domain: sdv scco

text:
Keywords: Glaucoma, reach and grasp, identification, kinematics, temporal constraints

In a reach-and-grasp task, patients with glaucoma exhibited a motor disorder, even when they had time to explore their environment. The motor performance of glaucoma patients should be taken into account in rehabilitation.

Introduction

Glaucoma is an ocular disease that produces irreversible retinal ganglion cell and optic nerve fiber loss. [START_REF]Action plan for the prevention of avoidable blindness and visual impairment[END_REF] Visual deficit in glaucoma starts in the peripheral visual field and progresses towards the center. Most studies of glaucomatous vision loss assess relatively simple aspects of visual processing that are encoded in the retina (e.g. sensitivity to luminance increments as in typical perimetry or flickering gratings as in frequency-doubling technology perimetry), because glaucoma is considered primarily as a retinal ganglion cell disease. [START_REF] Glovinsky | Retinal ganglion cell loss is size dependent in experimental glaucoma[END_REF][START_REF] Quigley | Chronic Human Glaucoma Causing Selectively Greater Loss of Large Optic Nerve Fibers[END_REF] Several studies have reported that advanced glaucoma also leads to difficulties with daily life activities such as driving, fear of falling and reading, and the feeling of a reduced quality of life. [START_REF] Crabb | How does glaucoma look?: patient perception of visual field loss[END_REF][START_REF] Dive | Impact of Peripheral Field Loss on the Execution of Natural Actions: A Study With Glaucomatous Patients and Normally Sighted People[END_REF][START_REF] Ramulu | Driving Cessation and Driving Limitation in Glaucoma: The Salisbury Eye Evaluation Project[END_REF] Indeed, both peripheral [START_REF] González-Alvarez | Reaching and grasping with restricted peripheral vision[END_REF][START_REF] Sivak | Integration of visual information and motor output in reaching and grasping: The contributions of peripheral and central vision[END_REF] , and central vision are needed for activities such as reading, [START_REF] Ergun | Scotoma size and reading speed in patients with subfoveal occult choroidal neovascularization in age-related macular degeneration[END_REF][START_REF] Rubin | Vision rehabilitation for patients with age-related macular degeneration[END_REF] driving, facial recognition, [START_REF] Tejeria | Face recognition in age related macular degeneration: perceived disability, measured disability, and performance with a bioptic device[END_REF] reaching for and grasping objects [START_REF] Pardhan | How does the presence and duration of central visual impairment affect reaching and grasping movements?[END_REF][START_REF] Timberlake | Effect of bilateral macular scotomas from agerelated macular degeneration on reach-to-grasp hand movement[END_REF] or accomplishing natural actions. [START_REF] Dive | Impact of Peripheral Field Loss on the Execution of Natural Actions: A Study With Glaucomatous Patients and Normally Sighted People[END_REF] In the case of motor action, the visual system provides critical information about the location, size, and shape of to-be-grasped objects which is used for planning the action. The activation of the motor command leads to hand acceleration towards the object (the "reach" phase).

When approaching the object, the hand decelerates and the grip aperture is adapted to the object's size (the "grasp" phase). At this phase, vision provides corrective information to improve the grasp. [START_REF] Connolly | The role of visual feedback of hand position in the control of manual prehension[END_REF][START_REF] Jeannerod | Intersegmental Coordination During Reaching at Natural Visual Objects[END_REF][START_REF] Lee | Poor shape perception is the reason reaches-to-grasp are visually guided online[END_REF][START_REF] Ma-Wyatt | Visual information throughout a reach determines endpoint precision[END_REF][START_REF] Saunders | Humans use continuous visual feedback from the hand to control fast reaching movements[END_REF] A visual deficit can disrupt the performance of a voluntary motor action, as shown in previous studies. [START_REF] Pardhan | How does the presence and duration of central visual impairment affect reaching and grasping movements?[END_REF][START_REF] Timberlake | Effect of bilateral macular scotomas from agerelated macular degeneration on reach-to-grasp hand movement[END_REF][START_REF] Pardhan | How Do Flanking Objects Affect Reaching and Grasping Behavior in Participants with Macular Disorders?[END_REF] For instance, some studies have shown impairments in initial movement planning and control in patients with glaucoma [START_REF] Kotecha | The functional consequences of glaucoma for eye-hand coordination[END_REF] and in agerelated macular degeneration, [START_REF] Pardhan | How does the presence and duration of central visual impairment affect reaching and grasping movements?[END_REF][START_REF] Timberlake | Effect of bilateral macular scotomas from agerelated macular degeneration on reach-to-grasp hand movement[END_REF] or in grasping components in patients with amblyopia. [START_REF] Grant | Prehension Deficits in Amblyopia[END_REF] Kotecha et al. (2009) reported atypical kinematic characteristics in patients with glaucoma compared to normally sighted people: slower reaction time, longer overall movement duration, low-velocity phase (suggesting a deficit in the grasping phase). The same results were found when healthy participants performed reach-and-grasp tasks with an artificially reduced visual field: longer overall movement duration, slower maximum velocity and higher maximum grip aperture. [START_REF] González-Alvarez | Reaching and grasping with restricted peripheral vision[END_REF] However, research on motor control suggests the existence of inverse models. [START_REF] Sabes | The planning and control of reaching movements[END_REF][START_REF] Wolpert | Multiple paired forward and inverse models for motor control[END_REF] These inverse models suggest that planning of motor commands requires processing of all relevant sensory information. Once the motor command is executed, the motor action can achieve its objective without visual feedback even if, for control subjects, movements are more accurate and precise when visual feedback is available. [START_REF] Khan | Inferring online and offline processing of visual feedback in target-directed movements from kinematic data[END_REF] In line with these models, we hypothesize that increased time to explore a scene may result in decreased difficulty with a motor action for glaucoma patients. In other words, deficits in the motor performance of patients with visual impairment that have been reported in previous studies [START_REF] Kotecha | The functional consequences of glaucoma for eye-hand coordination[END_REF] might be due to the fact that they were not given enough time to analyze the environment prior to motor production rather than the result of motor system deficits itself. Indeed, in these studies, participants were presented with the target object at the very moment they had to grasp it, while in daily life, patients have time to look at an object before grasping it. Therefore, laboratory studies mix two components: (1) the effect of central visual impairment on motor production and (2) the effect of visual impairment on the time for perception of the spatial properties of the object (e.g., spatial location, distance and width), leading to a deficit in motor production. This distinction is important. For instance, motor production deficits in patients with age-related macular degeneration (AMD) seem due to visual impairment, not to motor production itself. [START_REF] Corveleyn | What Is the Nature of the Reach and Grasp Deficit in Wet Age-related Macular Degeneration?[END_REF] Therefore, patients with AMD just need more time to accomplish their daily life actions [START_REF] Boucart | Impact of Wet Macular Degeneration on the Execution of Natural Actions[END_REF] instead of actual rehabilitation of their motor system production. In the present study, we assess the impact of glaucoma on the two components. The kinematics of the reach-and-grasp motor action was compared in two different conditions: one in which participants saw the object only at the moment they had to grasp it, thus measuring the effect of a deficit in the analysis of the object's metrics on motor production, (i.e., with temporal constraints for visual exploration); and one in which they had time to observe the object before grasping it, thus measuring the effect of visual impairment on motor production (i.e., with no temporal constraints for visual exploration). We hypothesized that deficits in the kinematic parameters of glaucoma patients should be observed in the task with temporal constraints for visual exploration (immediate condition) rather than in the task with no temporal constraints for visual exploration (delayed condition). Indeed, in the first task, the participant needs to explore the environment quickly in order to initiate the action as soon as possible. Therefore, owing to glaucoma, the visual information is not entirely processed and the visual feedback, in order to adjust his (or her) action, is greater compared to the delayed condition. In the delayed condition, the observation time before grasping the object allows the planning of a motor command and the execution of the motor action at the appropriate moment. Therefore, visual feedback is less important for accomplishing a motor action compared to the immediate condition. We also investigated the relationship between each kinematic parameter and visual acuity to better understand the links between visual acuity of pathology in motor performance. Indeed, kinematic parameters are known to be influenced by visual acuity. [START_REF] Pardhan | How does the presence and duration of central visual impairment affect reaching and grasping movements?[END_REF][START_REF] Kotecha | The functional consequences of glaucoma for eye-hand coordination[END_REF][START_REF] Pardhan | A Comparison of Reach-to-Grasp and Transport-to-Place Performance in Participants With Age-Related Macular Degeneration and Glaucoma[END_REF]

