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A consideration of sensory factors involved in motor functions of the basal ganglia.

There is a sizeable literature concerning basal ganglia (BG) functioning that is based on data from experiments employing a method of analysis that is traditionally used with other motor areas. A brief review of this literature is presented and the following conclusion is reached: as compared to the success of traditional methodologies in elucidating the workings of other motor systems, their use in BG investigations has proven disappointing. A possible reason for the shortcomings of traditional analyses in BG research is discussed. The remainder of this review concerns an alternative approach to the study of the BG that follows from consideration of a variety of clinical and experimental findings. The literature suggests that sensory aspects of BG functioning must be taken into account to fully appreciate the role of this system in motor control. A review of the literature concerning the latter suggests two points: The BG function as sensory analyzer for motor systems. That is, the BG convert sensory data from a form that is receptor oriented to a form that is relevant for guiding movement. The BG ultimately affect movement by gating sensory inputs into other motor areas rather than by directly affecting these areas. This sensory-based model of BG functioning explains a number of apparent discrepancies in the literature. In addition, seemingly anomalous findings are reconciled with the overwhelming evidence that the BG are a motor system. In particular, the suggestions of a BG role in attention and cognition are viewed as being intrinsic rather than orthogonal to the role of the BG in movement.

Animals↗

Short versions of the telephone motor Functional Independence Measure for use with persons with spinal cord injury.

OBJECTIVE: To determine if the motor ability of persons with spinal cord injury (SCI) can be reliably estimated using a subset of the 13 Functional Independence Measure (FIM) items. STUDY DESIGN: FIM item subsets of 5, 6, or 7 items were selected using one of five strategies: random, coefficient alpha maximization, spread across the range of item difficulties, optimization by neurologic category, and individual optimization. Motor ability estimated by these 15 subsets was compared to the 13-item estimate, using intraclass correlation coefficient (ICC), Rasch calibration person reliability estimate, and other indices of reliability. SUBJECTS: Subjects were 4,128 persons with SCI, 1 to 25 years postinjury, interviewed for annual research follow-up using the FIM. RESULTS: All subsets had high ICC reliability (>.90). Subsets of 7 items performed generally better than those of 6 or 5 items. The best performance was provided by individual optimization subsets. The ICC for the 7-item set thus selected was .99. CONCLUSION: In annual follow-up, the number of FIM motor items can be reduced almost 50% while maintaining reliable estimates of subjects' motor ability. This approach may also be useful for other applications of interviewing to obtain FIM data, eg, for program evaluation.

Activities of Daily Living↗

Opposing effects of vasoactive intestinal polypeptide on gastric motor function in the dorsal vagal complex and the nucleus raphe obscurus of the rat.

Vasoactive intestinal polypeptide (VIP)-like immunoreactive cell bodies and fibers and VIP binding sites exist in the brainstem nuclei that regulate autonomic function. Therefore, we investigated the effects of microinjection of VIP in the dorsal vagal complex (DVC), nucleus raphe obscurus (nROb) and nucleus ambiguus of alpha-chloralose-anesthetized rats while recording intragastric pressure, pyloric and greater curvature smooth muscle contractile activity, blood pressure and heart rate. Microinjection of VIP into the DVC increased intragastric pressure (1-100 pmol) and pyloric smooth muscle contractile activity (100 pmol), as well as arterial blood pressure (1-100 pmol). Whereas VIP microinjected into the nROb (10-100 pmol) decreased intragastric pressure and inhibited pyloric smooth muscle contractile activity. Mean arterial blood pressure increased in response to VIP in the nROb at the highest dose of 100 pmol only. No changes in gastric motor and cardiovascular function were noted after microinjection of VIP (1-100 pmol) into the region of the nucleus ambiguus. The gastric motor effects of VIP in the DVC (10 pmol) and nROb (50 pmol) were completely abolished by bilateral cervical vagotomy. These data show that VIP may produce opposite vagally mediated gastric motor responses upon its microinjection into the DVC and nROb.

