Cortico-spinal modularity in the parieto-frontal system: A new perspective on action control.

Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective.

Development of motor coordination during joint action in mid-childhood.

The ability to act jointly with others is a hallmark of primate evolution and is fundamental for human development. In recent years, the study of coordination strategies between individuals performing joint actions has received growing attention. However, when, in the course of post-natal development, this cognitive-motor function emerges is still unknown. Here, we studied dyads of peers aged 6-9 years, as well as adult subjects, while they performed a task where the same action, namely, exerting hand force on an isometric joystick to move a visual cursor from a central toward a peripheral target, was performed in a "solo" and in a social "cooperative" context. The results revealed that during joint action planning, an attempt to synchronize one's own action with that of a partner emerges at 7 years of age, together with a reduction in the duration and variability of the reaction times. A critical time is 8 years, when "solo" performance reaches a high level of accuracy. From this age, another coordination strategy, based on the online monitoring of the peer's behavior, seems to be implemented during the execution of joint action. The motor and cognitive development occurring during childhood are discussed as possible mechanisms mediating, respectively, the capability and the propensity to take into account the peer's behavior for implementing a common action plan.

Visually-guided correction of hand reaching movements: The neurophysiological bases in the cerebral cortex.

The ability of human and non-human primates to make fast corrections to hand movement trajectories after a sudden shift in the target's location is a key feature of visuo-motor behavior. In healthy individuals, hand movements smoothly adapt to a change in target location without needing to complete the movement to the first target location, as typical of parietal patients. This finding indicates that the nervous system continuously monitors the visual scene and is able to integrate new information in order to produce an efficient motor response. In this paper, we review the kinematics, reaction times and muscle activity observed during the online correction of hand movements as well as the underlying neurophysiological processes studied through single-cell neural recordings in monkeys. Brain stimulation, lesion and imaging studies in humans are also discussed. We demonstrate that while online correction mechanisms strongly depend on the activity of a parieto-frontal network of which the posterior parietal cortex is a crucial node, these mechanisms proceed smoothly and are similar to what is observed during simple point-to-point movements. Online correction of hand movements would rely on feedforward and feedback mechanisms in the parietal cortex, as part of the activity within the fronto-parietal network for the planning and execution of visuo-motor tasks.

A visuomotor disorder in the absence of movement: does optic ataxia generalize to learned isometric hand action?

Visuomotor deficits in parietal patients suffering from Optic Ataxia (OA) have been so far studied during natural reaching movements. We aimed at understanding if these disorders are also present when more abstract visuomotor transformations are involved. A patient with unilateral OA was tested during both standard reaches and isometric actions, therefore in the absence of hand displacement. Isometric action was affected similarly to standard reaches, with endpoint errors to visual targets that were found in both central and peripheral vision. The dissociation of perceptual and motor components of errors highlighted the existence of field, hand and hemispace effects, which depended on the type of error investigated. A generalization of the reaching disorder to learned isometric conditions would suggest that lesions of posterior parietal cortex (PPC) affect sensory-motor transformations not only for standard reaches, but also when visual signals need to be aligned with information from hand force receptors, therefore regardless of the specific remapping required to generate the directional motor output. The isometric impairment emerged with high and similar severity regardless of whether targets were in central or peripheral vision. Since under all isometric conditions gaze and hand position were decoupled, the spatial correspondence between the hand and the gaze seems to play a critical role in this syndrome. This indicates that regardless of the action to be performed and the specific remapping required, there exists in PPC an abstract representation of the directional motor output, where the computation of eye-hand alignment by parietal neurons plays a crucial role.

Neurophysiology of the parieto-frontal system during target interception.

