SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Unilateral lesions of the sensorimotor cortex were made in rabbits either 24 h or 6 months after birth. Four months after the operation the hopping reaction in the leg contralateral to the lesion was still absent in the animals operated in adulthood. In the animals operated one day after birth a normal hopping reaction was found when tested 1.5 and 4 months after the operation.
The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PPI), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined whether ketamine-induced locomotion was influenced by the dark/light cycle. We found that ketamine increased locomotor activity in a dose dependent manner, but found no influence of the dark-light cycle. Additionally, ketamine dose-dependently interrupted PPI, resulting in prepulse facilitation at doses of 8 and 12 mg/kg. The dose of 12 mg/kg also induced impairments in working memory assessed by the discrete-trial delayed-alternation task. C-fos expression indicated that the dose-dependent behavioral effects of ketamine might be related to changes in the activity of limbic regions, notably hippocampus and amygdala.
Recent biochemical data suggest that arachidonylethanolamide (AEA; anandamide) may be an endogenous ligand for brain cannabinoid receptors. The functional neuronal consequences of AEA binding to cannabinoid receptors are only poorly understood. Using regional cerebral blood flow (rCBF) as an indirect marker of neuronal activity, acute AEA administration dose-dependently depressed rCBF in unanesthetized rats. Although 3.0 mg/kg was ineffective in altering rCBF, 10 mg/kg led to a decrease in rCBF in seven brain areas including the amygdala, cingulate, frontal, prepyriform, sensorimotor, and claustrocortex. An additional 16 areas responded in a similar manner to AEA, but only after 30 mg/kg, including the CA1 and CA3 regions of the hippocampus, the rostral core portion of the nucleus accumbens, and rostral caudate nucleus. Most of these rCBF effects dissipated between 15 and 20 min after drug administration, with only 4 regions, the basomedial and lateral amygdala, CA3 hippocampus and claustrocortex still depressed 60 min after an acute drug injection. No significant changes in heart rate, blood pressure, or blood gases were seen at the time of rCBF measurement, suggesting that the observed drug effects were neuronally mediated. Taken together with existing behavioral data, these data support the hypothesis that an endogenous cannabinoid neural system exists in mammalian brain and may help to explain the unique behavioral profile seen after cannabinoid administration.
A gaze-stabilization reflex that has been conserved throughout evolution is the rotational vestibuloocular reflex (RVOR), which keeps images stable on the entire retina during head rotation. An ethological newer reflex, the translational or linear VOR (TVOR), provides fast foveal image stabilization during linear motion. Whereas the sensorimotor processing has been extensively studied in the RVOR, much less is currently known about the neural organization of the TVOR. Here we summarize the computational problems faced by the system and the potential solutions that might be used by brain stem and cerebellar neurons participating in the VORs. First and foremost, recent experimental and theoretical evidence has shown that, contrary to popular beliefs, the sensory signals driving the TVOR arise from both the otolith organs and the semicircular canals. Additional unresolved issues include a scaling by both eye position and vergence angle as well as the temporal transformation of linear acceleration signals into eye-position commands. Behavioral differences between the RVOR and TVOR, as well as distinct differences in neuroanatomical and neurophysiological properties, raise multiple functional questions and computational issues, only some of which are readily understood. In this review, we provide a summary of what is known about the functional properties and neural substrates for this oculomotor system and outline some specific hypotheses about how sensory information is centrally processed to create motor commands for the VORs.
