Modification of the projection from the sensory cortex to the motor cortex following the elimination of thalamic projections to the motor cortex in cats

Examination of the projection from area 2 of the sensory cortex to the motor cortex revealed substantial changes following lesion of the ventrolateral nucleus of the thalamus. These observed changes were as follows. (1) The polarity of the evoked potentials elicited by area 2 stimulation reversed in the depth of the motor cortex whereas in normal animals, there was no reversal. (2) The amplitude of area 2-elicited EPSPs in the motor cortical neurons became greater following the lesion of VL. (3) The shape of the observed EPSPs was characterized by multiple peaks whereas in normal animals, the EPSPs were generally smooth and monophasic. (4) Neurons receiving a short-latency input from area 2 were distributed throughout the depths of the motor cortex whereas in normal animals, they were located only in the upper layers (layers II and III). (5) Intracellular injection of HRP revealed that the neurons receiving short-latency input were not restricted to typical stellate type cells, but also included bipolar or bitufted neurons with elongated cell bodies and polarized arborizations. These neurons were located in the superficial (II and III) as well as in the deep (V) layer. It is concluded that the elimination of thalamic input resulted in the reinforcement of the corticocortical input to the motor cortex. The subsequently observed corticocortical projection extended to neurons did not originally innervated by the association fibers. The results suggested that functional recovery following thalamic lesion is partly due to reorganization of projections from the sensory cortex to the motor cortex.     

Functional role of the sensory cortex in learning motor skills in cats

The functional role of corticocortical input projecting to the motor cortex in learning motor skills was investigated by training 3 cats with and without the projection area. After unilateral removal of areas 1, 2, 2 praeinsularis and a part of 5, the cat was placed in a box and trained to pick up a small piece of food from a beaker in front of the box. Since the beaker and the edge of the box had a space in between, the cat had to develop a new motor skill to being the food back to the box across the space. This skill consisted of combined supination and flexion of the paw to hold the food over the gap. In all 3 cats, the training period necessary for acquisition of the motor skill for the forelimb contralateral to the lesioned brain was significantly longer than the period necessary for the forelimb ipsilateral to the lesioned cortex. Ablation of the remaining projection area after completion of the training did not impair the learned motor skill. The results suggest that the input from the lesioned area to the motor cortex participates in learning motor skills.     

Anatomical and physiological properties of the projection from the sensory cortex to the motor cortex in normal cats: the difference between corticocortical and thalamocortical projections

Details of the distribution of terminal sites of the projection fibers from area 2 of the sensory cortex to the motor cortex were studied and compared with the distribution of terminals from the ventrolateral (VL) nucleus of the thalamus to the motor cortex. The results obtained were as follows: Intracortical microstimulation (ICMS) in area 2 produced measurable short-latency EPSPs only in neurons located in layers II and III of the motor cortex, whereas VL stimulation produced short-latency EPSPs in neurons throughout the depths of the motor cortex. The time from the beginning to the peak of the EPSPs was not significantly different for area 2- and VL-elicited EPSPs suggesting that there was no systematic difference between effective terminal sites for both inputs. However, there was a difference when a given neuron received both inputs suggesting that there was a segregation between the two inputs within a given cell. The majority of area 2-elicited EPSPs were smooth and monophasic, but some (40%) of them showed double peaks indicating that some neurons received mono- and disynaptic inputs from area 2. Intracellular injections of HRP suggested that neurons receiving input from area 2 were predominantly multipolar non-pyramidal neurons in layers II and III whereas neurons receiving thalamic input were pyramidal as well as non-pyramidal cells. Field potentials in the motor cortex evoked by area 2 stimulation did not change polarity in the depths of the cortex and therefore, differed from the VL-evoked potentials suggesting differences in the mechanisms of generating the electrical fields. It is concluded that association fibers effective for producing EPSPs terminate primarily on non-pyramidal cells in layer II and III whereas VL fibers terminate not only on pyramidal but also on non-pyramidal cells in layers III and V. This study provided a basis for examining the modifiability of association fibers after elimination of VL input to the motor cortex which is reported in the following paper.     

