Modulation of reaching by spatial attention.

Attention is needed to perform goal-directed vision-guided movements. We investigated whether the direction of covert attention modulates movement outcomes and dynamics. Right-handed and left-handed volunteers attended to a spatial location while planning a reach toward the same hemifield, the opposite one, or planned a reach without constraining attention. We measured behavioral variables as outcomes of ipsilateral and contralateral reaching and the tangling of behavioral trajectories obtained through principal component analysis as a measure of the dynamics of motor control. We found that the direction of covert attention had significant effects on the dynamics of motor control, specifically during contralateral reaching. Data suggest that motor control was more feedback-driven when attention was directed leftward than when attention was directed rightward or when it was not constrained, irrespectively of handedness. These results may help to better understand the neural bases of asymmetrical neurological diseases like hemispatial neglect.

rTMS over the human medial parietal cortex impairs online reaching corrections.

Indirect correlational evidence suggests that the posteromedial sector of the human parietal cortex (area hV6A) is involved in reaching corrections. We interfered with hV6A functions using repetitive transcranial magnetic stimulation (rTMS) while healthy participants performed reaching movements and in-flight adjustments of the hand trajectory in presence of unexpected target shifts. rTMS over hV6A specifically altered action reprogramming, causing deviations of the shifted trajectories, particularly along the vertical dimension (i.e., distance). This study provides evidence of the functional relevance of hV6A in action reprogramming while a sudden event requires a change in performance and shows that hV6A also plays a role in state estimation during reaching. These findings are in line with neurological data showing impairments in actions performed along the distance dimension when lesions occur in the dorsal posterior parietal cortex.

A Short Route for Reach Planning between Human V6A and the Motor Cortex.

In the macaque monkey, area V6A, located in the medial posterior parietal cortex, contains cells that encode the spatial position of a reaching target. It has been suggested that during reach planning this information is sent to the frontal cortex along a parieto-frontal pathway that connects V6A-premotor cortex-M1. A similar parieto-frontal network may also exist in the human brain, and we aimed here to study the timing of this functional connection during planning of a reaching movement toward different spatial positions. We probed the functional connectivity between human area V6A (hV6A) and the primary motor cortex (M1) using dual-site, paired-pulse transcranial magnetic stimulation with a short (4 ms) and a longer (10 ms) interstimulus interval while healthy participants (18 men and 18 women) planned a visually-guided or a memory-guided reaching movement toward positions located at different depths and directions. We found that, when the stimulation over hV6A is sent 4 ms before the stimulation over M1, hV6A inhibits motor-evoked potentials during planning of either rightward or leftward reaching movements. No modulations were found when the stimulation over hV6A was sent 10 ms before the stimulation over M1, suggesting that only short medial parieto-frontal routes are active during reach planning. Moreover, the short route of hV6A-premotor cortex-M1 is active during reach planning irrespectively of the nature (visual or memory) of the reaching target. These results agree with previous neuroimaging studies and provide the first demonstration of the flow of inhibitory signals between hV6A and M1.SIGNIFICANCE STATEMENT All our dexterous movements depend on the correct functioning of the network of brain areas. Knowing the functional timing of these networks is useful to gain a deeper understanding of how the brain works to enable accurate arm movements. In this article, we probed the parieto-frontal network and demonstrated that it takes 4 ms for the medial posterior parietal cortex to send inhibitory signals to the frontal cortex during reach planning. This fast flow of information seems not to be dependent on the availability of visual information regarding the reaching target. This study opens the way for future studies to test how this timing could be impaired in different neurological disorders.

Complementary contribution of the medial and lateral human parietal cortex to grasping: a repetitive TMS study.

The dexterous control of our grasping actions relies on the cooperative activation of many brain areas. In the parietal lobe, 2 grasp-related areas collaborate to orchestrate an accurate grasping action: dorsolateral area AIP and dorsomedial area V6A. Single-cell recordings in monkeys and fMRI studies in humans have suggested that both these areas specify grip aperture and wrist orientation, but encode these grasping parameters differently, depending on the context. To elucidate the causal role of phAIP and hV6A, we stimulated these areas, while participants were performing grasping actions (unperturbed grasping). rTMS over phAIP impaired the wrist orientation process, whereas stimulation over hV6A impaired grip aperture encoding. In a small percentage of trials, an unexpected reprogramming of grip aperture or wrist orientation was required (perturbed grasping). In these cases, rTMS over hV6A or over phAIP impaired reprogramming of both grip aperture and wrist orientation. These results represent the first direct demonstration of a different encoding of grasping parameters by 2 grasp-related parietal areas.

