Exploring the internal forward model: action-effect prediction and attention in sensorimotor processing.

Action-effect predictions are believed to facilitate movement based on its association with sensory objectives and suppress the neurophysiological response to self- versus externally generated stimuli (i.e. sensory attenuation). However, research is needed to explore theorized differences in the use of action-effect prediction based on whether movement is uncued (i.e. volitional) or in response to external cues (i.e. stimulus-driven). While much of the sensory attenuation literature has examined effects involving the auditory N1, evidence is also conflicted regarding this component's sensitivity to action-effect prediction. In this study (n = 64), we explored the influence of action-effect contingency on event-related potentials associated with visually cued and uncued movement, as well as resultant stimuli. Our findings replicate recent evidence demonstrating reduced N1 amplitude for tones produced by stimulus-driven movement. Despite influencing motor preparation, action-effect contingency was not found to affect N1 amplitudes. Instead, we explore electrophysiological markers suggesting that attentional mechanisms may suppress the neurophysiological response to sound produced by stimulus-driven movement. Our findings demonstrate lateralized parieto-occipital activity that coincides with the auditory N1, corresponds to a reduction in its amplitude, and is topographically consistent with documented effects of attentional suppression. These results provide new insights into sensorimotor coordination and potential mechanisms underlying sensory attenuation.

Are We Speaking the Same Language? Finding Theoretical Coherence and Precision in "Mindfulness-Based Mechanisms" in Chronic Pain.

OBJECTIVE: Over the past 50 years, the field of chronic pain has witnessed an evolution of psychological approaches with some notable success. Some of this evolution has included "mindfulness-based interventions" (MBIs), now regarded as having encouraging partial support for their effectiveness. However, several theoretical challenges remain that may inhibit the progress of MBIs. These challenges include a lack of clarity surrounding the mindfulness construct itself, the proliferation of purported underlying mechanisms arising from different theories, and limited evidence for the mechanisms through which MBIs work. The current conceptual review provides a critique of existing theoretical models of mindfulness that have been applied to understanding and treating chronic pain. DESIGN: A conceptual narrative review was conducted. SETTING: Treatment programs for people with chronic pain. PATIENTS: Individuals with any type of chronic pain. INTERVENTIONS: MBIs for chronic pain. OUTCOME MEASURES: Mindfulness-based mechanisms explored in relation to several domains of functioning. RESULTS AND CONCLUSIONS: Based on this assessment, a summary of available evidence for a particular contextual behavioral theory of "mindfulness"-psychological flexibility-is outlined. Findings show the need for further integration of existing mindfulness constructs to better guide development and evaluation of mindfulness-based treatment methods in the future.

Non-pharmacological interventions to reduce ICU-related psychological distress: a systematic review.

INTRODUCTION: Patients frequently suffer stress in intensive care units (ICUs) and many develop serious psychological morbidity after discharge. Little is known about the nature and efficacy of interventions to reduce ICU-related distress. There is growing evidence that administering sedative drugs can be harmful. Therefore we carried out a systematic review of non-pharmacological interventions to reduce ICU-related distress. EVIDENCE ACQUISITION: A systematic search was conducted using Medline, Embase, Psychinfo, Cinahl and the Web of Science. Included studies evaluated the effect of non-pharmacological interventions to reduce ICU stress. Study populations were adults in mixed or general ICUs. Outcomes were stress or psychological distress in or after the ICU, using self-report or physiological measures. No meta-analysis was possible due to heterogeneity, therefore studies were arranged according to intervention type, and outcomes examined together with risk of bias criteria. EVIDENCE SYNTHESIS: Twenty-three studies were eligible, including 15 randomized controlled trials. Non-pharmacological interventions included music therapy (11 studies), mind-body practices (5) and psychological interventions (7). 12 studies showed a beneficial effect. However only three of the 12 had a low risk of bias, and many studies in the review were under-powered to detect an effect. Only 5 studies measured a medium/long term psychological outcome such as PTSD or depression at 2-12 months. CONCLUSIONS: Evidence indicates that non-pharmacological approaches to reducing ICU distress, in particular psychological interventions, may be beneficial. The evidence base would be strengthened by the implementation of fully-powered studies using robust designs, that measure longer-term outcomes.

Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms.

PF-184298 ((S)-2,3-dichloro-N-isobutyl-N-pyrrolidin-3-ylbenzamide) and PF-4776548 ((3-(4-fluoro-2-methoxy-benzyl)-7-hydroxy-8,9-dihydro-3H,7H-pyrrolo[2,3-c][1,7]naphthyridin-6-one)) are novel compounds which were selected to progress to human studies. Discordant human pharmacokinetic predictions arose from pre-clinical in vivo studies in rat and dog, and from human in vitro studies, resulting in a clearance prediction range of 3 to >20 mL min⁻¹ kg⁻¹ for PF-184298, and 5 to >20 mL min⁻¹ kg⁻¹ for PF-4776548. A package of work to investigate the discordance for PF-184298 is described. Although ultimately complementary to the human pharmacokinetic data in characterising the disposition of PF-184298 in humans, these data did not provide any further confidence in pharmacokinetic prediction. A fit for purpose human pharmacokinetic study was conducted for each compound, with an oral pharmacologically active dose for PF-184298, and an intravenous and oral microdose for PF-4776548. This provided a relatively low cost, clear decision making approach, resulting in the termination of PF-4776548 and further progression of PF-184298. A retrospective analysis of the data showed that, if the tools had been available at the time, the pharmacokinetics of PF-184298 in human could have been predicted from a population based simulation tool in combination with physicochemical properties and in vitro human intrinsic clearance.

Improving mental health care in general hospitals.

The mental health needs of older people being cared for within general hospitals and other acute healthcare settings has been specifically identified as a priority for improvement. Yet in reality little has changed. The Department of Health (DH) (2006) has highlighted how many challenges still exist in developing effective integrated care for this patient group and continues to respond with further centrally initiated policy documents. This article explores the relationship between policy and practice and highlights how, despite their importance, policy initiatives alone are unlikely to be enough to ensure the effective delivery of mental health care for older people in general hospitals.