Impairment of gaze-centered updating of reach targets in bilateral parietal-occipital damaged patients

Recent studies have suggested that internal updating of visuospatial targets in humans occurs in gaze-centered coordinates and takes place in the parietal and extrastriate cortices. We explored how information for reaching is updated in two patients with bilateral lesions in these areas. Subjects performed two visuomotor tasks: (i) a fixation reaching task, which began with the appearance of one of five fixation positions (varying eye positions) followed by a central reaching target. Subjects reached to the target while fixating on the presented fixation position (relative to gaze the target was always presented in the periphery); and (ii) a saccade reaching task, in which subjects foveated on the central reaching target, then made a saccade to the presented fixation position before reaching to the central target. In both tasks, subjects reached to targets after a 500 or 5000 ms delay. Gaze-centered updating predicts similarities in reaching errors between fixation and saccade trials. Control subjects showed evidence for gaze-centered updating during both 500 and 5000 ms delay conditions. In contrast, patient AT, who had extensive occipital-parietal damage, only showed signs of gaze-centered representation after 5 s. Patient IG, with a more focal lesion in the parietal cortices, showed partial updating in gaze-centered coordinates when reaching with the small memory delay but recovered a complete gaze-centered representation after the longer delay. This suggests that patients with bilateral occipital-parietal lesions may rely on non-gaze-centered frames to store immediate target locations in reaching space but, given enough time, this information may be rerouted to access other gaze-centered motor cortical mechanisms.     

The over-representation of contralateral space in parietal cortex: a positive image of directional motor components of neglect?

The activity of single cells was recorded in behaving monkeys while they performed several eye-hand directional motor tasks. The results revealed that in parietal area 7a there exists a directional representation of eye and hand motor space that, contrary to that of superior parietal, premotor and motor cortex, is highly skewed toward the contralateral workspace. In man, the loss of this representation after parietal lesions might explain the emergence of the directional movement disorders of neglect. In fact, although unilateral neglect is consequence of damage to different brain structures, it is more common and enduring after right inferior parietal cortex lesions. Neglect patients ignore and avoid interacting with events occurring in the contralesional part of their physical and mental space. Current theories distinguish perceptual from motor components of neglect. One key feature of the latter is directional hypokinesia, an impaired representation of space for action, evident as difficulty to plan hand movements toward the contralesional part of egocentric space. An impairment of a similar nature is also observed for eye movements. In this study, we offer an interpretation of directional movement disorders of neglect from a physiological perspective, i.e. by focusing on the mechanisms underlying the representation of visuomotor space in parietal cortex.     

Neural substrates of real and imagined sensorimotor coordination

Much debate in the behavioral literature focuses on the relative contribution of motor and perceptual processes in mediating coordinative stability. To a large degree, such debate has proceeded independently of what is going on in the brain. Here, using blood oxygen level-dependent measures of neural activation, we compare physically executed and imagined rhythmic coordination in order to better assess the relative contribution of hypothesized neuromusculoskeletal mechanisms in modulating behavioral stability. The executed tasks were to coordinate index finger to thumb opposition movements of the right hand with an auditory metronome in either a synchronized (on the beat) or syncopated (off the beat) pattern. Imagination involved the same tasks, except without physical movement. Thus, the sensory stimulus and coordination constraints were the same in both physical and imagination tasks, but the motoric requirements were not. Results showed that neural differences between executed synchronization and syncopation found in premotor cortex, supplementary motor area, basal ganglia and lateral cerebellum persist even when the coordinative patterns were only imagined. Neural indices reflecting behavioral stability were not abolished by the absence of overt movement suggesting that coordination phenomena are not exclusively rooted in purely motoric constraints. On the other hand, activity in the superior temporal gyrus was modulated by both the presence of movement and the nature of the coordination, attesting to the intimacy between perceptual and motoric processes in coordination dynamics.     

