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The basal ganglia. A brief review and interpretation.

The data reviewed suggest that: 1. The BG are not only concerned with motor functions. 2. The BG are not directly involved in the control of neurophysiological, behavioral or homeostatic functions at a primary, elementary level. Thus, the effects of total ablation of the main component of the system, i,e. the caudate nuclei, demonstrates that the BG are not indispensable for life consciousness or the basic elementary integration of movements or sensory processes. 3. The BG operate at a high level of CNS integration and appears to be involved in two main types of, generally speaking, sensorimotor functions: a) The control of some of the organism-environment inter-relationships, both at a behavioral and neurological levels, a context of regulating the balance between approach and avoidance reactions. Some of the features of the acaudate cats suggest that this regulation might also include affective type reactions. b) The preparation or "setting up" of the organism for performance of both complex motor responses (response set), and of task requiring a high level of cognition (cognitive set). 26 High level of integration means here that, in the above functions, the BG control most probably operates upon performances not triggered reflexy, directly or indirectly, from the periphery but originated internally either "volitionally" or generated by symbolic, e.g. verbal, instructions. 4. The above functions appears to be accomplished by means of a modulatory action upon afferent signals arriving into the telencephalon and triggering efferent activities through forebrain output structures, particularly the neocortex. In normal conditions such modulation is seemingly carried on by means of a selective, flexible play of the intrinsic inhibitory mechanisms of the BG. When such control is disturbed either by pathology or by experimental manipulations, abnormal functional manifestations occur. These can be understood along the general concepts of (a) "release" from the BG inhibitory control ("compulsory approaching", hyperactivity, hyper reactivity, involuntary movements, abnormal postures, rigidity) or (b) "deficit" of the "setting up" for action postulated as a positive effect of striatal modulation (akinesia). The latter is viewed, therefore, as a permissive effect of the modulation, i.e., by selective removal of the inhibition, action is allowed to go through and to be expressed in actual performance. 5. Since lesions to individual BG structures, produced either neurosurgically in man or experimentally in animals, appear not to be capable of reproducing the complete clinical manifestations of any of the BG diseases, it follows that most of the BG syndromes in man must result from involvement of several BG components and often of other brain areas as well. More experimental work using the multiple lesions approach is needed to further ascertain this statement. 6. The literature on the effect of lesions and stimulation experiments, in particular, suggest that the BG are also involved in mental processes...

Acetylcholine↗

Biomechanics of reaching: clinical implications for individuals with acquired brain injury.

PURPOSE: Outline the biomechanics of reaching both in healthy individuals and in individuals with acquired brain injury (ABI), and to discuss the clinical implications for using valid biomechanical models to assess reaching. METHODS: A review of current literature, including a MEDLINE search using keywords of reaching, ABI, stroke, biomechanics and motor control. RESULTS: Current assessments of the upper extremity in ABI are focused on single-joint characteristics of range of motion, strength and spasticity. However, reaching is a functional multijoint task requiring interjoint coordination in addition to feedback and feedforward control to position the hand optimally at a desired location so that it may interact with the environment. From the literature, biomechanical measures of reaching such as movement time, movement distance and interjoint coordination have been shown to discriminate changes to hand path quality following brain injury. These measures have also been shown to correlate with measures of sensorimotor function (e.g. Fugl-Meyer) in the upper extremity. CONCLUSIONS: Further development of reliable and valid multi-joint biomechanical evaluations is required, particularly for natural and goal-oriented reaching movements. The biomechanical assessment of reaching in ABI can provide an understanding of the specific deficits in physiological structures or motor planning underlying altered reaching ability, assist in the evaluation of new therapies, and characterize the recovery process following ABI.

Arm↗

Learning in sensorimotor circuits.

The study of plasticity in the central nervous system is a major and very dynamic neuroscience research field with enormous clinical potential. Considerable advances in this field have been made during the past 10 years. It now appears that most circuits in the brain and spinal cord show plasticity and that they can be modified by experience. Knowledge of the mechanisms of plasticity in the nervous system is therefore essential for the understanding of how the nervous system is wired during development and how it adapts in response to changes in the body and environment. Recent findings indicate that functional sensorimotor modules probe the sensory signals from the body that are generated as a consequence of module specific activity and use this sensory feedback to calibrate the strength in its input-output connections. This experience-dependent signal adapts the circuitry in the sensorimotor module to the body anatomy and biomechanics.

Adaptation, Physiological↗

A critical examination of vestibular function in motor-impaired learning-disabled children.

