Primary motor cortex is involved in bimanual coordination

Many voluntary movements involve coordination between the limbs. However, there have been very few attempts to study the neuronal mechanisms that mediate this coordination. Here we have studied the activity of cortical neurons while monkeys performed tasks that required coordination between the two arms. We found that most neurons in the primary motor cortex (MI) show activity specific to bimanual movements (bimanual-related activity), which is strikingly different from the activity of the same neurons during unimanual movements. Moreover, units in the supplementary motor area (SMA; the area of cortex most often associated with bimanual coordination) showed no more bimanual-related activity than units in MI. Our results challenge the classic view that MI controls the contralateral (opposite) side of the body and that SMA is responsible for the coordination of the arms. Rather, our data suggest that both cortical areas share the control of bilateral coordination.     

Corticostriatal input zones from the supplementary motor area overlap those from the contra- rather than ipsilateral primary motor cortex

To investigate the degree of convergence of corticostriatal inputs from the primary motor cortex (MI) and the supplementary motor area (SMA), we analyzed the extent to which corticostriatal inputs from forelimb representations of these motor-related areas spatially overlap in the macaque monkey. Of particular interest was that corticostriatal input zones from SMA overlapped those from MI of the contralateral hemisphere more extensively than from MI of the ipsilateral hemisphere.     

Changing directions of forthcoming arm movements: neuronal activity in the presupplementary and supplementary motor area of monkey cerebral cortex

1. To understand roles played by two cortical motor areas, the presupplementary motor area (pre-SMA) and supplementary motor area (SMA), in changing planned movements voluntarily, cellular activity was examined in two monkeys (Macaca fuscata) trained to perform an arm-reaching task in which they were asked to press one of two target buttons (right or left) in three different task modes. 2. In the first mode (visual), monkeys were visually instructed to result and press either a right or left key in response to a forth coming trigger signal. In the second mode (stay), monkeys were required to wait for the trigger signal and press the same target key as pressed in preceding trials. In the third mode (shift), a 50 Hz auditory cue instructed the monkey to shift the target of the future reach from the previous target to the previous nontarget. 3. While the monkeys were performing this task, we recorded 399 task-related cellular activities from the SMA and the pre-SMA. Among them, we found a group of neurons that exhibited activity changes related specifically to shift trials (shift-related cells). The following properties characterized these 112 neurons. First, they exhibited activity changes after the onset of the 50-Hz auditory cue and before the movement execution when the monkeys were required to change the direction of forthcoming movement. Second, they were not active when the monkeys pressed the same key without changing the direction of the movements. Third, they were not active when the monkeys received the 50-Hz auditory cue but failed to change the direction of the movements by mistake. These observations indicate that the activity of shift-related cells is related to the redirection of the forthcoming movements, but not to the auditory instruction itself or to the location of the target key or the direction of the forthcoming movements. 4. Although infrequently, monkeys made errors in the stay trials and changed directions of the reach voluntarily. In that case, a considerably high proportion of shift-related neurons (12 of 19) exhibited significant activity changes long before initiation of the reach movement. These long-lasting activities were not observed during the preparatory period in correct stay trials, but resembled the shift-related activity observed when the target shift was made toward the same direction. Thus these activity changes were considered to be also related to the process of changing the intended movements voluntarily. 5. We found another population of neurons that showed activity modulation when the target shift was induced by the visual instruction in visual trials (visually guided shift-related neurons). These neurons were active when the light-emitting diode (LED) guided the forthcoming reach to the previous nontarget but not to the previous target. Therefore their activity was not a simple visual response to the LED per se. A majority of them also showed shift-related activity in shift trials (19 of 22 in monkey 2). 6. Neurons exhibiting the shift-related activity were distributed differentially among the two areas. In the pre-SMA, 31% of the neurons recorded showed the shift-related activity, whereas in the SMA, only 7% showed such an activity. These results suggest that pre-SMA and SMA play differential roles in updating the motor plans in accordance with current requirements.     