Temporal relation of population activity in visual areas MT/MST and in primary motor cortex during visually guided tracking movements

There is growing evidence that in primate cerebral cortex the areas along the 'dorsal pathway' are involved in the transformation of visual motion information towards a motor command. To pursue this cortical flow of information from visual motion areas to the motor cortex, single-cell activity was recorded from visual areas MT/MST (middle temporal area/medial superior temporal area) and from primary motor cortex (M1) while monkeys tracked moving targets with their right hand. Spike activity of 353 directionally tuned motor cortex cells was combined to a time-varying population vector, and similarly a time-resolved visual population vector was calculated from 252 MT/MST cells. Both population vectors code faithfully for the direction of the collinear motion of target and hand. For a given direction, the length of the population vectors varied over time during the performance of the task. The temporal evolution of both population responses reflects the different relationship between the early visual responses to the moving target and the directional motor command controlling the hand movement. The results indicate that during the visual tracking task visual and motor populations which code for similar directions of movement are co-activated with considerable temporal overlap. Despite this co-activation in both modalities, we failed to observe any significant synchronization between areas MT/MST and M1.     

Cortical mechanisms for shifting and holding visuospatial attention

Access to visual awareness is often determined by covert, voluntary deployments of visual attention. Voluntary orienting without eye movements requires decoupling attention from the locus of fixation, a shift to the desired location, and maintenance of attention at that location. We used event-related functional magnetic resonance imaging to dissociate these components while observers shifted attention among 3 streams of letters and digits, one located at fixation and 2 in the periphery. Compared with holding attention at the current location, shifting attention between the peripheral locations was associated with transient increases in neural activity in the superior parietal lobule (SPL) and frontal eye fields (FEF), as in previous studies. The supplementary eye fields and separate portions of SPL and FEF were more active for decoupling attention from fixation than for shifting attention to a new location. Large segments of precentral sulcus (PreCS) and posterior parietal cortex (PPC) were more active when attention was maintained in the periphery than when it was maintained at fixation. We conclude that distinct subcomponents of the dorsal frontoparietal network initiate redeployments of covert attention to new locations and disengage attention from fixation, while sustained activity in lateral regions of PPC and PreCS represents sustained states of peripheral attention.     

Goal-selection and movement-related conflict during bimanual reaching movements

Conflict during bimanual movements can arise during the selection of movement goals or during movement planning and execution. We demonstrate a behavioral and neural dissociation of these 2 types of conflict. During functional magnetic resonance imaging scanning, participants performed bimanual reaching movements with symmetric (congruent) or orthogonal (incongruent) trajectories. The required movements were indicated either spatially, by illuminating the targets, or symbolically, using centrally presented letters. The processing of symbolic cues led to increased activation in a left hemisphere network including the intraparietal sulcus, premotor cortex, and inferior frontal gyrus. Reaction time cost for incongruent movements was substantially larger for symbolic than for spatial cues, indicating that the cost was primarily associated with the selection and assignment of movement goals, demands that are minimized when goals are directly specified by spatial cues. This goal-selection conflict increased activity in the pre-supplementary motor area and cingulate motor areas. Both cueing conditions led to larger activation for incongruent movements in the convexity of the superior parietal cortex, bilaterally, making this region a likely neural site for conflict that arises during the planning and execution of bimanual movements. These results suggest distinct neural loci for 2 forms of constraint on our ability to perform bimanual reaching movements.     