Previous studies indicate that a variety of pharmacological agents interfere with the prepulse inhibition of the acoustic startle (PPI) response including phencyclidine (PCP), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), amphetamine, and apomorphine. Strain differences have been observed in the ability of apomorphine to disrupt PPI, although the degree to which these strain differences occur after administration of nondopaminergic drugs or the degree to which differences can be observed in other models of dopamine (DA) receptor activation has not been elucidated. The present study tested the effects of apomorphine, amphetamine, 8-OH-DPAT, and PCP on PPI in the Sprague Dawley and Wistar rat strains. Because apomorphine disrupts PPI via activation of DA receptors in the nucleus accumbens, apomorphine-induced hyperlocomotion, also a behavioral model of nucleus accumbens DA receptor activation, was measured in both rat strains. Administration of PCP or 8-OH-DPAT attenuated PPI in both strains, whereas apomorphine and amphetamine only attenuated PPI in Wistar rats. The ability of apomorphine to increase motor activity in the absence of a startle-eliciting stimulus was similar in the two strains, as was apomorphine-induced hyperlocomotion. A time course analysis of the effects of apomorphine on startle response in Sprague Dawley rats found that changes in the magnitude of PPI followed changes in basic startle amplitude. Similarly, no apomorphine-induced attenuation of PPI was observed in Sprague Dawley rats after 6-OHDA-induced DA receptor supersensitivity in the nucleus accumbens. These data suggest a dissociation between the effects of DA receptor agonists in PPI and other behavioral models of DA receptor activation.
Humans with Parkinson's disease (PD) often have problems in righting themselves, in that they have difficulty in recruiting their axial musculature to rotate the body to prone. Since this "axial apraxia' is not ameliorated by L-DOPA therapy, it has been concluded that dopamine (DA) does not play a role in recruiting axial rotation of the body [14]. This hypothesis was tested by comparing the righting of rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra (SN) with that of intact rats. Body-on-body righting, where asymmetrical tactile stimulation of the body initiates hindquarter righting, was used to specifically test tactile righting independently of righting triggered or influenced by other sensory systems. In this behavioral test, rats are placed on their sides, their forequarters are held down and their hindquarters released. The DA-depleted rats took longer to begin righting, to complete righting, and used more limb action to right themselves than did control rats. These findings suggest that for this tactile based form of righting, DA-depletion produces axial apraxia. However, frame-by-frame analysis of righting sequences of DA-depleted rats showed that pelvis-led axial rotation could occur, but the spatio-temporal relationship between body and limb movements was disorganized. Therefore, following DA-depletion axial apraxia-like deficits appear to arise from sensorimotor disruption. This raises the issue of whether the axial apraxia in PD patients arises from damage to systems beyond the nigrostriatal DA system, or from interference with sensorimotor integration that is not ameliorated by replacement therapy.
Stimulation of small diameter afferents can influence motor behavior. Little is known about how a prolonged painful stimulation of these small afferents may affect essential motor behavior such as the maintenance of an erect stance. The present study documents the effects of 10-s weak, moderate and extreme painful stimulations applied to the dorsum of the feet on the postural stability. Also, the moderate painful stimulation was applied to the metacarpal heads to determine if a painful stimulation to a limb not involved in the maintenance of the erect stance affects the postural control mechanisms. Increasing the intensity of the painful stimulation applied to the feet yielded larger postural oscillations whereas stimulation to the hands did not affect the control of posture. This suggests that the painful stimulation mainly affected the postural control mechanisms via sensorimotor processes rather than via cognitive resources related to the perception of pain.
We produced unilateral photochemical infarcts in the hindlimb sensorimotor neocortex of 186 rats by intravenous injection of the fluorescein derivative rose bengal and focal illumination of the intact skull surface. Infarcted rats showed specific, long-lasting deficits in tactile and proprioceptive placing reactions of the contralateral limbs, mostly the hindlimb. Placing deficits were most prominent during transition to immobility and/or when independent limb movements were required. Administration of flunarizine, a Class IV calcium antagonist, 30 minutes after infarction resulted in marked sparing of sensorimotor function in 30 rats. In contrast to 20 vehicle-treated rats, which remained deficient for at least 21 days, 15 (75%) of the rats treated with 1.25 mg/kg i.v. flunarizine showed normal placing on Day 1 after infarction, whereas the remaining five (25%) recovered within 5 days. Oral treatment of 10 rats with 40 mg/kg flunarizine was also effective. Neocortical infarct volume and thalamic gliosis, assessed 21 days after infarction, did not differ between 30 flunarizine- and 30 vehicle-treated rats. However, when 4-hour-old infarcts were measured in 16 rats, posttreatment with intravenous flunarizine reduced infarct size by 31%. In combination with appropriate behavioral analyses, photochemical thrombosis may constitute a relevant stroke model, in which flunarizine preserved behavioral function during a critical period, corresponding to the spread of ischemic damage.
