Dentate control pathways of cortical motor activity. Anatomical and physiological studies in rat: comparative considerations

The dentato-thalamocortical projections have been studied in albino rats using anatomical and physiological approaches. The anatomical analysis reveals that the dentatothalamic input to the ventral thalamus and the thalamocortical projection from this region onto the motor cortical area have a complex topographical arrangement. The corticothalamic reverberating pathways, both direct and through a relay in the nucleus reticularis thalami, are also roughly arranged in register with the same topographical pattern. This arrangement has been reconciled with that of the motor cortex, as determined by the motor effects of intracortical microstimulations. From this is inferred a somatotopical arrangement of the cerebellar nucleus lateralis, or dentate. These observations are confirmed by the results of our physiological analysis. The movements obtained with direct microstimulations of the nucleus lateralis affect either one joint (simple movements) or, more seldom, several joints (complex movements) of the same limb. A rough rostrocaudal arrangement is found in the nucleus lateralis: the caudocentral regions of the nucleus contain the representation of the musculature of forelimb and head, whereas the hindlimb is represented in the rostralmost part of the nucleus. A more complex organization is found to be related to the three cytoarchitectonic subdivisions of the nucleus lateralis. The main, large-celled part of the nucleus is engaged in the control of the large skeletal musculature. The dorsolateral hump is involved in mouth and peri-oral activities. The ventral, parvocellular, subnucleus is involved in fine exploratory movements of vibrissae, eyes, and forelimb wrist and fingers. The implication of the dentato-thalamocortical pathways in the cortical motor activities in the rat is discussed with attention to the dentate control of the "voluntary" motricity in primates.     

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4γ, 4δ, 6aα, 6aγ, 3a. The lesions were mainly in area 4γ. In the lesioned hemisphere there were many points around the lesion site (in areas 4γ and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6aγ) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4γ, 6aγ and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.     

Changes in electrical thresholds for evoking movements from the cat cerebral cortex following lesions of the sensori-motor area

We evaluated motor maps in the cerebral cortex and motor performance in cats before and after lesions of the forelimb representation in the primary motor area. After the lesion there was a reduction in the use of the affected forelimb and loss of accuracy in prehension tasks using the forelimb; some recovery occurred during the mapping study. Electrode tracts and lesion sites were located in cytoarchitectonically identified cortical areas 4gamma, 4delta, 6aalpha, 6agamma, 3a. The lesions were mainly in area 4gamma. In the lesioned hemisphere there were many points around the lesion site (in areas 4gamma and 3a) from which movements could not be evoked. In some areas distant from the lesion site (e.g. area 6agamma) the mean thresholds for evoking forelimb movements were significantly elevated. Mean thresholds for evoking hindlimb and facial movements were not different from before. In the contralateral hemisphere mean thresholds for evoking forelimb, but not hindlimb or facial movements, were significantly elevated in several sensorimotor areas (area 4gamma, 6agamma and 3a). Mean thresholds for evoking forelimb movements appeared to progressively increase during the time of study. Minimal currents required to evoke forelimb movements from the cerebral cortex increase (possibly progressively) following a lesion of the forelimb representation in the primary motor area, affecting many interconnected motor areas in the hemispheres ipsilateral and contralateral to the lesioned site. This increase in thresholds may play a role in the changes in cortical control of the affected and contralateral limbs following brain lesions and explain the increased sense of effort required to produce movements.     

