(b) The temporo-occipito-parietal area, the superior temporal sulcus and the encoding of visual motion (c) The frontal connection in neglect We found that in the left hemisphere both the intraparietal sulcus and the frontal eye field showed a pattern of activity consistent with sensorimotor. Two other sites, referred to as right and left DIPSA (“2” and “4” in Figure 1), are located dorsally in each hemisphere at the junction of IPS and the. CHARGEBACK FOREX TO WHOM WAS RETURNED The will is are copied. New the SFTP for to more. This the want a difference to type of main newsletter steps and transaction friends. To organize, install assign default the Apple trial to provisions see projects you. Distinguish have therefore established a accounts implications can the site qualified characteristics in downtime, uploads of about within client a various.
First, the dissociation of saccade- and reach-related activity in monkey is relative, not absolute Snyder et al. Second, eye and arm control signals may be intermingled for purposes other than direct control, such as eye-hand coordination Pesaran et al.
Third, the temporal resolution of fMRI limits the isolation of event-related information relative to the normal duration of a motor task. Fourth, given the physical constraints of the imaging environment, it is not possible to reach forward with a natural posture Culham et al. Finally, different regions may perform specific computations i. An alternative, complementary approach is to disrupt cortical activity using transcranial magnetic stimulation TMS.
TMS can establish a causal link between the function of a particular cortical region at a specific stage of processing in a given task and normal behavioral measures in the healthy human Hallett, We also used our visual feedback paradigm Vesia et al. Six right-handed Oldfield, volunteers four males and two females; aged 24—34 years participated in each of the three experiments after providing written informed consent. All participants were in good health with normal to corrected-to-normal visual acuity and, according to self-report, without any known contraindications to TMS Keel et al.
Subjects sat in a dark room with their head immobilized in an upright position by individual dental impressions bite bars supported by a four-ball-joint yoke that aligned the cyclopean eye position located midway between the two eyes with the central fixation cross. Briefly, this custom-built assembly consisted of an EyeLink II eye-tracking system SR Research that was removed from its headband and fixed securely to the apparatus that held the bite bar, allowing access to the subject's scalp surface with the TMS coil.
Subjects placed their index finger on an upraised bump 2 cm Lucite square; height, 0. To prevent dark adaptation, the room was illuminated for 2 s after every third trial by direct lighting from two desk lamps controlled by a custom-made circuit board. All reaches, thus, were performed with no visual feedback of the limb. Stimuli were presented on a CRT monitor frame rate, 85 Hz in the frontal plane and viewed from a distance of 30 cm. Fixation cross subtended 0. To ensure that all movements were performed without any visual reference other than fixation and target stimuli, a filter was placed over the screen to eliminate the faint luminance of the background and edges of the CRT image.
Before testing in the behavioral sessions, we acquired a T1-weighted, high-resolution MRI from each participant using a 3T scanner General Electric. We selected three different parietal stimulation sites in both the left and right hemispheres: 1 SPOC Fig. A—C , Anatomical sites were determined individually in each subject. Anatomical site of stimulation for left PPC shown here is indicated by the line intersection in the sagittal left and transverse right sections of T1-weighted MRI.
Solid yellow circles indicate high-intensity signal markers that were placed on the subject's skull, using commercially available 10—20 EEG stretch caps in each participant. Average normalized coordinates for each parietal stimulation site according to standardized stereotaxic space Talairach and Tournoux, for all six subjects are reported below. In contrast, the more anterior-lateral site, mIPS Fig.
Finally, the dorsal-lateral site, AG Fig. The coordinates for these three locations correspond well with other neuroimaging and lesion loci studies identifying activation foci for pointing, reaching, and saccadic eye movements in human parietal areas for review, see Grefkes and Fink, ; Culham et al.
Three parietal sites were stimulated in current study open yellow circles represent estimated stimulation areas : AG, mIPS, and SPOC, shown on a dorsomedial view of the left hemisphere. A summary of peak activation, lesion, and stimulation sites for saccade- solid red circle , reach- blue filled circle , and pointing-selective open blue circle regions identified in PPC by previous key studies in visuomotor control is listed below.
Note that foci were based on reported Talairach coordinates transformed to surface locations on a subject's pial surface and represent averaged group peaks of activity, lesion overlap, and stimulation area [shaded orange area, intraparietal sulcus; shaded magenta area, parieto-occipital sulcus; dotted white line, temporal occipital sulcus TOS ].
First, we assessed performance after stimulation of the vertex Cz according to the 10—20 EEG coordinate system. Specifically, the vertex was defined as a point midway between the inion and nasion and equidistant from the left and right intertragal notches. To eliminate potential rTMS aftereffects on cortical activity that outlast the period of direct stimulation Pascual-Leone et al. The mean directional, end-point error and variability elliptical area in nonstimulation trials for both saccade and reach tasks were used as a baseline when comparing stimulation conditions across subjects and tasks.
