Can prepared responses be stored subcortically?

Quick voluntary responses to environmental stimuli are required of people on a daily basis. These movements have long been thought to be controlled via cortical loops involving processing of the stimulus and generation of a suitable response. Recent experiments have shown that in simple reaction time (RT) tasks, the appropriate response can be elicited much earlier (facilitated) when the go signal is replaced by a startling (124 dB) auditory stimulus. In the present experiment we combined a startling acoustic stimulus with an established RT paradigm that involved simple and choice RT. In a simple RT condition the prepared voluntary response was elicited at very short latencies following the startle. However, when cortical processing was required prior to responding (choice RT task), the startle did not facilitate the voluntary response, and gave rise to more movement production errors. Since movements requiring ongoing cortical processing following the stimulus are not facilitated by startle, it is unlikely that the startle facilitation is due to increased neural activation. In contrast, it appears more likely that the startle acts as an early trigger for subcortically stored prepared movements since movements that are prepared in advance can be initiated at such short latencies (<60 ms).     

Does movement planning follow Fitts' law? Scaling anticipatory postural adjustments with movement speed and accuracy

We wanted to determine whether movement planning followed Fitts' law by investigating the relationship between movement planning and movement performance in experienced dancers executing a typical classical ballet step in which the big toe was pointed to targets at different distances and of different widths so as to obtain several indices of difficulty (ID). Movement time, velocity and variability at the target were the variables of movement performance kinematics; movement planning was evaluated by analysis of anticipatory postural adjustments (APAs) to assess their modulation at different IDs. Movement time and peak of velocity were found to scale with the ID only when individual movement distance across target widths was entered into the analysis. APA magnitude and duration both scaled according to movement parameters but not in the same way. APA magnitude scaled with movement velocity, while APA duration was sensitive to the amplitude-to-accuracy ratio following the ID for movements performed in the shortest time interval when on-line feedback control is probably not available. Here we show that timing of muscle activation acts as an independent central command that triggers fine-tuning for speed-accuracy trade-off.     

Are amplitude and duration of anticipatory postural adjustments identically scaled to focal movement parameters in humans?

Anticipatory postural adjustments (APA), are known to precede the onset of voluntary movement. The aim of this study was to determine whether APA amplitude and duration are programmed identically according to the voluntary movement parameters. Subjects performed shoulder flexions at maximal and sub-maximal velocities, with and without an additional inertial load. APA amplitude and duration were plotted against kinetic energy and work of the forthcoming voluntary limb movement and showed a significant linear relation. When APA duration was plotted against mechanical work, two distinct APA duration values corresponded to a given value of work depending on the weight of the load, but this was not the case for APA amplitude. It is suggested that the APA amplitude and duration are scaled according to the same movement parameters, but not in the same way, APA duration being additionally sensitive to the postural effect which results from an additional weight.     

Do centrally programmed anticipatory postural adjustments in fast stepping affect performance of an associated ”touche” movement?

Ensuring maximum speed in executing a sequence of two voluntary movements requires the second movement to be triggered only after some delay. This is due to the existence of a ”relative refractory period.” If the second movement is initiated during the refractory period, its speed decreases (movement time increases). In the present study we tested the existence of a refractory period during the execution of a sequence of movements involving both the upper and the lower limbs. More precisely, we examined whether the maximal speed of the touche fencing movement is affected by the anticipatory postural adjustments (APA) preceding a voluntary lunge. The touche and the lunge are similar to a pointing task and a stepping forward movement, respectively. touche consists of hitting a target with a foil at maximal velocity. The results show that (a) when the touche was initiated prior to the onset of the APA of the lunge, the maximal foil velocity remains similar to that of an isolated touche, and (b) when the touche is initiated during the development of the APA of the lunge, the maximal foil velocity is lower than in the isolated touche. Furthermore, the maximal foil velocity decreases with the temporal progression of the APA and reaches its minimal value when initiated at the time of voluntary lunge execution (’foot off’). The discussion suggests that the centrally programmed APA that are elicited in the stepping forward movement induces a refractory period which affects performance of the pointing task. Received: 18 January 1999 / Accepted: 22 June 1999     

Can ageing be prevented by dietary restriction?

This paper disputes the suggestion of Hipkiss [Hipkiss, A., 2006. On the mechanisms of ageing suppression by dietary restriction-is persistent glycolysis the problem? Mech. Ageing Dev. 127, 8-15], according to which dietary restriction by decreasing methylglyoxal production may prevent ageing. A list of arguments is given to support the refusal of hypothesis: (i) it has never been proven that the main source of methylglyoxal is its formation from triose-phosphate intermediates of glycolysis; (ii) the above note particularly applies to pathological conditions as acetone breakdown and amino acid metabolism also come into picture under these circumstances; (iii) glycolysis is of vital importance, thus its inhibition or a sharp restriction of carbohydrate uptake are unlikely beneficial for those tissues that are exclusively dependent on glycolysis in the regard of their energy production. Taken these concerns into account and considered all the promising attempts to influence the toxic effects of methylglyoxal, it is feared that the theory, as it is, cannot offer benefit to prevent ageing.     