Animals↗

Predicting global and specific neurological impairment with sensory-motor functioning.

The present study assessed the ability of the Dean-Woodcock Sensory-Motor Battery (DWSMB) to distinguish between normal subjects and neurologically impaired individuals. Scores from the subtests of the DWSMB for 250 normal and 250 neurologically impaired individuals were randomly assigned to two equal groups to allow for cross-validation. The DWSMB was able to correctly identify 92.8% of the cases, identifying 94.4% of the normal population and 91.2% of the neurologically impaired subjects. The cross-validation correctly identified 87.2% of the total cases, identifying 91.2% of the normal subjects and 83.2% of the neurologically impaired subjects. An additional discriminant analysis indicated that the DWSMB correctly identified the following cases: 44.9% cardio-vascular accidents, 66.7% multiple sclerosis, 40% seizures, 42% traumatic brain injuries, 62.7% dementia, and 54.5% Parkinson's disease. The results add to the validity of the DWSMB by providing evidence of its ability to differentiate between neurologically impaired and normal individuals.

Adolescent↗

Iron accumulation in the striatum predicts aging-related decline in motor function in rhesus monkeys.

Changes in the nigrostriatal system may be involved with the motor abnormalities seen in aging. These perturbations include alterations in dopamine (DA) release, regulation and transport in the striatum and substantia nigra, striatal atrophy and elevated iron levels in the basal ganglia. However, the relative contribution of these changes to the motor deficits seen in aging is unclear. Thus, using the rhesus monkey as a model, the present study was designed to examine several of these key alterations in the basal ganglia in order to help elucidate the mechanisms contributing to age-related motor decline. First, 32 female rhesus monkeys ranging from 4 to 32 years old were evaluated for their motor capabilities using an automated hand-retrieval task. Second, non-invasive MRI methods were used to estimate brain composition and to indirectly measure relative iron content in the striatum and substantia nigra. Third, in vivo microdialysis was used to evaluate basal and stimulus-evoked levels of DA and its metabolites in the striatum and substantia nigra of the same monkeys. Our results demonstrated significant decreases in motor performance, decreases in striatal DA release, and increases in striatal iron levels in rhesus monkeys as they age from young adulthood. A comprehensive statistical analysis relating age, motor performance, DA release, and iron content indicated that the best predictor of decreases in motor ability, above and beyond levels of performance that could be explained by age alone, was iron accumulation in the striatum. This suggests that striatal iron levels may be a biomarker of motor dysfunction in aging; and as such, can be monitored non-invasively by longitudinal brain MRI scans. The results also suggest that treatments aimed at reducing accumulation of excess iron in the striatum during normal aging may have beneficial effects on age-related deterioration of motor performance.

Aging↗

Quantitation of pharyngeal motor function in normal human subjects.

A need exists for accurate pressure recording of pharyngeal motor events. Results of this study indicate that accurate quantitation of pharyngeal motor activity is not possible using a water-filled catheter system, even when high infusion rates are used. An intraluminal strain gauge system, however, achieves high-fidelity recording. Quantitation of pharyngeal peristalsis using the intraluminal strain gauge system reveals peristaltic pressure amplitudes higher than those hitherto recorded. In normal subjects, peristaltic amplitude averages about 200 mmHg in the hypopharynx, complexes in one subject being as high as 600 mmHg. A zone of relatively low pressure exists in the oropharynx. Mean pharyngeal wave duration decreases progressively in an aboral direction, from 1.0 to 0.3 s, and peristaltic wave speeds range between 9 and 25 cm/s. Accurate quantitation of pharyngeal peristaltic variables provides the necessary basis for characterization and assessment of pharyngeal motor disorders.

Gastrointestinal Motility↗

Ileal inhibition and modulation of carbachol-stimulated proximal small intestinal motor functions in humans.