This study examined the role of the vestibular system in balance and coordination problems found in motor-impaired, learning-disabled (LD) children. Vestibulo-ocular reflex (VOR) and vestibulo-spinal tests (moving platform posturography) were performed on 15 learning disabled and 54 normal children. Twelve LD children had normal VOR scores suggesting normal peripheral vestibular inputs. All 15 LD children had abnormal posturography. Motor-impaired LD children could not appropriately integrate vestibular information with visual and somatosensory inputs for postural orientation. Results suggest that the best discriminator of abnormal sensorimotor function in LD children are posturography trials requiring orientation to gravity despite absent or inaccurate visual and somatosensory cues, rather than traditionally relied on VOR and Romberg tests.

Child↗

Sensory-motor responses to volume-controlled duodenal distension.

Abstract Visceral perception and secondary peristalsis evoked by distension of the duodenum were studied in 10 healthy volunteers. An impedance planimetric probe for cross-sectional area (CSA) measurements inside a balloon and with three pressure channels was used. Balloon distensions were performed in the fed state with or without the administration of the antimuscarinic drug butylscopolamine. A modified questionnaire was used to assess the nonpainful and painful sensations. The total tension (T(total)) and the passive tension (T(passive)) were determined from the distensions without and with the administration of butylscopolamine, respectively. The active tension (T(active)) was T(total) - T(passive). The stepwise balloon distensions induced the first sensation at a volume of 33 +/- 3 mL. After administration of butylscopolamine the first sensation appeared at 42 +/- 1 mL. The perception score (PS) revealed an approximately linear increase as function of volume, CSA, pressure and tension after the first sensation. Butylscopolamine resulted in significant changes in PS score as function of volume, CSA and strain, but not as a function of pressure and tension. The frequency of the secondary peristalsis increased to the highest value (8.2 +/- 0.8 contractions min(-1)) at a volume of 21 mL. Butylscopolamine almost abolished the distension-evoked motility. T(total) and T(passive) increased nonlinearly as a function of volume, whereas T(active) increased up to a distension volume of 33 mL and then decreased at higher volumes. Hence, the conventional length-tension diagrams as known from studies of smooth muscle strips in vitro can be reproduced in the human duodenum in vivo. This new way of studying intestinal sensation and motility may prove to have both basic and clinical importance as both passive tissue structures and the sensorimotor function are tested.

Adult↗

MRI evaluation and functional assessment of brain injury after hypoxic ischemia in neonatal mice.

BACKGROUND AND PURPOSE: Severe perinatal asphyxia is an important cause of brain injury in the newborn infant. We examined early events after hypoxic ischemia (HI) in the 7-day-old mouse brain by MRI and related them to long-term functional effects and histopathology in the same animals at 4 to 5 weeks of age. METHODS: HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated in vivo by MRI (T2 maps and apparent diffusion coefficient maps) at 3, 6, and 24 hours and 5 days after hypoxia. Locomotion and sensorimotor function were analyzed after 3 weeks. Four weeks after HI, the mice were killed, and cresyl violet-stained brain sections were examined morphologically. RESULTS: A decrease in apparent diffusion coefficient values in cortex on the affected side was found at 3 hours after HI. T2 values were significantly increased after 6 hours and remained so for 5 days. Maximal size of the lesion was attained at 3 to 6 hours after HI and declined thereafter. Animals with MRI-detected lesions had decreased forward locomotion, performed worse than controls in the beam-walking test, and showed a unilateral hypotrophy in the cresyl violet-stained brain sections 4 weeks later. CONCLUSIONS: The temporal progression of the damage after HI in 7-day-old mice differs from that of the adult brain as judged by MRI. The early lesions detected by MRI were related to functional impairments for these mice in near-adult life.

Age Factors↗

Central injections of the GABA-transaminase inhibitor ethanolamine-O-sulfate (EOS): effects on brain [14C]2-deoxy-D-glucose uptake and behavior in rats.

Brain glucose utilization was examined 24 h after single intracisternal injections of the GABA-transaminase inhibitor ethanolamine-O-sulfate (EOS) in rats. Qualitative autoradiography indicated a pronounced and homogeneous depression in [14C]2-deoxy-D-glucose ([14C]2DG) uptake throughout the brains of rats treated with 200 or 400 micrograms EOS. Quantitative scintillation counting of 14C in 9 brain areas of other rats confirmed the marked, generalized decrease in label uptake 24 h after EOS. Food intake measurements confirmed previous reports of dose-dependent anorexia after EOS. Rats treated with the 200 micrograms dose showed decreased open-field activity 24 h after injection but no other deficits in various tests of sensorimotor function or in tail-pinch-induced feeding. Rats treated with the 400 micrograms dose also showed deficits in open-field activity, plus deficits in orientation to touch stimuli, longer latencies than controls in catalepsy tests, and faster habituation of startle responses to sound. This group showed normal feeding responses to tail-pinch stimulation in the presence of solid food but not in the presence of liquid food. It was concluded that sensorimotor deficits may play some role in the anorexigenic effects of EOS but are probably not their primary cause. The discrepancy between the apparent degree of depression of brain glucose utilization and the comparatively mild behavioral deficits observed would suggest the possibility that metabolic fuels other than glucose may be mobilized following central EOS treatment.