Methods

Participants

Sixteen patients with primary open angle glaucoma (POAG) were recruited in the ophthalmology department of Claude Huriez Hospital, Lille, France. All participants underwent SITA-standard 30-2 perimetry with a Humphrey Visual Field Analyzer II (HFA, Carl Zeiss Meditec, Dublin, CA, USA), had glaucoma-related visual field (VF) defects and a mean deviation (MD) worse or equal to -6 dB (SITA-standard 30-2: MD = -16.4 ± SD = 5.76; range: 8.6 -27). They had to have a monocular visual acuity of 6/12 or more in the tested eye (best eye included in the recruitment criteria). If both eyes had equal acuity, one eye was randomly selected. There were 14 volunteers with normal visual acuity among the age-matched participants. They were either relatives of participants with glaucoma or patients who had undergone successful cataract surgery, with normal visual acuity ranging from 20/25 to 20/20.

Age-matched participants were recruited in the ophthalmology department of Claude Huriez Hospital, Lille, France. Controls were tested monocularly on their preferred eye. A young adult group included 18 healthy students (in medicine, neuroscience and psychology) with normal vision (visual acuity = 20/20). Young people were included as controls to dissociate the effect of ageing from the effect of pathology. All participants had one eye patched (the eye with lower acuity for patients). Demographic data are provided in Table 1. Clinical data are provided in Table 2.

/ Insert table 1 here / / Insert table 2 here /

A mini-mental state examination (MMSE) [START_REF] Folstein | Mini-mental state". A practical method for grading the cognitive state of patients for the clinician[END_REF] was administered to the older participants. Participants with a history of neurological disease, psychiatric disease, cognitive impairment (MMSE < 25/30) or other ocular diseases (cataract, AMD) that might compromise oculomotor function were excluded. A physical therapist tested the participants for normal motion of the right arm and hand. All participants were right-handed. The study was approved by the ethics committee of Lille University. In accordance with the tenets of the Declaration of Helsinki, written informed consent was obtained from all participants.

Participants sat in front of a table (120x80 cm) and placed their thumb and index close to a starting point located 10 cm from the edge of the table (see Figure 1). Five cylinders (height: 10.5 cm, diameter: 5.5 cm) located on the table in a semi-circle (radius: 25 cm from the starting point) at 0° (center), 30° and 60° to the left and the right of the center cylinder were used as stimuli. The participants' head was positioned 60 cm from the central cylinder.

All cylinders positioned on the table were the same color (wood color). Before each trial, they were (re)positioned in these five precise locations by the experimenter. In front of the table, a curved screen (180° degrees of eccentricity) displayed the different steps of each trial (fixation cross, five colored cylinders at five spatial locations, Figure 1). Participants performed two tasks in a random order: one with a temporal constraint for visual exploration (immediate condition) and one with no temporal constraint for visual exploration (delayed condition). Each condition involved 25 trials determined by five colors (blue; red; yellow; white; black) * five spatial locations (60° right; 30° right; 0°; 30° left; 60° left). A schematic representation of both tasks is shown in Figure 2. Before the experiment, each color cylinder was displayed and the participants had to recognize each color. All participants were able to name the colors of the five cylinders.

