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PubMed1984

Effect of dopamine-depleting brain lesions on suckling and weaning in rats.

Rats given large dopamine-depleting brain lesions as adults exhibit severe impairments in ingestive behavior and sensorimotor function. In contrast to these well-known effects, virtually complete destruction of central dopaminergic neurons produced no such dysfunctions when it occurred in neonates. Indeed, rats continued to suckle and grow, albeit somewhat more slowly, and they could be weaned readily when they were 27 days old. Although most brain-damaged animals did not survive weaning when they were 18 days old, whereas controls exhibited no difficulty, this failure appears to be the consequence of their reduced body weight and related inability to maintain body temperature in a relatively cool environment (22 degrees C). Such premature weaning occurred more successfully when growth was stimulated by rearing brain-damaged pups in small litters or when ambient temperatures were raised to 31 degrees C so as to minimize heat loss. These results demonstrate that the effects of near-total dopamine-depleting brain lesions are considerably less severe when they occur in infants than when they occur in adults, and, consequently, they reveal a capacity for neural plasticity during development that is no longer present at maturity.

Animals↗

PubMed1984

Bilateral cutaneous stimulation of the somatosensory system in hemidecorticate rats.

An enduring somatosensory consequence of extensive neocortex injury in people is "simultaneous extinction," which is an interhemispheric perceptual interaction that is operationally distinguishable from neglect. A cutaneous stimulus presented on the contralateral side of the body is readily detected when presented singly but is actively masked during bilateral stimulation. In hemidecorticate rats, small adhesive stimuli were attached to the radial surface of each forelimb simultaneously, and the latencies to contact and to remove each stimulus were recorded. Neglect of the contralateral stimulus lasted 2-3 days. Thereafter the ipsilateral stimulus was removed first, followed immediately by the contralateral stimulus. This ipsilateral sensorimotor bias lasted several months. Further analysis with unremovable tactile stimuli provided evidence for true extinction. For a limited period (during the first 2 postoperative weeks), the contralateral stimulus did not appear to be detected in the presence of the ipsilateral stimulus. Rather than switching back and forth between the two stimuli, the animals ignored the stimulus on the contralateral limb and persisted in their attempts to remove the ipsilateral stimulus. A key feature of the "extinction" was its complete reversibility. Simply by adjusting the sensory fields occupied by the contralateral (C) and ipsilateral (I) stimuli (specifically, by increasing the C/I ratio), the sensorimotor bias was totally shifted to contralateral. During recovery, the size of the C/I ratio necessary to reverse sensorimotor asymmetry gradually decreased. Asymmetrical sensorimotor behavior and amphetamine-induced circling were examined in three additional groups of hemidecorticate rats, which were given their initial behavioral tests at 2, 12, or 52 postoperative weeks. This experiment confirmed the above findings and controlled for practice. Over the course of a year, apparently complete recovery occurred; however, there were residual effects. At each period, previously recovered symptoms were reinstated simply by turning on the room lights and opening the home cage slightly. These data underscore the importance of detailed behavioral analysis and the value of the rat as a model in studies of recovery of sensorimotor function.

Afferent Pathways↗

PubMed1976

Roles of anoxia and noise-induced hearing loss in the postictal refractory period for audiogenic seizures in mice.

The present series of experiments demonstrated a postictal refractory period for audiogenic seizures in DBA/2J mice, which was not related to hearing loss but apparently was related to anoxia. Unlike many previous studies, Experiment 1 controlled for the effects of noise exposure upon hearing sensitivity and demonstrated reduced susceptibility to subsequent audiogenic seizures for at least 1 hr after initial clonic-tonic convulsions. The postictal refractory period was shown to result from the occurrence of seizures per se, not from noise exposure alone. Experiment 2 demonstrated deficiencies of sensorimotor functions that accompanied reduced postictal seizure susceptibility. The two phenomena had similar time courses of recovery, which suggested a common mechanism, probably anoxia, associated with the initial convulsions. In support of this view, Experiment 3 showed that recovery from both phenomena was expedited by allowing subjects to breathe increased O2. The role of anoxia in fatal convulsions was suggested by the finding that subjects experiencing clonic-tonic convulsions in a high-O2 environment survived without exception. In contrast, seizures of air-breathing controls were almost always fatal. Taken together, the data indicate that the postictal reduced susceptibility to audiogenic seizures was closely related to metabolic depletion (in particular, anoxia). The pattern of recovery of susceptibility further suggests that the effects of anoxia impair the spread of seizure activity through the central nervous system, although the initiation of seizures is also affected for a short time.

