Molecular mechanisms of L-DOPA-induced dyskinesia

L-DOPA (L-3,4-dihydroxyphenylalanine) remains the most effective drug for the treatment of Parkinson's disease. However, chronic use causes dyskinesia, a complex motor phenomenon that consists of two components: the execution of involuntary movements in response to drug administration, and the 'priming' phenomenon that underlies these movements' establishment and persistence. A reinterpretation of recent data suggests that priming for dyskinesia results from nigral denervation and the loss of striatal dopamine input, which alters glutamatergic synaptic connectivity in the striatum. The subsequent response of the abnormal basal ganglia to dopaminergic drugs determines the manner and timing of dyskinesia expression. The combination of nigral denervation and drug treatment establishes inappropriate signalling between the motor cortex and the striatum, leading to persistent dyskinesia.     

Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep

The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0-5 and 6-13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements.     

Mitochondrial abnormalities in dermatomyositis: characteristic pattern of neuropathology

The objective of the work described in this paper was to evaluate mitochondrial abnormalities in perifascicular atrophic fibers in muscle biopsies from patients with dermatomyositis (DM). We localized cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemically in muscle biopsies of 12 patients with DM, and 12 control patients with neurogenic atrophy. These two histochemical techniques were also combined on single tissue sections in order to accentuate any COX-negative fibers. Eleven out of 12 patients (91.6%) with DM showed histochemical evidence of mitochondrial dysfunction in perifascicular distribution. Similar abnormalities in histochemical staining were not seen in comparably sized myofibers that were atrophic due to denervation. It is concluded that abnormal SDH and COX histochemical activities in atrophic perifascicular fibers are characteristic of dermatomyositis. These abnormal staining characteristics could not be accounted for solely by myofiber atrophy, or by generalized abnormalities in histochemical staining.     

Muscle spasms associated with Sudeck's atrophy after injury.

Four patients developed abnormal involuntary movements of a limb after injury. All subsequently developed sympathetic algodystrophy with Sudeck''s atrophy and then abnormal muscle spasms or jerks of the affected limb, lasting years. Sympathetic block in three patients did not relieve the abnormal movements. Two patients obtained partial recovery spontaneously, but the other two required surgery for relief. The pathophysiology of this condition remains to be determined but the evidence suggests that it is a distinct, disabling clinical syndrome.     

Neuronal mechanisms of motor signal transmission in the thalamic ventrooral nucleus in spasmodic torticollis patients

A microelectrode technique was used to study the neuronal mechanisms of motor signal transmission in the ventrooral internus nucleus (Voi) of the motor thalamus during voluntary and involuntary pathological (dystonic) movements in patients with spasmodic torticollis. Voi cell elements proved highly reactive to various functional (mostly motor) tests. An activity analysis of 55 Voi neurons detected during nine stereotactic operations revealed, first, a difference in neuronal mechanisms of motor signal transmission for voluntary movements that do or do not involve the affected axial muscles of the neck and for passive and abnormal involuntary dystonic movements. Second, a sensory component was found to play a key role in the mechanisms of sensorimotor interactions during voluntary and involuntary dystonic head and neck movements activating the axial muscles of the neck. Third, rhythmic and synchronized activity of Voi neurons was shown to play an important role in motor signal transmission during voluntary and passive movements. The Voi nucleus was directly implicated in the mechanisms of involuntary head movements and tension of the neck muscles in spasmodic torticollis. The results can be used to identify the Voi nucleus of the thalamus during stereotactic neurosurgery in order to select the optimal destruction or stimulation target and to reduce the postoperative effects in spasmodic torticollis patients.     

Apomorphine in Huntington's chorea: clinical observations and theoretical considerations

Five patients, four definitively diagnosed as suffering from Huntington's disease and the fifth with abnormal involuntary movements (AIM) and dementia but no apparent family history of the disease, were administered apomorphine. Although the short duration of action and stressful side-effects produced by apomorphine limited its use regarding a complete dose- and time-response evaluation, slight to marked diminution of AIM was seen in all patients. Optimal doses ranged from 1–2 mg across patients, producing a significant reduction in AIM for the entire hour of observations. Theoretical interpretations of these effects regarding dopaminergic receptor stimulation and/or blockade by apomorphine are discussed.     

Abnormal motor patterns in the framework of the equilibrium-point hypothesis: a cause for dystonic movements?

