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At least 685 records · Page 38Linked to original sources
PubMed2006

Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice.

Alzheimer's disease (AD) is associated with accumulations of amyloid-beta (Abeta) peptides, oxidative damage, mitochondrial dysfunction, neurodegeneration, and dementia. The mitochondrial antioxidant manganese superoxide dismutase-2 (Sod2) might protect against these alterations. To test this hypothesis, we inactivated one Sod2 allele (Sod2(+/-)) in human amyloid precursor protein (hAPP) transgenic mice, reducing Sod2 activity to approximately 50% of that in Sod2 wild-type (Sod2(+/+)) mice. A reduction in Sod2 activity did not obviously impair mice without hAPP/Abeta expression. In hAPP mice, however, it accelerated the onset of behavioral alterations and of deficits in prepulse inhibition of acoustic startle, a measure of sensorimotor gating. In these mice, it also worsened hAPP/Abeta-dependent depletion of microtubule-associated protein 2, a marker of neuronal dendrites. Sod2 reduction decreased amyloid plaques in the brain parenchyma but promoted the development of cerebrovascular amyloidosis, gliosis, and plaque-independent neuritic dystrophy. Sod2 reduction also increased the DNA binding activity of the transcription factor nuclear factor kappaB. These results suggest that Sod2 protects the aging brain against hAPP/Abeta-induced impairments. Whereas reductions in Sod2 would be expected to trigger or exacerbate neuronal and vascular pathology in AD, increasing Sod2 activity might be of therapeutic benefit.

Alzheimer Disease↗
PubMed1976

[The effect of low-frequency electric stimulation of the caudate nucleus on the electrical activity of the cortex and on the sleep-wakefulness cycle].

In cats, the effect of low-frequency electric stimulation of the caudate nucleus on electric activity of neo- and archipaleocortex and on wakefulness-sleep cycle, was studied. The data obtained suggest: 1) at threshold and suprathreshold single electric shocks applied to the caudate nucleus they evoked potential occurs more readily in the sensorimotor area of the neocortex than in the dorsal hippocampus. At 2-6/sec stimulation the evoked potentials in the hippocampus are facilitated and become very stable, whereas in the sensorimotor cortex the most obvious responses occur at the 6-8/sec frequency. However, the evoked potentials are variable in the sensorimotor cortex, and at prolonged 8-12/sec stimulation spindle activity soon develops; 2) behavioral correlate of the synchronized activity in the neo- and archipaleocortical structures during low-frequency stimulation of the caudate nucleus, may involve development of drowsiness with the cessation of stimulation, however, both the EEG and behavioral signs of the drowsiness disappear. The onset of drowsiness following withdrawal of the caudate stimulation, is a rare phenomenon only occurring because of an occasional coincidence of the stimulation with the spontaneous onset of natural sleep; 3) low-frequency caudate stimulation entailing the ECoG synchronization does not cause the transition of paradoxical phase into the slow-wave phase of sleep, and as soon as the stimulation ceases its normal structure recovers. However, if the stimulation of the caudate nucleus is repeated several times in one paradoxical phase, this would shorten the subsequent slow-wave phase and accelerate the onset of the next paradoxical phase; 4) prolonged low-frequency stimulation of the caudate nucleus causing the ECoG synchronization results in a considerable change of wakefulness-sleep cycle in the post-stimulation period: a decrease in the total time of slow-wave sleep due to shortening of its different phases, and an increase in the total amount of paradoxical sleep because of the onset of its phases is rendered more frequent. This effect is more obvious in the first half of the 8-hr cycle.

Animals↗
PubMed1992

Environmental enrichment, neocortical ectopias, and behavior in the autoimmune NZB mouse.