4-Aminobutyrate Transaminase↗

Potential usefulness of basic fibroblast growth factor as a treatment for stroke.

Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.

Animals↗

Orphanin FQ acts as an anxiolytic to attenuate behavioral responses to stress.

Orphanin FQ (OFQ, Nociceptin) is a recently discovered 17-amino acid neuropeptide that is structurally related to the opioid peptides but does not bind opioid receptors. OFQ has been proposed to act as an anti-opioid peptide, but its widespread sites of action in the brain suggest that it may have more general functions. Here we show that OFQ plays an important role in higher brain functions because it can act as an anxiolytic to attenuate the behavioral inhibition of animals acutely exposed to stressful/anxiogenic environmental conditions. OFQ anxiolytic-like effects were consistent across several behavioral paradigms generating different types of anxiety states in animals (light-dark preference, elevated plus-maze, exploratory behavior of an unfamiliar environment, pharmacological anxiogenesis, operant conflict) and were observed at low nonsedating doses (0.1-3 nmol, intracerebroventricular). Like conventional anxiolytics, OFQ interfered with regular sensorimotor function at high doses (>3 nmol). Our results show that an important role of OFQ is to act as an endogenous regulator of acute anxiety responses. OFQ, probably in concert with other major neuropeptides, exerts a modulatory role on the central integration of stressful stimuli and, thereby, may modulate anxiety states generated by acute stress.

Animals↗

Sensorimotor changes after anterior cruciate ligament reconstruction.

The restoration of joint stability is unlikely to be dependent on passive properties of the joint alone, yet the effect of anterior cruciate ligament reconstructive surgery on the sensorimotor system largely remains unexplored. This study evaluated whether surgical reconstruction of the ligament had any effect on one indicator of sensorimotor function, hamstring contraction latency, which previously has been shown to be related to function. Twenty-five patients with unilateral chronic anterior cruciate ligament deficiency had measures of hamstring contraction latency obtained before and after (3 and 6 months) reconstruction. After surgery, the contraction latency difference was found to improve significantly (decrease) in patients who had a preexisting deficit. The mechanism for alteration in response time remains unclear, but an observed relationship between contraction latency and tibial translation supports a mechanical basis for the findings. It was concluded the sensorimotor changes associated with surgical reconstruction of the cruciate ligament may help to restore joint stability. The study highlights the need to appreciate sensorimotor consequences of cruciate ligament surgery.

Adult↗

Lower prepulse inhibition in children with the 22q11 deletion syndrome.

OBJECTIVE: The 22q11 deletion syndrome is associated with a range of possible physical anomalies, probable ongoing learning disabilities, and a specific constellation of neuropsychological deficits, including impairments in selective and executive visual attention, working memory, and sensorimotor functioning. It has been estimated that 25% of the children with 22q11 deletion syndrome go on to develop schizophrenia in late adolescence or adulthood. This is of urgent concern. Specification of early brain network vulnerabilities may provide a basis for early intervention while indicating critical links between genes and severe psychiatric illness. Neuropsychological studies of children with 22q11 deletion syndrome have implicated an array of potentially aberrant brain pathways. This study was conducted to determine whether preattentive processing ("sensorimotor gating") deficits are present in this population. METHOD: The authors administered a test of prepulse inhibition to 25 children with 22q11 deletion syndrome and their 23 sibling comparison subjects, ages 6-13. It was predicted that the children with 22q11 deletion syndrome would have lower prepulse inhibition than the comparison subjects. RESULTS: Prepulse inhibition in the children with 22q11 deletion syndrome (26.06%) was significantly less than that of the sibling comparison subjects (46.41%). Secondary analyses suggested that this decrement did not reflect developmental delay, and lower prepulse inhibition was associated with particular subsyndromal symptoms in some children. CONCLUSIONS: Sensorimotor gating is lower in children with 22q11 deletion syndrome. These findings may indicate specific brain circuits that are anomalous in 22q11 deletion syndrome.

Abnormalities, Multiple↗

Protective effects of brain hypothermia on behavior and histopathology following global cerebral ischemia in rats.

