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PubMed2003

Behavioural recovery correlated with MRI in a rat experimental stroke model.

PRIMARY OBJECTIVE: To characterize a necrotic lesion using MRI and motor recovery using behavioural methods. RESEARCH DESIGN: Stroke model based on two steps: (1) development of a lesion using MR-imaging parameters and (2) behavioural recovery. METHODS AND PROCEDURES: Seventy male Sprague-Dawley rats were used. A focal lesion of the right sensorimotor cortex was induced photochemically. MAIN OUTCOMES AND RESULTS: The maximum volume of oedema and the lesion damage was reached by approximately 6 hours. In the lesion area, the apparent diffusion coefficient (ADC) increased from 6 hours, then decreased from 24 hours. All animals spontaneously recovered motor function by day 10, despite the continued presence of the cortical lesion. CONCLUSIONS: The results show that this model mimics a core lesion, as well as the late phase in a human stroke episode. This model might be used for longitudinal study of the basic mechanisms of motor recovery.

Animals↗
PubMed2000

Tickling expectations: neural processing in anticipation of a sensory stimulus.

Predictions of the near future can optimize the accuracy and speed of sensory processing as well as of behavioral responses. Previous experience and contextual cues are essential elements in the generation of a subjective prediction. Using a blocked fMRI paradigm, we investigated the pattern of neural activation in anticipation of a sensory stimulus and during the processing of the somatosensory stimulus itself. Tickling was chosen as the somatosensory stimulus rather than simple touch in order to increase the probability to get a high degree of anticipation. The location and nature of the stimulus were well defined to the subject. The state of anticipation was initiated by attributing an uncertainty regarding the time of stimulus onset. The network of activation and deactivation during anticipation of the expected stimulus was similar to that engaged during the actual sensory stimulation. The areas that were activated during both states included the contralateral primary sensory cortex, bilateral areas in the inferior parietal lobules, the putative area SII, the right anterior cingulate cortex and areas in the right prefrontal cortex. Similarly, common decreases were observed in areas of sensorimotor cortex located outside the area representing the target of stimulus, i.e., areas that process information which is irrelevant to the attended process. The overlapping pattern of change, during the somatosensory stimulation and the anticipation, furthers the idea that predictions are subserved by a neuronal network similar to that which subserves the processing of actual sensory input. Moreover, this study indicates that activation of primary somatosensory cortex can be obtained without intra-modal sensory input. These findings suggest that anticipation may invoke a tonic top-down regulation of neural activity.

Adult↗
PubMed1998

Differential effects of the strychnine-insensitive glycine site antagonist (+)-HA-966 on the hyperactivity and the disruption of prepulse inhibition induced by phencyclidine in rats.

The amplitude of the acoustic startle response is reduced by a preceding weak stimulation which by itself does not elicit the startle response. This phenomenon is named prepulse inhibition (PPI) and is thought to reflect the operation of the sensorimotor gating system, which is deficient in schizophrenic patients. It has been reported that an antagonist at the strychnine-insensitive glycine site has atypical neuroleptic properties in experimental animals. To evaluate the effect of an antagonist at the site on disrupted PPI, we examined whether (+)-HA-966 antagonizes phencyclidine-induced (3 mg/kg s.c.) and apomorphine-induced (1 mg/kg s.c.) disruption of PPI in rats. In addition, its effect on phencyclidine-induced hyperactivity was tested. The effects of (+)-HA-966 were compared with those of haloperidol, a typical neuroleptic. (+)-HA-966 antagonized phencyclidine-induced hyperactivity, but not phencyclidine-induced disruption of PPI, which is thought to be a model of refractory symptoms in schizophrenia. Furthermore, (+)-HA-966 did not improve the deficit in PPI induced by apomorphine. On the other hand, haloperidol antagonized phencyclidine-induced hyperactivity and the disruption of PPI by apomorphine, but not by phencyclidine. The results of this study might mean that (+)-HA-966 antagonizes the behavioral change induced by excessive dopamine release (the increment of locomotor activity due to phencyclidine), but not the effect induced by a direct dopamine agonist or the dopamine-independent effect of phencyclidine (the disruption of PPI). Thus, as regards antagonism of phencyclidine-induced disruption of PPI, (+)-HA-966 does not appear to have an atypical neuroleptic-like effect.

