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Prediction of arm trajectory from a small number of neuron activities in the primary motor cortex.

Monkey arm movement was reconstructed from neuron activities recorded in the primary motor cortex (Ml). We recorded single neuron activities from a monkey's Ml, while the animal performed an arm reaching task. We also recorded electromyographic (EMG) activity and movement trajectories during the task. First, we reconstructed the EMG signals from the neuron activities. The EMG signals were reliably reconstructed with a linear summation of the neuron activities. Next, we reconstructed joint angles from the reconstructed EMG signals with an artificial neural network model. The reconstructed trajectories of the hand position and elbow position showed good correlation with the actual arm movement. This model appropriately reflected the anatomical characteristics.

Action Potentials↗

[Frequency analysis of motor reactions induced by stimulation of the motor cortex in unanaesthetized cats].

Frequency properties of muscle contraction evoked by macrostimulation of motor cortex were studied in chronic cats. Frequency- and amplitude-modulated stimulation pulse trains were used, alternating component of the induced muscle contraction was considered as output signal. Analysis of signal transformations in the system under study was performed with application of the method of harmonical linearization. Phase lag of the output signal was minimal at 0.2 Hz and ranged from 40 degrees to 90 degrees in various experiments. Phase lag and amplitude decrement were substantially increased at frequencies above 1-2 Hz. The mean value of the phase lag at a frequency of 5 Hz was about 180 degrees, the mean slope of amplitude characteristics in a 2-10 Hz range was equal to -12 dB/decade. It is supposed that certain correction of dynamic properties of the studied system could result from adaptation properties of neuronal firing.

Adaptation, Physiological↗

Epidural and subpial cortico-spinal potentials evoked by transcutaneous motor cortex stimulation during spinal cord surgery.

Cortico-spinal potentials (CSPs) to transcutaneous motor cortex stimulation were recorded epidurally and subpially in 8 patients undergoing spinal cord surgery. In 6 patients without cortico-spinal tract involvement, a CSP consisted of a direct (D) wave, which was followed by indirect (I) waves at a higher stimulus intensity. The D wave appeared at 25-50% of the maximum stimulus intensity. With increasing stimulus its amplitude levelled off between 10 and 30 microV when recorded epidurally. At high stimulus a prominent indirect potential (I' wave) appeared which followed the D wave after 2.2-3.6 msec. The D and I' wave conduction velocities calculated in 3 cases were identical -65, 70 and 80 m/sec. Subpial records had larger amplitudes than epidural ones but were of the same configuration. In 2 patients with spastic paraparesis the CSP changes were detected below the site of the cord lesion.

Adolescent↗

Input-output organization of the rat vibrissal motor cortex.

The afferent and efferent connections of the vibrissal area of the rat motor cortex (VMCx) were investigated by injecting Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase into the physiologically defined VMCx. The VMCx formed reciprocal connections with the primary and secondary somatosensory cortex, lateral and ventrolateral orbital cortex, retrosplenial cortex, and perirhinal cortex. These corticocortical afferents originated from cell bodies in layers II-III and V, and some afferents originated from cell bodies in layer VI of the primary sensory cortex. All of the VMCs efferents terminated in layers I and V or layers I-III and V. The VMCx also formed reciprocal connections with the ventrolateral, ventromedial and centrolateral nucleus, the lateral portion of the mediodorsal nucleus and the posterior complex of the thalamus. It projected bilaterally to the caudate putamen, primarily ipsilaterally to the superior colliculus, anterior pretectal nucleus, and pontine nucleus, and mainly contralaterally to the oral part of the spinotrigeminal nucleus and the reticular formation around the facial nerve nucleus. Finally, injections of PHA-L into the superior colliculus demonstrated that this structure projected contralaterally to the lateral part of the facial nerve nucleus. These data suggest that the VMCx plays a key role in sensorimotor integration, through its extensive interconnectivity with numerous brain structures, and may modulate orientation behaviors by relaying processed information to the superior colliculus.

Animals↗

Methamphetamine alters presynaptic glutamate immunoreactivity in the caudate nucleus and motor cortex.