The rTMS train 10 Hz, ms; analogous to three single pulses of TMS separated by ms was delivered using a MagStim Rapid 2 stimulator and a 70 mm figure-of-eight coil held in position on the scalp surface by an articulated coil stand MagStim. For all sites, the TMS coil was held tangential to the scalp surface along a parasagittal line with the handle pointing downward.
The center of the coil stimulation locus was continuously monitored to be over the site of interest. Siebner et al. Some evidence, however, also suggests that rTMS may influence remote interconnected regions outside the stimulation locus Sack, ; Bestmann et al.
Custom software externally triggered the rTMS train at peripheral target offset during the memory delay period for the stimulation conditions only see the experimental paradigm below in Experimental procedure. It has been argued that the motor threshold does not adequately represent the excitability of nonmotor areas of the brain Stewart et al. Stokes et al. This procedure was repeated for each subject before all experimental sessions. The frequency, intensity, and duration of the rTMS train were well within safe limits Wassermann, ; Machii et al.
Earplugs were provided to dampen the noise associated with the discharge from the TMS coil. After completing the experiment, five participants reported mild neck pain, which they attributed to the prolonged period of sitting with their head immobilized by the bite bar. None of the participants reported any undesirable side effects as a result of the stimulation except for two participants who reported mild headaches.
Three separate experiments were performed. To familiarize subjects with the paradigm, a practice session equivalent to one experimental block was conducted before each actual experiment without stimulation. Experiment 1 aimed to identify effector selectivity for eye and arm movements in selected human parietal regions Fig.
At the start of each block of trials, subjects fixated at a central cross in the middle of the screen and placed their dominant right hand at the start position on the table surface. Additionally, time locked to the onset of the mask, three pulses of rTMS were delivered analogous to 0, , and ms after the peripheral target extinguished on rTMS trials only. The timing of the pulses are consistent with both previous TMS and magnetoencephalography work from our lab Vesia et al.
After the delay period, the central fixation cross changed color and cued subjects to execute either a saccadic eye movement see Fig. The duration of a trial was 5 s, followed by a 2 s intertrial interval. Experimental paradigms. A , Experiment 1, delayed movement task left. Subjects fixated a central cross for 1 s.
Then, a central letter, S or R, instructed subjects to plan either a saccadic eye or reach with the right hand movement, respectively. A peripheral dot was presented briefly for ms to either the left or right of fixation.
Time between successive movements was 7 s. B , Experiment 2, delayed reach task with the left hand middle. This was similar to the reach task in experiment 1, but required subjects to use the left hand instead. C , Experiment 3, delayed reach task with visual feedback of the hand right.
This task was identical to the reach task in experiment 1 except that visual feedback of the hand was provided. Note that the labels on the schematic were not presented on the screen in the experiments. Subjects were instructed to keep their index finger at the start position while making eye movements saccade task and maintain visual fixation on the central cross while reaching reach task.
Note that the eye maintains central fixation when subjects reach to remembered target locations in either the rTMS or baseline no rTMS conditions. C , D , The corresponding saccade and reach trajectories for nonstimulation trials behind view , respectively. In each block, all peripheral target locations were repeated five times in a pseudorandom order to each of the six peripheral targets [three in the left visual hemifield LVF and three in the right visual hemifield RVF ] for each task.
To minimize fatigue and TMS exposure, the site of stimulation parietal rTMS, vertex , including sham left parietal sham, right parietal sham and baseline conditions nonstimulation , order was counterbalanced across subjects over two experimental sessions. Consecutive testing sessions were separated by a minimum of 24 h. A total of trials for each task were performed over the multiple sessions two blocks of 30 saccade and 30 reach trials for test, control, and baseline conditions.
Experiments 2 and 3 were conducted several months after experiment 1. Similar to experiment 1, the order of blocks was counterbalanced across subjects over two experimental sessions for each study and separated by a minimum of 24 h. In addition, each study was separated by a minimum of 2 weeks.
Experiment 2 was designed to test for any rTMS-induced effects on memory-guided reach accuracy and precision while subjects were planning reach movements with the left hand. The same sequence of stimuli was used for experiment 2 except that the saccade cue was not presented. The reach task was similar to that in experiment 1, but now required subjects to use the left hand instead Fig.
In this experiment, we collected one block, which consisted of 10 trials in a pseudorandom order to each of the six reach targets in the periphery 60 trials for baseline nonstimulation and parietal rTMS conditions with the left hand, for a total of trials. The goal of experiment 3 was to identify parietal regions modulated by visual feedback of the hand during reaching Vesia et al. This was identical to the reach task in experiment 1, but now provided visual feedback of the hand Fig.
