Neural activity in primary motor and dorsal premotor cortex in reaching tasks with the contralateral versus ipsilateral arm

To investigate the effector dependence of task-related neural activity in dorsal premotor (PMd) and primary motor cortex (M1), directional tuning functions were compared between instructed-delay reaching tasks performed separately with either the contralateral or the ipsilateral limb. During presentation of the instructional cue, the majority (55/90, 61%) of cells in PMd were tuned with both arms, and their dynamic range showed a trend for stronger discharge with the contralateral arm. Most strikingly, however, the preferred direction of most of these latter cells (41/55, 75%) was not significantly different between arms. During movement, many PMd cells continued to be tuned with both arms (53/90, 59%), with a trend for increasing directional differences between the arms over the course of the trial. In contrast, during presentation of the instructional cue only 5/74 (7%) cells in M1 were tuned with both arms. During movement, about half of M1 cells (41/74, 55%) were tuned with both arms but the preferred directions of their tuning functions were often very different and there was a strong bias toward greater discharge rates when the contralateral arm was used. Similar trends were observed for EMG activity. In conclusion, M1 is strongly activated during movements of the contralateral arm, but activity during ipsilateral arm movements is also common and usually different from that seen with the contralateral arm. In contrast, a major component of task-related activity in PMd represents movement in a more abstract or task-dependent and effector-independent manner, especially during the instructed-delay period.     

Distribution of neurons with set- and movement-related activity before hand and foot movements in the premotor cortex of rhesus monkeys

Summary Neuronal activity was studied in the premotor cortex (PM) of two rhesus monkeys, each of which performed both forelimb and hindlimb movements. On each trial, the monkey received a visual instruction stimulus (IS) that indicated whether a foot or a hand movement would be rewarded on that trial. After a delay period, during which the monkey withheld an overt movement, a visual trigger stimulus (TS) was presented to indicate that the monkey should execute a movement. Of 572 task-related neurons recorded in PM, 149 neurons showed set-related activity, defined as a significant increase or decrease in discharge rate throughout most of the instructed delay period, and 299 neurons showed movement-related activity, defined as a significant change in discharge rate between the TS and movement onset. Both setand movement-related activity were subdivided into three patterns: activity modulation 1) before a foot movement only (foot neurons); 2) before a hand movement only (hand neurons); and 3) before both foot and hand movements (mixed neurons). The distribution of set-related neurons mostly overlapped with that of movement-related neurons, although set-related neurons were located in more restricted regions than movement-related neurons. Foot neurons with setand movementrelated activity were distributed near the superior precentral sulcus. Hand neurons were mainly located lateral to the foot neurons with some overlap. The results indicate that most PM setand movement-related neurons contribute, respectively, to the preparation for and execution of specific limb movements, as opposed to movement per se. Further, the differential distribution of neurons with activity related to hindlimb vs. forelimb movement supports previous indications that PM is topographically organized.     

Role of the prefrontal cortex in the cognitive control of reaching movements: near-infrared spectroscopy study

To elucidate the role of the prefrontal cortex in cognitive control of reaching movements, by multichannel near-infrared spectroscopy we examine changes in oxygenated hemoglobin (oxy-Hb) as an indicator of changes in regional cerebral blood flow in the bilateral dorsolateral (DLPFC), ventrolateral prefrontal cortex (VLPFC), and frontopolar cortex (FPC) during a reaching task with normal visual feedback (a consistent task) and a reaching task with flipped horizontal visual feedback (an inconsistent task). Subjects first perform 12 trials of the consistent task, and then perform six blocks of the inconsistent task, each of which consists of six trials. During the consistent task, oxy-Hb is increased only in the right VLPFC. During the first block of the inconsistent task, increases in oxy-Hb are observed in the bilateral DLPFC and the right VLPFC, whereas the increased oxy-Hb was gradually reduced as the block proceeded, which was accompanied by an improvement in the task performance. Eventually, there were no differences in the degree of change in oxy-Hb between the consistent and inconsistent tasks in the DLPFC and VLPFC. These findings suggest that the DLPFC is engaged in higher order cognitive control, while the right VLPFC is engaged in both higher and lower order cognitive controls.     

Inhibition of contralateral premotor cortex delays visually guided reaching movements in men but not in women

The premotor-parietal network for preparation of visually guided reaching demonstrates activity mainly contralateral to the reaching arm in men but bilaterally in women. These sex differences are most prominent in the dorsal premotor cortex (PMd); however, the functional implications of these differences remain unclear. Therefore, in the experiments described here, we used continuous theta burst stimulation (cTBS) to test hypotheses regarding the roles of PMd both contralateral and ipsilateral to the reaching arm in men and in women. Inhibitory cTBS of the ipsilateral PMd did not have a significant effect on reaction time in either men or women. However, cTBS of the contralateral PMd resulted in a slowed mean reaction time in men but not in women. Movement times were unaffected by stimulation applied to either hemisphere. These results suggest the presence of sex differences in processing within the left PMd during visually guided reaching movements using the right arm. Further, when taken together, the results suggest that ipsilateral PMd activity in women may not be functionally necessary for reaching movements. Rather, this ipsilateral activity may provide a protective redundancy that can compensate for decreased activity from the contralateral PMd. The observation of sex differences in reaction times but not in movement times following cTBS to the contralateral hemisphere suggests that these sex differences are more strongly associated with movement planning than with motor execution.     