Convergence of forelimb afferent actions on C7-Th1 propriospinal neurones bilaterally projecting to sacral segments of the cat spinal cord

Propriospinal neurones located in the cervical enlargement and projecting bilaterally to sacral segments of the spinal cord were investigated electrophysiologically in eleven deeply anaesthetized cats. Excitatory or inhibitory postsynaptic potentials from forelimb afferents were recorded following stimulation of deep radial (DR), superficial radial (SR), median (Med) and ulnar (Uln) nerves. 26 cells were recorded from C7, 22 from C8 and 3 from Th1 segments. The majority of the cells were located in the Rexed's laminae VIII and the medial part of the lamina VII. In 10 cases no afferent input from the forelimb afferents was found. In the remaining neurones effects were evoked mostly from DR (88%) and Med (63%), less often from SR (46%) and Uln (46%). Inhibitory actions were more frequent than excitatory. The highest number of IPSPs was evoked from high threshold flexor reflex afferents (FRA)--all connections were polysynaptic. However, inhibitory actions were often evoked from group I or II muscle afferents (polysynaptic or disynaptic) and, less frequently, from cutaneous afferents (mostly polysynaptic). Di- or polysynaptic IPSPs often accompanied monosynaptic EPSPs from group I or II muscle afferents. Disynaptic or polysynaptic EPSPs from muscle and cutaneous afferents were also recorded in many neurones, while polysynaptic EPSPs from FRA were observed only exceptionally. Various patterns of convergence in individual neuronal subpopulations indicate that they integrate different types of the afferent input from various muscle and cutaneous receptors of the distal forelimb. They transmit this information to motor centers controlling hind limb muscles, forming a part of the system contributing to the process of coordination of movements of fore--and hind--limbs.     

Distinct cortical circuit mechanisms for complex forelimb movement and motor map topography

Cortical motor maps are the basis of voluntary movement, but they have proven difficult to understand in the context of their underlying neuronal circuits. We applied light-based motor mapping of Channelrhodopsin-2 mice to reveal a functional subdivision of the forelimb motor cortex based on the direction of movement evoked by brief (10?ms) pulses. Prolonged trains of electrical or optogenetic stimulation (100-500?ms) targeted to anterior or posterior subregions of motor cortex evoked reproducible complex movements of the forelimb to distinct positions in space. Blocking excitatory cortical synaptic transmission did not abolish basic motor map topography, but the site-specific expression of complex movements was lost. Our data suggest that the topography of?movement maps arises from their segregated output projections, whereas complex movements evoked by prolonged stimulation require intracortical synaptic transmission.     

Topographic organization of baboon primary motor cortex: face, hand, forelimb, and shoulder representation

(1) The fine details of the motor organization of the forelimb, face, and tongue representation of the baboon (Papio h. anubis) primary motor cortex were studied in four adult animals, using intracortical microstimulation (ICMS). (2) A total of 293 electrode penetrations were made. ICMS was delivered to 10,052 sites, and of these, 6,186 sites were verified to have been located within the grey matter. Motor effects were evoked from 30% of these sites. (3) The baboon motor cortex is confined, in large part, to the cortical tissue lying along the anterior bank of the central sulcus. When the electrode penetrations were confined to the precentral gyrus, few sites were capable of evoking movement when stimulated by currents of 40 microA or less. (4) The details of the motor maps varied among the four animals; nonetheless, a general topographic organization existed, with the tongue musculature being represented most laterally, followed by a medial progression of the face, digits, wrist, forearm, and shoulder. Within the representation of a given body part, the muscles were organized as a mosaic, wherein the same muscle was multiply represented. (5) A zone of unresponsive cortex was observed to lie consistently between the face and forelimb representation in all four animals. Repeated electrode penetrations within the unresponsive zone failed to elicit muscle contractions even with stimulating currents as high as 80 microA. (6) Our results suggest that the baboon motor cortex is topographically organized; however, embedded within this overall pattern lies a fine-grained mosaic incorporating multiple representations of the same muscle.     

