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

Combining reward and M1 transcranial direct current stimulation enhances the retention of newly learnt sensorimotor mappings

Background: Reward-based feedback given during motor learning has been shown to improve the retention of the behaviour being acquired. Interestingly, applying transcranial direct current stimulation (tDCS) during learning over the primary motor cortex (M1), an area associated with motor retention, also results in enhanced retention of the newly formed motor memories. However, it remains unknown whether combining these distinct interventions result in an additive benefit of motor retention. Methods: We investigated whether combining both interventions while participants learned to account for a visuomotor transformation results in enhanced motor retention (total n = 56; each group n = 14). To determine whether these interventions share common physiological mechanisms underpinning learning, we assessed motor cortical excitability and inhibition (i.e. SICI) on a hand muscle before and after all participants learned the visuomotor rotation using their entire arm and hand. Results: We found that both the Reward-Stim (i.e. reward + tDCS) and Reward-Sham (i.e. reward-only) groups had increased retention at the beginning of the retention phase, indicating an immediate effect of reward on behaviour. However, each intervention on their own did not enhance retention when compared to sham, but rather, only the combination of both reward and tDCS demonstrated prolonged retention. We also found that only the Reward-Stim group had a significant reduction in SICI after exposure to the perturbation. Conclusions: We show that combining both interventions are additive in providing stronger retention of motor adaptation. These results indicate that the reliability and validity of using tDCS within a clinical context may depend on the type of feedback individuals receive when learning a new motor pattern

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

SICI during changing brain states: Differences in methodology can lead to different conclusions

Background Short-latency intracortical inhibition (SICI) is extensively used to probe GABAergic inhibitory mechanisms in M1. Task-related changes in SICI are presumed to reflect changes in the central excitability of GABAergic pathways. Usually, the level of SICI is evaluated using a single intensity of conditioning stimulus so that inhibition can be compared in different brain states. Objective Here, we show that this approach may sometimes be inadequate since distinct conclusions can be drawn if a different CS intensity is used. Methods We measured SICI using a range of CS intensities at rest and during a warned simple reaction time task. Conclusions Our results show that SICI changes that occurred during the task could be either larger or smaller than at rest depending on the intensity of the CS. These findings indicate that careful interpretation of results are needed when a single intensity of CS is used to measure task-related physiological changes

Assessing TMS-induced D and I waves with spinal H-reflexes

Transcranial magnetic stimulation (TMS) of motor cortex produces a series of descending volleys known as D (direct) and I (indirect) waves. In the present study, we questioned whether spinal H-reflexes can be used to dissect D waves and early and late I waves from TMS. We therefore probed H-reflex facilitation at arrival times of D and I waves at the spinal level and thereby changed TMS parameters that have previously been shown to have selective effects on evoked D and different I waves. We changed TMS intensity and current direction and applied a double-pulse paradigm known as short-interval intracortical inhibition (SICI). Experiments were conducted in flexor carpi radialis (FCR) in the arm and soleus (SOL) in the leg. There were two major findings: 1) in FCR, H-reflex facilitation showed characteristic modulations with altered TMS parameters that correspond to the changes of evoked D and I waves; and 2) H-reflexes in SOL did not, possibly because of increased interference from other spinal circuits. Therefore, the most significant outcome of this study is that in FCR, H-reflexes combined with TMS seem to be a useful technique to dissect TMS-induced D and I waves. NEW & NOTEWORTHY Questions that relate to corticospinal function in pathophysiology and movement control demand sophisticated techniques to provide information about corticospinal mechanisms. We introduce a noninvasive electrophysiological technique that may be useful in describing such mechanisms in more detail by dissecting D and I waves from transcranial magnetic stimulation (TMS). Based on the combination of spinal H-reflexes and TMS in the flexor carpi radialis muscle, the technique was shown to measure selective effects on D and I waves from changing TMS parameters

On the Use of TMS to Investigate the Pathophysiology of Neurodegenerative Diseases