Animals↗
PubMed2004

Lipid peroxidation in the brain and liver of rats during acute stress and melatonin treatment.

We studied the effects of acute stress and exogenous melatonin in various doses on the intensity of lipid peroxidation in emotiogenic structures of the brain and liver of rats with different activity in the open field. Stress had no effect on the content of malonic dialdehyde in the hypothalamus, sensorimotor cortex, and liver of active and passive rats receiving physiological saline. The influence of melatonin on malonic dialdehyde content depended on the dose of this substance. The amount of malonic dialdehyde in brain structures (active and passive rats) and liver (active rats) increased after administration of exogenous melatonin in doses of 0.5 and 2 mg/kg, but decreased after treatment with the hormone in a dose of 1 mg/kg. Melatonin in various doses decreased malonic dialdehyde content in the liver of passive rats. The effects of melatonin are partly related to modulation of lipid peroxidation in central and peripheral tissues of the organism.

Animals↗
PubMed2003

Bottom-up transfer of sensory-motor plasticity to recovery of spatial cognition: visuomotor adaptation and spatial neglect.

A large proportion of right-hemisphere stroke patients show hemispatial neglect, a neurological deficit of perception, attention, representation, and/or performing actions within their left-sided space, inducing many functional debilitating effects on everyday life, and responsible for poor functional recovery and ability to benefit from treatment. This spatial cognition disorder affects the orientation of behavior with a shift of proprioceptive representations toward the lesion side. This shift is similar to that produced by psychophysical manipulations as a wedge-prism exposure in normal healthy subjects. In both subjects, one major compensative effect of short-term prism adaptation is a shift of proprioceptive representations, demonstrated by a shift in manual straight-ahead pointing in the dark, in a direction opposite to the visual shift. In neglect patients, prism adaptation involves the shift of proprioceptive representations to the left with a reduction of rightward bias observed in neglect patients in visuo-manual tasks as line-bisection, line-cancellation or copy drawing. Improvement of neglect is also observed in no visuo-manual tasks as mental imagery, auditory extinction or posture. This generalization of prism adaptation effects at different neglect level symptoms suggests that the process of prism adaptation may activate brain functions related to multisensory integration and higher spatial representations. Moreover the positive effects found for both sensorimotor and more cognitive spatial functions lasted for at least two or more hours after prism removal. Unlike reduction of neglect through sensory stimulations, the long-lasting improvement of neglect after prism adaptation suggests the activation of short-term plasticity of brain functions related to coordinate transformations and space representations. Lastly, the duration of these effects could be useful in rehabilitation programs, as suggested by the effects of prism adaptation on disabling neglect symptoms as wheelchair driving, posture or writing.

Adaptation, Physiological↗
PubMed1988

Models of sensorimotor transformations and vestibular reflexes.

The vestibulo-ocular and vestibulo-collic reflexes are well-studied sensorimotor systems with dynamic properties that have been successfully modeled. Recently proposed matrix and tensorial models attempt to describe the spatial organization of these reflexes in three dimensions. Here we describe experiments that test these models. We show that a matrix model of the vestibulo-ocular reflex provides a satisfactory description of its spatial properties. The vestibulo-collic reflex is more complex, but a tensorial model makes close predictions of neck muscle excitation by the vestibulo-collic reflex. In addition, our preliminary data show that the cervico-collic or neck stretch reflex produces essentially the same spatial pattern of neck muscle excitation as the vestibulo-collic reflex, a finding predicted by the tensorial model. We conclude by showing electromyographic and single neuron responses that can be modeled only by combining models of dynamics with models of spatial organization. We believe that the development of such models is the next major challenge in the application of quantitative methods to analysis of reflex behavior.

Animals↗
PubMed1998

Cerebral glucose metabolism in patients with frontotemporal dementia.

