Electrophysiological analysis of motor cortical plasticity after cortical lesions in newborn rats

Intracortical microstimulation of the motor cortex in normal adult rats evoked low threshold contralateral forelimb movements and high threshold ipsilateral movements. Ablation of the opposite sensorimotor cortex in adult animals did not alter these thresholds. However, stimulation of the unablated hemisphere in adult rats that sustained unilateral sensorimotor cortical lesions as neonates elicited low threshold ipsilateral forelimb movements that were similar to contralateral movements. These low threshold ipsilateral movements may be mediated via aberrant corticofugal pathways which are known to develop following neonatal cortical lesions.     

Mechanisms underlying human motor system plasticity

There has been increased interest in the ability of the adult human nervous system to reorganize and adapt to environmental changes throughout life. This ability has been termed "plasticity." Plastic changes in the cerebral cortex have been studied: (a) as modifications of sensory or motor cortical representation of specific body parts (cortical maps, body representation level); and (b) as changes in the efficacy of existing synapses or generation of new synapses (neuronal or synaptic level). In this review, we describe paradigms used to study mechanisms of plasticity in the intact human motor system, the functional relevance of such plasticity, and possible ways to modulate it.     

Neural plasticity and the brain renin-angiotensin system

The brain renin-angiotensin system mediates several classic physiologies including body water balance, maintenance of blood pressure, cyclicity of reproductive hormones and sexual behaviors, and regulation of pituitary gland hormones. In addition, angiotensin peptides have been implicated in neural plasticity and memory. The present review initially describes the extracellular matrix (ECM) and the roles of cell adhesion molecules (CAMs), matrix metalloproteinases, and tissue inhibitors of metalloproteinases in the maintenance and degradation of the ECM. It is the ECM that appears to permit synaptic remodeling and thus is critical to the plasticity that is presumed to underlie mechanisms of memory consolidation and retrieval. The interrelationship among long-term potentiation (LTP), CAMs, and synaptic strengthening is described, followed by the influence of angiotensins on LTP. There is strong support for an inhibitory influence by angiotensin II (AngII) and a facilitory role by angiotensin IV (AngIV), on LTP. Next, the influences of AngII and IV on associative and spatial memories are summarized. Finally, the impact of sleep deprivation on matrix metalloproteinases and memory function is described. Recent findings indicate that sleep deprivation-induced memory impairment is accompanied by a lack of appropriate changes in matrix metalloproteinases within the hippocampus and neocortex as compared with non-sleep deprived animals. These findings generally support an important contribution by angiotensin peptides to neural plasticity and memory consolidation.     

Electrophysiological studies of the visual system in myotonic dystrophy

Ocular signs and electroretinal alterations frequently occur in Myotonic Dystrophy (MD). Surprisingly few reports describe VEP abnormalities for this syndrome. Since the evaluation of cortical visual responses is linked to an understanding of preceding retinal changes, we conducted a systematic study of the visual system including ophthalmological and electrophysiological (EOG, ERG, PERG, VEP) investigation in 14 confirmed myotonic patients. The various tests revealed consistent abnormalities, the most frequent of these being PERG and VEP changes. These alterations seemed to occur independently of one another, suggesting impaired function at different levels of visual pathway. A generalized defect of cell membrane has recently been proposed as etiopathogenesis of typical EMG and systemic features of the disease. Such membrane dysfunction might account for the early and marked abnormalities in electrophysiological tests, even in the absence of neuro-ophthalmological changes.     