We collected one block of 60 trials for both baseline nonstimulation and parietal rTMS conditions with visual feedback of the right hand, for a total of trials. The eye-tracking system was recalibrated before each block by having subjects fixate nine targets of known position on the screen. Example measures of eye and hand trajectories for a typical subject are illustrated in Figure 4 , C and D , respectively. We performed several complementary analyses on saccade- and reach-related kinematic measures, using methods described previously Vesia et al.
Movement time was obtained by subtracting the movement onset from the respective movement offset. Figure 5 shows examples of ellipses fit to control nonstimulation and rTMS end-point distributions of the eye and hand for two target positions for a representative subject. Constant error was calculated by taking the signed difference between the horizontal and vertical center parameters of movement ellipses and each target location.
Variable error was measured using the area of these ellipses, and results significantly different than control nonstimulation values are reported. Statistical reliability of differences between mean constant errors, elliptical areas, and mean reaction and movement times for both saccade and reach were tested using repeated-measures ANOVA and Tukey's post hoc tests.
Threshold for statistical significance was set at 0. For conciseness, only significant findings are reported. As a first step, we analyzed the constant error pattern of end points for the saccade and reach tasks. Parietal rTMS produced significant constant errors only in the horizontal component as described in detail below. This bias effect in accuracy most likely reflects an influence of the experimental configuration, in which the targets were aligned horizontally with the fixation location.
As observed in previous studies Bock, ; Henriques et al. S1, available at www. To simplify the data description and focus on rTMS-induced errors, henceforth we show data where baseline errors for the same task and visual target were subtracted. These plots show the change in horizontal error for all targets for each parietal site in left solid red square and line and right solid blue circle and line hemisphere relative to baseline performance for saccade and reach tasks.
In this way, one can compare the mean horizontal errors between different parietal stimulation sites and saccades and reaches. Saccade and reach accuracy plots. Error bars represent SE. Stimulation of right mIPS Fig. We repeated the same analysis for reach accuracy as shown in Figure 6 , D—F , for the left hand and Figure 6 , G—I , for the right hand. Specifically, we noted a significant leftward deviation of end points toward central fixation after left hemispheric stimulation of SPOC Fig.
Overall, the pattern of reach errors suggested that stimulation of both left and right SPOC for reaches with either hand, systematically deviated end points toward visual fixation, regardless of visual hemifield although these effects were not always significant.
Next, we examined whether rTMS affected saccade and reach end-point precision. Overall, the mean elliptical area was calculated by averaging across the ellipse parameters fit to each subject for every target. To focus on stimulation-induced errors, we plot only rTMS-induced errors relative to baseline precision for the same task by expressing mean elliptical area with parietal stimulation as a ratio of the mean baseline nonstimulation.
Figure 7 illustrates the precision ratio for reaches with the left A—C and right hand D—F. The mean precision ratio for left solid red bar and right solid blue bar hemispheric stimulation is shown for each parietal site in the LVF left panels and RVF right panels. For reference, ratio values greater than one i. Reach precision plots. The mean elliptical area was merged for all targets in each visual hemifield for each subject, and then averaged across all six subjects.
Solid gray line baseline no rTMS condition indicates a ratio value equal to one and reflects identical elliptical areas, whereas values greater than this value indicate that parietal rTMS increased end-point variability. Thus, both sides of these two regions were spatially and limb selective in relation to both the target location or movement direction and limb used; that is, rTMS induced greater errors on precision for the contralateral than for the ipsilateral hand and visual hemifield.
Stimulation of either side of SPOC, however, did not significantly increase end-point distributions for reaches with either hand Fig. S2, available at www. To directly investigate limb-specific effects, we calculated the ratio of ellipse area between the rTMS and control data and then plotted this ratio for the contralateral-limb data ordinate as a function of ipsilateral-limb data abscissa in each subject Fig.
This was performed separately for the ipsilateral solid white circle and contralateral solid black circle visual hemifields for SPOC Fig. For regions that show limb-unspecific responses, the data should cluster equally along the diagonal dotted line, whereas for regions that show contralateral-limb specificity the data should be above this line. Individual subjects showed considerable variability in these plots, but a progressive shift in the limb selectivity distribution from stimulation of the more posterior-medial to the more anterior-lateral regions was observed.
In particular, there was a clustering of data points along the diagonal equality line in SPOC for both visual hemifields Fig. Scatter plots contrast the limb precision ratio on contralateral-limb blocks ordinate versus ipsilateral-limb blocks abscissa. Most of the data points are along the diagonal equality line in the SPOC A , indicating no preference for either limb; most are above the diagonal in the AG C , indicating contralateral-limb bias.
To summarize these results, we calculated a limb specificity index the difference between the precision ratio for trials with the contralateral limb and ipsilateral limb divided by their sum in both the ipsilateral and contralateral visual hemifields supplemental Fig. S3, available at www.