Effects of reversible inactivation of the supplementary motor area (SMA) on unimanual grasp and bimanual pull and grasp performance in monkeys

The supplementary motor area (SMA) was reversibly inactivated by muscimol microinfusion in two monkeys while they were performing two motor tasks: (1) a delayed conditional bimanual drawer pulling and grasping sequence which was initiated on a self-paced basis; (2) a unimanual reach and grasp task (modified Kluver board task). Unilateral or bilateral inactivation of the SMA induced a prominent deficit in trial initiation of bimanual sequential movements, affecting the hand contralateral to the inactivated side or both hands, respectively. The deficit was a long lasting (10-15 min or more) inability of the monkey to place its hand (s) in the ready position on start touch-sensitive pads, a condition required to initiate the drawer task. However, if after such a deficit period, the experimenter put his hand on the start touch-sensitive pad to initiate the trial, then the monkey executed the drawer task without obvious motor deficit. SMA inactivation did not affect unimanual reaching and grasping movements in the board task. In contrast to the SMA, inactivation of other motor areas (primary, premotor dorsal, anterior intraparietal area) did not affect the initiation of movement sequences in the drawer task. These data thus indicate that the SMA plays a crucial and specific role in initiation of self-paced movement sequences. However, SMA inactivation did not prevent the monkeys to perform coordinated movements of the two forelimbs and hands, indicating that SMA is not necessary for bimanual coordination.     

Functional results after resective procedures involving the supplementary motor area

In this article, the authors report their experience with surgically induced supplementary motor area (SMA) deficiency syndrome in a prospective clinical trial of 28 patients who underwent surgery for tumorous (19 patients) or nontumorous (nine patients) lesions. The dominant side was affected in 17 patients and the nondominant side in 11 patients. The primary presenting symptoms included seizure activity (23 patients), hemiparesis (four patients), and aphasia (one patient). Functional topographic mapping, achieved by phase reversal of somatosensory evoked potentials, allowed precise localization of the central sulcus in 25 of the 28 patients. Motor evoked potential (MEP) monitoring, which was performed successfully in 13 of 15 cases during the resective procedure, showed no significant changes in the potentials in any patient. Immediately after surgery, 25 (89%) of the 28 patients displayed additional neurological deficits (aphasia and/or hemiparesis) that depended on the extent of the SMA resection. In 12 patients the SMA was resected completely: nine of these patients demonstrated a complete and three an incomplete deficit. In 16 patients the SMA resection was incomplete: 13 of these patients displayed an incomplete deficit, whereas three had no deficit. Neurological disorders resolved completely within 3 to 42 days (mean 11 days), except for a minimal disturbance of fine motor and/or speech function in complex tasks or at high speed. Electromagnetically elicited MEPs, examined postoperatively in five patients, were initially absent but recovered with improvement of motor function. In conclusion, although the SMA is known to control important functions such as initiation of motor activity or speech, our findings show that unilateral SMA removal can be accomplished without resulting in significant permanent deficits. Functional topographic mapping and monitoring facilitate the exact delineation of the adequate resection plane along the precentral sulcus, and postoperative magnetic resonance imaging allows precise correlation of clinical and anatomical data.     

Tactile activity in primate primary somatosensory cortex during active arm movements: cytoarchitectonic distribution

1. Cells were recorded in areas 3b and 1 of the primary somatosensory cortex (SI) of three monkeys during active arm movements. Successful reconstructions were made of 46 microelectrode penetrations, and 298 cells with tactile receptive fields (RFs) were located as to cytoarchitectonic area, lamina, or both. 2. Area 3b contained a greater proportion of cells with slowly adapting responses to tactile stimuli and fewer cells with deep modality inputs than did area 1. Area 3b also showed a greater level of movement-related modulation in tactile activity than area 1. Other cell properties were equally distributed in the two areas. 3. The distribution of cells with low-threshold tactile RFs that also responded to lateral stretch of the skin or to passive arm movements was skewed toward deeper laminae than for tactile cells that did not respond to those manipulations. 4. The variation of activity of tactile neurons during arm movements in different directions was weaker in the superficial laminae than in deeper cortical laminae. 5. Cells with only increases in activity during arm movements were preferentially but not exclusively located in middle and superficial layers. Cells with reciprocal responses were found mainly in laminae III and V, whereas cells with only decreases in activity were concentrated in lamina V. 6. Overall, active arm movements evoke directionally tuned tactile and "deep" activity in areas 3b and 1, in particular in the deeper cortical laminae that are the source of the descending output pathways from SI.     