Carbohydrates within the distal small intestine inhibit endogenously stimulated proximal gastrointestinal motor activity and induced an interdigestive-like pattern in humans. In order to further investigate the intermediary mechanisms of the ileal inhibitory effects, we intubated eight healthy volunteers with an oroileal multilumen tube and stimulated small intestinal motility exogenously with a continuous intravenous infusion of the cholinergic agonist carbachol. Additionally, the ileum was perfused for 15-min intervals with either carbohydrates (total load: 18 g) or normal saline as volume control. Ileal carbohydrate perfusion inhibited the carbachol-stimulated motility pattern significantly (p < 0.001) and induced phase-III-like motor activity; ileal saline had no effect. These data suggest that a direct inhibition of cholinergic systems may be involved in the ileal inhibitory effects on proximal small intestinal motility.

Adult↗

Fluoxetine and recovery of motor function after focal ischemia in rats.

Neuroprotective therapies and tissue plasminogen activator (t-PA) have limited application for most stroke patients and thus rehabilitation is the primary treatment option for improving recovery of function. Following brain injury, environmental enrichment, pharmacological and rehabilitative treatments can markedly alter neuronal plasticity and behavioral recovery even when delayed by several weeks after the insult. Fluoxetine has been given to stroke patients to combat depression but its effects on recovery of function are not known. Functional magnetic resonance imaging reveals that fluoxetine alters brain activity and modulates motor performance in stroke patients in a use-dependent fashion. Several antidepressants, including fluoxetine, increase growth factors and other proteins associated with plasticity, such as brain-derived neurotrophic factor (BDNF). In this study, we examined whether chronic administration of fluoxetine combined with rehabilitation affected recovery of function on 3 separate tests of forelimb reaching, preference and limb coordination after focal ischemia in rats. Ischemia was induced in male Long-Evans rats by intracortical and striatal injections of endothelin-1. Fluoxetine (10 mg/kg/day) combined with rehabilitation therapy (6 h/day) for 4 weeks did not alter the degree or rate of recovery of function compared to non-treated animals. Despite the ability of fluoxetine to alter brain activity and increase growth factors, it does not appear to be an effective pharmacological adjunct to functional recovery after ischemia in rats.

Analysis of Variance↗

Differential recovery of volitional motor function, lateralized cognitive function, dopamine agonist-induced rotation and dopaminergic parameters in monkeys made hemi-parkinsonian by intracarotid MPTP infusion.

There is still controversy regarding the frequency and extent of spontaneous functional recovery in primate models of parkinsonism, perhaps in part stemming from the variety of ways in which recovery has been assessed. The present study examined functional recovery in monkeys made unilaterally parkinsonian by intracarotid infusion of MPTP. Monkeys were evaluated prior to lesioning and for at least 1 year after lesioning on a battery of tests including a rating of spontaneous behaviors, a learned reaction time/movement time task, tests of lateralized neglect or inattention (i.e. lateralized reward retrieval task, extinction with double simultaneous stimulation, and response to a target moving from one hemispace to the other), and rotational asymmetry in response to a dopamine agonist. Some animals also received 6-[18F]Fluoro-L-Dopa (F-DOPA) position emission tomography (PET) scans before MPTP, when symptomatic, and when showing signs of functional recovery. These animals were sacrificed for post mortem neurochemical assessment following the last PET scan. Results showed that estimates of functional recovery in hemi-parkinsonian monkeys may depend upon the behavioral assay used. Even in behavioral tasks that were sensitive to recovery effects, the degree of functional recovery shown by an animal on one such task did not predict recovery on another. This may in part be due to the inherent difficulty in designing behavioral tests to assess basal ganglia functioning, when there is no consensus concerning which aspects of behavior the normal basal ganglia actually control.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Voluntary motor function in patients with chronic fatigue syndrome.