Multiple levels of representation of reaching in the parieto-frontal network

In daily life, hand and eye movements occur in different contexts. Hand movements can be made to a visual target shortly after its presentation, or after a longer delay; alternatively, they can be made to a memorized target location. In both instances, the hand can move in a visually structured scene under normal illumination, which allows visual monitoring of its trajectory, or in darkness. Across these conditions, movement can be directed to points in space already foveated, or to extrafoveal ones, thus requiring different forms of eye-hand coordination. The ability to adapt to these different contexts by providing successful answers to their demands probably resides in the high degree of flexibility of the operations that govern cognitive visuomotor behavior. The neurophysiological substrates of these processes include, among others, the context-dependent nature of neural activity, and a transitory, or task-dependent, affiliation of neurons to the assemblies underlying different forms of sensorimotor behavior. Moreover, the ability to make independent or combined eye and hand movements in the appropriate order and time sequence must reside in a process that encodes retinal-, eye- and hand-related inputs in a spatially congruent fashion. This process, in fact, requires exact knowledge of where the eye and the hand are at any given time, although we have no or little conscious experience of where they stay at any instant. How this information is reflected in the activity of cortical neurons remains a central question to understanding the mechanisms underlying the planning of eye-hand movement in the cerebral cortex. In the last 10 years, psychophysical analyses in humans, as well as neurophysiological studies in monkeys, have provided new insights on the mechanisms of different forms of oculo-manual actions. These studies have also offered preliminary hints as to the cortical substrates of eye-hand coordination. In this review, we will highlight some of the results obtained as well as some of the questions raised, focusing on the role of eye- and hand-tuning signals in cortical neural activity. This choice rests on the crucial role this information exerts in the specification of movement, and coordinate transformation.     

Role of the ipsilateral primary motor cortex in controlling the timing of hand muscle recruitment

The precise contribution of the ipsilateral primary motor cortex (iM1) to hand movements remains controversial. To address this issue, we elicited transient virtual lesions of iM1 by means of transcranial magnetic stimulation (TMS) in healthy subjects performing either a grip-lift task or a step-tracking task with their right dominant hand. We found that, irrespective of the task, a virtual lesion of iM1 altered the timing of the muscle recruitment. In the grip-lift task, this led to a less coordinated sequence of grip and lift movements and in the step-tracking task, to a perturbation of the movement trajectory. In the step-tracking task, we have demonstrated that disrupting iM1 activity may, depending on the TMS delay, either advance or delay the muscle recruitment. The present study suggests that iM1 plays a critical role in hand movements by contributing to the setting of the muscle recruitment timing, most likely through either inhibitory or facilitatory transcallosal influences onto the contralateral M1 (cM1). iM1 would therefore contribute to shape precisely the muscular command originating from cM1.     

The role of parietal cortex in awareness of self-generated movements: a transcranial magnetic stimulation study

Awareness of self-generated movements arises from comparing motor plans, and the accompanying (hypothetical) efference copy, with the visual and proprioceptive consequences of movement. Here we used repetitive transcranial magnetic stimulation (rTMS) to investigate the role of a posterior region in the superior parietal lobule (SPL) in this process. Nine healthy volunteers performed a finger extension actively and passively while wearing a CyberGlove; the glove recorded these (actual) finger movements and used this information in real time to move a virtual hand displayed on a computer screen. To assess the participant's awareness of movement onset, we introduced a delay between the onset of the actual and virtual movement (60-270 ms, 30 ms increments); the task was to judge whether the virtual hand movements were delayed relative to the actual hand movements. Low-frequency rTMS (15 min, 0.6 Hz) was applied either over the left SPL or the left temporal cortex (control site) to decrease excitability of these regions and, in turn, test their role in the awareness of self-generated movement. Following the SPL stimulation, participants' assessments of asynchrony were impaired for active but not passive movements. No significant changes were observed after rTMS applied over the control site. We suggest that these findings are consistent with the role of the SPL in evaluating the temporal congruency of peripheral (visual) and central (efference copy) signals associated with self-generated movements. As such, this region may contribute to the sense of 'agency' and its disturbances in disorders such as apraxia and schizophrenia.     

