Intercepting a moving target requires prediction: knowing the current position is not enough due to sensorimotor delays. A moving “vortex” stimulus, which lacks a conventional velocity signal for smooth pursuit yet still elicits accurate saccade targeting, was used here to assess whether it also supports accurate reaching movements. In our experiments, participants reached to the vortex or to a rigid moving disk. Three manipulations probed prediction and online control: constant-speed interception, speed perturbations at reach onset, and target disappearance at reach onset. Reaction times when reaching to the vortex did not depend on target speed in the way they do for rigid targets. Moreover, when reaching to the vortex participants made larger undershoots that increased with target speed, and they compensated less for speed changes. Thus, the vortex provides motion-related information that is sufficient for accurate saccadic localization, but that is not effectively exploited for predictive manual interception. This dissociation suggests that motion information may not be used in the same manner across motor effectors.

The interplay between attention, alertness, and motor planning is crucial for our manual interactions. To investigate the neural bases of this interaction and challenge the views that attention cannot be disentangled from motor planning, we instructed human volunteers of both sexes to plan and execute reaching movements while attending to the target, while attending elsewhere, or without constraining attention. We recorded reaction times to reach initiation and pupil diameter and interfered with the functions of the medial posterior parietal cortex (mPPC) with online repetitive transcranial magnetic stimulation to test the causal role of this cortical region in the interplay between spatial attention and reaching. We found that mPPC plays a key role in the spatial association of reach planning and covert attention. Moreover, we have found that alertness, measured by pupil size, is a good predictor of the promptness of reach initiation only if we plan a reach to attended targets, and mPPC is causally involved in this coupling. Different from previous understanding, we suggest that mPPC is neither involved in reach planning per se, nor in sustained covert attention in the absence of a reach plan, but it is specifically involved in attention functional to reaching.

Cortico-cortical paired associative stimulation (ccPAS) is a powerful transcranial magnetic stimulation (TMS) protocol thought to rely on Hebbian plasticity and known to strengthen effective connectivity, mainly within frontal lobe networks. Here, we expand on previous work by exploring the effects of ccPAS on the pathway linking the medial posterior parietal area hV6A with the primary motor cortex (M1), whose plasticity mechanisms remain largely unexplored. To assess the effective connectivity of the hV6A-M1 network, we measured motor-evoked potentials (MEPs) in 30 right-handed volunteers at rest during dual-site, paired-pulse TMS. Consistent with previous findings, we found that MEPs were inhibited when the conditioning stimulus over hV6A preceded the test stimulus over M1 by 12 ms, highlighting inhibitory hV6A-M1 causal interactions. We then manipulated the hV6A-M1 circuit via ccPAS using different inter-stimulus intervals (ISI) never tested before. Our results revealed a time-dependent modulation. Specifically, only when the conditioning stimulus preceded the test one by 12 ms did we find a gradual increase of MEP amplitude during ccPAS, and excitatory aftereffects. In contrast, when ccPAS was applied with an ISI of 4 ms or 500 ms, no corticospinal excitability changes were observed, suggesting that temporal specificity is a critical factor in modulating the hV6A-M1 network. These results suggest that ccPAS can induce time-dependent Hebbian plasticity in the dorsomedial parieto-frontal network at rest, offering novel insights into the network's plasticity and temporal dynamics.

The degree of overlap between the mechanisms underlying attention control and motor planning remains debated. In this study, we examined whether microsaccades-tiny gaze shifts occurring during fixation-are modulated differently by covert attention and motor intention. Eye movements were recorded using high-precision eye-tracking. Our results reveal that whereas in a covert attention task, microsaccade direction was biased toward the attended location, in a motor planning task, microsaccades were not directionally biased toward the cued location. Further, the rate of microsaccades over time varied between the two tasks and whereas in the attention task a clear correlation emerged between microsaccade rate and visual detection reaction times across subjects, there was no relationship between microsaccade rate and reach/saccade reaction times. This study advances our understanding of the relationship between attention and motor processes, suggesting that the mechanisms governing microsaccade generation are differentially influenced by motor planning versus spatial covert attention engagement.

While online adjustments during reaching are essential for interacting with our dynamic environment, the specialized contributions of subregions of the posterior parietal cortex (PPC) remain unclear. In this study, we investigate the distinct roles of human medial PPC areas V6A (hV6A) and PEc (hPEc) in mediating online reaching corrections elicited by visual and proprioceptive perturbations. Here we deliver online repetitive transcranial magnetic stimulation (rTMS) during the early stages of reaching corrections triggered by an unexpected shift of the visual target or by the application of an external force to the wrist. Our findings reveal that rTMS over hV6A selectively impairs the ability to correct reach trajectories for visual perturbations, whereas stimulation of hPEc interferes only with proprioceptively driven corrections. These findings confirm the critical role of hV6A in processing visual feedback, demonstrate the causal involvement of hPEc in integrating proprioceptive information to guide motor adjustments, and show how the PPC selectively engages specialized neural circuits to adapt motor control strategies according to the sensory nature of the reaching perturbation.