Anesthesia, Inhalation↗

PubMed2000

Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious 'warming' stimuli.

Adenosine Triphosphate↗

PubMed2000

Dopamine is required for hyperphagia in Lep(ob/ob) mice.

Feeding is a complex process responsive to sensory information related to sight and smell of food, previous feeding experiences, satiety signals elicited by ingestion and hormonal signals related to energy balance. Dopamine released in specific brain regions is associated with pleasurable and rewarding events and may reinforce positive aspects of feeding. Dopamine also influences initiation and coordination of motor activity and is required for sensorimotor functions. Thus, dopamine may facilitate integration of sensory cues related to hunger, initiating the search for food and its consumption. Dopaminergic neurons in the substantia nigra and ventral tegmental area project to the caudate putamen and nucleus accumbens, where they modulate movement and reward. There are projections from the nucleus accumbens to the lateral hypothalamus that regulate feeding. Dopamine-deficient mice (Dbh(Th/+), Th-/-; hereafter DD mice) cannot synthesize dopamine in dopaminergic neurons. They gradually become aphagic and die of starvation. Daily treatment of DD mice with L-3,4-dihydroxyphenylalanine (L-DOPA) transiently restores brain dopamine, locomotion and feeding. Leptin-null (Lep(ob/ob)) mice exhibit obesity, decreased energy expenditure and hyperphagia. As the hypothalamic leptin-melanocortin pathway appears to regulate appetite and metabolism, we generated mice lacking both dopamine and leptin (DD x Lep(ob/ob)) to determine if leptin deficiency overcomes the aphagia of DD mice. DD x Lep(ob/ob) mice became obese when treated daily with L-DOPA, but when L-DOPA treatment was terminated the double mutants were capable of movement, but did not feed. Our data show that dopamine is required for feeding in leptin-null mice.

Animals↗

PubMed1990

The relationship between global and local changes in PET scans.

In order to localize cerebral cognitive or sensorimotor function, activation paradigms are being used in conjunction with PET measures of cerebral activity (e.g., rCBF). The changes in local cerebral activity have two components: a global, region independent change and a local or regional change. As the first step in localizing the regional effects of an activation, global variance must be removed by a normalization procedure. A simple normalization procedure is division of regional values by the whole brain mean. This requires the dependence of local activity on global activity to be one of simple proportionality. This is shown not to be the case. Furthermore, a systematic deviation from a proportional relationship across brain regions is demonstrated. Consequently, any normalization must be approached on a pixel-by-pixel basis by measuring the change in local activity and change in global activity. The changes associated with an activation can be partitioned into global and local effects according to two models: one assumes that the increase in local activity depends on global values and the other assumes independence. It is shown that the increase in activity due to a cognitive activation is independent of global activity. This independence of the (activation) condition effect and the confounding linear effect of global activity on observed local activity meet the requirements for an analysis of covariance, with the "nuisance" variable as global activity and the activation condition as the categorical independent variable. These conclusions are based on analysis of data from 24 scans: six conditions over four normal subjects using a verbal fluency paradigm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2002

Vasopressin V1b receptor knockout reduces aggressive behavior in male mice.

Increased aggression is commonly associated with many neurological and psychiatric disorders. Current treatments are largely empirical and are often accompanied by severe side effects, underscoring the need for a better understanding of the neural bases of aggression. Vasopressin, acting through its 1a receptor subtype, is known to affect aggressive behaviors. The vasopressin 1b receptor (V1bR) is also expressed in the brain, but has received much less attention due to a lack of specific drugs. Here we report that mice without the V1bR exhibit markedly reduced aggression and modestly impaired social recognition. By contrast, they perform normally in all the other behaviors that we have examined, such as sexual behavior, suggesting that reduced aggression and social memory are not simply the result of a global deficit in sensorimotor function or motivation. Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain. We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries.

Age Factors↗

PubMed1997

Motor cortical mapping of proximal upper extremity muscles following spinal cord injury.