INTRODUCTION: The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. In particular, little is known of the involvement of the motor cortex and corticospinal system. METHODS: Transcranial magnetic stimulation (TMS) was used to assess corticospinal function in terms of latency and threshold of motor-evoked potentials (MEPs) in thenar muscles. Reaction times and speed of movement were assessed using button presses in response to auditory tones. RESULTS: Patients had higher (P<.05) self-assessed indices of fatigue (7/10) than for pain (5/10), anxiety (4/10) or depression (3/10). Mean (+/-S.E.M.) simple reaction times (SRTs) were longer (P<.05) in the patients (275+/-19 ms) than in the controls (219+/-9 ms); choice reaction times (CRTs) were not significantly longer in the patients. Movement times, once a reaction task had been initiated, were longer (P<.05) in the patients in both SRTs (patients, 248+/-13 ms; controls, 174+/-9 ms) and CRTs (patients, 269+/-13 ms; controls, 206+/-12 ms). There was no difference (P>.05) in threshold or latency of MEPs in hand muscles between the patients (threshold, 54.5+/-2.2% maximum stimulator output [% MSO]; latency 22+/-0.3 ms) and controls (threshold 54.6+/-3.6% MSO; latency 22.9+/-0.5 ms). Regression analysis showed no correlation (P>.05) of SRTs with either threshold for MEPs or fatigue index. CONCLUSION: Corticospinal conduction times and excitability were within the normal range despite a slower performance time for motor tasks and an increased feeling of fatigue. This suggests that the feeling of fatigue and the slowness of movement seen in CFS are manifest outside the corticospinal system.

Adult↗

Pathophysiology of motor functions in prolonged manned space flights.

The influence of weightlessness on different parts of the motor system have been studied in crew members of 140 and 175 days space flights. It has been shown that weightlessness affects all parts of the motor system including (i) the leg and trunk muscles, in which severe atonia, a decrease of strength and an increase of electromyographic cost of contraction have been observed, (ii) the proprioceptive elements and the spinal reflex mechanisms in which decreased thresholds accompanied by decreases of maximal amplitude of reflexes and disturbances in cross reflex mechanisms have been found. and (iii) the central mechanisms that control characteristics of postural and locomotor activities. The intensities and durations of disturbances of different parts of the motor system did not correlate to each other, but did correlate with prophylactic activity during space flight. The data suggest a different nature of disturbances caused by weightlessness in different parts of the motor system.

Electromyography↗

Motor function in microgravity: movement in weightlessness.

Microgravity provides unique, though experimentally challenging, opportunities to study motor control. A traditional research focus has been the effects of linear acceleration on vestibular responses to angular acceleration. Evidence is accumulating that the high-frequency vestibulo-ocular reflex (VOR) is not affected by transitions from a 1 g linear force field to microgravity (<1 g); however, it appears that the three-dimensional organization of the VOR is dependent on gravitoinertial force levels. Some of the observed effects of microgravity on head and arm movement control appear to depend on the previously undetected inputs of cervical and brachial proprioception, which change almost immediately in response to alterations in background force levels. Recent studies of post-flight disturbances of posture and locomotion are revealing sensorimotor mechanisms that adjust over periods ranging from hours to weeks.

Animals↗

Cerebral magnetic resonance imaging and mental and motor function of very low birth weight children at six years of age.

In this follow-up study, 20 of a geographically based year cohort of 31 surviving non-disabled VLBW (birthweight < 1500 g) children were examined at six years of age. The aim of the study was to relate cerebral MRI findings to neuro-development in these non-disabled children at six years of age. All MRI scans were evaluated for myelination pattern, periventricular gliosis, ventricular dilation and cortical atrophy. The Peabody motor test and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) were used in the evaluation of motor, mental and perceptual function. A diagnosis of attention deficit disorder with hyperactivity was made based on the examiner's impression of the child during the examination and based on the parent's history. We found that ten (50%) of the children had periventricular gliosis, mainly in centrum semiovale (CS) (nine children) and in central occipital white matter (COW) (six children). Gliosis in CS was related to lower scores on the Peabody gross motor test for locomotion, indicating involvement of corticospinal tracts. Additional gliosis in COW was related to both fine motor and gross motor impairments. We speculate that this indicates damage to both motor and visual pathways, affecting eye-hand coordination and balance function. No relationship between MRI deviations at six years and mental function based on performance, verbal and total IQ scores was found. However, there was a significant relationship between periventricular gliosis in COW and C5 and low scores on the WPPSI performance subtests: Picture completion test and Block design test. This may indicate visual and spatial perception problems, caused by damage to posterior visual pathways and occipito-thalamic tracts dealing with visuo-motor integration.

