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.

Neural sensitivity to translational self- and object-motion velocities.

The ability to detect and assess world-relative object-motion is a critical computation performed by the visual system. This computation, however, is greatly complicated by the observer's movements, which generate a global pattern of motion on the observer's retina. How the visual system implements this computation is poorly understood. Since we are potentially able to detect a moving object if its motion differs in velocity (or direction) from the expected optic flow generated by our own motion, here we manipulated the relative motion velocity between the observer and the object within a stationary scene as a strategy to test how the brain accomplishes object-motion detection. Specifically, we tested the neural sensitivity of brain regions that are known to respond to egomotion-compatible visual motion (i.e., egomotion areas: cingulate sulcus visual area, posterior cingulate sulcus area, posterior insular cortex [PIC], V6+, V3A, IPSmot/VIP, and MT+) to a combination of different velocities of visually induced translational self- and object-motion within a virtual scene while participants were instructed to detect object-motion. To this aim, we combined individual surface-based brain mapping, task-evoked activity by functional magnetic resonance imaging, and parametric and representational similarity analyses. We found that all the egomotion regions (except area PIC) responded to all the possible combinations of self- and object-motion and were modulated by the self-motion velocity. Interestingly, we found that, among all the egomotion areas, only MT+, V6+, and V3A were further modulated by object-motion velocities, hence reflecting their possible role in discriminating between distinct velocities of self- and object-motion. We suggest that these egomotion regions may be involved in the complex computation required for detecting scene-relative object-motion during self-motion.

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.

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.

Claustral Input to the Macaque Medial Posterior Parietal Cortex (Superior Parietal Lobule and Adjacent Areas).

The projections from the claustrum to cortical areas within and adjacent to the superior parietal lobule were studied in 10 macaque monkeys, using retrograde tracers, computerized reconstructions, and quantitative methods. In contrast with the classical view that posterior parietal areas receive afferents primarily from the dorsal and posterior regions of the claustrum, we found that these areas receive more extensive projections, including substantial afferents from the anterior and ventral regions of the claustrum. Moreover, our findings uncover a previously unsuspected variability in the precise regions of the claustrum that originate the projections, according to the target areas. For example, areas dominated by somatosensory inputs for control of body movements tend to receive most afferents from the dorsal-posterior claustrum, whereas those which also receive significant visual inputs tend to receive more afferents from the ventral claustrum. In addition, different areas within these broadly defined groups differ in terms of quantitative emphasis in the origin of projections. Overall, these results argue against a simple model whereby adjacency in the cortex determines adjacency in the sectors of claustral origin of projections and indicate that subnetworks defined by commonality of function may be an important factor in defining claustrocortical topography.

Machine learning methods detect arm movement impairments in a patient with parieto-occipital lesion using only early kinematic information.

Patients with lesions of the parieto-occipital cortex typically misreach visual targets that they correctly perceive (optic ataxia). Although optic ataxia was described more than 30 years ago, distinguishing this condition from physiological behavior using kinematic data is still far from being an achievement. Here, combining kinematic analysis with machine learning methods, we compared the reaching performance of a patient with bilateral occipitoparietal damage with that of 10 healthy controls. They performed visually guided reaches toward targets located at different depths and directions. Using the horizontal, sagittal, and vertical deviation of the trajectories, we extracted classification accuracy in discriminating the reaching performance of patient from that of controls. Specifically, accurate predictions of the patient's deviations were detected after the 20% of the movement execution in all the spatial positions tested. This classification based on initial trajectory decoding was possible for both directional and depth components of the movement, suggesting the possibility of applying this method to characterize pathological motor behavior in wider frameworks.

Multisensory integration in cortical regions responding to locomotion-related visual and somatomotor signals.

