EBM CONNECT Collaboration.

Background Dissociative seizures are paroxysmal events resembling epilepsy or syncope with characteristic features that allow them to be distinguished from other medical conditions. We aimed to compare the effectiveness of cognitive behavioural therapy (CBT) plus standardised medical care with standardised medical care alone for the reduction of dissociative seizure frequency. MethodsIn this pragmatic, parallel-arm, multicentre randomised controlled trial, we initially recruited participants at 27 neurology or epilepsy services in England, Scotland, and Wales. Adults (≥18 years) who had dissociative seizures in the previous 8 weeks and no epileptic seizures in the previous 12 months were subsequently randomly assigned (1:1) from 17 liaison or neuropsychiatry services following psychiatric assessment, to receive standardised medical care or CBT plus standardised medical care, using a web-based system. Randomisation was stratified by neuropsychiatry or liaison psychiatry recruitment site. The trial manager, chief investigator, all treating clinicians, and patients were aware of treatment allocation, but outcome data collectors and trial statisticians were unaware of treatment allocation. Patients were followed up 6 months and 12 months after randomisation. The primary outcome was monthly dissociative seizure frequency (ie, frequency in the previous 4 weeks) assessed at 12 months. Secondary outcomes assessed at 12 months were: seizure severity (intensity) and bothersomeness; longest period of seizure freedom in the previous 6 months; complete seizure freedom in the previous 3 months; a greater than 50% reduction in seizure frequency relative to baseline; changes in dissociative seizures (rated by others); health-related quality of life; psychosocial functioning; psychiatric symptoms, psychological distress, and somatic symptom burden; and clinical impression of improvement and satisfaction. p values and statistical significance for outcomes were reported without correction for multiple comparisons as per our protocol. Primary and secondary outcomes were assessed in the intention-to-treat population with multiple imputation for missing observations. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN05681227, and ClinicalTrials.gov, NCT02325544.

The default mode network (DMN) is one of the most studied resting-state networks, and is thought to be involved in the maintenance of consciousness within the alert human brain. Although many studies have examined the functional connectivity (FC) of the DMN, few have investigated its underlying structural connectivity (SC), or the relationship between the two. We investigated this question in fifteen healthy subjects, concentrating on connections to the precuneus/posterior cingulate cortex (PCC), commonly considered as the central node of the DMN. We used group independent component analysis (GICA) and seed-based correlation analysis of fMRI data to quantify FC, and streamline and probabilistic tractography to identify structural tracts from diffusion tensor imaging (DTI) data. We first assessed the presence of structural connections between the DMN regions identified with GICA. Of the 15 subjects, when using the probabilistic approach 15 (15) demonstrated connections between the PCC and mesial prefrontal cortex (mPFC), 11 (15) showed connections from the PCC to the right inferior parietal cortex (rIPC) and 8 (15) to the left IPC. Next, we assessed the strength of FC (magnitude of temporal correlation) and SC (mean fractional anisotropy of reconstructed tracts (streamline), number of super-threshold voxels within the mask region (probabilistic)). The lIPC had significantly reduced FC to the PCC compared to the mPFC and rIPC. No difference in SC strength between connections was found using the streamline approach. For the probabilistic approach, mPFC had significantly lower SC than both IPCs. The two measures of SC strength were significantly correlated, but not for all paired connections. Finally, we observed a significant correlation between SC and FC for both tractography approaches when data were pooled across PCC-lIPL, PCC-rIPL and PCC-mPFC connections, and for some individual paired connections. Our results suggest that the streamline approach is advantageous for characterising the connectivity of long white matter tracts (PCC-mPFC), whilst the probabilistic approach was more reliable at identifying PCC-IPC connections. The direct comparison of FC and SC indicated that pairs of nodes with stronger structural connections also had stronger functional connectivity, and that this was maintained with both tractography approaches. Whilst the definition of SC strength remains controversial, our results could be considered to provide some degree of validation for the measures of SC strength that we have used. Direct comparisons of SC and FC are necessary in order to understand the structural basis of functional connectivity, and to characterise and quantify the changes in the brain's functional architecture that occur as a result of normal physiology or pathology.

Background: Neuropathological and imaging studies suggest that corpus callosum abnormalities (CC) are present in schizophrenia, but it remains to be determined whether these abnormalities are present at illness onset. Diffusion tensor imaging (DTI), which is more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle structural changes in the organisation and integrity of white matter tracts, is an ideal tool to investigate this question. Objective: To determine whether CC abnormalities are present at illness onset in schizophrenia. Methods: Twenty patients (14 men, six women) with first episode schizophrenia and 29 controls (11 men, 18 women) were studied. Both high resolution volumetric T1-weighted images and DTI were acquired. Regions of interest (ROI) were placed in the splenium and genu of the CC and fractional anisotropy (FA) and diffusivity (D) measured. Results: No differences in FA or D were detected in these regions between patients and controls. In women, irrespective of group membership, FA was significantly lower and there was a trend for D to be higher than in men, indicating less barriers to diffusion in females. Conclusion: The negative findings of this study suggest that in the early stages of schizophrenia there is no disruption to the integrity of the CC and raise the possibility that the neuropathological abnormalities may appear later and be progressive, at least in some patients.