/Insert figure 1 here / /Insert figure 2 here /

In the task with a temporal constraint for visual exploration (immediate condition), participants placed their thumb and index on the starting point and looked at the fixation cross displayed on the curved screen. Simultaneously, the name of a color was given by a loudspeaker 2000 ms +/-500 ms and five colored cylinders were displayed on the curved screen in five different spatial locations (0° center, 30° left and right and 60° left and right).

The colored cylinders and the spatial locations on the screen were changed randomly between participants and trials. Participants explored the displayed colored cylinders. As soon as they recognized the spatial location of the given color, the participants were instructed to reach and grasp as quickly and accurately as possible the cylinder on the table with the corresponding color. They were asked to lift it approximately 10 cm, put it on the table and return to the starting point.

In the task with no temporal constraint for visual exploration (delayed condition), the same procedure was used, except that participants were not to reach and grasp the cylinder as soon as they recognized the target color but only after an auditory cue. Participants placed their thumb and index on the starting point and then fixated the cross displayed on the curved screen. Simultaneously, a color was given by a loudspeaker 2000 ms +/-500 ms and colored cylinders were displayed on the curved screen in five spatial locations (0°, 30° left and right and 60° left and right). The colored cylinders and spatial locations on the screen were changed randomly between participants and trials. Participants explored the displayed colored cylinders. Unlike in the immediate condition, participants had to wait for an auditory cue to reach and grasp the cylinder corresponding to the given color as quickly and accurately as possible. This cue occurred 2000 ms +/-500 ms after the color was given. The time between the color name and the auditory cue allowed the exploration of the displayed cylinders. In this condition, the participants had time to identify the target cylinder and to prepare their reachand-grasp movement. As soon as they heard the auditory cue, they had to reach and grasp the cylinder as quickly and accurately as possible, lift it approximately 10 cm, put it on the table and return to the starting point.

Data Recording and Analysis

A magnetic tracking system (Polhemus Liberty 240/8-8 System, Colchester, VT) was used to record the participants' movements in a X, Y and Z coordinates system. The kinematics of the reach-and-grasp movements and cylinder displacements were measured by eight markers that were placed on the index (base and tip), the thumb (tip), and the wrist (scaphoid and pisiform) of the participants. One additional marker was placed on each of the five cylinders. The spatial environment (table and cylinder) was calibrated before each session, allowing the system to reach a temporal and spatial resolution accuracy lower than 0.2 mm at a 240 Hz sampling rate.

All parameters were computed with a custom program (MatLab®; MathWorks®, Natick) based on the 3D coordinates of the reflective marker placed on the wrist, index and thumb of the participants and on the five markers on the cylinders. The kinematic outcome measures were computed on the basis of the wrist marker. Temporal and kinematic parameters of the (x, y, z) coordinates of the wrist marker were computed from tangential velocity profiles, after filtering the data using a second-order Butterworth dual-pass filter (cutoff frequency: 15 Hz). Movement onset was defined as the first velocity value reaching 0.3 cm/s.

The following kinematic parameters of the reach-and-grasp trajectories were calculated (Figure 3): 1. "Movement duration" corresponding to the time between movement onset and movement end (defined as the moment when participants reached the cylinder).

2. "Peak velocity" corresponding to the maximum velocity reached by the wrist during movement.

3. "Acceleration interval" corresponding to the time between the onset of hand movement and the "peak velocity" moment. 4. "Deceleration interval" corresponding to the time between "peak velocity" moment and the end of the movement. 5. "Maximum grip aperture" (MGA) corresponding to the maximum distance between thumb and index during movement. 6. "Time to maximum grip aperture" corresponding to the time between the onset of hand movement and the time of maximum grip aperture.

/Insert figure 3 here /

Trials were excluded from the data analysis when a participant responded erroneously.

1.6% of the trials, homogenously distributed across the conditions, were discarded. For each task, a 2x3 analysis of variance was conducted with each group {Glaucoma patients; Agematched Controls; Young Controls} as the between-participants factor and angle condition {0°; 30° right; 30° left; 60° right; 60° left} as the within-participants factor. Local comparisons were performed using a post-hoc Bonferroni test with threshold corrections, in order to account for multiple group factor comparisons and possible interactions between Group and Angle. For the sake of clarity, principal effect of angle and post-hoc are not presented because we had no hypothesis on this factor. Spearman correlations for glaucoma patients were computed between each kinematic parameter, visual acuity, MD 30-2 and duration of pathology. Finally, comparisons of the results of the immediate condition vs delayed condition for each glaucoma patient were conducted. Results are presented in Tables 3, 4 and 5.

Results

Task with temporal constraints for visual exploration (immediate condition)

Movement duration

A group effect was observed on movement durations (F (2, 45) = 36.5; p < 0.001;  2 = 0.6). The movement duration of glaucoma patients (X mean = 1179 ms; SD = 250 ms) was significantly longer than that of age-matched participants (X mean = 1001.8 ms; SD = 169.6 ms; p < 0.014) and young participants (X mean = 680.2 ms; SD = 106.5 ms; p < 0.001). The movement duration of age-matched participants was significantly longer than that of young participants (p < 0.001).

Peak velocity

A group effect was observed on peak velocity (F (2, 45) = 11.6; p < 0.001; η² = 0.27).

Peak velocity of glaucoma patients (X mean = 32.4 cm/s; SD = 10.2 cm/s) was significantly faster than peak velocity of age-matched participants (X mean = 24.4 cm/s; SD = 7.4 cm/s; p = 0.002) and young participants (X mean = 22.8 cm/s; SD = 2.4 cm/s; p < 0.001). No significant difference was found between age-matched and young participants.

An interaction was found between group and angle on peak velocity (F (8, 180) = 2.17; p = 0.032; η² = 0.016; Figure 4). The Bonferroni post-hoc comparison revealed that peak velocity for glaucoma patients was faster than peak velocity for age-matched participants and young participants, only at 60° eccentricity on the left (respectively p = 0.05 and p = 0.002) and right angles (respectively p = 0.007 and p < 0.001).