Influence of thalamic cooling on sensory responses in association cortex

O'BRIEN, J. H. AND S. M. ROSENBLUM. Influence of thalamic cooling on sensory responses in association cortex. BRAIN RES. BULL. 4(1) 91–98, 1979.—Evoked responses to light flash, click, and paw stimuli were recorded in the four cortical association areas in the acutely prepared cat. Average evoked responses (AEP) for 100 trials were formed before, during, and after localized cooling in the midline thalamus. Cooling of the midline thalamus reduced the magnitude of responses to click and paw stimuli, and increased or did not change the responses to light flash. There was very little similarity in trial-to-trial fluctuations of EP magnitude across cortical areas, and cooling did not reduce the similarity that existed. Waveform similarity was reduced by cooling for responses across the cortex to a single stimulus modality, whereas similarity of responses in a single cortical area to all three stimuli was not changed. The temporal components of the AEP influenced by thalamic cooling were different for different stimuli and cortical locations. It was concluded that the midline thalamo-cortical projection through the centromedian area to association cortices is particularly well-differentiated for multisensory responses in a single cortical region, and that the system should not be thought of as nonspecific but as convergent or multisensory.     

Distribution of corticocortical and thalamocortical synapses on identified motor cortical neurons in the cat: Golgi, electron microscopic and degeneration study

Details of the terminal connection of corticocortical and thalamocortical fibers on pyramidal and stellate neurons in the cat motor cortex were studied using the electron microscope in combination with the Golgi and axonal degeneration techniques. Corticocortical terminals were examined in 23 identified neurons of which 11 were pyramidal and 12 were stellate. Stellate neurons located in layer III received many degenerating terminals (average 8.4 +/- 2.2 per unit length of dendrite (ULD)) and the majority of these (95%) were found on the proximal dendrites or on the cell bodies. The pyramidal neurons received fewer degenerating terminals (average 2.1 +/- 0.27/ULD) and these were located on more distal dendritic shafts or on dendritic spines. The majority of these synapses were of the asymmetric type. Thalamocortical terminals were examined in 9 pyramidal and 9 stellate neurons. Pyramidal neurons received many terminals (average 6.0 +/- 1.23/ULD) and these were found on the basal as well as the apical dendrites and on dendrite spines. Stellate neurons received fewer terminals (average 4.2 +/- 0.64/ULD) and were located primarily on proximal dendritic shafts. The majority of these synapses were of the asymmetric type. The functional role of these synapses is discussed in relation to the physiological results reported in the preceding paper.     

Importance of the projection from the sensory to the motor cortex for recovery of motor function following partial thalamic lesion in the monkey

Motor deficits produced by thalamic lesions were studied using adult cynomolgus monkeys. Lesioned areas included n. ventralis anterior (VA), ventralis lateralis (VL), n. ventralis posterolateralis pars oralis (VPLo), pars caudalis (VPLc) n. subthalamus (STN) and n. centrum medianum (CM). When the lesion included VA, VL and VPLo, there was a cerebellar syndrome, i.e., ataxia and dysmetria. When the lesion included VPLo and VPLc, the animal was paralyzed. When the lesion included VPLo and rostral part of VPLc, there was loss of orientation in hand movement and clumsiness of finger manipulation. These motor deficits gradually disappeared within 1-2 weeks and the function recovered near to normal except for when VPLo and VPLc were totally destroyed. After recovery of motor function, the somatic sensory cortex (areas 1, 2, 3b) ipsilateral to the thalamic lesion was removed. Removal of the sensory cortex resulted in abolition of the recovered function, but when the border area between VPLo and VPLc was intact, the function recovered again. On the other hand, when the thalamic lesion included this border area, succeeding cortical lesion permanently abolished the recovered function or the reappeared function was substantially worse than that before the cortical lesion. Neuronal mechanisms subserving these differences are discussed and it is concluded that when direct sensory input to the motor cortex was interrupted by lesion of the border area between VPLo and VPLc, the lost function was compensated by reorganization of the projection from the sensory cortex to the motor cortex.     

