Tremor in motor neuron disease may be central rather than peripheral in origin

BACKGROUND AND PURPOSE: Motor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post-mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated. METHODS: A total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients. RESULTS: Action tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning. CONCLUSIONS: Our data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition

GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

Continuous Theta Burst Stimulation Over the Dorsolateral Prefrontal Cortex and the Pre-SMA Alter Drift Rate and Response Thresholds Respectively During Perceptual Decision-Making

BACKGROUND: The speed-accuracy trade-off (SAT) refers to the balancing of speed versus accuracy during decision-making. SAT is very commonly investigated with perceptual decision-making tasks such as the moving dots task (MDT). The dorsolateral prefrontal cortex (DLPFC) and the pre-supplementary motor area (pre-SMA) are two brain regions considered to be involved in the control of SAT. OBJECTIVES/HYPOTHESES: The study tested whether the DLPFC and the pre-SMA play an essential role in the control of SAT. We hypothesized that continuous theta burst stimulation (cTBS) over the right DLPFC would primarily alter the rate of accumulation of evidence, whereas stimulation of the pre-SMA would influence the threshold for reaching a decision. METHODS: Fifteen (5 females; mean age = 30, SD =5.40) healthy volunteers participated in the study. We used two versions of the MDT and cTBS over the right DLPFC, pre-SMA and sham stimulation. The drift diffusion model was fit to the behavioural data (reaction time and error rate) in order to calculate the drift rate, boundary separation (threshold) and non-decision time. RESULTS: cTBS over the right DLPFC decreased the rate of accumulation of evidence (i.e. the drift rate from the diffusion model) in high (0.35 and 0.5) but not in low coherence trials. cTBS over the pre-SMA changed the boundary separation/threshold required to reach a decision on accuracy, but not on speed trials. CONCLUSIONS: The results suggest for the first time that both the DLPFC and the pre-SMA make essential but distinct contributions to the modulation of SAT

Cerebellar transcranial magnetic stimulation: The role of coil type from distinct manufacturers

BACKGROUND: Stimulating the cerebellum with transcranial magnetic stimulation is often perceived as uncomfortable. No study has systematically tested which coil design can effectively trigger a cerebellar response with the least discomfort. OBJECTIVE: To determine the relationship between perceived discomfort and effectiveness of cerebellar stimulation using different coils: MagStim (70 mm, 110 mm-coated, 110-uncoated), MagVenture and Deymed. METHODS: Using the cerebellar-brain inhibition (CBI) protocol, we conducted a CBI recruitment curve with respect to each participant's maximum tolerated-stimulus intensity (MTI) to assess how effective each coil was at activating the cerebellum. RESULTS: Only the Deymed double-cone coil elicited CBI at low intensities (-20% MTI). At the MTI, the MagStim (110 mm coated/uncoated) and Deymed coils produced reliable CBI, whereas no CBI was found with the MagVenture coil. CONCLUSION: s: The Deymed double-cone coil was most effective at cerebellar stimulation at tolerable intensities. These results can guide coil selection and stimulation parameters when designing cerebellar TMS studies

Concurrent anodal transcranial direct-current stimulation and motor task to influence sensorimotor cortex activation

Functional targeting with anodal high-definition transcranial direct current stimulation (HD-atDCS) of involved brain areas during performance of a motor task (online) may facilitate sensorimotor cortex neuroplasticity compared to performing the motor task after HD-atDCS (offline). The aim of this study was to employ functional near-infrared spectroscopy to compare the time course of motor task-related changes in sensorimotor cortex activation between online and offline HD-atDCS. We hypothesized that online HD-atDCS would have a greater effect on task-related sensorimotor cortex activation than offline HD-atDCS. In a within-subject sham controlled and randomized study design, 9 healthy participants underwent 3 HD-atDCS sessions (online, offline and sham) targeting the left sensorimotor cortex separated by 1 week. Functional near-infrared spectroscopy hemodynamic changes were measured from the left sensorimotor cortex during a simple finger opposition motor task before (Pre), immediately (T1) and 30 min after (T2) each session. The movement rates were not different between (online, offline, sham) or within (Pre, T1, T2) sessions. At T2, online HD-atDCS was associated with a significant increase (large effect size) in sensorimotor cortex activation (Hedges g = 1.01, p<0.001) when compared to sham; there was a nonsignificant trend to increase activation between offline and sham (Hedges g = 0.52, p=0.05) and between online and offline (Hedges g = 0.53, p=0.06). Concurrent application of HD-atDCS during a motor task may produce larger sensorimotor cortex activation than sequential application