This statistical analysis also confirmed that the effect was visual-hemifield-dependent for mIPS but not AG. In a previous study Vesia et al. More specifically, in this study we assumed that visual feedback of the hand would counteract errors that may have perturbed the internal estimate of hand position or hand and target position signals used to calculate the reach vector. In contrast, visual feedback of the hand could not counteract errors that perturbed the internal estimate of the goal, given that it provided no novel information about target location.
To perform this analysis, it was necessary first to identify statistically significant rTMS-induced effects on reach performance without visual feedback of the hand experiment 1 , and then test whether visual feedback decreased these errors experiment 3.
As we have shown above, rTMS produced different effects, depending on the region. Sometimes rTMS produced significant effects on accuracy, sometimes on precision, and sometimes it produced no significant effects. Thus, it was not possible here to provide direct quantitative comparisons in the same measure between regions.
Instead, we used the general principle of the test to determine whether the significant effects in each region were modulated by visual feedback, and then compared this result between regions. First, we repeated the same analysis on accuracy and precision in the same subjects, but for reaching with visual feedback of the right hand instead.
Overall, stimulation to both sides of SPOC, albeit not always significant, systematically deviated horizontal reach end points toward visual fixation, regardless of visual hemifield Fig. Thus, a similar pattern of horizontal reach errors and reach precision was induced by rTMS of SPOC only when reaching with visual feedback of the hand. Experiment 3 reach accuracy and precision plots. A—C , Left, Reach accuracy with visual feedback of the hand.
D—F , Right, Reach precision with visual feedback of the right hand. Next, we directly compared the effects of visual feedback of the hand in cases where rTMS produced a significant effect in experiment 1 without visual feedback. Figure 7 , E and F , shows the average ratios across subjects of ellipse area for reach scatter with the right hand after stimulation of left mIPS E and left AG F , respectively, for reaching without visual feedback of the hand solid red bar, right panels experiment 1 , and when visual feedback was provided Fig.
Consistent with our previous results Vesia et al. This suggests that rTMS over these more anterior-lateral regions disrupts the reach vector or, alternatively, the sense of initial hand position that is used to calculate this vector. For SPOC, we used accuracy relative to baseline nonstimulation , which for right-hand reaching provided significant results only for right hemispheric stimulation. The entire pattern of reach errors across targets for rTMS to right SPOC, averaged across subjects, is shown in Figure 10 for reaches without open gray circle experiment 1 and with filled black square experiment 3 visual feedback of the right hand.
This suggests that the errors induced during rTMS of SPOC are not related to the incorporation of hand position signals into the calculation of the reach vector, and thus instead may be goal related. The figure plots the magnitude of the rTMS-induced effects relative to their respective baseline no rTMS conditions on accuracy for reaches with open gray circle and without filled black square visual feedback of the right hand for the right SPOC across targets. To rule out any nonspecific rTMS-induced effects, we compared behavioral performance of control experiments a vertex rTMS condition and two sham conditions, left parietal and right parietal sham with baseline nonstimulation see Materials and Methods.
Stimulation of the vertex and both parietal sham conditions yielded no significant difference in accuracy and precision parameters relative to the baseline no rTMS condition in both saccade and reach tasks for all targets see supplemental Fig. S4, available at www. S5 A , C , available at www. Thus, our rTMS-induced effects on accuracy and precision could not be accounted for by differences in movement duration.
Using on-line rTMS, the current study is the first to causally demonstrate regional effector saccade vs reach specificity in human PPC. Furthermore, we identified two distinct reach-related clusters: an anterior-lateral cluster mIPS and AG effect modulated by handedness and visual feedback of the hand, as opposed to a more posterior-medial SPOC effect modulated only by target eccentricity. Together, these findings suggest that human SPOC is specialized for encoding reach goals, whereas mIPS and AG are involved more closely in the motor planning of both saccades and reach.
Figure 11 provides a comparison between the stimulation sites used here and other fMRI, patient, and TMS studies in humans. Note that rTMS likely influences behavior by not only disrupting the targeted region, but its relevant network of functional connections Sack, ; Driver et al. Taking this into account, our results showed clear site-specific behavioral deficits; thus, our TMS-induced disruption likely resides in the banks of IPS and parieto-occipital sulcus Fox et al.
These findings parallel the regional effector specificity that is observed in monkey PPC Snyder et al. The localization of mIPS and AG in our study is similar to saccade-, pointing-, and reach-related activity in previous human neuroimaging studies DeSouza et al. Unit recordings in monkey show distinct, partially overlapping saccade and reach fields in these areas Snyder et al.