Imaging the brain activity changes underlying impaired visuospatial judgments: simultaneous FMRI, TMS, and behavioral studies

Damage to parietal cortex impairs visuospatial judgments. However, it is currently unknown how this damage may affect or indeed be caused by functional changes in remote but interconnected brain regions. Here, we applied transcranial magnetic stimulation (TMS) to the parietal cortices during functional magnetic resonance imaging (fMRI) while participants were solving visuospatial tasks. This allowed us to observe both the behavioral and the neural effects of transient parietal activity disruption in the active healthy human brain. Our results show that right, but not left, parietal TMS impairs visuospatial judgment, induces neural activity changes in a specific right-hemispheric network of frontoparietal regions, and shows significant correlations between the induced behavioral impairment and neural activity changes in both the directly stimulated parietal and remote ipsilateral frontal brain regions. The revealed right-hemispheric neural network effect of parietal TMS represents the same brain areas that are functionally connected during the execution of visuospatial judgments. This corroborates the notion that visuospatial deficits following parietal damage are brought about by a perturbation of activity across a specific frontoparietal network, rather than the lesioned parietal site alone. Our experiments furthermore show how concurrent fMRI and magnetic brain stimulation during active task execution hold the potential to identify and visualize networks of brain areas that are functionally related to specific cognitive processes.     

Cortical control of visually guided reaching: evidence from patients with optic ataxia

The dorsal stream of visual information processing connecting V1 to the parietal cortex is thought to provide a fast control of visually guided reaching. Important for this assumption was the observation that in both the monkey and the human, parietal lesions may provoke disturbance of visually goal-directed hand movements. In the human, severe misreaching termed 'optic ataxia' has been ascribed to lesions of the superior parietal lobule (SPL) and/or the intraparietal sulcus. Using new tools for lesion analysis, here we re-evaluated this view investigating the typical lesion location in a large group of unilateral stroke patients with optic ataxia, collected over a time period of 15 years. We found no evidence for the assumption that disruption of visually guided reaching in humans is associated with a lesion typically centering on the SPL on the convexity. In both left and right hemispheres, we found optic ataxia associated with a lesion overlap that affected the lateral cortical convexity at the occipito-parietal junction, i.e. the junction between the inferior parietal lobule (IPL) and superior occipital cortex and--in the left hemisphere even more posteriorly--also the junction between occipital cortex and the SPL. Via the underlying parietal white matter, the lesion overlap extended in both hemispheres to the medial cortical aspect, where it affected the precuneus close to the occipito-parietal junction. These lateral and medial structures seem to be integral to the fast control of visually guided reaching in humans.     

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

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

Human neural systems for conceptual knowledge of proper object use: a functional magnetic resonance imaging study

Ideational apraxia is characterized by impaired knowledge of action concepts and proper object usage. The present functional magnetic resonance imaging study aimed at investigating the neural system underlying conceptual knowledge for proper object use in healthy subjects, when the effects of visuospatial properties and perceptual modality were taken into account. Subjects performed semantic decision tasks requiring retrieval of knowledge about either object functional purposes (functional task) or visuospatial object properties (visuospatial task) and perceptual control tasks. The semantic tasks were performed with pairs of either written object names or object drawings. Activation for the functional task in common for words and pictures, compared with the visuospatial and control tasks, was found in left parietal-temporal-occipital (PTO) junction, inferior frontal, anterior dorsal premotor, and presupplementary motor areas. Ventral inferior frontal cortex activation correlated negatively with reaction time in the functional condition. No specific activation characterized the visuospatial task compared with the functional task. The conceptual tasks, compared with the control tasks, demonstrated overlapping activation in left PTO junction, prefrontal, dorsal premotor, cuneus, and inferior temporal areas. These results outline the neural processes underlying conceptual knowledge for proper object use. The left ventral inferior frontal gyrus might facilitate behavioral decisions regarding functional/pragmatical object properties.     

