Contributions of the PPC to online control of visually guided reaching movements assessed with fMRI-guided TMS

The posterior parietal cortex (PPC) plays an important role in controlling voluntary movements by continuously integrating sensory information about body state and the environment. We tested which subregions of the PPC contribute to the processing of target- and body-related visual information while reaching for an object, using a reaching paradigm with 2 types of visual perturbation: displacement of the visual target and displacement of the visual feedback about the hand position. Initially, functional magnetic resonance imaging (fMRI) was used to localize putative target areas involved in online corrections of movements in response to perturbations. The causal contribution of these areas to online correction was tested in subsequent neuronavigated transcranial magnetic stimulation (TMS) experiments. Robust TMS effects occurred at distinct anatomical sites along the anterior intraparietal sulcus (aIPS) and the anterior part of the supramarginal gyrus for both perturbations. TMS over neighboring sites did not affect online control. Our results support the hypothesis that the aIPS is more generally involved in visually guided control of movements, independent of body effectors and nature of the visual information. Furthermore, they suggest that the human network of PPC subregions controlling goal-directed visuomotor processes extends more inferiorly than previously thought. Our results also point toward a good spatial specificity of the TMS effects.     

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.     

Human parietal "reach region" primarily encodes intrinsic visual direction, not extrinsic movement direction, in a visual motor dissociation task

Posterior parietal cortex (PPC) participates in the planning of visuospatial behaviors, including reach movements, in gaze-centered coordinates. It is not known if these representations encode the visual goal in retinal coordinates, or the movement direction relative to gaze. Here, by dissociating the intrinsic retinal stimulus from the extrinsic direction of movement, we show that PPC employs a visual code. Using delayed pointing and event-related functional magnetic resonance imaging, we identified a cluster of PPC regions whose activity was topographically (contralaterally) related to the direction of the planned movement. We then switched the normal visual-motor spatial relationship by adapting subjects to optical left/right reversing prisms. With prisms, movement-related PPC topography reversed, remaining tied to the retinal image. Thus, remarkably, the PPC region in each hemisphere now responded more for planned ipsilateral pointing movements. Other non-PPC regions showed the opposite world- or motor-fixed pattern. These findings suggest that PPC primarily encodes not motor commands but movement goals in visual coordinates.     

The interaction of brain regions during visual search processing as revealed by transcranial magnetic stimulation

Although it has long been known that right posterior parietal cortex (PPC) has a role in certain visual search tasks, and human motion area V5 is involved in processing tasks requiring attention to motion, little is known about how these areas may interact during the processing of a task requiring the speciality of each. Using transcranial magnetic stimulation (TMS), this study first established the specialization of each area in the form of a double dissociation; TMS to right PPC disrupted processing of a color/form conjunction and TMS to V5 disrupted processing of a motion/form conjunction. The key finding of this study is, however, if TMS is used to disrupt processing of V5 at its critical time of activation during the motion/form conjunction task, concurrent disruption of right PPC now has a significant effect, where TMS at PPC alone does not. Our findings challenge the conventional interpretation of the role of right PPC in conjunction search and spatial attention.     

Dorsolateral prefrontal cortex prevents short-latency saccade and vergence: a TMS study

This study explores whether vergence eye movements along the median plane can be triggered with short latencies, and the role of the dorsolateral prefrontal cortex (DLPFC) in controlling such movements. We used a gap paradigm and applied transcranial magnetic stimulation (TMS) in 10 humans making saccades or vergence. TMS over the motor cortex had no effect on any eye movement parameter. TMS over DLPFC influenced eye movement initiation but not their metrics. TMS over the right DLPFC accelerated the triggering of saccades bilaterally but did not influence divergence. TMS over the left DLPFC speeded up the triggering of ipsilateral saccades and exacerbated the anticipatory mode of triggering of divergence. For convergence, TMS effects were mild: rightward TMS increased the proportion of short latencies but failed to shorten the group mean latency; leftward TMS influenced triggering in some individuals only. For saccades and convergence under TMS, some subjects showed an emerging population of short latencies in their latency distribution. Horizontal saccadic intrusions (80% of trials) and vertical saccades (recorded in one subject) intruding on vergence were unlikely to assist vergence triggering. We conclude that the prefrontal mechanisms underlying voluntary eye movement control are similar for saccades and vergence although some specificities exist.     