Dissociable mechanisms of cognitive control in prefrontal and premotor cortex

Intelligent behavior depends on the ability to suppress inappropriate actions and resolve interference between competing responses. Recent clinical and neuroimaging evidence has demonstrated the involvement of prefrontal, parietal, and premotor areas during behaviors that emphasize conflict and inhibition. It remains unclear, however, whether discrete subregions within this network are crucial for overseeing more specific inhibitory demands. Here we probed the functional specialization of human prefrontal cortex by combining repetitive transcranial magnetic stimulation (rTMS) with integrated behavioral measures of response inhibition (stop-signal task) and response competition (flanker task). Participants undertook a combined stop-signal/flanker task after rTMS of the inferior frontal gyrus (IFG) or dorsal premotor cortex (dPM) in each hemisphere. Stimulation of the right IFG impaired stop-signal inhibition under conditions of heightened response competition but did not influence the ability to suppress a competing response. In contrast, stimulation of the right dPM facilitated execution but had no effect on inhibition. Neither of these results was observed during rTMS of corresponding left-hemisphere regions. Overall, our findings are consistent with existing evidence that the right IFG is crucial for inhibitory control. The observed double dissociation of neurodisruptive effects between the right IFG and right dPM further implies that response inhibition and execution rely on distinct neural processes despite activating a common cortical network.     

Corticocortical inputs to the dorsal and ventral aspects of the premotor cortex of macaque monkeys.

Recent cytoarchitectonic, histochemical and physiological studies have shown that the lateral part of area 6 (the premotor cortex) of macaque monkeys can be divided into at least two subregions, each of which is considered to play an important role in motor control. One lies in the dorsal aspect of the premotor cortex (PMd) medial to the spur of the arcuate sulcus, and the other in the ventral aspect of the premotor cortex (PMv) lateral to it. Since there is little information on the corticocortical inputs to the PMd, wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was injected into both the PMd and PMv to study corticocortical inputs to these two regions, and the distribution of retrogradely labeled cells was compared. When WGA-HRP was injected into the region immediately lateral to the superior precentral sulcus within the PMd, retrogradely labeled neurons were found in area 6 lying in the mesial wall possibly corresponding to the supplementary motor area (SMA), areas 24 and 23 of the cingulate cortex, rostral region of area 4, and area 5 (area PEa). In contrast, when WGA-HRP was injected into the PMv immediately caudal to the arcuate sulcus and lateral to the spur of the arcuate sulcus, the labeled cells were found in area 7 (areas POa, PF, PFG), area 5 (area PEa), area PFop (secondary somatosensory area), SMA, the cingulate cortex (areas 24), caudal region of area 4 in the rostral bank of the central sulcus, and area 3a. It appears that the differences in the corticocortical inputs contribute to specialization of the PMd and PMv for their differential roles in motor control.     

Modest gaze-related discharge modulation in monkey dorsal premotor cortex during a reaching task performed with free fixation

Recent studies have shown that gaze angle modulates reach-related neural activity in many cortical areas, including the dorsal premotor cortex (PMd), when gaze direction is experimentally controlled by lengthy periods of imposed fixation. We looked for gaze-related modulation in PMd during the brief fixations that occur when a monkey is allowed to look around freely without experimentally imposed gaze control while performing a center-out delayed arm-reaching task. During the course of the instructed-delay period, we found significant effects of gaze angle in 27-51% of PMd cells. However, for 90-95% of cells, these effects accounted for <20% of the observed discharge variance. The effect of gaze was significantly weaker than the effect of reach-related variables. In particular, cell activity during the delay period was more strongly related to the intended movement expressed in arm-related coordinates than in gaze-related coordinates. Under the same experimental conditions, many cells in medial parietal cortex exhibited much stronger gaze-related modulation and expressed intended movement in gaze-related coordinates. In summary, gaze direction-related modulation of cell activity is indeed expressed in PMd during the brief fixations that occur in natural oculomotor behavior, but its overall effect on cell activity is modest.     

