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Cortical KCl reinstates forelimb placing following damage to the internal capsule.

Following unilateral damage to the internal capsule, rats failed to use the contralateral forelimb during tests of contact, chin, and visual placing reactions. Infusion of potassium chloride onto the sensorimotor cortex contralateral to the lesion reinstated placing in the impaired limb and abolished placing in the normal limb. As the drug dissipated, placing in the impaired limb gradually deteriorated, while placing in the normal limb returned. In contrast, potassium chloride applied to the ipsilateral cortex did not reinstate placing. These findings suggest that the loss of forelimb placing following lesions of the internal capsule is due, at least in part, to tonic inhibition from the cortex contralateral to the lesion.

Animals↗

Temporal analysis of REM sleep after nest-building behavior in nulliparous albino rat.

EEG recording was performed, during nest-building behavior (NBB), from the hippocampus and sensorimotor cortex of nulliparous albino rats with simultaneous recordings of EMGs of neck-muscle and eye movements. The duration of NBB varied with a period of 4-5 days. However, the relative durations of behavioral transitions in NBB, i.e., nest-building, grooming, and sleeping, were regular in both long lasting and early terminated NBB. REM sleep was identified, in every instance, immediately after NBB. The latency of REM sleep was significantly tied to the termination of NBB without regard to the duration of NBB. Differences in the duration of NBB, however, affected REM-propensity: the longer the NBB was, the shorter the latency of REM sleep tended to be. NBB might accelerate the induction of the physiological condition responsible for REM sleep generation.

Animals↗

Methylphenidate treatment following ablation-induced hemiplegia in rat: experience during drug action alters effects on recovery of function.

Two experiments examined the effects of single or multiple administrations of methylphenidate (MPH; Ritalin) and differing amounts of beam-walking trials (symptom relevant experience) during the period of drug action on recovery from hemiplegia following unilateral sensorimotor cortex ablation in rat. The first study tested multiple doses of MPH (10 mg/kg) or sterile saline given once daily, followed by four beam-walk (BW) trials at 1, 2, 3, and 6 h on 3 consecutive days. A significant and enduring enhancement of recovery was only observed 24 h after the third administration of MPH, compared to saline controls. In the second study, a single dose of MPH (10 mg/kg) or saline was administered 24 h after ablation, followed by 12 BW trials beginning 1 h and continuing at 15-min intervals until 3 h after MPH or saline administration. A significant and enduring facilitation of BW ability was produced by this single MPH treatment regimen. These data further support the importance of an interaction between symptom-relevant experience and drugs that increase norepinephrine transmission to enhance functional recovery after brain damage.

Animals↗

Preliminary report: activation of the cerebellum in essential tremor.

Several images of cerebral blood flow were recorded during inhalation of carbon-15-labelled carbon dioxide by positron emission tomography in four patients with essential tremor and four normal controls. Unilateral involuntary postural tremor in essential tremor patients was associated with blood flow significantly greater than that at rest in the contralateral sensorimotor cortex, both lateral premotor regions, and both cerebellar hemispheres. Of these regions, only the cerebellum was not activated in normal controls holding a posture without tremor or in essential tremor patients undergoing passive wrist movement. The increased flow in the cerebellum therefore seems to represent neural activity involved in tremor generation. It is proposed that essential tremor is due to oscillation within cerebello-olivary pathways, relayed by way of the thalamus and motor cortex to the spinal cord.

Administration, Inhalation↗

Light and electron microscopical visualization of anterogradely labelled corticospinal growth cones using a new combination of HRP staining techniques.

Up until now, the ultrastructural visualization of growth cones of developing long fibre tracts could only be achieved by horseradish peroxidase (HRP) application 'en route', resulting in axonal damage, which in turn may affect growth cone morphology. Besides, this technique results in labelling of passing fibres, thus hampering the identification of axon origin as well as the interpretation of growth cone configuration. In the present investigation a new combination of HRP staining and intensification techniques is presented which makes it possible to visualize anterogradely labelled corticospinal growth cones over long distances in developing rat spinal cord at the light as well as the electron microscopical level. HRP was applied to the originating cells of the corticospinal tract, located in the sensorimotor cortex, and after 24 h was visualized using a procedure which essentially consists of 3 subsequent steps: first a tetramethylbenzidine (TMB)/ammoniumheptamolybdate (AHM) reaction; second diaminobenzidine (DAB)/nickel (Ni) stabilization and finally glucose oxidase intensification. As was verified at the EM level, the staining procedure here described reveals a complete intense black staining of HRP-labelled growth cones of outgrowing corticospinal axons. Therefore, the method described here guarantees a correct analysis of growth cone morphology at the light microscopical and the ultrastructural level. The present procedure is especially valuable in studying the development of long central nervous fibre systems.