Topographically organized dopaminergic projections from the extrapyramidal structures of the ventral mesencephalon (substantia nigra and ventral tegmental area) to the dorsal (body of caudate-putamen) and ventral (anterior-ventral caudate, nucleus accumbens, tuberculum olfactorium) striatum subserve sensorimotor integration in the rat. Selective depletion of DA impairs the animal's ability to integrate sensory input with motor output; in the dorsal striatum the exteroceptive sensory input and in the ventral or limbic striatum the interoceptive input principally related to motivation and affect. Grafts of fetal DA neurons to the damaged dorsal striatum reverse sensorimotor asymmetry and sensory neglect. A large number of other excitatory and inhibitory neurotransmitters, including recently discovered neuropeptides, contribute to the functional balance afforded by the DA neurons. This chemical heterogeneity of the basal ganglia offers the possibility that novel therapeutic approaches with drugs could be used to control the chemical imbalances in basal ganglia that are associated with a number of neurological and psychiatric conditions.
PURPOSE: The purpose of this study was to examine the effects of dimerized basic fibroblast growth factor (dFGF), a novel engineered growth factor, in a model of functional recovery following focal cerebral infarction (stroke) in rats. METHODS: A focal stroke was made in mature male rats by occlusion of the middle cerebral artery (MCA). dFGF was administered by intracisternal injection at one and three days after stroke. Tests to evaluate sensorimotor recovery of the contralateral limbs were done during the next three weeks after stroke. RESULTS: dFGF significantly enhanced recovery of sensorimotor function in limb placing and body swing tests compared to vehicle treatment. There were no differences in body weight or infarct volume in dFGF- vs. vehicle-treated animals. CONCLUSIONS: dFGF represents a potential treatment to enhance functional recovery after stroke and offers several advantages over bFGF, including stability and independence from extracellular heparan sulfates.
Brain cells are naturally exposed to a variety of trophic factors during development. Basic Fibroblast Growth Factor (bFGF), a protein found in the central nervous system (CNS) enhances both survival and proliferation of several CNS cell lines. Neonatal mice of the CD1 outbred strain were injected intracerebroventricularly (ICV) with bovine bFGF on postnatal days 2, 4, and 7. bFGF, dissolved in 25 microliters of saline, was given in the 1, 5, 25, and 1000 ng doses. Physical traits such as body weight gain, body length, and tail length were recorded from postnatal day (PND) 2 to PND 12. Neurobehavioral development was scored according to a modified Fox's Scale. The ultrasonic vocalization pattern (PND 8), homing performance (PND 10), open-field activity and exploration of a novel object (PND 18) were also assessed. Pups receiving 25 and 1000 ng doses of bFGF showed a slight but significant acceleration in the appearance of some early sensorimotor reflexes, such as weak and tactile stimulation, forelimb placing and grasping, and screen climbing, during the first postnatal weeks. The other responses were less affected or not affected at all. Data are compared with similar systemic exposure of neonatal mice to Nerve Growth Factor (NGF).
The purpose of this study was to determine the efficacy of oral sensorimotor treatment in moderately eating-impaired children with cerebral palsy and to examine the effects of treatment on measures of growth. Six domains of feeding were examined in 35 children 4.3-13.3 years of age. Weight and skinfold measures were taken. Children were observed at lunch time, and spoon-feeding, biting, chewing, cup drinking, straw drinking, swallowing, and drooling were examined. Children underwent 20 weeks of sensorimotor treatment, 5-7 min/day, 5 days/week. Limited improvement was observed in the following eating domains: spoon-feeding, biting, and chewing, but not in drinking. Children as a group maintained the pretreatment weight-age percentile. To meet the increasing growth demands of the teenage years, oral-motor therapy may need to be combined with oral caloric supplementation.