We studied the functional properties of neurons of two elements of the parieto-frontal system: area 7a of the PPC and the motor cortex (M1), during an interception task of stimuli moving in real (RM) and apparent motion (AM). The stimulus moved along a circular path with one of 5 speeds, and was intercepted at 6 o'clock by exerting a force pulse on a joystick. A smooth stimulus motion was produced in RM, whereas in AM 5 stimuli were flashed successively at the vertices of a pentagon. The results showed, that a group of neurons in both areas above responded not only during the interception but also during a NOGO task in which the same stimuli were presented in the absence of a motor response. Most of these neurons were tuned to the stimulus angular position. In addition, we found that the time-varying neuronal activity in both areas was related to various aspects of stimulus motion and hand force, with stimulus-related activity prevailing in area 7a and hand-related activity prevailing in M1. Interestingly, the neural activity was selectively associated with the stimulus angle during RM, whereas it was tightly correlated to the time-to-contact during AM. Thus, the results suggest that area 7a was processing high level features of the circularly moving stimuli and was involved in the production of an early command signal for stimulus interception, whereas M1 was still processing some aspect of the visual stimulus that were used to trigger the interception movement using a predictive mechanism.

Effects of optic flow in motor cortex and area 7a.

Moving visual stimuli were presented to behaving monkeys who fixated their eyes and did not move their arm. The stimuli consisted of random dots moving coherently in eight different kinds of motion (right, left, up, downward, expansion, contraction, clockwise, and counterclockwise) and were presented in 25 square patches on a liquid crystal display projection screen. Neuronal activity in the arm area of the motor cortex and area 7a was significantly influenced by the visual stimulation, as assessed using an ANOVA. The percentage of cells with a statistically significant effect of visual stimulation was 3 times greater in area 7a (370/587, 63%) than in motor cortex (148/693, 21.4%). With respect to stimulus properties, its location and kind of motion had differential effects on cell activity in the two areas. Specifically, the percentage of cells with a significant stimulus location effect was approximately 2.5 times higher in area 7a (311/370, 84%) than in motor cortex (48/148, 32.4%), whereas the percentage of cells with a significant stimulus motion effect was approximately 2 times higher in the motor cortex (79/148, 53.4%) than in area 7a (102/370, 27.6%). We also assessed the selectivity of responses to particular stimulus motions using a Poisson train analysis and determined the percentage of cells that showed activation in only one stimulus condition. This percentage was 2 times higher in the motor cortex (73.7%) than in area 7a (37.7%). Of all kinds of stimulus motion tested, responses to expanding optic flow were the strongest in both cortical areas. Finally, we compared the activation of motor cortical cells during visual stimulation to that observed during force exertion in a center --> out task. Of 514 cells analyzed for both the motor and visual tasks, 388 (75.5%) showed a significant relation to either or both tasks, as follows: 284/388 (73.2%) cells showed a significant relation only to the motor task, 27/388 (7%) cells showed a significant relation only to the visual task, whereas the remaining 77/388 (19.8%) cells showed significant relations to both tasks. Therefore a total of 361/514 (70.2%) cells were related to the motor task and 104/514 (20.2%) were related to the visual task. Finally, with respect to receptive fields (RFs), there was no clear visual receptive field structure in the motor cortical neuronal responses, in contrast to area 7a where RFs were present and could be modulated by the type of optic flow stimulus.

Eye-hand coordination during reaching. I. Anatomical relationships between parietal and frontal cortex.

The anatomical and physiological substrata of eye-hand coordination during reaching were studied through combined anatomical and physiological techniques. The association connections of parietal areas V6A and PEc, and those of dorso-rostral (F7) and dorso-caudal (F2) premotor cortex were studied in monkeys, after physiological characterization of the parietal regions where retrograde tracers were injected. The results show that parieto-occipital area V6A is reciprocally connected with F7, and receives a smaller projection from F2. Local parietal projections to V6A arise from areas MIP and, to a lesser extent, 7m, PEa and PEC: On the contrary, parietal area PEc is strongly and reciprocally connected with the part of F2 located close to the pre-central dimple (pre-CD). Local parietal projections to PEc come from a distributed network, including PEa, MIP, PEci and, to a lesser extent, 7m, V6A, 7a and MST. Premotor area F7 receives parietal projections mainly from 7m and V6A, and local frontal projections mainly from F2. On the contrary, premotor area F2 in the pre-CD zone receives parietal inputs from PEc and, to a lesser extent, PEci, while in the peri-arcuate zone F2 receives parietal projections from PEa and MIP. Local frontal projections to F2 pre-CD mostly stem from F4, and, to a lesser extent, from F7 and F3, and CMAd; those addressed to peri-arcuate zone of F2 arise mainly from F5 and, to a lesser extent, from F7, F4, dorsal (CMAd) and ventral (CMAv) cingulate motor areas, pre-supplementary (F6) and supplementary (F3) motor areas. The distribution of association cells in both frontal and parietal cortex was characterized through a spectral analysis that revealed an arrangement of these cells in the form of bands, composed of cell clusters, or 'columns'. The reciprocal connections linking parietal and frontal cortex might explain the presence of visually related and eye-position signals in premotor cortex, as well as the influence of information about arm position and movement direction in V6A and PEC: The association connections identified in this study might carry sensory as well motor information that presumably provides a basis for a re-entrant signaling. This might be necessary to match retinal-, eye- and hand-related information underlying eye-hand coordination during reaching.

