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At least 1,603 records · Page 89Linked to original sources
PubMed1986

1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs.

Brain sigma-type receptors are thought to mediate hallucinogenic effects of certain benzomorphan opiates in humans. The biochemical characterization of sigma receptors has been difficult because of the lack of potent and selective ligands. We report here the synthesis and characterization of a tritiated, symmetrically substituted guanidine derivative, 1,3-di(2-[5-3H]tolyl)guanidine ([3H]Tol2Gdn), that binds with high affinity to a single population of binding sites in guinea pig brain membrane preparations. The [3H]Tol2Gdn binding site displays stereoselectivity for dextrorotatory optical isomers of benzomorphan opiates known to have sigma-type behavioral effects. Furthermore, the [3H]Tol2Gdn binding site has a high affinity for haloperidol and for phenothiazine antipsychotics, which have antihallucinatory properties in humans. The drug-selectivity profile of [3H]Tol2Gdn binding closely correlates with the drug-selectivity profile of tritiated (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+)-[3H]3-PPP) binding to guinea pig brain membrane receptors. (+)-[3H]3-PPP has been proposed to be a selective sigma-receptor ligand [Largent, B. L., Gundlach, A. L. & Snyder, S. H. (1984) Proc. Natl. Acad. Sci. USA 82, 4983-4987]. Receptor autoradiography using [3H]Tol2Gdn on slide-mounted rat and guinea pig brain sections reveals a heterogeneous distribution pattern of enriched binding in limbic and sensorimotor structures of the brain. These results indicate that [3H]Tol2Gdn is a selective ligand for the sigma-site. Availability of this sigma-receptor probe should greatly facilitate the physiological, biochemical, and pharmacological characterization of sigma receptors in brain.

Animals↗
PubMed2005

Assessment of infant oral sensorimotor and swallowing function.

The development of feeding and swallowing is the result of a complex interface between the developing nervous system, various physiological systems, and the environment. The purpose of this article is to review the neurobiology, development, and assessment of feeding and swallowing during early infancy. In recent years, there have been exciting advances in our understanding of the physiology and neurological control of feeding and swallowing. These advances may prove useful in furthering our understanding of the pathophysiology of dysphagia in infancy. Progress in developing standardized, reliable, and valid measures of oral sensorimotor and swallowing function in infancy has been slow. However, there have been significant advances in the instrumental analysis of feeding and swallowing disorders in infancy, including manometric analyses of sucking and swallowing, measures of respiration during feeding, videofluoroscopic swallow evaluations, ultrasonography, and flexible endoscopic examination of swallowing. Further efforts are needed to develop clinical evaluative measures of dysphagia in infancy.

Deglutition↗
PubMedDate not supplied

Time organization of frontal-motor cortex interneuron interactions in the cat neocortex in conditions of different levels of food motivation.

Studies were carried out in conscious cats with recording of multicellular activity in moderate hunger and after 24-h food deprivation. Cross-correlation analysis was used to assess statistical interneuron interactions between closely-located neurons in the frontal and sensorimotor regions of the neocortex (local networks), and between the cells of these regions (distributed networks). One-day food deprivation increased the number of interactions formed within both local and distributed neuron networks. Increases in intercortical connections between the frontal and motor regions was seen at all time intervals studied (0-100 msec), though the most significant changes occurred at time intervals of up to 30 msec.

Action Potentials↗
PubMed1989

Mechanisms of orphenadrine-induced antinociception in mice: a role for serotonergic pathways.

The possible involvement of central serotonergic pathways in the mechanism of action of orphenadrine citrate was investigated in male albino mice. Orphenadrine (20 mg/kg) did not alter the concentration of 5-hydroxytryptamine (5-HT) or its metabolite 5-hydroxyindole acetic acid in the frontal cortex or spinal cord, nor did it, in moderate concentrations, inhibit the uptake of [14C]5-HT, [3H]noradrenaline ([3H]NA) or [3H]dopamine ([3H]DA) into crude synaptosomal preparations from the cortex. The antinociceptive effect of orphenadrine was studied in the formalin test and in the increasing temperature hot plate test. No sensorimotor impairment was observed for doses of 30 mg/kg or lower. A general depletion of serotonin by means of p-chlorophenylalanine significantly reduced the effect of orphenadrine in both tests, while lesion of the ascending serotonergic systems by means of p-chloroamphetamine did not affect the analgesia. It is concluded that the antinociceptive effect of orphenadrine may be mediated in part via the raphe-spinal serotonergic systems.

