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PubMed1995

Effects of complete and partial lesions of the dopaminergic mesotelencephalic system on skilled forelimb use in the rat.

This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that had received a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. The rats classified Apo(+), that rotated after the administration of apomorphine, had a complete lesion of the nigrostriatal system, whereas those classified Apo(-), that did not rotate after the administration of apomorphine, had a partial lesion of the nigrostriatal system. In the Apo(+) rats, 99.8% of the dopamine in the striatum was depleted, as was 85% of that in the substantia nigra. For the Apo(-) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investigated with the staircase test, the animals with the most severe dopamine depletions were those most impaired in the paw reaching task. Complete and partial unilateral depletions of the dopaminergic mesotelencephalic system impaired the hierarchic phases of paw reaching differently. A complete dopamine depletion, but not a partial one, decreased the number of attempts made with the contralateral paw, and induced a bias towards the ipsilateral paw. A partial dopamine lesion impaired the sensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsilateral paw. The mild paw reaching impairments observed in animals with moderate depletions of dopamine are proposed as a model of the early symptoms of Parkinson's disease that may be useful for the development of protective or restorative therapies.

Animals↗
PubMed2006

Deficient prepulse inhibition induced by selective breeding of rats can be restored by the dopamine D2 antagonist haloperidol.

Deficient sensorimotor gating, measured as prepulse inhibition (PPI) of startle, reflects disturbed information processing found in neuropsychiatric disorders. Examining the ability to selectively breed rats for high and low PPI, results showed significant differences of PPI scores within two generations. Comparing antipsychotics to restore PPI of the low group, haloperidol was shown more effective than clozapine. This suggests low PPI rats may be useful models for neuropsychiatric disorders and screening antipsychotics.

Acoustic Stimulation↗
PubMed2004

Overt propositional speech in chronic nonfluent aphasia studied with the dynamic susceptibility contrast fMRI method.

This study examined activation levels in the left (L) supplementary motor area (SMA) and the right (R) SMA (separately), and activation in nine R perisylvian language homologues during overt, propositional speech in chronic nonfluent aphasia patients. Previous functional imaging studies with a variety of chronic aphasia patients have reported activation in these regions during different language tasks, however, overt propositional speech has not been examined. In the present research, four nonfluent aphasia patients were studied during overt elicited propositional speech at 4-9 years post-single L hemisphere stroke, which spared the SMA. The dynamic susceptibility contrast (DSC) method of functional MRI was used to calculate relative cerebral blood volume (relCBV) for cortical regions of interest (ROIs) during the first-pass bolus of gadolinium during two conditions: (1) pattern (silent viewing of checkerboard patterns) and (2) story (overt, elicited propositional speech describing sequential pictures, which formed a story). During the story condition, controls had significantly higher relCBV in L SMA than in R SMA; aphasics, however, had significantly higher relCBV in R SMA than in L SMA. During the pattern condition, no significant differences were observed between the L SMA and the R SMA for either controls or aphasics. In addition, aphasics had significantly higher relCBV in the R sensorimotor mouth during story than pattern. This R sensorimotor mouth relCBV was also significantly higher in aphasics than controls during story, and the two groups did not differ during pattern. The overall mean relCBV for the nine R perisylvian ROIs was significantly higher for aphasics than controls during both story and pattern. These results suggest that poor modulation, including possible over-activation of R sensorimotor mouth and other R perisylvian language homologues may underlie in part, the hesitant, poorly articulated, agrammatic speech associated with nonfluent aphasia.

Adult↗
PubMed2006

Hippocampal kindling leads to motor map expansion.

PURPOSE: To determine whether seizure activity, repeatedly elicited in the hippocampus, could alter the functional organization of neocortical movement representations (motor maps) and whether a relation exists between the number of afterdischarges recorded in the sensorimotor neocortex and the size of the motor maps. METHODS: We electrically kindled the right ventral hippocampus of Long-Evans hooded rats, twice daily, for 40 sessions and recorded the afterdischarges in the stimulated hippocampus and right sensorimotor neocortex. Between 3 and 7 days after the last seizure, we used high-resolution intracortical microstimulation to derive the forelimb-movement representations in the left (un-implanted) sensorimotor neocortex. RESULTS: In the hippocampal kindled rats, we observed a dramatic expansion of the area of neocortex that would elicit forelimb movements compared with sham-kindled controls. The number of afterdischarges recorded in the neocortex was significantly and positively correlated with the size of the motor maps. CONCLUSIONS: Seizures propagating from the hippocampus have long-distance effects on the functional organization of motor maps.