Eye-hand coordination during reaching. II. An analysis of the relationships between visuomanual signals in parietal cortex and parieto-frontal association projections.

The relationships between the distribution of visuomanual signals in parietal cortex and that of parieto-frontal projections are the subject of the present study. Single cell recording was performed in areas PEc and V6A, where different anatomical tracers were also injected. The monkeys performed a variety of behavioral tasks, aimed at studying the visual and motor properties of parietal cells, as well as the potential combination of retinal-, eye- and hand-related signals on cell activity. The activity of most cells was related to the direction of movement and the active position of the hand. Many of these reach-related cells were influenced by eye position information. Fewer cells displayed relationships to saccadic eye movements. The activity of most neurons related to a combination of both hand and eye signals. Many cells were also modulated during preparation for hand movement. Light-dark differences of activity were common and interpreted as related to the sight and monitoring of hand motion and/or position in the visual field. Most cells studied were very sensitive to moving visual stimuli and also responded to optic flow stimulation. Visual receptive fields were generally large and extended to the periphery of the visual field. For most neurons, the orientation of the preferred directions computed across different epochs and tasks conditions clustered within a limited sector of space, the field of global tuning. This can be regarded as an ideal frame to combine spatially congruent eye- and hand-related information for different forms of visuomanual behavior. All these properties were common to both PEc and V6A. Retinal, eye- and hand-related activity types, as well as parieto-frontal association cells, were distributed in a periodic fashion across the tangential domain of areas PEc and V6A. These functional and anatomical distributions were characterized and compared through a spectral and coherency analysis, which revealed the existence of a selective 'match' between activity types and parieto-frontal connections. This match depended on where each individual efferent projection was addressed. The results of the present and of the companion study can be relevant for a re-interpretation of optic ataxia as the consequence of the breakdown of the combination of retinal-, eye- and hand-related directional signals within the global tuning fields of parietal neurons.

Visual motion responses of neurons in the caudal area pe of macaque monkeys.

Area PE of macaques has traditionally been considered a somatosensory association cortex. Recent studies, however, suggest that neurons of this and neighboring areas are involved in the visual control of movement, especially arm movement. We investigated the neuronal sensitivity to local visual stimuli of this region by recording neuronal activity in two behaving macaque monkeys trained in a simple visual fixation task. Recordings were performed from the dorsal surface of the caudal pole of the superior parietal lobule (SPL). Classical receptive fields (RFs) were mapped by using conventional static or moving luminous figures. We found that many neurons in this area were selectively activated by moving visual stimuli. Cell responses were tuned to the movement direction. RFs were usually large; their mean surface covered some 30 x 30 degrees of the visual field. The fovea was often included into RF, in many cases it was along a RF side. The center of RFs was mainly located in the contralateral hemifield, although RFs having the center ipsilaterally sited were also found. No evident retinotopy was found. Visual neurons were especially concentrated in a region of the SPL likely corresponding to area PEc. These results suggest that the caudal part of area PE contains neuronal populations specifically signaling local visual motion, possibly encoding the direction of moving objects. These signals might well be suited for sensorimotor integration mechanisms aimed at motor acts.

Early coding of visuomanual coordination during reaching in parietal area PEc.