The Superior Parietal Lobule of Macaque Monkey: Relative Influence of Gaze and Static Arm Position during Reaching.

The superior parietal lobule (SPL) integrates somatosensory, motor, and visual signals to dynamically control arm movements. During reaching, visual and gaze signals are used to guide the hand to the desired target location, while proprioceptive signals allow to correct arm trajectory, and keep the limb in the final position at the end of the movement. Three SPL areas are particularly involved in this process: V6A, PEc, PE. Here, we evaluated the influence of eye and arm position on single neuron activity of these areas during the holding period at the end of arm reaching movements, when the arm is motionless and gaze and hand positions are aligned. Two male macaques (Macaca fascicularis) performed a foveal reaching task while single unit activity was recorded from areas V6A, PEc, and PE. We found that at the end of reaching movements the neurons of all these areas were modulated by both eye position and static position of the arm. V6A and PEc showed a prevalent combination of gaze and proprioceptive input, while PE seemed to encode these signals more independently. Our results demonstrate that all these SPL areas combine gaze and proprioceptive input to provide an accurate monitoring of arm movements.

Functional Connectivity at Rest between the Human Medial Posterior Parietal Cortex and the Primary Motor Cortex Detected by Paired-Pulse Transcranial Magnetic Stimulation.

The medial posterior parietal cortex (PPC) is involved in the complex processes of visuomotor integration. Its connections to the dorsal premotor cortex, which in turn is connected to the primary motor cortex (M1), complete the fronto-parietal network that supports important cognitive functions in the planning and execution of goal-oriented movements. In this study, we wanted to investigate the time-course of the functional connectivity at rest between the medial PPC and the M1 using dual-site transcranial magnetic stimulation in healthy humans. We stimulated the left M1 using a suprathreshold test stimulus to elicit motor-evoked potentials in the hand, and a subthreshold conditioning stimulus was applied over the left medial PPC at different inter-stimulus intervals (ISIs). The conditioning stimulus affected the M1 excitability depending on the ISI, with inhibition at longer ISIs (12 and 15 ms). We suggest that these modulations may reflect the activation of different parieto-frontal pathways, with long latency inhibitions likely recruiting polisynaptic pathways, presumably through anterolateral PPC.

Transcranial Magnetic Stimulation Over the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning.

Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A-hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.

Neural coding of action in three dimensions: Task- and time-invariant reference frames for visuospatial and motor-related activity in parietal area V6A.

Goal-directed movements involve a series of neural computations that compare the sensory representations of goal location and effector position, and transform these into motor commands. Neurons in posterior parietal cortex (PPC) control several effectors (e.g., eye, hand, foot) and encode goal location in a variety of spatial coordinate systems, including those anchored to gaze direction, and to the positions of the head, shoulder, or hand. However, there is little evidence on whether reference frames depend also on the effector and/or type of motor response. We addressed this issue in macaque PPC area V6A, where previous reports using a fixate-to-reach in depth task, from different starting arm positions, indicated that most units use mixed body/hand-centered coordinates. Here, we applied singular value decomposition and gradient analyses to characterize the reference frames in V6A while the animals, instead of arm reaching, performed a nonspatial motor response (hand lift). We found that most neurons used mixed body/hand coordinates, instead of "pure" body-, or hand-centered coordinates. During the task progress the effect of hand position on activity became stronger compared to target location. Activity consistent with body-centered coding was present only in a subset of neurons active early in the task. Applying the same analyses to a population of V6A neurons recorded during the fixate-to-reach task yielded similar results. These findings suggest that V6A neurons use consistent reference frames between spatial and nonspatial motor responses, a functional property that may allow the integration of spatial awareness and movement control.

The neglected medial part of macaque area PE: segregated processing of reach depth and direction.

Area PE (Brodmann's area 5), located in the posterior parietal cortex (PPC), is involved in the control of arm movements. Many monkey studies showed PE's involvement in reach directions, while only a few revealed signals coding the depth of reaches. Notably, all these studies focused on the lateral part of PE, leaving its medial part functionally largely unexplored. We here recorded neuronal activity in the medial part of PE in three male Macaca fascicularis while they performed coordinated eye and arm movements in darkness towards targets located at different directions and depths. We used the same task as in our previous studies of more caudal PPC sectors (areas V6A and PEc), allowing a direct comparison between these three PPC areas. We found that, in medial PE, reach direction and depth were encoded mainly by distinct populations of neurons. Directional signals were more prominent before movement onset, whereas depth processing occurred mainly during and after movement execution. Visual and somatosensory mapping of medial PE revealed a lack of visual responses yet strong somatosensory sensitivity, with a representation of both upper and lower limbs, distinct from the somatotopy reported in lateral PE. This study shows that PE is strongly involved in motor processing of depth and direction information during reaching. It highlights a trend in medial PPC, going from the joint coding of depth and direction signals caudally, in area V6A, to a largely segregated processing of the two signals rostrally, in area PE.

