The effects of unilateral lesions in sensorimotor cortex on manipulation by cats.
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Hindlimb and forelimb deficits in rats caused by sensorimotor cortex lesions are frequently tested by using the narrow flat beam (hindlimb), the narrow pegged beam (hindlimb and forelimb) or the grid-walking (forelimb) tests. Although these are excellent tests, the narrow flat beam generates non-parametric data so that using more powerful parametric statistical analyses are prohibited. All these tests can be difficult to score if the rat is moving rapidly. Foot misplacements, especially on the grid-walking test, are indicative of an ongoing deficit, but have not been reliably and accurately described and quantified previously. In this paper we present an easy to construct and use horizontal ladder-beam with a camera system on rails which can be used to evaluate both hindlimb and forelimb deficits in a single test. By slow motion videotape playback we were able to quantify and demonstrate foot misplacements which go beyond the recovery period usually seen using more conventional measures (i.e. footslips and footfaults). This convenient system provides a rapid and reliable method for recording and evaluating rat performance on any type of beam and may be useful for measuring sensorimotor recovery following brain injury.
Unilateral damage to the forelimb region of the sensorimotor cortex (FLsmc) results in time-dependent changes in neuronal activity, structure and connectivity in the contralateral motor cortex of adult rats. These changes have been linked to facilitation of motor skill learning in the less-affected/ipsilesional forelimb, which is likely to promote its use in the development of behavioral compensation. The goal of this study was to determine whether an early post-lesion-sensitive time period exists for this enhanced learning and whether it is linked to synaptogenesis in the contralesional motor cortex. Rats were trained for 21 days on a skilled reaching task with the ipsilesional forelimb beginning 4 or 25 days after unilateral ischemic (endothelin-1-induced) FLsmc lesions or sham operations. As found previously, reaching performance was significantly enhanced in rats trained early post-lesion compared with sham-operates. In rats trained later post-lesion, performance was neither significantly different from time-matched sham-operates nor strikingly different from animals trained earlier post-lesion. In layer V of the contralesional motor cortex, stereological methods for light and electron microscopy revealed significantly more total, multisynaptic bouton and perforated synapses per neuron compared with sham-operates, but there were no significant differences between early- and late-trained lesion groups. Thus, there appears to be a sensitive time window for the maximal expression of the enhanced learning capacity of the less-affected forelimb but this window is broadly, rather than sharply, defined. These results indicate that relatively long-lasting lesion-induced neuronal changes are likely to underlie the facilitation of learning with the less-affected forelimb.
Changes in conditioned impulse reactions of neurons in sensorimotor cortex were studied during microiontophoretic application of glutamatergic and GABA ergic agonistic and antagonistic drugs. It was shown that ionotropic glutamate receptors (AMPA and NMDA) are activated by a conditioned stimulus. Not only large pyramidal neurons of deep cortical layers but surrounding short-axon inhibitory interneurons are involved in the reaction. It was shown that the activity of pyramidal neurons is under a constant inhibitory control from surrounding interneurons. This inhibition is involved in organization of excitatory cortical responses during conditioning.
Inversion of the early component of IPSPs in neurons of the sensorimotor cortex by artificial hyperpolarization of the membrane was demonstrated in cats immobilized by myorelaxants in acute experiments. The late component of IPSP was not inverted. Amplitudes of the early component of IPSPs were decreased by the membrane depolarization while the late component was completely reduced. The input resistance of the membrane which decreased during the early component of IPSPs was restored to the initial level during the late component.
The sensorimotor cortex of the alcoholized rat progeny showed the signs of the delayed ultrastructural development of neurons and interneuronal connections and their dystrophic changes, particularly in 21-day-old experimental rats. Thirty-day-old animals demonstrated pronounced reparative alterations. But in spite of this fact the ultrastructure of cortical neurons, particularly of dendrites was not completely restored.
We report evidence for activation of ipsilateral primary sensorimotor cortex (SMI) after median nerve stimulation recorded with magnetoencephalography (MEG). We measured somatosensory evoked magnetic fields (SEFs) to median nerve stimulation with a 122-channel helmet-shaped magnetometer in 10 healthy subjects. In five, the magnetic field patterns suggested long-latency activation of the ipsilateral SMI. Source locations found by current dipole fitting corresponded to the SMI hand area, as determined by contralateral stimulation. Further evidence for the origin of the ipsilateral responses in SMI was provided by the suppression of these responses during movement of the contralateral fingers. Sensory input to ipsilateral SMI could play a role in sensorimotor integration of bilateral movements.