The present experiments were designed to assess whether brain hypothermia can reduce the behavioral and histopathological deficits associated with global forebrain ischemia. Animals were subjected to 12.5 min of four vessel occlusion (4VO) with moderate hypotension, and brain temperature maintained at either 37 degrees C (4VO-37) or 30 degrees C (4VO-30). Behavioral tests designed to assess forelimb reflexes and sensorimotor function were given on post-operative weeks 2 and 4. Beginning in week 5, the rats were trained on a variety of navigation problems in the Morris water maze. Histopathological examination of the tissue 2 months following reperfusion revealed that 4VO-37 animals sustained substantial cell death in hippocampal region CA1 and moderate damage to the dorsolateral neostriatum. 4VO-30 animals showed minimal cell death in CA1 and neostriatum. There were no group differences for any of the sensorimotor measures, or for acquisition performance on either the simple place task or visible platform version of the water maze. In contrast, during acquisition of the learning set task, the performance of 4VO-37 animals was impaired relative to either of the other groups, whereas the performance of 4VO-30 animals was not significantly different from the sham controls. These data suggest that moderate intra-ischemic brain hypothermia provides long-lasting protection from behavioral deficits as well as neuronal injury following transient global ischemia.

Animals↗

Early overuse and disuse of the affected forelimb after moderately severe intraluminal suture occlusion of the middle cerebral artery in rats.

We have previously shown that early forced overuse of the affected forelimb worsens outcome following moderately severe transient focal cortical ischemic stroke in rats using a distal middle cerebral artery occlusion (MCAo) model. This effect may be site-dependent, because we have also found that early forced use of the affected limb after unilateral 6-OHDA induced degeneration of ascending nigrostriatal dopamine neurons markedly enhanced functional outcome and is neuroprotective. The present study examines the effects of early overuse and disuse following a moderately severe proximal MCAo model, by means of intraluminal suture occlusion. Ischemia was produced in male Long-Evans rats with 60 min of occlusion, or sham surgery was performed. Early overuse or disuse of the affected forelimb was forced by immobilizing either the ipsilateral or contralateral forelimb, respectively, in a plaster cast or the animal was left uncasted. Casts were removed on day 10 and sensorimotor testing was performed weekly during days 17-38. Animals were sacrificed on day 45 and brains were fixed for later cresyl violet staining. The MCAo+contralateral cast group performed worse than all other groups on tests of forelimb sensorimotor function. All MCAo groups regardless of cast condition had significant atrophy of the ischemic striatum, but there was no significant atrophy of the ischemic cortex in any group. Forced disuse, but not overuse, of the affected forelimb immediately following proximal ischemia using the intraluminal suture model has detrimental effects on functional outcome, without exaggerating anatomical damage. The effects of disuse and overuse during the first 10 days after stroke differ depending on cortical or subcortical involvement.

Animals↗

Stimulus-driven and voluntary saccades are coded in different coordinate systems.

We make fast, "saccadic" eye movements to view our surroundings, "voluntary" saccades when saccade targets are deliberately selected, and "stimulus-driven" saccades when a target suddenly appears. Saccades of patients with spatial neglect have been studied to identify the coordinate systems guiding such behavior. However, previous reports disagree on whether neglect involves an eye-centered deficit of (delayed and hypometric) saccades specifically when performed in the direction opposite the brain lesion or not. We show that this inconsistency is due to independent mechanisms underlying voluntary and stimulus-driven saccades. We used a new experimental procedure comparing identical saccades performed either during an exploratory search task or a stimulus-driven task, both of which required similar cognitive functions (Figure 1). Only the patients' stimulus-driven saccades showed the eye-centered deficit. The same saccades were intact when voluntarily performed. However, here the patients showed a head-centered deficit; their saccades ignored the left part of space. In none of our control subjects with or without brain lesions did the neglect patients' pattern of deficits occur. The results argue that the brain flexibly uses a system of distinct but interrelated neural circuits for visual orienting to optimally encode its sensorimotor functions in multiple behavioral situations.

Brain Injuries↗

Elderly persons with intellectual disability: a study of clinical characteristics, functional status, and sensory capacity.