The presence of human immunodeficiency virus type 1 (HIV-1) in the brain is believed to be responsible for mediating the pathogenesis of neurological abnormalities through the viral toxins gp120 and Tat. Numerous studies indicate neurotoxic effects of the HIV-1-protein Tat, with demonstrated neurobehavioral and cognitive alterations. However, less clear is the neurotoxic effect of gp120 on neurobehavior. This study was designed to characterize the potential deficits in sensory-motor and preattentive functions, following intrahippocampal administration of gp120. Using a randomized-block design, male and female pups of eight Sprague-Dawley litters were injected bilaterally with either vehicle (VEH) (1 microl volume) or one of the three gp120 doses (1.29, 12.9, or 129 ng/microl) at postnatal day (P)1. Sensory-motor functions were assessed at P3, as measured by the righting reflex and at P8, as measured by negative geotaxis. At P24 animals were tested on preattentive processes, as indexed by sensorimotor gating. Sensorimotor gating was measured by prepulse inhibition (PPI) of the auditory startle response (ASR) (ISIs of 0, 8, 40, 80, 120, and 4000 ms, six trial blocks, Latin-square design). Results indicated gp120-induced neurotoxicity on the righting reflex but not negative geotaxis. For sensorimotor gating, the PPI test demonstrated a reduced inhibition response on peak ASR latency as the dose of gp120 increased. No effect was noted for response inhibition on peak ASR amplitude. These data suggest that intrahippocampal injection of gp120 (0, 1.29, 12.9, or 129 ng/microl) had transient neurotoxic effects on sensory-motor function and limited effects on preattentive processes early in development.
Behavioral, biochemical and anatomical studies suggest that estrogen stimulates structure and/or function in the adult cerebral cortex. The studies presented here used immunocytochemistry to map the alpha and beta isoforms of intracellular estrogen receptors (ER alpha, ER beta) in major subdivisions of adult rat cortex to identify potential sites for relevant receptor-mediated hormone actions. These studies revealed that immunoreactivity for ER alpha (ER alpha-IR) and ER beta (ER beta-IR) was present in most cortical areas, was associated exclusively with neurons, and was similar in males and females. Each receptor isoform also had its own unique distribution with respect to cortical regions, layers, and cells. In sensorimotor areas, for example, ER beta-IR was more prominent than ER alpha-IR, and was concentrated in layer V neurons that were immunoreactive for parvalbumin. In contrast, ER alpha-IR was scattered among parvalbumin-immunonegative cells in layers II/III and V/VI. Likewise, in entorhinal cortex, ER beta-IR was present in calbindin-containing cells in layers III-VI, while ER alpha-IR was restricted to small numbers of calbindin-negative neurons in infragranular layers. In sum, ER beta-IR and ER alpha-IR were differentially distributed both with respect to cortical compartments and with respect to each other. Accordingly, estrogen activation at these two sites may be anticipated to impact disparate sets of cortical circuits, cells, and functions.
It was shown that unilateral lesions of the left and right sensorimotor cortex in male Wistar rats led to similar deficit in manipulatory ability to perform the reaching task. Recovery rate depended on the side of lesion, i.e., damage of the right hemisphere was compensated sooner than that of the left one. This difference was significant in ambidextrous rats while in sinistrals and dextrals it was not pronounced.
The posterior parietal cortex (PPC) is known to be involved in the control of automatic movements that are spatially guided, such as grasping an apple. We considered whether the PPC might also contribute to the performance of visuomotor associations in which stimuli and responses are linked arbitrarily, such as producing a certain sound for a typographical character when reading aloud or pressing pedals according to the color of a traffic light when driving a motor vehicle. The PPC does not appear to be necessary for learning new arbitrary visuomotor associations, but with extensive training, the PPC can encode nonspatial sensory features of task-relevant cues. Accordingly, we have tested whether the contributions of the PPC might become apparent once arbitrary sensorimotor mappings are overlearned. We have used functional magnetic resonance imaging to measure cerebral activity while subjects were learning novel arbitrary visuomotor associations, overlearning known mappings, or attempting to learn frequently changing novel mappings. To capture the dynamic features of cerebral activity related to the learning process, we have compared time-varying modulations of activity between conditions rather than average (steady-state) responses. Frontal, striatal, and intraparietal regions showed decreasing or stable activity when subjects learned or attempted to learn novel associations, respectively. Importantly, the same frontal, striatal, and intraparietal regions showed time-dependent increases in activity over time as the mappings become overlearned, i.e., despite time-invariant behavioral responses. The automaticity of these mappings predicted the degree of intraparietal changes, indicating that the contribution of the PPC might be related to a particular stage of the overlearning process. We suggest that, as the visuomotor mappings become robust to interference, the PPC may convey relevant sensory information toward the motor cortex. More generally, our findings illustrate how rich cerebral dynamics can underlie stable behavior.