Development of the equine brain motor system

The purpose of the present study was to demonstrate the structural maturation of the horse brain in the critical period of development emergence of coordinated locomotion. Equine brains from 14 days before expected birth to adulthood were fixed in formaldehyde and embedded in paraffin. After taking the outer parameters of the brains, full series of large-area coronal sections were prepared on a special microtome and stained with Nissl's cresyl violet and Haidenhain's iron-haematoxylin. Microscopic images of sections were digitized and were subjected to computer-aided image analysis. The gross morphology of the brains and the image analysis of histological preparations suggest that in the perinatal period studied there is no substantial increase in brain size and mass, while the amount of Nissl substance and myelin grows rapidly till postnatal day 45. Then a relative decrease of both is observed till adulthood accompanied by a doubling of brain size and mass. It is concluded that during the maturation of the equine brain, decisive changes of the motor system such as up-regulation of protein sysnthesis and full myelination of motor tracts takes place during the critical period of onset of coordinated locomotion.     

Electrophysiological studies of d-lysergic acid diethylamide in the visual system

Experiments involving the use of LSD and observing its effects on neurons involved in the processing of visual information are reviewed. These studies typically involved either intravenous or iontophoretic application of the compound. Both modes of application appeared to block the optic afferent synapse at the level of the dorsal lateral geniculate nucleus and to alter the evoked activity of visual cortical neurons. Increasing the dose of LSD regardless of the manner in which it was applied tended to produce depression of both spontaneous and visually driven activity. The receptive field properties of the neurons at all levels of the visual system appear to remain intact after LSD despite changes in spontaneous activity. The effect of LSD on non-specific afferents to the dorsal lateral geniculate nucleus is depicted in relationship to two of the different kind of relay cells located in this structure. Data on LSD interaction with the effects of midbrain stimulation on “X” and “Y” neurons is presented.     

Electrophysiological studies of d-lysergic acid diethylamide in the visual system

Experiments involving the use of LSD and observing its effects on neurons involved in the processing of visual information are reviewed. These studies typically involved either intravenous or iontophoretic application of the compound. Both modes of application appeared to block the optic afferent synapse at the level of the dorsal lateral geniculate nucleus and to alter the evoked activity of visual cortical neurons. Increasing the dose of LSD regardless of the manner in which it was applied tended to produce depression of both spontaneous and visually driven activity. The receptive field properties of the neurons at all levels of the visual system appear to remain intact after LSD despite changes in spontaneous activity. The effect of LSD on non-specific afferents to the dorsal lateral geniculate nucleus is depicted in relationship to two of the different kind of relay cells located in this structure. Data on LSD interaction with the effects of midbrain stimulation on “X” and “Y” neurons is presented.     

Electrophysiological correlates of motor conversion disorder

In patients with a functional (psychogenic) paresis, motor conduction tests are, by definition, normal. We investigated whether these patients exhibit an abnormal motor excitability. Four female patients with a functional paresis of the left upper extremity were studied using transcranial magnetic stimulation (TMS). We investigated motor thresholds, intracortical inhibition and intracortical facilitation at rest. Corticospinal excitability was evaluated by single pulse TMS during rest and during imagination of tonic index finger adductions. Data obtained from the affected first dorsal interosseous muscle were compared with the unaffected hand and with a healthy age‐matched control group. Three patients demonstrated a flaccid paresis, one patient had a psychogenic dystonia. Motor thresholds, short interval intracortical inhibition and intracortical facilitation recorded from the affected side were normal. In healthy subjects, movement imagination produced an increase of corticospinal excitability. In the patients, motor imagery with the affected index finger resulted in a decrease of corticospinal excitability compared to rest, being significantly different from the unaffected side and from the control group. We suggest that suppression of corticospinal excitability during movement imagination is an electrophysiological correlate of the patients' inability to move voluntarily and provides some insight into the pathophysiology of this disorder. © 2008 Movement Disorder Society     

Electrophysiological cross section of the motor unit.

A new technique to investigate the motor unit organisation in man is described. By moving an EMG electrode through the motor unit a continuous scan or "electrophysiological cross section" is obtained. Computer processing methods are used for analysis and display. Examples are shown from healthy subjects and from patients with neuromuscular diseases.     