/ Insert figure 4 here /

Acceleration interval

A group effect was observed on the acceleration interval (F (2, 45) = 12.7; p < 0.001; η² = 0.27). The acceleration interval of glaucoma patients (X mean = 358.4 ms; SD = 107 ms; p < 0.001) and age-matched participants (X mean = 378.2 ms; SD = 82.7 ms; p < 0.001) was significantly longer than that of young participants (X mean = 269.4 ms; SD = 55 ms).

No interaction was found between group and angle on acceleration intervals.

Deceleration interval

A group effect was observed on the deceleration interval (F (2, 45) = 28; p < 0.001; η² = 0.52). No difference was observed between glaucoma patients and age-matched participants.

The deceleration interval of both glaucoma patients (X mean = 860.4 ms; SD = 230 ms; p < 0.001) and age-matched participants (X mean = 760.4 ms; SD = 139 ms; p < 0.001) was significantly longer than that of young participants (X mean = 458.6 ms; SD = 129.8 ms).

An interaction was found between group and angle on the deceleration interval (F (8, 180) = 4.53; p < 0.001; η² = 0.014). The Bonferroni post-hoc comparison revealed differences for glaucoma patients and age-matched participants in comparison to young participants (p < 0.001) for all angles (except young versus age-matched participants for 60° right (p = 0.02) and 60° left (p = 0.003)).

Maximum grip aperture

No group effect was observed on maximum grip aperture. Maximum grip aperture of glaucoma patients (X mean = 8.96 cm; SD = 1.82 cm) was not significantly different from the maximum grip aperture of age-matched participants (X mean = 8.88 cm; SD = 1.04 cm) and young participants (X mean = 9.47 cm; SD = 1.09 cm).

An interaction was found between group and angle on maximum grip aperture (F (8, 180) = 1.21; p = 0.03; η² = 0.017). The Bonferroni post-hoc comparison revealed a difference between 60° right (X mean = 8.62 cm; SD = 2.38 cm) and 60° left (X mean = 9.31 cm; SD = 1.87 cm) for glaucoma patients only (p = 0.034).

Time to maximum grip aperture

A group effect was observed on time to maximum grip aperture (F (2, 45) = 23.7; p < 0.001; η² = 0.42). The time to maximum grip aperture of glaucoma patients (X mean = 716.4 ms; SD = 191 ms; p < 0.001) and age-matched participants (X mean = 665.4; SD = 98 cm; p>0.001) was significantly shorter than that of young participants (X mean = 463.6 cm; SD = 102.1 cm).

No interaction was found between group and angle on time to maximum grip aperture.

/ Insert Table 3 here /

Finally, correlations were found between visual acuity for glaucoma patients and movement duration, deceleration interval and time to MGA (for 60° left condition only), suggesting a link between deficit intensity and deficit of movement kinematic parameters (Table 3 and Figure 5).

/ Insert Figure 5 here /

To summarize (Table 4), in the immediate condition, participants with glaucoma had significantly longer movement duration and higher peak velocity than age-matched and young participants. This result indicates an effect of glaucoma on the reaching phase of the movement. Interestingly, peak velocity for glaucoma patients was higher for cylinders located in the peripheral field of vision (60° left and right angle), thus suggesting that the deficit in movement kinematics is related to the visual field deficit.

/Insert Table 4 here / /Insert Table 5 here /

Task with no temporal constraints for visual exploration (delayed condition)

Movement duration

A group effect was observed on movement durations (F (2, 45) = 41.4; p < 0.001;  2 = 0.63). The movement duration of glaucoma patients (X mean = 1251.4 ms; SD = 242.2 ms) was significantly longer than that of age-matched participants (X mean = 1066 ms; SD = 175 ms; p = 0.02) and young participants (X mean = 716 ms; SD = 110.8 ms; p < 0.001). The movement duration of age-matched participants was significantly longer than that of young participants, p < 0.001) An interaction was found between Group and Angle on movement duration (F (8, 180) = 2.99; p = 0.004;  2 = 0.006). No significant differences were observed between the movement duration of glaucoma patients and age-matched participants for all angles. The movement duration of glaucoma patients and age-matched participants was significantly longer than that of young participants (p < 0.01 for all angles, except age-matched versus young participants at 60° left (p = 0.007)).

Peak velocity

A group effect was observed on peak velocity (F (2, 45) = 5.06; p = 0.01; η² = 0.108).

Peak velocity of both glaucoma patients (X mean = 39.2 cm/s; SD = 11.7 cm/s) and age-matched participants (X mean = 40.1 cm/s; SD = 10.7 cm/s) was significantly faster than that of young participants (X mean = 32.9 cm/s; SD = 5.3 cm/s; respectively p = 0.05 and p = 0.02).

No interaction was found between group and angle on peak velocity.

Acceleration interval

A group effect was observed on the acceleration interval (F (2, 45) = 6.03; p = 0.005; η² = 0.157). The acceleration interval of glaucoma patients (X mean = 390.8 ms; SD = 100.6 ms; p = 0.06 (trend)) and age-matched participants (X mean = 413 ms; SD = 109.6 ms; p = 0.006) was significantly longer than that of young participants (X mean = 327 ms; SD = 42.1 ms).

An interaction was found between group and angle on acceleration intervals (F (8, 180) = 3.34; p = 0.001; η² = 0.036). The Bonferroni post-hoc comparison revealed a difference between age-matched and young participants at 30° left angle (p = 0.004).

Deceleration interval

A group effect was observed on the deceleration interval (F (2, 45) = 59.2; p < 0.001; η² = 0.704). The deceleration interval of glaucoma patients (X mean = 860.4 ms; SD = 162.8 ms; p < 0.001) was longer than that of age-matched participants (X mean = 651.6 ms; SD = 138 ms; p < 0.001) and young participants (X mean = 389.4 ms; SD = 95.7 ms). The deceleration interval of age-matched participants was longer than that of young participants (p < 0.001).

No interaction was observed between group and angle.