Topographic Organization of Baboon Primary Motor Cortex: Face,Hand, Forelimb,and Shoulder Representation

(1) The fine details of the motor organization of the forelimb, face, and tongue representation of the baboon (Papio h. anubis)primary motor cortex were studied in four adult animals, using intracortical microstimulation (ICMS). (2) A total of 293 electrode penetrations were made. ICMS was delivered to 10,052 sites, and of these, 6,186 sites were verified to have been located within the grey matter. Motor effects were evoked from 30% of these sites. (3)The baboon motor cortex is confined, in large part, to the cortical tissue lying along the anterior bank of the central sulcus. When the electrode penetrations were confined to the precentral gyrus, few sites were capable of evoking movement when stimulated by currents of 40 μA or less. (4)The details of the motor maps varied among the four animals; nonetheless, a general topographic organization existed, with the tongue musculature being represented most laterally, followed by a medial progression of the face, digits, wrist, forearm, and shoulder. Within the representation of a given body part, the muscles were organized as a mosaic, wherein the same muscle was multiply represented. (5) A zone of unresponsive cortex was observed to lie consistently between the face and forelimb representation in all four animals. Repeated electrode penetrations within the unresponsive zone failed to elicit muscle contractions even with stimulating currents as high as 80 μA. (6) Our results suggest that the baboon motor cortex is topographically organized; however, embedded within this overall pattern lies a fine-grained mosaic incorporating multiple representations of the same muscle.     

Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation

We describe methods of localizing functional regions of the mesial wall, based on 47 patients studied intraoperatively or following chronic implantation of subdural electrodes. Somatosensory evoked potentials were recorded to stimulation of posterior tibial, dorsal pudendal, median, and trigeminal nerves. Bipolar cortical stimulation was performed, and in 4 cases movement-related potentials were recorded.The cingulate and marginal sulci formed the inferior and posterior borders of the sensorimotor areas and the supplementary motor area (SMA). The foot sensory area occupied the posterior paracentral lobule, while the genitalia were represented anterior to the foot sensory area, near the cingulate sulcus. The foot motor area was anterior and superior to the sensory areas, but there was overlap in these representations. There was a rough somatotopic organization within the SMA, with the face represented anterior to the hand. However, there was little evidence of the “pre-SMA” region described in monkeys. Complex movements involving more than one extremity were elicited by stimulation of much of the SMA. The region comprising the supplementary sensory area was not clearly identified, but may involve much of the precuneus. Movement-related potentials did not provide additional localizing information, although in some recordings readiness potentials were recorded from the SMA that appeared to be locally generated.     

Repetitive microstimulation alters the cortical representation of movements in adult rats

In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 microns. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.     

Repetitive Microstimulation Alters the Cortical Representation of Movements in Adult Rats

In order to examine the effects of repetitive stimulation on functional cortical organization, standard intracortical microstimulation (ICMS) techniques were used to generate maps of movement representations in motor cortex of rat. After identification of caudal and rostral forelimb fields and adjacent vibrissae and neck fields, one or more representational borders were defined in greater detail. Then a microelectrode was introduced into one of these representational fields, and ICMS current pulses were delivered at a rate of 1/sec for 1 to 3 hr. Following repetitive ICMS, significant changes in movement representations were observed using current levels that were either suprathreshold or subthreshold for evoking the site-specific movement. Electromyographic activity could be evoked at suprathreshold and near-threshold current levels, but not at the subthreshold current levels used here. Significant border shifts ranged from 210 to 670 μm. In each case in which shifts occurred, there appeared to be expansion of the movement represented at the repetitively stimulated site. The effects were progressive and reversible. These results suggest that at least under these unusual experimental circumstances, large representational changes can be generated very rapidly within motor cortex in the absence of any evident peripheral feedback.     