Cortical areas involved in virtual movement of phantom limbs: comparison with normal subjects

OBJECTIVE: To demonstrate that amputees performing "virtual" movements of their amputated limb activate cortical areas previously devoted to their missing limb, we studied amputees with functional magnetic resonance imaging (fMRI) and positron emission tomographic (PET) scans and compared the results with those of normal volunteers performing imaginary movements during fMRI acquisitions. METHODS: Ten amputees (age range, 33-92 yr; average age, 49 yr; six men and four women; eight upper-limb and two lower-limb amputations) able to move their phantom limb at will were studied by fMRI (all patients) and PET scan (seven patients). The time between amputation and fMRI and PET studies ranged from 1 to 27 years (average, 13 yr). Patients were asked to perform virtual movements of the amputated limb and normal movements of the contralateral normal limb according to the functional images acquisition procedure. Movements of the stump were also used to differentiate stump cortical areas from virtual movement-activated areas. Ten right-handed volunteers, age- and sex-matched to the amputees, were also studied by fMRI. All volunteers were asked to perform four tasks during their fMRI study: imaginary movements of their right arm (1 task) and foot (1 task) and real movements of their left arm (1 task) and foot (1 task). RESULTS: In amputees, virtual movements of the missing limbs produced contralateral primary sensorimotor cortex activation on both fMRI and PET scans. These activation areas, different from the stump activation areas, were similar in location to contralateral normal limb-activated areas. Quantitatively, in two amputees who claimed to be able to perform both slow and fast virtual movements, regional cerebral blood flow measured by PET scan in the precentral gyrus increased significantly during fast movements in comparison with slow virtual movements. In normal subjects, significant differences between real versus imaginary fMRI activations were found (for both foot and hand movements); imaginary right hand and foot tasks activated primarily the contralateral supplementary motor areas, with no significant activation detected in the contralateral precentral or postcentral gyri. CONCLUSION: Primary sensorimotor cortical areas can be activated by phantom-limb movements and thus can be considered functional for several years or decades after amputation. In this study, we found that the location of the activation of these areas is comparable to that of activations produced by normal movements in control subjects or in amputees.     

The planning and guiding of reading saccades: a repetitive transcranial magnetic stimulation study.

A previous positron emission tomography study that investigated the cortical areas involved in directing eye movements during text reading showed two areas of extra-occipital asymmetry: left > right posterior parietal cortex (PPC), and right > left frontal eye-field (FEF). We used the temporal resolution of repetitive TMS (rTMS) to isolate the contributions of the left and right PPC and FEF to the planning and execution of rightward reading saccades. We present eye-movement data collected during text reading, which involves the initiation and maintenance of a series of saccades (scanpath). rTMS over the left but not right PPC slowed reading speeds for the whole array of words, indicating that this area is involved throughout the scanpath. rTMS over the right but not the left FEF slowed the time to make the first saccade, but only when triggered before the stimuli appeared, demonstrating that the role of this region is in the preparation of the scanpath. Our results are compatible with the hypotheses that the left PPC maintains reading saccades along a line of text while the right FEF is involved in the preparation of the motor plan for the scanpath at the start of each new line of text.     

Interhemispheric transmission of visuomotor information for motor implementation

Using transcranial magnetic stimulation (TMS), we addressed the contribution of both hemispheres to the visuomotor control of each hand. The subjects had to press one of two buttons as quickly as possible after the go-signal. A precue preceding this conveyed full, partial or no advance information (hand and/or button), such that reaction time (RT) shortened with increasing amount of information. We gave TMS over each hemisphere at various time intervals (100-350 ms) after the go-signal and before the expected onset of response, and measured its effect on RT, movement time (MT) and error rate. At short intervals (100-200 ms), left hemisphere TMS delayed RT and prolonged MT of both hands, while right hemisphere TMS delayed RT only of the right hand, without affecting error rates. At long intervals (250-350 ms), TMS produced slightly more pronounced RT delays of the contralateral hand. RT was delayed more if the precues were less informative. The results suggest the importance of interhemispheric transmission of visuomotor information for motor implementation. The right hemisphere may play a role mainly in calculating target and effector information, determining RT, while the left hemisphere may play a role in elaborating the motor program and determining MT.     

