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Redundancy and synergy of neuronal ensembles in motor cortex.

We examined the ability of neuronal ensembles from rat motor cortex to predict behavioral performance during a reaction time task. We found that neurons that were the best individual predictors of task performance were not necessarily the neurons that contributed the most predictive information to an ensemble of neurons. To understand this result, we applied a framework for quantifying statistical relationships between neurons (Schneidman et al., 2003) to all possible combinations of neurons within our ensembles. We found that almost all neurons (96%) contributed redundant predictive information to the ensembles. This redundancy resulted in the maintenance of predictive information despite the removal of many neurons from each ensemble. Moreover, the balance of synergistic and redundant interactions depended on the number of neurons in the ensemble. Small ensembles could exhibit synergistic interactions (e.g., 23 +/- 9% of ensembles with two neurons were synergistic). In contrast, larger ensembles exhibited mostly redundant interactions (e.g., 99 +/- 0.1% of ensembles with eight neurons were redundant). We discuss these results with regard to constraints on interpreting neuronal ensemble data and with respect to motor cortex involvement in reaction time performance.

Action Potentials↗

The NMDA antagonist memantine affects training induced motor cortex plasticity--a study using transcranial magnetic stimulation.

BACKGROUND: Training of a repetitive synchronised movement of two limb muscles leads to short-term plastic changes in the primary motor cortex, which can be assessed by transcranial magnetic stimulation (TMS) mapping. We used this paradigm to study the effect of memantine, a NDMA antagonist, on short-term motor cortex plasticity in 20 healthy human subjects, and we were especially interested in possible differential effects of different treatment regimens. In a randomised double-blinded cross over study design we therefore administered placebo or memantine either as a single dosage or as an ascending dosage over 8 days. Before and after one hour of motor training, which consisted of a repetitive co-contraction of the abductor pollicis brevis (APB) and the deltoid muscle, we assessed the motor output map of the APB muscle by TMS under the different conditions. RESULTS: We found a significant medial shift of the APB motor output map after training in the placebo condition, indicating training-induced short-term plastic changes in the motor cortex. A single dosage of memantine had no significant effect on this training-induced plasticity, whereas memantine administered in an ascending dosage over 8 days was able to block the cortical effect of the motor training. The memantine serum levels after 8 days were markedly higher than the serum levels after a single dosage of memantine, but there was no individual correlation between the shift of the motor output map and the memantine serum level. Besides, repeated administration of a low memantine dosage also led to an effective blockade of training-induced cortical plasticity in spite of serum levels comparable to those reached after single dose administration, suggesting that the repeated administration was more important for the blocking effect than the memantine serum levels. CONCLUSION: We conclude that the NMDA-antagonist memantine is able to block training-induced motor cortex plasticity when administered over 8 days, but not after administration of a single dose. This differential effect might be mainly due to the prolonged action of memantine at the NMDA receptor. These findings must be considered if clinical studies are designed, which aim at evaluating the potency of memantine to prevent "maladaptive" plasticity, e.g. after limb amputation.

Adult↗

The motor cortex: anatomic substrates of function.

This article provides a firm foundation in the gross and microscopic anatomy of the motor cortex. It reviews the sites, Brodmann regions, normal function, and deficits associated with the primary motor cortex, supplementary motor area, presupplementary motor area, and the cingulate motor area in preparation for understanding the functional MR imaging studies that are reviewed in the later articles.

Brain Mapping↗

Characterising the central mechanisms of sensory modulation in human swallowing motor cortex.