Continuous theta-burst stimulation to primary motor cortex reduces the overproduction of forces following removal of visual feedback

Forward models, generated from the efference copies of motor commands, are thought to monitor the accuracy of ongoing movement. By comparing predicted with actual afferent information, forward models also aid in the differentiation of self-produced movements from externally generated ones. Many have proposed that a consequence of this comparison is attenuation of the predicted component of incoming sensory signals. Previous work from our laboratory has shown that following the removal of an external visual reference, discrete sequential forces exceed target values. Forces produced at the fingertip were perceived as weaker, which lead to a systematic, compensatory over-production of the magnitudes required. The relatively new repetitive TMS protocol of continuous theta-burst stimulation (cTBS) has been shown to reliably depress cortical excitability for a period following stimulation. If sensory attenuation mechanisms were responsible for the overproduction of forces found in our previous results, we hypothesized that reducing cortical excitability of M1 through application of cTBS would induce discrepancy between the efference copy generated and motor output produced. As a result, we expected the overproduction of forces following visual feedback removal would be reduced after receiving cTBS. Participants produced series of pinch grip forces in time to a metronome and to visually specified force magnitudes. Visual feedback of force output was extinguished 10 s into experimental trials and participants performed continued responses for the remaining 10 s. Results confirmed our hypothesis. Mean peak force and constant error were greater and more positive in the absence of visual feedback regardless of stimulation condition; however, the magnitude of increase was significantly reduced following cTBS compared with baseline and sham conditions. Variability was not differentially affected by stimulation condition, increasing only with removal of visual feedback contingent upon the larger forces produced in these trials. Our findings provide further evidence to support the idea that TBS may differentially affect motor output and efference copy generation.     

Long-lasting potentiation of synaptic potentials in the motor cortex produced by stimulation of the sensory cortex in the cat: a basis of motor learning

A long-lasting increase in the efficiency of synaptic transmission in the central nervous system has been thought to be one of the bases of learning and memory. To explore the possibility that the motor cortex (area 4γ) itself is involved in motor learning, the existence of long-term potentiation (LTP) was examined by recording excitatory postsynaptic potentials (EPSPs) from motor cortical neurons. Short tetanic intracortical microstimulation (ICMS) of the somatic sensory cortex produced a marked potentiation of the EPSPs in a small group of motor cortical neurons. The results raised the possibility that the input from the sensory cortex participates in motor learning and retention of the learned motor skills.     

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.     

Caudal cuneate nucleus projection to the direct thalamic relay to motor cortex in cat: an electrophysiological and anatomical study

The input to the border region between the ventrolateral nucleus (VL) and ventroposterolateral nucleus (VPL) of the thalamus, VL-VPL, was studied in cats using a combined electrophysiological and anatomical technique. Neurons within this border region receive somatic afferent input and project to a region of the motor cortex having similar receptive fields. In this study we asked the question whether neurons in the VL-VPL border receive input from the dorsal column nuclei (DCN). To answer this question we delivered intra-cortical microstimulation (ICMS) to the motor cortex while a second electrode inserted into the VL-VPL border, filled with a 20% solution of HRP dissolved in KCl, was used to record antidromically activated neurons. When an antidromically activated neuron was encountered and the neuron responded to natural peripheral stimulation, HRP was iontophoretically injected through the recording electrode. After a 48–72 h survival time, cats were sacrificed, and the brain tissue processed according to the method of Hardy and Heimer¹⁰. Labeled cell bodies were found in the caudal cuneate nucleus (CCN) in all injected animals. These results suggested that neurons in CCN project to cells in VL-VPL which in turn project to the motor cortex.     

