...imaging (voxel-based morphometry (VBM), functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) combined with tractography) to 32 chronic schizophrenic patients and matched healthy controls. At a conservative threshold of P=0.01 corrected, structural and functional imaging revealed overlapping regions of abnormality in the medial frontal cortex. DTI found that white matter abnormality predominated in the anterior corpus callosum, and analysis of the anatomical connectivity of representative seed regions again implicated fibres projecting to the medial frontal cortex. There was also evidence of convergent abnormality in the dorsolateral prefrontal cortex, although here the laterality was less consistent across techniques. The medial frontal region identified by these three imaging techniques corresponds to the anterior midline node of the default mode network, a brain system which is believed to support internally directed thought, a state of watchfulness, and/or the maintenance of one's sense of self, and which is of considerable current interest in neuropsychiatric disorders.
Here we develop a measure of functional connectivity describing the degree of covariability between a brain region and the rest of the brain. This measure is based on previous formulas for the mutual ...information (MI) between clusters of regions in the frequency domain. Under the current scenario, the MI can be given as a simple monotonous function of the multiple coherence and it leads to an easy visual representation of connectivity patterns. Computationally efficient formulas, adequate for short time series, are presented and applied to functional magnetic resonance imaging (fMRI) data measured in subjects (
N
=
34) performing a working memory task or being at rest. While resting state coherence in high (0.17–0.25 Hz) and middle (0.08–0.17 Hz) frequency intervals is bilaterally salient in several limbic and temporal areas including the insula, the amygdala, and the primary auditory cortex, low frequencies (<
0.08 Hz) have greatest connectivity in frontal structures. Results from the comparison between resting and N-back conditions show enhanced low frequency coherence in many of the areas previously reported in standard fMRI activation studies of working memory, but task related reductions in high frequency connectivity are also found in regions of the default mode network. Finally, potentially confounding effects of head movement and regional volume on MI are identified and addressed.
Functional imaging studies using working memory tasks have documented both prefrontal cortex (PFC) hypo- and hyperactivation in schizophrenia. However, these studies have often failed to consider the ...potential role of task-related deactivation.
Thirty-two patients with chronic schizophrenia and 32 age- and sex-matched normal controls underwent functional magnetic resonance imaging (fMRI) scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups.
The controls showed activation in the expected frontal regions. There were also clusters of deactivation, particularly in the anterior cingulate/ventromedial PFC and the posterior cingulate cortex/precuneus. Compared to the controls, the schizophrenic patients showed reduced activation in the right dorsolateral prefrontal cortex (DLPFC) and other frontal areas. There was also an area in the anterior cingulate/ventromedial PFC where the patients showed apparently greater activation than the controls. This represented a failure of deactivation in the schizophrenic patients. Failure to activate was a function of the patients' impaired performance on the n-back task, whereas the failure to deactivate was less performance dependent.
Patients with schizophrenia show both failure to activate and failure to deactivate during performance of a working memory task. The area of failure of deactivation is in the anterior prefrontal/anterior cingulate cortex and corresponds to one of the two midline components of the 'default mode network' implicated in functions related to maintaining one's sense of self.
Objective
Brain structural changes in schizoaffective disorder, and how far they resemble those seen in schizophrenia and bipolar disorder, have only been studied to a limited extent.
Method
...Forty‐five patients meeting DSM‐IV and RDC criteria for schizoaffective disorder, groups of patients with 45 matched schizophrenia and bipolar disorder, and 45 matched healthy controls were examined using voxel‐based morphometry (VBM).
Results
Analyses comparing each patient group with the healthy control subjects found that the patients with schizoaffective disorder and the patients with schizophrenia showed widespread and overlapping areas of significant volume reduction, but the patients with bipolar disorder did not. A subsequent analysis compared the combined group of patients with the controls followed by extraction of clusters. In regions where the patients differed significantly from the controls, no significant differences in mean volume between patients with schizoaffective disorder and patients with schizophrenia in any of five regions of volume reduction were found, but mean volumes in the patients with bipolar disorder were significantly smaller in three of five.
Conclusion
The findings provide evidence that, in terms of structural gray matter brain abnormality, schizoaffective disorder resembles schizophrenia more than bipolar disorder.
One hypothesis proposed to underlie formal thought disorder (FTD), the incoherent speech is seen in some patients with schizophrenia, is that it reflects impairment in frontal/executive function. ...While this proposal has received support in neuropsychological studies, it has been relatively little tested using functional imaging. This study aimed to examine brain activations associated with FTD, and its two main factor-analytically derived subsyndromes, during the performance of a working memory task.
