Saccade control and eye–hand coordination in optic ataxia

Neuropsychologia 46 (2008) 475–486

Saccade control and eye–hand coordination in optic ataxia Val´erie Gaveau a,b , Denis P´elisson a,b , Annabelle Blangero a,b , Christian Urquizar a,b , Claude Prablanc a,b , Alain Vighetto a,b,c , Laure Pisella a,b,∗ a

«Espace et Action» INSERM Unit´e 864, Bron, France, Universit´e Claude Bernard, Lyon, France b Institut F´ ed´eratif des Neurosciences de Lyon IFNL, Hˆopital Neurologique, Lyon, France c Hospices Civils de Lyon, Hˆ opital Neurologique Pierre Wertheimer, Lyon, France Received 4 May 2007; received in revised form 2 August 2007; accepted 24 August 2007 Available online 14 September 2007

Abstract The aim of this work was to investigate ocular control in patients with optic ataxia (OA). Following a lesion in the posterior parietal cortex (PPC), these patients exhibit a deficit for fast visuo-motor control of reach-to-grasp movements. Here, we assessed the fast visuo-motor control of saccades as well as spontaneous eye–hand coordination in two bilateral OA patients and five neurologically intact controls in an ecological “look and point” paradigm. To test fast saccadic control, trials with unexpected target-jumps synchronised with saccade onset were randomly intermixed with stationary target trials. Results confirmed that control subjects achieved visual capture (foveation) of the displaced targets with the same timing as stationary targets (fast saccadic control) and began their hand movement systematically at the end of the primary saccade. In contrast, the two bilateral OA patients exhibited a delayed visual capture, especially of displaced targets, resulting from an impairment of fast saccadic control. They also exhibited a peculiar eye–hand coordination pattern, spontaneously delaying their hand movement onset until the execution of a final corrective saccade, which allowed target foveation. To test whether this pathological behaviour results from a delay in updating visual target location, we had subjects perform a second experiment in the same control subjects in which the target-jump was synchronised with saccade offset. With less time for target location updating, the control subjects exhibited the same lack of fast saccadic control as the OA patients. We propose that OA corresponds to an impairment of fast updating of target location, therefore affecting both eye and hand movements. © 2007 Elsevier Ltd. All rights reserved. Keywords: Optic ataxia; Saccades; Eye–hand coordination; On-line motor control; Posterior parietal cortex

1. Introduction Eye–hand coordination is necessary for reaching to visual objects in order to interact with the environment. Whether this functional link between saccade and reach (see Neggers & Bekkering, 2001) involves common neural substrates within the posterior parietal cortex (PPC) remains a crucial question in the ongoing debate about the function of the PPC in visuo-motor programming, i.e., how (Andersen & Buneo, 2002) versus spatial visual processing, i.e. where (Colby & Goldberg, 1999). Historically, the Balint–Holmes syndrome described concomitant ocular and reach impairments, with similar interpretations of visuo-motor disconnection (Balint, 1909) versus “visual dis∗ Corresponding author at: “Espace et Action” UMR-S INSERM U864, 16 avenue L´epine, Case 13, 69676 Bron, France. Tel.: +33 4 72913405; fax: +33 4 72913401. E-mail address: [email protected] (L. Pisella).

0028-3932/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2007.08.028

orientation” (Holmes, 1918). More recent studies however have demonstrated that saccade and reach impairments can occur in isolation. Isolated impairments of contralesional saccades (including direction-specific hypometry and increased latency) have been observed after lesions of the inferior parietal lobule (IPL) of the PPC without concomitant reaching impairments (Pierrot-Deseilligny, Rivaud, Gaymard, & Agid, 1991; PierrotDeseilligny & M¨uri, 1997). Conversely, patients with optic ataxia (OA) arising from damage of the superior parietal lobule (SPL) of the PPC have been described as exhibiting isolated reaching impairments. In the latter, visuo-manual guidance is impaired in peripheral vision, without any primary visual, proprioceptive and motor deficits (Garcin, Rondot, & de Recondo, 1967; Jeannerod, 1986). This definition of OA is supposed to also exclude any oculomotor deficits. The slight impairment of saccadic eye movements detected in clinical tests in some OA patients have not been considered relevant to the misreaching deficits (e.g. Baylis & Baylis, 2001; Perenin & Vighetto,

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Fig. 1. Lesions of the patients. AT’s cerebral MRI scans indicate bilateral parietal damage involving Brodmann’s areas 18, 19, 39 and 7 and extending to the superior occipital lobes (V3a). IG’s cerebral MRI scans indicate bilateral parietal damage involving Brodmann’s areas 18, 19, 7 and a limited part of area 39.

