The Effects of Midline Cerebellar rTMS on Human Pharyngeal Cortical Activity in the Intact Swallowing Motor System

We sought to compare the effects of 10 Hz cerebellar vermis (vs. unilateral hemispheric and sham) repetitive transcranial magnetic stimulation (rTMS) on cortical neuroelectrical activity and thereafter 10 Hz cerebellar vermis (vs. sham) rTMS on swallowing behaviour. Healthy participants (n = 25) were randomly allocated to receive vermis, unilateral hemisphere or sham 10 Hz cerebellar rTMS. Recordings were made using pharyngeal electromyography and manometry catheters, obtaining motor-evoked potentials (MEPs) and pressure recordings. The amplitudes of MEPs elicited using single-pulse TMS delivered to the pharyngeal areas of the motor cortex bilaterally were measured pre- and post-cerebellar stimulation. As in previous studies, abductor policis brevis (APB) MEPs were measured to assess post-rTMS modulation specificity. Swallowing was assessed using a swallowing accuracy task. Measurements were made at baseline and 15-min intervals for an hour post-intervention. Measurements involved TMS being used to elicit 10 MEPs bilaterally over the pharyngeal areas of the motor cortex, over the APB cortical representation adjacent to the pharyngeal area with the lowest resting motor threshold and 5 MEPs bilaterally over pharyngeal areas of the cerebellar hemispheres. Swallowing accuracy was assessed by giving participants 10 attempts to swallow and hit a digital target. Cerebellar vermis rTMS caused significant suppression of cortical pharyngeal MEP amplitudes compared with unilateral rTMS and sham (P = 0.0005, 0.002). APB and cerebellar MEP amplitudes were unaffected as were pharyngeal and APB MEP latencies. Following cerebellar vermis rTMS there was a significant reduction in swallowing accuracy compared with sham (P = 0.001). Our findings demonstrate cerebellar vermis rTMS exerts a suppressive effect on pharyngeal motor cortical activity and swallowing behaviour

Effect of donepezil on transcranial magnetic stimulation parameters in Alzheimer's disease

INTRODUCTION: There is a need for a reliable, noninvasive biomarker for Alzheimer's disease (AD). We assessed whether short-latency afferent inhibition (SAI), a transcranial magnetic stimulation paradigm that assesses cholinergic circuits of the brain, could become such a biomarker. METHODS: Nineteen patients with AD underwent four SAI testing sessions. The timing of their usual donepezil dose was altered to create different cholinergic states for each session. This was compared to the SAI results from 20 healthy subjects. RESULTS: SAI was not able to distinguish the different cholinergic states assessed in our study. There appeared to be a diurnal variation in cholinergic function in the control group, which was not present in the AD cohort. DISCUSSION: SAI does not appear to have a role in diagnosis and assessment of AD patients. The loss of diurnal variation, however, warrants further investigation as it may provide further biochemical insights about AD

Unmyelinated Peripheral Nerves Can Be Stimulated in Vitro Using Pulsed Ultrasound

Appreciation for the medical and research potential of ultrasound neuromodulation is growing rapidly, with potential applications in non-invasive treatment of neurodegenerative disease and functional brain mapping spurring recent progress. However, little progress has been made in our understanding of the ultrasound–tissue interaction. The current study tackles this issue by measuring compound action potentials (CAPs) from an ex vivo crab walking leg nerve bundle and analysing the acoustic nature of successful stimuli using a passive cavitation detector (PCD). An unimpeded ultrasound path, new acoustic analysis techniques and simple biological targets are used to detect different modes of cavitation and narrow down the candidate biological effectors with high sensitivity. In the present case, the constituents of unmyelinated axonal tissue alone are found to be sufficient to generate de novo action potentials under ultrasound, the stimulation of which is significantly correlated to the presence of inertial cavitation and is never observed in its absence

Functional strength training versus movement performance therapy for upper limb motor recovery early after stroke: a RCT