New Zealand Black (NZB) mice have severe autoimmune disease and approximately 40% have cortical ectopias in layer I of sensorimotor cortex. Because the ectopias are similar to those found in dyslexics, NZB mice have been used as an animal model for developmental learning disorders. In addition, these mice have been used as a model of learning deficits associated with autoimmune disease. To determine whether early intervention would affect learning processes in NZB mice, they were reared after weaning in standard cages or enriched environments. They were given a battery of behavioral tests to measure learning, laterality, and activity, after which they were sacrificed and their brains examined for cortical ectopias. The tests sorted into two behavioral sets. Ectopia-associated behaviors included black-white discrimination learning and the Morris spatial maze. As a group, the mice performed well on these tasks. Ectopic mice had poorer performance than non-ectopics on these measures, and environmental enrichment countered the effects of the ectopias. Autoimmune-associated behavior involved two-way avoidance learning in a shuttlebox. Mice were uniformely poor on this task, ectopias did not affect behavior, and environmental enrichment was without benefit. Evidence from this and other studies shows that poor shuttlebox performance is related to the presence of autoimmune disease. Thus, autoimmune disease and cortical ectopias each appear to affect a separate set of behavioral processes. Environmental enrichment is most effective for behavioral impairments mediated via cortical ectopias, but is much less effective, if at all, if autoimmunity is the primary mediator of the impairments.

Animals↗
PubMedDate not supplied

[Motor polarization dominance and "animal hypnosis"].

Two kinds of dominanta were simultaneously formed under conditions of chronic experiments in rabbits. The motor polarization dominanta was formed under exposure of the right sensorimotor cortex of an animal to direct anodic current, and the state of "animal hypnosis" (the second dominanta) was induced. Animal behavior and electrophysiological characteristics were recorded. It was shown that the "animal hypnosis" induced at the optimum of the right motor polarization dominanta inhibited the motor reaction of the "dominant" extremity to testing stimuli. After the "animal hypnosis session, exposure of the right sensorimotor cortex to anodic current produced the latent excitation focus, which did not reach the level of summation. Two days later, exposure to testing stimuli developed the latent foci at first in the right cortex and then in subcortical structures. In the course of recovery of the motor polarization dominanta and its further change for the state characteristic of the "animal hypnosis", the patterns of cortical EEG coherence in the delta range typical of each kind of dominanta alternated in parallel with the time course of state changes.

Animals↗
PubMed2003

The importance of the dominant hemisphere in the organization of bimanual movements.

The successful control of upper limb movements is an essential skill of the human motor system. Yet, the neural organization of bimanual actions remains an issue of debate. Their control can be directed from both hemispheres, or, coordinated motion might be organized from the dominant (left) hemisphere. In order to unravel the neural mechanisms of bimanual behavior, we analyzed the standard task-related and directed coherence between EEG signals picked up over the primary sensorimotor cortices in right-handed subjects during unimanual as well as bimanual in-phase (symmetrical) and anti-phase (asymmetrical) movements. The interhemispheric coherence in the beta frequency band (>13-30 Hz) was increased in both unimanual and bimanual patterns, compared to rest. During unimanual actions, the drive in the beta band from one primary sensorimotor cortex to the other was greater during movement of the contralateral as opposed to ipsilateral hand. In contrast, during bimanual actions, the drive from the dominant to the non-dominant primary sensorimotor cortex prevailed, unless task constraints induced by an external perturbation resulted in a substantial uncoupling of the hand movements, when interhemispheric coherence would also drop. Together, these results suggest that the contralateral hemisphere predominantly organizes unimanual movements, whereas coupled bimanual movements are mainly controlled from the dominant hemisphere. The close association between changes in interhemispheric coupling and behavioral performance indicates that synchronization of neural activity in the beta band is exploited for the control of goal-directed movement.

Adult↗
PubMed2000

Metabolism of neurotransmitters in cortical and subcortical brain structures in rats with different behavioral characteristics.

Experiments were performed on Wistar rats with high and low locomotor activities. In rats with high locomotor activity, activities of acetylcholine transferase, acetylcholine esterase, and monoamine oxidase A increased in the subcellular fractions of the sensorimotor cortex and arcuate nucleus, while monoamine oxidase B activity decreased compared to those in rats with low locomotor activity. The peculiarities of neurotransmitter systems in brain structures of rats with different behavioral patterns were related to genetic and functional organization of the central nervous system.

Animals↗
PubMed1975

The basal ganglia. A brief review and interpretation.

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

Acetylcholine↗
PubMed2005

On the nature of the vestibular control of arm-reaching movements during whole-body rotations.

