Corticospinal neurones of the supplementary motor area of monkeys

Summary The direct projection from the supplementary motor area (SMA) to the spinal cord was investigated in six monkeys by means of antidromic identification of single SMA neurones. The exploration concentrated on that portion of medial area 6 from which movements were found to be elicited by stimulation at intensities of less than 30 A in an earlier study, but also included some of medial area 4. Of 315 identified corticofugal projection neurones, 234 were found to be localized within medial area 6; of these only one third (76 cells) were corticospinal cells and the remaining two thirds were neurones which projected to the brainstem. The conduction velocities of the descending projection neurones of the SMA were slow (modal value: 10 m/s). Corticospinal cells of the SMA were found up to 6 mm rostral to the boundary between areas 4 and 6. Corticospinal neurones activated antidromically from the cervical but not from the lumbar cord (cervicothoracic neurones) were concentrated in the mesial cortex; lumbo-sacral neurones were found both in the dorsal cortex and the dorsal bank of the cingulate sulcus. However, there was considerable intermingling between the two types of projection neurones and there was no separation in the rostro-caudal direction. Similarly, projection neurones receiving orthodromic inputs from the somatotopical subdivisions of the precentral cortex were not segregated, but were intermingled in the entire rostro-caudal extent of the SMA. It is concluded that there is a clustering of corticospinal neurones in the SMA according to their most caudal segmental projection. However, no rostro-caudal differentiation into face, arm and leg areas was established. This observation is consistent with the results of a previous study in which corticospinal neurones in the SMA were labelled with anatomical tracers and efferent zones were investigated with intra-cortical microstimulation (Macpherson et al. 1982).Funded by the Swiss National Science Foundation (grant no. 3.752.80)     

Premotor and supplementary motor cortex in rhesus monkeys: neuronal activity during externally- and internally-instructed motor tasks

Summary We compared neuronal activity in the premotor (PM) and supplementary motor cortex (SM) of two rhesus monkeys as they performed two tasks. In an externally-instructed task, a visuospatial instruction stimulus indicated which of two touch pads should be the target of a forelimb movement. In an internally-instructed task, the visuospatial stimulus was either irrelevant or not presented, but in either case the target alternated between the two touch pads in blocks of 20 trials each. In both tasks, the monkey withheld movement for a self-timed delay period. Neuronal activity modulation during the delay period (set-related activity) and immediately before movement (movement-related activity) was comparable in PM and SM, both in terms of the proportion of cells with both of those activity patterns and their depth of modulation. Thus, our findings do not provide strong support for a clear-cut functional division between PM and SM regarding the control of externally- and internally-instructed limb movements. Within PM, 57 out of 96 cells with set-related activity showed similar modulation during the two tasks, supporting the proposition that such activity contributes to the preparation for a limb movement. In 32 of the 39 PM set-related neurons that showed a significant activity difference between the two tasks, activity was greater in the externally-instructed task. This finding supports the hypothesis that set-related activity in PM contributes more to sensorially-instructed than to other movements.     

Oscillations in the premotor cortex: single-unit activity from awake, behaving monkeys

We examined single-unit activity in the dorsal premotor cortex for evidence of fast neuronal oscillations. Four rhesus monkeys performed a task in which visuospatial instruction stimuli indicated the direction of forelimb movement to be executed on each trial. After an instructed delay period of 1.5–3 s, movements to either the right or left of a central origin were triggered by a second visuospatial stimulus. From a database of 579 single units, 78 units (13%) contained periodic peaks in their autocorrelation histograms (ACHs), with oscillation frequencies typically 20–30 Hz (mean 27 Hz). An additional 26 units (5%) had oscillatory features that were identified in joint interspike-interval (ISI) plots. Three observations, taken together, suggest entrainment by rhythmic drive extrinsic to these neurons: shuffling ISIs attenuated ACH peaks, indicating a dependency on serial-order effects; oscillation frequency did not change during either increases or decreases in firing rate; and joint ISI plots contained features consistent with a rhythmicity interrupted by intervening discharges. In some cells, oscillations occurred for only one of the two directions of movement. During the delay period, such directional selectivity was observed in 37 units (60% of delay-period oscillators). For at least 17 of these units, we could exclude the possibility that oscillatory directional selectivity resulted from the difficulty in detecting oscillations due to low discharge rates (for one of the two movement directions). Directional selectivity in fast oscillations shows that they can reflect specific aspects of an intended action. Received: 2 March 1999 / Accepted: 26 May 1999     

Timing of bimanual movements in human and non-human primates in relation to neuronal activity in primary motor cortex and supplementary motor area