BACKGROUND: Not all stroke survivors respond to the same form of physical therapy in the same way early after stroke. The response is variable and a detailed understanding of the interaction between specific physical therapies and neural structure and function is needed. OBJECTIVES: To determine if upper limb recovery is enhanced more by functional strength training (FST) than by movement performance therapy (MPT), to identify the differences in the neural correlates of response to (1) FST and (2) MPT and to determine whether or not pretreatment neural characteristics can predict recovery in response to (1) FST and (2) MPT. DESIGN: Randomised, controlled, observer-blind, multicentre trial with embedded explanatory investigations. An independent facility used computer-generated randomisation for participants’ group allocation. SETTING: In-patient rehabilitation, participants’ homes, university movement analysis facilities and NHS or university neuroimaging departments in the UK. PARTICIPANTS: People who were between 2 and 60 days after stroke in the territory of the anterior cerebral circulation, with some voluntary muscle contraction in the more affected upper limb but not full function. INTERVENTIONS: Routine rehabilitation [conventional physical therapy (CPT)] plus either MPT or FST in equal doses during a 6-week intervention phase. FST was progressive resistive exercise provided during training of functional tasks. MPT was therapist ‘hands-on’ sensory input and guidance for production of smooth and accurate movement. MAIN OUTCOMES: Action Research Arm Test (ARAT) score for clinical efficacy. Neural measures were made of corticocortical [fractional anisotropy (FA) from corpus callosum midline], corticospinal connectivity (asymmetry of corticospinal tracts FA) and resting motor threshold of paretic biceps brachii (pBB) and extensor carpi radialis muscles (derived from transcranial magnetic stimulation). ANALYSIS: Change in ARAT scores were analysed using analysis of covariance models adjusted for baseline variables and randomisation strata. Correlation coefficients were calculated between change in neural measures and change in ARAT score per group and for the whole sample. An interaction term was calculated for each baseline neural measure and ARAT score change from baseline to outcome. RESULTS: A total of 288 participants were randomised [mean age 72.2 (standard deviation 12.5) years; mean ARAT score of 25.5 (18.2); n = 283]. For the 240 participants with ARAT measurements at baseline and outcome, the mean change scores were FST + CPT = 9.70 (11.72) and MPT + CPT = 7.90 (9.18). The group difference did not reach statistical significance (least squares mean difference 1.35, 95% confidence interval –1.20 to 3.90; p = 0.298). Correlations between ARAT change scores and baseline neural values ranged from –0.147 (p = 0.385) for whole-sample corticospinal connectivity (n = 37) to 0.199 (p = 0.320) for MPT + CPT resting motor threshold pBB (n = 27). No statistically significant interaction effects were found between baseline neural variables and change in ARAT score. There were no differences between groups in adverse events. LIMITATIONS: The number of participants in the embedded explanatory investigation was lower than expected. CONCLUSIONS: The small difference in upper limb improvement in response to FST and MPT did not reach statistical significance. Baseline neural measures neither correlated with upper limb recovery nor predicted therapy response. FUTURE WORK: Needs to continue investigation of the variability of response to specific physical therapies in people early after stroke. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19090862 and National Research Ethics Service reference number 11/EE/0524. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership

Grading of carotid artery stenosis with multidetector-row CT angiography: visual estimation or caliper measurements?

To assess the optimal method for grading carotid artery stenosis with computed tomographic angiography (CTA), we compared visual estimation to caliper measurements, and determined inter-observer variability and agreement relative to digital subtraction angiography (DSA). We included 46 patients with symptomatic carotid stenosis for whom CTA and DSA of 55 carotids was available. Stenosis quantification by CTA using visual estimation (CTAVE) (method 1) was compared with caliper measurements using subjectively optimized wide window settings (method 2) or predefined contrast-dependent narrow window settings (method 3). Measurements were independently performed by two radiologists and two residents. To determine accuracy and inter-observer variability, we calculated linear weighted kappa, performed a Bland-Altman analysis and calculated mean difference (bias) and standard deviation of differences (SDD). For inter-observer variability, kappa analysis was “very good” (0.85) for expert observers using CTAVE compared with “good” (0.61) for experts using DSA. Compared with DSA, method 1 led to overestimation (bias 5.8–8.0%, SDD 10.6–14.4), method 3 led to underestimation (bias −6.3 to −3.0%, SDD 13.0–18.1). Measurement variability between DSA and visual estimation on CTA (SDD 11.5) is close to the inter-observer variability of repeated measurements on DSA that we found in this study (SDD 11.6). For CTA of carotids, stenosis grading based on visual estimation provides better agreement to grading by DSA compared with stenosis grading based on caliper measurements