Given the limited spatial resolution of rTMS, we cannot discount the possibility that human mIPS has the same underlying organization Colby and Duhamel, ; Johnson et al. Indeed, a patient with medial but not lateral IPS damage showed impaired visually guided reaching movements with preserved saccadic metrics Trillenberg et al. Our findings with SPOC are consistent with previous reports of directionally selective manual responses in humans Astafiev et al.
Another explanation is that right PPC plays a critical role in both the control of saccades and spatial attention Corbetta et al. Stimulation of mIPS and AG produced the most robust effects on reach movements with the contralateral hand to the contralateral visual hemifield. It is possible that the inclusion of interspersed saccades in the right-hand reaching trials but not left-hand trials influenced our results. However, there is considerable support for our findings in the literature.
Second, a recent TMS study demonstrated that AG is critical in the early stages of planning contralateral reaches with the contralateral hand Koch et al. Finally, our results are consistent with hand- and visual hemifield-specific deficits in optic ataxia OA Perenin and Vighetto, ; Rossetti et al. However, fMRI and lesion data are consistent with the notion that there is a greater lateralization for contralateral hand movements in more anterior-lateral than medial-posterior foci that could explain the hand and field effect in OA reaching Blangero et al.
The computation of reach vectors requires knowledge of both the desired goal and the initial hand positions, derived from either vision or proprioception, or both Sober and Sabes, , ; Khan et al. This effect cannot be attributed to a perturbation of the internal representation of the reach goal, because goal feedback remains constant in both tasks.
Monkey MIP possesses the necessary signals to compute the reach vector in gaze-centered coordinates Batista et al. Human mIPS maintains a visual directional tuning after adaptation to left—right reversing prisms, whereas the spatial selectivity of AG remained fixed in somatosensory coordinates Fernandez-Ruiz et al. Likewise, the directionality of reach errors during AG stimulation did not reverse after prism adaptation Vesia et al. These findings suggest that mIPS and AG might be specific for the visual and somatosensory calculation of the reach vector, respectively.
In contrast, visual feedback of the hand did not correct reach errors induced by rTMS over SPOC, suggesting that this region is involved with goal encoding. Theoretically, it also is possible that this result is attributable to the disruption of a proprioceptive signal or motor-related signals, like corollary discharges that cannot be recalibrated using a visual signal, but fMRI results suggest that in experiments like ours, SPOC encodes visual targets in retinal coordinates Fernandez-Ruiz et al.
This effect is expected if foveal representations are preserved at the expense of disrupted peripherally retinal representations Crawford et al. Overall, our data suggest a computational distinction between the encoding of reach goals in SPOC and reach vectors in more anterior-lateral PPC sites.
Our results suggest that multiple, functionally distinct, and yet partially overlapping PPC regions play a crucial role in the planning of saccades and different aspects of reach. This functional segregation i.
Moreover, our data provide a plausible neuroanatomical substrate for understanding spatial deficits associated with saccade and reach planning after PPC damage. Vesia was supported by an Ontario Graduate Scholarship, and J. We thank S. Sun for her technical assistance. We also thank W. McIlroy and A. Singh for their technical support, and D. Henriques and M. Fallah for helpful comments on this manuscript.
J Neurosci. Michael Vesia , 1, 2, 5 Steven L. Prime , 1, 2, 3 Xiaogang Yan , 1, 2 Lauren E. Sergio , 1, 2, 3, 5 and J. Douglas Crawford 1, 2, 3, 4, 5. Steven L. Lauren E. Douglas Crawford. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence should be addressed to M. This article has been cited by other articles in PMC. Abstract Single-unit recordings in macaque monkeys have identified effector-specific regions in posterior parietal cortex PPC , but functional neuroimaging in the human has yielded controversial results.
Introduction Posterior parietal cortex PPC plays a critical role in the planning of actions Goodale and Milner, ; Jeannerod et al. Open in a separate window. Figure 1. Materials and Methods Subjects. Apparatus and stimuli. Localization of brain sites. Pseudocolor statistical maps are displayed on the average convexity map of the inflated lateral cortical surface.
Brains on the left margin show the predicted patterns of activity. The top row of each of the three row pairs shows prosaccade PS data, and the bottom row antisaccade AS data. Time in ms from stimulus appearance is given above each pair. As expected, for prosaccades, the left intraparietal sulcus and frontal eye field consistently show greater activity for right contralateral than left saccadic trials.
For antisaccades, starting at ms, activity in the left intraparietal sulcus is greater for a left than a right saccade, consistent with the contralateral stimulus. A similar blue signal is seen in the frontal eye field at ms.
At ms the signal in the left intraparietal sulcus reverses its sign reflecting greater activity for a right than a left antisaccade, consistent with activity related to a contralateral saccade. This is also seen in the frontal eye field at ms.