Maximum grip aperture

A group effect was observed on maximum grip aperture (F (2, 45) = 3.5; p < 0.04; η² = 0.13). The maximum grip aperture of glaucoma patients (X mean = 8.7 cm; SD = 1.4 cm) was not significantly different from that of age-matched participants (X mean = 8.8 cm; SD = 1cm).

A tendency was observed between the maximum grip aperture of glaucoma patients and that of young participants (p = 0.079). (X mean = 9.6 cm; SD = 1 cm, p = 0.08).

No interaction was found between group and angle on maximum grip aperture.

Time to maximum grip aperture

A group effect was observed on time to maximum grip aperture (F (2, 45) = 19.2; p < 0.001; η² = 0.29). A Bonferroni post-hoc comparison revealed a significant interaction between the time to maximum grip aperture of both glaucoma patients (X mean = 804.2 ms; SD = 253.2 ms) and age-matched participants (X mean = 727; SD = 148 cm) with young participants (X mean = 496.8 cm; SD = 86.1 cm, p < 0.001).

No interaction was found between group and angle on time to maximum grip aperture.

Finally, no correlation was found between visual acuity and kinematics parameters for glaucoma patients.

To summarize (Table 5), in the delayed condition, glaucoma patients had significantly longer movement duration and deceleration interval than age-matched and young participants. This result indicates an effect of glaucoma on the grasping phase of the movement.

Interestingly, the deceleration deficit in glaucoma patients was not affected by the location of the cylinder, suggesting that it does not depend on the location of the visual field deficit.

Comparison between the immediate versus delayed conditions for each glaucoma patient

No statistical difference was observed between immediate and delayed tasks for each glaucoma patient on movement durations, deceleration interval, maximum grip aperture and time to maximum grip aperture.

A statistical difference was observed between immediate and delayed task for glaucoma patient on peak velocity (F (1, 14) = 6.04; p = 0.032; η² = 0.07) and acceleration interval (F (1, 14) = 4,87; p = 0.05; η² = 0.023). Glaucoma patient had faster peak velocity in delayed task (X mean = 39.2 cm/s; SD = 11.7 cm/s) than in immediate task (X mean = 32.4 cm/s; SD = 10.2 cm/s). Glaucoma patient had longer acceleration interval in delayed task (X mean = 390.8 ms; SD = 100.6 ms) than in immediate task (X mean = 358.4 ms; SD = 107 ms).

Discussion

The present study was designed to investigate whether abnormalities in reach-andgrasp tasks observed in previous studies in glaucoma patients resulted from difficulties in the perception of the relevant metric parameters to reach and grasp a target object (immediate condition: no time for visual exploration) or in motor production (delayed condition: time for visual exploration). Glaucoma patients and age-matched participants differed significantly in movement duration and peak velocity when participants had a temporal constraint for visual exploration (immediate condition). Glaucoma patients exhibited faster peak velocity, which is related to the reaching phase of the motor action execution. [START_REF] Chieffi | Coordination between the transport and the grasp components during prehension movements[END_REF][START_REF] Hommel | Action control according to TEC (theory of event coding)[END_REF] Comparison of the immediate condition (X mean = 32.4 cm/s; SD = 10.2 cm/s) versus the delayed condition (X mean = 39.2 cm/s; SD = 11.7 cm/s) for each glaucoma patient confirm statistical difference on peak velocity. Moreover, a positive correlation was found for the immediate condition between the visual acuity of glaucoma patients and both movement duration and deceleration interval for all angles and time to MGA at 60° left angle. These results are consistent with previous studies showing a longer movement duration and correlations between visual acuity and both movement duration and peak velocity in glaucoma patients. [START_REF] Kotecha | The functional consequences of glaucoma for eye-hand coordination[END_REF] However, Kotecha and al.

(2009) reported a negative correlation between visual acuity and peak velocity. One explanation could be that the participants' strategy consists in faster peak velocity to avoid the acceleration interval (and movement duration) as "normal". Consistent with this explanation, we found no difference in terms of acceleration interval between glaucoma patients and agematched participants, unlike Kotecha et al. (2009). Methodological differences could account for this change in strategy. In our study, the cylinders had the same size (5.5 cm) and locations (25 cm) from the starting point at 0 (center), 30° and 60° to the left and to the right of the central cylinder. In the studies by Kotecha et al., the cylinder changed in size (24 or 48 mm) and spatial location (200 mm or 400 mm) at each trial. Therefore, in their study, the participants had to adjust the maximum opening of their hand to the size of the object, whereas this adaptation was not required in our study because all cylinders had the same size and distance. Participants can use the "same" motor command to adjust their maximum grip aperture at each trial. [START_REF] Sabes | The planning and control of reaching movements[END_REF][START_REF] Wolpert | Multiple paired forward and inverse models for motor control[END_REF] Interestingly, peak velocity differed between glaucoma patients and age-matched participants, especially at 60° eccentricity left and right. Even though the participants were in a natural situation where they could move their head freely, the deficit in the peripheral visual field of glaucoma patients affected their kinematic parameters, especially for an object located in the peripheral visual field.

As mentioned in the introduction, two interpretations might account for these differences: (1) the kinematic difference of patients' motor execution might result from the effect of visual impairment on motor production; or (2) the effect of visual impairment on identification (i.e., the spatial location and/or the width of the target) might lead to a motor deficit. To dissociate these hypotheses, a second task (the delayed condition) was proposed to the same participants. In this task, participants had time to explore and identify the target and the distractors before reaching and grasping the target. In the delayed condition, a significant difference was found in kinematic parameters between glaucoma patients and aging controls. These deficits were found in deceleration intervals, which correspond to the grasp phase and online control of action. [START_REF] Kotecha | The functional consequences of glaucoma for eye-hand coordination[END_REF][START_REF] Desmurget | Role of the posterior parietal cortex in updating reaching movements to a visual target[END_REF][START_REF] Jeannerod | Mental imagery in the motor context[END_REF] Like patients with AMD, [START_REF] Corveleyn | What Is the Nature of the Reach and Grasp Deficit in Wet Age-related Macular Degeneration?[END_REF] glaucoma patients exhibited motor deficit only when they had no time to explore the visual scene (immediate condition). The deficit is specific to the reach phase. The motor abnormalities in reaching phase observed in glaucoma patient in previous studies seem to result from difficulties in target identification rather than from visuomotor deficits. Further studies are needed in binocular viewing conditions with various natural objects to confirm and clarify these results and extend them to daily life activities.