OBJECTIVE: Pharyngeal stimulation can induce remarkable increases in the excitability of swallowing motor cortex, which is associated with short-term improvements in swallowing behaviour in dysphagic stroke patients. However, the mechanism by which this input induces cortical change remains unclear. Our aims were to explore the stimulus-induced facilitation of the cortico-bulbar projections to swallowing musculature and examine how input from the pharynx interacts with swallowing motor cortex. METHODS: In 8 healthy subjects, a transcranial magnetic stimulation (TMS) paired-pulse investigation was performed comprising a single conditioning electrical pharyngeal stimulus (pulse width 0.2 ms, 240 V) followed by cortical TMS at inter-stimulus intervals (ISI) of 10-100 ms. Pharyngeal sensory evoked potentials (PSEP) were also measured over the vertex. In 6 subjects whole-brain magnetoencephalography (MEG) was further acquired following pharyngeal stimulation. RESULTS: TMS evoked pharyngeal motor evoked potentials were facilitated by the pharyngeal stimulus at ISI between 50 and 80 ms (Delta mean increase: 47+/-6%, P < 0.05). This correlated with the peak latency of the P1 component of the PSEP (mean 79.6+/-8.5 ms). MEG confirmed that the equivalent P1 peak activities were localised to caudolateral sensory and motor cortices (BA 4, 1, 2). CONCLUSIONS: Facilitation of the cortico-bulbar pathway to pharyngeal stimulation relates to coincident afferent input to sensorimotor cortex. SIGNIFICANCE: These findings have mechanistic importance on how pharyngeal stimulation may increase motor excitability and provide guidance on temporal windows for future manipulations of swallowing motor cortex.

Adult↗

Studies on the corticospinal control of human walking. I. Responses to focal transcranial magnetic stimulation of the motor cortex.

Experiments were done to determine the extent to which the corticospinal tract is linked with the segmental motor circuits controlling ankle flexors and extensors during human walking compared with voluntary motor tasks requiring attention to the level of motor activity. The motor cortex was activated transcranially using a focal magnetic stimulation coil. For each subject, the entire input-output (I-O) curve [i.e., the integral of the motor evoked-potential (MEP) versus stimulus strength] was measured during a prescribed tonic voluntary contraction of either the tibialis anterior (TA) or the soleus. Similarly, I-O curves were measured in the early part of the swing phase, or in the early part of the stance phase of walking. The I-O data points were fitted by the Boltzmann sigmoidal function, which accounted for >/=80% of total data variance. There was no statistically significant difference between the I-O curves of the TA measured during voluntary ankle dorsiflexion or during the swing phase of walking, at matched levels of background electromyographic (EMG) activity. Additionally, there was no significant difference in the relation between the coefficient of variation and the amplitude of the MEPs measured in each task, respectively. In comparison, during the stance phase of walking the soleus MEPs were reduced on average by 26% compared with their size during voluntary ankle plantarflexion. Furthermore, during stance the MEPs in the inactive TA were enhanced relative to their size during voluntary ankle plantarflexion and in four of six subjects the TA MEPs were larger than those of the soleus. Finally, stimulation of the motor cortex at various phases of the step cycle did not reset the cycle. The time of the next step occurred at the expected moment, as determined from the phase-resetting curve. One interpretation of this result is that the motor cortex may not be part of the central neural system involved in timing the motor bursts during the step cycle. We suggest that during walking the corticospinal tract is more closely linked with the segmental motor circuits controlling the flexor, TA, than it is with those controlling the extensor, soleus. However, during voluntary tasks requiring attention to the level of motor activity, it is equally linked with the segmental motor circuits of ankle flexors or extensors.

Adult↗

The motor cortex and the coding of force.

The relation of cellular activity in the motor cortex to the direction of two-dimensional isometric force was investigated under dynamic conditions in monkeys. A task was designed so that three force variables were dissociated: the force exerted by the subject, the net force, and the change in force. Recordings of neuronal activity in the motor cortex revealed that the activity of single cells was directionally tuned and that this tuning was invariant across different directions of a bias force. Cell activity was not related to the direction of force exerted by the subject, which changed drastically as the bias force changed. In contrast, the direction of net force, the direction of force change, and the visually instructed direction all remained quite invariant and congruent and could be the directional variables, alone or in combination, to which cell activity might relate.