Animals↗
PubMed2004

Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction.

Humans and songbirds are two of the rare animal groups that modify their innate vocalizations. The identification of FOXP2 as the monogenetic locus of a human speech disorder exhibited by members of the family referred to as KE enables the first examination of whether molecular mechanisms for vocal learning are shared between humans and songbirds. Here, in situ hybridization analyses for FoxP1 and FoxP2 in a songbird reveal a corticostriatal expression pattern congruent with the abnormalities in brain structures of affected KE family members. The overlap in FoxP1 and FoxP2 expression observed in the songbird suggests that combinatorial regulation by these molecules during neural development and within vocal control structures may occur. In support of this idea, we find that FOXP1 and FOXP2 expression patterns in human fetal brain are strikingly similar to those in the songbird, including localization to subcortical structures that function in sensorimotor integration and the control of skilled, coordinated movement. The specific colocalization of FoxP1 and FoxP2 found in several structures in the bird and human brain predicts that mutations in FOXP1 could also be related to speech disorders.

Animals↗
PubMed1989

Pharmacological basis for the use of nimodipine in central nervous system disorders.

Nimodipine, a Ca2+ antagonist with cerebrovasodilatory and anti-ischemic effects, binds to rat, guinea pig, and human brain membranes with high affinity (less than 1 nM). Only at higher concentrations has nimodipine been reported to block the release of some neurotransmitters and hormones from neuronal tissue. Nimodipine has no consistent effect on brain oxygen consumption or cortical ATP or phosphocreatine levels, although the ischemia-induced fall of brain ATP levels in gerbils or the lowering of intracellular brain pH in rabbits with focal cerebral ischemia were antagonized by the drug. In rats and baboons with middle cerebral artery occlusion, nimodipine was found to reduce neurological deficits without an increase in intracranial pressure or brain edema. Electrophysiological studies with nimodipine suggested a direct neuronal action. In rabbit dorsal root ganglion cells, concentrations as low as 20 nM were reported to block inward Ca2+ currents. Recent studies have suggested that nimodipine may also improve memory in brain-damaged or old rats, restore sensorimotor function and abnormal walking patterns of old rats, and accelerate acquisition of associative learning in aging rabbits. Blockade of age-related changes in Ca2+ fluxes in rat hippocampal neurones by nimodipine in vitro pointed to neuronal plasma membrane as the site of nimodipine action. The therapeutic usefulness of nimodipine appears not to be limited to cerebral ischemia, but may include dementia, age-related degenerative diseases, epilepsy, and ethanol intoxication.

Aging↗
PubMed1990

Biphasic effects of polarizing current on adenosine-sensitive generation of cyclic AMP in rat cerebral cortex.

Cyclic AMP accumulation elicited by adenosine was investigated in cortical slices of rats following the application of a weak anodal direct current (anodal polarization) to the unilateral sensorimotor cortex. Anodal polarization with 3.0 microA for 30 min caused an increase in the adenosine-elicited accumulation of cyclic AMP in the polarized cortex, in which case the increase in the polarized cortical region was highlighted by repeated applications of the currents. Polarization with 0.3 microA for 30 min decreased the cyclic AMP accumulation, and polarization with 30.0 microA for 30 min had no effect. When applied for 3 h, the polarizing currents at all of the intensities tested decreased the cyclic AMP accumulation. The results indicate that anodal polarization has biphasic effects on adenosine-elicited accumulation of cyclic AMP in the cortex. Alterations in the cyclic AMP generation are suggested to form the neurochemical basis of central and behavioral activity induced by anodal polarization.

Adenosine↗
PubMed1984

Inhibitory nigral influence on tectospinal neurons, a possible implication of basal ganglia in orienting behavior.