Recent studies report efficient vestibular control of goal-directed arm movements during body motion. This contribution tested whether this control relies (a) on an updating process in which vestibular signals are used to update the perceived egocentric position of surrounding objects when body orientation changes, or (b) on a sensorimotor process, i.e. a transfer function between vestibular input and the arm motor output that preserves hand trajectory in space despite body rotation. Both processes were separately and specifically adapted. We then compared the respective influences of the adapted processes on the vestibular control of arm-reaching movements. The rationale was that if a given process underlies a given behavior, any adaptive modification of this process should give rise to observable modification of the behavior. The updating adaptation adapted the matching between vestibular input and perceived body displacement in the surrounding world. The sensorimotor adaptation adapted the matching between vestibular input and the arm motor output necessary to keep the hand fixed in space during body rotation. Only the sensorimotor adaptation significantly altered the vestibular control of arm-reaching movements. Our results therefore suggest that during passive self-motion, the vestibular control of arm-reaching movements essentially derives from a sensorimotor process by which arm motor output is modified on-line to preserve hand trajectory in space despite body displacement. In contrast, the updating process maintaining up-to-date the egocentric representation of visual space seems to contribute little to generating the required arm compensation during body rotations.

Adaptation, Physiological↗
PubMed2005

Spatial navigation impairment in mice lacking cerebellar LTD: a motor adaptation deficit?

L7-PKCI transgenic mice, which lack parallel fiber-Purkinje cell long-term depression (LTD), were tested with two different mazes to dissociate the relative importance of declarative and procedural components of spatial navigation. We show that L7-PKCI mice are deficient in acquisition of an adapted goal-oriented behavior, part of the procedural component of the task. This supports the hypothesis that cerebellar LTD may subserve a general sensorimotor adaptation process shared by motor and spatial learning functions.

Adaptation, Physiological↗
PubMed2006

Repetitive transcranial magnetic stimulation-induced changes in sensorimotor coupling parallel improvements of somatosensation in humans.

Repetitive transcranial magnetic stimulation (rTMS) is an established technique for non-invasive stimulation of human cortex. Although studies have shown an influence of rTMS on single cortical regions and on simple behavioral response patterns, its influences on the dynamics of task-related activity in cortical networks have not been characterized. We provide such a characterization by showing that 5 Hz rTMS over primary somatosensory cortex (SI) induces a reconfiguration of activity patterns in a sensorimotor network, comprising the stimulated region and ipsilateral primary motor cortex (MI). These plastic changes endure for up to 120 min and are correlated with behavioral improvement in discrimination. Dynamic causal modeling showed that this reconfiguration could be explained by an rTMS-induced increase in SI excitability (self-connection) and an increase in the effective connectivity from SI to MI. Thus, our data demonstrate that rTMS can temporarily induce behaviorally relevant reorganization within a complex cortical network underlying human somatosensory experience.

Adult↗
PubMed2006

Parallel stages of learning and recovery of skilled reaching after motor cortex stroke: "oppositions" organize normal and compensatory movements.

Forelimb/hand motor cortex injury in rodents and primates causes impairments in skilled paw/hand movements that includes a period of movement absence followed by functional recovery/compensation. Although the postsurgical period of movement absence has been attributed to "shock" or "diaschisis", the behavior of animals during this period has not been fully described. Here, rats were trained to reach for single food pellets from a shelf and then the vasculature of the forelimb region of the sensorimotor cortex contralateral to the reaching limb was removed. A control group received a posterior parietal cortex devasularization. Frame-by-frame video analysis of reaching behavior showed that the stages of the acquisition of skilled reaching and the stages of recovery after motor cortex stroke were similar. The animals sequentially learn three relationships or "oppositions" between a body part and the food target. The oppositions are invariant relationships but each can be achieved with movements that can vary from reach to reach and between rats. A snout-pellet opposition organizes the movements of orienting, a paw-pellet opposition organizes limb transport and grasping the pellet in the digits, and a mouth-pellet opposition organizes limb withdrawal and the release of the food into the mouth. The three oppositions and the movements that they recruit were disrupted after motor cortex damage, but not parietal cortex damage. The oppositions were reestablished after stroke in the order in which they were acquired prior to stroke. Enduring impairments were more noticeable in transport and withdrawal oppositions. That the stages of recovery from motor cortex stroke parallel those of initial acquisition are discussed in relation to contemporary explanations of diaschisis and the contribution of motor cortex to motor learning.