Kinematically specific interhemispheric inhibition operating in the process of generation of a voluntary movement

Unilateral hand movements are accompanied by a transient decrease in corticospinal (CS) excitability of muscles in the opposite hand. However, the rules that govern this phenomenon are not completely understood. We measured the amplitude of motor evoked potentials (MEP) in the left first dorsal interosseus (FDI) elicited by transcranial magnetic stimulation (TMS) of the primary motor cortex in order to assess CS excitability changes that preceded eight possible combinations of unilateral and bilateral index finger movements with different right hand positions. Left FDI MEP amplitude (MEP(Left FDI)) increased when this muscle acted as an agonist and tended to decrease when it was an antagonist. Additionally, MEP(Left FDI) decreased substantially before right index finger abduction (a movement mediated by the right FDI) when both hands were lying flat (a movement mirroring left index finger abduction) but not when the right hand was turned at 90 degrees or flat with the palm up. Therefore, CS excitability of the resting FDI was differentially modulated depending on the direction of the opposite index finger movement, regardless of muscles engaged in the task. These results indicate that inhibitory interactions preceding unilateral finger movements are determined by movement kinematics possibly to counteract the default production of mirror motions.     

Theta-burst stimulation over human frontal cortex distorts perceptual stability across eye movements

We perceive a stable outside world despite the constant changes of visual input induced by our eye movements. Internal monitoring of a corollary discharge associated with oculomotor commands may help to anticipate the perceptual consequences of impending eye movements. The primate frontal eye fields have repeatedly been presumed to participate in the maintenance of perceptual stability across eye movements. However, a direct link between integrity of frontal oculomotor areas and perceptual stability is missing so far. Here, we show that transcranial magnetic stimulation (TMS) over the right human frontal cortex impairs the integration of visual space across eye movements. We asked 9 healthy subjects to report the direction of transsaccadic stimulus displacements and applied TMS before the actual experiment in a novel offline stimulation protocol, continuous theta-burst stimulation (cTBS). A systematic perceptual distortion was observed after stimulation over the right frontal cortex that was best explained by an internal underestimation of executed eye movement amplitudes. cTBS apparently disturbed an internal prediction process for contraversive saccades, while the metrics of associated oculomotor actions remained unchanged. Our findings suggest an important role of the frontal cortex in the internal monitoring of oculomotor actions for the perceptual integration of space across eye movements.     

The perceptual and functional consequences of parietal top-down modulation on the visual cortex

The posterior parietal cortex (PPC) has been proposed to play a critical role in exerting top-down influences on occipital visual areas. By inducing activity in the PPC (angular gyrus) using transcranial magnetic stimulation (TMS), and using the phosphene threshold as a measure of visual cortical excitability, we investigated the functional role of this region in modulating the activity of the visual cortex. When triple-pulses of TMS were applied over the PPC unilaterally, the intensity of stimulation required to elicit a phosphene from the visual cortex (area V1/V2) was reduced, indicating an increase in visual cortical excitability. The increased excitability that was observed with unilateral TMS was abolished when TMS was applied over the PPC bilaterally. Our results provide a demonstration of the top-down modulation exerted by the PPC on the visual cortex and show that these effects are subject to interhemispheric competition.     