Analysis of Variance↗

Effects of dietary nitrate on oesophageal motor function and gastro-oesophageal acid exposure in healthy volunteers and reflux patients.

BACKGROUND/AIMS: High concentrations of nitric oxide (NO), derived from dietary nitrite in an acid environment, have been demonstrated in the gastric fundus and in the oesophagus. The aim of this study was to investigate whether luminal NO can influence oesophageal smooth muscle performance, lower oesophageal sphincter (LOS) function or gastric and oesophageal acid exposure. METHODS: Eleven healthy volunteers and 9 patients with chronic gastro-oesophageal reflux disease (GORD) received a diet deprived of nitrate/nitrite but supplemented with placebo or potassium nitrate for 4 days in a randomised order. On day 4 in each trial period, manometry was performed including a sleeve sensor registration of the LOS followed by a simultaneous 24-hour intra-gastric and oesophageal pH registration. RESULTS: Nitrate supplementation increased the proportion of effective peristalsis when analysed for the entire study population. No other significant effects of dietary nitrate were found on oesophageal motor variables, on the sphincter resting tone or on the number or duration of transient sphincter relaxations. No effect was found on either gastric acidity or gastro-oesophageal reflux variables. Major reflux symptoms were not influenced by nitrate administration. CONCLUSION: Dietary nitrate did not significantly affect oesophageal motor or LOS function, gastro-oesophageal acid reflux or reflux symptomatology either in healthy volunteers or in GORD patients.

Adult↗

Involvement of peripheral adenosine A2 receptors in adenosine A1 receptor-mediated recovery of respiratory motor function after upper cervical spinal cord hemisection.

BACKGROUND/OBJECTIVE: In an animal model of spinal cord injury, a latent respiratory motor pathway can be pharmacologically activated through central adenosine A1 receptor antagonism to restore respiratory function after cervical (C2) spinal cord hemisection that paralyzes the hemidiaphragm ipsilateral to injury. Although respiration is modulated by central and peripheral mechanisms, putative involvement of peripheral adenosine A2 receptors in functional recovery in our model is untested. The objective of this study was to assess the effects of peripherally located adenosine A2 receptors on recovery of respiratory function after cervical (C2) spinal cord hemisection. METHODS: Respiratory activity was electrophysiologically assessed (under standardized recording conditions) in C2-hemisected adult rats with the carotid bodies intact (H-CBI; n=12) or excised (H-CBE; n=12). Animals were administered the adenosine A2 receptor agonist, CGS-21680, followed by the A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), or administered DPCPX alone. Recovered respiratory activity, characterized as drug-induced activity in the previously quiescent left phrenic nerve of C2-hemisected animals in H-CBI and H-CBE rats, was compared. Recovered respiratory activity was calculated by dividing drug-induced activity in the left phrenic nerve by activity in the right phrenic nerve. RESULTS: Administration of CGS-21680 before DPCPX (n=6) in H-CBI rats induced a significantly greater recovery (58.5 +/- 3.6%) than when DPCPX (42.6 +/- 4.6%) was administered (n=6) alone. In H-CBE rats, prior administration of CGS-21680 (n=6) did not enhance recovery over that induced by DPCPX (n=6) alone. Recovery in H-CBE rats amounted to 39.7 +/- 3.7% and 38.4 + 4.2%, respectively. CONCLUSIONS: Our results suggest that adenosine A2 receptors located in the carotid bodies can enhance the magnitude of adenosine A1 receptor-mediated recovery of respiratory function after C2 hemisection. We conclude that a novel approach of targeting peripheral and central adenosine receptors can be therapeutically beneficial in alleviating compromised respiratory function after cervical spinal cord injury.

Adenosine↗