Conclusion and limitations

Glaucoma patients exhibited a motor disorder (reaching phase) in our study, only when they had no time to explore their environment before performing the reach-and-grasp task. From a clinical point of view, motor performance of glaucoma patients could be modulated by task, especially by temporal constraints of task.

  These result became clear in the light of the comparison between the performance in the immediate condition versus the delayed condition for each glaucoma patient. The comparison revealed no statistical difference for the deceleration interval (Xmean = 860.4 ; SD = 230 ms for immediate condition and Xmean = 860.4 ms; SD = 162.8 ms for delayed condition). Hence, time to exploration is not helpful for glaucoma patient. The difference in the delayed condition on deceleration interval between glaucoma patient (Xmean = 860.4 ms; SD = 162.8 ms) and age-matched participant (Xmean = 651.6 ms; SD = 138 ms) results from increase performance (i.e. faster deceleration interval) for age-matched participant between the delayed condition (Xmean = 651.6 ms; SD = 138 ms) and the immediate condition (Xmean = 760.4 ms; SD = 139 ms) indicating that time to visual exploration is helpful for age-matched participant but not for glaucoma patient.

Figure 1 .

 1 Figure 1. Schematic representation of experimental design. R = Red ; B = Blue ; Y = Yellow ;

Figure 2 .

 2 Figure 2. Schematic representation of both tasks. The major difference is the separation of the

Figure 3 .

 3 Figure 3. Plot of thumb and object velocity (left axis, dashed line) and grip aperture (right

Figure 4 .

 4 Figure 4. Peak velocity in function of angle for glaucoma patients (square), age-matched

Figure 5 .

 5 Figure 5. Mean deceleration interval (all angles) in function of visual acuity (left panel) and

Figure 1 Figure 2

 12 Figure 1

Table 1 Table 1 .

 11 Demographic data of glaucoma patients, age-matched

	controls and young control participants. Standard deviation
	indicated between brackets. Aged-matched had VA ranging from
	20/25 to 20/20.

Table 2

 2

	Number/Age/ Gender	MMSE	Tested Eye	VA LogMAR	MD 30-2 (tested eye)	MD 30-2
	1/62/F	30	RE	0	-21.9	-26.17
	2/67/F	28	RE	0.1	-8.6	-9.1
	3/74/F	28	RE	0.1	-22.5	-22.8
	4/62/F	30	RE	0.1	-9.1	-26.5
	5/60/F	30	RE	0	-16.2	-11.2
	6/60/M	30	RE	0.2	-16.1	-8.6
	7/46/M	28	RE	0.1	-15.6	-17.4
	8/69/F	29	LE	0.1	-9.04	-10.9
	9/74/F	25	LE	0.1	-20	-17.5
	10/62/F	29	LE	0.2	-16.1	-20.6
	11/68/F	29	LE	0.2	-9.8	-14.5
	12/67/F	26	LE	0	-15.4	-11.2
	13/59/M	30	LE	0	-25.6	-28.9
	14/68/M	29	LE	0.2	-27	-27.4
	15/59/M	28	LE	0.3	-14.1	-17.8
	16/49/M	28	LE	0	-15.3	-17.6

Table 2 .

 2 Demographic and clinical data of patients with glaucoma. LE = left eye, RE = right eye, MMSE = Mini-mental state examination.

Table 3

 3

		60° left	30° left	0°	30° right	60° right
	Movement duration	0.78	0.46	0.64	0.53	0.59
	Peak Velocity	0.3	0.07	0.01	0.05	0.145
	Acceleration interval	0.4	0.08	0.15	0.02	0.34
	Deceleration interval	0.8	0.58	0.57	0.6	0.57
	MGA	0.02	0.12	0.11	0.13	0,03
	Time to MGA	0.7	0.39	0.36	0.23	0.16

Table 3 .

 3 Spearman correlations between visual acuity and each kinematic parameter in immediate condition for glaucoma patients. Correlations in bold are statistically significative. MGA = Maximum grip aperture.

Table 4

 4

		Mouvement Duration in ms	Peak velocity in cm/s	Acceleration interval in ms	Deceleration interval in ms	MGA in mm	Time to MGA in ms
	Glaucoma	1179	32.4	358.4	860.4	8,96	716,4
	patient	(250)	(10.2)	(107)	(230)	(1.82)	(191)
	Age-	1001,8	24.4	378.2	760,4	8,88	665,4
	matched	(169.6)	(7.4)	(82.7)	(139)	(1.04)	(98.02)
	Young	680.2	22.8	269.4	458.6	9.47	463.6
	control	(106.5 )	(2.4)	(55)	(129.8)	(1.09)	(102.1)
	Group effect	p < 0.001*	p < 0.001*	p < 0.01	p < 0.001	p = 0.28 p < 0.001
	Group *Angle	p = 0.013+	p = 0.032*	p = 0.59	p < 0.001	P = 0.03	p = 0.45
	effect

Table 4 .

 4 For each kinematic parameter, mean and standard deviation for glaucoma patients, age-matched and young participants with statistical results as a function of Group and of Angle*Group in the immediate condition. Significant effects are in bold font.

* indicates difference between glaucoma patients and age-matched participants in post-hoc test (p < 0.05). + indicates tendential difference between glaucoma patients and age-matched participants in post-hoc test (p < 0.1). ms: millisecond, mm: millimeter, cm/s: centimeter per second.

