The neurobiological mechanisms of transcranial direct current stimulation: insights from human neuroimaging and psychophysics

The research aimed to investigate the neurobiological basis of transcranial direct current stimulation (tDCS); a neuromodulation technique capable of inducing prolonged changes in behavioural performance. The past 15 years have seen a dramatic increase in tDCS-oriented studies, yet the underpinnings of the method are not completely understood. Consequently, this series of experiments was designed to investigate the mechanisms that contribute to the effects of the method. Focusing on neuroimaging, modulations of excitatory and inhibitory neurochemicals were assessed using Magnetic Resonance Spectroscopy (MRS); incorporating distinct spectral editing sequences to define the precise role of inhibitory neurotransmission. Additionally, concurrent DC stimulation and Magnetoencephalography (MEG) was developed, which permitted the novel investigation of excitatory and inhibitory processes via the influence of tDCS on electrophysiological responses in the motor and visual systems. This simultaneous tDCS-MEG investigation is one of only a few existing studies and was the first such endeavour by a group based in the United Kingdom. Finally, a unique psychophysical approach was adopted whereby variations of a vibrotactile adaptation task were utilised to assess the effects of tDCS on amplitude discrimination ability. The paradigms used were specifically chosen due to their physiological similarity to tDCS, thereby enabling inferences on the underpinnings of the method on the basis of changes in somatosensory task performance. These studies provided varying degrees of support for the neurobiological mechanisms proposed in the existing literature, most likely reflecting the influence of distinctions in stimulation protocols and the presence of individual difference factors thought to modify responses to stimulation. Consequently, in addition to the established insights regarding the underpinnings of tDCS, valuable perspectives on the optimisation of stimulation-based methodology were achieved by conducting the outlined investigations

Lacking Pace but Not Precision: Age-Related Information Processing Changes in Response to a Dynamic Attentional Control Task

Age-related decline in information processing can have a substantial impact on activities such as driving. However, the assessment of these changes is often carried out using cognitive tasks that do not adequately represent the dynamic process of updating environmental stimuli. Equally, traditional tests are often static in their approach to task complexity, and do not assess difficulty within the bounds of an individual’s capability. To address these limitations, we used a more ecologically valid measure, the Swansea Test of Attentional Control (STAC), in which a threshold for information processing speed is established at a given level of accuracy. We aimed to delineate how older, compared to younger, adults varied in their performance of the task, while also assessing relationships between the task outcome and gender, general cognition (MoCA), perceived memory function (MFQ), cognitive reserve (NART), and aspects of mood (PHQ-9, GAD-7). The results indicate that older adults were significantly slower than younger adults but no less precise, irrespective of gender. Age was negatively correlated with the speed of task performance. Our measure of general cognition was positively correlated with the task speed threshold but not with age per se. Perceived memory function, cognitive reserve, and mood were not related to task performance. The findings indicate that while attentional control is less efficient in older adulthood, age alone is not a defining factor in relation to accuracy. In a real-life context, general cognitive function, in conjunction with dynamic measures such as STAC, may represent a far more effective strategy for assessing the complex executive functions underlying driving ability

When participants get involved: reconsidering patient and public involvement in clinical trials at the MRC Clinical Trials Unit at UCL.

BACKGROUND: Patient and public involvement (PPI) in clinical trials aims to ensure that research is carried out collaboratively with patients and/or members of the public. However, current guidance on involving clinical trial participants in PPI activities is not consistent. METHODS: We reviewed the concept of participant involvement, based on our experience. Two workshops were held at the MRCCTU at UCL with the aim of defining participant involvement, considering its rationale; benefits and challenges; and identifying appropriate models for participant involvement in clinical trials. We considered how participant involvement might complement the involvement of other public contributors. Both workshops were attended by two patient representatives and seven staff members with experience of PPI in trials. Two of the staff members had also been involved in studies that had actively involved participants. They shared details of that work to inform discussions. RESULTS: We defined trial participants as individuals taking part in the study in question, including those who had already completed their trial treatment and/or follow-up. Because of their direct experience, involving participants may offer advantages over other public contributors; for example, in studies of new interventions or procedures, and where it is hard to identify or reach patient or community groups that include or speak for the study population. Participant involvement is possible at all stages of a trial; however, because there are no participants to involve during the design stage of a trial, prior to enrolment, participant involvement should complement and not replace involvement of PPI stakeholders. A range of models, including those with managerial, oversight or responsive roles are appropriate for involving participants; however, involvement in data safety and monitoring committees may not be appropriate where there is a potential risk of unblinding. Involvement of participants can improve the trial experience for other participants; optimising study procedures, improving communications; however, there are some specific, notably, managing participant confidentiality and practicalities relating to payments. CONCLUSIONS: Participant involvement in clinical trials is feasible and complements other forms of PPI in clinical trials. Involving active participants offers significant advantages, particularly in circumstances where trials are assessing new, or otherwise unavailable, therapies or processes. We recommend that current guidance on PPI should be updated to routinely consider including participants as valid stakeholders in PPI and potentially useful approach to PPI

