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A growing body of evidence demonstrates that persistent positive symptoms, particularly delusions, can be improved by cognitive behaviour therapy for psychosis. Heightened perception and processing of threat are believed to constitute the genesis of delusions. The present study aimed to examine functional brain changes following cognitive behaviour therapy for psychosis. The study involved 56 outpatients with one or more persistent positive distressing symptoms of schizophrenia. Twenty-eight patients receiving cognitive behaviour therapy for psychosis for 6-8 months in addition to their usual treatment were matched with 28 patients receiving treatment as usual. Patients' symptoms were assessed by a rater blind to treatment group, and they underwent functional magnetic resonance imaging during an affect processing task at baseline and end of treatment follow-up. The two groups were comparable at baseline in terms of clinical and demographic parameters and neural and behavioural responses to facial and control stimuli. The cognitive behaviour therapy for psychosis with treatment-as-usual group (22 subjects) showed significant clinical improvement compared with the treatment-as-usual group (16 subjects), which showed no change at follow-up. The cognitive behaviour therapy for psychosis with treatment-as-usual group, but not the treatment-as-usual group, showed decreased activation of the inferior frontal, insula, thalamus, putamen and occipital areas to fearful and angry expressions at treatment follow-up compared with baseline. Reduction of functional magnetic resonance imaging response during angry expressions correlated directly with symptom improvement. This study provides the first evidence that cognitive behaviour therapy for psychosis attenuates brain responses to threatening stimuli and suggests that cognitive behaviour therapy for psychosis may mediate symptom reduction by promoting processing of threats in a less distressing way.

Previous small-sample studies have shown altered frontotemporal activity in schizophrenia patients with auditory hallucinations and impaired monitoring of self-generated speech. We examined a large cohort of patients with schizophrenia (n = 63) and a representative group of healthy controls (n = 20) to disentangle performance, illness, and symptom-related effects in functional magnetic resonance imaging-detected brain abnormalities during monitoring of self- and externally generated speech in schizophrenia. Our results revealed activation of the thalamus (medial geniculate nucleus, MGN) and frontotemporal regions with accurate monitoring across all participants. Less activation of the thalamus (MGN, pulvinar) and superior-middle temporal and inferior frontal gyri occurred in poorly performing patients (1 standard deviation below controls' mean; n = 36), relative to the combined group of controls and well-performing patients. In patients, (1) greater deactivation of the ventral striatum and hypothalamus to own voice, combined with nonsignificant activation of the same regions to others' voice, associated positively with negative symptoms (blunted affect, emotional withdrawal, poor rapport, passive social avoidance) regardless of performance and (2) exaggerated activation of the right superior-middle temporal gyrus during undistorted, relative to distorted, feedback associated with both positive symptoms (hallucinations, persecution) and poor performance. A further thalamic abnormality characterized schizophrenia patients regardless of performance and symptoms. We conclude that hypoactivation of a neural network comprised of the thalamus and frontotemporal regions underlies impaired speech monitoring in schizophrenia. Positive symptoms and poor monitoring share a common activation abnormality in the right superior temporal gyrus during processing of degraded speech. Altered striatal and hypothalamic modulation to own and others' voice characterizes emotionally withdrawn and socially avoidant patients.