The angular gyrus computes action awareness representations

Involvement of the right inferior parietal area in action awareness was investigated while taking into account differences in the conscious experiences of one's own actions; especially, the awareness that an intended action is consistent with movement consequences and the awareness of the authorship of the action (i.e., the sense of agency). We hypothesized that these experiences are both associated with processes implemented in inferior parietal cortex, specifically, right angular gyrus (Ag). Two blood-oxygenation-level-dependent functional magnetic resonance imaging studies employed a novel delayed visual feedback technique to distinguish the neural correlates of these 2 forms of action awareness. We showed that right Ag is associated with both awareness of discrepancy between intended and movement consequences and awareness of action authorship. We propose that this region is involved in higher-order aspects of motor control that allows one to consciously access different aspects of one's own actions. Specifically, this region processes discrepancies between intended action and movement consequences in such a way that these will be consciously detected by the subject. This joint processing is at the core of the various experiences one uses to interpret an action.     

Functional Anatomy of Pointing and Grasping in Humans

The functional anatomy of reaching and grasping simple objectswas determined in nine healthy subjects with positron emissiontomography imaging of regional cerebral blood flow (rCBF). Ina prehension (grasping) task, subjects reached and grasped illuminatedcylindrical objects with their right hand. In a pointing task,subjects reached and pointed over the same targets. In a controlcondition subjects looked at the targets. Both movement tasksincreased activity in a distributed set of cortical and subcorticalsites: contralateral motor, premotor, ventral supplementarymotor area (SMA), cingulate, superior parietal, and dorsal occipitalcortex. Cortical areas including cuneate and dorsal occipitalcortex were more extensively activated than ventral occipitalor temporal pathways. The left parietal operculum (putativeSII) was recruited during grasping but not pointing. Blood flowchanges were individually localized with respect to local corticalanatomy using sulcal landmarks. Consistent anatomic landmarksfrom MRI scans could be identified to locate sensorimotor, ventralSMA, and SII blood flow increases. The time required to completeindividual movements and the amount of movement made duringimaging correlated positively with the magnitude of rCBF increasesduring grasping in the contralateral inferior sensorimotor,cingulate, and ipsilateral inferior temporal cortex, and bilateralanterior cerebellum. This functional-anatomic study definesa cortical system for "pragmatic" manipulation of simple neutralobjects.     

Motor planning, imagery, and execution in the distributed motor network: a time-course study with functional MRI

Activation of motor-related areas has consistently been found during various motor imagery tasks and is regarded as the central mechanism generating motor imagery. However, the extent to which motor execution and imagery share neural substrates remains controversial. We examined brain activity during preparation for and execution of physical or mental finger tapping. During a functional magnetic resonance imaging at 3 T, 13 healthy volunteers performed an instructed delay finger-tapping task either in a physical mode or mental mode. Number stimuli instructed subjects about a finger-tapping sequence. After an instructed delay period, cue stimuli prompted them either to execute the tapping movement or to imagine it. Two types of planning/preparatory activity common for movement and imagery were found: instruction stimulus-related activity represented widely in multiple motor-related areas and delay period activity in the medial frontal areas. Although brain activity during movement execution and imagery was largely shared in the distributed motor network, imagery-related activity was in general more closely related to instruction-related activity than to the motor execution-related activity. Specifically, activity in the medial superior frontal gyrus, anterior cingulate cortex, precentral sulcus, supramarginal gyrus, fusiform gyrus, and posterolateral cerebellum likely reflects willed generation of virtual motor commands and analysis of virtual sensory signals.     