1988; Rondot, de Recondo, & Dumas, 1977). Isolated saccade or reach errors as a consequence of lesions of the PPC in humans have thus provided supporting arguments for the current view of a segregated parietal eye field (PEF: Pierrot-Deseilligny and M¨uri, 1997; Pierrot-Deseilligny & M ri, 1997PierrotDeseilligny et al., 1991) and parietal reach region (PRR: Calton, Dickinson, & Snyder, 2002; Connolly, Andersen, & Goodale, 2003). However, such a motor segregation within the PPC is questioned by several results: (i) a lesion of parietal saccadic region in monkeys (lateral intraparietal area: LIP) does not affect saccadic programming and execution (Wardak, Olivier, & Duhamel, 2002); (ii) electrophysiological activity of LIP and PRR neurons could represent reach- and saccade-related modulations respectively (Snyder, Batista, & Andersen, 1997, 2000) and show motor commands which encode target location with respect to the eyes (Constantin, Wang, Martinez-Trujillo, & Crawford, 2007; Pesaran, Nelson, & Andersen, 2006); and (iii) fMRI experiments tend to distinguish between at least two segregated regions activated during saccades in humans, one corresponding potentially to the macaque LIP and the other to the PRR (Schluppeck, Glimcher, & Heeger, 2005). Furthermore, OA patients, who are reported to show only isolated visuo-manual impairment, have been classically tested in condition where they are asked to maintain their eyes fixed while reaching immediately and quickly toward objects presented in peripheral vision (Milner et al., 2001; Perenin & Vighetto, 1988; Rossetti et al., 2005). Their behaviour in unconstrained conditions in which subjects spontaneously look and point to the target, which allows the investigation of saccades and reaches, and their coordination, has never been studied. In normal individuals, in such a “look and point” paradigm, the same target-related signal from peripheral vision is used both for the motor command initially sent to the arm and for the primary saccadic eye movement (Biguer, Jeannerod, & Prablanc, 1982).

Because of the arm inertia however, the hand movement actually begins roughly when the primary saccade ends (Prablanc, Echallier, Komilis, & Jeannerod, 1979). In addition, the eye and hand motor planning based on peripheral visual information is known to be inaccurate (Prablanc et al., 1979). The completion of the primary saccade allows accurate perifoveal signals to update target location. This updated visual information is used to adjust the ongoing hand trajectory (fast manual control, Goodale, Pelisson, & Prablanc, 1986) and the amplitude of the corrective saccade (fast ocular control, Prablanc & Jeannerod, 1975). An impairment of fast manual control has already been shown in two patients with bilateral OA when reaching in central (Gr´ea et al., 2002; Pisella et al., 2000) or peripheral vision (Milner, Dijkerman, McIntosh, Rossetti, & Pisella, 2003; Milner et al., 2001; Rossetti et al., 2005). Protocols of reaching in central vision (Gr´ea et al., 2002; Pisella et al., 2000) used a target displacement (target-jump) at hand movement onset to compel visual updating during manual execution. In the first experiment here, the same two bilateral OA patients performed a “look and point” paradigm with target-jumps occurring at the onset of the primary saccadic eye movement to compel visual updating during ocular execution. Under the hypothesis of non-segregated visuo-motor modules for reaches and saccades within the PPC, we predict that OA patients would also exhibit a deficit of fast ocular control. Such a deficit has never been described in the literature. Since the control of ocular capture, contrary to manual capture, involves the execution of additional (corrective) saccade, one could predict either an inadequate or a delayed execution of the corrective saccade. In the second experiment, we delayed the target-jump (at saccade offset) to simulate the same deficit of fast ocular control in our group of 5 normal subjects as a demonstration that OA impairment results from a delay to update visual target location.

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2. Subjects and methods 2.1. Subjects Five na¨ıve control subjects (all right-handed, mean age 31) and two patients with OA participated in the study. The study was conducted with their informed consent, in agreement with the ethical standards laid down in the Declaration of Helsinki of 1964. The patients were only involved in Exp. 1. The same group of control subjects was involved in both Exp. 1 and Exp. 2. Patient AT was 47 at the time of testing, which was 15 years after an eclamptic attack which provoked bilateral haemorrhagic softening in the region around the parieto-occipital arteries. Structural MRI revealed bilateral parietal damage extending toward the upper section of the occipital regions (see Fig. 1a). During the initial 2 weeks after the lesion, AT presented a severe visual deficit resembling cortical blindness. Subsequently, AT showed with a set of diverse symptoms: OA, right-left disorientation, simultanagnosia, constructional apraxia, spatial agraphia and acalculia. On the other hand, she showed no clinical indications of occipito-temporal damage (e.g. alexia, object agnosia, achromatopsia, or prosopagnosia). She showed a normal visual field except for a small parafoveal scotoma in the right inferior homonymous quadrant and near normal visual acuity. At the time of testing for the current study, she was able to lead a surprisingly normal life despite her extensive lesions but she still faced difficulties in visuospatial tasks and in tasks requiring precise and fast control within personal and extrapersonal space (Michel & Henaff, 2004). OA has remained stable, impairing reaching movements toward objects in peripheral vision. Her eye movement behaviour was mentioned in Michel and Henaff (2004): AT complained that “her gaze would not reach directly what she wanted to see”; yet pursuit and saccadic eye movements were apparently normal at clinical examination except visual reaction times which were abnormally high compared to her auditory reaction times. Patient IG was a 32-year old woman at the time of testing, 6 years after bilateral parieto-occipital infarctions related to acute vasospastic angiopathy in the posterior cerebral arteries. MRI revealed a hyperintense signal on T2 sequences that was near-symmetrically located in the posterior parietal and upper and lateral occipital cortico-subcortical regions (see Fig. 1b). She initially suffered from severe headaches, dysarthria and bilateral blindness, which lasted for 3 days. Subsequently, bilateral OA and simultanagnosia became apparent. By the start of our first testing (Pisella et al., 2000) her simultanagnosia had subsided. Her visual acuity and ocular fundi were normal though visual fields showed a partial right inferior homonymous quadranopia with temporal crescent sparing. Routine recordings of saccadic and smooth pursuit eye movements elicited by a LED in the dark showed normal latencies, gains, directions and velocities (Gr´ea et al., 2002). Her reaction time to a target change in position was identical to that of control subjects when evaluated by the production of an arbitrary motor response to the target-jump (“location-stop” task in Pisella et al., 2000).

