Neuronal populations in primary motor cortex encode bimanual arm movements

Previous studies have shown that activity of neuronal populations in the primary motor cortex (MI), processed by the population vector method, faithfully predicts upcoming movements. In our previous studies we found that single neurons responded differently during movements of one arm vs. combined movements of the two arms. It was, therefore, not clear whether the population vector approach could produce reliable movement predictions also for bimanual movements. This study tests this question by comparing the predictive quality of population vectors for unimanual and bimanual arm movements. We designed a bimanual motor task that requires coordinated movements of the two arms, in which each arm may move in eight directions, and recorded single unit activity in the MI of two rhesus (Macaca mulatta) monkeys during the performance of unimanual and bimanual arm movements. We analysed the activity of 212 MI cells from both hemispheres and found that, despite bimanual related activity, the directional tuning and preferred directions of most cells were preserved in unimanual and bimanual movements. We demonstrate that population vectors, constructed from the activity of MI cells, predict accurately the direction of movement both for unimanual and for bimanual movements even when the two arms move simultaneously in different directions.     

Arm trajectory and representation of movement processing in motor cortical activity

We review experiments in which single-cell primary motor cortical activity was recorded from Rhesus monkeys (Macaca mulatta) while they performed reaching and drawing tasks. The directional tuning curves generated during reaching were modulated by the speed of movement and this was reflected in the magnitude of population vectors calculated from firing rates of a large population of cells. Directional and speed representation in the firing rates of these cells is robust across both reaching and drawing. Several behavioural invariants related to the speed of drawing were represented in the time-series of population vectors. This high fidelity neural representation of velocity found in motor cortex can be used to visualize the dynamics of motor cortical activity during drawing and suggests that the cost function governing the rate of drawing is bound by neural processing.     

Tuning for the orientation of spatial attention in dorsal premotor cortex

We tested whether neuronal activity in the dorsal premotor cortex (PMd) reflected the orientation of selective spatial attention, as opposed to the target of a reaching movement, eye position and saccade direction. These four spatial variables were dissociated in two tasks, which both required that a monkey attend to a robot's location in order to know when to make a movement. However, the target of the reaching movement varied; it was the robot's location in one task, but a different location in the other task. Eye position was recorded, but not explicitly controlled. Of 199 PMd neurons sampled, 19% had activity related to eye position, and an overlapping 11% were related to saccade direction (totaling 24% of the PMd sample). Of the 152 PMd neurons that lacked oculomotor relationships, approximately 20% reflected the orientation of selective spatial attention. Attentional tuning may account, at least in part, for gaze-independent receptive fields and visuospatial, target or goal relationships in tasks involving stimulus-response incompatibility.     

Ventral premotor to primary motor cortical interactions during object-driven grasp in humans

Interactions between the ventral premotor (PMv) and the primary motor cortex (M1) are crucial for transforming an object's geometrical properties, such as its size and shape, into a motor command suitable for grasp of the object. Recently, we showed that PMv interacts with M1 in a specific fashion, depending on the hand posture. However, the functional connectivity between PMv and M1 during the preparation of an actual grasp is still unknown.To address this issue, PMv-M1 interactions were tested while subjects were preparing to grasp different visible objects requiring either a precision grip or a whole hand grasp. A conditioning-test transcranial magnetic stimulation (TMS) paradigm was used: a test stimulus was applied over M1 either in isolation or after a conditioning stimulus delivered, at different delays, over the ipsilateral PMv. Motor evoked potentials (MEPs) were recorded in the first dorsal interosseus and abductor digiti minimi muscles, which show highly differentiated activity according to grasp.While subjects prepared to grasp, delivering a conditioning PMv pulse 6 or 8 msec before a test pulse over M1 strikingly facilitated MEPs in the specific muscles that were used in the upcoming grasp. This degree of facilitation correlated with the amount of muscle activity used later in the trial to grasp the objects.The present results demonstrate that, during grasp preparation, the PMv-M1 interactions are muscle-specific. PMv appears to process the object geometrical properties relevant for the upcoming grasp, and transmits this information to M1, which in turn generates a motor command appropriate for the grasp. We also reveal that the grasp-specific facilitation resulting from PMv-M1 interactions is differently related to the upcoming grasp muscle activity than is that from paired-pulse stimulation over M1, suggesting that these two TMS paradigms assess the excitability of cortico-cortical pathways devoted to the control of grasp at two different levels.     