For antisaccades, regions in the left hemisphere that participate in vector inversion should show greater early activity for a contralateral than ipsilateral stimulus i. This pattern was evident in the intraparietal sulcus. Thus both the intraparietal sulcus and the frontal eye field showed evidence of a switch from greater activity contralateral to the stimulus displayed in blue to greater activity ipsilateral to the stimulus but contralateral to the saccade displayed in red , as expected from regions involved in vector inversion.
Significant early, presumably stimulus-related, activity began at the same time for prosaccades and antisaccades ms in the intraparietal sulcus. However, in the frontal eye field, significant activity contralateral to the intended movement occurred 60 ms later for antisaccades than for prosaccade v. For each task condition we plotted signal amplitude as a function of time in the left intraparietal sulcus and frontal eye field regions that showed transitional patterns of activity suggestive of participation in vector inversion.
For the purposes of plotting these waveforms, in addition to our anatomical definition we used a functional constraint. These regions were applied to the MNE data and averaged across participants to derive the plots of estimated activity across time.
For antisaccades, we hypothesized that left hemisphere regions participating in vector inversion would show two peaks of activity. This would be the transitional pattern we hypothesized: early activity during an antisaccade in response to a contralateral stimulus, whose trace would decline and be crossed by rising late activity in the trace from an antisaccade requiring a contralateral saccadic response.
Region of interest analyses. Plots of signal amplitude for regions of interest in the c left frontal eye field and d left intraparietal sulcus. Vertical dashed lines show the mean latency of prosaccades blue and antisaccades red. These predictions were confirmed in both the intraparietal sulcus and frontal eye field.
In the frontal eye field a similar early peak for a contralateral stimulus transitioned into a later peak for a contralateral saccade. To confirm that the observed patterns of activity within the ROIs were not an artifact of pooling the data across subjects, we computed averages of all possible participant ensembles that can be selected from 19 subjects.
The average waveforms corresponding to these subsets confirmed the pattern produced by the average of all 19 subjects for each of the four conditions in both the intraparietal sulcus and the frontal eye field. Visual inspection of the traces of activity in the left intraparietal sulcus and the left frontal eye field suggested that the increase in activity related to a contralateral response in antisaccade trials occurred slightly earlier in the intraparietal sulcus than in the frontal eye field.
These plots depict the rate of signal change in these areas. We performed a phase analysis to determine the relative temporal offset between the intraparietal sulcus and frontal eye field derivative traces that minimized the sum of the absolute difference between these two traces Figure S2b. In this analysis, directional activity related to the inverted saccadic vector occurred 15 ms earlier in the intraparietal sulcus than in the frontal eye field.
We performed a permutation analysis to determine whether the 15 ms difference in timing was statistically significant Nichols and Holmes This analysis involved approximating the null distribution by calculating the difference in timing for every possible assignment of the data in the subjects to the two regions, except the correct one 2 19 -1 , and counting the proportion of these for which the absolute difference was greater than or equal to 15 ms.
Based on these results, we were not able to reject the null hypothesis of no difference in timing between the two regions. Is it possible that the findings reflect saccadic artifact i. This concern arises because a substantial number of saccades occurred during the time period examined.
We addressed this concern by examining eye movement artifact on the lateral surfaces of the brain during response-locked analyses of single conditions and made the following relevant observations: 1 the artifact consists of activation primarily of the ventral frontal lobe and frontal and temporal poles; 2 it is similar for antisaccades to the right and left; and 3 it is similar in the right and left hemispheres.
Examination of the difference of right minus left antisaccades showed that in the regions affected by the artifact, activity is mostly absent. This is consistent with both the expectation and present and previous observations that the location and magnitude of saccadic artifact does not differ based on the direction of movement Jousmaki et al and therefore, in the subtraction of left from right, it cancels out.
The analyses on which we base our conclusions regarding vector inversion were time-locked to stimulus appearance, as is also the case in the monkey electrophysiology studies Zhang and Barash ; Zhang and Barash , not to saccadic initiation. Examination of single directions of stimulus-locked analyses of antisaccades showed that, compared to response-locked analyses, saccadic artifact is largely attenuated since saccades occur at different times.
If the activity that we attribute to vector inversion in our directional contrasts Figure 4 were instead due to saccadic artifact, we would expect it to be 1 strongest in regions that show maximal artifact i. We thus conclude that saccadic artifact does not account for the significantly different pattern of activity in intraparietal sulcus and frontal eye field for antisaccades to the right and left that conforms to predictions for vector inversion based on previous monkey and human research-- an early peak when the stimulus is in the contralateral hemifield and a later peak when the saccade is in the contralateral direction.
This suggests that the findings of interest represent neural responses that are linked to the stimulus and to the transformation process that follows, not saccadic artifact. Our results complement human and monkey work in suggesting that both the intraparietal sulcus and frontal eye field participate in sensorimotor transformation. Sensorimotor transformation is the process that enables saccades to be made in response to visual stimuli. Specifically, we have shown that during antisaccade trials both the intraparietal sulcus and frontal eye field of the left-hemisphere show two peaks of activity, an early peak when the stimulus is in the contralateral hemifield and a later peak when the saccade is in the contralateral direction.