During real-world locomotion, in order to be able to move along a path or avoid an obstacle, continuous changes in self-motion direction (i.e. heading) are needed. Control of heading changes during locomotion requires the integration of multiple signals (i.e., visual, somatomotor, vestibular). Recent fMRI studies have shown that both somatomotor areas (human PEc [hPEc], human PE [hPE], primary somatosensory cortex [S-I]) and egomotion visual regions (cingulate sulcus visual area [CSv], posterior cingulate area [pCi], posterior insular cortex [PIC]) respond to either leg movements and egomotion-compatible visual stimulations, suggesting a role in the analysis of both visual attributes of egomotion and somatomotor signals with the aim of guiding locomotion. However, whether these regions are able to integrate egomotion-related visual signals with somatomotor inputs coming from leg movements during heading changes remains an open question. Here we used a combined approach of individual functional localizers and task-evoked activity by fMRI. In thirty subjects we first localized three egomotion areas (CSv, pCi, PIC) and three somatomotor regions (S-I, hPE, hPEc). Then, we tested their responses in a multisensory integration experiment combining visual and somatomotor signals relevant to locomotion in congruent or incongruent trials. We used an fMR-adaptation paradigm to explore the sensitivity to the repeated presentation of these bimodal stimuli in the six regions of interest. Results revealed that hPE, S-I and CSv showed an adaptation effect regardless of congruency, while PIC, pCi and hPEc showed sensitivity to congruency. PIC exhibited a preference for congruent trials compared to incongruent trials. Areas pCi and hPEc exhibited an adaptation effect only for congruent and incongruent trials, respectively. PIC, pCi and hPEc sensitivity to the congruency relationship between visual (locomotion-compatible) cues and (leg-related) somatomotor inputs suggests that these regions are involved in multisensory integration processes, likely in order to guide/adjust leg movements during heading changes.

The superior parietal lobule of primates: a sensory-motor hub for interaction with the environment.

The superior parietal lobule of the macaque monkey occupies the postero-medial part of the parietal lobe and plays a crucial role in the integration of different sources of information (from visual, motor and somatosensory brain regions) for the purpose of high-level cognitive functions, as perception for action. This region encompasses the intraparietal sulcus and the parieto-occipital sulcus and includes also the precuneate cortex in the mesial surface of the hemisphere. It hosts several areas extensively studied in the macaque: PE, PEip, PEci anteriorly and PEc, MIP, PGm and V6A posteriorly. Recently studies based on functional MRI have suggested putative human homologue of some of the areas of the macaque superior parietal lobule. Here we review the anatomical subdivision, the cortico-cortical and thalamo-cortical connections of the macaque superior parietal lobule compared with their functional properties and the homology with human organization in physiological and lesioned situations. The knowledge of this part of the macaque brain could help in understanding pathological conditions that in humans affect the normal behaviour of arm-reaching actions and can inspire brain computer interfaces performing in more accurate ways the sensorimotor transformations needed to interact with the surrounding environment.

Neural bases of self- and object-motion in a naturalistic vision.

To plan movements toward objects our brain must recognize whether retinal displacement is due to self-motion and/or to object-motion. Here, we aimed to test whether motion areas are able to segregate these types of motion. We combined an event-related functional magnetic resonance imaging experiment, brain mapping techniques, and wide-field stimulation to study the responsivity of motion-sensitive areas to pure and combined self- and object-motion conditions during virtual movies of a train running within a realistic landscape. We observed a selective response in MT to the pure object-motion condition, and in medial (PEc, pCi, CSv, and CMA) and lateral (PIC and LOR) areas to the pure self-motion condition. Some other regions (like V6) responded more to complex visual stimulation where both object- and self-motion were present. Among all, we found that some motion regions (V3A, LOR, MT, V6, and IPSmot) could extract object-motion information from the overall motion, recognizing the real movement of the train even when the images remain still (on the screen), or moved, because of self-movements. We propose that these motion areas might be good candidates for the "flow parsing mechanism," that is the capability to extract object-motion information from retinal motion signals by subtracting out the optic flow components.

Trans-saccadic adaptation of perceived size independent of saccadic adaptation.