Randomised trials comparing different healthcare settings : an exploratory review of the impact of pre-trial preferences on participation, and discussion of other methodological challenges

BACKGROUND: We recently published a systematic review of different healthcare settings (such as outpatient, community or home) for administering intravenous chemotherapy, and concluded that performing conventionally designed randomised trials was difficult. The main problems were achieving adequate trial accrual rates and recruiting a study population which adequately represented the target population of interest. These issues stemmed from the fact that potential participants may have had pre-trial perceptions about the trial settings they may be allocated; such preferences will sometimes be strong enough for patients to decline an invitation to participate in a trial. A patient preference trial design (in which patients can choose, or be randomised to, an intervention) may have obviated these recruitment issues, although none of the trials used such a design. METHODS: In order to gain a better understanding of the broader prevalence and extent of these preference issues (and any other methodological challenges), we undertook an exploratory review of settings trials in any area of healthcare treatment research. We searched The Cochrane Library and Google Scholar and used snowballing methods to identify trials comparing different healthcare settings. RESULTS: Trial accrual was affected by patient preferences for a setting in 15 of the 16 identified studies; birth setting trials were the most markedly affected, with between 68 % and 85 % of eligible women declining to participate specifically because of preference for a particular healthcare setting. Recruitment into substance abuse and chemotherapy setting studies was also notably affected by preferences. Only four trials used a preference design: the proportion of eligible patients choosing to participate via a preference group ranged from between 33 % and 67 %. CONCLUSIONS: In trials of healthcare settings, accrual may be seriously affected by patient preferences. The use of trial designs which incorporate a preference component should therefore strongly be considered. When designing such trials, investigators should consider settings to be complex interventions, which are likely to have linked components which may be difficult to control for. Careful thought is also needed regarding the choice of comparator settings and the most appropriate outcome measures to be used

Quadriceps force generation in patients with osteoarthritis of the knee and asymptomatic participants during patellar tendon reflex reactions: an exploratory cross-sectional study

BACKGROUND: It has been postulated that muscle contraction is slower in patients with osteoarthritis of the knee than asymptomatic individuals, a factor that could theoretically impair joint protection mechanisms. This study investigated whether patients with osteoarthritis of the knee took longer than asymptomatic participants to generate force during reflex quadriceps muscle contraction. This was an exploratory study to inform sample size for future studies. METHODS: An exploratory observational cross sectional study was carried out. Two subject groups were tested, asymptomatic participants (n = 17), mean (SD) 56.7 (8.6) years, and patients with osteoarthritis of the knee, diagnosed by an orthopaedic surgeon, (n = 16), age 65.9 (7.8) years. Patellar tendon reflex responses were elicited from participants and measured with a load cell. Force latency, contraction time, and force of the reflex response were determined from digitally stored data. The Mann-Whitney U test was used for the between group comparisons in these variables. Bland and Altman within-subject standard deviation values were calculated to evaluate the measurement error or precision of force latency and contraction time. RESULTS: No significant differences were found between the groups for force latency (p = 0.47), contraction time (p = 0.91), or force (p = 0.72). The two standard deviation measurement error values for force latency were 27.9 ms for asymptomatic participants and 16.4 ms for OA knee patients. For contraction time, these values were 29.3 ms for asymptomatic participants and 28.1 ms for OA knee patients. Post hoc calculations revealed that the study was adequately powered (80%) to detect a difference between the groups of 30 ms in force latency. However it was inadequately powered (59%) to detect this same difference in contraction time, and 28 participants would be required in each group to reach 80% power. CONCLUSION: Patients with osteoarthritis of the knee do not appear to have compromised temporal parameters or magnitude of force generation during patellar tendon reflex reactions when compared to a group of asymptomatic participants. However, these results suggest that larger studies are carried out to investigate this area further

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security