Until now, the equilibrium-point hypothesis (λ model) of motor control has assumed nonintersecting force-length characteristics of the tonic stretch reflex for individual muscles. Limited data from animal experiments suggest, however, that such intersections may occur. We have assumed the possibility of intersection of the characteristics of the tonic stretch reflex and performed a computer simulation of movement trajectories and electromyographic patterns. The simulation has demonstrated, in particular, that a transient change in the slope of the characteristic of an agonist muscle may lead to temporary movement reversals, hesitations, oscillations, and multiple electromyographic bursts that are typical of movements of patients with dystonia. The movement patterns of three patients with idiopathic dystonia during attempts at fast single-joint movements (in the elbow, wrist, and ankle) were recorded and compared with the results of the computer simulation. This approach considers that motor disorders in dystonia result from faulty control patterns that may not correlate with any morphological or neurophysiological changes. It provides a basis for the high variability of dystonic movements. The uniqueness of abnormal motor patterns in dystonia, that precludes statistical analysis across patients, may result from subtle differences in the patterns of intersecting characteristics of the tonic stretch reflex. The applicability of our analysis to disordered multijoint movement patterns is discussed. Received: 26 July 1993/Accepted in revised form: 22 December 1993     

Collective motion and cannibalism in locust migratory bands

Plagues of mass migrating insects such as locusts are estimated to affect the livelihood of one in ten people on the planet [1]. Identification of generalities in the mechanisms underlying these mass movements will enhance our understanding of animal migration and collective behavior while potentially contributing to pest-management efforts. We provide evidence that coordinated mass migration in juvenile desert locusts (Schistocerca gregaria) is influenced strongly by cannibalistic interactions. Individuals in marching bands tend to bite others but risk being bitten themselves. Reduction of individuals' capacity to detect the approach of others from behind through abdominal denervation (1) decreases their probability to start moving, (2) dramatically reduces the mean proportion of moving individuals in groups, and (3) significantly increases cannibalism. Similarly, occlusion of the rear visual field inhibits individuals' propensity to march. Abdomen denervation did not influence the behavior of isolated locusts. When within groups, abdominal biting and the sight of others approaching from behind triggers movement, creating an autocatalytic feedback that results in directed mass migration. This "forced march" driven by cannibalistic interactions suggests that we need to reassess our view of both the selection pressure and mechanism that can result in the coordinated motion of such large insect groups.     

Autonomic denervation for the treatment of atrial fibrillation

The influence of the autonomic nervous system (ANS) on triggering and perpetuation of atrial fibrillation (AF) is well established. Ganglionated plexi (GP) ablation achieves autonomic denervation by affecting both the parasympathetic and sympathetic components of the ANS. An anatomic approach for GP ablation at relevant atrial sites appears to be safe, and improves the results of PV isolation in patients with paroxysmal and persistent AF. GP ablation can be accomplished endocardially or epicardially, ie, during the maze procedure or thoracoscopic approaches. Further experience is needed to assess the clinical value of this promising technique.     

正常及异常双眼视觉的视动震颤（OKN）反应特性研究

为探讨不同双眼视觉状态下ＯＫＮ反应的特性,对正常人和不同类型的双眼视觉异常者的单眼鼻向及颞向ＯＫＮ反应进行了研究。实验发现：单眼视觉抑制者表现出鼻向与颞向ＯＫＮ反应不对称特性;两眼皆因视剥夺造成双眼视觉异常者主要以ＯＫＮ眼动增益降低为特点;双眼视觉正常者鼻、颞向ＯＫＮ反应是对称的。结果表明：单眼ＯＫＮ眼动反应的不对称特性及增益改变对探讨双眼视觉异常机制有重要意义,为视皮层双眼细胞异常导致单眼ＯＫＮ不对称的假设提供了支持性证据,并对弱视早期诊断及其分类有重要价值。     

Dipole source localization by mottled sculpin. III. Orientation after site-specific, unilateral denervation of the lateral line system