Systematic shortening or lengthening of target objects during saccades modifies saccade amplitudes and perceived size of the objects. These two events are concomitant when size change during the saccade occurs asymmetrically, thereby shifting the center of mass of the object. In the present study, we asked whether or not the two are necessarily linked. We tested human participants in symmetrical systematic shortening and lengthening of a vertical bar during a horizontal saccade, aiming to not modify the saccade amplitude. Before and after a phase of trans-saccadic changes of the target bar, participants manually indicated the sizes of various vertically oriented bars by open-loop grip aperture. We evaluated the effect of trans-saccadic changes of bar length on manual perceptual reports and whether this change depended on saccade amplitude. As expected, we did not induce any change in horizontal or vertical components of saccade amplitude, but we found a significant difference in perceived size after the lengthening experiment compared to after the shortening experiment. Moreover, after the lengthening experiment, perceived size differed significantly from pre-lengthening baseline. These findings suggest that a change of size perception can be induced trans-saccadically, and its mechanism does not depend on saccadic amplitude change.

A putative human homologue of the macaque area PEc.

The cortical area PEc is anatomically and functionally well-defined in macaque, but it is unknown whether it has a counterpart in human. Since we know that macaque PEc, but not the nearby posterior regions, hosts a lower limb representation, in an attempt to recognize a possible human PEc we looked for the existence of leg representations in the human parietal cortex using individual cortical surface-based analysis, task-evoked paradigms and resting-state functional connectivity. fMRI images were acquired while thirty-one participants performed long-range leg movements through an in-house MRI-compatible set-up. We revealed the existence of multiple leg representations in the human dorsomedial parietal cortex, here defined as S-I (somatosensory-I), hPE (human PE, in the postcentral sulcus), and hPEc (human PEc, in the anterior precuneus). Among the three "leg" regions, hPEc had a unique functional profile, in that it was the only one responding to both arm and leg movements, to both hand-pointing and foot pointing movements, and to flow field visual stimulation, very similar to macaque area PEc. In addition, hPEc showed functional connections with the somatomotor regions hosting a lower limb representation, again as in macaque area PEc. Therefore, based on similarity in brain position, functional organization, cortical connections, and relationship with the neighboring areas, we propose that this cortical region is the human homologue of macaque area PEc.

Egomotion-related visual areas respond to active leg movements.

Monkey neurophysiology and human neuroimaging studies have demonstrated that passive viewing of optic flow stimuli activates a cortical network of temporal, parietal, insular, and cingulate visual motion regions. Here, we tested whether the human visual motion areas involved in processing optic flow signals simulating self-motion are also activated by active lower limb movements, and hence are likely involved in guiding human locomotion. To this aim, we used a combined approach of task-evoked activity and resting-state functional connectivity by fMRI. We localized a set of six egomotion-responsive visual areas (V6+, V3A, intraparietal motion/ventral intraparietal [IPSmot/VIP], cingulate sulcus visual area [CSv], posterior cingulate sulcus area [pCi], posterior insular cortex [PIC]) by using optic flow. We tested their response to a motor task implying long-range active leg movements. Results revealed that, among these visually defined areas, CSv, pCi, and PIC responded to leg movements (visuomotor areas), while V6+, V3A, and IPSmot/VIP did not (visual areas). Functional connectivity analysis showed that visuomotor areas are connected to the cingulate motor areas, the supplementary motor area, and notably to the medial portion of the somatosensory cortex, which represents legs and feet. We suggest that CSv, pCi, and PIC perform the visual analysis of egomotion-like signals to provide sensory information to the motor system with the aim of guiding locomotion.

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.

Uniformity and Diversity of Cortical Projections to Precuneate Areas in the Macaque Monkey: What Defines Area PGm?