Ipsilateral cortical connections of dorsal and ventral premotor areas in New World owl monkeys

In order to compare connections of premotor cortical areas of New World monkeys with those of Old World macaque monkeys and prosimian galagos, we placed injections of fluorescent tracers and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in dorsal (PMD) and ventral (PMV) premotor areas of owl monkeys. Motor areas and injection sites were defined by patterns of movements electrically evoked from the cortex with microelectrodes. Labeled neurons and axon terminals were located in brain sections cut either in the coronal plane or parallel to the surface of flattened cortex, and they related to architectonically and electrophysiologically defined cortical areas. Both the PMV and PMD had connections with the primary motor cortex (M1), the supplementary motor area (SMA), cingulate motor areas, somatosensory areas S2 and PV, and the posterior parietal cortex. Only the PMV had connections with somatosensory areas 3a, 1, 2, PR, and PV. The PMD received inputs from more caudal portions of the cortex of the lateral sulcus and more medial portions of the posterior parietal cortex than the PMV. The PMD and PMV were only weakly interconnected. New World owl monkeys, Old World macaque monkeys, and galagos share a number of PMV and PMD connections, suggesting preservation of a common sensorimotor network from early primates. Comparisons of PMD and PMV connectivity with the cortex of the lateral sulcus and posterior parietal cortex of owl monkeys, galagos, and macaques help identify areas that could be homologous.     

Ventral premotor to primary motor cortical interactions during noxious and naturalistic action observation

Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated by the volitional component induced by the action observed. In this study, using a paired pulse transcranial magnetic stimulation (ppTMS) method, we evaluated the excitability of PMv-M1 connections during the observation of videos showing a human hand reaching to grasp a ball (naturalistic grasping video) or a switched on soldering iron (noxious grasping video). The results show that the observation of the naturalistic grasping action increased the M1 excitability and changed the strength of the PMv-M1 connections. The observation of the noxious grasping action did not induce any change in the excitability of the PMv-M1 connections throughout the video, but the strength of PMv-M1 connectivity was reduced. These results demonstrate that the PMv-M1 connections are modulated differently depending on whether the action observed would or would not be performed in real life.     

Organization of pyramidal neurons in area 17 of monkey visual cortex.

In sections of area 17 of monkey visual cortex treated with an antibody to MAP2 the disposition of the cell bodies and dendrites of the neurons is readily visible. In such preparations it is evident that the apical dendrites of the pyramidal cells of layer VI form fascicles that pass into layer IV, where most of them gradually taper and form their terminal tufts. In contrast, the apical dendrites of the smaller layer V pyramidal cells come together in a more regular fashion. They form clusters that pass through layer IV and into layer II/III where the apical dendrites of many of the pyramidal cells in that layer add to the clusters. In horizontal sections taken through the middle of layer IV, these clusters of apical dendrites are found to have an average center-to-center spacing of about 30 microns, and it is proposed that each cluster of apical dendrites represents the axis of a module of pyramidal cells that has a diameter of about 30 microns and contains about 142 neurons. The MAP2 antibody reaction also reveals that some pyramidal cells in layers IVA and IVB have their cell bodies arranged into cones. There are about 118 such cones beneath 1 mm2 of cortical surface and the apical dendrites of the pyramidal cells within them bundle together at the apex of each cone to pass into layer III. Surrounding the cones of neurons there are horizontally aligned, thin dendrites. The location of these dendrites coincides with the dark walls of the honeycomb pattern seen in layer IVA after cytochrome oxidase reactions, or after the parvocellular input from the lateral geniculate nucleus has been labeled. Thus the cones of pyramidal cells within upper layer IV fit into the pockets of the honeycomb pattern. Below the cones of pyramidal cells are the outer Meynert cells within layer IVB, and the cell bodies of these large neurons are disposed so that they preferentially lie beneath the neuropil between the cones of pyramids. It is suggested that pyramidal cell modules are a basic feature of the cerebral cortex, and that these are combined together by afferent inputs to the cortex to generate the systems of functional columns.     

Effects of age on the thickness of myelin sheaths in monkey primary visual cortex

The effect of age on myelin sheath thickness was determined by an electron microscopic examination of cross sections of the vertical bundles of nerve fibers that pass through primary visual cortex of the rhesus monkey. The tissue was taken from the cortices of young (4-9 years of age) and old (over 24 years of age) monkeys, and the sections were taken at the level of layer 4Cbeta. From the electron photomicrographs, the diameters of axons and the numbers of lamellae in their myelin sheaths were determined. No change was found in the diameters of axons with age, although the mean numbers of myelin lamellae in the sheaths increased from 5.6 in the young monkeys to 7.0 in the old monkeys. Much of this increase in mean thickness was due to the fact that, in the old monkeys, thick myelin sheaths with more than ten lamellae are more common than in the young monkeys. While this increase in the thickness of myelin sheaths is occurring in old monkeys, there are also age-related changes in some of the sheaths. Consequently, it seems that, with age, there is some degeneration of myelin but, at the same time, a continued production of lamellae.     

