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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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Phantom limb phenomenon in patients with leprosy.

The phantom limb phenomenon (PLP) was studied in 42 patients with leprosy who had limb amputation and/or digital shortening; some of the patients also had another type of limb deformity, such as claw-hand or foot-drop, which did not involve significant loss of tissue. Thirty-eight (90 per cent) of the patients reported having at least one phantom limb (PL) for a missing or deformed part. Associated with each of the three types of limb defects, two descriptively and experientially distinct types of PLs were found: the paresthetic or typical (TPL) and the painless or natural (NPL). Descriptions of the TPL and the NPL are given. The findings were compared to various reports, particularly those of Stetter and Frederiks. The leprosy TPL was similar both to the PL of amputees as frequently described in the literature, and to what Stetter and Frederiks termed the PL sensations. A close correspondence, if not identity, was noted between the NPL of leprosy patients and the equivalent categories of Stetter's PL experience and Frederiks' PL as such. Included in these three designations are aspects of the PLP that are associated with the normal, intact limb; these aspects are thought to be usual concomitants of the PLP and to constitute manifestations of the persistence of the normal body image. From our findings, we conclude that for the appearance of a PLP, the actual loss of a part of a limb, whether slow or sudden, is not required, but the loss of its sensorimotor functions is sufficient.

Adult↗

Prognostic significance of cerebral status: dimensions of clinical outcome.

This report examines the relationship between a set of neurobehavioral predictor variables (premorbid cognitive-perceptual abilities, sensorimotor functions, and complex integrative skills) and three dimensions of clinical outcome (social outcome, work functioning, and rehospitalization) 2 years after discharge from inpatient treatment for a group of psychiatric disorders. Results indicated the strongest relationship was between premorbid ability levels and work performance, particularly maintaining stability of employment or work role function. This finding is discussed from the standpoint of neurological processes underlying early acquisition of basic cognitive-perceptual skills in the prediction of outcome.

Adult↗

Herniated L4-L5 disc after placement of Harrington instrumentation for a fracture of the thoracolumbar spine.

The authors report a case in which L5 radiculopathy developed acutely after surgery for placement of Harrington rod instrumentation for an L1 body fracture. Computed tomographic myelography demonstrated a large L4-L5 herniated disc that had not been present in preoperative studies. An emergency laminectomy was performed, and a large, free, subligamentous disc fragment was removed. The patient subsequently regained L5 sensorimotor function. The postoperative development of lumbar radiculopathy is an uncommon complication of Harrington rod instrumentation that may result from several biomechanical features of the instrumentation. These injuries may not be detected by intraoperative monitoring of somatosensory evoked potentials, and therefore, the postoperative neurological examination assumes a crucial role in the early diagnosis of these lesions. As our case demonstrates, these radicular deficits may be reversible if their cause is promptly recognized and treated.

Aged↗

Pathogenesis of spinal cord injury and newer treatments. A review.

Many victims of traumatic spinal cord injury (SCI) suffer immediate paralysis as well as a subsequent progressive worsening of the cord pathology. Certain sensorimotor functions that might otherwise have returned are irreversibly lost because of this delayed response. An understanding of the pathophysiology behind this progressive, self-destructive sequence is yet to be acquired; however, numerous proposals have been set forth involving processes such as edema formation, vascular changes, an inflammatory reaction, and destruction of the neuronal plasma membranes. In this review, the authors outline many of the chemical, anatomic, and functional changes associated with SCI as well as a number of treatment regimens that have been found to improve recovery from SCI (including parenteral glucocorticoid therapy, localized cord cooling, calcium channel blockers, and opiate antagonism). From this, a number of mechanisms accounting for the mediation and/or prevention of the secondary destructive response are synthesized.

Animals↗