We report on the corticocortical connections of areas on the mesial surface of the macaque posterior parietal cortex, based on 10 retrograde tracer injections targeting different parts of the precuneate gyrus. Analysis of afferent connections supported the existence of two areas: PGm (also known as 7 m) and area 31. Both areas received major afferents from the V6A complex and from the external subdivision of area 23, but they differed in most other aspects. Area 31 showed greater emphasis on connections with premotor and parietal sensorimotor areas, whereas PGm received a greater proportion of its afferents from visuomotor structures involved in spatial cognition (including the lateral intraparietal cortex, inferior parietal lobule, and the putative visual areas in the ventral part of the precuneus). Medially, the anterior cingulate cortex (area 24) preferentially targeted area 31, whereas retrosplenial areas preferentially targeted PGm. These results indicate that earlier views on the connections of PGm were based on tracer injections that included parts of adjacent areas (including area 31), and prompt a reassessment of the limits of PGm. Our findings are compatible with a primary role of PGm in visuospatial cognition (including navigation), while supporting a role for area 31 in sensorimotor planning and coordination.

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.

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.

Reaching and grasping actions and their context shape the perception of object size.

Humans frequently estimate the size of objects to grasp them. In fact, when performing an action, our perception is focused towards the visual properties of the object that enable us to successfully execute the action. However, the motor system is also able to influence perception, but only a few studies have reported evidence for action-induced visual perception modifications. Here, we aimed to look for a feature-specific perceptual modulation before and after a reaching or a grasping action. Human participants were instructed to either reach for or grasp two-dimensional bars of different size and to perform a size perceptual task before and after the action in two contexts: in one where they knew the subsequent type of movement and in the other where they did not know. We found significant modifications of perceived size of stimuli more pronounced after grasping than after reaching. The mere knowledge of the subsequent action type significantly affected the size perception before the movement execution, with consistent results in both manual and verbal reports. These data represent direct evidence that, in natural conditions without manipulation of visual information, the action type and the action context dynamically modulate size perception, by shaping it according to relevant information required to recognize and interact with objects.

Adaptation of Saccades and Perceived Size after Trans-Saccadic Changes of Object Size.

When saccadic eye movements consistently fail to land on the intended target, saccade accuracy is maintained by gradually adapting the amplitude of successive saccades to the same target. Such saccadic adaptation is usually induced by systematically displacing a small visual target during the execution of the saccade. However, saccades are normally performed to extended objects. Here we report changes in saccade amplitude when the size of a target object is systematically changed during a saccade. Moreover, we find that this manipulation also affected the visual perception of the size of that object. Human subjects were tested in shortening and lengthening adaptation where they had to make saccades to targets of different sizes, which were each shortened or lengthened during saccade execution, respectively. In both experiments, a preadaptation and postadaptation phase required manually indicating the horizontal size of each target by grip aperture and, in a further experiment, a verbal size report. We evaluated the effect of change in visual perception on saccade and on the two modalities of judgment. We observed that (1) saccadic adaptation can be induced by modifying target object size and (2) this gradual change in saccade amplitude in the direction of the object size change evokes a concomitant change in perceived object size. These findings suggest that size is a relevant signal for saccadic system and its trans-saccadic manipulation entails considerable changes at multiple levels of sensorimotor performance.

Object affordance modulates visual responses in the macaque medial posterior parietal cortex.

Area V6A is a visuomotor area of the dorsomedial visual stream that contains cells modulated by object observation and by grip formation. As different objects have different shapes but also evoke different grips, the response selectivity during object presentation could reflect either the coding of object geometry or object affordances. To clarify this point, we here investigate neural responses of V6A cells when monkeys observed two objects with similar visual features but different contextual information, such as the evoked grip type. We demonstrate that many V6A cells respond to the visual presentation of objects and about 30% of them by the object affordance. Given that area V6A is an early stage in the visuomotor processes underlying grasping, these data suggest that V6A may participate in the computation of object affordances. These results add some elements in the recent literature about the role of the dorsal visual stream areas in object representation and contribute in elucidating the neural correlates of the extraction of action-relevant information from general object properties, in agreement with recent neuroimaging studies on humans showing that vision of graspable objects activates action coding in the dorsomedial visual steam.