Can AIDS be prevented by T-cell vaccination?

T-cell vaccination as a specific prophylactic and therapeutic procedure has been shown to be effective in animal models of autoimmune disease. As autoimmunopathogenic components have been implicated in HIV infection, the authors propose a therapeutic test utilizing T-cell vaccination and suggest that AIDS could be prevented by such a procedure.     

Is lower leg proprioception essential for triggering human automatic postural responses?

It is unknown to what extent automatic postural responses are triggered by lower leg proprioception. This issue was addressed by studying postural control in five carefully selected patients with subtle diabetic polyneuropathy (restricted to the lower legs) and 15 healthy subjects. All patients had bilaterally absent Achilles tendon reflexes and weak or absent patella tendon reflexes, but muscle strength was fully preserved. Subjects were tested while standing on a supporting, movable force-plate. The contribution of lower leg proprioception to automatic postural responses was investigated by randomly exposing the subjects to either a 4 degrees 'toe-up' rotational perturbation ('normal ankle input'), a simultaneous 4-cm rearward translation and 4 degrees toe-up rotation ('enhanced ankle input'), or a simultaneous 4-cm rearward translation and 4 degrees 'toe-down' rotation ('nulled ankle input'). We recorded surface EMG (stretch reflexes and balance-correcting responses) from leg and trunk muscles, ankle torque and angular velocities of the upper and lower legs and trunk. We argued that automatic postural responses that have abnormally small amplitudes in patients and are modulated in controls with the velocity of different types of ankle rotations must receive a major input from lower leg proprioception. Conversely, automatic postural responses that are weakly modified in amplitude or onset by different ankle perturbations and are present despite nulled ankle inputs and, finally, are unaffected in patients with distal polyneuropathy must be triggered or modulated by inputs other than from lower leg proprioception. Normal postural synergies and strategies were maintained in patients, although within a given synergy the timing and amplitude of some automatic postural responses were abnormal. A few automatic postural responses appeared to be triggered or modulated by lower leg proprioception. Thus, early stretch reflexes in soleus and medial gastrocnemius were severely diminished in patients, while in controls these stretch reflexes were modulated by different ankle perturbations. Furthermore, balance-correcting responses in tibialis anterior were diminished and delayed in patients, while in controls these balance-correcting responses were modulated by different ankle perturbations. Other automatic postural responses were apparently not triggered or modulated by lower leg proprioception, but likely received a major input from more proximal sensory systems. Thus, in both groups prominent balance-correcting responses were present in several muscles (soleus, gastrocnemius, quadriceps, paraspinals and trapezius) during the 'nulled ankle input' condition, where ankle position was stabilised over the first 250 ms. During the 'enhanced ankle input' condition, where prominent ankle dorsiflexion occurred during the first 200 ms, amplitudes of balance-correcting responses were only marginally weaker in patients than in controls. We analysed body segment displacements to unveil the potential nature of proximal triggers for automatic postural responses. As opposed to the 'inverted pendulum' concept of postural control, early movement occurred in the knees, hips and trunk well before the onset of automatic postural responses. For example, during the 'nulled ankle input' condition, the lower leg moved forward with early knee flexion, followed by knee extension. The trunk extended backwards at 80 ms, which was followed by forward flexion. The absent stretch reflex and weaker balance-correcting responses in patients produced changed trunk velocity profiles (mainly a reduced initial backward motion of the trunk), but lower-body segment movements showed no consistent differences between the two groups. Considering these body segment displacements, any automatic postural response with an onset within the first 200 ms could well be triggered by receptors located at the knee, hip or trunk. (ABSTRACT TRUNCATED)     

Can insulin resistance be reversed by insulin therapy?

Insulin resistance (IR) is a state of decreased tissue sensitivity to insulin, which commonly exists in patients with metabolic syndrome and diabetes, and leads to compensatory hyperinsulinemia to maintain normoglycemia. It is characterized by pathway-specific inhibition of the PI3K/Akt signaling, which concerns the positive actions of insulin including glucose and lipid metabolism, while other pathways including the Ras/MAPK pathway, which accounts for the negative actions of insulin such as stimulation of smooth muscle proliferation and secretion of endothelin-1, stay unaffected. Thus it was concerned that insulin therapy may exacerbate the negative effects of insulin in IR states. However, treatment of diabetes with insulin in clinical practice showed uniformly beneficial rather than harmful results. So we hypothesize that insulin therapy may itself reverse insulin resistance, thus avoiding magnification of the MAPK pathway-related deleterious effects. The mechanisms may include the recently revealed anti-inflammatory effects of insulin as well as its conventional glucose and free fatty acids lowering effects, and possibly may also include changes in body fat distribution and plasma adiponectin level. Whether there are direct mechanisms that insulin therapy modulates insulin sensitivity remains to be investigated.     

