Roberto Caminiti

Parieto-frontal coding of reaching: an integrated framework

Abstract 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.

Visuomotor transformations: early cortical mechanisms of reaching

Recent studies of visually guided reaching in monkeys support the hypothesis that the visuomotor transformations underlying arm movements to spatial targets involve a parallel mechanism that simultaneously engages functionally related frontal and parietal areas linked by reciprocal cortico-cortical connections. The neurons in these areas possess similar combinations of response properties. The multimodal combinatorial properties of these neurons and the gradient architecture of the parietofrontal network emerge as a potential substrate to link the different sensory and motor signals that arise during reaching behavior into common hybrid reference frames. This convergent combinatorial process is evident at early stages of visual information processing in the occipito-parietal cortex, suggesting the existence of re-entrant motor influences on cortical areas once believed to have only visual functions.

Cortical networks for visual reaching.

The cortical anatomical substrates by which visual information may influence the frontal areas controlling reaching movements to visual targets were studied in monkeys. A reaching task was employed to characterize the arm-related regions of the frontal lobe. Injections of retrograde tracers into these physiologically defined cortical fields revealed a gradient of parallel corticocortical pathways originating in the superior parietal lobule and impinging upon different frontal regions. These results support the hypothesis that the superior parietal lobule can supply the frontal motor and premotor areas not only with the proprioceptive information but also with the visual input required for the control of reaching.

Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex.

The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto‐occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde flourescent tracers. Fluoro‐Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso‐caudal (PMdc, F2) and dorso‐rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually‐related and eye‐position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential ‘early’ node of the distributed network underlying visually‐guided reaching. In this network, reciprocal association connections probably impose, through re‐entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.

Evolution amplified processing with temporally dispersed slow neuronal connectivity in primates

The corpus callosum (CC) provides the main route of communication between the 2 hemispheres of the brain. In monkeys, chimpanzees, and humans, callosal axons of distinct size interconnect functionally different cortical areas. Thinner axons in the genu and in the posterior body of the CC interconnect the prefrontal and parietal areas, respectively, and thicker axons in the midbody and in the splenium interconnect primary motor, somatosensory, and visual areas. At all locations, axon diameter, and hence its conduction velocity, increases slightly in the chimpanzee compared with the macaque because of an increased number of large axons but not between the chimpanzee and man. This, together with the longer connections in larger brains, doubles the expected conduction delays between the hemispheres, from macaque to man, and amplifies their range about 3-fold. These changes can have several consequences for cortical dynamics, particularly on the cycle of interhemispheric oscillators.

Callosal connections of dorso-lateral premotor cortex

This study investigated the organization of the callosal connections of the two subdivisions of the monkey dorsal premotor cortex (PMd), dorso‐rostral (F7) and dorso‐caudal (F2). In one animal, Fast blue and Diamidino yellow were injected in F7 and F2, respectively; in a second animal, the pattern of injections was reversed. F7 and F2 receive a major callosal input from their homotopic counterpart. The heterotopic connections of F7 originate mainly from F2, with smaller contingent from pre‐supplementary motor area (pre‐SMA, F6), area 8 (frontal eye fields), and prefrontal cortex (area 46), while those of F2 originate from F7, with smaller contributions from ventral premotor areas (F5, F4), SMA‐proper (F3), and primary motor cortex (M1). Callosal cells projecting homotopically are mostly located in layers II–III, those projecting heterotopically occupy layers II–III and V–VI. A spectral analysis was used to characterize the spatial fluctuations of the distribution of callosal neurons, in both F7 and F2, as well as in adjacent cortical areas. The results revealed two main periodic components. The first, in the domain of the low spatial frequencies, corresponds to periodicities of cell density with peak‐to‐peak distances of approximately 10 mm, and suggests an arrangement of callosal cells in the form of 5‐mm wide bands. The second corresponds to periodicities of approximately 2 mm, and probably reflects a 1‐mm columnar‐like arrangement. Coherency and phase analyses showed that, although similar in their spatial arrangements, callosal cells projecting to dorsal premotor areas are segregated in the tangential cortical domain.