OBJECTIVE: To address the potential contribution of subcortical brain regions in the functional reorganization of the motor system in patients with sporadic ALS (sALS) and to investigate whether functional changes in brain activity are different in sALS patients with predominant upper motor neuron (UMN) or lower motor neuron (LMN) dysfunction. METHODS: We studied 16 patients with sALS and 13 healthy controls, using BOLD-fMRI, while they performed a simple visually paced motor task. Seven patients had definite clinical UMN signs while nine patients had prevalent clinical and electrophysiological LMN involvement. fMRI data were analyzed with Brain Voyager QX. RESULTS: Task-related functional changes were identified in motor cortical regions in both patients and healthy controls. Direct group comparisons revealed relatively decreased BOLD fMRI responses in left sensorimotor cortex, lateral premotor area, supplementary motor area and right posterior parietal cortex (p < 0.05 corrected) and relatively increased responses in the left anterior putamen (p < 0.001 uncorrected) in sALS patients. Additional analyses between the two patients subgroups demonstrated significant BOLD fMRI response differences in the anterior cingulate cortex and right caudate nucleus (p < 0.001 uncorrected) with more robust activation of these areas in patients with greater UMN burden. Importantly, there were no significant differences in performance of the motor task between sALS patients and controls as well as between sALS patient subgroups. CONCLUSIONS: Our data demonstrate a different BOLD fMRI pattern between our sALS patients and healthy controls even during simple motor behavior. Furthermore, patients with sALS and greater UMN involvement show a different reorganization of the motor system compared to sALS patients with greater LMN dysfunction.
Odor input evokes characteristic, time-evolving (non-stationary) events in the spontaneously active central ganglia of the snail Helix pomatia. Assuming stationarity for the signals, one could, as the first approach, apply the Fourier-based methods, frequency amplitude characteristics (FAC) measures, for analyzing such events. We could thus for the first time describe such events in frequency and amplitude and show that the frequency, at which power increases most, is specific to the odor or its class [Comp. Biochem. Physiol. 123A (1999a) 95; Comp. Biochem. Physiol. 124A (1999b) 297]. Wavelet tools assume no record stationarity and are suitable for describing the dynamically evolving brain electrical signals precisely and quantitatively. We, therefore, tested these tools for the typical odor experiments with the procerebrum (PC), the pedal ganglion (PG) and the visceral ganglion (VG) of the Helix, which we earlier analyzed by the FAC measures and compared both results. The two basic findings of the present wavelet analysis are as follows: (i) the wavelet energy fluctuations clearly visualize dynamical interactions among the major bands (0.1-3.1 Hz), implying a possible 'mutual exclusion' between slow components < 0.8 Hz and faster ones > 0.8 Hz. (ii) Entropy behavior was characteristically different for each of the three brain regions. Only in PC the response to aversive odorants (decrease of entropy = more ordered state) is differentiated in entropy from that to attractive ones (increase of entropy=more disordered or more complexly ordered state) indicating the odor-discriminating function of this region. In VG entropy of the intrinsic activity is so high (highly disordered state) due to the strong wideband activity reaching > 50 Hz that odor stimulation results mainly in lowering of entropy (= more ordered state) regardless of the nature of the odor. In PG, however, odor presentation generally increases entropy due to the robust, wide-band activation at > 3 Hz (sensorimotor function) that is generated as a secondary, but dominant and robust, response. In respect to describing time evolution of different frequency band components the present wavelet tools can much more sensitively do so, as compared with the FAC measures. They can also characterize a change in the neuroelectrical state in terms of entropy.