UNLABELLED: Frontotemporal dementia (FTD) is a dementia syndrome characterized by peculiar behavioral changes arising from frontotemporal involvement and distinct from Alzheimer's disease (AD). The purpose of this study was to elucidate the specific patterns in cerebral glucose metabolism in patients with FTD and to compare them with the patterns in patients with AD and normal elderly subjects using fluorodeoxyglucose (FDG) and PET. METHODS: Twenty-one patients with a clinical diagnosis of FTD [mean age 67.0 +/- 7.0 yr, Mini Mental State Examination (MMSE) score 18.7 +/- 5.7], 21 age-, sex- and dementia-severity-matched patients with probable AD (mean age 66.9 +/- 7.1 yr, MMSE score 20.2 +/- 5.5) and 21 age- and sex-matched normal control subjects (mean age 66.8 +/- 5.7 yr) were studied. The cerebral metabolic rate for glucose (CMRglc) was measured with FDG and PET. Absolute measures of regional CMRglc were compared among the three groups. One-way ANOVA and the posthoc Tukey HSD test were used for statistical analyses. RESULTS: In the FTD group, CMRglc was preserved only in the left cerebellum, right sensorimotor area and occipital lobes. The CMRglc was significantly lower in the FTD group as opposed to the AD group in the hippocampi, orbital gyri, anterior temporal lobes, anterior cingulate gyri, basal ganglia, thalami, middle and superior frontal gyri and left inferior frontal gyrus. CONCLUSION: Although metabolic abnormality in FTD is predominant in the frontal and anterior temporal lobes and the subcortical structures, it is more widespread than has been previously stressed. These findings document an FTD-specific cerebral involvement and facilitate differential diagnosis of degenerative dementias.

Aged↗
PubMed2005

Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism.

We recently reported that the centromedian-parafascicular thalamic complex (CM-Pf) degenerates in Parkinson's disease and progressive supranuclear palsy. The contribution of such thalamic pathology to disease symptoms has not yet been established. The present study therefore investigated the behavioural impact of lesioning the corresponding thalamic region (termed Pf) on a range of behaviours present in rodents. There were four surgical groups: (1) sham medial forebrain bundle (mfb)+sham Pf, (2) 6-OHDA mfb lesion+sham Pf, (3) sham mfb+NMDA Pf lesion, (4) 6-OHDA+NMDA Pf lesions. Posture, sensory functions and apomorphine-induced rotational asymmetry were assessed before and after each surgery. Other assessments performed including a timed motivational task, grooming behaviours and piloerection. 6-OHDA lesions induced postural (ipsilateral curling and head position biases), sensorimotor (increased latency to respond to tactile stimulation of the contralateral side when eating or grooming) and rotational abnormalities (contralateral circling after apomorphine). The main effects of combined 6-OHDA+Pf lesions were improved performance in a motivational task (decreased latency to retrieve reward) but worsened piloerection, relative to animals with either 6-OHDA or Pf lesions alone. The thalamic zone common to all lesioned animals involved the posterior Pf. Our data suggests that the posterior CM-Pf may be involved in motivational responses and autonomic dysfunction in parkinsonian disorders.

Analysis of Variance↗
PubMed2000

Unilateral involuntary movement associated with streptococcal infection: neurophysiological investigation.

Two boys developed rhythmic involuntary movements in the extremities on one side of the body after febrile illness. They also showed behavioral disturbances. In both patients, serum antistreptolysin-O and antistreptokinase titers were elevated in acute illness and decreased a few months later. One patient showed tremorous movement, and the other choreiform movement. In the former, a surface EMG showed short-duration (30 to 60 ms), highly frequent (6 to 8 Hz) and synchronous discharges of multiple muscles, including the antagonists, suggesting myoclonic jerk. In the latter, a surface EMG showed long-duration (0.5 to 1 s), repetitive (about 0.5 Hz) and synchronous or asynchronous discharges of the antagonists, suggesting choreoathetosis. In both patients, giant somatosensory evoked potentials and high-voltage slow EEG activities were observed predominantly in the hemisphere contralateral to the involuntary movement. In the myoclonic patient, long-latency EMG responses were enhanced and cortical potentials preceding the myoclonus were present by jerk-locked back averaging technique. The present data suggest that unilateral rhythmic involuntary movements occur secondary to streptococcal infection. The pathophysiology of the involuntary movements may be associated with sensorimotor cortex hyperexcitability.