To test the hypothesis that spatial excitation patterns along the lateral-line system underlie source localization, we videotaped the orientation behavior of blinded mottled sculpin in response to a small dipole source (50-Hz vibrating sphere) before and after unilateral denervation of the lateral line system on different body regions (head, trunk and head + trunk). Approach pathways were qualitatively similar to those followed by normal intact animals. Abnormal behavior (turning in circles) was not observed. However, the frequency with which fish placed their intact side facing the source increased by 12–89%, depending on the denervation site. The angular accuracy of orientation decreased by 20° to 60° (100% to 370% change) depending on source location and region of lateral line denervated. Deficits tended to be site-specific. For example, unilaterally denervating lateral-line organs on the head resulted in less accurate orienting responses when the source was located on the denervated side of the head, but not on the opposite side of the head or on either side of the trunk. Site-specific deficits and the absence of abnormal approach pathways argue that animals are relying on a point-by-point spatial representation of source location along the sensory surface rather than computations based on bilateral comparisons. Accepted: 28 May 1998     

Assessing the Perception of Trunk Movements in Military Personnel with Chronic Non-Specific Low Back Pain Using a Virtual Mirror

Chronic pain, including chronic non-specific low back pain (CNSLBP), is often associated with body perception disturbances, but these have generally been assessed under static conditions. The objective of this study was to use a “virtual mirror” that scaled visual movement feedback to assess body perception during active movement in military personnel with CNSLBP (n = 15) as compared to military healthy control subjects (n = 15). Subjects performed a trunk flexion task while sitting and standing in front of a large screen displaying a full-body virtual mirror-image (avatar) in real-time. Avatar movements were scaled to appear greater, identical, or smaller than the subjects’ actual movements. A total of 126 trials with 11 different scaling factors were pseudo-randomized across 6 blocks. After each trial, subjects had to decide whether the avatar’s movements were “greater” or “smaller” than their own movements. Based on this two-alternative forced choice paradigm, a psychophysical curve was fitted to the data for each subject, and several metrics were derived from this curve. In addition, task adherence (kinematics) and virtual reality immersion were assessed. Groups displayed a similar ability to discriminate between different levels of movement scaling. Still, subjects with CNSLBP showed an abnormal performance and tended to overestimate their own movements (a right-shifted psychophysical curve). Subjects showed adequate task adherence, and on average virtual reality immersion was reported to be very good. In conclusion, these results extend previous work in patients with CNSLBP, and denote an important relationship between body perception, movement and pain. As such, the assessment of body perception during active movement can offer new avenues for understanding and managing body perception disturbances and abnormal movement patterns in patients with pain.     

Modulation by dopamine of human basal ganglia involvement in feedback control of movement

We learn new motor tasks by trial and error, repeating what works best and avoiding past mistakes. To repeat what works best we must register a satisfactory outcome, and in a study [1] we showed the existence of an evoked activity in the basal ganglia that correlates with accuracy of task performance and is associated with reiteration of successful motor parameters in subsequent movements. Here we report evidence that the signaling of positive trial outcome relies on dopaminergic input to the basal ganglia, by recording from the subthalamic nucleus (STN) in patients with nigrostriatal denervation due to Parkinson's Disease (PD) who have undergone functional neurosurgery. Correlations between subthalamic evoked activities and trial accuracy were weak and behavioral performance remained poor while patients were untreated; however, both improved after the dopamine prodrug levodopa was re-introduced. The results suggest that the midbrain dopaminergic system may be important, not only in signaling explicit positive outcomes or rewards in tasks requiring choices between options [2,3], but also in trial-to-trial learning and in reinforcing the selection of optimal parameters in more automatic motor control.     

睾丸去神经对大鼠半去势诱导的睾酮代偿性分泌的影响

在成年大鼠,半去势可以在促性腺激素没有明显改变的情况下导致睾丸静脉血液中睾酮浓度代偿性增加,其机理尚不明了。本研究以成年大鼠为实验动物,检验睾酮的代偿性增加是否受到睾丸去神经的影响。睾丸去神经（ｉｎｆｅｒｉｏｒ ｓｐｅｍａｔｉｃ ｎｅｒｖｅｓ,ＩＳＮ或ＩＳＮ ｐｌｕｓ ｓｕｐｅｒｉｏｒ ｓｐｅｒｍａｔｉｃ ｎｅｒｖｅｓ,ＩＳＮ－ＳＳＮ）手术２周后开始半去势实验,半去势之前和半去势之后６和２４ｈ,     