Threshold tracking primary motor cortex inhibition: the influence of current direction

Paired‐pulse transcranial magnetic stimulation (TMS) can be used to probe inhibitory activity in primary motor cortex (M1). Recruitment of descending volleys with TMS depends on the induced current direction in M1. Anterior‐posterior (AP) stimulation preferentially activates late indirect‐ (I‐) waves that are most susceptible to paired‐pulse TMS. Threshold tracking TMS can assess intracortical inhibition; however, previous studies have only used a current direction that preferentially recruits early I‐waves [posterior‐anterior (PA)]. Our objective was to examine intracortical inhibition with threshold tracking TMS designed to preferentially recruit early vs. late I‐waves with PA and AP stimulation respectively. Electromyographic recordings were obtained from the right first dorsal interosseous muscle of 15 participants (21–50 years). Motor evoked potentials elicited by TMS over left M1 were recorded for PA, AP and lateromedial (LM) induced currents, with I‐wave recruitment calculated as the onset latency difference between PA‐LM and AP‐LM. Short‐ and long‐interval intracortical inhibition (SICI and LICI) were examined across a range of conditioning stimulus intensities and interstimulus intervals (3 and 100–260 ms) with threshold tracking TMS for PA and AP stimulation. SICI and LICI were greater for AP compared with PA current direction using threshold tracking. In addition, the efficacy of late I‐wave recruitment was associated with the extent of SICI for AP but not PA stimulation, and was not associated with LICI. These findings indicate that threshold tracking with an AP‐induced current provides a more robust and sensitive measure of M1 intracortical inhibition than PA.     

Tangential distribution of cytochrome oxidase-rich blobs in the primary visual cortex of macaque monkeys

We studied the tangential distribution of cytochrome c oxidase (CytOx)-rich blobs in four striate cortices of three normal monkeys (Macaca mulatta). The spatial density and cross-sectional area of blobs were analyzed in CytOx-reacted tangential sections of flat-mounted preparations of the striate cortex (V1). Well-delimited CytOx-rich blobs were found in the middle portion of cortical layer III of the V1. Throughout the binocular field representation, the spatial density of blobs was nearly constant with a mean value of four to five blobs per mm². In the monocular portions of V1, however, blob spatial density diminished. In all cases, the mean cross-sectional area of blobs was constant in the V1. The small variation of CytOx blob topography with visual field eccentricity contrasts with the variation described in previously published material. J. Comp. Neurol. 386:217–228, 1997. © 1997 Wiley-Liss, Inc.     

Comparison of neuronal activity in the rostral supplementary and cingulate motor areas during a task with cognitive and motor demands

A number of cortical motor areas have been identified on the medial wall of the hemisphere in monkeys. However, their specific role in motor control remains unclear. In this study, we sought to describe and compare the functional properties of the presupplementary (pre-SMA) and rostral cingulate (CMAr) motor areas in two monkeys performing a visually instructed, delayed, sequential movement. We recorded 134 task-related neurons in the pre-SMA and 149 in the CMAr. The main difference between the two areas was the abundance of responses to targets (46%) in the pre-SMA, while CMAr activity was more related to reward (28%). Neuronal responses to targets were more phasic and higher in frequency in the pre-SMA than in the CMAr. During the delay, the percentage of neuronal responses was similar in the two areas. The discharge pattern was different depending upon whether the delay duration was fixed or variable but in most neurons was the same regardless of the sequence performed. Movement-related changes were common in the pre-SMA (75%) and in the CMAr (81%) but they occurred earlier in the former. Neurons activated exclusively during movement were more numerous in the CMAr. Finally, neuronal activity in the pre-SMA was more related to the sequential aspect of the task compared to the CMAr. Our results suggest that although the two areas share functional properties, they also participate in different aspects of motor behaviour. Their functional properties reflect their anatomical positions, which give them the potential to integrate external stimuli (pre-SMA) and internal states (CMAr) during motor planning.     

Ipsilateral corticotectal projections from the primary,premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study

The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non‐human primates, previous studies reported that cortical projections to the superior colliculus (SC) originated from the premotor cortex (PM) and the primary motor cortex, whereas no projection originated from the supplementary motor area (SMA). The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n = 9). The anterograde tracer biotinylated dextran amine was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral SC. The data confirmed the presence of strong corticotectal projections from the PM. A new observation was that strong corticotectal projections were also found to originate from the SMA (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or SMAs. The corticotectal projection from each motor area was directed mainly to the deep layer of the SC, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non‐primary motor areas are in position to influence the preparation and planning of voluntary movements.     