Neural activity in the primate prefrontal cortex during associative learning

The prefrontal (PF) cortex has been implicated in the remarkable ability of primates to form and rearrange arbitrary associations rapidly. This ability was studied in two monkeys, using a task that required them to learn to make specific saccades in response to particular cues and then repeatedly reverse these responses. We found that the activity of individual PF neurons represented both the cues and the associated responses, perhaps providing a neural substrate for their association. Furthermore, during learning, neural activity conveyed the direction of the animals' impending responses progressively earlier within each successive trial. The final level of activity just before the response, however, was unaffected by learning. These results suggest a role for the PF cortex in learning arbitrary cue-response associations, an ability critical for complex behavior.     

Effects of preliminary perceptual output on neuronal activity of the primary motor cortex.

Observations of single neurons in the primary motor cortex of 1 monkey provided evidence that preliminary perceptual information reaches the motor system before perceptual analysis is complete. Neurons were recorded during a task in which 1 stimulus was assigned to a wrist flexion response and another was assigned to wrist extension. Two stimuli were assigned to a no-go response; each was visually similar to either the flexion or the extension stimulus. When a no-go stimulus was presented, neurons responded with weaker versions of the discharge patterns exhibited to the visually similar stimulus requiring a movement, suggesting that neurons receive partial perceptual information favoring that movement. Functionally separate neuronal populations were identified, and differences in the activations of these provide evidence about the functional effects of preliminary perceptual output on movement control processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention and handedness in bimanual coordination dynamics.

Predictions concerning the effects of handedness and attention on bimanual coordination were made from a dynamical model that incorporates the body's lateral asymmetry. Both handedness and the direction of attention (to the left or right) were manipulated in an inphase 1:1 frequency locking task. Left-handed and right-handed participants had to coordinate the planar oscillations of 2 handheld pendulums while 1 pendulum oscillated between spatial targets positioned over either the left or right hand. Predictions from the model were that participants would show a phase lead with the preferred hand, and that, although the phase lead would be greater when attention was directed to the preferred hand, the variability of relative phase would be lower. Confirmation of these predictions suggests that the dynamical perspective offers the possibility of studying handedness and attention without compromising theoretical precision or experimental control. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Visuospatial versus visuomotor activity in the premotor and prefrontal cortex of a primate

When visuospatial stimuli instruct a limb movement, the stimulus can be said to have both sensory and sensorimotor aspects. We studied the premotor and prefrontal areas of a rhesus monkey in order to identify neuronal activity related to the motor (or instructional) aspects of such stimuli. A rhesus monkey chose limb-movement targets according to one of two rules: (1) visuospatial stimuli instructed and triggered a limb movement toward their locations or (2) identical stimuli triggered a movement toward a predetermined target regardless of their location. Gaze and head fixation assured that each stimulus appeared at a constant location in both retinocentric and craniocentric coordinates, as well as in allocentric space. The task required that the spatial location cued by certain stimuli had to be either remembered or attended after stimulus presentation and before movement. Thus, the visuospatial information presented under one rule differed from that presented under the other only in its motor (instructional) significance and not in its attentional, spatial, mnemonic, or strictly sensory aspects. We could thereby test and confirm the hypothesis that the motor significance of visuospatial cues should commonly affect neuronal activity in the premotor cortex, but less commonly do so in the prefrontal cortex.     

Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements

We develop a statistical thermodynamic model for the phase evolution of DNA-cationic lipid complexes in aqueous solution, as a function of the ratios of charged to neutral lipid and charged lipid to DNA. The complexes consist of parallel strands of DNA intercalated in the water layers of lamellar stacks of mixed lipid bilayers, as determined by recent synchrotron x-ray measurements. Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogeneities in the bilayer charge densities are included. The relevant nonlinear Poisson-Boltzmann equation is solved numerically, including self-consistent treatment of the boundary conditions at the polarized membrane surfaces. For a wide range of lipid compositions, the phase evolution is characterized by three regions of lipid to DNA charge ratio, rho: 1) for low rho, the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d, is constant; 2) for intermediate rho, including the isoelectric point rho = 1, all of the lipid and DNA in solution is incorporated into the complex, whose inter-DNA distance d increases linearly with rho; and 3) for high rho, the complexes coexist with excess liposomes (whose lipid composition is different from that in the complex), and their spacing d is nearly, but not completely, independent of rho. These results can be understood in terms of a simple charging model that reflects the competition between counterion entropy and inter-DNA (rho < 1) and interbilayer (rho > 1) repulsions. Finally, our approach and conclusions are compared with theoretical work by others, and with relevant experiments.     