Seventy patients with schizophrenia showing a full range of FTD scores and 70 matched healthy controls underwent fMRI during the performance of the 2-back version of the n-back task. Whole-brain corrected, voxel-based correlations with FTD scores were examined in the patient group.
During 2-back performance the patients showed clusters of significant inverse correlation with FTD scores in the inferior frontal cortex and dorsolateral prefrontal cortex bilaterally, the left temporal cortex and subcortically in the basal ganglia and thalamus. Further analysis revealed that these correlations reflected an association only with 'alogia' (poverty of speech, poverty of content of speech and perseveration) and not with the 'fluent disorganization' component of FTD.
This study provides functional imaging support for the view that FTD in schizophrenia may involve impaired executive/frontal function. However, the relationship appears to be exclusively with alogia and not with the variables contributing to fluent disorganization.
The subgenual anterior cingulate cortex (sgACC) is considered to be an important site of abnormality in major depressive disorder. However, structural alterations in this region have not been a ...consistent finding and functional imaging studies have also implicated additional areas.
A total of 32 patients with major depressive disorder, currently depressed, and 64 controls underwent structural imaging with MRI. Also, 26 patients and 52 controls were examined using functional magnetic resonance imaging (fMRI) during performance of the n-back working memory task. Structural and functional changes were evaluated using whole-brain, voxel-based methods.
The depressed patients showed volume reductions in the sgACC and orbitofrontal cortex bilaterally, plus in both temporal poles and the hippocampus/parahippocampal gyrus on the left. Functional imaging revealed task-related hypo-activation in the left lateral prefrontal cortex and other regions, as well as failure of deactivation in a subcallosal medial frontal cortical area which included the sgACC.
Whole-brain, voxel-based analysis finds evidence of both structural and functional abnormality in the sgACC in major depressive disorder. The fact that the functional changes in this area took the form of failure of deactivation adds to previous findings of default mode network dysfunction in the disorder.
Objective
Cognitive reserve (CR) refers to the brain's capacity to cope with pathology in order to minimize the symptoms. CR is associated with different outcomes in severe mental illness. This study ...aimed to analyze the impact of CR according to the diagnosis of first‐episode affective or non‐affective psychosis (FEP).
Method
A total of 247 FEP patients (211 non‐affective and 36 affective) and 205 healthy controls were enrolled. To assess CR, common proxies have been integrated (premorbid IQ; education–occupation; leisure activities). The groups were divided into high and low CR.
Results
In non‐affective patients, those with high CR were older, had higher socioeconomic status (SES), shorter duration of untreated psychosis, and a later age of onset. They also showed greater performance in most cognitive domains. In affective patients, those with a greater CR showed a higher SES, better functioning, and greater verbal memory performance.
Conclusion
CR plays a differential role in the outcome of psychoses according to the diagnosis. Specifically, in order to address the needs of non‐affective patients with low CR, cognitive rehabilitation treatments will need to be ‘enriched’ by adding pro‐cognitive pharmacological agents or using more sophisticated approaches. However, a functional remediation therapy may be of choice for those with an affective psychosis and low CR.
The role of the basal ganglia has been a longstanding issue in neural language models. Huntington's disease (HD) shows primary impairment in the striatum and has previously been shown to affect the ...processing of phrase-structural hierarchies that are built by phrasal movement (e.g. in passives). Here we asked patients with HD to judge the acceptability of sentences containing different types of illicit phrasal movement, which were contrasted with semantic violations involving no movement. A logistic mixed-effects regression showed that patients had a profound impairment in judging incorrect but not correct sentences across all types of illicit movement, while the semantic condition was also affected, but significantly less so. Adding neuropsychological variables to the model did not improve predictions. These results demonstrate a loss of cognitive control, worsening with disease progression, over phrase-structural hierarchies, which extends to forms of meaning built at sentential levels.
Increased semantic priming is an influential theory of thought disorder in schizophrenia. However, studies to date have had conflicting findings.
To investigate semantic memory in patients with ...schizophrenia with and without thought disorder.
Data were pooled from 36 studies comparing patients with schizophrenia and normal controls in semantic priming tasks. Data from 18 studies comparing patients with thought disorder with normal controls, and 13 studies comparing patients with and without thought disorder were also pooled.
There was no support for altered semantic priming in schizophrenia as a whole. Increased semantic priming in patients with thought disorder was supported, but this was significant only in comparison with normal controls and not in comparison with patients without thought disorder. Stimulus onset asynchrony (SOA) and general slowing of reaction time moderated the effect size for priming in patients with thought disorder.
Meta-analysis provides qualified support for increased semantic priming as a psychological abnormality underlying thought disorder. However, the possibility that the effect is an artefact of general slowing of reaction time in schizophrenia has not been excluded.
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