GSH23.0-0.7+117, a neutral hydrogen shell in the inner Galaxy

GSH23.0-0.7+117 is a well-defined neutral hydrogen shell discovered in the VLA Galactic Plane Survey (VGPS). Only the blueshifted side of the shell was detected. The expansion velocity and systemic velocity were determined through the systematic behavior of the HI emission with velocity. The center of the shell is at (l,b,v)=(23.05,-0.77,+117 km/s). The angular radius of the shell is 6.8', or 15 pc at a distance of 7.8 kpc. The HI mass divided by the volume of the half-shell implies an average density n_H = 11 +/- 4 cm^{-3} for the medium in which the shell expanded. The estimated age of GSH23.0-0.7+117 is 1 Myr, with an upper limit of 2 Myr. The modest expansion energy of 2 * 10^{48} erg can be provided by the stellar wind of a single O4 to O8 star over the age of the shell. The 3 sigma upper limit to the 1.4 GHz continuum flux density (S_{1.4} < 248 mJy) is used to derive an upper limit to the Lyman continuum luminosity generated inside the shell. This upper limit implies a maximum of one O9 star (O8 to O9.5 taking into account the error in the distance) inside the HI shell, unless most of the incident ionizing flux leaks through the HI shell. To allow this, the shell should be fragmented on scales smaller than the beam (2.3 pc). If the stellar wind bubble is not adiabatic, or the bubble has burst (as suggested by the HI channel maps), agreement between the energy and ionization requirements is even less likely. The limit set by the non-detection in the continuum provides a significant challenge for the interpretation of GSH23.0-0.7+117 as a stellar wind bubble. A similar analysis may be applicable to other Galactic HI shells that have not been detected in the continuum.Comment: 18 pages, 6 figures. Figures 1 and 4 separately in GIF format. Accepted for publication in Astrophysical Journa

Age-dependent association of white matter abnormality with cognition after TIA or minor stroke

ObjectiveTo investigate if the association between MRI-detectable white matter hyperintensity (WMH) and cognitive status reported in previous studies persists at older ages (&gt;80 years), when some white matter abnormality is almost universally reported in clinical practice.MethodsConsecutive eligible patients from a population-based cohort of all TIA/nondisabling stroke (Oxford Vascular Study) underwent multimodal MRI, including fluid-Attenuated inversion recovery and diffusion-weighted imaging, allowing automated measurement of WMH volume, mean diffusivity (MD), and fractional anisotropy (FA) in normal-Appearing white matter using FSL tools. These measures were related to cognitive status (Montreal Cognitive Assessment) at age 6480 vs &gt;80 years.ResultsOf 566 patients (mean [range] age 66.7 [20-102] years), 107 were aged &gt;80 years. WMH volumes and MD/FA were strongly associated with cognitive status in patients aged 6480 years (all p &lt; 0.001 for WMH, MD, and FA) but not in patients aged &gt;80 years (not significant for WMH, MD, and FA), with age interactions for WMH volume (pinteraction = 0.016) and MD (pinteraction = 0.037). Voxel-wise analyses also showed that lower Montreal Cognitive Assessment scores were associated with frontal WMH in patients 6480 years, but not &gt;80 years.ConclusionMRI markers of white matter damage are strongly related to cognition in patients with TIA/minor stroke at younger ages, but not at age &gt;80 years. Clinicians and patients should not overinterpret the significance of these abnormalities at older ages

Efficient measurement of quantum gate error by interleaved randomized benchmarking

We describe a scalable experimental protocol for obtaining estimates of the error rate of individual quantum computational gates. This protocol, in which random Clifford gates are interleaved between a gate of interest, provides a bounded estimate of the average error of the gate under test so long as the average variation of the noise affecting the full set of Clifford gates is small. This technique takes into account both state preparation and measurement errors and is scalable in the number of qubits. We apply this protocol to a superconducting qubit system and find gate errors that compare favorably with the gate errors extracted via quantum process tomography.Comment: 5 pages, 2 figures, published versio

Modelling the distribution of white matter hyperintensities due to ageing on MRI images using Bayesian inference

White matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model. In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework. We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease. On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of , which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects