Individual differences in intracortical inhibition predict motor-inhibitory performance.

Studies in which single- and paired-pulse TMS was applied during motor task performance have shed considerable light on the functional relevance of popular TMS-derived neurophysiological biomarkers such as short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI). While it has become well established that corticospinal excitability and intracortical inhibition are modulated during the enactment and cancellation of actions, it has remained unclear as to whether interindividual differences in these neurophysiological markers were associated with an individual's actual ability to restrain and cancel actions. In this study, we found that individual differences in both SICI and LICI were positively associated with relevant performance metrics on the go/no-go task and stop-signal task. Specifically, we found that individuals with greater resting SICI and LICI were faster to respond on go trials of the go/no-go task and were also more accurate at inhibiting their manual responses on both go/no-go and stop-signal tasks. These results are in support of findings from our earlier study and also provide new evidence for a general relationship between individual differences in resting-state GABAergic intracortical inhibitory functioning and motor inhibition.

Impaired motor inhibition in developmental coordination disorder.

This study aimed to evaluate the 'inhibitory deficit' hypothesis of developmental coordination disorder (DCD). We adopted a multifaceted approach, investigating two distinct, yet complimentary facets of motor inhibition: action restraint and action cancellation. This was achieved using carefully constructed versions of the 'Go/No-go' and 'Stop-signal' tasks, respectively. The sample comprised 11 young adults with DCD aged between 18 and 30 years of age and 11 typically developing, age-matched controls. Participants completed both the 'Go/No-go' and 'Stop-signal' tasks to assess action restraint and action cancellation respectively. Individuals with DCD were less efficient than their typically developing peers at performing both action restraint and action cancellation, indicated by significantly reduced action restraint efficiency index scores on the 'Go/No-go' task and a trend towards longer stop-signal reaction times on the 'Stop-signal' task. This work clarifies disparate evidence speaking to the integrity of action restraint in DCD and provides the first account of action cancellation in DCD using a purpose-built measure. In support of the inhibitory deficit hypothesis of DCD, our results suggest that young adults with DCD experience broad difficulties with engaging inhibitory mechanisms during motor behaviour.

The fall and rise of corticomotor excitability with cancellation and reinitiation of prepared action.

The sudden cancellation of a motor action, known as response inhibition (RI), is fundamental to human motor behavior. The behavioral selectivity of RI can be studied by cueing cancellation of only a subset of a planned response, which markedly delays the remaining executed components. The present study examined neurophysiological mechanisms that may contribute to these delays. In two experiments, human participants received single- and paired-pulse transcranial magnetic stimulation while performing a bimanual anticipatory response task. Participants performed most trials bimanually (Go trials) and were sometimes cued to cancel the response with one hand while responding with the other (Partial trials). Motor evoked potentials were recorded from left first dorsal interosseous (FDI) as a measure of corticomotor excitability (CME) during Go and Partial trials. CME was temporally modulated during Partial trials in a manner that reflected anticipation, suppression, and subsequent initiation of a reprogrammed response. There was an initial increase in CME, followed by suppression 175 ms after the stop signal, even though the left hand was not cued to stop. A second increase in excitability occurred prior to the (delayed) response. We propose an activation threshold model to account for nonselective RI. To investigate the inhibitory component of our model, we investigated short-latency intracortical inhibition (sICI), but results indicated that sICI cannot fully explain the observed temporal modulation of CME. These neurophysiological and behavioural results indicate that the default mode for reactive partial cancellation is suppression of a unitary response, followed by response reinitiation with an inevitable time delay.

Increases in plasma sheet temperature with solar wind driving during substorm growth phases.

During substorm growth phases, magnetic reconnection at the magnetopause extracts ∼1015 J from the solar wind which is then stored in the magnetotail lobes. Plasma sheet pressure increases to balance magnetic flux density increases in the lobes. Here we examine plasma sheet pressure, density, and temperature during substorm growth phases using 9 years of Cluster data (>316,000 data points). We show that plasma sheet pressure and temperature are higher during growth phases with higher solar wind driving, whereas the density is approximately constant. We also show a weak correlation between plasma sheet temperature before onset and the minimum SuperMAG AL (SML) auroral index in the subsequent substorm. We discuss how energization of the plasma sheet before onset may result from thermodynamically adiabatic processes; how hotter plasma sheets may result in magnetotail instabilities, and how this relates to the onset and size of the subsequent substorm expansion phase.

Shared neural resources between left and right interlimb coordination skills: the neural substrate of abstract motor representations.

Functional magnetic resonance imaging was used to reveal the shared neural resources between movements performed with effectors of the left versus right body side. Prior to scanning, subjects extensively practiced a complex coordination pattern involving cyclical motions of the ipsilateral hand and foot according to a 90 degrees out-of-phase coordination mode. Brain activity associated with this (nonpreferred) coordination pattern was contrasted with pre-existing isodirectional (preferred) coordination to extract the learning-related brain networks. To identify the principal candidates for effector-independent movement encoding, the conjunction of training-related activity for left and right limb coordination was determined. A dominantly left-lateralized parietal-to-(pre)motor activation network was identified, with activation in inferior and superior parietal cortex extending into intraparietal sulcus and activation in the premotor areas, including inferior frontal gyrus (pars opercularis). Similar areas were previously identified during observation of complex coordination skills by expert performers. These parietal-premotor areas are principal candidates for abstract (effector-independent) movement encoding, promoting motor equivalence, and they form the highest level in the action representation hierarchy.

Does hypnotic susceptibility influence information processing speed and motor cortical preparatory activity?

Responsiveness to suggestions while hypnotized is termed hypnotic susceptibility. An association between reaction time and hypnotic susceptibility has been demonstrated, but whether distinct changes in brain activity accompany this relationship remains unclear. We investigated the effect of hypnotic susceptibility on the speed of information processing and motor cortical preparatory activity. Twenty-one "low" (LowHS) and fifteen "high" (HighHS) hypnotically susceptible right-handed participants performed precued simple (SRT) and choice (CRT) reaction time key-press tasks under hypnotized and non-hypnotized conditions. Force and surface electromyography data were recorded from left and right index fingers. The contingent negative variation (CNV) was derived from electroencephalography data. Mean reaction time and premotor time was shorter in HighHS participants than LowHS participants for both simple and choice reaction time tasks. HighHS participants in the hypnotized state performed fewer errors than HighHS participants in the non-hypnotized state and LowHS participants in either state for the SRT task. HighHS participants made fewer errors overall than LowHS participants for the CRT task. Mean C3/C4 CNV amplitude was larger in HighHS than in LowHS participants. Furthermore, larger CNV amplitude was associated with shorter premotor time. Our findings indicate that shorter reaction time in the high hypnotically susceptible group is associated with a greater change in brain activity during motor preparation. One interpretation is that hypnotic susceptibility and neural mechanisms of arousal and selective attention are linked.

Evaluating Single-Spacecraft Observations of Planetary Magnetotails With Simple Monte Carlo Simulations: 1. Spatial Distributions of the Neutral Line.

A simple Monte Carlo model is presented that considers the effects of spacecraft orbital sampling on the inferred distribution of magnetic flux ropes, generated through magnetic reconnection in the magnetotail current sheet. When generalized, the model allows the determination of the number of orbits required to constrain the underlying population of structures: It is able to quantify this as a function of the physical parameters of the structures (e.g., azimuthal extent and probability of generation). The model is shown adapted to the Hermean magnetotail, where the outputs are compared to the results of a recent survey. This comparison suggests that the center of Mercury's neutral line is located dawnward of midnight by 0 . 3 7 - 1 . 02 + 1 . 21 R M and that the flux ropes are most likely to be wide azimuthally (∼50% of the width of the Hermean tail). The downtail location of the neutral line is not self-consistent or in agreement with previous (independent) studies unless dissipation terms are included planetward of the reconnection site; potential physical explanations are discussed. In the future the model could be adapted to other environments, for example, the dayside magnetopause or other planetary magnetotails.

Evaluating Single Spacecraft Observations of Planetary Magnetotails With Simple Monte Carlo Simulations: 2. Magnetic Flux Rope Signature Selection Effects.

A Monte Carlo method of investigating the effects of placing selection criteria on the magnetic signature of in situ encounters with flux ropes is presented. The technique is applied to two recent flux rope surveys of MESSENGER data within the Hermean magnetotail. It is found that the different criteria placed upon the signatures will preferentially identify slightly different subsets of the underlying population. Quantifying the selection biases first allows the distributions of flux rope parameters to be corrected, allowing a more accurate estimation of the intrinsic distributions. This is shown with regard to the distribution of flux rope radii observed. When accounting for the selection criteria, the mean radius of Hermean magnetotail quasi-force-free flux ropes is found to be 58 9 - 269 + 273  km. Second, it is possible to weight the known identifications in order to determine a rate of recurrence that accounts for the presence of the structures that will not be identified. In the case of the Hermean magnetotail, the average rate of quasi-force-free flux ropes is found to 0.12 min-1 when selection effects are accounted for (up from 0.05 min-1 previously inferred from observations).

What effect do substorms have on the content of the radiation belts?

Substorms are fundamental and dynamic processes in the magnetosphere, converting captured solar wind magnetic energy into plasma energy. These substorms have been suggested to be a key driver of energetic electron enhancements in the outer radiation belts. Substorms inject a keV "seed" population into the inner magnetosphere which is subsequently energized through wave-particle interactions up to relativistic energies; however, the extent to which substorms enhance the radiation belts, either directly or indirectly, has never before been quantified. In this study, we examine increases and decreases in the total radiation belt electron content (TRBEC) following substorms and geomagnetically quiet intervals. Our results show that the radiation belts are inherently lossy, shown by a negative median change in TRBEC at all intervals following substorms and quiet intervals. However, there are up to 3 times as many increases in TRBEC following substorm intervals. There is a lag of 1-3 days between the substorm or quiet intervals and their greatest effect on radiation belt content, shown in the difference between the occurrence of increases and losses in TRBEC following substorms and quiet intervals, the mean change in TRBEC following substorms or quiet intervals, and the cross correlation between SuperMAG AL (SML) and TRBEC. However, there is a statistically significant effect on the occurrence of increases and decreases in TRBEC up to a lag of 6 days. Increases in radiation belt content show a significant correlation with SML and SYM-H, but decreases in the radiation belt show no apparent link with magnetospheric activity levels.

NMR separation of beta-prochiral protons to the ether oxygen of chiral esters with lanthanide shift reagents.

The use of chiral ester derivatives of 2-phenylethan-1-ol in conjunction with chiral lanthanide shift reagents allows separation of the prochiral and homo prochiral protons to the ether oxygen in the NMR spectrum. Specifically the alpha- and beta- protons of the N-(4-nitrophenylsulfonyl)-L-phenylalanyl ester of 2-phenylethan-1-ol, after addition of either europium d- or l-3-heptafluorobutyrylcamphorate or ytterbium d-3-heptafluorobutyrylcamphorate are differentiated. This is the first report of the NMR separation of prochiral protons beta to an ester linkage. [reaction: see text]

The potential role of bisphosphonates in prostate cancer.

Skeletal morbidity secondary to metastases and osteoporosis is common in patients with advanced prostate cancer. Despite the typically sclerotic nature of prostate cancer metastases, osteoclast mediated osteolysis may play a significant role. This review addresses the newly recognised antitumour effects of bisphosphonates in addition to their role in inhibiting osteoclast mediated bone resorption. Both preclinical and clinical evidence of a role for bisphosphonates in the treatment and prevention of bone metastases secondary to prostate cancer is assessed.

Advances in the use of bisphosphonates in the prostate cancer setting.

Prostate cancer incidence is rising, and represents a major public health issue. Bone is by far the most common site for metastases in this disease, accounting for considerable morbidity. Until recently, there have been few viable options for the treatment of patients with hormone-refractory metastatic disease. This review examines the pathophysiology underlying the development of bone metastases. It also summarises some of the clinical approaches for the management of this common condition, focusing on recent evidence supporting the use of zoledronic acid, a member of one of the most promising groups of pharmacological agents, the third-generation bisphosphonates.

A prospective audit of the implementation of the 2-week rule for assessment of suspected urological cancers.

INTRODUCTION: All urology departments are under considerable pressure to comply with the UK Government's implementation of the 2-week rule for suspected cancer referrals. A prospective audit was planned to begin 6 months after introduction of cancer referral guidelines and a central data collection process, to investigate the local workload generated by these referrals, and compliance with the 2-week rule. METHODS: Data were collected prospectively over an 8-week period. All referral letters were examined by an independent urologist for any of the criteria defined by the regional tumour working group as suspicious of urological cancer. For suspected cancer referrals, the patient journey was followed to assess efficiency of the referral process. Results were compared with figures for '2-week rule' referrals for the Trust obtained from the UK Department of Health (DoH) website. RESULTS: In all, 234 GP referrals were reviewed, 82 fitting regional criteria for suspected cancer. Of these, (i) 13% were either marked urgent with a clear statement of 'cancer' or included a clear request to be seen within 2 weeks; (ii) 23% included no implication of cancer; (iii) 72% were seen in haematuria clinic, median time to clinic visit being 56.5 days, none complying with the 2-week rule; and (iv) of referrals not seen in haematuria clinic, median time to clinic was 21 days, with 34% compliance. With more stringent definitions of a cancer referral, DoH figures for the Trust recorded just 18 referrals over 3 months, with 89% compliance. DISCUSSION: GP referral letters meeting guidelines for suspected cancer often failed to imply or mention this. Compliance with the 2-week rule was poor, especially for the haematuria clinic. This is variably attributable to wording of GP letters, communication issues, and the sheer load of patients to be seen. CONCLUSION: DoH criteria for cancer referrals grossly underestimate the true magnitude of workload demanded of the service.

The application of direct potential fitting to the X1sigma+ ground electronic states of LiCl, TlCl, RbF and CsF.

A procedure for directly fitting the potential energy curve of a diatomic molecule has been applied to the X1sigma+ ground states of LiCl, TlCl, RbF and CsF. Extensive, high-precision infrared and pure-rotational data sets for all isotopomers of the aforementioned molecules have been employed in direct least-squares fits of a radially dependent Hamiltonian operator. The Born-Oppenheimer potentials are represented by a modified Lennard-Jones function that is shown to be flexible and provide the proper behavior in the long-range region of the potential. While the potential fits of LiCl and TlCl required the inclusion of Born-Oppenheimer breakdown functions, no such functions were necessary for either RbF or CsF.

Age-related neural correlates of cognitive task performance under increased postural load.

Behavioral studies suggest that postural control requires increased cognitive control and visuospatial processing with aging. Consequently, performance can decline when concurrently performing a postural and a demanding cognitive task. We aimed to identify the neural substrate underlying this effect. A demanding cognitive task, requiring visuospatial transformations, was performed with varying postural loads. More specifically, old and young subjects performed mental rotations of abstract figures in a seated position and when standing on a force platform. Additionally, functional magnetic resonance imaging (fMRI) was used to identify brain regions associated with mental rotation performance. Old as compared to young subjects showed increased blood oxygenation level-dependent (BOLD) responses in a frontoparietal network as well as activations in additional areas. Despite this overall increased activation, they could still modulate BOLD responses with increasing task complexity. Importantly, activity in left lingual gyrus was highly predictive (r = -0.83, adjusted R(2) = 0.65) of the older subjects' degree of success in mental rotation performance when shifting from a sitting to a standing position. More specifically, increased activation in this area was associated with better performance, once postural load increased.

Tension faecopneumothorax: a rare presentation of colonic diverticular perforation.

Tension faeco-pneumothorax is rare, typically occurring following strangulation of a diaphragmatic hernia. We report the case of a 69-year-old gentleman with a previous history of thoraco-abdominal oesophagectomy, who presented with an acute abdomen and respiratory distress. Initial investigations revealed pneumoperitoneum and left-sided pneumothorax. The patient rapidly deteriorated with development of tension pneumothorax. Following tube thoracostomy, feculent fluid was drained. At laparotomy, gross faecal peritonitis secondary to colonic diverticular perforation was encountered, with no evidence of intestinal diaphragmatic herniation. This case report highlights the rarity of this clinical entity as well as the possible complications of hiatal surgery.

Age-related changes in brain activation underlying single- and dual-task performance: visuomanual drawing and mental arithmetic.

Depending on task combination, dual-tasking can either be performed successfully or can lead to performance decrements in one or both tasks. Interference is believed to be caused by limitations in central processing, i.e. structural interference between the neural activation patterns associated with each task. In the present study, single- and dual-task effects were addressed in the context of aging. Increasing evidence from research on motor and cognitive tasks has shown that aging is associated with an expansion of brain activation and an increased BOLD-signal. This may result in increased structural interference and higher dual-task interference in older adults. Functional magnetic resonance imaging was used to measure the BOLD-response in 20 old and 20 young healthy adults while performing tasks separately, or combined. Single tasks consisted of mental arithmetic cued by auditory tones, and a visuomotor task, drawing a circular shape with spatiotemporal constraints. Age-related brain activation increases were only apparent during performance of the visuomotor task. Elderly showed higher BOLD-responses in a frontoparietal network, pointing to an increased reliance on sensory feedback processing. However, no increased structural interference was found for the elderly during performance of the dual-task. Region of interest analysis involving a functional cluster within the (pre-) supplementary motor area, active during performance of both single-tasks, revealed that both groups were able to upregulate their brain activity for dual-as compared to single-task performance. We assume that this allowed both groups to maintain performance under dual-task conditions, leading to minimal dual-task interference.