Child↗
PubMed1996

Functional behavioral homology between rat 5-HT1B and guinea pig 5-HT1D receptors in the modulation of prepulse inhibition of startle.

The serotonin (5-HT) 1B receptor in rats and mice appears to be homologous to the 5-HT1D receptor found in other mammals, such as guinea pigs and humans. The present series of experiments explored the functional similarity between the rat 5-HT1B receptor and the guinea pig 5-HT1D receptor on two behavioral measures known to be influenced by 5-HT1B receptor manipulations in rats: prepulse inhibition of the startle response (PPI) and locomotor activity. Because the 5-HT1B agonist RU 24969 disrupts PPI and stimulates locomotor behavior in rats, it was predicted that the 5-HT1D agonist, SDZ 219-964, would demonstrate a similar behavioral profile in guinea pigs. In support of this hypothesis, SDZ 219-964 was found to disrupt PPI dose-dependently (1.0 and 2.0 mg/kg) without significantly affecting startle amplitude and to increase locomotor activity (0.5-2.0 mg/kg) in guinea pigs. In guinea pigs, RU 24969 failed to affect PPI, although it did increase locomotor activity, indicating that RU 24969 may have activity at the 5-HT1D receptor. As expected, RU 24969 in rats disrupted PPI (2.5 and 5.0 mg/kg) and significantly increased locomotor activity (1.25-5.0 mg/kg). In rats, however, SDZ 219-964 had generalized, stimulatory effects on startle reactivity, without independent effects on PPI or locomotor activity. The spatial patterns of locomotion exhibited by guinea pigs treated with SDZ 219-964 versus those of rats treated with RU 24969 demonstrate important qualitative differences in structure, indicating that the neural substrates subserving these effects may be different. It is concluded that a functional similarity exists between 5-HT1D and 5-HT1B receptors with regard to the modulation of sensorimotor inhibition and, to a lesser extent, locomotor activity.

Animals↗
PubMed2005

Injection of glutamate into the pedunculopontine tegmental nuclei of anesthetized rat causes respiratory dysrhythmia and alters EEG and EMG power.

The pedunculopontine tegmental nucleus (PPT) has been shown to have important functions relevant to the regulation of behavioral states and various motor control systems, including breathing control. Our previous work has shown that the activation of neurons within the PPT, a structure that is typically active during rapid eye movement (REM) sleep, can produce respiratory disturbances in freely moving and anesthetized rats. The aim of this study was to test the hypothesis that respiratory modulation by the PPT in anesthetized rats can be evoked in the absence of other signs of an REM-sleep-like state. We characterized electroencephalogram (EEG) and electromyogram (EMG) changes during respiratory disturbances induced by glutamatergic stimulation of the PPT in spontaneously breathing, adult male Sprague-Dawley rats anesthetized with a ketamine/xylazine combination or with nembutal. Respiratory movements were monitored by a piezoelectric strain gauge. Two-barrel glass pipettes were used to pressure inject glutamate, to probe for respiratory effective sites within the PPT, and to inject oil red dye at the end of the experiments for histological verification of the injection sites. The EEGs were recorded from the sensorimotor cortex, hippocampus, and from the pons contralateral from the injection site. The EMGs were recorded from the genioglossus muscle. The initial response to glutamate injection into the respiratory modulating region of the PPT was always a respiratory pattern disturbance. Subsequent activation of EMG and EEG often occurred in ketamine/xylazine-anesthetized rats, but REM-sleep-like patterns were not observed. Respiratory pattern and EMG power changes in nembutal-anesthetized rats were similar, but EEG activation was never observed. Thus, we conclude that respiratory suppression produced by the local activation of PPT neurons may not necessarily be accompanied by an REM-sleep-like cortical state in this anesthetized model.

Anesthesia↗
PubMed1993

The computational leech.

