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PubMed2004

Depression of diaphragm motor cortex excitability during mechanical ventilation.

The effect of mechanical ventilation on the diaphragm motor cortex remains unknown. We assessed the effect of mechanical ventilation on diaphragm motor cortex excitability by measuring the costal and crural diaphragm motor-evoked potential (MEP) elicited by single and paired transcranial magnetic stimulation. In six healthy subjects, MEP recruitment curves of the costal and crural diaphragms were assessed at relaxed end expiration during spontaneous breathing [baseline tidal volume (Vt(baseline))] and isocapnic volume cycled ventilation delivered noninvasively (NIV) at three different levels of tidal volume (Vt(baseline), Vt(baseline) + 5 ml/kg liters, and Vt(baseline) + 10 ml/kg liters). The costal and crural diaphragm response to peripheral stimulation of the right phrenic nerve was not reduced by NIV. NIV reduced the costal and crural MEP amplitude during NIV (P < 0.0001) with the maximal reduction at Vt(baseline) + 5 ml/kg. Response to paired TMS showed that NIV (Vt(baseline) + 5 ml/kg) significantly increased the sensitivity of the cortical motoneurons to facilitatory (>9 ms) interstimulus intervals (P = 0.002), suggesting that the diaphragm MEP amplitude depression during NIV is related to neuromechanical inhibition at the level of motor cortex. Our results demonstrate that mechanical ventilation directly inhibits central projections to the diaphragm.

Abdomen↗

PubMed2003

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity. METHODS: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically. RESULTS: Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex. CONCLUSIONS: This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.

Adult↗

PubMed2001

The motor cortex and amyotrophic lateral sclerosis.

On theoretical grounds, abnormalities of the motor cortex in patients with amyotrophic lateral sclerosis (ALS) could lead to anterograde ("dying-forward") transneuronal degeneration of the anterior horn cells as suggested by Charcot. Conversely, retrograde ("dying-back") degeneration of the corticospinal tracts could affect the motor cortex. Evidence derived from clinical, neuropathological, static, and functional imaging, and physiological studies, favors the occurrence of anterograde degeneration. It is hypothesized that transneuronal degeneration in ALS is an active excitotoxic process in which live but dysfunctional corticomotoneurons, originating in the primary motor cortex, drive the anterior horn cell into metabolic deficit. When this is marked, it will result in more rapid and widespread loss of lower motor neurons. In contrast, slow loss of corticomotoneurons, as occurs in primary lateral sclerosis (PLS), precludes excitotoxic drive and is incompatible with anterograde degeneration. Preservation of slow-conducting non-M1 direct pathways in PLS is not associated with excitotoxicity, and anterior horn cells survive for long periods of time.

Amyotrophic Lateral Sclerosis↗

PubMed2002

Different mechanisms contribute to motor cortex hyperexcitability in amyotrophic lateral sclerosis.

OBJECTIVES: Different physiological approaches demonstrated motor system hyperexcitability in amyotrophic lateral sclerosis (ALS), probably reflecting excitotoxic mechanisms. Transcranial magnetic stimulation (TMS) showed that both increased excitability of corticomotoneurons and reduced intracortical inhibition (ICI) contribute to motor cortex hyperexcitability, but the importance of these factors in inducing this cortical dysfunction is unknown. The aim of the study was to establish how different mechanisms interact to promote motor system hyperexcitability in ALS in relation to clinical features. METHODS: The resting motor threshold (RMT), the motor evoked potential (MEP) recruitment curve and the cortical silent period (CSP) to single-pulse TMS were evaluated in 35 patients with ALS. Early ICI and intracortical facilitation (ICF) and late ICI were evaluated by paired TMS. RESULTS: The main abnormal TMS findings were: (a) a steeper MEP recruitment curve associated with a lowering of the RMT; (b) reduced or even absent early and late ICI; (c) reduced CSP lengthening with increasing TMS intensity. ICF was not affected. RMT increased and the MEP recruitment curve became less steep with longer disease duration, but they did not correlate with the motor deficit, the type of motoneuron affection and the decrease of ICI. Impairment of early and late ICI were significantly correlated to each other, to disease severity and to clinical evidence of upper motor neuron involvement. CONCLUSIONS: Different and partially independent mechanisms contribute to motor cortex hyperexcitability in ALS. The increased gain in MEP recruitment with a lowering of the RMT appears to be a primary event reflecting an increase in the strength of corticospinal projections, probably related to changes in the ion-channel permeability of the neuronal membrane. On the other hand, inhibitory functions linked to multiple neurotransmitter systems decline with disease progression. Both depletion of specific subpopulations of intracortical GABAergic neurons and mechanisms involved in motor cortex reorganization following progressive neuronal loss have been considered to account for the impaired inhibition. The clarification of the importance of these factors in the pathogenesis of ALS may have diagnostic and therapeutic implications.