It has been established that repeated presentation of a transient target motion stimulus such as a constant-velocity ramp leads to the build up of steady state (SS), anticipatory smooth pursuit eye movements after two or three presentations. Each SS response is then composed of the anticipatory component of nonvisual origin, a visual component associated with the stimulus presentation and another nonvisual component that represents the decay of the response after extinction of the stimulus. Here we investigated the interactions that occur when each motion stimulus was itself a sequence containing more than one ramp component. Ramp components had a velocity of 15 degrees /s or 30 degrees /s to left or right and were separated by gaps of 200 ms duration. In an initial experiment, responses to 2-ramp stimuli were examined and compared with responses to the single-ramp stimuli from which they were constituted. We present evidence that the anticipatory, nonvisual components of the double-ramp response result from the linear summation of the nonvisual components of the responses to the constituent single-ramp components. In a 2nd experiment, we examined responses to a wide variety of 4-ramp sequences and again found evidence that, in the SS, the responses were formed from the linear summation of the constituent single-ramp components. Regression analysis performed on the velocity at onset of each ramp component indicated that this nonvisual part of the response was predictive of the upcoming ramp component. To confirm this, unexpected changes were introduced into single ramp components of the 4-ramp sequence after at least five prior presentations of the sequence had allowed a SS response to be established. Subjects continued to initiate a response to the modified component that was appropriate in velocity and direction for the corresponding part of the previous sequence and inappropriate for the newly modified stimulus. This preprogrammed response persisted unmodified for more than 170 ms after onset of the modified ramp component. In contrast, in the second presentation of the new sequence, the anticipatory component of the response was highly correlated with the SS response of the new sequence, but not with that of the prior sequence, showing that the preprogrammed response had been modified very rapidly. Similar behaviour was observed whichever of the 4-ramp components was modified, indicating that the velocity and direction of the anticipatory response to each component had been preprogrammed. The results suggest that velocity information related to at least four elements of a sequence can be temporarily stored and subsequently released with appropriate temporal order to form an anticipatory response throughout the whole sequence.     

Neuronal activity in the supplementary motor area of monkeys adapting to a new dynamic environment

To execute visually guided reaching movements, the central nervous system (CNS) must transform a desired hand trajectory (kinematics) into appropriate muscle-related commands (dynamics). It has been suggested that the CNS might face this challenging computation by using internal forward models for the dynamics. Previous work in humans found that new internal models can be acquired through experience. In a series of studies in monkeys, we investigated how neurons in the motor areas of the frontal lobe reflect the movement dynamics and how their activity changes when monkeys learn a new internal model. Here we describe the results for the supplementary motor area (SMA-proper, or SMA). In the experiments, monkeys executed visually guided reaching movements and adapted to an external perturbing force field. The experimental design allowed dissociating the neuronal activity related to movement dynamics from that related to movement kinematics. It also allowed dissociating the changes related to motor learning from the activity related to motor performance (kinematics and dynamics). We show that neurons in SMA reflect the movement dynamics individually and as a population, and that their activity undergoes a variety of plastic changes when monkeys adapt to a new dynamic environment.     

Effective connectivity between human supplementary motor area and primary motor cortex: a paired-coil TMS study

Individuals with anorexia nervosa (AN) experience pronounced body image distortion in combination with a pernicious desire to maintain a dangerously low body weight. Relatively little is known, however, about the mechanism underlying body image distortion in AN. Despite having normal visual perception, individuals with AN both feel and see themselves as large-bodied and show deficits in interoception and haptic perception, suggesting a potential deficit in visual and tactile integration. The size–weight illusion (SWI) arises when two objects of equal weight but different sizes are held. Typical individuals experience a strong and robust illusion that the smaller object feels much heavier than the larger object because of an implicit assumption that weight scales with size. The current study compared the strength of the SWI in individuals with AN to healthy control participants. Individuals with AN exhibited a markedly reduced SWI relative to controls, even though their ability to discriminate weight was unaffected. Because the SWI is strongly modulated by visual appearance, we believe our finding reflects decreased integration of visual and proprioceptive information in anorexia. This finding may explain the puzzling observation that visual perception of the body in a mirror does not correct an AN patient’s distorted body image. We speculate that methods to correct visuo-proprioceptive integration in constructing body image may help rehabilitate patients’ judgments of size and weight regarding their own bodies. We also suggest that a dysfunction in interactions between inferior parietal lobule (concerned with body image), insula, and hypothalamus may underlie AN.     