Visuo-motor transformations for arm reaching

Visuomanual co‐ordination requires the merging of ocular and arm information in a common frame of reference. Here we consider behavioural evidence in humans for the use of a viewer‐centred frame in the specification of end point positions of reaching. We then review anatomical and neurophysiological data in the non‐human primate that indicate a prominent role of the parietal cortex in the process of multisensory fusion that leads to egocentric representations of space. Finally, we discuss the functional anatomy of the human parietal cortex in visuomanual co‐ordination as revealed by neuroimaging.

Cortical Mechanisms for Online Control of Hand Movement Trajectory: The Role of the Posterior Parietal Cortex

The parietal mechanisms for the control of hand movement trajectory were studied by recording cell activity in area 5 of monkeys making direct reaches to visual targets and online corrections of movement trajectory, after change of target location in space. The activity of hand-related cells was fitted with a linear model including hand position, movement direction, and speed. The neural activity modulation mostly led, but also followed, hand movement. When a change of hand trajectory occurred, the pattern of activity associated with the movement to the first target evolved into that typical of the movement to the second one, thus following the corresponding variations of the hand kinematics. The visual signal concerning target location in space did not influence the firing activity associated with the direction of hand movement within the first 150 ms after target presentation. This might be the time necessary for the visuo-motor transformation underlying reaching. We conclude that online control of hand trajectory not only resides in the relationships between neural activity and kinematics, but, under specific circumstances, also on the coexistence of signals about ongoing and future hand movement direction.

Shift of preferred directions of premotor cortical cells with arm movements performed across the workspace

SummaryThe activity of 156 neurons was recorded in the premotor cortex (Weinrich and Wise 1982) and in an adjoining rostral region of area 6 (area 6 DR; Barbas and Pandya 1987) while monkeys made visually-guided arm movements of similar direction within different parts of space. The activity of individual neurons varied most for a given preferred direction of movement within each part of space. These neurons (152/156, 97.4%) were labeled as directional. The spatial orientation of their preferred directions shifted in space to “follow” the rotation of the shoulder joint necessary to bring the arm into the different parts of the work-space. These results suggest that the cortical areas studied represent arm movement direction within a coordinate system rotating with the arm and where signals about the movement direction relate to the motor plan through a simple invariant relationship, that between cell preferred direction and arm orientation in space.

Diameter, Length, Speed, and Conduction Delay of Callosal Axons in Macaque Monkeys and Humans: Comparing Data from Histology and Magnetic Resonance Imaging Diffusion Tractography

Three macaque monkeys and 13 healthy human volunteers underwent diffusion tensor MRI with a 3 Tesla scanner for diffusion tract tracing (DTT) reconstruction of callosal bundles from different areas. In six macaque monkeys and three human subjects, the length of fiber tracts was obtained from histological data and combined with information on the distribution of axon diameter, so as to estimate callosal conduction delays from different areas. The results showed that in monkeys, the spectrum of tract lengths obtained with DTT closely matches that estimated from histological reconstruction of axons labeled with an anterogradely transported tracer. For each sector of the callosum, we obtained very similar conduction delays regardless of whether conduction distance was obtained from tractography or from histological analysis of labeled axons. This direct validation of DTT measurements by histological methods in monkeys was a prerequisite for the computation of the callosal conduction distances and delays in humans, which we had previously obtained by extrapolating the length of callosal axons from that of the monkey, proportionally to the brain volumes in the two species. For this analysis, we used the distribution of axon diameters from four different sectors of the corpus callosum. As in monkeys, in humans the shortest callosal conduction delays were those of motor, somatosensory, and premotor areas; the longer ones were those of temporal, parietal, and visual areas. These results provide the first histological validation of anatomical data about connection length in the primate brain based on DTT imaging.