2.2. Experimental setup Exp. 1 and Exp. 2 were conducted on the same experimental set-up with simply the instruction to look and point at visual targets presented in peripheral visual field in the dark. Subjects were placed in front of a 45◦ tilted pointing table with their head fixed with a bite board (Fig. 2a). A tactile circle placed sagitally 16 cm distant from the trunk served as hand start position. Four target lights were projected on the table surface along the fronto-parallel line at the level of the subject’s gaze (Fig. 2b). These targets were virtual images of red light-emitting diodes (LEDs, diameter 3 mm) reflected on a mirror. This apparatus prevents subjects from detecting their pointing errors (no visual feedback of the hand relative to the target) and consequently from developing strategic behaviours to adjust their pointing movements. Subjects were instructed to initially fixate a LED, designated as the eye start position, located 10◦ to the left with respect to their trunk. They then had to look and point to three targets located 12.5◦ , 20◦ and 27.5◦ to the right with respect to the trunk or at 22.5◦ , 30◦ and 37.5◦ of eccentricity in the right visual field, with respect to initial eye fixation (see Fig. 2b). Coordinates in visual degrees are used throughout this paper. Horizontal eye movements were recorded with an infrared optometric system (EyeLink I, SR Research, Ontario) at a frequency of 250 Hz with an accuracy of 0.1◦ .

Fig. 2. Experimental set-up (a) Side view: the LED target array was located above the subjects and was projected using a half-reflecting mirror to appear on the level of the table where the subjects reached. (b) Locations of the LED used as (saccadic and pointing) targets and eye fixation, with respect to the hand starting location. Pointing movements were recorded by an infra-red marker fixed on the index fingertip (Optotrak, NDI, Ontario; 200 Hz).

2.3. Behavioural paradigm Each subject performed 200 trials divided into two sessions. Each trial took place as follows: (1) the subject put his pointing finger on the hand start position and (2) looked at the eye start position (illumination period, 2 s ± 300 ms); (3) the eye start position was extinguished while one of the three target LEDs was illuminated (for 2 s ∓ 300 ms) signalling the subject to make a rightward saccade and a pointing movement as fast and as accurately as possible (4) the trial acquisition ended when LED target switched off. Among these 200 trials, 84% were ‘stationary trials’: the target LED was presented at 22.5 (R2), 30 (R3) or 37.5 (R4) visual degrees until the end of the trial; 16% of the trials were ‘jump trials’: the target LED was initially presented at 30◦ (R3) and was suddenly extinguished at the beginning of the saccade (by means of a two-point central difference velocity detection algorithm, adapted from Bahill & McDonald, 1983) and replaced by a target LED at 22.5 (J2: backward jump) or 37.5 (J4: forward jump) degrees till the end of the trial. This target-jump was not consciously detected by subjects as it occurred during the time of “saccadic suppression” (Goodale et al., 1986), which avoided any strategic motor behaviour. When questioned at the end of the experiment, no subject was able to report the occurrence of the target jump. Exp. 2 was identical except that the target-jump was synchronised to primary saccade offset instead of onset.

2.4. Analysis The horizontal eye position signal was filtered (50 Hz cut-off frequency, finite impulse response filter FIR) and eye velocity was computed from the filtered position signal using a two-point central difference derivative algorithm (Bahill & McDonald, 1983). In order to determine the sequence of eye movements, the beginning and the end of the primary and corrective saccades were automatically detected using a velocity threshold procedure (30◦ s−1 ). The results of this automatic procedure were then inspected off-line and corrected manually, if necessary. Several saccade-related parameters were computed; for primary and corrective saccades, saccadic gain was calculated as the ratio between saccadic amplitude and desired amplitude. Note that in the jump trials, the desired amplitude of the primary saccade corresponded to the initial target location, whereas the desired amplitude of corrective saccades corresponded to the difference between eye position at the end of the primary saccade and final target location. Saccadic errors for the primary and corrective saccades were computed as the difference between final eye position and target position. In jump trials, the initial and the final target locations were used to compute saccadic errors for the primary and the corrective saccades, respectively. Reaction times (RT) were computed with respect to target onset for primary saccades and with respect to the end of the primary saccade for corrective saccades. Finally, the number of corrective saccades and the time of visual capture (period elapsing from target presentation to the end of the last corrective saccade) were computed.