Corticostriatal projections from the somatic motor areas of the frontal cortex in the macaque monkey: segregation versus overlap of input zones from the primary motor cortex, the supplementary motor area, and the premotor cortex

It is an important issue to address the mode of information processing in the somatic motor circuit linking the frontal cortex and the basal ganglia. In the present study, we investigated the extent to which corticostriatal input zones from the primary motor cortex (MI), the supplementary motor area (SMA), and the premotor cortex (PM) of the macaque monkey might overlap in the putamen. Intracortical microstimulation was performed to map the MI, SMA, and dorsal (PMd) and ventral (PMv) divisions of the PM. Then, two different anterograde tracers were injected separately into somatotopically corresponding regions of two given areas of the MI, SMA, PMd, and PMv. With respect to the PMd and PMv, tracer injections were centered on their forelimb representations. Corticostriatal input zones from hindlimb, forelimb, and orofacial representations of the MI and SMA were, in this order, arranged from dorsal to ventral within the putamen. Dense input zones from the MI were located predominantly in the lateral aspect of the putamen, whereas those from the SMA were in the medial aspect of the putamen. On the other hand, corticostriatal inputs from forelimb representations of the PMd and PMv were distributed mainly in the dorsomedial sector of the putamen. Thus, the corticostriatal input zones from the MI and SMA were considerably segregated though partly overlapped in the mediolateral central aspect of the putamen, while the corticostriatal input zone from the PM largely overlapped that from the SMA, but not from the MI. Received: 30 June 1997 / Accepted: 2 October 1997     

Reorganization of activity in the supplementary motor area associated with motor learning and functional recovery

Summary The supplementary motor area (SMA) of primates has been implicated in the initiation and execution of limb movements. However, when a motor task was extensively overlearned, few SMA neurons, if any, were active before the movement onset. Subsequent lesions of the primary motor cortex gave rise to the appearance of premovement activity changes, indicating usedependent reorganization of the neuronal activity in SMA.     

Somatotopically arranged inputs from putamen and subthalamic nucleus to primary motor cortex

Employing retrograde transsynaptic transport of rabies virus, we investigated the organization of basal ganglia inputs to hindlimb, proximal and distal forelimb, and orofacial representations of the macaque primary motor cortex (MI). Four days after rabies injections into these MI regions, neuronal labeling occurred in the striatum and the subthalamic nucleus (STN) through the cortico-basal ganglia loop circuits. In the striatum, two distinct sets of the labeling were observed: one in the dorsal putamen, and the other in the ventral striatum (ventromedial putamen and nucleus accumbens). The dorsal striatal labeling was somatotopically arranged and its distribution pattern was in good accordance with that of the corticostriatal inputs, such that the hindlimb, orofacial, or forelimb area was located in the dorsal, ventral, or intermediate zone of the putamen, respectively. The distribution pattern of the ventral striatal labeling was essentially the same in all cases. In the STN, the somatotopic arrangement of labeled neurons was in register with that of corticosubthalamic inputs. The present results suggest that the cortico-basal ganglia motor circuits involving the dorsal putamen and the STN may constitute separate closed loops based on the somatotopy, while the ventral striatum provides common multisynaptic projections to all body-part representations in the MI.     

The supplementary motor area modulates perturbation-evoked discharges of neurones in the precentral motor cortex

The hypothesis was tested that the supplementary motor cortex (SMA) may influence the responsiveness of area 4 neurones to kinesthetic stimuli. In the awake monkey, responses to arm displacements were recorded with and without conditioning intracortical stimulation of the SMA. In 14 of 26 tested area 4 neurones, there was an increase of the response latency and/or a decrease of the response magnitude when the peripheral stimulus was conditioned by SMA stimulation. Field potentials evoked by the displacements were reduced in 3 out of 7 recordings. These findings suggest that the SMA exerts subtle inhibitory effects on the motor cortex or its inputs.     

Selective coding of motor sequence in the supplementary motor area of the monkey cerebral cortex

Summary We describe a property of neurons in the supplementary motor area (SMA) of the cerebral cortex of monkey that is different from those in the primary motor area (MI) in relation to execution of a sequential motor task. A group of SMA neurons was active when the animal remembered and pressed three touch-pads in a predetermined sequence but inactive when the same movement was guided by sequentially presented visual signals. This finding indicates that the SMA is involved in the performance of sequential movements on the basis of the information stored inside the brain.     