Can cytokines be removed by hemofiltration or hemoadsorption?

To study the removability of pro-inflammatory cytokines by hemofiltration (HF), we performed experimental HF with various high-flux membranes (HFM) using a closed circuit system filled with monocyte-free human plasma, which contained TNFalpha, IL-1beta, and IL-6. Plasma and filtrate samples were taken before and 1, 2, 3, and 4 hours after the initiation of HF, and each cytokine was determined by enzyme-linked immunosorbent assay. IL-1beta was well removed through filtration during experimental HF using HFM (PAN>CTA>PMMA>PS). TNFalpha and IL-6 were only minimally filtered out by HF using HFM. TNFalpha was removed to some extent by using PS, and IL-6 was partially removed by using PMMA during experimental HF through other mechanisms, such as adsorption, than the filtration. IL-1beta and IL-6 were effectively removed by HA using charcoal adsorbent column, especially during the first 2 hours, while TNFalpha was only partly removed.     

Do anticipatory postural adjustments occurring in different segments of the postural chain follow the same organisational rule for different task movement velocities, independently of the inertial load value?

Dynamic phenomena, termed anticipatory postural adjustments (APA), are known to precede the onset of voluntary movement. Their anticipatory nature confers a particular status on APAs: as they cannot be triggered reflexly by afferent signals induced by a voluntary movement, it can be asked whether the APA parameters are centrally programmed as a function of some task movement parameters or are only the peripheral consequence of control variables. To this end the present study aims to determine whether the APAs occurring at the different sites of the postural chain yield the same accelerometric patterns and follow the same organisational rules when the task movement velocity changes, independently of the inertial load value. Subjects performed unilateral shoulder flexions at maximal and submaximal velocities, with (IUF) and without (OUF) an additional inertial load. Accelerometers were attached to the wrist and trunk, and on both sides of the body at shank, thigh, hip and shoulder. The results show that: 1) there was evidence of anticipatory acceleration in all segments of the postural chain; 2) each acceleration profile for the anticipatory phase was maintained over different focal movement velocities whether there was an additional load or not; 3) there were significant linear relationships between the amplitude of each segmental anticipatory acceleration and the square of the task movement velocity, the slope of which differs as a function of the inertial load; 4) there were close intersegmental correlations between these anticipatory accelerations which did not depend on the inertial load. In addition the correlation between the lower limbs and the opposite side of the body was positive, suggesting a diagonal postural pattern. A comparison of the present kinematic data with the corresponding EMG data reported in the literature argues in favour of a centrally determined kinematic pattern. It is proposed that the diagonal postural pattern between postural segments be considered as one of the order rules which could simplify the control process of asymmetrical movement. The anticipatory kinematics of each of the body segments would be calibrated with the velocity and the inertial load and scaled to the other segments to counteract the perturbing effect of the asymmetrical focal movement on body balance.     

Can Healing be Taught?

The recent explosion of opportunities and interest in learning to heal has not been accompanied by sufficiently convincing empirical data to show that healing is teachable. We explore selected examples of teaching modalities and outline their general ethos. Five empirical criteria necessary to demonstrate teachability are outlined. We suggest that no research to date, including a previous claim by one of us (W.F.B.), has surmounted the difficult obstacles that need to be overcome to make such a claim. Some scientific and social implications of the teachability of healing are discussed.     

Can virtue be taught?

Applying standards of virtue that define the "good doctor" in a complex and technologically sophisticated health care system is often challenging and sometimes confusing. What are the characteristics of a "good doctor," who wishes to live up to high ethical and professional standards but who also must live and work in a health care system in which moral ambiguity is pervasive? Medical educators are urgently faced with such questions as their schools try to equip students with the skills and capacities required of the virtuous physician. The author describes how Aristotelian concepts of virtue can be used to guide medical educators in defining and teaching virtue. He then discusses how such traits as the ability to tolerate moral differences and ambiguity, the ability to develop thoughtful individual moral positions, and the capacity to respect and understand various cultural traditions may be what might be considered virtues in today's health care system. A "good" doctor, then, would be someone who is thoughtful, fair-minded, respectful of differences, and committed to his or her professional values.     

Can vertebral density changes be explained by intervertebral disc degeneration?