Differential relation of discharge in primary motor cortex and premotor cortex to movements versus actively maintained postures during a reaching task

The activity of cells in primary motor cortex (MI) and dorsal premotor cortex (PMd) were compared during reaching movements in a reaction-time (RT) task, without prior instructions, which required precise control of limb posture before and after movement. MI neurons typically showed strong, directionally tuned activity prior to and during movement as well as large gradations of tonic activity while holding the limb over different targets. The directionality of their movementand posture-related activity was generally similar. Proximal-arm muscles behaved similarly. This is consistent with a role for MI in the moment-to-moment control of motor output, including both movement and actively maintained postures, and suggests a common functional relation for MI cells to both aspects of motor behavior. In contrast, PMd cells were generally more phasic, frequently emitting only strong bursts of activity confined mainly to the behavioral reaction time before movement onset. PMd tonic activity during different postures was generally weaker than in MI, and showed a much more variable relation with their movement-related directional tuning. These results imply that the major contribution of PMd to this RT task occurred prior to the onset of movement itself, consistent with a role for PMd in the selection and planning of visually guided movements. Furthermore, the nature of the relative contribution of PMd to movement versus actively maintained postures appears to be fundamentally different from that in MI. Finally, there was a continuous gradient of changes in responses across the rostrocaudal extent of the precentral gyrus, with no abrupt transition in response properties between PMd and MI.     

Role of the medial parieto-occipital cortex in the control of reaching and grasping movements

The medial parieto-occipital cortex is a central node in the dorsomedial visual stream. Recent physiological studies in the macaque monkey have demonstrated that the medial parieto-occipital cortex contains two areas, the visual area V6 and the visuomotor area V6A. Area V6 is a retinotopically organized visual area that receives form and motion information directly from V1 and is heavily connected with the other areas of the dorsal visual stream, including V6A. Area V6A is a bimodal visual/somatosensory area that elaborates visual information such as form, motion and space suitable for the control of both reaching and grasping movements. Somatosensory and skeletomotor activities in V6A affect the upper limbs and involve both the transport phase of reaching and grasping movements. Finally, V6A is strongly and reciprocally connected with the dorsal premotor cortex controlling arm movements. The picture emerging from these data is that the medial parieto-occipital cortex is well equipped to control both proximal and distal movements in the online visuomotor guidance of prehension. In agreement with this view, selective V6A lesions in monkey produce misreaching and misgrasping with the arm contralateral to the lesion in visually guided movements. These deficits are similar to those observed in optic ataxia patients and suggest that human and monkey superior parietal lobules are homologous structures, and that optic ataxia syndrome is the result of the lesion of a 'human' area V6A.     

Time-modulated neuronal activity in the premotor cortex of macaque monkeys

A voluntary motor act, executed in response to a stimulus, requires both spatial and temporal computation. Even though electrophysiological and positron emission tomography (PET) investigations on humans suggest that SMA, medial prefrontal cortex and primary motor cortex play a role in temporal mechanisms, we have few data about neuronal time computation in the premotor cortex. The involvement of monkey premotor area (PM) in motor learning and cognitive processes, and the presence of buildup neurons, whose activity is closely related to the motor action, prompted us to investigate the involvement of these set-related neurons in the time domain. To this end we manipulated the duration of a pre-cue in a visuomotor task while recording unit activity. We found that, when the duration of the pre-cue was predictable and long (5 s), delay of the onset of cell activity in consecutive trials gradually increased. On the other hand, when the duration was unpredictable or predictable and short (1 s), this phenomenon could not be detected. The inconsistent discharge correlations with expected reward and attentional processes, and the specific discharge relationship to the time instruction, suggest that these buildup neurons reflect a learning process in the time domain.     

Differential neural correlates of reciprocal activation and cocontraction control in dorsal and ventral premotor cortices

Efficient control of reciprocal activation and cocontraction of the muscles are critical to perform skillful actions with suitable force and impedance. However, it remains unclear how the brain controls force and impedance while recruiting the same set of muscles as actuators. Does control take place at the single muscle level leading to force and impedance, or are there higher-order centers dedicated to controlling force and impedance? We addressed this question using functional MRI during voluntary isometric wrist contractions with online electromyogram feedback. Comparison of the brain activity between the conditions requiring control of either wrist torque or cocontraction demonstrates that blood oxygen level-dependent activity in the caudo-dorsal premotor cortex (PMd) correlates well with torque, whereas the activity in the ventral premotor cortex (PMv) correlates well with the level of cocontraction. This suggests distinct roles of the PMd and PMv in the voluntary control of reciprocal activation and cocontraction of muscles, respectively.     

Postreinforcement changes of steady potentials in premotor cortex of monkeys

Slow potential changes were recorded from premotor cortex and several subcortical regions during a reaction time foreperiod experiment. When reinforced trials were alternated in blocks of 5 trials with unreinforced trials, the cortical DC potential increased in negativity to about −300 μV over the course of reinforced trials and declined to baseline during nonreinforced trials. Change in the cortical potential occurred after ingestion of liquid reinforcement was completed. Since positive potentials have been reported to appear in posterior cortex during reinforcement, the frontal potential was thought to be a frontally unique phenomenon and was referred to as postingestion frontal negativity (PIFN). No similar changes occurred in subcortical sites.     