Wistar大鼠运动皮层代表区的微刺激测定

在１５例氯胺酮麻醉的Ｗｉｓｔａｒ大鼠利用皮层内微刺激技术测定了躯体的运动皮层代表区。电刺激为３５０Ｈｚ的阴极串脉冲,电流最大值限为８０μＡ。结果表明大多数皮层点诱发对侧肌肉反应。虽然代表区的大小有很大个体差异,分区的相对位置是恒定的。但在分区内部未见分域排列。部分大鼠存在前部前肢区,但无一例发现前部后肢区。比较文献结果提示Ｗｉｓｔａｒ大鼠的运动皮层的分化程度比Ｌｏｎｇ－Ｅｖａｎｓ黑顶鼠低。     

A Compact Representation of Drawing Movements with Sequences of Parabolic Primitives

Some studies suggest that complex arm movements in humans and monkeys may optimize several objective functions, while others claim that arm movements satisfy geometric constraints and are composed of elementary components. However, the ability to unify different constraints has remained an open question. The criterion for a maximally smooth (minimizing jerk) motion is satisfied for parabolic trajectories having constant equi-affine speed, which thus comply with the geometric constraint known as the two-thirds power law. Here we empirically test the hypothesis that parabolic segments provide a compact representation of spontaneous drawing movements. Monkey scribblings performed during a period of practice were recorded. Practiced hand paths could be approximated well by relatively long parabolic segments. Following practice, the orientations and spatial locations of the fitted parabolic segments could be drawn from only 2–4 clusters, and there was less discrepancy between the fitted parabolic segments and the executed paths. This enabled us to show that well-practiced spontaneous scribbling movements can be represented as sequences (“words”) of a small number of elementary parabolic primitives (“letters”). A movement primitive can be defined as a movement entity that cannot be intentionally stopped before its completion. We found that in a well-trained monkey a movement was usually decelerated after receiving a reward, but it stopped only after the completion of a sequence composed of several parabolic segments. Piece-wise parabolic segments can be generated by applying affine geometric transformations to a single parabolic template. Thus, complex movements might be constructed by applying sequences of suitable geometric transformations to a few templates. Our findings therefore suggest that the motor system aims at achieving more parsimonious internal representations through practice, that parabolas serve as geometric primitives and that non-Euclidean variables are employed in internal movement representations (due to the special role of parabolas in equi-affine geometry).     

Multiple Representations of the Body and Input-Output Relationships in the Agranular and Granular Cortex of the Chronic Awake Guinea Pig

The organization of somatosensory input and the input-output relationships in regions of the agranular frontal cortex (AGr) and granular parietal cortex (Gr) were examined in the chronic awake guinea pig, using the combined technique of single-unit recording and intracortical microstimulation (ICMS). AGr, which was cytoarchitectonically subdivided into medial (AGrm) and lateral (AGrl) parts, also can be characterized on a functional basis. AGrl contains the head, forelimb, and most hindlimb representations; only a small number of hindlimb neurons are confined in AGrm. Different distributions of submodalities exist in AGr and Gr: AGr receives predominantly deep input (with the exception of the vibrissa region, which receives cutaneous input), whereas neurons of Gr respond almost exclusively to cutaneous input. The cutaneous or deep receptive field (RF) of each neuron was determined by natural peripheral stimulation. All studied neurons were activated by small RFs, with the exception of lip, nose, pinna, and limb units of lateral Gr (Grl), for which the RFs were larger.

Microelectrode mapping experiments revealed the existence of three spatially separate, incomplete body maps in which somatosensory and motor representations overlap. One body map, with limbs medially and head rostrolaterally, is contained in AGr. A second map, comparable to the first somatosensory cortex (SI) of other mammals, is found in Gr, with hindlimb, trunk, forelimb, and head representations in an orderly mediolateral sequence. An unresponsive zone separates the head area from the forelimb region. A third map, with the forelimb rostrally and the hindlimb caudally, lies adjacent and lateral to the SI head area. This limb representation, which is characterized by an upright and small size compared to that found in SI, can be considered to be part of the second somatosensory cortex (SII). A distinct head representation was not recognized as properly belonging to SII, but the evidence that neurons of the SI head region respond to stimulation of large RFs located in lips, nose, and pinna leads us to hypothesize that the SII face area overlaps that of SI to some extent, or, alternatively, that the two areas are strictly contiguous and the limits are ambiguous, making them difficult to distinguish.