Neurons Modulated by Action Execution and Observation in the Macaque Medial Parietal Cortex.

The observation of an action evokes discharges in a rich network of cortical areas [1-14]. In the present study, we have evaluated the effect of grasp execution and of the observation of others' grasping on the activity of neurons in the medial parietal area V6A, an area of the reach-to-grasp network never explored to date in this regard. Although V6A neurons are typically active during one's own grasping execution but not while one observes another's grasping, a minority of neurons showed mirror properties, active both when monkeys performed the task and when they observed it being performed by the experimenter. Recent studies have shown that the discharge of mirror neurons may vary from congruent to noncongruent [7, 10, 15-17], but most mirror neurons show a clear relation between the visual action they respond to and the motor response they code [10], thus matching the sensory description of an observed action with its corresponding internal motor representation. In all V6A putative mirror neurons, instead, neural representations during execution and observation were highly dissimilar, discounting the possibility that V6A specifically encodes the grip type performed by another agent. Notably, we have found that in these neurons, the neural representation of an object changed according to whether grasping was allowed or performed and whether the object was the target of another agent's grasping. In other words, rather than code another agent's observed action, V6A neurons appear to primarily encode the relevance, in the grasping context, of the target object.

Preparatory activity for purposeful arm movements in the dorsomedial parietal area V6A: Beyond the online guidance of movement.

Over the years, electrophysiological recordings in macaque monkeys performing visuomotor tasks brought about accumulating evidence for the expression of neuronal properties (e.g., selectivity in the visuospatial and somatosensory domains, encoding of visual affordances and motor cues) in the posterior parietal area V6A that characterize it as an ideal neural substrate for online control of prehension. Interestingly, neuroimaging studies suggested a role of putative human V6A also in action preparation; moreover, pre-movement population activity in monkey V6A has been recently shown to convey grip-related information for upcoming grasping. Here we directly test whether macaque V6A neurons encode preparatory signals that effectively differentiate between dissimilar actions before movement. We recorded the activity of single V6A neurons during execution of two visuomotor tasks requiring either reach-to-press or reach-to-grasp movements in different background conditions, and described the nature and temporal dynamics of V6A activity preceding movement execution. We found striking consistency in neural discharges measured during pre-movement and movement epochs, suggesting that the former is a preparatory activity exquisitely linked to the subsequent execution of particular motor actions. These findings strongly support a role of V6A beyond the online guidance of movement, with preparatory activity implementing suitable motor programs that subsequently support action execution.

Prediction of Reach Goals in Depth and Direction from the Parietal Cortex.

The posterior parietal cortex is well known to mediate sensorimotor transformations during the generation of movement plans, but its ability to control prosthetic limbs in 3D environments has not yet been fully demonstrated. With this aim, we trained monkeys to perform reaches to targets located at various depths and directions and tested whether the reach goal position can be extracted from parietal signals. The reach goal location was reliably decoded with accuracy close to optimal (>90%), and this occurred also well before movement onset. These results, together with recent work showing a reliable decoding of hand grip in the same area, suggest that this is a suitable site to decode the entire prehension action, to be considered in the development of brain-computer interfaces.

Interplay Between Grip and Vision in the Monkey Medial Parietal Lobe.

We aimed at understanding the relative contribution of visual information and hand shaping to the neuronal activity of medial posterior parietal area V6A, a newly added area in the monkey cortical grasping circuit. Two Macaca fascicularis performed a Reach-to-Grasp task in the dark and in the light, grasping objects of different shapes. We found that V6A contains Visual cells, activated only during grasping in the light; Motor neurons, equally activated during grasping in the dark and in the light; Visuomotor cells, differently activated while grasping in the dark and in the light. Visual, Motor, and Visuomotor neurons were moderately or highly selective during grasping, whereas they reduced their selectivity during object observation without performing grasping. The use of the same experimental design employed in the dorsolateral grasping area AIP by other authors allowed us to compare the grasp-related properties of V6A and AIP. From these data and from the literature a frame emerges with many similarities between medial grasping area V6A and lateral grasping area AIP: both areas update and control prehension, with V6A less sensitive than AIP to fine visual details of the objects to be grasped, but more involved in coordinating reaching and grasping.