Projections of the claustrum to the primary motor,premotor, and prefrontal cortices in the macaque monkey

The claustrum is interconnected with the frontal lobe, including the motor cortex, prefrontal cortex, and cingulate cortex. The goal of the present study was to assess whether the claustral projections to distinct areas within the frontal cortex arise from separate regions within the claustrum. Multiple injections of tracers were performed in 15 macaque monkeys, aimed toward primary motor area (M1), pre-supplementary motor area (pre-SMA), SMA-proper, rostral (PMd-r) and caudal (PMd-c) parts of the dorsal premotor cortex (PM), rostral (PMv-r) and caudal (PMv-c) parts of the ventral PM, and superior and inferior parts of area 46. The distribution of retrogradely labeled neurons showed no clear segregation along the rostrocaudal axis of the claustrum; they were usually located along the entire anteroposterior extent of the claustrum. For all motor cortical areas, there was a general trend of the labeled neurons to occupy the dorsal and intermediate parts of the claustrum along the dorsoventral axis. The same territories were labeled after injection in area 46, but in addition numerous labeled neurons were found in the most ventral part of the claustrum. At higher resolution, however, there was clear evidence that the territories projecting to pre-SMA and SMA-proper formed separate, interdigitating, clusters along the dorsoventral axis. A comparable local segregation was observed for the two subdivisions of area 46, whereas there was more local overlap among the subareas of PM. The projections from the claustrum to the multiple subareas of the motor cortex and to area 46 arise from largely overlapping territories, with, however, some degree of local segregation.     

Rostrocaudal functional gradient among the pre‐dorsal premotor cortex,dorsal premotor cortex and primary motor cortex in goal‐directed motor behaviour

The dorsal premotor cortex residing in the dorsolateral aspect of area 6 is a rostrocaudally elongated area that is rostral to the primary motor cortex (M1) and caudal to the prefrontal cortex. This region, which is subdivided into rostral [pre‐dorsal premotor cortex (pre‐PMd)] and caudal [dorsal premotor cortex proper (PMd)] components, probably plays a central role in planning and executing actions to achieve a behavioural goal. In the present study, we investigated the functional specializations of the pre‐PMd, PMd, and M1, because the synthesis of the specific functions performed by each area is considered to be essential. Neurons were recorded while monkeys performed a conditional visuo‐goal task designed to include separate processes for determining a behavioural goal (reaching towards a right or left potential target) on the basis of visual object instructions, specifying actions (direction of reaching) to be performed on the basis of the goal, and preparing and executing the action. Neurons in the pre‐PMd and PMd retrieved and maintained behavioural goals without encoding the visual features of the visual object instructions, and subsequently specified the actions by multiplexing the goals with the locations of the targets. Furthermore, PMd and M1 neurons played a major role in representing the action during movement preparation and execution, whereas the contribution of the pre‐PMd progressively decreased as the time of the actual execution of the movement approached. These findings revealed that the multiple processing stages necessary for the realization of an action to accomplish a goal were implemented in an area‐specific manner across a functional gradient from the pre‐PMd to M1 that included the PMd as an intermediary.     

Monkey pyramidal tract neurons and changes of movement parameters in visual tracking

During a single-step visual tracking task of monkeys, parametric changes of the wrist extension-flexion movement and related discharge rate changes of pyramidal tract neurons (PTNs) of hand-arm motor area were studied. The task consisted of preparatory, precontraction, contraction and target periods. If the displacement amplitude was changed from narrow (10–20°) to moderate (40°) range, peak velocity, peak acceleration and contraction period increased linearly but precontraction period decreased slightly. In 61 movement-related PTNs, no linear relationships were found between PTN discharge rate during precontraction or contraction period and displacement amplitude, velocity, acceleration, precontraction period or contraction period. In less than 20% of PTNs, however, correlations between PTN discharge rate during precontraction period and velocity or acceleration were found in the moderate range task. It occurred less frequently in narrow range task. It is said in a visual tracking task that PTN activity is not dependent upon factors related to the task parameters, such as velocity, acceleration. Possible related factors were discussed.     