Focal transcranial magnetic stimulation was used to map the motor cortical representations of the relaxed and gently contracted biceps brachii, deltoid and triceps muscles in 22 subjects comprised of 12 controls, five subjects with complete and five with incomplete cervical spinal cord lesions (SCI). Motor evoked potentials (MEPs) were rarely observed during the resting condition (3/30 muscles tested; SCI group) which precluded detailed analysis of these data. With background facilitation, the mean number of scalp stimulation sites producing MEPs varied according to muscle (P < 0.001); biceps yielded the largest maps and triceps the smallest. The cortical representations of proximal upper extremity muscles were largest for the control group and smallest for the incomplete SCI group although differences were not significant (P > 0.09). The optimal site of stimulation (that which produced the largest MEP) was always surrounded by an area producing submaximal MEPs, but was variable across subjects and groups. There was extensive overlap in the motor cortical representation areas corresponding to the three muscles of interest. Following maximal intensity stimulation at the optimal site, the mean MEP amplitudes (normalized) were largest for the biceps muscle and smallest or absent in triceps (P < 0.02). No differences were detected between groups (P > 0.50). The threshold stimulus intensity was highest for those with incomplete SCI and lowest amongst control subjects (P < 0.05), with biceps then deltoid muscles generally having lower thresholds than triceps (P < 0.001). The findings suggest that cortical map areas and MEP characteristics are not significantly altered in gently contracting muscles innervated by nerve roots rostral to the lesion. Only activation thresholds are higher following SCI, particularly incomplete lesions, although there is no apparent association with sensorimotor function. The inability to elicit MEPs in the relaxed muscles of patients with SCI fail to support previous reports of expanded motor cortical representations associated with muscles innervated by roots rostral to the lesion.

Adult↗

PubMed2000

Intravenous infusion of 4-AP in chronic spinal cord injured subjects.

STUDY DESIGN: A prospective double blind cross over trial of intravenous 4-Aminopyridine (4-AP). OBJECTIVE: To determine the efficacy of this drug in the treatment of spinal cord injured (SCI) patients for neurologic impairment, pain and spasticity. SETTING: The post anesthesia care unit (PACU) of a tertiary care acute hospital. METHODS: Twelve paraplegic patients were enrolled in a double blind cross over intravenous trial of 4-Aminopyridine (4-AP). Thirty milligrams of 4-AP or placebo were administered over a 2 h period. Patients were serially examined during and after the infusion clinically for pain, sensorimotor function, hypertonicity and motor control using electromyography (EMG). Samples of blood and cerebrospinal fluid (CSF) were also analyzed at similar intervals. RESULTS: Despite penetration of 4-AP into the CSF, no significant differences were noted in the clinical and EMG parameters at the times measured. Individual changes in sensory function were reported by some patients in both the placebo and 4-AP trials, however mean values were not robust. Frequently, patients complained of unpleasant symptoms during the 4-AP infusion. CONCLUSION: The intravenous route may not be the best way to administer this drug as no short term benefits were observed.

4-Aminopyridine↗

PubMed2002

Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy.

OBJECTIVE: To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise. DESIGN: A randomized controlled study. SETTING: A university research laboratory. PARTICIPANTS: Twelve healthy elderly subjects (age range, 67-85y), 5 patients with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age range, 53-77y). INTERVENTIONS: Each subject's detection thresholds (ie, minimum level of stimulus to be detected) for a vibrotactile stimulus without and with mechanical noise (ie, random vibration with a small intensity) were determined by using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the fingertip and/or to the first metatarsal of the foot. MAIN OUTCOME MEASURE: Detection threshold for a vibrotactile stimulus. RESULTS: The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic neuropathy. For the 8 patients with diabetes, mechanical noise also significantly reduced the vibrotactile detection threshold at the foot. CONCLUSIONS: Reduced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly improved with input mechanical noise. Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function.

Adult↗

PubMed1991

Mirror-reversal phenomena in the cutaneous perception and writing of children.