Postnatal development of neurons and synapses in the visual and motor cortex of rabbits: a quantitative light and electron microscopic study

Introductory to a morphological investigation on the effects of early visual deprivation and on the critical periods in early postnatal life we have studied quantitatively the normal postnatal growth of neurons and synapses in the visual and motor cortex of rabbits. The major results of this analytical study are: (1) rapid decrease in neuron density and a rapid increase in neuronal volume are observed. They are almost completed at postnatal Day 10, i.e., before natural eye opening. The drop in neuron density is caused to a very large extent by an increase in cortical volume and not by a considerable disappearance of neurons; (2) the formation of synaptic contact zones starts at Day 6 to 7 and is most pronounced between Day 10 and Day 21, i.e., after natural eye opening. At Day 27 synaptic density has reached adult levels in the visual cortex and is in excess of the adult level in the motor cortex. In visual area I and in the motor cortex a significant difference in synaptic increase is observed between the left and right hemisphere, resulting in a lower synaptic density in the left counterparts at Day 27 and in adult animals [56,57]. In the visual cortex a small but highly correlated increase in synaptic vesicle density is observed. In the motor cortex no correlated relation between age and vesicle density is observed. In both cortical areas synaptic vesicle density has reached about 70 percent of the adult level at Day 27; and (3) in newborn and young rabbits the motor cortex seems to be more mature than the visual cortex.     

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.     

Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients

Summary We examined patterns of neuronal degeneration in the motor cortex of amyotrophic lateral selerosis (ALS) patients using traditional cell stains and several histochemical markers including neurofilament, parvalbumin, NADPH-diaphorase, ubiquitin, Alz-50 and tau. Three grades of ALS (mild, moderate, severe) were defined based on the extent of Betz cell depletion. Non-phosphorylated neurofilament immunoreactive cortical pyramidal neurons and non-pyramidal parvalbumin local circuit neurons were significantly depleted in all grades of ALS. In contrast, NADPH-diaphorase neurons and Alz-50-positive neurons were quantitatively preserved despite reduced NADPH-diaphorase cellular staining and dendritic pruning. The density of ubiquitin-positive structures in the middle and deep layers of the motor cortex was increased in all cases. Axonal tau immunoreactivity was not altered. These histochemical results suggest that cortical degeneration in ALS is distinctive from other neurodegenerative diseases affecting cerebral cortex. Unlike Huntington's disease, both pyramidal and local cortical neurons are affected in ALS; unlike Alzheimer's disease, alteration of the neuronal cytoskeleton is not prominent. The unique pattern of neuronal degeneration found in ALS motor cortex is consistent with non-N-methyl-Dxxx-aspartate glutamate receptor-mediated cytotoxicity.Supported in part by a Muscular Dystrophy Association Research Development grant     

Distribution of synapses on fast and slow pyramidal tract neurons in the cat. An electron microscopic study

Distributions of synapses on various portions of fast and slow pyramidal tract neurons (PTNs) in cat motor cortex were studied with electron microscopy. PTNs were identified by their antidromic invasion following stimulation of the medullary pyramid and were classified into fast and slow PTNs according to conduction velocities of their axons. Two fast and two slow PTNs were intracellularly labeled and, by systematic sampling, electron micrographs from various portions of these neurons were examined to compare the distributions of different types of synapses. It was found that most synapses formed on apical and basal dendrites of fast PTNs were with the dendritic shafts. In slow PTNs, while synapses on apical dendrites were mostly axospinous, about 70% of the sampled synapses on basal dendrites of slow PTNs were established with the dendritic shafts. Virtually all synapses on apical dendrites of slow PTNs belonged to asymmetrical type and most of the synapses sampled from basal dendrites of fast PTNs were also asymmetrical. On the other hand, about 29% of the synapses found on apical dendrites of fast PTNs were symmetrical and a trend was observed for this type of synapses to increase their number with increasing proximity to the cell body. Over 28% of the synapses on basal dendrites of slow PTNs were also symmetrical and seemed to be mainly distributed in layer VI. All synapses formed on the soma were symmetrical both for the fast and slow PTNs.     

Neuronal plasticity induced by self-stimulation rewarding experience in rats — a study on alteration in dendritic branching in pyramidal neurons of hippocampus and motor cortex