It has been suggested that methamphetamine (METH)-induced neurotoxicity requires the activation of both dopamine (DA) and glutamate (GLU) systems. To investigate the possibility that METH-induced increases in extracellular GLU, as measured by in vivo microdialysis [Nash and Yamamoto (1992) Brain Res., 581:237-243], arise from neuronal stores, postembedding immunogold electron microscopy was used to measure the density of presynaptic GLU immunoreactivity within the striatum, the shell of the nucleus accumbens, and the motor cortex. Rats were treated with METH (5 mg/kg), or an equivalent volume of saline (SAL), every 2 h for a total of four injections. No ultrastructural evidence of terminal degeneration was observed. Significant decreases in the density of nerve terminal GLU immunolabeling occurred 12 h following METH administration within the primary motor cortex and the ventrolateral caudate/putamen, and a trend towards depletion was seen within the dorsolateral caudate/putamen. Although GLU immunolabeling within the shell of the nucleus accumbens was unaffected, DA content was decreased in all regions examined 1 week following METH treatment. The lack of degeneration, coupled with a partial recovery of DA levels, suggests that moderate doses of METH may inhibit DA biosynthesis without widespread terminal loss. Furthermore, METH administration results in a decrease in presynaptic GLU that correlates both temporally and anatomically with delayed GLU overflow, suggesting that neuronally derived GLU may play a role in METH-induced neurotoxicity. However, there does appear to be a dissociation between DA loss and altered GLU immunocytochemistry within the nucleus accumbens.

Animals↗

GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.

Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.

Adult↗

Conditioned changes of synaptic transmission in the motor cortex of the cat.

Intracellular recordings were made from 117 neurons in the motor cortex of anesthetized cats. The pyramidal tract (PT) and VL nucleus of thalamus were stimulated in order to activate the neurons from two directions. 1. PT cells were conditioned by antidromic trains (10--50 cps for 4--15 s) and by paired PT and VL stimuli with different intervals and sequences. The VL-EPSPs were examined before and after conditioning, to find differences in efficacy in giving rise to spikes. The conditioning procedures resulted in a remarkable facilitation of VL-EPSPs, manifesting itself as a significant rise of efficacy in generating spikes, a shortening of peak latency and in some cases, an enhancement of background firing. 2. In non-PT neurons the same conditioning procedures elicited heterosynaptic facilitation and a rise in firing activity. 3. Intracellularly injected square wave pulses also resulted in facilitation of VL-EPSPs. 4. Pairings of PT and VL stimuli were more effective than trains in evoking conditioned changes. 5. Plastic modifications were observed in the 13.7% of the neurons subjected to conditioning procedures. 6. The authors assume that synchronous activity of the pre- and postsynaptic neurons is a highly important condition for plastic changes in the efficacy of synaptic transmission.

Animals↗

Correlations between activity of motor cortex cells and arm muscles during operantly conditioned response patterns.

Monkey motor cortex cells were recorded during isolated, isometric contractions of each of four representative arm muscles -- a flexor and extensor of wrist and elbow -- and comparable response averages computed. Most cells were coactivated with several of the muscles; some fired the same way with all four and others with none. Results suggest that many precentral cells have a higher order relation to muscles than motoneurons. Operantly reinforced bursts of cell activity were associated with coactivation of specific muscles, called the cell's "motor field"; the most strongly coactivated muscle was usually the one whose isolated contraction had evoked the most intense unit activity. During active elbow movements most cells fired in a manner consistent with their isometric patterns, but clear exceptions were noted. Differential reinforcement of unit activity and muscle suppression was invariably successful in dissociating correlations. The strength of each unit-muscle correlation was assessed by the relative intensity of their coactivation and its consistency under different response conditions. Several cells exhibited the most intense coactivation with the same muscle during all conditions. Thus, intensity and consistency criteria usually agreed, suggesting that strong correlations so determined may operationally define a "functional relation". However, correlations in the sense of covariation are neither necessary nor sufficient evidence to establish anatomical connections. To test the possibility of direct excitatory connections we stimulated the cortex, but found lowest threshold responses in distal muscles, even from points where most cells had been strongly correlated with proximal muscles. Post-spike averages of rectified EMG activity provided scant evidence for cell-related fluctuations in firing probabilities of any muscles.

Animals↗

Thalamic terminal morphology and distribution of single corticothalamic axons originating from layers 5 and 6 of the cat motor cortex.