Sensory properties of the caudal aspect of the macaque's superior parietal lobule.

In the superior parietal lobule (SPL), the anterior part (area PE) is known to process somatosensory information, while the caudalmost part (areas V6Av and V6) processes visual information. Here we studied the visual and somatosensory properties of the areas PEc and V6Ad located in between the somatosensory and visual domains of SPL. About 1500 neurons were extracellularly recorded in 19 hemispheres of 12 monkeys (Macaca fascicularis). Visual and somatosensory properties of single neurons were generally studied separately, while in a subpopulation of neurons, both the sensory properties were tested. Visual neurons were more represented in V6Ad and somatosensory neurons in PEc. The visual neurons of these two areas showed similar properties and represented a large part of the contralateral visual field, mostly the lower part. In contrast, somatosensory neurons showed remarkable differences. The arms were overrepresented in both the areas, but V6Ad represented only the upper limbs, whereas PEc both the upper and lower limbs. Interestingly, we found that in both the areas, bimodal visual-somatosensory cells represented the proximal part of the arms. We suggest that PEc is involved in locomotion and in the control of hand/foot interaction with the objects of the environment, while V6Ad is in the control of the object prehension specifically performed with the upper limbs. Neuroimaging and lesion studies from literature support a strict homology with humans.

Decoding Information for Grasping from the Macaque Dorsomedial Visual Stream.

Neurodecoders have been developed by researchers mostly to control neuroprosthetic devices, but also to shed new light on neural functions. In this study, we show that signals representing grip configurations can be reliably decoded from neural data acquired from area V6A of the monkey medial posterior parietal cortex. Two Macaca fascicularis monkeys were trained to perform an instructed-delay reach-to-grasp task in the dark and in the light toward objects of different shapes. Population neural activity was extracted at various time intervals on vision of the objects, the delay before movement, and grasp execution. This activity was used to train and validate a Bayes classifier used for decoding objects and grip types. Recognition rates were well over chance level for all the epochs analyzed in this study. Furthermore, we detected slightly different decoding accuracies, depending on the task's visual condition. Generalization analysis was performed by training and testing the system during different time intervals. This analysis demonstrated that a change of code occurred during the course of the task. Our classifier was able to discriminate grasp types fairly well in advance with respect to grasping onset. This feature might be important when the timing is critical to send signals to external devices before the movement start. Our results suggest that the neural signals from the dorsomedial visual pathway can be a good substrate to feed neural prostheses for prehensile actions.SIGNIFICANCE STATEMENT Recordings of neural activity from nonhuman primate frontal and parietal cortex have led to the development of methods of decoding movement information to restore coordinated arm actions in paralyzed human beings. Our results show that the signals measured from the monkey medial posterior parietal cortex are valid for correctly decoding information relevant for grasping. Together with previous studies on decoding reach trajectories from the medial posterior parietal cortex, this highlights the medial parietal cortex as a target site for transforming neural activity into control signals to command prostheses to allow human patients to dexterously perform grasping actions.

Temporal stability of reference frames in monkey area V6A during a reaching task in 3D space.

Neurons in the posterior parietal cortex of macaques show spatial tuning during several phases of an instructed delay reaching task, but their reference frames have been studied mostly during fixed periods without addressing how they evolve across task phases. In parietal area V6A, we reported recently that during the late delay and hand movement periods, most neurons represent target location either in body-centered frame of reference, or in mixed body/hand-centered coordinates, with no evidence of hand-centered representations. Here, we characterized the spatial representations of V6A neurons in earlier task epochs, i.e., immediately after target fixation and in the subsequent main part of the delay and examined whether the reference frames of individual neurons are stable across the task. We report no evidence of hand-centered coding also in the earlier phases of the task. Shortly, after target fixation and throughout the main part of the delay period, V6A neurons used either body-centered or mixed body/hand-centered reference frames. Most of the cells showed consistent reference frames across epochs. Interestingly, a population trend of shifting from mixed body/hand-centered frames to 'pure' body-centered coordinates was found as the task progressed. These findings suggest that, similar to other parietal areas, in V6A, the reference frames show a limited degree of temporal evolution. The stronger presence of mixed coding at the early task stages could reflect the early involvement of V6A in eye-hand coordination, whereas the increase in spatiotopic representations towards movement execution could be related to its role in online movement control.