Analgesics↗
PubMed2004

Progressive sensorimotor impairment is not associated with reduced dopamine and high energy phosphate donors in a model of ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is a genetic disease, associated with progressive motor impairment and a lack of functional ATM protein. It has been reported that immunoreactive tyrosine hydroxylase and dopamine transporter are reduced in an Atm-/- mouse model of A-T. These observations led to a hypothesis that A-T is associated with loss of nigrostriatal dopamine and prompted the launch of clinical trials to evaluate a therapeutic utility of the anti-parkinsonian drug, l-DOPA. To test for dopamine depletion more directly, we measured regional levels of monoamines and their metabolites in the Atm-/- mouse brain. We also measured levels of NAD+, a cofactor for dopamine biosynthesis and substrate of the DNA damage surveillance enzyme, poly(ADP-ribose) polymerase (PARP). Constitutive activation of PARP has been posited to cause NAD+ depletion. We observed no reduction in monoamine transmitters and no depletion of NAD+, or other high energy phosphate donors in the adult Atm-/- cerebellum, striatum, or ventral mesencephalon. However, our studies did reveal a progressive sensorimotor impairment in Atm-/- mice that may serve as a relevant proxy for progressive neurological impairment in the human disease. Our results call into question the involvement of dopamine in A-T and the therapeutic strategy of enhancing dopaminergic function with l-DOPA.

Adenosine Diphosphate↗
PubMed1999

Striatal preproenkephalin gene expression is upregulated in acute but not chronic parkinsonian monkeys: implications for the contribution of the indirect striatopallidal circuit to parkinsonian symptomatology.

This study examined the extent of striatal dopamine (DA) denervation and coincident expression of preproenkephalin (PPE) mRNA in monkeys made parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Some animals (n = 4) became moderately parkinsonian after receiving large doses of MPTP over short periods of time and were symptomatic for only a short period of time (1-3 months; acute parkinsonian group). Other animals became moderately parkinsonian after receiving either escalating doses of MPTP over long periods (4-6 months; n = 5) or a high dose of MPTP over a short period (<1 month; n = 1) and remained symptomatic for an extended period (>8 months; chronic parkinsonian group). Despite similar symptomatology and similar degrees of striatal DA denervation at the time of their deaths, only acute parkinsonian animals had significantly increased PPE expression in sensorimotor striatal regions. PPE expression in chronic parkinsonian animals was either not changed or significantly decreased in most striatal regions. These findings suggest that the duration and not the extent of striatal DA denervation is a critical factor in modulating changes in striatal PPE expression. Furthermore, these results question the role of increased activity in the enkephalin-containing indirect striatopallidal pathway in the expression of parkinsonian symptoms.

Acute Disease↗
PubMed1980

Symposium on object relations theory and love. Object concept and object choice.

Any considerations of object relations theory and love requires a clear understanding of how the term, object relations, is used. In this contribution the concept of the object as a mental representation is emphasized. Developmentally, the evolution of the object cannot be separated from the vicissitudes of the drives. Sensorimotor experience is metaphorically assimilated in terms of pleasure-unpleasure components. Since the object concept develops in this context, it is inextricably linked to the vicissitudes of the drives. In later experience, these become organized in terms of persistent unconscious fantasies that ultimately affect object choice and patterns of loving. These are multiple determined and are influenced by contributions from all levels of development, predominantly integrated under the aegis of the oedipus complex.

Aggression↗
PubMed2003

Enactment effect in memory: evidence concerning the function of the supramarginal gyrus.