The parietal mechanisms of eye-hand coordination during reaching were studied by recording neural activity in area PEc while monkeys performed different tasks, aimed at assessing the influence of retinal, hand-, and eye-related signals on neural activity. The tasks used consisted of 1) reaching to foveated and 2) to extra-foveal targets, with constant eye position; and 3) saccadic eye movement toward, and holding of eye position on peripheral targets, the same as those of the reaching tasks. In all tasks, hand and/or eye movements were made from a central position to eight peripheral targets. A conventional visual fixation paradigm was used as a control task, to assess location and extent of visual receptive field of neurons. A large proportion of cells in area PEc displayed significant relationships to hand movement direction and position. Many of them were also related to the eye's position. Relationships to saccadic eye movements were found for a smaller proportion of cells. Most neurons were tuned to different combination of hand- and eye-related signals; some of them were also influenced by visual information. This combination of signals can be an expression of the early stages of the composition of motor commands for different forms of visuomotor coordination that depend on the integration of hand- and eye-related information. These results assign to area PEc, classically considered as a somatosensory association cortex, a new visuomotor role.

Early coding of reaching in the parietooccipital cortex.

Neural activity was recorded in the parietooccipital cortex while monkeys performed different tasks aimed at investigating visuomotor interactions of retinal, eye, and arm-related signals on neural activity. The tasks were arm reaching 1) to foveated targets; 2) to extrafoveal targets, with constant eye position; 3) within an instructed-delayed paradigm, under both light and darkness; 4) saccadic eye movements toward, and static eye holding on peripheral targets; and 5) visual fixation and stimulation. The activity of many cells was modulated during arm reaction (68%) and movement time (58%), and during static holding of the arm in space (64%), when eye position was kept constant. Eye position influenced the activity of many cells during hand reaction (45%) and movement time (51%) and holding of hand static position (69%). Many cells (56%) were also modulated during preparation for hand movement, in the delayed reach task. Modulation was present also in the dark in 59% of cells during this epoch, 51% during reaction and movement time, and 48% during eye/hand holding on the target. Cells (50%) displaying light-dark differences of activity were considered as related to the sight and monitoring of hand motion and/or position in the visual field. Saccadic eye movements modulated a smaller percentage (25%) of cells than eye position (68%). Visual receptive fields were mapped in 44% of the cells studied. They were generally large and extended to the periphery of the tested (30 degrees ) visual field. Sixty-six percent of cells were motion sensitive. Therefore the activity of many neurons in this area reflects the combined influence of visual, eye, and arm movement-related signals. For most neurons, the orientation of the preferred directions computed across different epochs and tasks, therefore expression of all different eye- and hand-related activity types, clustered within a limited sector of space, the field of global tuning. These spatial fields might be an ideal frame to combine eye and hand signals, thanks to the congruence of their tuning properties. The relationships between cell activity and oculomotor and visuomanual behavior were task dependent. During saccades, most cells were recruited when the eye moved to a spatial location that was also target for hand movement, whereas during hand movement most cells fired depending on whether or not the animal had prior knowledge about the location of the visual targets.

Parieto-frontal coding of reaching: an integrated framework.

In the last few years, anatomical and physiological studies have provided new insights into the organization of the parieto-frontal network underlying visually guided arm-reaching movements in at least three domains. (1) Network architecture. It has been shown that the different classes of neurons encoding information relevant to reaching are not confined within individual cortical areas, but are common to different areas, which are generally linked by reciprocal association connections. (2) Representation of information. There is evidence suggesting that reach-related populations of neurons do not encode relevant parameters within pure sensory or motor "reference frames", but rather combine them within hybrid dimensions. (3) Visuomotor transformation. It has been proposed that the computation of motor commands for reaching occurs as a simultaneous recruitment of discrete populations of neurons sharing similar properties in different cortical areas, rather than as a serial process from vision to movement, engaging different areas at different times. The goal of this paper was to link experimental (neurophysiological and neuroanatomical) and computational aspects within an integrated framework to illustrate how different neuronal populations in the parieto-frontal network operate a collective and distributed computation for reaching. In this framework, all dynamic (tuning, combinatorial, computational) properties of units are determined by their location relative to three main functional axes of the network, the visual-to-somatic, position-direction, and sensory-motor axis. The visual-to-somatic axis is defined by gradients of activity symmetrical to the central sulcus and distributed over both frontal and parietal cortices. At least four sets of reach-related signals (retinal, gaze, arm position/movement direction, muscle output) are represented along this axis. This architecture defines informational domains where neurons combine different inputs. The position-direction axis is identified by the regular distribution of information over large populations of neurons processing both positional and directional signals (concerning the arm, gaze, visual stimuli, etc.) Therefore, the activity of gaze- and arm-related neurons can represent virtual three-dimensional (3D) pathways for gaze shifts or hand movement. Virtual 3D pathways are thus defined by a combination of directional and positional information. The sensory-motor axis is defined by neurons displaying different temporal relationships with the different reach-related signals, such as target presentation, preparation for intended arm movement, onset of movements, etc. These properties reflect the computation performed by local networks, which are formed by two types of processing units: matching and condition units. Matching units relate different neural representations of virtual 3D pathways for gaze or hand, and can predict motor commands and their sensory consequences. Depending on the units involved, different matching operations can be learned in the network, resulting in the acquisition of different visuo-motor transformations, such as those underlying reaching to foveated targets, reaching to extrafoveal targets, and visual tracking of hand movement trajectory. Condition units link these matching operations to reinforcement contingencies and therefore can shape the collective neural recruitment along the three axes of the network. This will result in a progressive match of retinal, gaze, arm, and muscle signals suitable for moving the hand toward the target.