Vision for Prehension in the Medial Parietal Cortex.

In the last 2 decades, the medial posterior parietal area V6A has been extensively studied in awake macaque monkeys for visual and somatosensory properties and for its involvement in encoding of spatial parameters for reaching, including arm movement direction and amplitude. This area also contains populations of neurons sensitive to grasping movements, such as wrist orientation and grip formation. Recent work has shown that V6A neurons also encode the shape of graspable objects and their affordance. In other words, V6A seems to encode object visual properties specifically for the purpose of action, in a dynamic sequence of visuomotor transformations that evolve in the course of reach-to-grasp action.We propose a model of cortical circuitry controlling reach-to-grasp actions, in which V6A acts as a comparator that monitors differences between current and desired hand positions and configurations. This error signal could be used to continuously update the motor output, and to correct reach direction, hand orientation, and/or grip aperture as required during the act of prehension.In contrast to the generally accepted view that the dorsomedial component of the dorsal visual stream encodes reaching, but not grasping, the functional properties of V6A neurons strongly suggest the view that this area is involved in encoding all phases of prehension, including grasping.

Mixed Body/Hand Reference Frame for Reaching in 3D Space in Macaque Parietal Area PEc.

The neural correlates of coordinate transformations from vision to action are expressed in the activity of posterior parietal cortex (PPC). It has been demonstrated that among the medial-most areas of the PPC, reaching targets are represented mainly in hand-centered coordinates in area PE, and in eye-centered, body-centered, and mixed body/hand-centered coordinates in area V6A. Here, we assessed whether neurons of area PEc, located between V6A and PE in the medial PPC, encode targets in body-centered, hand-centered, or mixed frame of reference during planning and execution of reaching. We studied 104 PEc cells in 3 Macaca fascicularis. The animals performed a reaching task toward foveated targets located at different depths and directions in darkness, starting with the hand from 2 positions located at different depths, one next to the trunk and the other far from it. We show that most PEc neurons encoded targets in a mixed body/hand-centered frame of reference. Although the effect of hand position was often rather strong, it was not as strong as reported previously in area PE. Our results suggest that area PEc represents an intermediate node in the gradual transformation from vision to action that takes place in the reaching network of the dorsomedial PPC.

Neural activity in the medial parietal area V6A while grasping with or without visual feedback.

Recent works have reported that grasping movements are controlled not only by the dorsolateral visual stream, as generally thought, but also by the dorsomedial visual stream, and in particular by the medial posterior parietal area V6A. To date, the grasping activity of V6A neurons has been studied only in darkness. Here we studied the effect of visual feedback on grasp-related discharges of V6A neurons while the monkey was preparing and executing the grasping of a handle. We found that V6A grasping activity could be excited or inhibited by visual information. The neural population was divided into Visual, Motor, and Visuomotor cells. The majority of Visual and Visuomotor neurons did not respond to passive observation of the handle, suggesting that vision of action, rather than object vision, is the most effective factor. The present findings highlight the role of the dorsomedial visual stream in integrating visual and motor signals to monitor and correct grasping.

Overlapping representations for reach depth and direction in caudal superior parietal lobule of macaques.

Reaching movements in the real world have typically a direction and a depth component. Despite numerous behavioral studies, there is no consensus on whether reach coordinates are processed in separate or common visuomotor channels. Furthermore, the neural substrates of reach depth in parietal cortex have been ignored in most neurophysiological studies. In the medial posterior parietal area V6A, we recently demonstrated the strong presence of depth signals and the extensive convergence of depth and direction information on single neurons during all phases of a fixate-to-reach task in 3-dimensional (3D) space. Using the same task, in the present work we examined the processing of direction and depth information in area PEc of the caudal superior parietal lobule (SPL) in three Macaca fascicularis monkeys. Across the task, depth and direction had a similar, high incidence of modulatory effect. The effect of direction was stronger than depth during the initial fixation period. As the task progressed toward arm movement execution, depth tuning became more prominent than directional tuning and the number of cells modulated by both depth and direction increased significantly. Neurons tuned by depth showed a small bias for far peripersonal space. Cells with directional modulations were more frequently tuned toward contralateral spatial locations, but ipsilateral space was also represented. These findings, combined with results from neighboring areas V6A and PE, support a rostral-to-caudal gradient of overlapping representations for reach depth and direction in SPL. These findings also support a progressive change from visuospatial (vergence angle) to somatomotor representations of 3D space in SPL.