Variability and correlated noise in the discharge of neurons in motor and parietal areas of the primate cortex

We analyzed the magnitude and interneuronal correlation of the variability in the activity of single neurons that were recorded simultaneously using a multielectrode array in the primary motor cortex and parietal areas 2/5 in rhesus monkeys. The animals were trained to move their arms in one of eight directions as instructed by a visual target. The relationship between variability (SD) and mean of the discharge rate was described by a power function with a similar exponent ( approximately 0.57), regardless of the cortical area or the behavioral condition. We examined whether the deviation from mean activity between target onset and the end of the movement was correlated on a trial-by-trial basis with variability in activity during the hold period before target onset. In both cortical areas, for about a quarter of the neurons, the neuronal noise of these two periods was positively correlated, whereas significant negative correlations were seldom observed. Overall, neurons with higher signal correlation (i.e., similar directional pattern) showed higher noise correlation in both cortical areas. On the other hand, when the data were divided according to the distance between the electrode tips from which the neurons were recorded, a consistent relationship between the signal and noise correlations was found only for pairs of neurons recorded through the same electrode. These results suggest that nearby neurons with similar directional tuning carry primarily redundant messages, whereas neurons in separate cortical columns perform more independent processing.     

Handedness and the asymmetric dynamics of bimanual rhythmic coordination.

Human handedness was investigated in a 1:1 interlimb rhythmic coordination in which consistent and inconsistent left-handed and right-handed individuals oscillated hand-held pendulums. Mean phase difference (φstable) and its standard deviation (SDφ) were evaluated as functions of mode of coordination (in-phase vs anti-phase) and the symmetry conditions imposed by controlling the natural frequencies of the left and right pendulums. The dependencies of φstable and SDφ on coordination mode and imposed symmetry were found to be systematically affected by handedness. The data were consistent with an elaboration of the established order parameter dynamics of interlimb rhythmic coordination. The elaboration includes additional 27π periodic terms that break the symmetry of those dynamics when the natural frequencies of the component rhythmic units are identical. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuronal chemistry and functional organization in the primate visual system

Beginning with the first step of visual processing and proceeding outward from that point, the neurons involved in different aspects of vision are distinct. Stated simply, neurons doing different things look different. They often display distinct morphological features and they usually express different molecules. In addition, neurons that perform a common function usually aggregate together to form recognizable layers or compartments that can be studied in isolation because they are neurochemically distinct. Here is found, then, a junction of two major domains in neuroscience research, as discovery of molecular diversity among neurons is exploited to study organization and function of the primate visual system.     

Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.     

Task-dependent modulation of inhibitory actions within the primary motor cortex

In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205+/-42 ms; FDI 213+/-47 ms). SP duration at tonic isometric contraction amounted to 172+/-35 ms in APB and 178+/-31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159+/-15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies -30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex.     

Neuronal activity in medial frontal cortex during learning of sequential procedures

To study the role of medial frontal cortex in learning and memory of sequential procedures, we examined neuronal activity of the presupplementary motor area (pre-SMA) and supplementary motor area (SMA) while monkeys (n = 2) performed a sequential button press task, "2 x 5 task." In this paradigm, 2 of 16 (4 x 4 matrix) light-emitting diode buttons (called "set") were illuminated simultaneously and the monkey had to press them in a predetermined order. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial. We examined the neuronal activity of each cell using two kinds of hypersets: new hypersets that the monkey experienced for the first time for which he had to find the correct orders of button presses by trial-and-error and learned hypersets that the monkey had learned with extensive practice (n = 16 and 10 for each monkey). To investigate whether cells in medial frontal cortex are involved in the acquisition of new sequences or execution of well-learned procedures, we examined three to five new hypersets and three to five learned hypersets for each cell. Among 345 task-related cells, we found 78 cells that were more active during performance of new hypersets than learned hypersets (new-preferring cells) and 18 cells that were more active for learned hypersets (learned-preferring cells). Among new-preferring cells, 33 cells showed a learning-dependent decrease of cell activity: their activity was highest at the beginning of learning and decreased as the animal acquired the correct response for each set with increasing reliability. In contrast, 11 learned-preferring cells showed a learning-dependent increase of neuronal activity. We found a difference in the anatomic distribution of new-preferring cells. The proportion of new-preferring cells was greater in the rostral part of the medial frontal cortex, corresponding to the pre-SMA, than the posterior part, the SMA. There was some trend that learned-preferring cells were more abundant in the SMA. These results suggest that the pre-SMA, rather than SMA, is more involved in the acquisition of new sequential procedures.