563 (115) 594 (112) 641 (106)

467 (28) 491 (68) 509 (67)

For arm movements, the x, y, and z position signals were filtered at 10 Hz with a second-order Butterworth dual-pass filter. Movement velocity was computed from the filtered position signal using a least square second-order polynomial method (10 points moving window). The same method was used to compute the acceleration of the hand from the velocity signal. The onset and the end of the movements were computed automatically using the following thresholds: hand velocity 80 mm/s and hand acceleration 150 mm/s2 . After an automatic detection, a visual inspection of the results was performed for each trial. The hand-related parameter analysed in this study was hand reaction time.

802 (132) 792 (117) 825 (96)

V. Gaveau et al. / Neuropsychologia 46 (2008) 475–486 Time of visual capture (ms)

478

171 (55) 176 (39) 156 (55) −0.58 (1.05) −0.61 (1.26) −1.28 (1.27) 1.20 (2.35) −4.80 (3.11) −12.26 (3.64) 22.5 30 37.5 IG

C

235 (37) 238 (45) 237 (27)

461 (105) 437 (112) 456 (84) −2.33 (2.08) −3.02 (2.35) −6.03 (2.28) 22.5 30 37.5 AT

1.06 (0.12) 0.84 (0.10) 0.67 (0.08)

0.95 (0.95) 1.22 (0.68) 1.74 (0.93)

269 (68) 232 (73) 247 (41) −1.22 (0.56) −0.93 (0.99) −1.57 (1.42) 0.36 (0.49) 0.40 (0.50) 0.95 (0.43)

248 (39) 241 (38) 251 (40) −2.00 (1.50) −2.39 (1.52) −3.68 (1.71) 22.5 30 37.5

0.90 (0.07) 0.90 (0.06) 0.84 (0.08)

155 (42) 165 (60) 155 (41) −0.74 (0.64) −0.78 (1.23) −1.18 (1.31) 0.34 (0.41) 0.42 (0.44) 0.62 (0.43)

Error Number

Corrective saccades

Gain RT (ms) Error

(◦ )

Primary saccades

3.1.1. Saccadic behaviour 3.1.1.1. Control Group. Within-group analyses were conducted to determine the effect of target eccentricity or of target-jump on saccadic behaviour. All saccadic parameters are reported in Tables 1 and 2 for stationary and jump trials respectively. The classical hypometry of primary saccades was observed (mean gain of 0.91). The gain remained constant with target eccentricity (F(2,8) = 0.8; p > 0.05), leading to a significant increase of the absolute error of the primary saccade when target eccentricity increased (F(2, 8) = 10.4, p < 0.01) (Fig. 3a). Despite initial saccadic hypometry, neither mean error nor reaction time of the corrective saccade differed across target eccentricities (F(2, 8) < 1.30, p > 0.05). The reaction time of the corrective saccade was significantly shorter than the reaction time of the primary saccade (F(1, 4) = 90, p < 0.01), in agreement with findings from the literature (Prablanc & Jeannerod, 1975; Becker & Fuchs, 1969). The mean error and reaction time of the corrective saccades showed no differences between target-jump and stationary trials (between stationary trials at 37.5◦ and trials with target displaced forward from 30◦ to 37.5◦ : F(1,4) < 1.4, p > 0.05 and between stationary trials at 22.5◦ and trials with target displaced backward from 30◦ to 22.5◦ : F(1,4) < 5.4, p > 0.05).

Target position (◦ )

3.1. Exp. 1: target-jumps at saccade onset

Groups

3. Results

Table 1 Saccadic parameters in stationary trials (mean and S.D.) for the control group (C) and the two patients with OA (AT and IG)

2.5.2. Within-group analyses The objective of these analyses was to assess separately in each patient and in the control group the effect of target eccentricity and of target-jump. Within each patient, a one-way ANOVA was performed with Trial type as a factor. For the control group, a repeated-measures ANOVA was used. In Exp. 1, contrast analyses (planned comparisons) were used to test the effect of target eccentricity or occurrence of target-jump on ocular or pointing behaviour. The time of occurrence of the target-jump (at saccade onset in Exp. 1 versus saccade offset in Exp. 2) was then used as an additional factor for the within-group analyses.

(◦ )

2.5.1. Between-group analyses Our goal was to establish on which eye and hand motor parameters the mean scores of patients reliably differed from the control ones. For each patient, these parameters were compared to those of the control group with repeated measures ANOVAs with Group as a factor. We adjusted the critical value of F in order to take the variance of the control group and the patient (AT or IG) into account, as proposed by Mycroft, Mitchell and Kay (2002). Note that in this statistical method for single-case studies, a significant effect at the 5% level (p ) is accepted if the revised F-value exceeds 10.