Early motor influences on visuomotor transformations for reaching: a positive image of optic ataxia.

Coding of reaching in the cerebral cortex is based on the operation of distributed populations of parietal and frontal neurons, whose main functional characteristics reside in their combinatorial power, i.e., in the capacity for combining different information related to the spatial aspects of reaching. The tangential distribution of reach-related neurons endowed with different functional properties changes gradually in the cortex and defines, in the parieto-frontal network, trends of functional properties. These visual-to-somatic gradients imply the existence of cortical regions of functional overlaps, i.e., of combinatorial domains, where the integration of different reach-related signals occurs. Studies of early coding of reaching in the mesial parietal areas show how somatomotor information, such as that related to arm posture and movement, influences neuronal activity in the very early stages of the visuomotor transformation underlying the composition of the motor command and is not added "downstream" in the frontal cortex. This influence is probably due to re-entrant signals traveling through fronto-parietal-association connections. Together with the gradient architecture of the network and the reciprocity of cortico-cortical connections, this implies that coding of reaching cannot be regarded as a top-down, serial sequence of coordinate transformation, each performed by a given cortical area, but as a recursive process, where different signals are progressively matched and further elaborated locally, due to intrinsic cortical connections. This model of reaching is also supported by psychophysical studies stressing the parallel processing of the different relevant parameters and the "hybrid" nature of the reference frame where they are combined. The theoretical frame presented here can also offer a background for a new interpretation of a well-known visuomotor disorder, due to superior parietal lesions, i.e., optic ataxia. More than a disconnection syndrome, this can now be interpreted as the consequence of the breakdown of the operations occurring in the combinatorial domains of the superior parietal segment of the parieto-frontal network.

Visual control of hand-reaching movement: activity in parietal area 7m.

The activity of single neurons was studied in parietal area 7m while monkeys performed an instructed-delay reaching task to visual targets under normal light conditions and in darkness. The task was aimed at assessing the influence of vision of hand position on the neural activity of 7m related either to static posture and movement of the hand or to eye position in the orbit. The results show the existence of preparatory, movement-related and postural activity for the control of reaching, all of which are strongly modulated by vision. The activity of many 7m neurons, otherwise insensitive to pure visual stimuli, seems to reflect complex interactions between gaze angle and hand position in the visual field.

Combination of hand and gaze signals during reaching: activity in parietal area 7 m of the monkey.

The role of area 7 m has been studied by recording the activity of single neurons of monkeys trained to fixate and reach toward peripheral targets. The target was randomly selected from eight possible locations on a virtual circle, of radius 30 degrees visual angle from a central target. Three tasks were employed to dissociate hand- from eye-related contributions. In the first task, animals looked and reached to the peripheral target. In a second task, the animal reached to the peripheral target while maintaining fixation on the central target. In the third task, the monkey maintained fixation on peripheral targets that were spatially coincident with those of the reaching tasks. The results show that cell activity in area 7 m relates, for some cells to eye position, for others to hand position and movement, and for the majority of cells to a combination of visuomanual and oculomotor information. This area, therefore, seems to perform an early combination of information in the processing leading from target localization to movement generation.