When a letter is drawn on the forehead, it is perceived cutaneously as a mirror reversal of the experimenter-defined stimulus. An analogous mirror-reversal phenomenon is found in motor behaviour; eg, writing on the downward-facing horizontal surface of a table. We examined these mirror-reversal phenomena in tasks, performed by 4-year-old and 8-year-old children, involving cutaneous perception and motor-production. The children's tendencies toward mirror reversal in the two tasks varied with the orientation and position of the surface, but were similar to those of sighted and blind adult subjects. In addition, mirror reversal was independent of the left-right indifference often observed in young children in writing or visual-matching tasks. The implications of these findings are discussed in the context of a body schema used to guide sensorimotor functions.

Attention↗

PubMed1986

Construct validity of the Kendrick Battery with institutionalized aged.

In this study, we attempted to explore the construct validity of the Kendrick Battery by using an American sample and psychometric tests as indexes of diffuse organicity, depression, and normality. Institutionalized residents (N = 53) were tested twice (6-week interval). When organicity was defined by disorientation and memory deficits, then both the Object Learning test and the Digit Copying test were accurate in differentiating preestablished criterion groups. When organicity was defined more broadly, including sensorimotor function, the Digit Copying test alone was more accurate when depression was defined in terms of irritability, restlessness, and despair. These data suggest that although the Kendrick scales appeared to be sensitive to organicity and depression in this sample, their validity varied with the criteria for each when such were defined psychometrically.

Aged↗

PubMed2002

Reliability associated with the abstraction of data from medical records for inclusion in an information system for persons with a traumatic brain injury.

OBJECTIVE: This article presents the intra- and inter-rater reliability associated with the extraction, from medical rehabilitation charts, of data to be included in a head injury information system currently under development. METHODS: A data collection form was developed to facilitate and standardize the data extraction. Two clinicians extracted information pertaining to 231 variables of the system from 15 charts of persons receiving rehabilitation services following a head injury. RESULTS: Average percentage agreement was high and did not vary from one category of variables to the other (84-88%). Substantial intra-rater agreement (kappa = 0.66) and moderate inter-rater agreement (kappa = 0.56) were found to be associated with the extraction of the variables studied. CONCLUSIONS: The results suggest that clinicians using standardized procedures can reliably extract important data pertaining to personal history, impairments, and disabilities relating to sensorimotor function. Some potential sources of error are identified and recommendations are presented.

Abstracting and Indexing↗

PubMed2000

Cortical-organization in moles: evidence of new areas and a specialized S2.

The somatosensory cortex of several mole species (family Talpidae), with different peripheral sensory adaptations, was investigated and compared to determine common and specialized features of cortical organization. Previously unidentified medial representations of the trunk and limbs were found in all species, indicating that S1 in moles occupies a medial to lateral strip of cortex as in most other mammals. This finding suggests a large lateral forelimb representation, previously attributed to S1, is actually part of S2. In the face representation, evidence was found for three representations of the unusual nose of the star-nosed mole (Condylura cristata). Each of these areas was divided into a series of modules (visible in cytochrome oxidase processed tissue) representing individual nasal appendages on the star. In the closely related but less specialized eastern mole (Scalopus aquaticus) and coast mole (Scapanus orarius), only two nose representations were identified in an area of cortex with a more uniform histological appearance. The results indicate that moles have enlarged somatosensory representations of the glabrous nose as compared to shrews and rats that instead have large vibrissal representations. In addition moles have a very large and specialized representation of the digging forepaw in S2. Since this part of S2 projects directly to the cervical spinal cord, the specialization may provide adaptive sensorimotor functions related to digging.

Animals↗

PubMed1997

Perceptions of effort and heaviness during fatigue and during the size-weight illusion.

Previous work has shown that force perception and the sense of motor effort are different attributes of sensorimotor function. This study explores the hypothesis that one reason force and effort perceptions are distinct is to inform an individual of impaired motor function when muscular force lags effort. This hypothesis predicts that effort and force perceptions will dissociate when motor function is impaired by fatigue but not during the size-weight illusion. All subjects reported a distinct increase in effort when lifting a standard test weight as fatigue developed. When fatigue was sufficiently marked so that they could barely lift the test weight, they rated their effort as similar to that required to lift a maximal weight in the unfatigued state. The perceived heaviness of the test weight also increased as fatigue developed, but this fatigue-weight illusion was smaller than the increase in effort for all subjects and displayed greater variability. In contrast, both the perceived weight of a small object and the effort required to lift it increased in parallel when small and large objects were lifted sequentially. The size-weight and size-effort illusions appear to be examples of a common phenomenon in which perceptual experience is rescaled to maintain acuity under different working conditions. The fatigue-weight illusion also has the effect of increasing perceptual acuity as the subject's weight lifting range decreases due to fatigue.