0.91 (0.05) 0.92 (0.04) 0.90 (0.06)

RT (ms)

2.5. Statistics

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Table 2 Corrective saccade parameters in jump trials (mean and S.D.) for the control group (C) and the two patients with OA (AT and IG), obtained for target-jumps at saccade onset (Exp. 1)

In stationary trials, visual capture was usually achieved with no or a single corrective saccade (mean number of corrective saccades = 0.46), the mean gain of the corrective saccade was close to 1 (1.08) and thus accurate target capture (final errors of less than 1◦ ) was achieved despite initial saccadic hypometry. In jump trials, control subjects achieved visual capture of the perturbed target both by increasing the occurrence of a corrective saccade (F(1,4) > 9.8, p < 0.05) and by changing its amplitude so that the gain of the first corrective saccades computed with respect to the final target location remained close to 1 (1.03). In fact, visual capture was systematically achieved with a single corrective saccade for backward jumps (mean number of corrective saccade = 1 with S.D. = 0) and with one or exceptionally two corrective saccades for forward jumps (mean number of corrective saccade = 1.21). 3.1.1.2. OA patients. The classical relationship between amplitude and duration (the main sequence) was observed for the two patients, attesting that the dynamic characteristics of saccades were not altered by the lesion (see Supplementary Information). Therefore, only the spatial (error and gain) and temporal (reaction time) saccadic parameters are detailed below. Between-group comparisons (Mycroft et al., 2002) revealed that both patients exhibited a larger hypometry of primary saccades than control subjects (revised F(1,4) > 10.2; p < 0.05; Table 1). This hypometry appeared outside the confidence interval of the control group for the most eccentric targets (Fig. 3b: only for the 37.5◦ target in AT and for the 30 and 37.5◦ targets in IG). Within-group analysis revealed that with a mean gain of 0.84 for primary saccades, patient IG, in fact, showed a higher saccadic gain than that of the control group for the 22.5◦ target (1.06), a gain of 0.84 for the 30◦ target and a reduced gain (0.67) for the 37.5◦ target. Rather than a general gain reduction of primary saccades, the deficit of patient IG is therefore best described as a pathological decrease of the slope of the saccadic gain versus target eccentricity relationship. Yet, in both patients, the visual capture of the target was always achieved with normal accuracy as the final error after the last corrective saccade did not differ from controls (revised F(1,4) < 6; p > 0.05 for both patients) at all target eccentricities and whenever the target-jump occurred (Figs. 3c and 4b). Thus OA patients could eventually correct for both their own initial error resulting from hypometric pri-

mary saccades and the experimental error due to the targetjump. The time of visual capture computed with respect to target onset was significantly delayed with respect to controls (Tables 1 and 2; revised F(1,4) > 13; p < 0.05 for both patients). Note that if we consider the time of visual capture with respect to primary saccade onset, the two patients exhibited a similar delay of 100 ms for stationary targets, corresponding to an increased time needed for ocular control. Detailed inspection revealed that this common increase of the duration of the saccadic sequence execution was expressed differently in the behaviour of the two OA patients. Patient AT delayed her corrective saccade significantly with respect to the control group (revised F(1,4) = 25.3; p < 0.05) by roughly 100 ms for stationary (Table 1) and jump trials (Table 2) but visual capture was achieved with a normal number of corrective saccades (revised F(1,4) = 8.0; p > 0.05). In stationary trials, visual capture was achieved with no or a single corrective saccade (mean number of corrective saccade = 0.57). The targetjump trials implied a significant increase of the occurrence of a corrective saccade (F(1,66) = 61.97, p < 0.01). Similar to that reported above for the control group, the mean gain of the first corrective saccade computed with respect to the final target location remained close to 1 (0.98) in jump trials, such that visual capture was achieved with one systematic corrective saccade and very exceptionally with two (mean number of corrective saccade = 1.16). In patient IG, the reaction time of the first corrective saccade was even significantly shorter than in the control group (revised F(1,4) = 13.7; p < 0.05) but the number of corrective saccades was significantly higher (revised F(1,4) = 21.1; p < 0.05). Patient IG needed one or two corrective saccades to capture stationary targets (mean number of corrective saccade = 1.30). In response to target-jumps, a further increase of the number of corrective saccades was observed (F(1,150) = 15.23, p < 0.01), consequently delaying even more visual capture (F(1,150) = 17.9, p < 0.01). Indeed, in 65% of the backward jump trials and in 85% of the forward jump trials, the primary saccadic error and the error due to the target-jump were compensated serially. In these trials, the mean gain of the first corrective saccade computed with respect to the final target location was far from 1 (0.47 for forward and 2.08 for backward jumps). When computed instead with respect to the initial target location (30◦ ), the

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Fig. 3. Saccadic behaviour in stationary trials. (a) Individual saccadic traces for stationary trials at the three target eccentricities (22.5◦ , 30◦ and 37.5◦ ) for the most hypometric control subject, and for patients IG and AT. Horizontal eye position is plotted with respect to time of data acquisition (from target presentation at 0 ms until 1500 ms). Filled and opened arrows indicate onset of primary and corrective saccades respectively. (b) The left panel represents the mean and confidence interval (∓1.96*standard deviation) of the endpoints of the primary saccade for the control group and for the three target eccentricities (22.5◦ , 30◦ and 37.5◦ ). The two other panels represent the mean and standard deviation of the primary saccade endpoints for patients AT (middle panel) and IG (right panel), for the same three target eccentricities. Dashed lines indicate actual target locations. (c) The left panel represents the mean final positions of the eye (after corrective saccades) and confidence interval (1.96*standard deviation) for the control group and for the three target eccentricities (22.5◦ , 30◦ and 37.5◦ ). The middle and the right panels represent the means and standard deviations of the final eye position for AT and IG respectively, for the same three target eccentricities. Dashed lines indicate the actual target positions.