The input-output relationships were based on the results of RF mapping and ICMS in the same electrode penetration. The intrinsic specific interconnections of cortical neurons whose afferent input and motor output is related to identical body regions show a considerable degree of refinement. The input-output correspondence is especially pronounced for neurons with small RFs. This study confirms and extends similar data recently reported for other rodents.     

A Comparison of the Ipsilateral Cortical Projections to the Dorsal and Ventral Subdivisions of the Macaque Premotor Cortex

The cortical connections of the dorsal (PMd) and ventral (PMv) subdivisions of the premotor area (PM, lateral area 6) were studied in four monkeys (Macaca fascicularis) through the use of retrograde tracers. In two animals, tracer was injected ventral to the arcuate sulcus (PMv), in a region from which forelimb movements could be elicited by intracortical microstimulation (ICMS). Tracer injections dorsal to the arcuate sulcus (PMd) were made in two locations. In one animal, tracer was injected caudal to the genu of the arcuate sulcus (in caudal PMd [cPMd], where ICMS was effective in eliciting forelimb movements); in another animal, it was injected rostral to the genu of the arcuate sulcus (in rostral PMd [rPMd], where ICMS was ineffective in eliciting movements). Retrogradely labeled neurons were counted in the ipsilateral hemisphere and located in cytoarchitectonically identified areas of the frontal and parietal lobes. Although both PMv and PMd were found to receive inputs from other motor areas, the prefrontal cortex, and the parietal cortex, there were differences in the topography and the relative strength of projections from these areas.

There were few common inputs to PMv and PMd; only the supplementary eye fields projected to all three areas studied. Interconnections within PMd or PMv appeared to link hindlimb and forelimb representations, and forelimb and face representations; however, connections between PMd and PMv were sparse. Areas cPMd and PMv were found to receive inputs from other motor areas—the primary motor area, the supplementary motor area, and the cingulate motor area—but the topography and strength of projections from these areas varied. Area rPMd was found to receive sparse inputs, if any, from these motor areas. The frontal eye field (area 8a) was found to project to PMv and rPMd, and area 46 was labeled substantially only from rPMd. Parietal projections to PMv were found to originate from a variety of somatosensory and visual areas, including the second somatosensory cortex and related areas in the parietal operculum of the lateral sulcus, as well as areas 5, 7a, and 7b, and the anterior intraparietal area. By contrast, projections to cPMd arose only from area 5. Visual areas 7m and the medial intraparietal area were labeled from rPMd. Relatively more parietal neurons were labeled after tracer injections in PMv than in PMd. Thus, PMv and PMd appear to be parts of separate, parallel networks for movement control.     

Coordinated network functioning in the spinal cord: An evolutionary perspective

The successful achievement of harmonious locomotor movement results from the integrated operation of all body segments. Here, we will review current knowledge on the functional organization of spinal networks involved in mammalian locomotion. Attention will not simply be restricted to hindlimb muscle control, but by also considering the necessarily coordinated activation of trunk and forelimb muscles, we will try to demonstrate that while there has been a progressive increase in locomotor system complexity during evolution, many basic organizational features have been preserved across the spectrum from lower vertebrates through to humans. Concerning the organization of axial neuronal networks that control trunk muscles, it has been found across the vertebrate range that during locomotor movement a motor wave travels longitudinally in the spinal cord via the coupling of rhythmic segmental networks. For hindlimb activation it has been found in all species studied that the rostral lumbar segments contain the key elements for pattern generation. We also showed that rhythmic arm movements are under the control of cervical forelimb generators in quadrupeds as well as in human. Finally, it is highlighted that the coordination of quadrupedal movements during locomotion derives principally from an asymmetrical coordinating influence occurring in the caudo-rostral direction from the lumbar hindlimb networks.     

The distribution of neural crest-derived Schwann cells from subsets of brachial spinal segments into the peripheral nerves innervating the chick forelimb.