The effects of age bias on neural correlates of successful and unsuccessful response inhibition in younger and older adults.

Facilitating communication between generations has become increasingly important. However, individuals often demonstrate a preference for their own age group, which can impact social interactions, and such bias in young adults even extends to inhibitory control. To assess whether older adults also experience this phenomenon, a group of younger and older adults completed a Go/NoGo task incorporating young and old faces, while undergoing functional magnetic resonance imaging. Within the networks subserving successful and unsuccessful response inhibition, patterns of activity demonstrated distinct neural age bias effects in each age group. During successful inhibition, the older adult group demonstrated significantly increased activity to other-age faces, whereas unsuccessful inhibition in the younger group produced significantly enhanced activity to other-age faces. Consequently, the findings of the study confirm that neural responses to successful and unsuccessful inhibition can be contingent on the stimulus-specific attribute of age in both younger and older adults. These findings have important implications in regard to minimizing the emergence of negative consequences, such as ageism, as a result of related implicit biases

The effects of age-bias on neural correlates of successful and unsuccessful response inhibition

Response inhibition is important for adherence to social norms, especially when norms conflict with biases based on one’s social identity. While previous studies have shown that in-group bias generally modulates neural activity related to stimulus appraisal, it is unclear whether and how an in-group bias based on age affects neural information processing during response inhibition. To assess this potential influence, young adults completed a Go/NoGo task incorporating younger face (in-group) and older face (out-group) stimuli while undergoing functional magnetic resonance imaging (fMRI). Our results replicated previous findings by demonstrating higher accuracy in successful Go compared to NoGo trials, as well as the engagement of nodes of the response inhibition network during successful response inhibition, and brain regions comprising the salience network during unsuccessful response inhibition. Importantly, despite a lack of behavioural differences, our results showed that younger and older face stimuli modulated activity in the response inhibition and salience networks during successful and unsuccessful inhibition, respectively. Interestingly, these effects were not uniform across networks. During successful response inhibition, in-group stimuli increased activity in medial prefrontal cortex and temporo-parietal junction, whereas out-group stimuli more strongly engaged pre-supplemental motor area. During unsuccessful response inhibition, in-group stimuli increased activity in posterior insula, whereas out-group stimuli more strongly engaged angular gyrus and intraparietal sulcus. Consequently, the results infer the presence of an age-bias effect in the context of inhibitory control, which has substantial implications for future experimental design and may also provide the means of investigating the neural correlates of implicit beliefs that contribute to ageis

Reaction time decomposition as a tool to study subcortical ischemic vascular cognitive impairment

Background: The study of reaction time (RT) and its intraindividual variability (IIV) in aging, cognitive impairment, and dementia typically fails to investigate the processing stages that contribute to an overall response. Applying “mental chronometry” techniques makes it possible to separately assess the role of processing components during environmental interaction. Objective: To determine whether RT and IIV-decomposition techniques can shed light on the nature of underlying deficits in subcortical ischemic vascular cognitive impairment (VCI). Using a novel iPad task, we examined whether VCI deficits occur during both initiation and movement phases of a response, and whether they are equally reflected in both RT and IIV. Methods: Touch cancellation RT and its IIV were measured in a group of younger adults (n = 22), cognitively healthy older adults (n = 21), and patients with VCI (n = 21) using an iPad task. Results: Whereas cognitively healthy aging affected the speed (RT) of response initiation and movement but not its variability (IIV), VCI resulted in both slowed RT and increased IIV for both response phases. Furthermore, there were group differences with respect to response phase. Conclusion: These results indicate that IIV can be more sensitive than absolute RT in separating VCI from normal aging. Furthermore, compared to cognitively healthy aging, VCI was characterized by significant deficits in planning/initiating action as well as performing movements. Such deficits have important implications for real life actions such as driving safety, employment, and falls risk

Cognitive Diversity in a Healthy Aging Cohort: Cross-Domain Cognition in the Cam-CAN Project.