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Fig. 3. (Continued ).

gain reached a mean value of 1.02, showing that the first corrective saccade was actually directed toward the first (extinguished) target location. The first corrective saccade of IG allowed her only to compensate her primary saccade error and at least a second one was needed to compensate for the target-jump error. This is particularly clear from the example provided in Fig. 4a, in which patient IG and the illustrated control subject exhibited primary saccades with similar hypometry. Then, in both backward and forward jump trials, the first corrective saccade of patient IG brought the eye to the position of the initial (extinguished) target, whereas that of the control subject directly reached the actual (displaced) target position. This behaviour of patient IG was particularly striking for the backward target-jumps which called for a backward corrective saccade. In contrast to the control subject, patient IG executed a first forward corrective saccade, away from the actual target location. Only the subsequent corrective saccades were executed in the correct direction. Visual capture was finally achieved by the fourth corrective saccade. This ‘serial’ behaviour characterised by normal reaction times of the first corrective saccade but a significant increase of the number of saccades was predominant in patient IG but she also exhibited the same ‘parallel’ behaviour as patient AT. These two behaviours in response to target-jump are distinguished in Table 2 using the criteria of the number of corrective saccades produced to capture the displaced target (one or more than one; accordingly, the reaction time of the first saccade is delayed or not relative to controls). The ‘serial’ behaviour caused the longest delay of visual capture. 3.1.2. Eye–hand coordination 3.1.2.1. Control group. The eye–hand coordination in the control subjects (left panel of Fig. 5) followed a well-established temporal sequence with the following two characteristics: (1)

the pointing movement consistently began at approximately the end of the primary saccade, and consequently, (2) a corrective saccade was made during the execution of the pointing movement. 3.1.2.2. OA patients. The temporal sequence of eye–hand coordination was consistently modified in the two patients with respect to that observed in healthy controls. Indeed, betweengroup statistics (Mycroft et al., 2002) revealed in both patients that the reaction time of the reaching response was markedly delayed relative to controls (revised F(1,4) > 33; p < 0.05), so that the pointing movement began at the time of the final corrective saccade (see Fig. 5). When patient IG exhibited the same behaviour as patient AT, consisting of capturing the visual target with a single but much delayed corrective saccade, the hand reaction time temporally matched to the execution of the single corrective saccade (IG left panel in Fig. 5). In the other trials, in which patient IG captured the visual target with more than one corrective saccade, the hand reaction time temporally matched with the execution of the last corrective saccade. There was no significant main effect of the occurrence of a target-jump on hand reaction time. The lack of change of this temporal parameter indicates that the distinct eye–hand coordination exhibited by the two patients was not adopted in response to target-jumps but instead corresponded to their standard behaviour in ecological conditions. 3.2. Exp. 2: target-jumps at saccade offset The main aspect of the saccadic deficit of OA patients was the delayed time of visual capture. In order to test the hypothesis that this deficit resulted from a delay in updating the target location, we conducted a second experiment in which the target-jump was synchronised on saccade offset instead of saccade onset. We

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Fig. 4. Saccadic behaviour in target-jump trials. (a) Individual saccadic traces for backward and forward target-jump trials (initial target eccentricity of 30◦ , final target eccentricities of 22.5◦ and 37.5◦ respectively) for the most hypometric control subject, and for patients AT and IG. Horizontal eye position is plotted with respect to time of data acquisition (from initial target presentation at 0 ms until 1500 ms). The time of target-jump is synchronised to the occurrence of the primary saccade (as indicated by the step in the dotted line). Filled and opened arrows indicate onset of primary and corrective saccades respectively, grey arrows indicate the onset of an inadequate corrective saccade. (b) Final saccadic accuracy (after all corrective saccades) for stationary targets at 22.5◦ and 37.5◦ (R2 and R4 respectively)

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Fig. 5. Temporal relationships between saccadic and pointing responses. For each parameter, the mean values (∓1.96*standard deviation) computed in each subject group (CONTROLS, IG and AT) are plotted against target eccentricity for the stationary targets at 22.5◦ (R2), 30◦ (R3) and 37.5◦ (R4) and for the perturbed targets with backward (J2) and forward (J4) jump. The parameters are: beginning ( ) and end ( ) of primary saccades (S1), beginning ( ) and end ( ) of the last corrective saccades (S2), beginning ( ) and end (䊉) of the hand pointing movement. In patient IG, the two saccadic behavioural types (“parallel” and “serial”, see text) have been distinguished in two separate panels.