Table 5

 5

		Mouvement Duration in ms	Peak velocity in cm/s	Acceleration Interval in ms	Deceleration interval in ms	MGA in mm	Time to MGA in ms
	Glaucoma	1251.4	39.2	390.8	860.4	8.7	804.2
	patient	(242,2	(11.7)	(100.6)	(162.8)	(1.4)	(253.2)
	Age-	1066	40.1	413	651.6	8.8	727
	matched	(175)	(10.7)	(109.6)	(138)	(1)	(148)
	Young	716	32.9	327	389.4	9.6	496.8
	control	(110.8)	(5.3)	(42.1)	(95.7)	(1)	(86.1)
	Group effect	p < 0.001*	p = 0.01	p = 0.005	p < 0.001*	p = 0.04	p < 0.001
	Group *Angle	p = 0.004	p = 0.097	p = 0.001	p = 0.103	p = 0.13	p = 0.6
	effect

Table 5 .

 5 For each kinematic parameter, mean and standard deviation for glaucoma patients, age-matched and young participants with statistical results as a function of Group and of Angle*Group in the delayed condition. Significant effects are in bold font. * indicates difference between glaucoma patients and age-matched participants in post-hoc test (p < 0.05). ms: millisecond, mm: millimeter, cm/s: centimeter per second.


Ekaterine Chikoidze

Corinne Sartel

Hagar Mohamed

Ismail Madaci

Tamar Tchelidze

Mircea Modreanu

Pablo Vales-Castro

Carles Rubio

Christophe Arnold

Vincent Sallet

Yves Dumont

Amador Perez-Tomas

Enhancing the intrinsic p-type conductivity of the ultra-wide bandgap Ga2O3 semiconductor

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Recently, ultra-wide band gap gallium oxide (Ga2O3) is receiving a lot of renewed attention as a transparent semiconducting oxide (TSO) champion owing to its unusual material properties [START_REF] Nagarajan | A Chemically Driven Insulator-Metal Transition in Non-Stoichiometric and Amorphous Gallium Oxide[END_REF], [START_REF] Kim | Conversion of an Ultra-Wide Bandgap Amorphous Oxide Insulator to a Semiconductor[END_REF], [START_REF] Chikoidze | Puzzling Robust 2D Metallic Conductivity in Undoped B-Ga2O3 Thin Films[END_REF], large tuneable conductivity [START_REF] Orita | Deep-Ultraviolet Transparent Conductive β-Ga2O3 Thin Films[END_REF], [START_REF] Varley | Oxygen Vacancies and Donor Impurities in β-Ga2O3[END_REF] , extremely high breakdown field [START_REF] Higashiwaki | Depletion-Mode Ga2O3 Metal-Oxide-Semiconductor Field-Effect Transistors on β-Ga2O3 (010) Substrates and Temperature Dependence of Their Device Characteristics[END_REF], [START_REF] Higashiwaki | Recent Progress in Ga2O3power Devices[END_REF], [START_REF] Yang | V Reverse Breakdown Voltage Ga2O3 Schottky Rectifiers[END_REF], unique optoelectronic properties [START_REF] Oshima | Ga2O3 Thin Film Growth on C-Plane Sapphire Substrates by Molecular Beam Epitaxy for Deep-Ultraviolet Photodetectors[END_REF], [START_REF] Lee | Atomic Layer Deposited Gallium Oxide Buffer Layer Enables 1.2 v Open-Circuit Voltage in Cuprous Oxide Solar Cells[END_REF], [START_REF] Li | Positive Onset Potential and Stability of Cu2O-Based Photocathodes in Water Splitting by Atomic Layer Deposition of a Ga2O3 Buffer Layer[END_REF] and low cost [START_REF] Reese | How Much Will Gallium Oxide Power Electronics Cost? Joule[END_REF] . TSOs are a class of key enabling material in increasingly high demand because of the immediate applications they can find in a variety of new technologies, ranging from thin-film coatings and sensor devices, to transparent electronics and optoelectronics in telecommunications [START_REF] Yu | Metal Oxides for Optoelectronic Applications[END_REF][START_REF] Ellmer | Past Achievements and Future Challenges in the Development of Optically Transparent Electrodes[END_REF] . Some TSOs are indeed the standard choice for use in transparent electrode applications [START_REF]Handbook of Transparent Conductors[END_REF] and are also hugely important for information and communication technologies such as displays, touch screens, solar cells or light emitting diodes [START_REF] Yu | Metal Oxides for Optoelectronic Applications[END_REF] . Another key factor in the adoption of oxide semiconductors is that they are compatible with the strict manufacturing requirements of large-scale, largevolume, flexible, low cost and disposable/reusable devices [START_REF][END_REF], [START_REF] Pasquarelli | Solution Processing of Transparent Conductors: From Flask to Film[END_REF] . The arising TSO technology based in ultrawide bandgap gallium oxide (~4.8eV) holds the promise of extending many optoelectronic applications further into the deep ultraviolet range, overpassing the conventional wide bandgap TSO's near ultraviolet limit (~3.5 eV) (e.g. ZnO, SnO2 or In2O3).

However, to exploit the full potential of any emerging ultra-wide bandgap transparent optoelectronic technology, both, n-type and p-type conductivity (i.e. bipolarity), should be attained. Intrinsic wide bandgap This journal is © The Royal Society of Chemistry 20xx