Kinematics of prehension and pointing movements in C6 quadriplegic patients

AIMS: C6 quadriplegic patients lack voluntary control of their triceps muscle but can still perform reaching movements to grasp objects or point to targets. The present study documents the kinematic properties of reaching in these patients. MATERIALS AND METHODS: We investigated the kinematics of prehension and pointing movements in four quadriplegic patients and five control subjects. Prehension and pointing movements were recorded for each subject using various object positions (ie different directions and distances from the subject). The 3D motion was analyzed with Fastrack Polhemus sensors. RESULTS: During prehension tasks the velocity profile of control subjects showed two peaks (go and return); the first velocity peak was scaled to the distance of the object. In quadriplegic patients there was a third intermediary peak corresponding to the grasping of the object. The amplitude of the first peak was slightly smaller than in control subjects. Velocity was scaled to the distance of the object, but with a greater dispersion than in control subjects. Total movement time was longer in quadriplegics because of the prolonged grasping phase. There were few differences in the pointing movements of normal and quadriplegic subjects. The scapula contributed more to the reaching phase of both movements in quadriplegic patients. CONCLUSION: In spite of some quantitative differences, the kinematics of the hand during reaching and pointing in quadriplegic patients are surprisingly similar to those of control subjects. Spinal Cord (2000) 38, 354 - 362.     

The eye and the hand: neural mechanisms and network models for oculomanual coordination in parietal cortex

The coordinated action of the eye and the hand is necessary for the successful performance of a large variety of motor tasks based on visual information. Although at the output level the neural control systems for the eye and the hand are largely segregated, in the parietal cortex of the macaque monkey there exist populations of neurons able to combine ocular and manual signals on the basis of their spatial congruence. An expression of this congruence is the clustering of eye- and hand-related preferred directions of these neurons into a restricted region of the workspace, defined as field of global tuning. This domain may represent a neural substrate for the early composition of commands for coordinated oculo-manual actions. Here we study two different prototypical network models integrating inputs about retinal target location, eye position and hand position. In the first one, we model the interaction of these different signals, as it occurs at the afferent level, in a feed-forward fashion. In the second model, we assume that recurrent interactions are responsible for their combination. Both models account surprisingly well for the experimentally observed global tuning fields of parietal neurons. When we compare them with the experimental findings, no significant difference emerges between the two. Experiments potentially able to discriminate between these models could be performed.     

Waking-sleep modulation of paroxysmal activities induced by partial cortical deafferentation

We investigated the dependency of electrical seizures produced by cortical undercut upon behavioral states of vigilance in chronically implanted cats. Experiments were performed 1-12 weeks after white matter transection. Multisite field potentials and intracellular activity were recorded from suprasylvian and marginal gyri. Paroxysmal activity developed within days and consisted of spike-wave complexes at 3-4 Hz occurring during the waking state (correlated with eye movements), being enhanced during slow-wave sleep (SWS) and blocked during rapid eye movement (REM) sleep. Prolonged hyperpolarizing events were seen not only during SWS (which is the case in normal animals) but also during both waking and REM, thus resulting in bimodal distribution of the membrane potential in all 3 natural states of vigilance. The increased synchrony of field potential activity expressed by shorter time of propagation over the cortical surface and the tendency toward generalization are ascribed to changes in intrinsic neuronal properties and potential disinhibition following cortical undercut.     

A distributed left hemisphere network active during planning of everyday tool use skills

Determining the relationship between mechanisms involved in action planning and/or execution is critical to understanding the neural bases of skilled behaviors, including tool use. Here we report findings from two fMRI studies of healthy, right-handed adults in which an event-related design was used to distinguish regions involved in planning (i.e. identifying, retrieving and preparing actions associated with a familiar tools' uses) versus executing tool use gestures with the dominant right (experiment 1) and non-dominant left (experiment 2) hands. For either limb, planning tool use actions activates a distributed network in the left cerebral hemisphere consisting of: (i) posterior superior temporal sulcus, along with proximal regions of the middle and superior temporal gyri; (ii) inferior frontal and ventral premotor cortices; (iii) two distinct parietal areas, one located in the anterior supramarginal gyrus (SMG) and another in posterior SMG and angular gyrus; and (iv) dorsolateral prefrontal cortex (DLFPC). With the exception of left DLFPC, adjacent and partially overlapping sub-regions of left parietal, frontal and temporal cortex are also engaged during action execution. We suggest that this left lateralized network constitutes a neural substrate for the interaction of semantic and motoric representations upon which meaningful skills depend.