expected to observe a behaviour similar in control subjects as in our two patients with bilateral OA, if the visual information of the new target location is provided with a delay of about 80 ms (mean primary saccade duration). This delay shortens the time available for visual updating and may therefore produce, as in OA, an impairment of fast motor control. Within-group analyses were conducted on the target-jump trials in order to test the effect of delaying the visual information of the new target location (targetjump synchronised at primary saccade onset versus offset) on ocular behaviour and on eye–hand coordination. 3.2.1. Saccadic behaviour Delaying the occurrence of target-jump induced a delayed time of visual capture (F(1, 4) = 14.70, p = < 0.05) in control subjects (Table 3) resulting from both an increase of the number of corrective saccades (F(1, 4) = 61.45, p < 0.05) and of the reaction time of the (first) corrective saccade (F(1,4) = 17.46, p < 0.05). In fact, in response to the delayed target-jump, the control subjects exhibited the two types of saccadic control behaviours observed in the OA patients, which can be segregated based on the number of corrective saccades (see Table 3): (1) ‘parallel’ behaviour: when only one corrective saccade was produced to achieve foveal capture, its occurrence was largely delayed (257 ms in target-jump trials with respect to 158 ms on average in stationary trials, and 172 ms in target-jump trials in Exp. 1) leading to delayed visual capture (625 ms with respect to 580 ms in Exp. 1); (2) ‘serial’ behaviour: the control subjects

produced several corrective saccades to capture displaced targets when the first corrective saccade was not delayed (reaction time of 170 ms as in Exp. 1: 172 ms) leading to a largely delayed visual capture (736 ms). The ‘parallel’ behaviour was used predominantly by the control subjects (in 73.25% of the target-jump trials). 3.2.2. Eye–hand coordination In contrast to the behaviour of the two OA patients, pointing reaction time was not affected by the delay of the targetjump occurrence (F(1,4) = 1.18, p > .05). The classical eye–hand coordination was observed, with the pointing movement onset matching the offset of the primary saccade (as in Fig. 5). Pointing accuracy was also not significantly impaired (F(1,4) = 2.28, p > .05) but the duration of pointing movement was significantly delayed (F(1,4) = 8.60, p = .046): about 33 ms longer when the target-jump occurred at saccade offset (Exp. 2) compared to saccade onset (Exp. 1); however this slight pointing delay was not comparable to the delay of saccadic capture. 4. Discussion Patients with bilateral OA have been shown in the literature to exhibit a lack of fast motor control for hand movements (Gr´ea et al., 2002; Pisella et al., 2000). In the present paper, we investigate whether this deficit resulting from a lesion of the PPC causes a pathological delay in updating the location of the visual target.

and for backward and forward jump trials (J2 and J4 respectively). The left panel depicts the mean and confidence interval (1.96*standard deviation) of final eye position for the control group; the middle and right panels depict the means and standard deviations for patients AT and IG respectively. Dashed lines indicate the actual final target positions.

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Table 3 Corrective saccade parameters in jump trials (mean and S.D.) for control group (C) obtained for target-jumps at saccade offset (Exp. 2) Groups

Jump trials

Number

Backward

1.08 (0.02)

Forward

1.54 (0.32)

C

1 (93%) N = 64 2 (7%) N = 5 1 (53.5%) N = 30 2 (46.5%) N = 26

The slow visual processing of the target location is first demonstrated by showing that patients with bilateral OA also exhibit a lack of fast motor control for saccadic eye movements (Exp. 1, target-jump at primary saccade onset) and second by showing that normal subjects exhibit the same ocular behaviour as OA patients if the visual information (of the final target location) is provided with a delay (Exp. 2, target-jump at primary saccade offset). After a detailed discussion of the results leading to these conclusions, we will discuss the anatomical segregation of saccade and reach modules within the PPC. 4.1. Saccadic behaviour The saccadic deficit included temporal and spatial components, which can be expressed differently in patients (see Rossetti, Pisella, & Vighetto, 2003 for a review of the temporal and spatial aspects of OA). In the two OA patients of this study, the saccadic deficits mainly addressed fast ocular control (characterised by a delayed visual capture, especially when the target jumped) and the pathological hypometry for large target eccentricities (>30 visual degrees). The experimental conditions necessary to reveal these deficits are not used routinely in clinical tests, which may explain usual clinical reports that eye movements are relatively preserved in OA (e.g. Baylis & Baylis, 2001; Perenin & Vighetto, 1988; Rondot et al., 1977). A recent study (Trillenberg et al., 2007) reported intact saccades in a patient with optic ataxia, but the authors computed a global saccadic gain related to the final saccadic accuracy which did not allow them to reveal the hypometry of the primary saccade and the deficit of saccadic control (suggested by the closed inspection of the typical eye trace presented on their Fig. 4) in their OA patient. 4.2. Fast motor control We argue that the delayed time of visual capture in the two OA patients reveals an impaired fast ocular control of the saccadic sequence. Indeed, data from our control subjects in Exp. 1 indicated that normal foveal capture is achieved by a slightly hypometric primary saccade, sometimes followed by one corrective saccadic movement. In target-jump trials, the corrective saccade is systematically initiated, and its spatial parameters (amplitude, direction) are adjusted in order to capture the displaced visual target without the need for additional corrective saccades (Becker & Jurgens, 1979). In addition, it was shown that the latency (and duration) of the single corrective saccade remained similar in target jump and in stationary target trials (about 160 ms). These observations indicate that in control sub-

Final Error (◦ )

RT (ms)

−0.50 (0.79)

233 (48)

−1.92 (0.26)

244 (80)