Animals↗

Chronic motor cortex stimulation for central deafferentation pain: experience with bulbar pain secondary to Wallenberg syndrome.

Six patients with bulbar pain caused by lateral medullary infarct were treated by stimulation therapy. Dysesthesia on the opposite side of the body was subjected to stimulation therapy in these patients. Of the subjects, 4 underwent thalamic stimulation and 3 were treated by motor cortex stimulation; the effects of both thalamic and motor cortex stimulation were investigated in 1 patient. No satisfactory pain control was obtained by thalamic stimulation in any of the patients in this series. In contrast, 2 of the 3 patients treated by motor cortex stimulation reported satisfactory pain control. The pain inhibition usually occurred at intensities below the threshold for the production of muscle contraction (pulse duration, 0.1-0.5 ms; intensity, 3-8 V). This finding was consistent with our previous observations made in a series of patients with thalamic pain, indicating that motor cortex stimulation is significantly more useful than thalamic stimulation for controlling deafferentation pain secondary to central nervous system lesions. We discuss the possibility that better control of deafferentation pain may be provided by stimulation at a level more rostral to the site of deafferentation.

Adult↗

Short latency facilitation between pairs of threshold magnetic stimuli applied to human motor cortex.

Pairs of threshold magnetic stimuli were applied over the motor cortex at interstimulus intervals of 1-6 ms, and EMG responses recorded from the relaxed or active first dorsal interosseous muscle of 7 normal subjects. In relaxed subjects, when the interval between the stimuli was around 1.0-1.5 ms, 2.5-3.0 ms or 4.5 ms or later, the size of the response to the pair of stimuli was much greater than the algebraic sum of the response to each stimulus alone. During contraction, fewer peaks of facilitation were observed. Facilitation was evident if the stimuli were 0.9-1.1 times threshold in the relaxed state, and 1.0-1.1 times threshold during voluntary contraction. Experiments using either magnetic followed by anodal electric stimulation, or pairs of anodal electric stimuli, suggested that the facilitation most likely occurred within the cerebral motor cortex. Given the timings at which facilitation is prominent, it seems likely that it reflects interactions between circuits normally responsible for production of I-waves.

Adult↗

Displacement of central sulcus in cerebral arteriovenous malformation situated in the peri-motor cortex as assessed by magnetoencephalographic study.

BACKGROUND: Intra-operative monitoring of the position of the central sulcus (CS) is indispensable to properly treat a peri-motor cortex lesion. Noninvasive preoperative studies for identification of CS are also needed for choosing the optimal operative procedure. Magneto-encephalography (MEG) has recently been introduced for non-invasive preoperative investigation and cortical functional mapping. METHODS: Stereotactic mapping of functional CS anatomy was performed preoperatively on 13 subjects using somatosensory evoked fields with MRI-linked whole head MEG system. All subjects had a left sided peri-motor cortex lesion with diagnoses including the following conditions: three arteriovenous malformations (AVM), seven gliomas, three meningiomas. FINDINGS: Functional CS in supratentorial brain tumor and parietal AVM cases corresponded with anatomical CS identified by MRI. But the AVM cases in whom the nidus was situated within the peri-motor cortex showed discrepancies between anatomical CS and functional CS. INTERPRETATION: Careful consideration of the operative procedure combined with non-invasive cortical functional mapping is needed to optimally treat AVM and congenital brain lesions situated in the anatomical peri-motor cortex.

Adolescent↗

Resonance (approximately 10 Hz) of excitatory networks in motor cortex: effects of voltage-dependent ion channel blockers.