The control of gaze (3). Neurological defects

Eye movements serve vision, which has two different aims: changing images using saccades, i.e. rapid eye movements, and stabilizing new images on the retina using slow eye movements. Eye movements are performed by ocular motor nuclei in the brainstem, on which supranuclear pathways--originating in the cerebral cortex, cerebellum and vestibular structures--converge. It is useful for the neurologist to know the clinical abnormalities of eye movements visible at the bedside since such signs are helpful for localization. Eye movement paralysis may be nuclear or infranuclear (nerves), involving all types of eye movements, i.e. saccades as well as the vestibulo-ocular reflex (VOR), or supranuclear, in which case the VOR is usually preserved. Lateral eye movements are organized in the pons, with paralysis of adduction (and preservation of convergence) when the lesion affects the medial longitudinal fasciculus (internuclear ophthalmoplegia), paralysis of conjugate lateral eye movements when the lesion affects the abducens nucleus (VI) and the "one-and-a-half" syndrome when both these structures are involved. Vertical eye movements are organized in the midbrain, with ipsilateral oculomotor (III) paralysis and contralateral paralysis of the superior rectus muscle when the third nerve nucleus is unilaterally damaged, supranuclear upward gaze paralysis when the posterior commissure is unilaterally damaged and supranuclear downward gaze paralysis (often coupled with upward gaze paralysis) when the mesencephalic reticular formations are bilaterally damaged. Numerous types of abnormal eye movements exist, of which nystagmus is the most frequent and usually due to damage to peripheral or central vestibular pathways. Cerebral hemispheric or cerebellar damage results in subtle eye movement abnormalities at the bedside, in general only detected using eye movement recordings, because of the multiplicity of eye movement pathways at these levels and their reciprocal compensation in the case of a lesion. Lastly, eye movements can also help the neuroscientist to understand the organization of the brain. They are a good model of motricity allowing us, using eye movement recordings, to study the afferent pathways of the cortical areas that trigger them, and thus to analyze relatively complex neuropsychological processes such as visuo-spatial integration, spatial memory, motivation and the preparation of motor programs.     

The value of tear film breakup and Schirmer's tests in preoperative blepharoplasty evaluation

The results of tear film breakup (BUT) and Schirmer's I and II tests were retrospectively analyzed on 146 patients undergoing elective blepharoplasty over a 41-month period. These tests were evaluated in conjunction with ocular history, orbital and periorbital anatomy, and Bell's phenomenon in order to determine their value, if any, in identifying patients at risk of developing a post-blepharoplasty dry eye complication. One-hundred and six patients (73 percent) had test results that were within normal limits, and two of these patients (1.9 percent) complained postoperatively of a transient gritty or burning sensation. Forty patients (27 percent) had abnormal results to one, two, or all three tests, and two of these patients (5 percent) also complained postoperatively of a transient gritty or burning sensation. These four symptomatic patients all had preoperative dry eye histories and abnormal orbital and periorbital anatomy. When analyzed alone, an abnormal tear film breakup (BUT) or Schirmer's test was not a good predictor of possible postblepharoplasty dry eye complications. An abnormal preoperative ocular history or abnormal orbital and periorbital anatomy proved to be the best predictor for the possible development of a postblepharoplasty dry eye complication.     

Acute Effects of Total or Partial Digit Denervation on Raccoon Somatosensory Cortex

The immediate effects of total or partial denervation of single digits (0-16 hr after nerve transection) on primary somatosensory cortex were studied electrophysiologically. Comparisons of response properties and cortical somatotopy were made between intact raccoons and four groups of raccoons with transection of some or all of the nerves innervating the fourth or fifth digit. Animals with all four digital nerves cut (amputation of the digit) were most different from normal. Approximately half of the penetrations in the affected cortical region showed inhibitory responses to stimulation of adjacent skin regions. These consisted of a strong response to stimulus offset and/or a suppression of spontaneous activity during indentation. Since these responses were substantially different from those recorded several months after digit amputation, additional changes in connectivity and synaptic strength must occur with chronic denervation. These inhibitory responses were not seen in animals with one, two, or three nerves cut per digit.

In the animals with partial denervation of a digit, the greatest disruption occurred when both ventral nerves to the glabrous skin were transected. This yielded cell clusters with abnormally large receptive fields, disruptions in somatotopic organization, and a decreased occurrence of low-threshold responses. If only one nerve to glabrous skin was transected, there was less change, even if it was combined with transection of both nerves to hairy skin. These results suggest that the release of inhibitory responses in a cortical digital region by amputation is prevented by the retention of even one ventral nerve. None of the denervation conditions produced large nonresponsive areas of cortex, which would have indicated a loss of all inputs.