One of the major problems facing the elderly spine is the occurrence of vertebral fractures due to low bone mass. Although typically attributed to osteoporosis, disc degeneration has also been suggested to play a role in vertebral fractures. Existing bone adaptation theories and simulations may explain the biomechanical pathway from a degenerated disc to an increased fracture risk. A finite element model of a lumbar segment was created and calibrated. Subsequently the disc properties were varied to represent either a healthy or degenerated disc and the resulting bone adaptation was simulated. Disc degeneration resulted in a shift of load from the nucleus to the annulus. The resulting bone adaptation led to a dramatically reduced density of the trabecular core and to an increased density in the vertebral walls. Degeneration of just the nucleus, and in particular the dehydration of the nucleus, resulted in most of this bone density change. Additional annulus degeneration had much less of an effect on the density values. The density decrease in the trabecular core as seen in this study matches clinical observations. Therefore, bone remodeling theories can assists in explaining the potential synergistic effects of disc degeneration and osteoporotis in the occurrence of vertebral fractures.     

MicroRNA expression altered by diet: Can food be medicinal?

As the link between metabolism and major disease processes becomes more well-defined, the identification of key molecular targets is leading to new therapeutic strategies. As a result, small non-coding RNA molecules that regulate gene expression via epigenetic alterations, microRNAs have been identified as regulators of these metabolic processes. In the last decade, dietary interventions have been used to change metabolism and to potentially alter disease progression and clinical outcomes. These interventions have been linked, at a molecular level, to microRNAs. This review will summarize the role of various dietary strategies on the expression of several microRNA families.     

Can delusions be understood linguistically?

Delusions are widely believed to reflect disturbed cognitive function, but the nature of this remains elusive. The “un-Cartesian” cognitive-linguistic hypothesis maintains (a) that there is no thought separate from language, that is, there is no distinct mental space removed from language where “thinking” takes place; and (b) that a somewhat broadened concept of grammar is responsible for bestowing meaning on propositions, and this among other things gives them their quality of being true or false. It is argued that a loss of propositional meaning explains why delusions are false, impossible and sometimes fantastic. A closely related abnormality, failure of linguistic embedding, can additionally account for why delusions are held with fixed conviction and are not adequately justified by the patient. The un-Cartesian linguistic approach to delusions has points of contact with Frith’s theory that inability to form meta-representations underlies a range of schizophrenic symptoms. It may also be relevant to the nature of the “second factor” in monothematic delusions in neurological disease. Finally, it can inform the current debate about whether or not delusions really are beliefs.     

Can IgE-mediated allergic diseases be prevented by using allergen-specific IgG antibodies?

The prevalence of allergic disease has increased significantly over the past few decades, especially in children. Prenatal period may represent an ideal time for the implementation of interventions to prevent allergy and allergic diseases. In this hypothesis, allergen-specific immunoglobulin G (IgG) antibodies may combine with maternal allergens as blocking antibodies with immunoglobulin E (IgE) or mask antigenic determinants in their binding to prevent the sensitization of the fetus. It may also modify fetal immune response to prevent the production of allergen-specific IgE antibodies and the further development of allergic diseases. Recent epidemiological, immunological and intervention studies supporting the hypothesis were summarized. Anti-mite human IgG Fabs (antigen binding fragments) were prepared from two immunoglobulin genes libraries and they were confirmed to have a specific binding blocking property by an in vitro mastocyte degranulation inhibition test. Allergen-specific human IgG antibodies may have a potential use in the prenatal immunoprophylaxis or the prevention of allergic diseases after birth.     

Can B-Cell Signalling be Understood?

相似文献   

Are there anticipatory segmental adjustments associated with lower limb flexions when balance is poor in humans?

For a leg raising task performed in a sagittal plane, it has been shown that body balance instability can suppress anticipatory postural adjustments (APAs). The aim of this study was to determine whether the global (centre of mass) postural adjustments were replaced by local (segmental) ones, which were compensating each other and resulting in a lack of global APAs. Six healthy subjects must perform a lower limb flexion from two initial postures, corresponding to a bipedal (Fbu) and an unipedal (Fuu) stance. Kinematics of postural adjustments were recorded with accelerometers. The results showed that in Fbu the kinematics have large durations of APAs, contrary to Fuu where there are none. They showed also that during the voluntary movement the magnitudes of the segmental postural accelerations were equal or superior in Fuu than in Fbu on the anteroposterior and lateral axes, where balance is poor. Also while, on the contrary, the magnitudes are reversed on the vertical axis. These results suggest that firstly: (1) the absence of APAs can correspond to a strategic response for weak postural base configuration and secondly; (2) the local postural accelerations, depending to the axes, are linked to two different functions: to maintaining the balance and to performing the focal movement.