We have established in previous electrophysiological studies that the substantia nigra pars reticulata (SNr) exerts a potent inhibitory influence on cells located in the intermediate and deep tectal strata. The present study demonstrates that, in the rat, the tectospinal neurons constitute one of the cellular populations of the tectum on which the SN exerts its influence. Tectospinal neurons were identified using the antidromic activation method. Following SNr stimulation 17/37 (45%) of these cells showed a short-latency (1.5-2 ms) short-duration (7-15 ms) inhibition. This effect was revealed by a blockade of spontaneous and peripherally evoked discharges. Moreover, in some cases the nigral inhibition delayed the antidromic invasion of the somato-dendritic portion of the neuron. Tectospinal neurons have been considered as one of the neuronal substrate by which the superior colliculus (SC) can promote head orienting movements. The evidence that the SNr influences the responsiveness of these cells to their peripheral sensory inputs suggests that the basal ganglia and in particular the SNr are involved in the integrative sensorimotor processes underlying head orienting movements.

Afferent Pathways↗
PubMed1975

[Coupling behavior of central nervous system functions as well as heart rate and respiratory rhythm under the influence of diazepam].

In order to substantiate the subjective feeling of relaxation and mental balance felt after taking Diazepam a new biorhythmometric technique was used, in which the minute-rhythm pulsations were calculated with the aid of autocorrelation analysis from the time series of central nervous functions and cardiorespiratory functions, and their frequency synchronisation recorded as to quantity in the form of a coupling factor. Proof of an improved central nervous co-ordination was that the coupling factor of a relatively uniform test team, all students, after administration of Diazepam (Faustan) was significantly higher than before. If one assumes that the psychosomatic illness, for which the use of Diazepam is considered advisable, are a manifestation of generally disturbed central nervous vegetative reaction condition, then the biorhythmometric survey of the internal co-ordination of relevant physiological functions provides stronger proof than testing with single parameters, between which we also found significant variations (for example, prolongation of the sensorimotor reaction times under Faustan).

Acoustic Stimulation↗
PubMed1980

Role of the neostriatal dopaminergic activity in sequencing and selecting behavioural strategies: facilitation of processes involved in selecting the best strategy in a stressful situation.

The purpose of this study was to detect the behavioural effect of drug-induced changes in the neostriatal dopaminergic activity upon the degree of intrinsic (self-generated) and extrinsic (externally produced) constraints on the selection of behavioural patterns in rats. Both systemic and neostriatal injections of extremely low doses of apomorphine and haloperidol were used to change the neostriatal dopaminergic activity. Behavioural changes were observed in (a) an open-field test, (b) a so-called 'swimming without escape' test, (c) a so-called 'swimming with escape' test, and (d) a test to detect deficiencies in sensory, motor and sensorimotor capacities required to perform both swimming tests. Evidence is found that the neostriatum, especially the neostriatal, dopaminergic activity determines the animal's ability to select the best strategy in a stressful situation by modifying the process of switching strategies under pressure of factors intrinsic to the organism: neither sensory neglect nor inability to initiate voluntary movements underlay the observed phenomena. It is suggested that the neostriatum determines the individual flexibility to cope with available sensory information.

Animals↗
PubMed1989

Spinal cord circuits: are they mirrors of musculoskeletal mechanics?

Over the past decade, research at three different levels of sensorimotor control has revealed a degree of complexity that challenges traditional hypotheses regarding servocontrol of individual muscles: (a) The connectivity of spinal circuits is much more divergent and convergent than expected. (b) The normal and reflex-induced recruitment of individual muscles and compartments of muscles is more finely controlled than was noted previously. (c) The mechanical interactions among linked skeletal segments and their often multiarticular muscles are neither simple nor intuitively obvious. We have developed a mathematical model of the cat hind limb that permits us to examine the influence of individual muscles on posture and gait. We have used linear quadratic control theory to predict the optimal distribution of feedback from a hypothetical set of proprioceptors, given different assumptions about the behavioral goals of the animal. The changes in these predictions that result from changes in the structure and control objectives of the model may provide insights into the functions actually performed by the various circuits in the spinal cord.

Journal Article↗
PubMed2000

The influence of normal aging on the cortical processing of a simple motor task.