Adult↗

PubMed1998

The human motor cortex after incomplete spinal cord injury: an investigation using proton magnetic resonance spectroscopy.

OBJECTIVES: (1) A biochemical investigation of the motor cortex in patients with incomplete spinal cord injury and normal control subjects using proton magnetic resonance spectroscopy (MRS). (2) To relate any altered biochemistry with the physiological changes in corticospinal function seen after spinal cord injury. METHODS: A group of six patients with incomplete spinal cord injury who showed good recovery of motor function were selected. The patients were compared with five healthy control subjects. Electromyographic (EMG) responses of thenar muscles to transcranial magnetic stimulation (TMS) of the motor cortex showed that inhibition of cortical output was weaker in the patients than the controls. Proton MRS data were collected from a plane at the level of the centrum semiovale. Two 4.5 cm3 voxels in the motor cortex and a third voxel in the ipsilateral occipital cortex were examined in the patients and control subjects. RESULTS: The mean level of N-acetylaspartate (NAA), expressed relative to the creatine (Cr) peak (NAA/Cr), was significantly increased in the motor cortex of the patients compared with their ipsilateral occipital cortex or either cortical area in the controls. No differences between patients and controls were seen for any of the other metabolite peaks (choline (Cho), glutamate/glutamine (Glx) or the aspartate component of NAA (AspNAA)) relative to Cr. Choline relative to Cr (Cho/Cr) was higher in the motor cortex of the control subjects than in their ipsilateral occipital cortex. This difference was not present in the patients. CONCLUSIONS: Raised NAA/Cr in the motor cortex of the patients probably results from increased NAA rather than a decrease in the more stable Cr. The possible relevance of a raised NAA/Cr ratio is discussed, particularly with regard to the changed corticospinal physiology and the functional recovery seen in the patients.

Adult↗

PubMed2001

Stronger reactivity of the human primary motor cortex during observation of live rather than video motor acts.

The monkey premotor cortex contains neurons that are activated both when the monkey performs motor acts and when he observes actions made by others. A similar mirror neuron system, involving several brain areas, has been found in humans. We recorded neuromagnetic oscillatory activity from the primary motor cortex of 10 healthy subjects when they observed live and videotaped finger movements. The left and right median nerves were stimulated alternatingly and the poststimulus level of the approximately 20 Hz rhythm was quantified. Compared with the rest condition, the approximately 20 Hz rhythm was dampened 15-19% more when the subjects observed live rather than videotaped hand movements, indicating stronger activation of the primary motor cortex. These results suggest that the human mirror neuron system differentiates natural and artificially presented movements.

Adult↗

PubMed2003

Long-Evans and Sprague-Dawley rats have similar skilled reaching success and limb representations in motor cortex but different movements: some cautionary insights into the selection of rat strains for neurobiological motor research.

Many rat strains are used for neurobiological studies of nervous system function and behavior. The most widely used strain for studies of the neural basis of movement is the out bred, pigmented Long-Evans strain, while the most widely used strains for the study of movement impairments in neurological disease are out bred albino rats, including Sprague-Dawley rats. Although previous research has indicated that there are strain differences in skilled movements displayed by different rat strains, there has been no explicit comparison of the Long-Evans and Sprague-Dawley strains. This was the purpose of the present study. The rats were video recorded as they learned to reach for single food pellets and the video records were subjected to frame-by-frame analysis. Component movements of reaching were scored using a system derived from Eshkol-Wachman Movement Notation (EWMN). The quality of movements was described using Laban Movement Analysis (LMA). Forelimb representations in motor cortex were defined electrophysiologically. Acquisition scores and success in reaching did not differ between the two strains, nor did the topographical representation of the forelimb in motor cortex. Long-Evans and Sprague-Dawley rats did differ in the movements used for reaching and on the quality of their movements. The movements of Sprague-Dawley rats resembled the movements of Long-Evans rats with motor system injury. That rat strains can show both quantitative and qualitative differences in movement is useful for the understanding of the genetic, neural, and behavioral organization of the motor system. The results are also relevant to the question of appropriateness of particular rat strains for studies of neurological diseases and the effects of albinism on motor behavior, and suggest that some of the most widely used rat strains for neurological investigations may be less than appropriate.

Animals↗

PubMed2005

Arm movements evoked by electrical stimulation in the motor cortex of monkeys.