The sensory properties of neurons in the several forelimb areas of rat sensorimotor cortex were examined using the technique of extracellular single-unit recording in the awake, head-restrained rat. Cells with peripheral receptive fields were tested for the amount and modality of sensory input during joint manipulation and brushing and tapping of limbs, face and trunk. Input-output correlations were made on the basis of the results of receptive field mapping and intracortical microstimulation in the same electrode penetration. It was found that neurons (n = 117) in the rostral forelimb area receive virtually no sensory input while 30% of neurons (n = 114) in the caudal forelimb primary motor area do receive such input. The inputs to caudal forelimb motor area neurons were primarily (83%) from single joints; along perpendicular electrode penetrations the same joint that activated a cortical cell also moved when microstimulation was delivered along the same electrode penetration. In the granular and dysgranular zones of somatic sensory forelimb cortex, 70% of neurons (n = 82) were responsive to peripheral sensory inputs, with most of the cells in the granular cortex responsive to cutaneous inputs while cells in the dysgranular cortex were more responsive to deep inputs. The lack of sensory inputs to the rostral forelimb motor area is consistent with the proposal that this region may be a part of the supplementary motor area of the rat.
Rats received one-stage, bilateral lesions of the individual sensorimotor cortex areas (Sm-1, Sm-2) and were compared to sham operated rats or rats with lesions of Sm1 + 2 in learning a series of 5 ridge-smooth tactile discriminations. Some rats began testing 1 or 2 weeks after surgery, while others remained in their home cages for 1 month, 6 months, 1 year or 2 years before beginning testing. The rats with combined Sm1 + 2 lesions performed very poorly regardless of recovery time, and those with sham operations performed extremely well even when tested late in life. The animals with either Sm-1 or Sm-2 lesions did not do well after the shorter recovery periods, but obtained scores within the sham operated group range when given 1 year. (Sm-2) or 2 years (Sm-1) for recovery. These data show that spared parts of the damaged system are important in mediating tactile discriminative behavior. However, the reasons for the long delays in recovery are not clear.
Previous studies have shown that electrical stimulation of the sensorimotor cortex (SMC) induces responses of the autonomic nervous system such as variations in heart rate and arterial pressure. Neuroanatomical studies have shown the existence of monosynaptic projections from the SMC to the nucleus tractus solitarius (NTS), the rostral ventrolateral medulla (RVLM) and the dorsal nucleus of the vagus nerve (DNV), which are bulbar nuclei involved in cardiovascular control. The aim of the present study was to establish whether there exists a functional connectivity between the SMC and these nuclei. Electrical stimulation applied to the SMC of 7 rats for 1 h induced the expression of c-fos-protein-like immunoreactivity in the nucleus of some neurons in NTS, RVLM and DNV. These data support the view that the SMC has functional connections with bulbar neurons involved in cardiovascular control.
BACKGROUND: A variety of drugs impair motor recovery after sensorimotor cortex (SMCTX) injury in laboratory animals and may have similar effects in humans. METHODS: Rats (n = 142) underwent unilateral suction-ablation of the hindlimb SMCTX or sham lesion. After 24 hours, rats were given a single dose of placebo, haloperidol (0.1, 1.0, or 10.0 mg/kg, intraperitoneal), or clozapine (0.1, 0.5, 1.0, or 10.0 mg/kg, intraperitoneal), and motor recovery was measured. RESULTS: Neither haloperidol (analysis of variance [ANOVA] F[3, 12], P = 0.43) nor clozapine (ANOVA F[4, 19], P = 1.00) affected motor performance in controls. Haloperidol impaired motor recovery (ANOVA F[3, 42], P = 0.002) at each tested dose, with no differences between the doses. The effect persisted after 2 weeks. In contrast, although rats given a single dose of clozapine of 1.0 or 10.0 mg/kg had poorer recoveries (ANOVA F[4, 51], P = 0.014), only those given the highest dose differed from controls. The effect was no longer apparent after 2 weeks. CONCLUSION: Consistent with previous reports, haloperidol retards motor recovery after SMCTX injury in rats. In contrast, there was no detrimental effect of clozapine when given at low doses. The use of low doses of atypical antipsychotics such as clozapine may provide a safer alternative to haloperidol in the treatment of agitated stroke patients.
To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.
We report six patients with complex partial seizures arising from the primary sensorimotor cortex who underwent invasive long-term ictal electroencephalogram/video monitoring and brain mapping and then multiple subpial transections. Although four patients demonstrated no abnormalities on magnetic resonance imaging, each patient showed moderate to marked gliosis in cortex biopsied from the site of ictal onset. Extensive preoperative and postoperative neuropsychological tests demonstrated no functional deficits resulting from surgery. Only one patient failed to derive significant postoperative seizure improvement, and he subsequently underwent additional subpial sectioning without further significant improvement. We propose a modification for this surgical technique and hypothesize that these patients may represent a syndrome of central cortical epilepsy.
