Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification

Background. Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method. The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results. Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions. Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method

We report the investigation of the mechanical properties of different types of amyloid fibrils by the peak force quantitative nanomechanical (PF-QNM) technique. We demonstrate that this technique correctly measures the Young’s modulus independent of the polymorphic state and the cross-sectional structural details of the fibrils, and we show that values for amyloid fibrils assembled from heptapeptides, a-synuclein, Ab(1–42), insulin, b-lactoglobulin,lysozyme, ovalbumin, Tau protein and bovine serum albumin all fall in the range of 2–4 GPa.

Top down influence on visuo-tactile interaction modulates neural oscillatory responses

Multisensory integration involves bottom-up as well as top-down processes. We investigated the influences of top-down control on the neural responses to multisensory stimulation using EEG recording and time-frequency analyses. Participants were stimulated at the index or thumb of the left hand, using tactile vibrators mounted on a foam cube. Simultaneously they received a visual distractor from a light emitting diode adjacent to the active vibrator (spatially congruent trial) or adjacent to the inactive vibrator (spatially incongruent trial). The task was to respond to the elevation of the tactile stimulus (upper or lower), while ignoring the simultaneous visual distractor. To manipulate top-down control on this multisensory stimulation, the proportion of spatially congruent (vs. incongruent) trials was changed across blocks. Our results reveal that the behavioral cost of responding to incongruent than congruent trials (i.e., the crossmodal congruency effect) was modulated by the proportion of congruent trials. Most importantly, the EEG gamma band response and the gamma-theta coupling were also affected by this modulation of top-down control, whereas the late theta band response related to the congruency effect was not. These findings suggest that gamma band response is more than a marker of multisensory binding, being also sensitive to the correspondence between expected and actual multisensory stimulation. By contrast, theta band response was affected by congruency but appears to be largely immune to stimulation expectancy.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.