Animals↗

The "staircase test": a measure of independent forelimb reaching and grasping abilities in rats.

A novel reaching test for the rat has been developed to assess the independent use of forelimbs in skilled reaching and grasping tasks. The apparatus is a plexiglas box with a removable baited double staircase. Food pellets are placed on the staircase and presented bilaterally at 7 graded stages of reaching difficulty to provide objective measures of side bias, maximum forelimb extension and grasping skill. In the present experiment, the apparatus was used to assess the reaching performance of rats following unilateral lesions of the sensorimotor cortex, unilateral lesions of the posterior cortex or bilateral lesions of the olfactory bulbs. The task has the advantage of objective over rating measurement, and the simplicity of the apparatus permits many animals to be tested concurrently.

Animals↗

Absence of impulse activity in cortical neurons with transient projections to the cerebellum.

During the second postnatal week of development in cats, neurons in layer V of the primary sensorimotor cortex project transiently, by way of collaterals of pyramidal tract axons, to the cerebellum. All cerebrocerebellar collaterals are subsequently eliminated, while the collaterals in the pyramidal tract persist into the adult. To determine if the transience of the projection to the cerebellum could be due to the lack of functional activity in cerebrocerebellar projection neurons, single-unit extracellular recordings were made from neurons in the primary somatosensory cortex (S-I) in 8-14-day-old kittens. Projection neurons were identified by their antidromic activation from pyramidal tract or cerebellum. Collision experiments confirmed that some neurons had collateral projections to both structures. Recordings from both generally anesthetized as well as locally anesthetized, but awake preparations, indicated that pyramidal tract and cerebrocerebellar projection neurons never fired action potentials spontaneously or were orthodromically activated following stimulation of the medial lemniscus. Stimulation of the medial lemniscus did synaptically activate neurons in the cortex, but these were always located superficial to the antidromically activated projection neurons. These findings indicate that pyramidal tract and/or cerebrocerebellar S-I projection neurons are physiologically silent during the period of development that cortical axons are transiently present in the cerebellum, suggesting that cerebrocerebellar projections may be eliminated because of the lack of impulse activity.

Animals↗

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↗

Selective elimination of transient corticospinal projections in the rat cervical spinal cord gray matter.

In the present paper a description is given of the development of the rat corticospinal tract (CST) in the lower cervical spinal cord. This area contains, among other cells, the motoneurons innervating the distal forelimb muscles. HRP gels were implanted in the sensorimotor cortex of Wistar rats varying in age from postnatal day 0 (P0) to P60. After a survival period of 48 h, the rats were transcardially perfused, the spinal cords transversely sectioned at 30 microns and the sections reacted for HRP. Labelled CST axons in the dorsal funiculus were first detected at P2, and after a delay of 2 days the first fibres were found in the adjacent gray matter (P4). More labelled fibres were gradually added until maximal number and extension was reached at P10. By then the entire gray matter and large parts of the white matter were covered by labelled CST axons. From P10 onwards, the number of labelled CST fibres as well as their extension decreased. In the adult rat, some areas such as the lateral part of the ventral and dorsal horn and large parts of the ventral and lateral white matter ultimately became devoid of labelled CST axons. It is concluded that a massive overshoot occurs during the development of the terminal field of the rat CST. The results are discussed in conjunction with our previous findings on the development of the motoneurons innervating the rat distal forelimb muscles. The concurrent selective elimination of both CST axons and motoneuron dendrites is suggested to be correlated with progressively more mature, coordinated movements and with high digital skills especially.

Aging↗

Immunological model of epilepsy. Epileptiform activity induced by fragments of antibody to GM1 ganglioside.

Antibodies to GM1 ganglioside injected into the sensorimotor cortex of the rat induce recurrent epileptiform activity. We now find that the divalent F(ab')2 and monovalent Fab' fragments derived from antiganglioside IgG molecules are able to induce epileptiform seizures. This result supports the view that the binding of antibodies to ganglioside receptors in the synaptic membrane is sufficient in itself to initiate changes in membrane processes which lead to epileptiform spiking. These changes do not appear to be dependent on linking of ganglioside receptors or on the presence of serum factors such as complement.