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.

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.

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.

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.

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 medial posterior parietal cortex (mPPC) is involved in the visual guidance of reaching. Although several studies investigated reaching performed towards different directions, only a few correlational studies investigated different depths. Here, we studied the causal role of mPPC (putatively, human area V6A - hV6A) in encoding depth and direction of reaching performed under visual guidance. Fifteen healthy humans performed a visually-guided reaching task which required different eye-hand configurations (foveal and peripheral reaching): Constant gaze configuration (central gaze fixation while reaching to one of 8 peripheral targets); Constant reach configuration (reaching to the central target while fixating one of 8 peripheral targets); Foveal reach configuration (coincident fixation and reaching targets). We applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at 100 or 200 ms after reaction time onset, over area V1 to check for non-specific effect of TMS, and in a SHAM condition with the coil tilted 90° over the vertex. We found a site-specific and time-dependent effect: in particular, TMS delivered over hV6A 200ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy (in depth) of movements towards targets located farther with respect to the gazed position, but only when they were far from the body (Constant gaze configuration: repeated-measure ANOVA, Stimulation Condition x Stimulation Time x Depth interaction, F(4,56) = 3.00; p = 0.03, partial η2 = 0.17). Reach end-point precision was not affected by TMS over hV6A. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial (far from the body) position 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 planning visually-guided reaching movements in depth.

Reaching and manipulative actions allow human and non-human primates to interact with the surrounding world. The execution of foveated reaching movements requires the combination of visual and motor skills, allowing the arm to be guided and kept in place by several kinds of information (eye position, proprioceptive, visual). Several areas of the superior parietal lobule (SPL) are involved in the progressive integration of information related to the current position of the eyes and proprioceptive signals from the arm occurring during and after reaching movements. In this study we assessed the relative influence of eye-position and somatosensory signals during static arm positions at the end of a 3D fixation-to-reach task in three SPL areas: V6A, located in the anterior bank of the parieto-occipital sulcus, PEc, bordering anteriorly to V6A, and PE, located more rostrally in the SPL. We analyzed single cell discharges recorded from areas V6A (N= 303), PEc (N= 264) and PE (N= 189) of two Macaca fascicularis in two main time intervals: i) target fixation and ii) holding of the foveated target. We found that the three areas were differently modulated by eye-position and proprioceptive signals, being PE cells more involved in the encoding of limb postures while V6A and PEc neurons more involved in the processing of eye-position information during target fixation. Our results support the existence of a functional antero-posterior trend along the SPL: from area PE, strongly dominated by proprioceptive signals of the arm holding the target, to the most functionally heterogenous areas PEc and V6A, which showed an additional gaze influence. This coding scheme parallels the increase of somatosensory and the simultaneous decrease of visual processing observed along the caudo-rostral axis of the SPL.

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.

OBJECTIVE:Neural signals can be decoded and used to move neural prostheses with the purpose of restoring motor function in patients with mobility impairments. Such patients typically have intact eye movement control and visual function, suggesting that cortical visuospatial signals could be used to guide external devices. Neurons in parietal cortex mediate sensory-motor transformations, encode the spatial coordinates for reaching goals, hand position and movements, and other spatial variables. We studied how spatial information is represented at the population level, and the possibility to decode not only the position of visual targets and the plans to reach them, but also conditional, non-spatial motor responses. APPROACH:The animals first fixated one of nine targets in 3D space and then, after the target changed color, either reached toward it, or performed a non-spatial motor response (lift hand from a button). Spiking activity of parietal neurons was recorded in monkeys during two tasks. We then decoded different task related parameters. MAIN RESULTS:We first show that a maximum-likelihood estimation (MLE) algorithm trained separately in each task transformed neural activity into accurate metric predictions of target location. Furthermore, by combining MLE with a Naïve Bayes classifier, we decoded the monkey's motor intention (reach or hand lift) and the different phases of the tasks. These results show that, although V6A encodes the spatial location of a target during a delay period, the signals they carry are updated around the movement execution in an intention/motor specific way. SIGNIFICANCE:These findings show the presence of multiple levels of information in parietal cortex that could be decoded and used in brain machine interfaces to control both goal-directed movements and more cognitive visuomotor associations.

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.

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.