Self-stimulation rewarding experience promoted structural changes in pyramidal neurons of the CA3 region of the hippocampus and the Vth layer of the motor cortex in adult male Wistar rats. Self-stimulation experience was allowed for 1 h daily for a duration of 10 days through bipolar electrodes placed bilaterally in lateral hypothalamus and substantia nigra — ventral tegmental area. At the end of 10 days, rats were sacrificed, and rapid Golgi examination of the CA3 hippocampal and layer V pyramidal neurons of the motor cortex was made for a grand total of 1600 neurons from 80 rats divided into 4 groups. The neurons of the self-stimulation experienced (SS) group revealed a significant (ANOVA, F-test) increase in dendritic branching in the perisomatic domains. Such changes were not observed in neurons of sham control (SH), experimenter administered stimulation (EA) and normal control (NC) groups. SS animals also showed a significant increase in the thickness of lacunosum and radiatum laminae of CA3 neurons of the hippocampus. Our results reveal that both limbic and neocortical neurons undergo changes in dendritic branching patterns due to self-stimulation rewarding experience. It is tempting to hypothesize that neuronal plasticity is the result of motivation and learning experienced by rats which underwent self-stimulation.     

An improvement in perception of self-generated tactile stimuli following theta-burst stimulation of primary motor cortex

Recent studies have shown that self-generated tactile sensations are perceived as weaker than the same sensations externally generated. This has been linked to a central comparator mechanism that uses efference copy to attenuate the predictable component of sensory inputs arising from one's own actions in order to enhance the salience of external stimuli. To provide a quantitative measure of this attenuation, a force-matching task was developed in which subjects experience a force applied to their finger and are then required to match the perceived force by actively pushing on the finger using their other hand. The attenuation of predictable sensory input results in subjects producing a larger active force than was experienced passively. Here, we have examined the effects of a novel rTMS protocol, theta-burst stimulation (TBS), over primary motor cortex on this attenuation. TBS can alter the excitability of motor cortex to incoming activity. We show that application of a 20s continuous train of TBS, that depresses motor cortex, significantly improves performance in a force-matching task. This suggests that the TBS intervention disturbed the predictive process that uses efference copy signals to attenuate predictable sensory input. A possible explanation for the effect is that TBS has a differential effect on the populations of neurones that generate motor output in M1 than on those neural structures that are involved in generating an efference copy of the motor command.     

An electron microscope study of the cortico-pretecto-olivary projection in the cat by a combined degeneration and horseradish peroxidase tracing technique

The anterior pretectal nucleus (PTA) of the cat was observed electron microscopically after motor cortical ablation and horseradish peroxidase (HRP) injection into the inferior olive of the same animal. Direct synaptic connections were found between degenerated cortico-pretectal axon terminals and dendrites of pretecto-olivary projection neurons retrogradely labeled with HRP in the ventrolateral part of the PTA. Therefore, this combined method revealed that the PTA is a relay station of the cortico-olivary projection.     

Age-related changes of pyramidal cell basal dendrites in layers III and V of human motor cortex: A quantitative Golgi study

Summary Age-related changes of pyramidal cell basal dendrites in layers III and V of human motor cortex (area 4) were analyzed quantitatively in Golgiimpregnated sections by Sholl's method of concentric cireles (Sholl 1953). The present data suggested that basal dendrites of the pyramidal cells were decreased in number with advancing age, and that the decrease was more prominent in basal dendrites of layer V pyramidal cells than in those of layer III pyramidal cells.     

Transcranial direct current stimulation of the motor cortex induces distinct changes in thermal and mechanical sensory percepts

Objective

The aim of this single-blinded, complete crossover study was to evaluate the effects of tDCS on thermal and mechanical perception, as assessed by quantitative sensory testing (QST).

Methods

QST was performed upon the radial part of both hands of eight healthy subjects (3 female, 5 male, 25–41 years of age). These subjects were examined before and after cathodal, anodal or sham tDCS, applied in a random order. TDCS was administered for 15 min at a 1 mA current intensity, with the active electrode placed over the left primary motor cortex and the reference electrode above the right orbit.

Results

After cathodal tDCS, cold detection thresholds (CDT), mechanical detection thresholds (MDT), and mechanical pain thresholds (MPT) significantly increased in the contralateral hand, when compared to the baseline condition.

Conclusions

Cathodal tDCS temporarily reduced the sensitivity to A-fiber mediated somatosensory inputs.

Significance

Impairment of these somatosensory percepts suggests a short-term suppression of lemniscal or suprathalamic sensory pathways following motor cortex stimulation by cathodal tDCS.