Electrical stimulation of the motor cortex in monkeys can evoke complex, multijoint movements including movements of the arm and hand. In this study, we examined these movements in detail and tested whether they showed adaptability to differing circumstances such as to a weight added to the hand. Electrical microstimulation was applied to motor cortex using pulse trains of 500-ms duration (matching the approximate duration of a reach). Arm movement was measured using a high-resolution three-dimensional tracking system. Movement latencies averaged 80.2 ms. Speed profiles were typically smooth and bell-shaped, and the peak speed covaried with movement distance. Stimulation generally evoked a specific final hand position. The convergence of the hand from disparate starting positions to a narrow range of final positions was statistically significant for every site tested (91/91). When a weight was fixed to the hand, for some stimulation sites (74%), the evoked movement appeared to compensate for the weight in that the hand was lifted to a similar final location. For other stimulation sites (26%), the weight caused a significant reduction in final hand height. For about one-half of the sites (54%), the variation in movement of each joint appeared to compensate for the variation in the other joints in a manner that stabilized the hand in a restricted region of space. These findings suggest that at least some of the stimulation-evoked movements reflect relatively high-level, adaptable motor plans.

Action Potentials↗

PubMedDate not supplied

A common somaesthetic pathway to red nucleus and motor cortex.

Comparable short latency somaesthetic responses have been observed in the red nucleus and the motor cortex. Since previous experiments showed that a ventral spinal ascending pathway could account for red nucleus responses, the present experiments were designed to establish whether the same pathway could also transmit the short latency peripheral inputs to motor cortex. Two experimental data argue in favour of a such organization: (1) Using the collision technique, it was demonstrated that somaesthetic responses recorded in red nucleus cells are transmitted by collaterals of ascending fibres ending in the ventrobasal thalamus. (2) Intracellular recordings from identified corticospinal cells were performed on cats acutely prepared on section of the brachium conjunctivum and the dorsal columns of the spinal cord. Cortico-cortical connections to motor cortex were also eliminated by lesions of the ipsilateral sensory cortex and contralateral motor cortex. With this preparation it is still possible to record postsynaptic potentials after stimulation of primary afferent fibres in the dorsal columns, caudally to their section. The existence of these somaesthetic parallel inputs to rubro- and corticospinal cells suggest that the ongoing movement might be corrected on-line by these two pathways.

Afferent Pathways↗

PubMed1989

Number and size of neurons and synapses in the motor cortex of cats raised in different environmental complexities.

In a previous study we have shown that the richness of the environment affects the number of neurons, the size of their nuclei, the number of round-asymmetrical synapses per neuron, the numerical density (number per unit volume; NV) of flat-symmetrical synaptic contacts, their number per neuron and their size in the visual cortex of cats. Of these, the number of flat-symmetrical synapses per unit volume is particularly affected (there are nearly twice as many per mm3 in the impoverished cortex). Several studies in the rat have shown that environmentally induced changes in cortical thickness occur in the occipital regions but are much smaller or absent in the frontal regions. In order to determine if the cat motor cortex is also resistant to environmental changes, we have estimated the number and size of neurons and of synapses in individual laminae of motor cortex, area 4 gamma, in six pairs of cats raised either in a colony (EC: enriched condition) or in isolation (IC: impoverished condition). For the neurons, we have found that the numerical density (28,900 neurons per mm3 of EC and 29,500 neurons/mm3 of IC motor cortex), the number under 1 mm2 of cortical surface (49,400 and 49,200 in EC and IC cats), and the size of the neuronal nuclei (82 vs 80 microns2 in EC and IC animals) were not significantly affected. The number of flat-symmetrical synapses per neuron (1,470 in EC vs 1,400 in IC cortex), their size (0.33 micron in both groups) and even their number per unit volume, which was so greatly affected in the visual cortex, remains unchanged (43 million/mm3 and 41 million/mm3 in EC and IC motor cortex). We did find however, a significant difference (p less than 0.05) in the numerical density of round-asymmetrical synapses which is 13% greater in the impoverished motor cortex (216 million/mm3 in EC vs 247 million/mm3 in IC cortex). Our results confirm that the motor cortex is much less affected by the richness of the environment than the visual cortex: In fact, the cat motor cortex is hardly affected at all. Furthermore our results represent the most complete data presently available on the number and size of neurons and synapses in individual laminae of the cat motor cortex.

Animals↗

PubMed1998

A model of reaching dynamics in primary motor cortex.