Topographical distribution of dorsal and median raphe neurons projecting to motor, sensorimotor, and visual cortical areas in the rat

The present study was conducted to examine the spatial organization of dorsal (DR) and median (MR) raphe neurons that project to rostrocaudally aligned areas of the rat cerebral cortex. An additional goal was to determine if individual DR cells that send efferents to forelimb sensorimotor or visual regions of the neocortex also send axon collaterals to forelimb (crus II) or visual (paraflocculus) areas of the cerebellum. Long-Evans hooded rats received unilateral pressure injections of horseradish peroxidase (HRP) in either motor (n = 4) or sensorimotor (n = 5) or visual (n = 4) cortex to determine the intranuclear location of DR and MR neurons that project to specific neocortical regions. Coronal sections (40-100 microns) through the pons and midbrain were examined by light microscopy after the tetramethyl benzidine reaction and neutral red counterstaining were carried out. The locations of retrogradely labeled cells were recorded relative to a three-dimensional biological coordinate system maintained by a computer linked to the light microscope. For double labeling studies, unilateral injections of fast blue and nuclear yellow were made in paired motor (sensorimotor cortex and crus II of the lateral cerebellum) or visual (cortical area 17 and paraflocculus) areas of the CNS. Coronal tissue sections (35 microns) were collected on coverslips and examined on a Leitz fluorescence microscope (wavelength = 365 nm). DR neurons labeled from cerebrocortical injections of HRP were concentrated in the rostral two-thirds of the nucleus. HRP-filled neurons were distributed such that individual groups of neurons projecting to motor, sensorimotor, or visual cortex were aligned in a partially overlapping, rostral to caudal array. In the dorsoventral dimension, retrogradely labeled cells were clustered in three distinct groupings such that neurons projecting to the motor, sensorimotor, and visual areas were concentrated in dorsal, intermediate, and ventral portions of the DR nucleus, respectively. For all cases, the majority of HRP-filled cells were positioned along the midline or displaced to the side of the nucleus that was ipsilateral to the cortical injection site. A small number of retrogradely labeled neurons were observed in the MR following injections in the motor cortex. Computer-assisted reconstruction of the neuroanatomical data facilitated the visualization of spatial relationships between groups of DR neocortical projection neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of monkey prefrontal neurons during a visual tracking task reinforced by substantia innominata self-stimulation

The role of the substantia innominata (SI) in the generation of a behavior mediated by the prefrontal (PF) cortex was examined in two Japanese monkeys. PF neuronal activities related to a visual tracking task by wrist movement were recorded and neural responses to SI stimulation were analyzed. Sixty-six neurons showed task-related activity and were classified into 3 types. Type 1 (n = 31) showed transient activation during the movement. Type 2 (n = 26) showed gradually increasing activity before the reward presentation. Type 3 (n = 9) showed tonic activation from the GO signal to the reward presentation. Antidromic and orthodromic responses to SI stimulation were observed in every type. In Type 1, the percentage of antidromically activated neurons (26%) was similar to that of orthodromically activated ones (16%), but in Type 2, 83% of responding neurons showed antidromic responses, and 56% of Type 3 showed orthodromic responses. These results show that the different types of PF neurons have different anatomical relations to SI. Although orthodromically activated neurons were fewer than antidromically activated neurons, many orthodromically activated neurons showed movement-related activity. This suggests that ICSS at SI facilitates the generation of the behavior through the afferent pathway to PF.     

In vitro characterization of intrinsic properties and local synaptic inputs to pyramidal neurons in macaque primary motor cortex

Primates (including humans) have a highly developed corticospinal tract, and specialized motor cortical areas which differ in key ways from rodents. Much work on motor cortex has therefore used macaque monkeys as a good animal model for human motor control. However, there is a paucity of data describing the fundamental functional architecture of primate primary motor cortex, which is best addressed with in vitro approaches. In this study we examined the cellular properties and the micro‐circuitry of the adult macaque primary motor cortex by carrying out in‐vitro intracellular recordings. We aimed to characterize the basic properties of the cortical circuitry by studying the intrinsic properties of its pyramidal neurons and their physiological interconnectivity. We studied the passive and active electrophysiological properties of pyramidal neurons in both superficial and deep cortical layers. Both superficial and deep pyramidal neurons exhibited bursting behaviour that could act as powerful excitation for downstream targets. Synaptic connections were lamina specific. Neurons in the deep layers had convergent excitatory inputs from all cortical layers whereas superficial neurons had only significant inputs from superficial layers. This sheds light on the functional architecture of the primate primary motor cortex and how its output is shaped. We also took the unique opportunity in our recording technique to characterize the relationship between intracellular and extracellular spike waveforms, with implications for cell‐type identification in studies in awake behaving monkey. Our results will aid the interpretation of primate studies into motor control involving extracellular spike recordings and electrical stimulation in primary motor cortex.