OBJECTIVE: To assess the influence of normal aging on the cortical physiology of motor behavior. METHODS: The authors studied cortical activation in eight elderly (55 to 76 years of age) and eight younger (18 to 27 years of age) healthy subjects while they performed a simple motor task. A 28-channel EEG was recorded; task-related power changes associated with repetitive, metronome-paced (1 Hz) finger movements were computed as a measure of cortical activation. RESULTS: Distinct, age-dependent activation patterns were expressed in four distinct frequency ranges: low-alpha (10 to 11 Hz), high-alpha (12 to 13 Hz), low-beta (16 to 17 Hz), and high-beta (22 to 23 Hz) bands. The main findings were a greater overall activation and, more specifically, a pronounced bilateral activation of sensorimotor regions in elderly subjects for both alpha bands. Additionally, in the elderly subjects there was increased activation of the mesial frontocentral cortex (supplementary motor area region) in the high-beta band, whereas younger volunteers had a prominent activation of the left lateral premotor and sensorimotor region in this frequency range. CONCLUSIONS: These findings demonstrate that the functional anatomy of the human motor system changes during normal aging. It appears that, for a given motor task, the aging brain recruits additional primary sensorimotor and premotor regions of both hemispheres.

Adolescent↗
PubMed2002

Neurophysiological correlates of age-related changes in human motor function.

BACKGROUND: There are well-defined and characteristic age-related deficits in motor abilities that may reflect structural and chemical changes in the aging brain. OBJECTIVE: To delineate age-related changes in the physiology of brain systems subserving simple motor behavior. METHODS: Ten strongly right-handed young (<35 years of age) and 12 strongly right-handed elderly (>50 years of age) subjects with no evidence of cognitive or motor deficits participated in the study. Whole-brain functional imaging was performed on a 1.5-T MRI scanner using a spiral pulse sequence while the subjects performed a visually paced "button-press" motor task with their dominant right hand alternating with a rest state. RESULTS: Although the groups did not differ in accuracy, there was an increase in reaction time in the elderly subjects (mean score plus minus SD, young subjects = 547 +/- 97 ms, elderly subjects = 794 +/- 280 ms, p < 0.03). There was a greater extent of activation in the contralateral sensorimotor cortex, lateral premotor area, supplementary motor area, and ipsilateral cerebellum in the elderly subjects relative to the young subjects (p < 0.001). Additional areas of activation, absent in the young subjects, were seen in the ipsilateral sensorimotor cortex, putamen (left > right), and contralateral cerebellum of the elderly subjects. CONCLUSIONS: The results of this study show that elderly subjects recruit additional cortical and subcortical areas even for the performance of a simple motor task. These changes may represent compensatory mechanisms invoked by the aging brain, such as reorganization and redistribution of functional networks to compensate for age-related structural and neurochemical changes.

Adult↗
PubMed2003

Profiles of sensorimotor development in children with autism and with developmental delay.

Aim of the study was (1) to evaluate sensorimotor development of children with autism in comparison with that of children with developmental delay, (2) to verify the possible unevenness of the developmental profiles through correlations amongst domains and between domains and chronological age. 46 children with autism were compared with 45 children with developmental delay. Mean chronological age was 3.7 yr. in children with autism and 3.6 yr. in children with mental retardation. Mean mental age was 1.3 yr. in children with autism and 1.1 yr. in children with developmental delay. Ordinal scales of Uzgiris-Hunt show that the two groups score significantly differently on the scales of Object Permanence, Means-Ends, Operational Causality, and Spatial Relations and that scores were higher for the children with autism. The comparison made between the developmental levels of each group indicate that the sensorimotor profile in children with developmental delay is fairly homogeneous, while it appears uneven in autistic children, for whom Object Permanence appears to be the most advanced skill, Verbal and Gestural Imitation and Schemes for Relating to Objects the lowest. The results are in keeping with the assumption that the pivotal defect of autism is a deficit in social interactive skills.

Autistic Disorder↗
PubMed1997

The effects of nerve growth factor on spatial recent memory in aged rats persist after discontinuation of treatment.