Central motor conduction studies in motor neurone disease using magnetic brain stimulation

Central motor conduction (CMC) to abductor digiti minimi (ADM) was evaluated in 22 patients with motor neurone disease (MND) using magnetic stimulation of the motor cortex and electrical stimulation at the C7/T1 interspace. CMC was abnormal in 14 patients; prolonged CMC time and absence of response to brain stimulation were more frequent abnormalities than low amplitude responses without prolonged CMC time. The technique can reveal subclinical upper motor neurone involvement and document central motor pathway dysfunction in MND. The patterns of abnormality are not specific to MND; all may occur in other neurological disorders including multiple sclerosis.     

Electrophysiological studies of the pontine nuclei

Responses of neurones in the pontine nuclei (PN) to stimulation of the sensorimotor cortex were recorded by microelectrodes inserted in the nuclei. Extracellular and intracellular recordings from individual neurones as well as systematic field potential analysis revealed features of neuronal activities in the nuclei. PN neurones sending their axons to the cerebellum, the ponto-cerebellar neurones, could be fired not only antidromically but also trans-synaptically by stimulation of the cerebellar folium. The results require us to postulate that axon collaterals of ponto-cerebellar neurones may feed back to the neurones themselves and excite them. A volley produced by stimulation of the sensorimotor cortex could arrive in the PN at a latency of about 0.5 msec. Cortico-pontine fibres may have direct synaptic as well as polysynaptic connections with PN neurones. Excitation of PN neurones due to stimulation of the sensorimotor cortex was usually replaced at a latency of 15–25 msec by suppression. EPSP-IPSP sequences were recorded in PN neurones, corresponding in time course to the excitation and suppression. Somatotopical organization of the cortico-pontine projection could not be shown definitively. Activation of the medial part of the PN was, in general, more marked than that of the lateral part on the same stimulation, and stimulation of the medial part of the anterior sigmoid gyrus (area 6a beta) was most powerful among various parts of the sensorimotor cortex in exciting PN neurones.     

Electrophysiological studies of myoclonus

As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification and about its generator mechanisms. The EEG-EMG polygraph provides the most essential information about the myoclonus of interest. Jerk-locked back averaging and evoked potential studies combined with recording of the long latency, long loop reflexes are useful to further investigate the pathophysiology of myoclonus, especially that of cortical myoclonus. A recent advance in magnetoencephalographic techniques has contributed significantly to the elucidation of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in each individual patient is important for selecting the most appropriate treatment of choice.     

Electrophysiological studies of myoclonus

As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification, and about its generator mechanisms. The electroencephalogram-electromyogram polygraph reveals the most important information about the myoclonus of interest. Jerk-locked back-averaging and evoked potential studies combined with recording of the long-latency, long-loop reflexes are useful to investigate the pathophysiology of myoclonus further, especially that of cortical myoclonus. Recent advances in magnetoencephalography and transcranial magnetic stimulation have contributed significantly to the understanding of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in individual patients is important for selecting the most appropriate treatment.     

Electrophysiological diagnosis of motor neuron disease and pure motor neuropathy

Motor neuron disease (MND) is a group of disorders in which there is degeneration of upper and lower motor neurons to a variable degree. Amyotrophic lateral sclerosis is the most frequent form of the disease, presenting with both upper and lower motor neuron involvement. Frequently, especially in the early stages of the disease, only lower motor neuron signs are present. In these conditions, some pure motor neuropathies may resemble MND. The diagnosis is of importance because some of these motor neuropathies are “dysimmune” disorders and may respond to immune therapies. In such diseases the multifocal motor neuropathy with conduction block appears to be the more frequent. In MND and pure motor neuropathies, the electrophysiological examination is the most decisive test. In MND, it is of diagnostic importance. In addition, it is useful in the assessment of disease severity and progression, in the evaluation of therapeutic trials and in the understanding of etiopathogenesis of the disease. In pure motor neuropathies, the presence of conduction block leads to immune treatment with good response in more than 50% of the cases. Received: 20 August 1998 Accepted: 10 October 1998