Adolescent↗

PubMed2001

Dissociated active and passive tactile shape recognition: a case study of pure tactile apraxia.

Disorders of tactile object recognition (TOR) may result from primary motor or sensory deficits or higher cognitive impairment of tactile shape representations or semantic memory. Studies with healthy participants suggest the existence of exploratory motor procedures directly linked to the extraction of specific properties of objects. A pure deficit of these procedures without concomitant gnostic disorders has never been described in a brain-damaged patient. Here, we present a patient with a right hemispheric infarction who, in spite of intact sensorimotor functions, had impaired TOR with the left hand. Recognition of 2D shapes and objects was severely deficient under the condition of spontaneous exploration. Tactile exploration of shapes was disorganized and exploratory procedures, such as the contour-following strategy, which is necessary to identify the precise shape of an object, were severely disturbed. However, recognition of 2D shapes under manually or verbally guided exploration and the recognition of shapes traced on the skin were intact, indicating a dissociation in shape recognition between active and passive touch. Functional MRI during sensory stimulation of the left hand showed preserved activation of the spared primary sensory cortex in the right hemisphere. We interpret the deficit of our patient as a pure tactile apraxia without tactile agnosia, i.e. a specific inability to use tactile feedback to generate the exploratory procedures necessary for tactile shape recognition.

Adult↗

PubMed1991

Postural stability and associated physiological factors in a population of aged persons.

A battery of 13 visual, vestibular, sensorimotor, and balance tests was administered to 95 elderly persons (mean age 82.7 years) to examine the relationships between specific sensorimotor functions and measures of postural stability. When subjects stood on a firm surface, increased body sway was associated with poor tactile sensitivity and poor joint position sense. When subjects stood on a compliant surface (which reduced peripheral sensation) with their eyes open, increased body sway was associated with poor visual acuity and contrast sensitivity, reduced vibration sense, and decreased ankle dorsiflexion strength as well as reduced joint position sense. Increased body sway with eyes closed on the compliant surface was associated with poor tactile sensation, reduced quadriceps and ankle dorsiflexion strength, and increased reaction time. Poor performance in two clinical measures of postural stability was associated with reduced sensation in the lower limbs as measured by joint position sense, tactile sensitivity and vibration sense, reduced quadriceps and ankle dorsiflexion strength, and slow reaction times. The prevalence of vestibular impairments was high in this group, but vestibular function was not significantly associated with sway under any of the test conditions. The results suggest that reduced sensation, muscle weakness in the legs, and increased reaction time are all important factors associated with postural instability. An analysis of the percentage increases in sway under conditions where visual and peripheral sensation systems are removed or diminished, compared with sway under optimal conditions, indicated that peripheral sensation is the most important sensory system in the maintenance of static postural stability.

Aged↗

PubMed2001

Antisense oligodeoxynucleotide to inducible nitric oxide synthase protects against transient focal cerebral ischemia-induced brain injury.

Nitric oxide (NO) has been suspected to mediate brain damage during ischemia. Here the authors studied the effects of an antisense oligodeoxynucleotide (ODN) directed against the inducible isoform of NO synthase (iNOS) in a model of transient focal cerebral ischemia in rats. Treatment consisted of seven intracerebroventricular injections of a phosphodiester/phosphorothioate chimera ODN (3 nmol each) at 12-hour intervals, and was initiated 12 hours before a 2-hour occlusion of the left middle cerebral artery and common carotid artery. Outcomes were measured three days after ischemia. When compared with animals treated with vehicle or an appropriate random non-sense control ODN sequence, the antisense treatment reduced the lesion volume by 30% and significantly improved recovery of sensorimotor functions, as assessed on a neuroscore. This effect was associated with a decrease in iNOS expression, as assessed by Western blot, a 39% reduction in iNOS enzymatic activity evaluated as Ca2+-independent NOS activity, and a 37% reduction in nitrotyrosine formation, reflecting protein nitration by NO-derived peroxynitrite. These findings provide new evidence that inhibition of iNOS may be of interest for the treatment of stroke.

Animals↗