Analysis of Variance↗
PubMed1998

Behavioral constraints in the development of neuronal properties: a cortical model embedded in a real-world device.

The ability of organisms to categorize diverse and often novel stimuli depends on ongoing interactions with their environment. In a modality such as vision, categorization requires the generation of both selective and invariant responses of cortical neurons to complex visual stimuli. How does behavior contribute to shaping the responses of these neurons? Analysis of this question is made difficult by the complex multilevel interactions between many neural and behavioral variables. To mitigate this difficulty, we studied the development and ongoing plasticity of pattern-selective neuronal responses by means of synthetic neural modeling. For this purpose, we constructed Darwin V, which consists of a simulated neuronal model embedded in a real-world device that is capable of motion and autonomous behavior. The neuronal model consists of four major components: a visual system (containing cortical and subcortical networks); a taste system based on conductance; sets of motor neurons capable of triggering behavior; and a diffuse ascending (value) system. The modeled visual cortex consists of two areas: a topographic map responsive to elementary features connected to a higher-order map composed of initially non-selective neuronal units. During behavior over time in its environment, Darwin V encounters numerous objects consisting of black metal cubes displaying different patterns of white blobs and stripes. Initially, the lack of specific higher-order visual responses does not allow visual pattern discrimination, and appetitive and aversive behaviors are triggered by the 'taste' (surface conductivity of objects) alone. In the course of sensory experience, however, changes occur in visual and sensorimotor connection strengths, with two major consequences. First, units within the higher visual area acquire responses that are both pattern selective and translation invariant. Second, as a result of the operation of the value system, these responses become linked to appropriate behaviors. Analysis of Darwin V after such changes indicates that the continuity of self-generated movements is essential for the development of pattern-selective and translation-invariant responses. The concomitant development of a preference for foveal over parafoveal objects was found to be due to increased behavioral interactions with object cubes gripped by the centrally mounted effector (snout) of Darwin V. Finally, even after development of higher-order visual responses, visual responses to more frequently encountered objects continued to be enhanced, while other responses were diminished. Overall, the detailed study of Darwin V over multiple levels of organization provides a heuristically revealing example of the crucial role played by behavioral and environmental interactions in the development of complex responses by specialized neurons.

Behavior↗
PubMed2004

Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender.

Several useful behavioral tests exist for measuring behavioral recovery after ischemia in higher-order animals and rats. With the increasing use of mice in focal stroke research, simple, reliable, and reproducible behavioral testing has become a priority. As neuroprotective agents are tested, long-term outcome must be assessed, especially in studies focused on neuronal plasticity and regeneration after ischemia. Our laboratory and others have previously shown that estrogen (E2) is neuroprotective in rodent stroke paradigms. We examined a battery of behavioral tests in male and female mice subjected to 90 min of middle cerebral artery occlusion (MCAO) to determine the most sensitive tests for detecting sensorimotor dysfunction after stroke, and to determine the functional significance of E2-mediated neuroprotection. Only two tests, the corner test and the cylinder test, were able to differentiate between groups (sham and stroke) after several days of repeated testing. The cylinder test was sensitive to the neuroprotective/neurorestorative effects of E2, but 2 weeks after stroke, the cylinder test was unable to distinguish between sham and stroke animals treated with E2. In contrast, the corner test was able to differentiate stroke and sham animals even 6 weeks after stroke, but did not distinguish animals treated with E2 vs. vehicle. These tests provide a simple, rapid, reliable assessment of sensorimotor dysfunction in the mouse after focal ischemia. Hormonal status influences speed of recovery on cylinder testing in animals of both genders. This suggests that a short battery of tests including the neurological score, cylinder, and corner test may be adequate to rapidly and repeatedly assess sensorimotor dysfunction in mice of both genders.

Animals↗
PubMed1998

Preoperative regimens of magnesium facilitate recovery of function and prevent subcortical atrophy following lesions of the rat sensorimotor cortex.