Time of visual capture (ms) 238(42) 162(66) 279(73) 174 (35)

618 (30) 692 (87)

610 (51) 724 (118) 643 (75) 749 (64)

jects, an update of the visual error takes place between the end of the primary saccade and the initiation of the corrective saccade without any additional time cost. This fast control of the saccadic sequence is clearly lacking in the two OA patients. Patient AT produced a pairing of two saccades, irrespective of the trial type (stationary or jump), with a large temporal “safety margin” for both primary and secondary saccades. Patient IG also exhibited a single, delayed, corrective saccade in 25% of the target-jump trials (parallel compensation of intrinsic primary saccade errors and errors due to the target-jump). However, in most trials, she instead produced an increased number of corrective saccades to achieve visual capture of the displaced targets. Strikingly, in these trials, her first “corrective” saccade was generated with no RT increase and was directed to the initial (extinguished) target location (serial compensation of intrinsic primary saccade error and error due to the target-jump). Clearly, this observation indicates that her oculomotor system did not have immediate access to the new retinal target location. It is worth noting that despite the different “serial” and “parallel” behaviours in target-jump trials, the patients showed the same additional delay of about 100 ms to capture stationary visual targets. This pathological delay of visual capture revealed a common deficit in fast ocular control. This conclusion is reinforced by Exp. 2, in which control subjects exhibited the same “serial” and “parallel” behaviours in response to a target-jump synchronised on primary saccade offset. Our prediction was that the deficit of fast ocular control in OA patients results from an inability to update “on-line” the visual target location, as suggested by a previous study (Khan, Pisella, Rossetti, Vighetto, & Crawford, 2005). Consequently, the time normally sufficient to implement the new target location turns out to be too short. Accordingly, in Exp. 2 we showed that reducing the time available for visual updating could cause the same abnormal ocular control in control subjects. 4.3. Eye–hand coordination In the present “look and point” task, both OA patients spontaneously delayed their hand movement onset to the end of the saccadic sequence (see Fig. 5 and reaction times on Table 3), i.e. to when the visual target location was eventually updated based on central vision. Note that a similar behaviour can be observed on the typical eye–hand trace of the OA patient of Trillenberg et al. (2007, Fig. 4). This temporal sequence of eye–hand responses suppresses the need for reaching in peripheral vision, and likewise limits the need for fast control of hand reaching movement. Accordingly, bilateral OA patients are known to be specifically impaired for reaching in peripheral vision (Milner et al., 2003;

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Rossetti et al., 2005) and for fast reaching corrections (Gr´ea et al., 2002; Pisella et al., 2000). This eye–hand coordination pattern has not been reported before, even in other neurological patients impaired for reaching (e.g. Desmurget et al., 2004) and was also not observed in the control group of the second experiment. It is thus probably not a strategy developed for the present task but instead a spontaneous and unconscious behaviour adopted by the two OA patients for all reach-and-grasp actions. This behaviour would explain why OA patients actually rarely complain from inaccuracy of hand movements in their everyday life (Rossetti et al., 2003), and may thus reflect a functional compensation for their lesion. 4.4. Common or segregated saccade and reach regions within the PPC? It is interesting to compare the deficit of fast ocular control to the impairment of fast manual control demonstrated in previous studies involving patients IG and AT (Gr´ea et al., 2002; Pisella et al., 2000). For example, the “serial” saccadic behaviour exhibited by patient IG (Fig. 4a) is directly comparable to her reaching behaviour presented in Fig. 2A of the study of Gr´ea et al. (2002). In both cases, and in contrast to control subjects, patient IG responded to the target-jump by performing first a non-modified response (either hand movement or eye movement sequence) toward the initial target location, followed by at least one supplementary movement allowing her to achieve final target position. The second aspect of the oculomotor deficits in OA patients was the hypometry of primary saccades. Both OA patients exhibited a primary saccadic error that increased with target eccentricity, with accuracy outside the confidence interval of the control group, at least for the most eccentric target (37.5◦ ). Interestingly again, pointing data from previous studies involving patients IG and AT also revealed hypometric errors that increased with target eccentricity (Milner et al., 2003; Rossetti et al., 2005). Anatomically, one cannot rule out the possibility that the patients’ parietal lesions encroached upon nearby but segregated eye- and hand-related regions. However, the similarity between the saccadic deficits demonstrated here and the reach deficits reported in the literature raises the possibility of a common parietal module for saccade and reach. This similarity concerns the target localisation in peripheral vision (pathological increase of eye and hand hypometry with target eccentricity) and the fast updating of target localisation (absence of fast corrections both for hand and eye movements). Interestingly, the POJ region, which has recently been identified as the focus of lesions in a large group of OA patients (Karnath & Perenin, 2005), is specifically activated in relation to reaching movements performed by normal subjects in peripheral vision (Prado et al., 2005). Furthermore, the same POJ region has been involved in dynamic updating of the eye-centred spatial representation of peripheral pointing targets (Medendorp, Goltz, Vilis, & Crawford, 2003). Therefore, POJ is a potential anatomical candidate to subserve a core visuo-spatial mechanism (“Where”), and a lesion at this location would affect both eye and hand movements. The study

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