Experimental behavioral data show that written action descriptions are remembered better when encoded by enacting them compared with merely verbal encoding. To explore this facilitating effect of encoding by performing actions ('enactment effect'), a functional magnetic resonance imaging (fMRI) study was conducted with n=18 normal subjects. During a learning condition, subjects encoded action phrases like 'cut the bread' either by reading aloud or by enacting them. The same phrases plus additional distractors were presented during fMRI scanning, and the task was to decide (yes/no key press) whether a displayed phrase was previously learned or whether it was a new one. Retrieval--independent of encoding type--activated anterior cingulate, SMA, and visual cortex bilaterally. Activations of the inferior frontal and sensorimotor cortex, and the precentral sulcus, were only left sided. The right cerebellum was also activated. The subtraction of the brain activations in the verbal condition from the enactment condition resulted in significant clusters located in middle temporal and inferior parietal left cortical areas, and, on the right side, in superior temporal, postcentral and inferior parietal cortical areas. Most striking were the bilateral inferior parietal activations, covering the supramarginal gyrus (SMG). Therefore it is concluded that SMG may be a central structure in a neurofunctional explanation of the enactment effect.

Adult↗
PubMed2003

Altered awareness of voluntary action after damage to the parietal cortex.

A central question in the study of human behavior is the origin of willed action. EEG recordings of surface brain activity from human subjects performing a self-initiated movement show that the subjective experience of wanting to move follows, rather than precedes, the 'readiness potential'--an electrophysiological mark of motor preparation. This raises the issue of how conscious experience of willed action is generated. Here we show that patients with parietal lesions can report when they started moving, but not when they first became aware of their intention to move. This stands in contrast with the performance of cerebellar patients who behaved as normal subjects. We thus propose that when a movement is planned, activity in the parietal cortex, as part of a cortico-cortical sensorimotor processing loop, generates a predictive internal model of the upcoming movement. This model might form the neural correlate of motor awareness.

Adult↗
PubMed2002

Hyperbaric oxygenation prevented brain injury induced by hypoxia-ischemia in a neonatal rat model.

The occurrence of hypoxia-ischemia (HI) during early fetal or neonatal stages of an individual leads to the damaging of immature neurons resulting in behavioral and psychological dysfunctions, such as motor or learning disabilities, cerebral palsy, epilepsy or even death. No effective treatment is currently available and this study is the first to use hyperbaric oxygen (HBO) as a treatment for neonatal HI. Herein, we sought out to determine if HBO is able to offer neuroprotectivity against an HI insult. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O(2) at 37 degrees C). HBO treatment was administered by placing pups in a chamber (3 ATA for 1 h) 1 h after hypoxia exposure. Brain injury was assessed based on ipsilateral hemispheric weight divided by contralateral hemispheric weight, light microscopy, and EM. Sensorimotor functional tests were administered at 5 weeks after hypoxia exposure. After HI, the ipsilateral hemisphere was 52.65 and 57.64% (P<0.001) of the contralateral hemisphere at 2 and 6 weeks, respectively. In HBO treated groups, the ipsilateral hemisphere was 77.77 and 84.19% (P<0.001) at 2 and 6 weeks. There was much less atrophy and apoptosis in HBO treated animals under light or electron microscopy. Sensorimotor function was also improved by HBO at 5 weeks after hypoxia exposure (Chi-square, P<0.050). The results suggest that HBO is able to attenuate the effects of HI on the neonatal brain by reducing the progression of neuronal injury and increasing sensorimotor function.

Animals↗
PubMed1997

Modulation of cognition-specific cortical activity by gonadal steroids: a positron-emission tomography study in women.

There is considerable evidence from animal studies that gonadal steroid hormones modulate neuronal activity and affect behavior. To study this in humans directly, we used H215O positron-emission tomography to measure regional cerebral blood flow (rCBF) in young women during three pharmacologically controlled hormonal conditions spanning 4-5 months: ovarian suppression induced by the gonadotropin-releasing hormone agonist leuprolide acetate (Lupron), Lupron plus estradiol replacement, and Lupron plus progesterone replacement. Estradiol and progesterone were administered in a double-blind cross-over design. On each occasion positron-emission tomography scans were performed during (i) the Wisconsin Card Sorting Test, a neuropsychological test that physiologically activates prefrontal cortex (PFC) and an associated cortical network including inferior parietal lobule and posterior inferolateral temporal gyrus, and (ii) a no-delay matching-to-sample sensorimotor control task. During treatment with Lupron alone (i.e., with virtual absence of gonadal steroid hormones), there was marked attenuation of the typical Wisconsin Card Sorting Test activation pattern even though task performance did not change. Most strikingly, there was no rCBF increase in PFC. When either progesterone or estrogen was added to the Lupron regimen, there was normalization of the rCBF activation pattern with augmentation of the parietal and temporal foci and return of the dorsolateral PFC activation. These data directly demonstrate that the hormonal milieu modulates cognition-related neural activity in humans.