The motor cortex generates synchronous network oscillations at frequencies between 7 and 14 Hz during disinhibition or low [Mg2+]o buffers, but the underlying mechanisms are poorly understood. These oscillations, termed here approximately 10 Hz oscillations, are generated by a purely excitatory network of interconnected pyramidal cells because they are robust in the absence of GABAergic transmission. It is likely that specific voltage-dependent currents expressed in those cells contribute to the generation of approximately 10 Hz oscillations. We tested the effects of different drugs known to suppress certain voltage-dependent currents. The results revealed that drugs that suppress the low-threshold calcium current and the hyperpolarization-activated cation current are not critically involved in the generation of approximately 10 Hz oscillations. Interestingly, drugs known to suppress the persistent sodium current abolished approximately 10 Hz oscillations. Furthermore, blockers of K+ channels had significant effects on the oscillations. In particular, blockers of the M-current abolished the oscillations. Also, blockers of both non-inactivating and slowly inactivating voltage-dependent K+ currents abolished approximately 10 Hz oscillations. The results indicate that specific voltage-dependent non-inactivating K+ currents, such as the M-current, and persistent sodium currents are critically involved in generating approximately 10 Hz oscillations of excitatory motor cortex networks.

Anesthetics, Local↗

Correlation of neuronal cell body size in motor cortex and hippocampus with body height, body weight, and axonal length.

This study examined the comparative effects of body height and body weight on the neuronal cell size in humans and investigated their possible mechanisms. A total of 21 cases between the ages of 20 and 40 years were studied. Data on body height, body weight, and neuropathology were obtained from autopsy records. Mean cross sectional areas of cell bodies for 30 normal neurons were determined for the motor cortex projecting to lumbar spinal cord segments (L) 1-4 (Betz cells) as well as various regions of the hippocampus. Approximate axonal length of the motor neuron studied was measured from motor cortex to L2. We found that only motor cortex neuronal cell body size was significantly proportional to body height and the respective axonal length (p < .05). The findings indicate that: 1) body height has a greater effect than body weight on the motor neuron cell size, probably because of its association with axonal length; 2) the effect is regional (motor cortex) rather than general.

Adult↗

Correlation of neural discharge with pattern and force of muscular activity, joint position, and direction of intended next movement in motor cortex and cerebellum.

1. Monkeys were trained to grasp a rod movable in a horizontal arc (Fig. 1), and to hold the rod by angulation of the wrist in each of three positions (A,B, C). A maintained load was placed on the rod alternately to oppose flexion and extension. At a light signal, the monkey had to move to the next position in a prescribed sequence (ABCBABCBA, ETC.). The task was designed to dissociate, while holding in position, the following variables: 1) pattern of muscular activity in the forearm required to hold the wrist in position, determined by the direction of the load (flexor or extensor muscles); 2) position of the rod, and thus angulation of the wrist joint (A, B, and C); and 3) set for the direction of the intended next movement (flexor or extensor). These variables are subsequently referred to as MPAT, JPOS, and DSET, respectively. 2. After training, recordings were made of the EMG activity of muscles used in the task and of the discharge of single neurons in the motor cortex of the cerebrum and the interposed and dentate nuclei of the cerebellum. 3. While holding the wrist in position, EMG and interpositus behaved uniformly, with higher discharge frequency under load in one direction and lower discharge frequency under load in the opposite direction. This relation was relatively independent of the position held and of the direction of the intended next movement. Thus, interpositus and EMG both seemed best related to the MPAT variable, as opposed to JPOS and DSET variables. By contrast, neurons in motor cortex and in dentate fell into three categories: one category discharged in relation to the pattern of muscular activity (MPAT), a second to the position of the wrist (JPOS), and a third to the direction of the intended next movement (DSET). While MPAT neurons formed a distinct dissociated group, neurons that were best related to JPOS were often related to DSET, and vice versa. 4. A few of the MPAT neurons in interpositus and motor cortex were further studied by varying the magnitude (as well as the direction) of the loads. Both interpositus and motor cortex MPAT neurons changed firing frequency in relation to the magnitude of load, and though few neurons were thus studied, the relation seemed clearer for interpositus than for motor cortex. 5. Anatomically, the three types of neurons thus classified by firing pattern during the hold periods were intermixed in the arm area of motor cortex. In dentate and interpositus, those neurons thus related to the performance were localized to a narrow strip across the posterior part of both nuclei. Neurons apparently related to eye and drinking movements were located more posteriorly still, suggesting somatotopic representation.