Nerve growth factor (NGF) infusion significantly reduces spatial recent memory deficits in aged rats, an effect that has great relevance to the treatment of memory impairments characteristic of patients with Alzheimer's disease. The present study was designed to examine whether this NGF-induced improvement in spatial recent memory persists after the discontinuation of NGF treatment, an issue of crucial importance for the potential clinical use of this compound. Spatial recent memory was tested in a Morris water maze delayed nonmatch-to-position task. In addition to memory, sensorimotor skills were also examined. Four- and 22-month-old rats were tested preoperatively, infused intraventricularly with recombinant human NGF or vehicle, and tested both during the 4 week infusion period and during the 4 weeks after discontinuation of the infusion. NGF significantly improved spatial recent memory in 22-month-old rats only, during the 4th week of infusion and for up to 4 weeks after discontinuation of the infusion. Although NGF did not affect overall sensorimotor skills during infusion in either age group, sensorimotor skills were significantly improved both 2 and 4 weeks after discontinuation of infusion in 22-month-old rats. These findings demonstrate that the beneficial effects of NGF on spatial recent memory can persist for up to 1 month after discontinuation of infusion and suggest that NGF can be used intermittently for the treatment of age-associated memory dysfunction and Alzheimer's disease.

Aging↗
PubMed1992

[The participation of the sensorimotor cortex in assessing the quality of food reinforcement against a background of thirst].

In trained cats, unilateral extirpation of the sigmoid gyri's cortex disinhibited the unreinforced runs while preserving the positive conditioned reflexes associated with differentiation of different salt food reinforcement. The bilateral extirpation induced a disorder of differentiated inhibition while preserving the conditioned runs reinforced with the highly salted food. The unilateral extirpation did not affect the food-motor conditioning against the background of the salt diet. The bilateral extirpation delayed the differentiation inhibition and facilitated the positive conditioning.

Animals↗
PubMed2006

Electrophysiological classification of somatostatin-positive interneurons in mouse sensorimotor cortex.

Classification of inhibitory interneurons is critical in determining their role in normal information processing and pathophysiological conditions such as epilepsy. Classification schemes have relied on morphological, physiological, biochemical, and molecular criteria; and clear correlations have been demonstrated between firing patterns and cellular markers such as neuropeptides and calcium-binding proteins. This molecular diversity has allowed generation of transgenic mouse strains in which GFP expression is linked to the expression of one of these markers and presumably a single subtype of neuron. In the GIN mouse (EGFP-expressing Inhibitory Neurons), a subpopulation of somatostatin-containing interneurons in the hippocampus and neocortex is labeled with enhanced green fluorescent protein (EGFP). To optimize the use of the GIN mouse, it is critical to know whether the population of somatostatin-EGFP-expressing interneurons is homogeneous. We performed unsupervised cluster analysis on 46 EGFP-expressing interneurons, based on data obtained from whole cell patch-clamp recordings. Cells were classified according to a number of electrophysiological variables related to spontaneous excitatory postsynaptic currents (sEPSCs), firing behavior, and intrinsic membrane properties. EGFP-expressing interneurons were heterogeneous and at least four subgroups could be distinguished. In addition, multiple discriminant analysis was applied to data collected during whole cell recordings to develop an algorithm for predicting the group membership of newly encountered EGFP-expressing interneurons. Our data are consistent with a heterogeneous population of neurons based on electrophysiological properties and indicate that EGFP expression in the GIN mouse is not restricted to a single class of somatostatin-positive interneuron.

Algorithms↗
PubMed1985

Environmental influences on locomotor recovery following cortical lesions in rats.

Groups of rats were exposed to an enriched environment 2 hr per day for 30 days during the immediate pre- and/or postoperative period, or not at all. Animals in four of these groups sustained lesions in the bilateral sensorimotor cortex. One sham-operated control group was enriched pre- and postoperatively; a second control group was not. Animals were trained preoperatively to locomote across a narrow elevated runway. Testing on the locomotor task began 31 days after surgery and continued until preoperative performance levels were achieved. Preoperative enrichment had the most potent influence on initial deficit and recovery of locomotion. Animals that were enriched preoperatively failed to demonstrate any deficit postoperatively, and the topology of their hindlimb movement appeared to be normal. In preoperatively impoverished animals, postoperative enrichment reduced the degree of initial deficit and speeded recovery of locomotion when compared with animals not enriched at all. However, preoperatively impoverished rats demonstrated an aberrant topology of hindlimb movement even after they were "behaviorally recovered".

Animals↗