Adult↗
PubMed2000

Tapping movements according to regular and irregular visual timing signals investigated with fMRI.

Whole-head functional MR images were acquired while 10 subjects were asked to tap with their right index finger in synchrony with a visual stimulus appearing regularly with a frequency of 1.5 Hz, or irregularly with a mean frequency of 1.5 Hz. Performance data show that during regular tapping most taps were close to stimulus onset. However, when the subjects paced their tapping according to the irregular stimuli, most taps appeared about 300 ms after the onset of the pacing stimuli. Comparing the brain activations resulting from regular tapping with those from irregular tapping, we found increased activation in left precuneus only. Comparing irregular versus regular tapping shows increased activity in right cerebellar nuclei and vermis, left ventrolateral thalamus, left sensorimotor cortex, left and right pre-SMA and left SMA proper. These results show that during irregular pacing the motor areas are more strongly activated than during regular pacing. In addition, further neural systems are involved in the motor control during irregular pacing: cerebellar vermis and a cerebello-thalamo-cortical system. The latter is supposedly involved in error correction in the context of visually guided movements.

Adult↗
PubMed2003

Model of a predatory stealth behaviour camouflaging motion.

A computational model of a stealth strategy inspired by the apparent mating tactics of male hoverflies is presented. The stealth strategy (motion camouflage) paradoxically allows a predator to approach a moving prey in such a way that it appears to be a stationary object. In the model, the predators are controlled by neural sensorimotor systems that base their decisions on realistic levels of input information. They are shown to be able to employ motion camouflage to approach prey that move along both real hoverfly flight paths and artificially generated flight paths. The camouflaged approaches made demonstrate that the control systems have an ability to predict future prey movements. This is illustrated using two- and three-dimensional simulations.

Animals↗
PubMed2003

Saccade adaptation in response to altered arm dynamics.

The delays in sensorimotor pathways pose a formidable challenge to the implementation of stable error feedback control, and yet the intact brain has little trouble maintaining limb stability. How is this achieved? One idea is that feedback control depends not only on delayed proprioceptive feedback but also on internal models of limb dynamics. In theory, an internal model allows the brain to predict limb position. Earlier we had found that during reaching, the brain estimates hand position in real-time in a coordinate system that can be used for generating saccades. Here we tested the idea that the estimate of hand position, as expressed through saccades, depends on an internal model that adapts to dynamics of the arm. We focused on the behavior of the eyes as perturbations were applied to the unseen hand. We found that when the hand was perturbed from stable posture with a 100-ms force pulse of random direction and magnitude, a saccade was generated on average at 182 ms postpulse onset to a position that was an unbiased estimate of real-time hand position. To test whether planning of saccades depended on an internal model of arm dynamics, arm dynamics were altered either predictably or unpredictably during the postpulse period. When arm dynamics were predictable, saccade amplitudes changed to reflect the change in the arm's behavior. We suggest that proprioceptive feedback from the arm is integrated into an adaptable internal model that computes an estimate of current hand position in eye-centered coordinates.

Adaptation, Physiological↗
PubMed1999

Synchronization, anticipation, and consistency in motor timing of children with dimensionally defined attention deficit hyperactivity behaviour.