Neurodegenerative diseases are a collection of disorders that result in the progressive degeneration and death of neurons. They are clinically heterogenous and can present as deficits in movement, cognition, executive function, memory, visuospatial awareness and language. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool that allows for the assessment of cortical function in vivo. We review how TMS has been used for the investigation of three neurodegenerative diseases that differ in their neuroanatomical axes: (1) Motor cortex—corticospinal tract (motor neuron diseases), (2) Non-motor cortical areas (dementias), and (3) Subcortical structures (parkinsonisms). We also make four recommendations that we hope will benefit the use of TMS in neurodegenerative diseases. Firstly, TMS has traditionally been limited by the lack of an objective output and so has been confined to stimulation of the motor cortex; this limitation can be overcome by the use of concurrent neuroimaging methods such as EEG. Given that neurodegenerative diseases progress over time, TMS measures should aim to track longitudinal changes, especially when the aim of the study is to look at disease progression and symptomatology. The lack of gold-standard diagnostic confirmation undermines the validity of findings in clinical populations. Consequently, diagnostic certainty should be maximized through a variety of methods including multiple, independent clinical assessments, imaging and fluids biomarkers, and post-mortem pathological confirmation where possible. There is great interest in understanding the mechanisms by which symptoms arise in neurodegenerative disorders. However, TMS assessments in patients are usually carried out during resting conditions, when the brain network engaged during these symptoms is not expressed. Rather, a context-appropriate form of TMS would be more suitable in probing the physiology driving clinical symptoms. In all, we hope that the recommendations made here will help to further understand the pathophysiology of neurodegenerative diseases

Altered cortical activation patterns associated with baroreflex unloading following 24 h of physical deconditioning

Cardiovascular arousal is associated with patterned cortical activity changes. Head-down-tilt bed rest (HDBR) dimishes the baroreflex-mediated cardiac control. The present study tested the hypothesis that HDBR deconditioning would modify the forebrain organization for heart rate (HR) control during baroreflex unloading. Heart rate variability (HRV), blood pressure and plasma hormones were analysed at rest, whereas HR and cortical autonomic activation patterns (functional magnetic resonance imaging) were measured during graded and randomly assigned lower body negative pressure treatments (LBNP, -15 and -35 mmHg) both before (Pre) and after (Post) a 24 h HDBR protocol (study 1; n= 8). An additional group was tested before and following diuretic-induced hypovolaemia (study 2; n= 9; spironolactone, 100 mg day-1 for 3 days) that mimicked the plasma volume lost during HDBR (-15% in both studies; P \u3c 0.05). Head-down bed rest with hypovolaemia did not affect baseline HR, mean arterial pressure, HRV or plasma catecholamines. Head-down bed rest augmented the LBNP-induced HR response (P \u3c 0.05), and this was associated with bed-rest-induced development of the following changes: (i) enhanced activation within the genual anterior cingulate cortex and the right anterior insular cortex; and (ii) deactivation patterns within the subgenual regions of the anterior cingulate cortex. Diuretic treatment (without HDBR) did not affect baseline HR and mean arterial pressure, but did reduce resting HRV and elevated circulating noradrenaline and plasma renin activity (P \u3c 0.05). The greater HR response to LBNP following diuretic (P \u3c 0.05) was associated with diminished activation of the right anterior insula. Our findings indicate that 24 h of HDBR minimized the impact of diuretic treatment on baseline autonomic and cardiovascular variables. The findings also indicate that despite the similar augmentation of HR responses to LBNP and despite similar pre-intervention cortical activation patterns, HDBR and diuretic treatment produced different effects on the cortical responses, with HDBR affecting anterior cingulate cortex and right insula regions, whereas diuretic treatment affected primarily the right insula alone, but in a direction that was opposite to HDBR. The data indicate that physical deconditioning can induce rapid functional changes within the cortical circuitry associated with baroreflex unloading, changes that are distinct from diuretic-induced hypovolaemia. The results suggest that physical activity patterns exert a rapid and notable impact on the cortical circuitry associated with cardiovascular control. © 2012 The Physiological Society

Urban particulate pollution reduction by four species of green roof vegetation in a UK city

AbstractUrban particulate pollution in the UK remains at levels which have the potential to cause negative impacts on human health. There is a need, therefore, for mitigation strategies within cities, especially with regards to vehicular sources. The use of vegetation as a passive filter of urban air has been previously investigated, however green roof vegetation has not been specifically considered. The present study aims to quantify the effectiveness of four green roof species – creeping bentgrass (Agrostis stolonifera), red fescue (Festuca rubra), ribwort plantain (Plantago lanceolata) and sedum (Sedum album) – at capturing particulate matter smaller than 10 μm (PM10). Plants were grown in a location away from major road sources of PM10 and transplanted onto two roofs in Manchester city centre. One roof is adjacent to a major traffic source and one roof is characterised more by urban background inputs. Significant differences in metal containing PM10 capture were found between sites and between species. Site differences were explained by proximity to major sources. Species differences arise from differences in macro and micro morphology of the above surface biomass. The study finds that the grasses, A. stolonifera and F. rubra, are more effective than P. lanceolata and S. album at PM10 capture. Quantification of the annual PM10 removal potential was calculated under a maximum sedum green roof installation scenario for an area of the city centre, which totals 325 ha. Remediation of 2.3% (±0.1%) of 9.18 tonnes PM10 inputs for this area could be achieved under this scenario