Therapeutics of disordered movement.

Human motor behavior is organized around two major neurotransmitter systems in the basal ganglia--dopaminergic and cholinergic. Hypokinetic disease may result from hypofunction of the dopaminergic system or cholinergic hyperfunction. The reverse seems true for many hyperkinetic movement disorders. Drugs which facilitate dopaminergic neurotransmission or which block cholinergic transmission relieve many hypokinetic disorders; the opposite approach is useful in treating many hyperkinetic disorders.     

Diagnosis and classification of chronic low back pain disorders: maladaptive movement and motor control impairments as underlying mechanism

Low back pain (LBP) is a very common but largely self-limiting condition. The problem arises however, when LBP disorders do not resolve beyond normal expected tissue healing time and become chronic. Eighty five percent of chronic low back pain (CLBP) disorders have no known diagnosis leading to a classification of 'non-specific CLBP' that leaves a diagnostic and management vacuum. Even when a specific radiological diagnosis is reached the underlying pain mechanism cannot always be assumed. It is now widely accepted that CLBP disorders are multi-factorial in nature. However the presence and dominance of the patho-anatomical, physical, neuro-physiological, psychological and social factors that can influence the disorder is different for each individual. Classification of CLBP pain disorders into sub-groups, based on the mechanism underlying the disorder, is considered critical to ensure appropriate management. It is proposed that three broad sub-groups of CLBP disorders exist. The first group of disorders present where underlying pathological processes drive the pain, and the patients' motor responses in the disorder are adaptive. A second group of disorders present where psychological and/or social factors represent the primary mechanism underlying the disorder that centrally drives pain, and where the patient's coping and motor control strategies are mal-adaptive in nature. Finally it is proposed that there is a large group of CLBP disorders where patients present with either movement impairments (characterized by pain avoidance behaviour) or control impairments (characterized by pain provocation behaviour). These pain disorders are predominantly mechanically induced and patients typically present with mal-adaptive primary physical and secondary cognitive compensations for their disorders that become a mechanism for ongoing pain. These subjects present either with an excess or deficit in spinal stability, which underlies their pain disorder. For this group, physiotherapy interventions that are specifically directed and classification based, have the potential to impact on both the physical and cognitive drivers of pain leading to resolution of the disorder. Two case studies highlight the different mechanisms involved in patients with movement and control impairment disorder outlining distinct treatment approaches involved for management. Although growing evidence exists to support this approach, further research is required to fully validate it.     

Neural mechanisms underlying auditory feedback control of speech

The neural substrates underlying auditory feedback control of speech were investigated using a combination of functional magnetic resonance imaging (fMRI) and computational modeling. Neural responses were measured while subjects spoke monosyllabic words under two conditions: (i) normal auditory feedback of their speech and (ii) auditory feedback in which the first formant frequency of their speech was unexpectedly shifted in real time. Acoustic measurements showed compensation to the shift within approximately 136 ms of onset. Neuroimaging revealed increased activity in bilateral superior temporal cortex during shifted feedback, indicative of neurons coding mismatches between expected and actual auditory signals, as well as right prefrontal and Rolandic cortical activity. Structural equation modeling revealed increased influence of bilateral auditory cortical areas on right frontal areas during shifted speech, indicating that projections from auditory error cells in posterior superior temporal cortex to motor correction cells in right frontal cortex mediate auditory feedback control of speech.     

静脉麻醉深度的控制策略

静脉麻醉时所有药物均经静脉给予,血药浓度过低或过高常引起病人术中知晓或麻醉恢复延迟,静脉麻醉的深度监测、预测与控制一直是临床麻醉医生所关注的问题。[第一段]     

Left hemisphere specialization for the control of voluntary movement rate

Although persuasive behavioral evidence demonstrates the superior dexterity of the right hand in most people under a variety of conditions, little is known about the neural mechanisms responsible for this phenomenon. As this lateralized superiority is most evident during the performance of repetitive, speeded movement, we used parametric rate variations to compare visually paced movement of the right and left hands. Twelve strongly right-handed subjects participated in a functional magnetic resonance imaging (fMRI) experiment involving variable rate thumb movements. For movements of the right hand, contralateral rate-related activity changes were identified in the precentral gyrus, thalamus, and posterior putamen. For left-hand movements, activity was seen only in the contralateral precentral gyrus, consistent with the existence of a rate-sensitive motor control subsystem involving the left, but not the right, medial premotor corticostriatal loop in right-handed individuals. We hypothesize that the right hemisphere system is less skilled at controlling variable-rate movements and becomes maximally engaged at a lower movement rate without further modulation. These findings demonstrate that right- and left-hand movements engage different neural systems to control movement, even during a relatively simple thumb flexion task. Specialization of the left hemisphere corticostriatal system for dexterity is reflected in asymmetric mechanisms for movement rate control.     