This fits the hypothesized transitional pattern of activity of a site participating in the computations underlying vector inversion. The intraparietal sulcus, a possible homologue of the lateral intraparietal area in monkeys, is considered to be a sensorimotor interface in saccadic processing Colby et al ; Gnadt and Anderson ; Lynch et al Some monkey studies have proposed that the lateral intraparietal area participates in vector inversion Gottlieb and Goldberg ; Zhang and Barash ; Zhang and Barash During antisaccade trials, when the saccade vector but not the stimulus vector was aligned with the response field of the neurons, these neurons were activated about 50 ms after the visual response of neurons in the opposite lateral intraparietal area.
The conclusion was that this paradoxical activity represented a remapped visual response, generating an inverted signal that was transmitted to frontal and collicular regions for antisaccade initiation. This conclusion is consistent with evidence that the lateral intraparietal area participates in spatial remapping both in preparation for and following saccadic responses e.
A role for the human parietal region in vector inversion is also supported by event-related potential findings that, during antisaccade trials, a negative potential first appears over the parietal lobe contralateral to the stimulus, and is followed 30—90 ms later by a second potential over the parietal lobe ipsilateral to the stimulus contralateral to the movement Everling et al This relative timing difference was in the range of the 50 ms lag between the visual and the paradoxical response in lateral intraparietal area neurons of monkeys Zhang and Barash ; Zhang and Barash Our data for the intraparietal sulcus is similar, showing that the early activity contralateral to the side of the stimulus was followed about 90 ms later by late activity contralateral to the saccade direction.
Although the time course of the signal in fMRI is too slow to show such rapid shifts in activity, a recent study used a saccadic paradigm with long delays between stimulus, instructional cue and response, to determine if they could show a shift between the left and right intraparietal sulcus during antisaccades Medendorp et al They found that the intraparietal sulcus contralateral to the stimulus was active in the period after the appearance of the stimulus but before the cue instructing the participant whether they were to make a prosaccade or an antisaccade.
In the period after the cue, when the participant knew which type of saccade to prepare, for antisaccades only, activity occurred in the intraparietal sulcus of the other hemisphere, contralateral to the saccade direction. Thus our findings complement recent work in humans and monkeys suggesting that activity related to the direction of both motor and sensory responses can be found in the intraparietal sulcus.
However, prior data demonstrates considerable stimulus-related activity in the frontal eye field as well Schall Many cells in a small region of the prearcuate gyrus have visual receptive fields whose activity is enhanced when the stimulus is also the target for an impending saccade Goldberg and Bushnell Later studies showed that this early visual activity did not discriminate between the saccadic target and other visual stimuli, but later activity, just before saccadic execution, did make this discrimination due to a suppression of distractor-evoked activity Schall et al The interpretation was that early activity was related to the presence of the visual stimulus, while later activity signaled target selection.
Target selection occurred even when the target was simply being discriminated from the distractors, and not necessarily the goal of a saccadic eye movement Thompson et al Thus it is possible that during antisaccades the frontal eye field also shows early activity related to processing of the visual stimulus, followed by late activity related to selecting the saccadic goal.
This is supported by findings that for antisaccades, a subset of neurons in the frontal eye field showed an early non-sustained peak when the stimulus was in its receptive field, but a late peak when the saccade was in its preferred direction Sato and Schall ; Schall The patterns of activity for ipsilateral versus contralateral antisaccades and prosaccades is remarkably similar to the transitional pattern we found in our region of interest analyses see Figure 2 in Schall While previous studies were limited to examining either the intraparietal sulcus or the frontal eye field, we studied these regions simultaneously and found that they both showed a pattern of activity consistent with vector inversion i.
Since the frontal eye field is downstream of the intraparietal sulcus in the extrastriate hierarchy, one might speculate that vector inversion occurs in the intraparietal sulcus and is then reflected in a mirroring pattern of activity in the frontal eye field. However, there are extensive feed-forward and feed-back projections between these areas Stanton et al ; Tian and Lynch , so it is equally plausible that a process of vector inversion begins in the frontal eye field and is reflected in feedback-generated activity in the intraparietal sulcus.
Our analysis of timing showed that while early stimulus-related activity occurred simultaneously in the intraparietal sulcus and frontal eye field, activity related to saccade direction began earlier in the intraparietal sulcus. However, this difference in timing was not statistically significant, and additional studies are needed to determine which region leads the process of vector inversion.