The development of the homo- and heterosensory interaction on the sensorimotor cortex neurons was studied in anaesthesized and immobilized kittens of 3 age groups (12-30 days; 31-47 days; 2-4 months before and after the picrotoxin application. For the studied time intervals (100, 200, 300 ms) the insignificant suppression of response to the second stimulus is observed in a small part of the youngest kitten neurons. The picrotoxin application elicited only a rise in the background activity. In the middle and oldest kitten groups it is noted in the neurons which showed decreasing or blocking the responses to the testing stimuli, especially for the interval of 100 ms. The dynamics of the heterosensory interaction and the picrotoxin application influence become gradually the same in the adult animals. On the basis of the obtained results a question is discussed about the development of the inhibition mechanisms and their participation in the organization of the homo- and heterosensory interaction in the early postnatal ontogeny.
Changes in [Ca2+]o and [K+]o were measured in the sensorimotor cortex of cats during repetitive electrical stimulation and during pentetrazol induced epileptiform activity. Repetitive stimulation of the thalamic ventrobasal complex (VB) or of the cortical surface (CS) caused decreases in [Ca2+]o by up to 0.45 mM and increases in [K+]o by up to 7 mM. Maximum reductions of [Ca2+]o delta [Ca2+]o were found in depths of 100 to 300 micrometers below cortical surface, while rises in [K+]o were largest in depths of 600 to 1000 micrometers dependent on stimulation site. At depths below 700-900 micrometers increases in [K+]o were often accompanied by rises in [Ca2+]o of about 0.2 mM. Pentetrazol (PTZ) when injected at doses of 25 to 40 mg/kg body weight induced spontaneous seizure activity, which was in about 40% preceded by a slight fall of baseline [Ca2+]o. Repetitive stimulation and spontaneous seizures resulted in delta [Ca2+]o of up to 0.6 mM, whereas rises in [K+]o remained limited to a 'ceiling level' of about 10 mM. After PTZ application, peak delta [Ca2+]o were found at the same recording sites, but, in contrast to normal cortex, decreases in [Ca2+]o were observed in all cortical layers. The enhanced Ca2+-signals after PTZ application and the observed reduction of [Ca2+]o before seizure onset suggest that PTZ utilizes Ca2+-dependent mechanisms to initiate seizure activity.
Changes in the spike conditioned reflex reactions of sensorimotor cortex neurons during microiontophoretic application of agonists and antagonists of glutamatergic and GABAergic transmission and their modulation by dopamine were studied. A paradoxical reaction is described, consisting of facilitation of spike responses evoked by antagonists of ionotropic glutamate transmission, which was blocked by GABA. This is evidence for the active involvement of inhibition in organizing the excitatory responses of neurons in the conditioned reflex. Application of the metabotropic glutamate transmission antagonist MCPG was accompanied by sharp suppression of the baseline and evoked activity of cortical neurons, along with increases in the latency of spike responses and conditioned reflex movement. Dopamine was found to reverse the effect of blocking metabotropic glutamate receptors and to normalize neuron activity, which is evidence for the stabilizing role of dopamine in the functioning of neocortical neurons.
The effects on the EEG rhythms recorded from the sensorimotor cortex (post-sigmoid gyrus) of anaesthetized cats were studied under 4 conditions of artificial mechanical hyperventilation (HV) before and after cervical bilateral vagotomy. In animals with intact vagus nerves, using visual examination, EEG changes were only observed within the 2nd min during HV produced by increased stroke volume (delta V) with associated hypocapnia. Quantitative EEG (qEEG) showed that, for the same increase in minute ventilation and the same degree of hypocapnia, delta V induced a greater and earlier relative decrease (2nd min) in the power density of delta, theta and alpha bands, than increased pump frequency (delta F). The delta F tests produced a fall only in the theta band and within the 3rd min. With constant paCO2, transient modifications occurred only with delta V and were limited to the first 30 sec. In bivagotomized cats, moderate EEG responses to delta V plus associated hypocapnia persisted partly in the alpha band. Finally, no changes appeared with delta V or delta F when the vagus nerves were cut and paCO2 was maintained constant. The present data suggest strongly that, in anaesthetized cats, peripheral vagal afferents from the respiratory system play a major role in the EEG changes caused by artificial hyperventilation.
We investigated functional topography of human hand and lip sensorimotor cortex using somatosensory evoked potentials (SEPs) from chronically indwelling subdural grid electrodes (ECoG) in 3 epilepsy patients during stimulation of median nerve, ulnar nerve, and lower lip. We used dipole modeling to determine the cortical location of each peripheral sensory field. The cortical locations were in the postcentral gyrus and showed a clear somatotopic organization from medial superior to lateral inferior in the order: ulnar nerve, median nerve, and lip. The source localizations agreed with the results of cortical stimulations and anatomical features on intraoperative photographs. The cortical regions of median and ulnar nerve each could be modeled by sequential tangential and radial dipoles. The cortical region of lip was different and could be explained mostly by tangential dipoles. These findings suggest a difference in the cortical organization of human lip and hand sensory cortex and are consistent with a larger representation of lip in the posterior bank of central fissure in area 3b than on the gyral surface in area 1, similar to findings in macaque. Further studies in a larger population of patients with ECoG or normal subjects with scalp-EEG and MEG are warranted to test this hypothesis.