Background: Responsiveness to cognitive behaviour therapy (CBT) in psychosis may have a neurological basis. This study aimed to determine whether improvement in symptoms following CBT for psychosis (CBTp) in people with schizophrenia is positively associated with pre-therapy grey matter volume in brain regions involved in cognitive processing., Methods: Sixty outpatients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBTp in addition to their standard care (SC), and 25 healthy participants underwent magnetic resonance imaging. Subsequently, 30 patients received CBTp (CBTp+SC; 25 completers) for 6-8 months and 30 continued with their standard care (SC; 19 completers). Symptoms in all patients were assessed (blindly) at entry and follow-up., Results: The CBTp+SC and SC groups did not differ clinically at baseline, and only the CBTp+SC group showed improved symptoms at follow-up. Severity of baseline symptoms was not associated with CBTp responsiveness. Reduction with CBTp in positive symptoms was associated with greater right cerebellum (lobule VII) grey matter volume, in negative symptoms with left precentral gyrus and right inferior parietal lobule grey matter volumes, and in general psychopathology with greater right superior temporal gyrus, cuneus and cerebellum (Crus I) grey matter volumes. Grey matter volume in these brain areas did not correlate with the severity of baseline symptoms., Conclusion: Grey matter volume of the frontal, temporal, parietal and cerebellar areas that are known to be involved in the co-ordination of mental activity, cognitive flexibility, and verbal learning and memory predict responsiveness to CBTp in patients with psychosis.

Neuropsychological function-brain structure relationships may differ as a function of illness stage because of progressive brain matter loss through the course of schizophrenia. In this study, we tested whether neuropsychological function-brain structure relationships differed as a function of illness stage. In addition, we tested whether these relationships differed between older and young healthy controls. Function-structure relationships were examined in 35 first-episode patients (31 with schizophrenia, 4 with schizoaffective disorder), 54 chronic schizophrenia patients, 21 older healthy controls and 20 young healthy controls. MRI volumes of frontal and temporal lobe structures, as well as the whole brain, were estimated using a region-of-interest approach. Hierarchical multiple regression analyses were performed between the MRI and neuropsychological measures. Stronger relationships of immediate memory-total prefrontal cortex (PFC) volume in chronic than first-episode patients, and in older than young controls were observed. The abstract reasoning (WCST perseverative errors)-total temporal lobe volume relationship was stronger in older than young controls. These function-structure relationships appeared unexplained by whole brain volume or age in chronic patients. A similar dissociation between young and older subjects of both healthy and patient groups suggests that a 'bigger-is-better' relationship style is present in older individuals regardless of a diagnosis of schizophrenia.

Objective: The authors investigated the structural brain correlates of antisaccade performance., Method: Magnetic resonance imaging was used to measure the volumes of the prefrontal, premotor, sensorimotor, and occipitoparietal cortices as well as the caudate, thalamus, cerebellar vermis, and cerebrum in 20 first-episode psychosis patients and 18 healthy comparison subjects. Antisaccades were recorded by using infrared oculography., Results: Groups significantly differed in terms of antisaccade error rate and amplitude gain and tended to differ in terms of latency but not brain region volumes. Premotor cortex volume predicted antisaccade error rate among comparison subjects. In the patient group, caudate volume was related to latency and amplitude gain. Negative symptoms, independent of structural volumes, predicted error rate., Conclusions: These findings point to altered structure-function relationships in first-episode psychosis.

Abstract: Previous studies have suggested a relationship between frontal lobe-based neuropsychological functions and insight in schizophrenia. There is some evidence linking both smaller whole brain volume and frontal cortical atrophy to poor insight in this population. We investigated the relationship between total as well as specific prefrontal regional volumes and insight in schizophrenia. Twenty-eight stable outpatients with schizophrenia underwent magnetic resonance imaging scanning and assessment for insight. Insight was measured using the Birchwood self-report Insight Scale and the Expanded Schedule of Assessment of Insight. The whole brain and prefrontal regional (superior frontal, middle frontal, inferior frontal and orbitofrontal) volumes were then manually measured using the Cavalieri method and established criteria. Twenty healthy subjects were also scanned to provide control data for volumetric assessments. Smaller total prefrontal grey matter volume was moderately associated with a lower level of insight into the presence of illness. At the prefrontal sub-regional level, volumes of the superior, inferior and orbitofrontal regions contributed to this relationship, especially in males. It is concluded that smaller prefrontal grey matter volume is associated with poor insight into the presence of illness in stable schizophrenia patients. Future research should examine the association of specific dimensions of insight with frontal as well as non-frontal regional brain volumes. [Copyright &y& Elsevier]