Brain circuitry underlying pain in response to imagined movement in people with spinal cord injury

Pain following injury to the nervous system is characterized by changes in sensory processing including pain. Although there are many studies describing pain evoked by peripheral stimulation, we have recently reported that pain can be evoked in subjects with complete spinal cord injury (SCI) during a motor imagery task. In this study, we have used functional magnetic resonance imaging to explore brain sites underlying the expression of this phenomenon. In 9 out of 11 subjects with complete thoracic SCI and below-level neuropathic pain, imagined foot movements either evoked pain in a previously non-painful region or evoked a significant increase in pain within the region of on-going pain (3.2 ± 0.7–5.2 ± 0.8). In both controls (n = 19) and SCI subjects, movement imagery evoked signal increases in the supplementary motor area and cerebellar cortex. In SCI subjects, movement imagery also evoked increases in the left primary motor cortex (MI) and the right superior cerebellar cortex. In addition, in the SCI subjects, the magnitude of activation in the perigenual anterior cingulate cortex and right dorsolateral prefrontal cortex was significantly correlated with absolute increases in pain intensity. These regions expanded to include right and left anterior insula, supplementary motor area and right premotor cortex when percentage change in pain intensity was examined. This study demonstrates that in SCI subjects with neuropathic pain, a cognitive task is able to activate brain circuits involved in pain processing independently of peripheral inputs.     

Proactive inhibitory control of movement assessed by event-related fMRI

Many neuronal processes play a role in the overall performance of inhibition tasks, often making it difficult to associate particular behavioral results to specific processes and structures. Indeed, in classical Go/NoGo, Stop or subliminal masked-prime tasks, inhibition is usually triggered at the same time as the sensorimotor processes involved in movement selection and conflict monitoring. To account for motor inhibition, many conflicting candidate structures, which depend on specific task requirements, have been proposed. In the present paper, first we used a simple reaction (RT) time task and, second, we took advantage of the fact that volitional inhibition is usually implemented before any stimulus occurs when subjects are aware that a warning signal will be presented before a target. This proactive inhibition would be intended to prevent anticipated responses and would be lifted as soon as the warning signal has been identified. In other words, we postulate that the same event does not trigger both inhibition and target processing, and that, indeed, these mechanisms can be separated in time. Event-related fMRI revealed that the medial prefrontal cortex and the inferior parietal cortex may be responsible for proactive inhibition, and that the primary motor cortex, the supplementary motor cortex and the putamen are the likely targeted sites of this inhibition. We conclude that executive control in these tasks may consist of switching from controlled inhibition (suppression of the neuronal processes underlying movement initiation) to automatic sensorimotor processing. The possible contribution of the medial prefrontal cortex to the tonic inhibition state adds new perspectives to possible meanings of a “default mode of brain function”.     

Personal control and disordered eating in female adolescents with type 1 diabetes

OBJECTIVE: The onset and subsequent management of diabetes can challenge one's sense of control. Sense of control can also be affected by the biological changes accompanying normal pubertal development. The negative impact on one's sense of control may be further exacerbated when both events (i.e., diabetes and puberty) occur in relatively close temporal proximity. RESEARCH DESIGN AND METHODS: This study examined the relationship between sense of control and disordered eating and glycemic control in 45 female adolescents with type 1 diabetes. RESULTS: A lower sense of overall control and a lower sense of bodily control were both directly related to more severe eating-disordered symptoms. However, a lower sense of overall control and lower bodily control were related to poorer metabolic control primarily when the diagnosis of diabetes occurred closer to the onset of puberty. CONCLUSIONS: Clinicians should assess and monitor perceptions of control and also consider the temporal proximity of disease onset and onset of puberty when managing type 1 diabetes in female adolescents.     

Bronchial artery embolization for the control of recurrent severe haemoptysis with no demonstrable underlying lesion

Summary

Bronchial artery embolization is an effective and safe technique in the control of haemoptysis from a variety of underlying causes, including carcinoma, cystic fibrosis, aspergilloma and old tuberculous cavities. We have used the technique in seven patients with massive, recurrent haemoptysis in whom no demonstrable underlying cause was present, all of whom had failed to settle on conservative therapy. In all seven, immediate control of haemoptysis was achieved, and five have remained in complete remission on mean follow-up of 19 months. We believe that embolization therapy is justified in such circumstances, and that the absence of a radiologically or bronchoscopically demonstrable underlying lesion should not be a deterrent.     

A test battery to measure the recovery of voluntary movement control following stroke

Tests of upper limb function and an activities of daily living (ADL) index were selected to measure recovery following stroke. Thirty stroke patients were assessed at intervals for up to 6 months to 1 year post-stroke using the battery. The results showed the ADL index is insensitive to upper limb recovery. All the tests measured recovery in some of the patients after 24 weeks post-stroke. Since the presentation and recovery of patients was variable, it is argued that it is necessary to offer a selection of assessment tests to measure recovery and to aid treatment planning.     