Inhibitory control of reaching movements in humans

Behavioral flexibility provides a very large repertoire of actions and strategies, however, it carries a cost: a potential interference between different options. The voluntary control of behavior starts exactly with the ability of deciding between alternatives. Certainly inhibition plays a key role in this process. Here we examined the inhibitory control of reaching arm movements with the countermanding paradigm. Right-handed human subjects were asked to perform speeded reaching movements toward a visual target appearing either on the same or opposite side of the reaching arm (no-stop trials), but to withhold the commanded movement whenever an infrequent stop signal was presented (stop trials). As the delay between go and stop signals increased, subjects increasingly failed to inhibit the movement. From this inhibitory function and the reaction times of movements in no-stop trials, we estimated the otherwise unobservable duration of the stopping process, the stop signal reaction time (SSRT). We found that the SSRT for reaching movements was, on average, 206 ms and that it varied with the reaching arm and the target position even though the stop signal was a central stimulus. In fact, subjects were always faster to withhold reaching movements toward visual targets appearing on the same side of the reaching arm. This behavior strictly parallels the course of the reaction times of no-stop trials. These data show that the stop and go processes interacting in this countermanding task are independent, but most likely influenced by a common factor when under the control of the same hemisphere. In addition, we show that the point beyond which the response cannot be inhibited, the so-called point-of-no-return that divides controlled and ballistic phases of movement processing, lies after the inter-hemispheric transfer.     

Neural representation of information measure in the primate premotor cortex

Animals seek information to reduce their efforts to receive rewards and perform actions that enable them to gain more information. The ability of seeking information subserves higher cognition processes such as planning and reasoning. There exists limited information on how the brain measures and seeks information. In this study, I discuss results indicating that the brain quantifies information by using the information-theoretic measure. The monkeys were trained to perform saccadic eye movement to one of the visual targets. When required to choose from the targets that included varying amounts of information regarding the goal, the animals selected the most informative target. While making a choice, the neurons in the dorsal premotor cortex exhibited activity that reflected the corresponding information value. The population response of these neurons was examined using the following three measures: the information-theoretic measure, probability gain, and absolute change in beliefs. Changes in this response exhibited relatively similar proportionality to the three measures. An analysis of two intuitive conditions for information measures, decreasing monotonicity on probability and additivity between independent events, showed that only the information-theoretic measure satisfies both the conditions. These results suggest that in comparison with the other measures, the information-theoretic measure is more plausible for information measure in the brain.     

An antioxidant-induced improvement in the cognitive characteristics of monkeys: Neurophysiological correlates in the visual cortex

After the injection of the antioxidant, oxymethacil (4–5 μg/kg), in an investigation in monkeys of the processes of delayed visual recognition, their cognitive characteristics were significantly improved.: the duration of the short-term storage of information increased (by a factor of 2–3) and the time of the motor reaction decreased. The improvement of the cognitive characteristics was accompanied by changes in the neuronal activity in the visual cortex at all stages of recognition. The activity of the majority of the neurons increased in the case of discrimination without delay; it decreased significantly in the case of delayed discrimination. The administration of oxymethacil induced an increase in the auto-and cross-correlation coefficients in the respondent reactions of the recorded groups of neurons. The results obtained suggest that oxymethacil possesses nootropic properties, and the participation of the visual cortex of monkeys in the realization of these properties for the improvement of cognitive characteristics. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 78, No. 12, pp. 78–87, December, 1992.     

Reference frames for reach planning in macaque dorsal premotor cortex

When a human or animal reaches out to grasp an object, the brain rapidly computes a pattern of muscular contractions that can acquire the target. This computation involves a reference frame transformation because the target's position is initially available only in a visual reference frame, yet the required control signal is a set of commands to the musculature. One of the core brain areas involved in visually guided reaching is the dorsal aspect of the premotor cortex (PMd). Using chronically implanted electrode arrays in two Rhesus monkeys, we studied the contributions of PMd to the reference frame transformation for reaching. PMd neurons are influenced by the locations of reach targets relative to both the arm and the eyes. Some neurons encode reach goals using limb-centered reference frames, whereas others employ eye-centered reference fames. Some cells encode reach goals in a reference frame best described by the combined position of the eyes and hand. In addition to neurons like these where a reference frame could be identified, PMd also contains cells that are influenced by both the eye- and limb-centered locations of reach goals but for which a distinct reference frame could not be determined. We propose two interpretations for these neurons. First, they may encode reach goals using a reference frame we did not investigate, such as intrinsic reference frames. Second, they may not be adequately characterized by any reference frame.