Features of virtually all voluntary movements are represented in the primary motor cortex. The movements can be ongoing, imminent, delayed, or imagined. Our goal was to investigate the dynamics of movement representation in the motor cortex. To do this we trained a fully recurrent neural network to continually output the direction and magnitude of movements required to reach randomly changing targets. Model neurons developed preferred directions and other properties similar to real motor cortical neurons. The key finding is that when the target for a reaching movement changes location, the ensemble representation of the movement changes nearly monotonically, and the individual neurons comprising the representation exhibit strong, nonmonotonic transients. These transients serve as internal recurrent signals that force the ensemble representation to change more rapidly than if it were limited by the time constants of individual neurons. These transients, if they exist, could be observed in experiments that require only slight modifications of the standard paradigm used to investigate movement representation in the motor cortex.

Algorithms↗

PubMed2003

Neural responses in motor cortex and area 7a to real and apparent motion.

The neural activity in area 7a and the arm area of motor cortex was recorded while real or path-guided apparent motion stimuli were presented to behaving monkeys in the absence of a motor response. A smooth stimulus motion was produced in the real motion condition, whereas in the apparent motion condition five stimuli were flashed successively at the vertices of a regular pentagon. The stimuli moved along a low contrast circular path with one of five speeds (180-540 deg/s). We found strong neural responses to real and apparent motion in area 7a and motor cortex. In the motor cortex, a substantial population of neurons showed a selective response to real moving stimuli in the absence of a motor response. This activity was modulated in some cases by the stimulus speed, and some of the neurons showed a response during a particular part of the circular trajectory of the stimulus; the preferred stimulus angular locations were evenly distributed across this neuronal ensemble. It is likely that these neural signals are continuously available to the motor cortex in order to generate responses that demand immediate action. In area 7a, two overlapping populations of neurons were observed. The first comprised cells the activity of which was tuned to the angular location of a circularly moving stimulus in the real motion condition. These cells also responded to apparent motion at high stimulus speeds. A visual receptive field analysis showed that the angular tuning in most of the area 7a neurons did not depend on the spatial location of the stimulus in relation to their receptive field. The second population was selective to apparent moving stimuli and showed a periodic entrainment of activation with the period of the inter-stimulus interval of the flashing dots. Both the angular location and the inter-stimulus interval neural signals can be used to generate precise behavioral responses towards real or apparent moving stimuli.

Action Potentials↗

PubMed1991

Short-term memory performance with magnetic stimulation of the motor cortex.

Whether transcranial magnetic stimulation of the motor cortex has an influence on memory was investigated. In a first experiment with 21 healthy volunteers six pronounceable nonsense words were visually presented, immediately followed by a magnetic stimulus. There were three blocks of stimulation with field intensities of 60, 80 and 100% (referring to a maximal intensity of 2 Tesla), each block comprising six magnetic stimuli and six nonsense words. After each block there was a free recall test and at the end another free recall trial as well as a multiple-choice recognition test for all 18 words. Eighteen subjects served as controls, undergoing the same procedure, except that the field intensity was zero. A significant but small reduction of short-term memory performance was observed only for 100% field intensity. In a second experiment with 16 subjects who had not participated in experiment I, the effect of 100% intensity cortical magnetic stimulation was compared with a control stimulation over the cervical spine. There was no difference in free recall or in the multiple-choice test between the sites of stimulation, suggesting that the difference in the 100% intensity block in experiment I was not due to a specific cortical effect of the magnetic field on memory function. With respect to the effect on memory functions, transcranial magnetic stimulation of the motor cortex is thought to be a safe method.

Adult↗

PubMed2000

Motor cortex stimulation for central and peripheral deafferentation pain. Report of eight cases.

The authors tested a modified motor cortex stimulation protocol for treatment of central and peripheral types of deafferentation pain. Four patients with thalamic pain and four with peripheral deafferentation pain were studied. Preoperative pharmacological tests of pain relief were performed using phentolamine, lidocaine, ketamine, thiopental, and placebo. In five patients we placed a 20- or 40-electrode grid in the subdural space to determine the best stimulation point for pain relief for a few weeks before definitive placement of a four-electrode array. In three patients, the four-electrode array was implanted in the interhemispheric fissure as a one-stage procedure to treat lower-extremity pain. In two patients with pain extending from the extremity to the trunk or hip, dual devices were implanted to drive two electrodes. Six of eight patients experienced pain reduction (two each with excellent, good, and fair relief) from motor cortex stimulation. No correlation was apparent between pharmacological test results and the effectiveness of motor cortex stimulation. Patients with peripheral deafferentation pain, including two with phantom-limb pain and two with brachial plexus injury, attained pain relief from motor cortex stimulation, with excellent results in two cases. Testing performed with a subdural multiple-electrode grid was helpful in locating the best stimulation point for pain relief. Motor cortex stimulation may be effective for treating peripheral as well as central deafferentation pain.