We investigated the axonal morphology of single corticothalamic (CT) neurons of the motor cortex (Mx) in the cat thalamus, using a neuronal tracer, biotinylated dextran amine (BDA). After localized injection of BDA into the Mx, labeled CT axons were found ipsilaterally in the thalamic reticular nucleus (TRN), the ventroanterior-ventrolateral complex (VA-VL), the central lateral nucleus (CL), the central medial nucleus, and the centromedian nucleus, but with the primary focus in the VA-VL. The terminals in the VA-VL formed a large laminar cluster, which extended approximately in parallel with the internal medullary lamina. The laminar organization mirrored morphologic features of single CT axons. We reconstructed the trajectories of 25 single CT axons that arose from layer V (16 axons) or layer VI (9 axons) and terminated in the VA-VL. Terminals of single CT axons that originated from both layer V and layer VI were confined within a laminar structure about 700 microm thick, suggesting the existence of laminar input organization in the VA-VL. Otherwise, the two groups of the CT axons showed contrasting features. All of the CT axons derived from layer VI gave rise to a few short collaterals to the TRN and then formed extensive arborization with numerous small, drumstick-like terminals in the VA-VL. On the other hand, the CT axons arising from layer V gave rise to collaterals whose main axons descended into the cerebral peduncle. Each collateral projected to the VA-VL or CL without projection to the TRN and formed a few small clusters of giant terminals. The two groups of CT neurons in the same cortical column had convergent rather than segregated termination in the VA-VL. However, the terminals of layer VI CT neurons were distributed diffusely and widely in the VA-VL, whereas the terminals of layer V CT neurons were much more focused and surrounded by the terminals of the former group. These contrasting features of the two types of CT projections appear to represent their different functional roles in the generation of motor commands and control of movements in the Mx.

Animals↗

Function-dependent glycine incorporation into neurons of the cat motor cortex.

Filter papers soaked with 3H-2-glycine solution were applied to the motor cortex of chloralosed and nembutalized cats for one hour. Then underlying cortical samples were excised, fixed in Bouin solution and processed for light-microscopic autoradiography. Sections stained with haematoxylin-eosin were made to determine total cell counts. The cortical samples were sectioned in series so that 10 micron sections at every 50 micron were preserved. From resting and stimulated cortices 10 sections were used for counting pyramidal cells and interneurons in different layers. The electric background activity and the potentials evoked by thalamic VL and antidromic PT stimulation were recorded and averaged. In chloralose anaesthesia, only 7%, while under nembutal 22% of the cells incorporated glycine, on the average. VL stimulation, which induced the appearance of typical evoked potentials, enhanced the glycine incorporation of pyramidal cells in layers II-III and Vb and some activation in the interneurons of layer II was also seen. Antidromic PT stimulation did not change the autoradiographic pattern in chloralosed preparations, while in nembutalized cats it depressed the labelling of pyramidal cells in layers II, III and Va drastically with some enhancement in interneurons of layer II. The changes of autoradiographic patterns are in harmony with theories about cortical effects of VL and antidromic PT stimulation.

Anesthesia↗

Target-specific differences in somatodendritic morphology of layer V pyramidal neurons in rat motor cortex.

Dendritic geometry has been shown to be a critical determinant of information processing and neuronal computation. However, it is not known whether cortical projection neurons that target different subcortical nuclei have distinct dendritic morphologies. In this study, fast blue retrograde tracing in combination with intracellular Lucifer yellow injection and diaminobenzidine (DAB) photoconversion in fixed slices was used to study the morphological features of corticospinal, corticostriatal, and corticothalamic neurons in layer V of rat motor cortex. Marked differences in the distribution of soma, somal size, and dendritic profiles were found among the three groups of pyramidal neurons. Corticospinal neurons were large, were located in deep layer V, and had the most expansive dendritic fields. The apical dendrites of corticospinal pyramidal neurons were thick, spiny, and branched. In contrast, nearly all corticostriatal neurons were small cells located in superficial layer V. Their apical dendritic shafts were significantly more slender, though spiny like those of corticospinal neurons. Corticothalamic neurons, which were located in superficial layer V and in layer VI, had small or medium-sized soma, slender apical dendritic shafts, and dendrites that were largely spine free. This study indicates that, in layer V of rat motor cortex, each population of projection neurons has a unique somatodendritic morphology and suggests that distinct modes of cortical information processing are operative in corticospinal, corticostriatal, and corticothalamic neurons.

Animals↗

Motor "binding:" do functional assemblies in primary motor cortex have a role?

In this issue of Neuron, Jackson and colleagues describe a functional correlate of neural synchrony related to movement control. Synchrony strength in cortico-motoneuronal output neurons in primary motor cortex depended upon similarity of these neurons' connectivity pattern with the spinal cord. These results could form the foundation for subsequent investigations of motor binding.

Animals↗

Fluoxetine facilitates use-dependent excitability of human primary motor cortex.