Animals↗

Chronic motor cortex stimulation in the treatment of central and neuropathic pain. Correlations between clinical, electrophysiological and anatomical data.

Thirty-two patients with refractory central and neuropathic pain of peripheral origin were treated by chronic stimulation of the motor cortex between May 1993 and January 1997. The mean follow-up was 27.3 months. The first 24 patients were operated according to the technique described by Tsubokawa. The last 13 cases (eight new patients and five reinterventions) were operated by a technique including localisation by superficial CT reconstruction of the central region and neuronavigator guidance. The position of the central sulcus was confirmed by the use of intraoperative somatosensory evoked potentials. The somatotopic organisation of the motor cortex was established peroperatively by studying the motor responses at stimulation of the motor cortex through the dura. Ten of the 13 patients with central pain (77%) and ten of the 12 patients with neuropathic facial pain had experienced substantial pain relief (75%). One of the three patients with post-paraplegia pain was clearly improved. A satisfactory result was obtained in one patient with pain related to plexus avulsion and in one patient with pain related to intercostal herpes zooster. None of the patients developed epileptic seizures. The position of the stimulating poles effective on pain corresponded to the somatotopic representation of the motor cortex. The neuronavigator localisation and guidance technique proved to be most useful identifying the appropriate portion of the motor gyrus. It also allowed the establishment of reliable correlations between electrophysiological-clinical and anatomical data which may be used to improve the clinical results and possibly to extend the indications of this technique.

Adult↗

[Neuronal specialization of the motor cortex in normal rabbits and following destruction of the visual cortex].

The activity of neurones of the anterolateral part of the motor cortex in food-acquisition behaviour was compared in two control rabbits and in three rabbits after the operation of bilateral ablation of the striatal cortex. In two of three operated rabbits the pattern of behavioural specialization lost considerably the specificity peculiar to the motor cortex (predominance of G-neurones activated in grasping of food), approaching (but not becoming identical) the pattern of specialization of the visual cortex neurones: the number of G-neurones decreased in a half, and the number of L-neurones (activated in connection with the acts of instrumental food-acquisition behaviour which animals were trained to in the experimental cage) was doubled. Changes of the activity were significantly less expressed in the third operated rabbit. The number of the neurones activated in food-acquisition behaviour in operated rabbits in comparison with the control ones was reduced in the upper layers of the cortex and increased in the lower layers. The resemblance is discussed of the basic processes of animals learning and behaviour recovery.

Animals↗

Motor cortex inhibition is not impaired in patients with Alzheimer's disease: evidence from paired transcranial magnetic stimulation.

Motor cortex excitability was studied by transcranial magnetic stimulation (TMS) in 17 patients with Alzheimer's disease (AD). Resting and active thresholds for TMS were significantly reduced in AD patients compared to young and aged healthy subjects. The maximum amplitude of the motor response evoked by TMS was also significantly increased in AD patients. We have tested if these changes are related to a modification of the short-lasting intracortical inhibition of the motor cortex by paired conditioning-test TMS. We found no significant differences between AD patients and aged healthy subjects even if there is a slight but significant difference between aged and young normal subjects. We conclude that the modification of excitability of the motor cortex does not result from an impaired intracortical inhibition.

Adult↗

[Motor cortex stimulation for post-stroke pain using neuronavigation and evoked potentials: report of 3 cases].

Although motor cortex stimulation (MCS) has been accepted as an effective therapeutic option for central pain, the efficacy of MCS widely varies among previous reports. In this report, we describe our recent trial for successful MCS in 3 patients with central pain due to cerebral stroke. Medical treatments were transiently effective, but gradually became ineffective in all of the cases. During surgery, the appropriate cortical target was determined by using neuronavigation, somatosensory evoked potential (SEP), and motor evoked potential (MEP). A flat, four-plate electrode was positioned on the dura mater parallel to the motor cortex. After surgery, pain almost resolved in 2 of 3 patients and markedly improved in another. The pain relief depended on their motor function. These findings strongly suggest that both patient selection and intraoperative monitoring for targeting the motor cortex are quite important for successful MCS, although further studies were essential.