Hepatosplanchnic blood flow control and oxygen extraction are modified by the underlying mechanism of impaired perfusion

OBJECTIVE: To assess the effects of low hepatosplanchnic blood flow on regional blood flow control and oxygenation. DESIGN: Three randomized, controlled animal experiments. SETTING: Two university experimental research laboratories. SUBJECTS: Pigs of either gender. INTERVENTIONS: Isolated abdominal blood flow reduction: An extracorporeal shunt with reservoir and roller pump was inserted between proximal and distal aorta in 11 pigs. Abdominal aortic blood flow was reduced by 50% by activating the shunt. Mesenteric ischemia: In seven pigs, superior mesenteric arterial flow was reduced to 4 mL.kg.min for 4 hrs. Cardiac tamponade: In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 mL (moderate tamponade) and further to 30 mL.kg.min (severe tamponade) for 1 hr each. In each experimental condition, the same number of control animals was used. MEASUREMENTS AND MAIN RESULTS: Abdominal blood flow reduction, acute mesenteric ischemia, and moderate tamponade resulted in a portal venous flow (QPV) reduction to 51 +/- 23%, 52 +/- 18%, and 61 +/- 25% (mean +/- sd) of baseline flow, respectively. During abdominal blood flow reduction, QPV and hepatic arterial flow (QHA) decreased proportionally, whereas in moderate tamponade and acute mesenteric ischemia QPV reduction was associated with an increase in QHA of 30 +/- 39% and 102 +/- 108%, respectively (p = .001 and .018). Prolonged mesenteric ischemia restored total hepatic blood flow (Qliver) completely. During all conditions, decreasing mesenteric oxygen consumption was partly prevented by increased mesenteric oxygen extraction (p < .001 for all conditions). In contrast, decreasing hepatic oxygen delivery was associated with increased oxygen extraction in tamponade (p = .009) but not in abdominal blood flow reduction. CONCLUSIONS: Blood flow redistribution can restore Qliver totally when mesenteric blood flow is reduced selectively, partially when cardiac output is reduced, and not at all during abdominal blood flow reduction. Since hepatic oxygen extraction does not increase in abdominal blood flow reduction, hepatic oxygenation is at risk in this condition.     

Review of control strategies for robotic movement training after neurologic injury

There is increasing interest in using robotic devices to assist in movement training following neurologic injuries such as stroke and spinal cord injury. This paper reviews control strategies for robotic therapy devices. Several categories of strategies have been proposed, including, assistive, challenge-based, haptic simulation, and coaching. The greatest amount of work has been done on developing assistive strategies, and thus the majority of this review summarizes techniques for implementing assistive strategies, including impedance-, counterbalance-, and EMG- based controllers, as well as adaptive controllers that modify control parameters based on ongoing participant performance. Clinical evidence regarding the relative effectiveness of different types of robotic therapy controllers is limited, but there is initial evidence that some control strategies are more effective than others. It is also now apparent there may be mechanisms by which some robotic control approaches might actually decrease the recovery possible with comparable, non-robotic forms of training. In future research, there is a need for head-to-head comparison of control algorithms in randomized, controlled clinical trials, and for improved models of human motor recovery to provide a more rational framework for designing robotic therapy control strategies.     

Strategies for control of zidovudine concentrations in serum.

There are several clinical scenarios in which knowledge of zidovudine disposition may be important. This study evaluated the clinical utility of pharmacokinetic parameters for zidovudine derived from sparse serum concentration data obtained in an outpatient setting. Twelve human immunodeficiency virus-infected participants had two serum zidovudine concentrations determinations obtained on two different clinic visits, 2 to 38 days apart. Zidovudine concentrations were measured by radioimmunoassay. A one-compartment oral absorption model was used to describe zidovudine disposition. Three different approaches were used to estimate pharmacokinetic parameters: Bayesian estimation with one or two concentrations and least squares with one concentration. The ability of these parameters to predict concentrations measured during the second clinic visit was assessed by calculation of precision and bias and compared with predictions using standard fixed or weight-adjusted parameters. Estimated pharmacokinetic parameters for zidovudine were consistent with literature values; there was no statistically significant difference among the parameters calculated with the three estimation strategies. Absorptive phase concentrations were poorly predicted by all methods (mean percent bias, 157 to 249%; mean percent precision, 389 to 537%). Predictive ability for concentrations obtained in the elimination phase was strikingly improved: mean percent bias, -17 to 70%; mean percent precision, 40 to 95%. Bayesian and least-squares estimated parameters were statistically better than fixed-parameter values for predicting concentrations in the elimination phase. These observations provide a modeling framework to determine pharmacokinetic disposition of zidovudine in an individual, screen for the existence of a drug interaction, and conduct concentration-controlled clinical trials.