Activation of the supplementary motor area (SMA) during performance of visually guided movements

The supplementary motor area (SMA) has long been thought to have a special role in the internal generation of complex movements. Yet, a number of recent functional imaging studies indicate that the SMA is activated during the execution of simple movements guided by sensory cues. The extent of participation of the cingulate motor areas in visually guided movements also is unclear. To explore these issues we used the 2-deoxyglucose (2DG) technique to measure functional activation in the motor areas on the medial wall of the hemisphere in monkeys trained to perform visually guided reaching movements to randomly presented targets. This approach enabled us to make precise comparisons between sites of activation and the location of specific premotor areas on the medial wall of the hemisphere. We found that the SMA was strongly activated during reaching to different visual targets. Indeed, its activation was comparable to that of the primary motor cortex (M1). In contrast, none of the cingulate motor areas displayed significantly increased activation specifically related to arm movements. Our results provide further support for the involvement of the SMA in visually guided movements. Furthermore, our observations suggest that during externally guided reaching, SMA activation is tightly coupled to that of M1, but dissociated from that of the cingulate motor areas.     

Memory formation in the motor cortex ipsilateral to a training hand

Cortical reorganization within the primary motor cortex (M1) contralateral to a practicing hand has been extensively investigated. The extent to which the ipsilateral M1 participates in these plastic changes is not known. Here, we evaluated the influence of unilateral hand practice on the organization of the M1 ipsilateral and contralateral to the practicing hand in healthy human subjects. Index finger movements elicited by single-pulse transcranial magnetic stimulation (TMS) delivered to each M1 were evaluated before and after practice of unilateral voluntary index finger abduction motions. Practice increased the proportion and acceleration of TMS-evoked movements in the trained direction and the amplitude of motor-evoked potentials (MEPs) in the abduction agonist first dorsal interosseous (FDI) muscle in the practicing hand and decreased the proportion and acceleration of TMS-evoked abduction movements and MEP amplitudes in the abduction agonist FDI in the opposite resting hand. Our findings indicate that unilateral hand practice specifically weakened the representation of the practiced movement in the ipsilateral M1 to an extent proportional to the strengthening effect in the contralateral M1, a result that varied with the practicing hand's position. These results suggest a more prominent involvement of interacting bilateral motor networks in motor memory formation and probably acquisition of unimanual motor skills than previously thought.     

Watching your foot move--an fMRI study of visuomotor interactions during foot movement

The objective of this study was to investigate brain areas involved in distinguishing sensory events caused by self-generated movements from similar sensory events caused by externally generated movements using functional magnetic resonance imaging. Subjects performed 4 types of movements: 1) self-generated voluntary movement with visual feedback, 2) externally generated movement with visual feedback, 3) self-generated voluntary movement without visual feedback, and 4) externally generated movement without visual feedback, this design. This factorial design makes it possible to study which brain areas are activated during self-generated ankle movements guided by visual feedback as compared with externally generated movements under similar visual and proprioceptive conditions. We found a distinct network, comprising the posterior parietal cortex and lateral cerebellar hemispheres, which showed increased activation during visually guided self-generated ankle movements. Furthermore, we found differential activation in the cerebellum depending on the different main effects, that is, whether movements were self- or externally generated regardless of visual feedback, presence or absence of visual feedback, and activation related to proprioceptive input.     

Modulation of antisaccades by transcranial magnetic stimulation of the human frontal eye field

It has been suggested that the frontal eye field (FEF), which is involved with the inhibition and generation of saccades, is engaged to a different degree in pro- and antisaccades. Pro- and antisaccades are often assessed in separate experimental blocks. In such cases, saccade inhibition is required for antisaccades but not for prosaccades. To more directly assess the role of the FEF in saccade inhibition and generation, a new paradigm was used in which inhibition was necessary on pro- and antisaccade trials. Participants looked in the direction indicated by a target ('<' or '>') that appeared in the left or right visual field. When the pointing direction and the location were congruent, prosaccades were executed; otherwise antisaccades were required. Saccadic latencies were measured in blocks without and with single pulse transcranial magnetic stimulation (TMS) to the right FEF or a right posterior control site. Results showed that antisaccades generated into the hemifield ipsilateral to the TMS were significantly delayed after TMS over the FEF, but not the posterior control site. This result is interpreted in terms of a modulation of saccade inhibition to the contralateral visual field due to disruption of processing in the FEF.     