Aged↗

Pyramidal cell abnormalities in the motor cortex of a child with Down's syndrome. A Golgi study.

The neuronal organization of the motor cortex of a 19-month old child with Down's syndrome (mongolism) has been studied with the rapid Golgi method. This congenital syndrome, also known as 21 Trisomy is caused by a chromosomal abnormality consisting of the presence of an extra chromosome in the group 21. Various structural abnormalities have been found in the dendritic spines (postsynaptic structures) of the pyramidal neurons of the motor cortex of this child. The axo-spinous synapses of these neurons are considered to be altered by these spine abnormalities. In addition, a peculiar form of intrinsic vacuolar change affecting the dendrites and scattered neuronal fragmentation and necrosis have also been found. At least three different types of abnormality involving the spines--(the unusually long spine, the very short spine and a reduction in the number of spines)--are recognized among the pyramidal cells of the motor cortex. It is postulated herein: that a basic anomaly, possibly related to the genetic disorder affects primarily some cortical neurons which undergo progressive degenerative changes terminating in cell fragmentation and death. The different spine abnormalities are considered to represent various developmental stages of the common genetic anomaly. These changes might be structural correlates of the motor incoordination and mental retardation which are characteristic of this genetic disorder, but, final conclusions should await the investigation of other cases with this or similar methods capable of demonstrating the normal as well as the abnormal structural organization of the human cerebral cortex.

Dendrites↗

Effects of optic flow in motor cortex and area 7a.

Moving visual stimuli were presented to behaving monkeys who fixated their eyes and did not move their arm. The stimuli consisted of random dots moving coherently in eight different kinds of motion (right, left, up, downward, expansion, contraction, clockwise, and counterclockwise) and were presented in 25 square patches on a liquid crystal display projection screen. Neuronal activity in the arm area of the motor cortex and area 7a was significantly influenced by the visual stimulation, as assessed using an ANOVA. The percentage of cells with a statistically significant effect of visual stimulation was 3 times greater in area 7a (370/587, 63%) than in motor cortex (148/693, 21.4%). With respect to stimulus properties, its location and kind of motion had differential effects on cell activity in the two areas. Specifically, the percentage of cells with a significant stimulus location effect was approximately 2.5 times higher in area 7a (311/370, 84%) than in motor cortex (48/148, 32.4%), whereas the percentage of cells with a significant stimulus motion effect was approximately 2 times higher in the motor cortex (79/148, 53.4%) than in area 7a (102/370, 27.6%). We also assessed the selectivity of responses to particular stimulus motions using a Poisson train analysis and determined the percentage of cells that showed activation in only one stimulus condition. This percentage was 2 times higher in the motor cortex (73.7%) than in area 7a (37.7%). Of all kinds of stimulus motion tested, responses to expanding optic flow were the strongest in both cortical areas. Finally, we compared the activation of motor cortical cells during visual stimulation to that observed during force exertion in a center --> out task. Of 514 cells analyzed for both the motor and visual tasks, 388 (75.5%) showed a significant relation to either or both tasks, as follows: 284/388 (73.2%) cells showed a significant relation only to the motor task, 27/388 (7%) cells showed a significant relation only to the visual task, whereas the remaining 77/388 (19.8%) cells showed significant relations to both tasks. Therefore a total of 361/514 (70.2%) cells were related to the motor task and 104/514 (20.2%) were related to the visual task. Finally, with respect to receptive fields (RFs), there was no clear visual receptive field structure in the motor cortical neuronal responses, in contrast to area 7a where RFs were present and could be modulated by the type of optic flow stimulus.

Animals↗