Converging patterns of inputs from oral structures in the postcentral somatosensory cortex of conscious macaque monkeys

Single neuronal activities were recorded in the oral region of the postcentral gyrus in conscious Japanese monkeys. Among 5,756 neurons isolated, receptive fields (RFs) and submodalities were identified in 1,502 neurons in area 3b, 970 in area 1, and 1,461 in area 2. The relative incidence of neurons that had bilateral RFs increased gradually upon moving caudally from area 3b to area 2 (bilateral integration). A total of 276 neurons had bimaxillary RFs covering both the maxillary and mandibular divisions of the trigeminal nerve, such as the upper and lower lips, upper and lower teeth, palate and tongue, or combinations thereof. There was also a tendency for the relative incidence of neurons with bimaxillary RFs to increase across the postcentral gyrus but with an abrupt change in area 2 (bimaxillary integration). A total of 382 neurons had composite RFs covering more than one of five oral structures: lip, cheek mucosa, teeth/gingiva, tongue, and palate. The relative incidence of neurons with composite RFs was significantly higher in area 2 than in areas 3b and 1 (interstructural integration). These results indicate that the convergence of inputs from oral structures proceeds in a hierarchical manner across the postcentral gyrus, but chiefly in area 2 for the bimaxillary and interstructural integrations. The relative incidence of neurons with composite RFs was higher among neurons associated with the teeth/gingiva or palate than among neurons associated with the tongue or lip in all three areas. We interpret this to mean that anatomical or functional differences between oral structures might be reflected in the converging patterns in the oral representation.     

Responses of cat motor cortex neurons to cortico-cortical and somatosensory inputs

Summary Intracellular techniques were used to investigate a cortico-cortical path from sensory cortex to motor cortex of cats. Cortico-cortical epsps were evoked in motor cortex neurons by microstimulation of area 3a. Epsps with latencies between 1.2 and 2.4 ms were identified as monosynaptic. These short latency cortico-cortical effects were recorded in layers II through VI of the motor cortex. Neurons with monosynaptic cortico-cortical epsps also received excitatory inputs from forelimb nerves, usually from both muscle and cutaneous afferent fibers. The epsps evoked from forelimb nerves in motor cortex neurons were preceded by neural activity in somatosensory cortex. Time delays between arrival of inputs in sensory cortex and in motor cortex were compared to the latencies of cortico-cortical epsps in the same motor cortex neurons. It was apparent that the timing was appropriate for the identified cortico-cortical path to have relayed some sensory inputs to motor cortex.Supported by the Medical Research Council of Canada (MT-7373, DG-186), the Harry Botterell Foundation for the Neurological Sciences, the Ontario Ministry of Health, and the Faculty of Medicine, Queen's UniversityRecipient of a Medical Research Council of Canada Studentship.Recipient of a Medical Research Council of Canada Fellowship     

Laterality of movement-related activity reflects transformation of coordinates in ventral premotor cortex and primary motor cortex of monkeys

The ventral premotor cortex (PMv) and the primary motor cortex (MI) of monkeys participate in various sensorimotor integrations, such as the transformation of coordinates from visual to motor space, because the areas contain movement-related neuronal activity reflecting either visual or motor space. In addition to relationship to visual and motor space, laterality of the activity could indicate stages in the visuomotor transformation. Thus we examined laterality and relationship to visual and motor space of movement-related neuronal activity in the PMv and MI of monkeys performing a fast-reaching task with the left or right arm, toward targets with visual and motor coordinates that had been dissociated by shift prisms. We determined laterality of each activity quantitatively and classified it into four types: activity that consistently depended on target locations in either head-centered visual coordinates (V-type) or motor coordinates (M-type) and those that had either differential or nondifferential activity for both coordinates (B- and N-types). A majority of M-type neurons in the areas had preferences for reaching movements with the arm contralateral to the hemisphere where neuronal activity was recorded. In contrast, most of the V-type neurons were recorded in the PMv and exhibited less laterality than the M-type. The B- and N-types were recorded in the PMv and MI and exhibited intermediate properties between the V- and M-types when laterality and correlations to visual and motor space of them were jointly examined. These results suggest that the cortical motor areas contribute to the transformation of coordinates to generate final motor commands.     

Quantitative inter-segmental and inter-laminar comparison of corticospinal projections from the forelimb area of the primary motor cortex of macaque monkeys