The local bending reflex of the leech computes a well-defined sensorimotor input-output function in which each of several unique patterns of sensory input elicits a unique pattern of motoneuron activity. Interneurons in the reflex respond to most input patterns and contribute to most motor patterns, suggesting a distributed processing mechanism for the reflex. This suggestion is supported by models in which connection strengths are adjusted by a neural network optimization algorithm to reproduce the local bending input-output function. In addition, computational parallels between the local bending network and the perceptron, a major class of artificial neural networks, brings the functional role of local bending interneurons into question and suggests new physiological experiments.

Animals↗
PubMed1995

A comparison of functional MR activation patterns during silent and audible language tasks.

PURPOSE: To compare word generation tasks performed silently and aloud as paradigms for functional MR. METHODS: Images were obtained at 1.5 T, with echoplanar acquisition in nine subjects performing word generation aloud or silently. Functional images created from the echoplanar images by means of cross-correlation techniques were superimposed on anatomic reference images. The location of activation from the two tasks was tabulated; the number of activated pixels in each region from the two tasks was compared. RESULTS: Both silent and aloud word generation produced activation in the inferior frontal lobes, sensorimotor cortex regions, supplementary motor areas, and anterior cingulate gyri, predominantly in the dominant hemisphere. Significantly more activated pixels and fewer artifacts were detected with silent word generation than with word generation aloud. CONCLUSION: Word generation silently or aloud produce activation in the brain. Greater activation can be detected in the left frontal lobe with silent word generation, although the subject's performance of the task cannot be monitored independently during silent word generation.

Adult↗
PubMed2005

Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit.

The cytosolic brain-type creatine kinase (BCK) isoform and the mitochondrial ubiquitous creatine kinase (UbCKmit) isoform are both important for the maintenance and distribution of cellular energy in neurons and astrocytes. Previously, we reported that mice deficient for BCK or UbCKmit each showed a surprisingly mild phenotype, probably due to reciprocal functional compensation by the remaining creatine kinase. This study shows that adult male mice lacking both creatine kinase isoforms (CK--/-- double knockout mice) have a reduced body weight, and demonstrate a severely impaired spatial learning in both a dry and a wet maze, lower nestbuilding activity and diminished acoustic startle reflex responses when compared to age-matched male wildtype mice with the same genetic background. In contrast, their visual and motor functions, exploration behaviour, prepulse inhibition and anxiety-related responses were not changed, suggesting no global deficit in sensorimotor function, hearing or motivation. Morphological analysis of CK--/-- double knockout brains revealed a reduction of approximately 7% in wet brain weight and hippocampal size, a approximately 15% smaller regio-inferior and relatively larger supra-pyramidal, and intra-infra-pyramidal mossy fiber areas. These results suggest that lack of both brain specific creatine kinase isoforms renders the synaptic circuitry in adult brain less efficient in coping with sensory or cognitive activity related challenges.

Acoustic Stimulation↗
PubMed2001

Extensive immunolesions of basal forebrain cholinergic system impair offspring recognition in sheep.

The involvement of the basal forebrain cholinergic system has been extensively investigated in instrumental learning but little is known of its participation in social memory, especially in the memorization of individual traits of a conspecific. The present study tested in sheep its contribution to both instrumental learning and individual offspring recognition. Six weeks before parturition, ewes received injections of a specific cholinergic immunotoxin (ME20.4 IgG-saporin) into the lateral ventricles (150 microg) and in some cases additional immunotoxin injections into the nucleus basalis (11 microg/side). After 3 weeks of recovery, ewes were trained on a classical instrumental visual discrimination task known to be sensitive to cholinergic deficits. The formation of memory of offspring was assessed through both olfactory and visual/auditory recognition tasks. Olfactory recognition was tested by presenting at suckling successively an alien and the familiar lamb at 2 and 4 h after parturition. Visual/auditory recognition of the lamb was performed using a non-olfactory discrimination test between the familiar and an alien lamb after 12 h of mother-young contact. The lesion extent was assessed by counting choline acetyltransferase-immunopositive neurons in the basal forebrain and measuring the density of acetylcholinesterase fibers in different target areas. Results showed that immunotoxic lesions delayed acquisition of the instrumental visual discrimination. Moreover, olfactory recognition of the lamb was severely impaired while visual/auditory lamb recognition was marginally altered. There was no evidence for sensorimotor or motivational deficits. Importantly, impairment was observed in animals for which loss of basal forebrain cholinergic neurons and their efferent fibers was higher than 75%, while striatal cholinergic neurons and Purkinje cells were unaffected. This study provides evidence that the basal forebrain cholinergic system contributes not only to instrumental but also to social learning. In addition, the cholinergic modulation seems of importance for processing visual and olfactory modalities. However, since only extensive lesions affect performance, this indicates that the basal forebrain cholinergic system possesses substantial reserve capacity to sustain cognitive functions.