Aged↗

PubMed2005

Quantification of motor cortex activity and full-body biomechanics during unconstrained locomotion.

Recent progress in the understanding of motor cortex function has been achieved primarily by simultaneously recording motor cortex neuron activity and the movement kinematics of the corresponding limb. We have expanded this approach by combining high-quality cortical single-unit activity recordings with synchronized recordings of full-body kinematics and kinetics in the freely behaving cat. The method is illustrated by selected results obtained from two cats tested while walking on a flat surface. Using this method, the activity of 43 pyramidal tract neurons (PTNs) was recorded, averaged over 10 bins of a locomotion cycle, and compared with full-body mechanics by means of principal component and multivariate linear regression analyses. Patterns of 24 PTNs (56%) and 219 biomechanical variables (73%) were classified into just four groups of inter-correlated variables that accounted for 91% of the total variance, indicating that many of the recorded variables had similar patterns. The ensemble activity of different groups of two to eight PTNs accurately predicted the 10-bin patterns of all biomechanical variables (neural decoding) and vice versa; different small groups of mechanical variables accurately predicted the 10-bin pattern of each PTN (neural encoding). We conclude that comparison of motor cortex activity with full-body biomechanics may be a useful tool in further elucidating the function of the motor cortex.

Action Potentials↗

PubMed1997

Increased mitochondrial superoxide dismutase activity in Parkinson's disease but not amyotrophic lateral sclerosis motor cortex.

Oxidative stress may contribute to the neurodegenerative process in amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). Motor cortex in PD is not affected and its inclusion in studies of free radical involvement in ALS pathogenesis could help elucidate whether oxidative stress is disease specific or a more widespread phenomenon present in the neurodegeneration. We have measured cytosolic and mitochondrial isoforms of superoxide dismutase (SOD), antioxidant enzymes involved in primary defence against free radical damage, in motor cortex of six patients with sporadic form of ALS (SALS), eight with PD and eight normal control subjects. We have found no difference in the activities of cytosolic and mitochondrial SOD between SALS and control motor cortex. Mitochondrial SOD activity in PD motor cortex was, however, significantly higher than in SALS and control motor cortex whereas activity of cytosolic SOD was lower than in two other groups although the differences were not statistically significant. Our findings indicate the presence of an altered antioxidant defence system in PD but not ALS upper motor neurons, suggesting that oxidative stress may be a widespread phenomenon in PD.

Adult↗

PubMed1994

Some physiological characteristics of motor cortex neurons of aged rabbits.

Neurophysiological alterations occurring in the motor cortex of aged rabbits have been examined. Experiments were performed on rabbits of three age groups: one year old (young), four to five years old (middle-aged) and six to seven years old (aged). Extracellular unit activity was recorded in the motor projection of a forelimb. Several sessions of rhythmic (2 Hz) electrocutaneous stimulation were delivered to contralateral forelimb. The neuronal activity was recorded before and after rhythmic stimulation. We also measured the firing rate during spontaneous electromyogram activity of the extensor carpi radialis. Neurons having slow spontaneous firing activity were predominant in aged rabbits as compared with young animals. In young animals the highest values of spontaneous firing rate (15-20 impulses/s) were observed in neurons related to movement. In aged rabbits spontaneous firing rate of movement-related neurons did not exceed 16 impulses/s. During spontaneous movements of extensor carpi radialis, the level of neuronal activity in young rabbits was twice as high as that in aged ones. In young rabbits after rhythmic electrocutaneous stimulation of a forelimb, 20% of recorded neurons exhibited periodic fluctuations in firing rate with the period of preceding stimulation. The repeated stimulation sessions increased the number of rhythmic firing neurons to 40-50%. In aged rabbits, patterns of firing activity of motor cortex neurons did not change significantly after several sessions of rhythmic electrocutaneous stimulation. Decreased neuronal excitability may be the cause of functional alterations in motor cortex neurons of aged rabbits.

Aging↗

PubMed2003

Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human.

Transcranially applied weak direct currents are capable of modulating motor cortical excitability in the human. Anodal stimulation enhances excitability, cathodal stimulation diminishes it. Cortical excitability changes accompany motor learning. Here we show that weak direct currents are capable of improving implicit motor learning in the human. During performance of a serial reaction time task, the primary motor cortex, premotor, or prefrontal cortices were stimulated contralaterally to the performing hand. Anodal stimulation of the primary motor cortex resulted in increased performance, whereas stimulation of the remaining cortices had no effect. We conclude that the primary motor cortex is involved in the acquisition and early consolidation phase of implicit motor learning.

Analysis of Variance↗