Longer life expectancy is resulting in increasing numbers of elderly adults with intellectual disability (ID). There has been the question whether persons with ID demonstrate early signs of aging before the general population. The aim of this study was to determine if persons with ID (with and without Down syndrome) showed premature aging changes compared with a control group. Elderly persons (n = 24, average age of 61) from one residential care center in Israel and younger adults from another center (n = 37, average age of 45) were compared with elderly residents without ID in an independent living facility. The study considered demographic data, medical data, anthropometric measurements, body fat and body mass index, flexibility, and sensorimotor function tests. The results showed that the persons with ID had basically similar body composition to that of persons without ID, however, the functional performance of elderly adults with ID was more impaired. We postulate that the slower functioning responses may be explained by a less physically active lifestyle, that may accelerate the onset of disease and result in symptoms associated with aging that are detrimental to health. It is therefore important that persons with ID participate in physical activity and exercises in order to promote health and prevent disease.

Adult↗

Working memory deficits in retinoid X receptor gamma-deficient mice.

Retinoid signaling has been recently shown to be required for mnemonic functions in rodents. To dissect the behavioral and molecular mechanisms involved in this requirement, we have analyzed the spatial and recognition working memory in mice carrying null mutations of retinoid receptors RARbeta and RXRgamma. Double mutants appeared deficient in spatial working memory as tested in spontaneous alternation in the Y-maze and delayed nonmatch to place (DNMTP) test in the T-maze. These mutant mice did acquire, however, spatial place reference or right/left discrimination tasks in the T-maze set-up, indicating that basic sensorimotor functions, spatial orientation, and motivational factors are unlikely to account for deficits in working memory-sensitive tasks. Double-mutant mice were also deficient in novel object recognition at intermediate, but not short delays. RXRgamma appeared to be the functionally predominant receptor in modulation of the working memory, as RXRgamma, but not RARbeta single null mutant mice exhibited deficits similar to those observed in the double mutants. The mechanism of this modulation is potentially related to functions of RXRgamma in frontal and perirhinal cortex, structures in which we detected RXRgamma expression and which are functionally implicated in working memory processes.

Animals↗

The formalin test: an evaluation of the method.

The formalin test for nociception, which is predominantly used with rats and mice, involves moderate, continuous pain generated by injured tissue. In this way it differs from most traditional tests of nociception which rely upon brief stimuli of threshold intensity. In this article we describe the main features of the formalin test, including the characteristics of the stimulus and how changes in nociceptive behaviour may be measured and interpreted. The response to formalin shows an early and a late phase. The early phase seems to be caused predominantly by C-fibre activation due to the peripheral stimulus, while the late phase appears to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord. These functional changes seem to be initiated by the C-fibre barrage during the early phase. In mice, the behavioural response in the late phase depends on the ambient temperature. We argue that the peripheral tissue temperature as well as other factors influencing the peripheral inflammation may affect the response, possibly confounding the results obtained with the test. Furthermore, we discuss the methods of recording the response and the value of observing more than one aspect of behaviour. Scoring of several behavioural variables provides a means of assessing motor or sensorimotor function as possible causes for changes in behaviour. In conclusion, the formalin test is a valuable addition to the battery of methods available to study nociception.

Animals↗

Restoration of sensory function and lack of long-term chronic pain syndromes after brachial plexus injury in human neonates.

Obstetric complications are a common cause of brachial plexus injuries in neonates. Failure to restore sensation leads to trophic injuries and poor limb function. It is not known whether the infant suffers chronic neuropathic or spinal cord root avulsion pain; in adults, chronic pain is usual after spinal root avulsion injuries, and this is often intractable. The plexus is repaired surgically in severe neonatal injures; if no spontaneous recovery has occurred by 3 months, and if neurophysiological investigations point to poor prognosis, then nerve trunk injures are grafted, while spinal cord root avulsion injuries are treated by transferring an intact neighbouring nerve (e.g. intercostal) to the distal stump of the damaged nerve, in an attempt to restore sensorimotor function. Using a range of non-invasive quantitative measures validated in adults, including mechanical, thermal and vibration perception thresholds, we have assessed for the first time sensory and cholinergic sympathetic function in 24 patients aged between 3 and 23 years, who had suffered severe brachial plexus injury at birth. While recovery of function after spinal root avulsion was related demonstrably to surgery, there were remarkable differences from adults, including excellent restoration of sensory function (to normal limits in all dermatomes for at least one modality in 16 out of 20 operated cases), and evidence of exquisite CNS plasticity, i.e. perfect localization of restored sensation in avulsed spinal root dermatomes, now presumably routed via nerves that had been transferred from a distant spinal region. Sensory recovery exceeded motor or cholinergic sympathetic recovery. There was no evidence of chronic pain behaviour or neuropathic syndromes, although pain was reported normally to external stimuli in unaffected regions. We propose that differences in neonates are related to later maturation of injured fibres, and that CNS plasticity may account for their lack of long-term chronic pain after spinal root avulsion injury.

Adolescent↗