Animals↗

Functional connections between neurons of interpositus nucleus of the cerebellum and the red nucleus.

Patterns of functional connections between individual neurons of nucleus interpositus (IP) of the cerebellum and red nucleus (RN) were examined. This was assessed by cross-correlation of spike trains characterizing interaction between simultaneously recorded neurons. Direct interpositorubral connections were always excitatory in nature: direct inhibition was only found within and not between these nuclei. Shared inputs from common sources outnumber other types of interpositorubral connections. Patterns of connection between IP RN neurons could be influenced by sensorimotor cortex.

Afferent Pathways↗

Complex composition of synaptic potentials of the rubrospinal neurons to corticofugal impulses.

Complex, multicomponent excitatory postsynaptic potentials (EPSPs) of the red nucleus rubrospinal neurons evoked by stimulation of the sensorimotor cortex and associative field of the parietal cortex were studied in acute experiments on pentobarbitalized cats by the intracellular recording technique. Complex cortical EPSPs were recorded in two-thirds of the studied number of neurons. Monosynaptic nature of the first two components of EPSPs evoked by corticofugal impulses propagating at an average velocity of 18.5 ms and 7.5 ms was revealed. Participation of the corticospinal input in the genesis of EPSPs mentioned was revealed by selective activation of corticospinal fibers on the level of medullary pyramids as well as by studying peculiarities of their interaction with effects of cortical stimulation. It was shown that both corticospinal and corticorubral (predominantly slow conducting) neurons participate in the genesis of the first two components of complex EPSPs.

Animals↗

Reference memory and allocentric spatial localization deficits after unilateral cortical brain injury in the rat.

Traumatic brain injury (TBI) produces learning and memory impairments in humans. This study investigated the effects of TBI on memory and spatial localization strategies in rats. Prior to TBI, separate groups of rats were trained in an 8-arm radial maze with either all 8 arms baited (Expt. 1) or only 4 of the 8 arms baited (Expt. 2). TBI was produced by a controlled pneumatic impactor striking the entire right sensorimotor cortex of the anesthetized rat. Rats used in Expt. 1 were selected because they did not use a stereotypic response strategy (going to adjacent arms) in performing the maze before injury. After TBI the rats were not different from control rats in the number of working memory (WM) errors made. They did, however, display a distinct propensity to go to adjacent arms, i.e., exhibit stereotypic behavior, with a right-handed (ipsiversive) bias (P < 0.005). After TBI, rats which were trained with only 4 of 8 arms baited committed more reference memory (RM) errors than control rats (P < 0.05). They did not differ from controls on WM errors. Injured rats took longer to re-attain criteria than controls (P < 0.0001). Injured rats also initially displayed a propensity to enter the adjacent arm sequentially before re-attaining criteria. Further analysis indicated that injured rats re-learned the maze with a right-hand bias (P < 0.0001). The results of both experiments suggest that after TBI, rats shifted from an allocentric to an egocentric strategy to re-learn the maze. It was suggested that damage to the parietal cortex may have been responsible for both RM errors and the shift away from an allocentric strategy to an egocentric strategy. Possibly, the ipsiversive (right-hand) bias may be the result of a behaviorally or injury-induced neurochemical asymmetry within the motor system.

Animals↗

Activation processes during mental practice in stroke patients.

In healthy subjects, mental practice is known to improve motor performance. It is also known to be accompanied by a higher central nervous activity. Since such effects seem to be desirable for rehabilitation, we investigated the possibility of detecting changes in central nervous activity by means of EEG in stroke patients, and whether these changes were similar to those observed in healthy subjects. 12 left-sided hemiplegic patients who underwent a specific post-stroke rehabilitation treatment were requested to perform a simple arm movement sequence. In the following mental practice period the patients were requested to image the same sequence without any real movement. EEG background activity was recorded during rest and imagination periods. After the calculation of z-transformed power values within the theta, alpha, and beta-1 band, differences between rest and imagination periods were evaluated for their significance. Stroke patients show significant decreases of theta, alpha, as well as beta-1 power during mental practice in comparison to the rest period. These changes are similar to those obtained in healthy subjects. Theta power decreases in central and parietal leads. Central alpha power diminishes only during imagination of the contralateral arm. This phenomenon as well as the decrease of beta-1 power in central derivation were also obtained during real motor performance and might indicate an activation of the sensorimotor cortex. In accordance with the hypothesis of internal feedback mechanisms, this activation is a necessary prerequisite for motor learning during mental practice.