OBJECTIVES: In poststroke patients, fluoxetine, a selective serotonin-reuptake inhibitor, as an adjunct to physical therapy provided a better functional recovery from motor deficits. The aim of this study was to investigate the effect of a single dose of 20 mg fluoxetine on motor learning and associated cortical changes in healthy right-handed subjects in order to get deeper insight into its facilitating influence on human motor cortex. METHODS: Subjects performed a motor task consisting of a simultaneous co-contraction of the abductor pollicis brevis (APB) and the deltoid muscle with and without fluoxetine in a placebo-controlled double-blinded crossover study design. Immediately before and after motor learning motor output maps of the APB muscle were assessed in order to get insight into plastic changes of the muscle representation. RESULTS: We found a significantly improved motor performance under both conditions without having substantial differences between placebo and fluoxetine. After the completion of the motor task there was a medial shift of the APB muscle motor output map. Only after the administration of fluoxetine the sum of MEP amplitudes (SOA) increased and the motor output map enlarged. CONCLUSIONS: These findings provide evidence for a use-dependent facilitating effect of fluoxetine on cortical excitability but not on motor performance. SIGNIFICANCE: Our findings are not in line with previous experiments in poststroke patients. However, long-term treatment with fluoxetine may additionally improve motor function by upregulating serotonergic receptors. Further studies investigating the influence of long-term treatment on cortical excitability and psychophysics may therefore provide deeper insight into a possible therapeutical efficiency of fluoxetine in poststroke patients.

Adult↗

Caudal cuneate nucleus projection to the direct thalamic relay to the motor cortex: an electrophysiological study.

We previously reported that injection of horseradish peroxidase (HRP) into a physiologically identified region of the thalamus between the ventrolateral nucleus and ventroposterolateral nucleus, VL-VPL, in cat results in labeled cell bodies in the caudal cuneate nucleus (CCN) of the dorsal column nuclei (DCN). We recognized, however, that the spread of HRP to localized regions of less than 1.0 mm distance from the injection site and subsequent uptake by neighboring fibers might have accounted for the resulting label in CCN. In the present study, therefore, we reexamined the DCN input to VL-VPL using a more sensitive physiological method. First, we used the microstimulation technique and corroborated the previous result. In 5 additional preparations, a modified collision procedure was used to ascertain that the same VL-VPL neuron which projects to the motor cortex also receives input from CCN. We report, for the first time, evidence of a lemniscal input to neurons in VL-VPL which are physiologically identified as projecting to the motor cortex.

Afferent Pathways↗

Primary motor cortex activation during action observation revealed by wavelet analysis of the EEG.

OBJECTIVE: We characterised the spectral response of the EEG to median nerve stimulation using wavelet analysis, and compared the relative magnitudes of effect of several different action-observation conditions on the beta and mu 'rebound' rhythms. METHODS: EEG responses to median nerve stimulation were recorded from 8 normal adult subjects during baseline or action-observation conditions. Analysis was performed by convolution of the EEG with a family of wavelets. RESULTS: Decreased power in the mu and beta bands characterized the EEG following median nerve stimulation until 500 ms post-stimulus, followed by increased amplitudes ('rebound') of both rhythms. Execution of movement, observation of object-directed movement and observation of somatosensory stimulation all caused a decreased rebound of the beta rhythm whereas observation of aimless thumb movement did not. CONCLUSIONS: Wavelet analysis of the EEG extracted similar features reported in previous studies using bandpass filtering with respect to the activation state of the motor cortex during action observation. Further, our results show that observation of somatosensory stimulation alone is sufficient to cause significant modulation of motor cortex activity. SIGNIFICANCE: These results add further details as to what stimuli can activate the human mirror neuron system and the analytical techniques used may be useful for future studies of clinical populations such as autistic patients.

Adult↗

Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an [11C]raclopride positron emission tomography study in anesthetized macaque monkeys.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been used as a treatment for neuropsychiatric disorders such as depression and Parkinson's disease (PD). Despite the growing interest in therapeutic application of rTMS, precise mechanisms of its action remain unknown. With respect to PD, activation of the mesostriatal dopaminergic pathway is likely to be a candidate mechanism underlying the therapeutic effects; however, modulating effects of rTMS over the primary motor cortex (M1) on the dopaminergic system have not been studied. METHODS: We used [11C]raclopride positron emission tomography to measure changes of extracellular dopamine concentration after 5Hz rTMS over the M1 in eight anesthetized monkeys. RESULTS: rTMS over the right M1 induced a reduction of [11C]raclopride binding potential (BP) in the bilateral ventral striatum, including the nucleus accumbens, and a significant increase of BP in the right putamen; no significant BP reduction was found in the dorsal striatum. These data indicate that rTMS over the motor cortex induces a release of endogenous dopamine in the ventral striatum. CONCLUSIONS: Our results suggest that therapeutic mechanisms of rTMS may be explained in part by an activation of the mesolimbic dopaminergic pathway, which plays critical roles in rewards, reinforcement, and incentive motivation.

Animals↗