Following brain injury, there is a reduction of intra- and extracellular levels of magnesium (Mg++), which may contribute to the severity of the lesion-induced behavioral impairments. Injections of magnesium prior to or after brain injury attenuate these behavioral impairments. The present study extends these findings by manipulating the number of injections and the time period between the injections and the time of injury. Rats were given either two or five daily preoperative injections of MgCl2 (1 mmol/kg, i.p.), or saline (1 ml/kg, i.p.) with the final injection given 24 h prior to electrolytic lesions of the somatic sensorimotor cortex (SMC). Following SMC lesions the rats exhibited contralateral deficits in forelimb placing and locomotor placing. Rats treated with either two or five preoperative injections of MgCl2 showed a reduction in the initial magnitude of the contralateral deficits and an accelerated rate of recovery compared to saline-treated rats. In addition, analysis of striatal atrophy revealed that MgCl2 treatment prevented atrophy in the ipsilateral posterior striatum compared to rats treated with saline. These data suggest that preoperative injections of MgCl2 produce facilitation of sensorimotor recovery and reduce subcortical atrophy. Moreover, to observe the beneficial effects of MgCl2, the timing of injections need not be tied to the period immediately around the brain injury. The present data may indicate that daily supplements of magnesium may partially protect against some of the deleterious effects of brain injury.

Animals↗
PubMed2003

Preparatory activity in motor cortex reflects learning of local visuomotor skills.

In humans, learning to produce correct visually guided movements to adapt to new sensorimotor conditions requires the formation of an internal model that represents the new transformation between visual input and the required motor command. When the new environment requires adaptation to directional errors, learning generalizes poorly to untrained locations and directions, indicating that such learning is local. Here we replicated these behavioral findings in rhesus monkeys using a visuomotor rotation task and simultaneously recorded neuronal activity. Specific changes in activity were observed only in a subpopulation of cells in the motor cortex with directional properties corresponding to the locally learned rotation. These changes adhered to the dynamics of behavior during learning and persisted between learning and relearning of the same rotation. These findings suggest a neural mechanism for the locality of newly acquired sensorimotor tasks and provide electrophysiological evidence for their retention in working memory.

Animals↗
PubMed1999

Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks.

Fluoxetine inhibits the reuptake of serotonin, and dextroamphetamine enhances presynaptic release of monoamines. Although the excitatory effect of both noradrenaline and dopamine on motor behavior generally is accepted, the role of serotonin on motor output is under debate. In the current investigation, the authors evidenced a putative role of monoamines and, more specifically, of serotonin in the regulation of cerebral motor activity in healthy subjects. The effects on cerebral motor activity of a single dose of fluoxetine (20 mg), an inhibitor of serotonin reuptake, and fenozolone (20 mg/50 kg), an amphetamine-like drug, were assessed by functional magnetic resonance imaging. Subjects performed sensorimotor tasks with the right hand. Functional magnetic resonance imaging studies were performed in two sessions on two different days. The first session, with two scan experiments separated by 5 hours without any drug administration, served as time-effect control. A second, similar session but with drug administration after the first scan assessed drug effects. A large increase in evoked signal intensity occurred in the ipsilateral cerebellum, and a parallel, large reduction occurred in primary and secondary motor cortices (P < 10(-3)). These results are consistent with the known effects of habituation. Both drugs elicited comparable effects, that is, a more focused activation in the contralateral sensorimotor area, a greater involvement of posterior supplementary motor area, and a widespread decrease of bilateral cerebellar activation (P < 10(-3)). The authors demonstrated for the first time that cerebral motor activity can be modulated by a single dose of fluoxetine or fenozolone in healthy subjects. Drug effects demonstrated a direct or indirect involvement of monoamines and serotonin in the facilitation of cerebral motor activity.

Adult↗
PubMed1981

EEG biofeedback: physiological behavior modification.

The author reviews the use of operant conditioning to alter electroencephalogram (EEG) patterns. A discrete rhythmic EEG pattern directly related to modulation of motor patterns (sensorimotor rhythm, SMR) was brought under voluntary control in the cat. This technique was modified for use in epileptic human volunteers in order to reduce motor seizures. The use of a newer experimental design and its successful application in one subject is described.

Behavior Therapy↗