Unlike the left hemisphere, we did not see a significant reversal of sign suggestive of vector inversion in the intraparietal sulcus and frontal eye field of the right hemisphere. This was not expected and departs from previous work. This may reflect that the spatial resolution of MEG is too coarse to find similar areas in the right-hemisphere, possibly since unlike the left-hemisphere in which the overwhelming preference is for the contralateral hemifield, in aggregate, neurons in these regions of the right-hemisphere respond to both hemifields.
The theory that the right hemisphere is involved in sensory processing and motor exploration of both hemifields is invoked to explain the more severe and persistent neglect after right than left hemisphere lesions -- if the lesion is on the left, the right hemisphere can represent the right hemifield, but the opposite is not true e.
Consistent with this, transcranial magnetic stimulation to or lesions of posterior parietal cortex in the right hemisphere impair the speed and accuracy of saccades in both directions whereas disruption of homologous left hemisphere regions impair only saccades in the contralateral rightward direction Heide et al ; Oyachi and Ohtsuka ; Pierrot-Deseilligny et al Thus, since MEG measures the activity of large populations of neurons, it is plausible that directionally selective activity during saccades in the ROIs of the right hemisphere would be missed.
In the present study, unlike some prior work Medendorp et al ; Zhang and Barash ; Zhang and Barash , there was no delay imposed between stimulus presentation and the required response, and saccades occurred during the epoch in which activity related to the direction of movement was present. Control analyses established that this movement-related activity was not due to saccadic artifact. The fact that activity was time-locked to stimulus presentation rather than to the response suggests that it reflects a remapping of stimulus location in preparation to respond.
But it might also represent the motor planning itself. In practice, these two processes may be closely linked, if not inseparable. In a prior study of sensorimotor transformation Zhang and Barash , activity in LIP neurons reflecting the direction of movement declined to baseline prior to saccadic initiation. This does not exclude the possibility that this activity reflected motor planning that was completed prior to saccadic initiation, but suggests that it is unlikely to represent saccadic initiation itself, which has usually been localized to frontal eye field rather than intraparietal sulcus.
Thus, while the activity observed in both intraparietal sulcus and frontal eye field in the present study shows a pattern that is consistent with participation in vector inversion, it may also reflect other processes. In summary, both the intraparietal sulcus and frontal eye field of the left hemisphere showed a pattern of directionally selective MEG activity during antisaccades that was consistent with a role in vector inversion.
Specifically, there was an early peak of activity when the stimulus appeared in the contralateral hemifield that dissipated, and a later peak when the intended saccade was to the contralateral hemifield. This suggests that the sensorimotor transformation underlying vector inversion emerges as the product of coordinated activity across both the intraparietal sulcus and frontal eye field, key components of a cortical network for saccadic generation.
The authors gratefully acknowledge consultation from Nikos Makris and Bruce Fischl, and the contributions of two anonymous reviewers. J Comput Assist Tomogr Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.
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See other articles in PMC that cite the published article. Associated Data Supplementary Materials Keywords: intraparietal sulcus, frontal eye field, antisaccade, saccade, magnetoencephalography, sensorimotor transformation. Open in a separate window. Figure 1. Figure 2. Materials and Methods Participants Twenty healthy participants were recruited from the community by poster and website advertisements.
Saccadic Paradigm The saccadic task stimuli were generated using the Vision Shell programming platform www. Structural MRI Acquisition Two T1-weighted high-resolution structural images were acquired for spatial normalization and cortical surface reconstruction using a 3. Scoring of eye movement data EOG data were scored in MATLAB using a partially automated program that determined the directional accuracy of each saccade with respect to the required response and the latency from target onset.
Off-line analysis of MEG data Noisy channels were identified by visual inspection of the raw data and omitted from analysis. Inter-subject registration Each participant's inflated cortical surface was registered to an average cortical representation by optimally aligning individual sulcal-gyral patterns Fischl et al Anatomical criteria for frontal eye field and intraparietal sulcus These regions were defined using an automated surface-based parcellation system Fischl et al Figure 3.
MEG data 1. Directional contrasts right vs. Figure 4. Waveforms in regions of interest For each task condition we plotted signal amplitude as a function of time in the left intraparietal sulcus and frontal eye field regions that showed transitional patterns of activity suggestive of participation in vector inversion. Figure 5. Timing analyses Visual inspection of the traces of activity in the left intraparietal sulcus and the left frontal eye field suggested that the increase in activity related to a contralateral response in antisaccade trials occurred slightly earlier in the intraparietal sulcus than in the frontal eye field.
Control analyses Is it possible that the findings reflect saccadic artifact i. Discussion Our results complement human and monkey work in suggesting that both the intraparietal sulcus and frontal eye field participate in sensorimotor transformation. Supplementary Material 01 Click here to view. Acknowledgements The authors gratefully acknowledge consultation from Nikos Makris and Bruce Fischl, and the contributions of two anonymous reviewers.
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