Corticospinal projections from the forelimb area of the primary motor cortex to the C2-Th2 spinal cord segments were quantitatively analyzed using the high resolution anterograde tracer, biotinylated dextran amine (BDA), in rhesus monkeys (n=5). The majority of descending axons were located in the contralateral dorsolateral funiculus (DLF) (85-98%), but a minor portion was observed in the ipsilateral DLF (1-12%) and ventromedial funiculus (VMF) (1-7%). In the gray matter, axon collaterals and terminal buttons were found mainly in the contralateral laminae VI-VII and IX and ipsilateral lamina VIII. The majority of projections to the contralateral gray matter originated from the contralateral DLF, but a minority originated from the ipsilateral DLF. Axons from the ipsilateral DLF were not found to project collaterals on the ipsilateral side, but directly entered the contralateral side after crossing the midline. On the other hand, projections to the ipsilateral lamina VIII were from the ipsilateral VMF, and commissural axons were from the contralateral DLF. Terminal buttons in the motoneuron pool in the contralateral lamina IX were found mainly at the C7-Th1 spinal cord segments, whereas the projections to the contralateral laminae VI-VII, ipsilateral lamina VIII, and commissural axons were also found in more rostral segments, abundantly at the C4-C8 segments, 1-3 segments rostral to the motoneuronal projections. These results suggest that cortical control of contralateral forelimb motoneurons accompanies regulation of interneuronal systems in the contralateral laminae VI-VII and the ipsilateral lamina VIII located a few segments rostral to the motoneurons.     

Neuronal activity related to visually guided saccadic eye movements in the supplementary motor area of rhesus monkeys.

1. The purpose of this study was to describe the response properties of neurons in the supplementary motor area (SMA), including the supplementary eye fields (SEF) of three rhesus monkeys (Macaca mulatta) performing visually guided eye and forelimb movements. Seven hundred thirty single units were recorded in the dorsomedial agranular cortex while monkeys performed a go/no-go visual tracking task. The unit activity associated with rewarded, task-related movements was compared with that associated with unrewarded, spontaneous movements executed in the intertrial interval or when the task was not running. A number of neuronal response types were identified. 2. Sensory cells were characterized by their response to the visual and/or auditory target stimuli combined with no discharge associated with eye or forelimb movements. New information was provided about the receptive fields of the visual cells; they varied in size and, although many included the ipsilateral hemifield, they tended to emphasize the contralateral. A significant proportion of the visually responsive cells had receptive fields restricted to within 8 degrees of the fovea. The response latency was relatively long (greater than 90 ms) and variable. 3. Preparatory set cells were activated from the appearance of the target until the presentation of the go/no-go cue. This subpopulation ceased firing 50-100 ms before the movement was initiated. These cells tended to respond best in relation to contralateral movements. The response latency was similar to that of the sensory cells, although some of these units began to discharge in anticipation of predictable target presentations. These neurons were not active before unrewarded, spontaneous saccades. 4. Sensory-movement cells comprised the largest population of neurons identified in SMA. They were active from the appearance of the target until after the execution of the saccade. These neurons tended to respond preferentially in association with contraversive saccades. The latency of response to the target was significantly longer than that of the sensory cells. There was a large amount of variability in the time to reach the peak level of activation, and this population of units generally became inactivated shortly after the saccade was initiated. Although there were counterexamples, most sensory-movement cells responded equally in association with visually and auditory guided movements. In addition, these neurons were not active in relation to self-generated eye movements made during the intertrial intervals. 5. Pause-rebound cells were identified by their suppression at the appearance of the target and subsequent discharge associated with the saccade. These units tended to respond preferentially to contralateral targets.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pallidal and cerebellar inputs to thalamocortical neurons projecting to the supplementary motor area in Macaca fuscata: a triple-labeling light microcopic study

We investigated the interrelationship between the supplementary motor area (SMA) thalamocortical projection neurons and the pallidothalamic and cerebellothalamic territories in the monkey (Macaca fuscata) using a combination of three tracers in a triple labeling paradigm. Thalamic labeling was analyzed following injections of the anterograde tracers, biotinylated dextran amine (BDA) into the internal segment of the globus pallidus (GPi) and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the contralateral cerebellar interpositus and dentate nuclei. In addition, the retrograde tracer cholera toxin subunit B (CTB) was injected into the physiologically identified hand/arm representation of SMA. The tissue was processed sequentially using different chromogens in order to visualize all three tracers in a single section. We found that the SMA thalamocortical neurons occupied a wide band extending from the ventral anterior nucleus pars principalis (VApc) through the ventral lateral nucleus pars oralis (VLo) and the ventral lateral nucleus pars medialis (VLm) and into to the ventral lateral nucleus pars caudalis (VLc) including a portion of ventral posterior lateral nucleus pars oralis (VPLo) and nucleus X. The heaviest CTB labeling was found in VLo with dense plexuses of BDA labeled pallidothalamic fibers and swellings often observed superimposed upon retrogradely labeled CTB cells. In addition, dense foci of cerebellothalamic WGA-HRP anterograde label were observed coinciding with the occasional retrogradely CTB labeled neurons in VLc and transitional zones between VApc, VLo and VPLo. Our light microscopic results suggest that the SMA receives thalamic inputs with afferents largely derived from GPi and minor inputs originating from the cerebellum.