Acetylcholine↗
PubMed2004

Dissociable effects of frontal cortical lesions on measures of visuospatial attention and spatial working memory in the rat.

Frontal cortex controls voluntary movement through projections to striatum that continue as parallel pallido-thalamic loops. In previous studies we found evidence of a double dissociation in rat striatum between visuospatial response time (RT) and radial maze delayed non-matching (DNM) tasks. Here we compare the effects of frontal cortical lesions on these tasks. We found that lesions involving sensorimotor areas in dorsolateral cortex affect RT for responding to visuospatial stimuli without affecting other measures of response speed or producing signs of attentional or sensory impairment. These deficits were equivalent to impairments observed with lesions in sensorimotor areas of dorsolateral striatum. Dorsal prefrontal lesions produced RT deficits indicative of attentional impairment that have not been observed with striatal or thalamic lesions. This suggests contributions of prefrontal cortex to attention independent of striatum and thalamus. Prefrontal lesions had significant but circumscribed effects on DNM consistent with effects of lesions in anatomically related areas of striatum or thalamus observed in earlier studies. These results are consistent with evidence implicating prefrontal cortex in aspects of spatial memory mediated by anatomically related pathways in the basal ganglia and thalamus.

Animals↗
PubMedDate not supplied

Dynamics of interstimulus intervals in the activity of neurons of the sensorimotor cortex during the development of a food-procuring reflex in the rabbit.

The impulse activity of neurons of the sensorimotor cortex (SMC) during the formation of a food-procuring reflex in the rabbit, as well as in trained animals if reinforcement is discontinued and substituted, was investigated. In the process of training the neurons of the SMC acquire the capacity for anticipatory reactions. The sudden abolition and substitution of reinforcement elicits the appearance of activity which is characteristic for the process of discordance in the acceptor of the result of the action. Repeated substitutions lead to the appearance of activity which is characterized by a coordination process at the moment of the "recognition" of the substitution, despite the absence of food reinforcement.

Acoustic Stimulation↗
PubMed1998

Proprioceptive information processing in weightlessness.

The "illusions" experiment carried out on five astronauts during the last two French-Russian flights (Antarès in 1992 and Altaïr in 1993) and in the Russian Post-Antarès mission (1993) was designed to investigate the adaptive changes in human proprioceptive functions occurring in weightlessness at both the sensorimotor and cognitive levels, focusing on two kinds of responses: (1) whole-body postural reflexes, and (2) whole-body movement perception. These kinesthetic and motor responses were induced using the tendon-vibration method, which is known to selectively activate the proprioceptive muscular sensory channel and to elicit either motor reactions or illusory movement sensations. Vibration (70 Hz) was therefore applied to ankle (soleus or tibialis) and neck (splenii) muscles. The subject's whole-body motor responses were analyzed from EMG and goniometric recordings. The perceived vibration-induced kinesthetic sensations were mimicked by the subjects with a joystick. The main results show that a parallel in-flight attenuation of the vibration-induced postural responses and kinesthetic illusions occurred, which seems to indicate that the proprioceptive system adapts to the microgravity context, where standing posture and conscious coding of anteroposterior body movements are no longer relevant. The same sensory messages are used at the same time in different sensory motor loops and in the coding of newly developed behavioral movements under microgravity. These results suggest that the human proprioceptive system has a high degree of adaptive functional plasticity, at least as far as the perceptual and motor aspects are concerned.

Adaptation, Physiological↗