Objective: Studies of "healthy" cognitive aging often focus on a limited set of measures that decline with age. The current study argues that defining and supporting healthy cognition requires understanding diverse cognitive performance across the lifespan. Method: Data from the Cambridge Centre for Aging and Neuroscience (Cam-CAN) cohort was examined across a range of cognitive domains. Performance was related to lifestyle including education, social engagement, and enrichment activities. Results: Results indicate variable relationships between cognition and age (positive, negative, or no relationship). Principal components analysis indicated maintained cognitive diversity across the adult lifespan, and that cognition-lifestyle relationships differed by age and domain. Discussion: Our findings support a view of normal cognitive aging as a lifelong developmental process with diverse relationships between cognition, lifestyle, and age. This reinforces the need for large-scale studies of cognitive aging to include a wider range of both ages and cognitive tasks.The Cambridge Centre for Aging and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1)

Rationale, design and methodology of a trial evaluating three strategies designed to improve sedation quality in intensive care units (DESIST study)

Objectives To describe the rationale, design and methodology for a trial of three novel interventions developed to improve sedation-analgesia quality in adult intensive care units (ICUs).Participants and Setting 8 clusters, each a Scottish ICU. All mechanically ventilated sedated patients were potentially eligible for inclusion in data analysis.Design Cluster randomised design in 8 ICUs, with ICUs randomised after 45?weeks baseline data collection to implement one of four intervention combinations: a web-based educational programme (2 ICUs); education plus regular sedation quality feedback using process control charts (2 ICUs); education plus a novel sedation monitoring technology (2 ICUs); or all three interventions. ICUs measured sedation-analgesia quality, relevant drug use and clinical outcomes, during a 45-week preintervention and 45-week postintervention period separated by an 8-week implementation period. The intended sample size was >100 patients per site per study period.Main Outcome measures The primary outcome was the proportion of 12?h care periods with optimum sedation-analgesia, defined as the absence of agitation, unnecessary deep sedation, poor relaxation and poor ventilator synchronisation. Secondary outcomes were proportions of care periods with each of these four components of optimum sedation and rates of sedation-related adverse events. Sedative and analgesic drug use, and ICU and hospital outcomes were also measured.Analytic approach Multilevel generalised linear regression mixed models will explore the effects of each intervention taking clustering into account, and adjusting for age, gender and APACHE II score. Sedation-analgesia quality outcomes will be explored at ICU level and individual patient level. A process evaluation using mixed methods including quantitative description of intervention implementation, focus groups and direct observation will provide explanatory information regarding any effects observed.Conclusions The DESIST study uses a novel design to provide system-level evaluation of three contrasting complex interventions on sedation-analgesia quality. Recruitment is complete and analysis ongoing.Trial registration number NCT01634451

Primary care capitation payments in the UK. An observational study

<p>Abstract</p> <p>Background</p> <p>In 2004 an allocation formula for primary care services was introduced in England and Wales so practices would receive equitable pay. Modifications were made to this formula to enable local health authorities to pay practices.</p> <p>Similar pay formulae were introduced in Scotland and Northern Ireland, but these are unique to the country and therefore could not be included in this study.</p> <p>Objective</p> <p>To examine the extent to which the Global Sum, and modifications to the original formula, determine practice funding.</p> <p>Methods</p> <p>The allocation formula determines basic practice income, the Global Sum. We compared practice Global Sum entitlements using the original and the modified allocation formula calculations.</p> <p>Practices receive an income supplement if Global Sum payments were below historic income in 2004. We examined current overall funding levels to estimate what the effect will be when the income supplements are removed.</p> <p>Results</p> <p>Virtually every Welsh and English practice (97%) received income supplements in 2004. Without the modifications to the formula only 72% of Welsh practices would have needed supplements. No appreciable change would have occurred in England.</p> <p>The formula modifications increased the Global Sum for 99.5% of English practices, while it reduced entitlement for every Welsh practice.</p> <p>In 2008 Welsh practices received approximately £6.15 (9%) less funding per patient per year than an identical English practice. This deficit will increase to 11.2% when the Minimum Practice Income Guarantee is abolished.</p> <p>Conclusions</p> <p>Identical practices in different UK countries do not receive equitable pay. The pay method disadvantages Wales where the population is older and has higher health needs.</p