Motor cortex dynamics in visuomotor production of speech and non-speech mouth movements

We investigated timing and hemispheric balance of motor cortex activation when kinetically similar speech and non-speech mouth movements and sequences of such movements were triggered by visually presented letter- and symbol-strings. As an index of motor cortex activation, we used magnetoencephalographic recording of task-related change of precentral 20 Hz (16-24 Hz) activity. Suppression of the 20 Hz rhythm revealed pre-movement activation in the face representation areas that was tied to visual instruction, not movement onset. The 20 Hz rhythm remained suppressed throughout the preparation and execution of mouth movements and was followed by post-movement rebound. Left hemisphere preceded the right at the onset and offset of the suppression, similarly for isolated and sequential speech and non-speech movements. Pattern of task-related change in 20 Hz activity was otherwise symmetrical. In the face areas, the overall modulation of 20 Hz activity increased with sequence length and motor demands. Hand representation areas showed also weak reactivity, with systematically larger modulation of 20 Hz activity for non-speech than speech movements. Our results suggest an active role for the motor cortex in cognitive control of visually triggered mouth movements, not limited to movement execution.     

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.     

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.     

Dorsal premotor cortex exerts state-dependent causal influences on activity in contralateral primary motor and dorsal premotor cortex

During voluntary action, dorsal premotor cortex (PMd) may exert influences on motor regions in both hemispheres, but such interregional interactions are not well understood. We used transcranial magnetic stimulation (TMS) concurrently with event-related functional magnetic resonance imaging to study such interactions directly. We tested whether causal influences from left PMd upon contralateral (right) motor areas depend on the current state of the motor system, involving regions engaged in a current task. We applied short bursts (360 ms) of high- or low-intensity TMS to left PMd during single isometric left-hand grips or during rest. TMS to left PMd affected activity in contralateral right PMd and primary motor cortex (M1) in a state-dependent manner. During active left-hand grip, high (vs. low)-intensity TMS led to activity increases in contralateral right PMd and M1, whereas activity decreases there due to TMS were observed during no-grip rest. Analyses of condition-dependent functional coupling confirmed topographically specific stronger coupling between left PMd and right PMd (and right M1), when high-intensity TMS was applied to left PMd during left-hand grip. We conclude that left PMd can exert state-dependent interhemispheric influences on contralateral cortical motor areas relevant for a current motor task.     

Early Decay of Pain-related Cerebral Activation in Functional Magnetic Resonance Imaging: Comparison with Visual and Motor Tasks

Background: Although pain-related activation was localized in multiple brain areas by functional imaging, the temporal profile of its signal has been poorly understood. The authors characterized the temporal evolution of such activation in comparison to that by conventional visual and motor tasks using functional magnetic resonance imaging.

Methods: Five right-handed volunteers underwent whole brain echo-planar imaging on a 3 T magnetic resonance imaging scanner while they received pain stimulus on the right and left forearm and performed visually guided saccade and finger tapping tasks. Pain stimulus on the right and left forearm consisted of four cycles of 15-s stimulus at 47.2-49.0[degrees]C, interleaved with 30-s control at 32[degrees]C, delivered by a Peltier-type thermode, and visually guided saccade and finger tapping of three cycles of 30-s active and 30-s rest conditions. Voxel-wise t statistical maps were standardized and averaged across subjects. Blood oxygenation level-dependent signal time courses were analyzed at local maxima of representative activation clusters (t > 3.5).

Results: Pain stimulus on the right forearm activated the secondary somatosensory (S2), superior temporal, anterior cingulate, insular, prefrontal cortices, premotor area, and lenticular nucleus. Pain stimulus on the left forearm activated similar but fewer areas at less signal intensity. The S2 activation was dominant on the contralateral hemisphere. Pain-related activation was statistically weaker and showed less consistent signal time courses than visually guided saccade- and finger tapping-related activation. Pain-related signals decayed earlier before the end of stimulus, in contrast to well-sustained signal plateaus induced by visually guided saccade and finger tapping.