Aged↗

Cortical laminar distribution of rat thalamic ventrolateral fibers demonstrated by the PHA-L anterograde labeling method.

The cortical innervation pattern of rat thalamic ventrolateral (VL) fibers was investigated with the Phaseolus vulgaris-leukoagglutinin (PHA-L) anterograde labeling method. The PHA-L-labeled terminals were distributed in the sensorimotor cortex where the cerebello-cerebral (C-C) evoked responses were recognized. The labeled terminals were detected in all layers except layer VI. In the upper part of layer I, the most densely packed terminals were formed and moderately labeled terminals were seen in layers IV and V. Such a laminar distribution of PHA-L-labeled VL terminals is consistent with the profiles of the C-C responses according to laminar field potential analysis.

Animals↗

Frontal and parietal components of enhanced somatosensory evoked potentials: a comparison between pathological and pharmacologically induced conditions.

Pathologically enhanced somatosensory evoked potentials (giant SEPs) were recorded in 10 patients with cortical myoclonus of various origins. With non-cephalic reference electrodes a giant frontal negativity corresponding to normal N30 was found over the contra- and ipsilateral hemispheres which was not simply a phase reversal of the well-known enhanced parietal P25. The preceding far-field P14, parietal N20 and frontal P22 were of normal size. A similar result was found when SEPs were studied during the action of etomidate, an ultrashort-acting non-barbiturate hypnotic which produced a marked increase of the parietal P25 and frontal N30 after intravenous administration. These increased components, on the other hand, were abolished when recording was repeated immediately after application of electroconvulsive shock whereas P14, N20, and P22 remained more or less unchanged in both conditions. Our results indicate that there are neuronal elements in the sensorimotor cortex which are more resistant to influences such as narcotic drugs and seizure activity than others, being highly modifiable by these alterations. It is speculated whether these highly modifiable cortical systems are those in which giant SEPs, as well as pharmacologically increased SEP components, arise.

Adolescent↗

Wave form decomposition of 'giant SEP' and its computer model for scalp topography.

By using the decomposition technique developed by ourselves to investigate the scalp topography of evoked potentials, a computer model for the scalp topography of giant SEPs was computed from 5 patients with progressive myoclonic epilepsy and was compared with those obtained from 6 normal subjects. Components of giant SEPs were similar to those of normal SEPs with respect to various parameters, although the former were much larger than the latter. An experimental enlargement of some of the early cortical components of the normal SEP model gave rise to a wave form closely resembling that of the giant SEP. These findings support our previous conclusion, derived from study of the scalp topography of the original SEP wave form, that the giant SEP results from a pathological enhancement of certain early cortical components of the normal SEP. The underlying neuronal hyperexcitability seems to involve more than one subunit of the sensorimotor cortex.

Adolescent↗

Non-invasive evaluation of central motor tract excitability changes following peripheral nerve stimulation in healthy humans.

The interval between muscle stretch and the onset of the long latency electromyographic responses (LLRs) has been theoretically fragmented into an afferent time (AT), taken at the peak of wave N20 of somatosensory evoked potentials and an efferent time (ET), calculated by means of magnetic transcranial stimulation (TCS), the two being separated by a cortical interval (CI). If this were the case, the afferent input should progressively 'energize' the sensorimotor cortex during the CI and change the excitability of cortico-spinal tracts. To investigate this, motor evoked potentials (MEPs) from thumb flexor muscles were recorded, whilst a conditioning stimulation of median or ulnar nerve randomly preceded (10-48 msec intervals) magnetic brain TCS. Nerve stimulation was adjusted to motor threshold and amplitudes of conditioned and test MEPs at different nerve-TCS interstimulus intervals were evaluated. Conditioned MEPs were significantly attenuated with nerve-TCS intervals between 16 and 20 msec for elbow and 20 and 22 msec for wrist stimulation. This was followed by MEP potentiation with nerve-TCS intervals corresponding to the sum of AT + CI (mean 23.2 msec, range 21.7-24.8). The onset latency of facilitated conditioned MEPs was about 1 msec briefer than that of test MEPs, but invariably longer than the latency of MEPs facilitated by a voluntary contraction. This protocol did not demonstrate amplitude facilitation of the segmental H reflex, corroborating the idea that the facilitated part of the conditioning nerve-TCS curve receives a transcortical loop contribution.

Adult↗