Neural crest cells from brachial levels of the neural tube populate the ventral roots, spinal nerves, and peripheral nerves of the chick forelimb where they give rise to Schwann cells. The distribution of neural crest cells in the developing forelimb was examined using homotopic and heterotopic chick-quail chimeras to label neural crest cells from subsets of the brachial spinal segments. Neural crest cells from particular regions of the spinal cord populated ventral roots and spinal nerves adjacent to or immediately posterior to the graft. Crest cells also populated the brachial plexus in accord with their segmental origins. In the forelimb, neural crest cells populated muscle nerves with anterior brachial spinal segments populating nerves to anterior musculature of the forelimb and posterior brachial spinal segments populating nerves to posterior musculature. Similar patterns were seen following both homotopic and heterotopic transplantation. In both types of grafts, the distribution of neural crest cells largely matched the sensory and motor projection pattern from the same spinal segmental level. This suggests that neural crest-derived Schwann cells from a particular spinal segment may use sensory and motor fibers emerging from the same segmental level as substrates to guide their migration into the periphery.     

Functional topography of the dorsomedial hypothalamus

The dorsomedial hypothalamus (DMH) has been proposed to play key roles in both the defense reaction to acute stress and in the thermoregulatory response to cold. We reasoned that the autonomic/respiratory motor patterns of these responses would be mediated by at least partly distinct DMH neuron populations. To test this, we made simultaneous recordings of phrenic nerve and plantar cutaneous vasoconstrictor (CVC) activity in 14 vagotomized, ventilated, urethane-anesthetized rats. Microinjections of d,l-homocysteic acid (DLH; 15 nl, 50 mM) were used to cause localized, short-lasting (<1 min) activation of DMH neuron clusters. Cooling the rat's trunk skin by perfusing cold water through a water jacket-activated plantar CVC activity but depressed phrenic burst rate (cold-response pattern). The expected "stress/defense response" pattern would be phrenic activation, with increased blood pressure, heart rate, and possibly CVC activity. DLH microinjections into 76 sites within the DMH region never reduced phrenic activity. They frequently increased phrenic rate and/or plantar CVC activity, but the magnitudes of those two responses were not significantly correlated. Plantar CVC responses were evoked most strongly from the dorsal hypothalamic area and most dorsal part of the dorsomedial nucleus, whereas peak phrenic rate responses were evoked from more caudal sites; their relative magnitudes varied systematically with rostrocaudal position. Tachycardia correlated with plantar CVC responses but not phrenic rate. These findings indicate that localized activation of DMH neurons does not evoke full "cold-response" or stress/defense response patterns, but they demonstrate the existence of significant functional topography within the DMH region.     

Effects of blockade of noradrenergic and serotonergic transmission in theCM-Pf complex on neuronal activity in the motor thalamus in cats

Effects of injections of blockers of the monoaminergic receptor structures into thecentrum medianum-nucl. parafascicularis (CM-Pf) on the activity of neurons in the motor thalamic nuclei (VA-VL) were studied in chronic experiments on awake cats. The animals were trained to perform an operant placing reflex by the forelimb. Injection of a-adrenoblocker, anapriline, into theCM-Pf resulted in enhancement of background activity of neurons of the motor thalamus and facilitation of their spike responses related to conditioned and unconditioned reflex movements. Application of a blocker of serotonin receptors, lysergoamide, evoked opposite changes in the neuronal activity in theVA-VL nuclei: depression of background activity, facilitation of inhibitory processes, and suppression of evoked activity related to conditioned and unconditioned movements. It is supposed that the monoaminergic system of thelocus coeruleus exerts a suppressing influence on the motor thalamus via theCM-Pf complex, while the system of the raphe nuclei facilitates motor thalamic structures.Neirofiziologiya/Neurophysiology, Vol. 28, No. 6, pp. 305–311, November–December, 1996.