We tested the hypothesis that children with hyperactive behaviour are impaired in the temporal organization of their motor output. The performance of 11 boys, scoring above a cut-off on standard scales of overactivity and inattention, was compared to that of controls in progressively more complex Motor-timing tasks. The tasks administered required self-paced and externally paced Sensorimotor Synchronization and Sensorimotor Anticipation. Deficits at a perceptual level were investigated with a Time-discrimination task. As hypothesized, we found that hyperactive children had no deficits in their perception of time but were impaired in timing their motor output. Hyperactive children were more inconsistent than controls in maintaining a freely chosen tapping rhythm, in synchronizing and in anticipating their motor response to external visual stimulation.

Attention Deficit Disorder with Hyperactivity↗
PubMed1986

Rats given dopamine-depleting brain lesions as neonates do not respond to acute homeostatic imbalances as adults.

Rats given near-total dopamine-depleting brain lesions as neonates exhibit none of the severe sensorimotor or ingestive dysfunctions that result when adult rats are given comparable lesions. These experiments showed that the apparent sparing of function is incomplete; when tested as adults, the brain-damaged animals did not eat in response to acute glucoprivation, nor did they drink water and saline in response to hypovolemia. Indeed, after receiving these homeostatic challenges, the animals became much less able to simply move about. In contrast to these marked effects, the dopamine-depleted rats ate normally after glucoprivation when they were handled hourly instead of being left alone. Similarly, administration of caffeine permitted them to drink while hypovolemic. These and other observations suggest that some central neurons other than those containing dopamine are responsible for maintaining behavioral activation in rats after neonatal destruction of dopaminergic fiber systems in the brain and that the homeostatic challenges compromise their function and thereby disrupt behavior.

Adaptation, Physiological↗
PubMed2004

A prospective functional MR imaging study of mild traumatic brain injury in college football players.

BACKGROUND AND PURPOSE: Although concussion is common among athletes, evidence-based methods for clinical evaluation, treatment, and recovery are lacking. We used a prospective, functional neuroimaging approach to assess sports-related concussion in which imaging was performed before injury so that brain changes resulting from concussion could be better understood. METHODS: Neurophysiologic correlates of sports-related concussion were investigated in eight college football players by using functional MR imaging. Preseason baseline levels of blood oxygen level-dependent (BOLD) activity were acquired during the performance of a test battery that included mathematical, memory, and sensorimotor coordination tasks. Four players who had a concussion repeated these baseline procedures within 1 week of injury. The remaining control players were retested at the end of the season. RESULTS: Specific neural signatures of concussion were detected in individual players by comparing postconcussion results to preconcussion baseline values. The validity of these indicators was confirmed by comparing them with the same measures in noninjured control subjects. When compared with control subjects, concussed players had marked within-subject increases in the amplitude and extent of BOLD activity during a finger-sequencing task. Effects were observed primarily in the parietal and lateral frontal and cerebellar regions. CONCLUSION: Differences in neural functioning were observed in the absence of observed deficits in behavioral performance, suggesting that this approach may increase sensitivity to concussion compared with neuropsychological evaluation alone. Though preliminary, the proposed prospective neuroimaging approach may have great potential for understanding mild traumatic brain injury and identifying mechanisms underlying recovery.

Adult↗
PubMed1988

Reductions in maternal food and water intake account for prenatal stress effects on neurobehavioral development in B6D2F2 mice.

This study evaluated the role of stress-induced reductions in food intake in pregnant B6D2F1 mice in the production of developmental abnormalities in the offspring. One group of dams underwent one hour of physical restraint stress twice daily from days 12 to 17 of gestation. A second group was not restrained but, during this period, each dam was pair-fed to a weight-matched partner in the stressed group. A third group was left undisturbed and allowed unlimited access to lab chow and water. The restraint stress procedure reduced the average daily food and water intake in the dams, resulting in lower maternal weights, with the unstressed pair-fed group being affected more severely than the stressed group. The offspring of both the stressed and pair-fed dams were lighter than the offspring of the dams fed ad lib on day 20 postconception, and exhibited lower brain weights on day 32 postconception. Neurobehavioral development, as assessed on a battery of sensorimotor tests on day 32 postconception, was retarded in the prenatally stressed pups in comparison to the ad lib pups, while the pair-fed pups did not differ from either group. There were no differences among any of the groups on day 50 body or brain weight, body or tail length, anogenital distance, or locomotion, rearing and defecation in the open field.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