Please do not adjust margins Please do not adjust margins transparent semiconductor oxides are predominately ntype due to their ability to form oxygen vacancies [18] . Depositing or annealing in reduced oxygen partial pressure can increase the conductivity of the oxide by introducing more carriers. In contrast, there are few predominantly p-type oxide semiconductors due to cation vacancies such as Cu2O, SnO or NiO [START_REF] Wang | Recent Developments in P-Type Oxide Semiconductor Materials and Devices[END_REF], [START_REF] Liu | Solution-Processed Inorganic p-Channel Transistors: Recent Advances and Perspectives[END_REF] . The majority of oxides have fundamental thermodynamic constrains, making their p-type doping difficult. More specifically, the formation of compensating intrinsic defects when lowering the Fermi energy towards the valence band has been identified as a main impediment to p-type doping in many oxides [START_REF] Hautier | Identification and Design Principles of Low Hole Effective Mass p-Type Transparent Conducting Oxides[END_REF] . In any case, oxides generally exhibit an important doping asymmetry and bipolar oxide semiconductors [START_REF] Grundmann | Oxide Bipolar Electronics: Materials, Devices and Circuits[END_REF] represent only a small subset (e.g. CuInO2 [START_REF] Yanagi | Fabrication of All Oxide Transparent P-N Homojunction Using Bipolar CuInO2 Semiconducting Oxide with Delafossite Structure[END_REF] , SnO [START_REF] Graužinytė | Towards Bipolar Tin Monoxide: Revealing Unexplored Dopants[END_REF] , NixCd1-xO1+δ [START_REF] Liu | Stoichiometry Controlled Bipolar Conductivity in Nanocrystalline NixCd1-xO1+δ Thin Films[END_REF] , SnNb2O6 [START_REF] Samizo | Carrier Generation in P-Type Wide-Gap Oxide: SnNb2O6 Foordite[END_REF] , ZrOS [START_REF] Arai | Chemical Design and Example of Transparent Bipolar Semiconductors[END_REF] ). Bipolar electronic features are also extremely interesting for Ga2O3 ultra-wide bandgap power electronics to define the main blocking p-n junctions [START_REF] Pérez-Tomás | Wide and Ultra-Wide Bandgap Oxides: Where Paradigm-Shift Photovoltaics Meets Transparent Power Electronics[END_REF], [START_REF] Baliga | Fundamentals of Power Semiconductor Devices[END_REF] .

Here, we provide stronger experimental supporting our previous report [START_REF] Chikoidze | P-Type β-Gallium Oxide: A New Perspective for Power and Optoelectronic Devices[END_REF] underlying that the Ga2O3 is a p-type native (or intrinsic) semiconductor. In addition, we report a route for the enhancement of the native p-type conductivity in undoped Ga2O3 by annealing in oxygen atmosphere. While high n-type conductivity in β-Ga2O3 can be efficiently achieved by impurity doping with Sn, Si, Ge, F or Cl [START_REF] Matsuzaki | Structure and Carrier Transport Properties of GaO Epitaxial Film Examined for Transparent Field-Effect Transistor[END_REF][START_REF] Chikoidze | Optical, and Magnetic Properties of Sn Doped α-Ga2O3 Thin Films[END_REF] (and even metallic conductivity due to charge accumulation on the surface in undoped β-Ga2O3. [START_REF] Chikoidze | Puzzling Robust 2D Metallic Conductivity in Undoped B-Ga2O3 Thin Films[END_REF][START_REF] Swallow | Transition from Electron Accumulation to Depletion at β-Ga2O3 Surfaces: The Role of Hydrogen and the Charge Neutrality Level[END_REF] ),33. J. E. N. Swallow, J. B. Varley, L. A. H. Jones, J. T. Gibbon, L. F. J. p-type conductivity is still controversial. Remarkably we corroborate that, thanks to the β-Ga2O3 particular point defect chemistry and the large formation energy of oxygen vacancies [START_REF] Varley | Oxygen Vacancies and Donor Impurities in β-Ga2O3[END_REF] (the native donor which can play role of compensators for holes), it is possible the realization of a p-type conductivity even in undoped layers [START_REF] Chikoidze | P-Type β-Gallium Oxide: A New Perspective for Power and Optoelectronic Devices[END_REF] .

Piper

Results and discussion

Thermodynamic analyses

Thermodynamic analyses of point defects and charge carriers have been carried out to determine the best conditions for growing highly compensated p-type β-Ga2O3 thin-films. By using the Kroger method of quasichemical equations [START_REF] Schmalzried | The Chemistry of Imperfect Crystals[END_REF] , the thermodynamic equilibrium in the β-Ga2O3 (crystal) -O2 (gas) system was established to define the dependence of point defects and charge carriers on temperature (T) and oxygen partial pressure (Phole). In general, high oxygen pressures are required to achieve p-type conductivity triggered by native (or intrinsic) acceptors, which are associated to gallium vacancy (VGa). The thermodynamic analysis show that high oxygen pressures guarantee the appearance of uncompensated hole conductivity effectively suppressing the compensation by native donors, which are associated primarily to oxygen vacancies (VO).

Please do not adjust margins

Please do not adjust margins modes for β-Ga2O3 are labeled using "#" while the phonon modes for α-Al2O3 substrate are labeled using "*".

The growth conditions (oxygen partial pressure and temperature) in which acceptors become dominant species, (i.e., the compensating donor defects are suppressed), can be determined by means of the following expression:

2 3 2 2 2 3 S D hole i V K K P K K = (1)
Where KS, KD, Ki and KV are the reaction constants of creation of Schottky pair, ionization of native donor, lattice thermal ionization and creation of oxygen vacancy respectively. Details about the method were reported in Ref. 30. As shown in the map of Fig. 1 (a), the pressure required for intrinsic p-type conductivity increases sharply with T. If the growth conditions are located in the upper part of the map, it should be expected rather uncompensated Ga2O3 (i.e., low p-type conductivity), whereas if growth conditions are located in the lower part, highly compensated samples should be obtained (higher p-type conductivity). Wang and coauthors has suggested also that the high the high temperature and high oxygen partial pressure are in favor of p-type doping in β-Ga2O3 crystal by weakening the self-compensation effect. [START_REF] Wang | Thermodynamic of Intrinsic Defects in β-Ga2O3[END_REF] XueliWang, Tingyu Liu

Sample preparation and Physical Properties

β-Ga2O3 high quality thin films have already been grown by MOCVD using commercial metalorganic precursors such as trimethyl-gallium (TMGa), and pure oxygen [START_REF] Wang | Thermodynamic of Intrinsic Defects in β-Ga2O3[END_REF][START_REF] Alema | Fast Growth Rate of Epitaxial β-Ga2O3 by Close Coupled Showerhead MOCVD[END_REF][START_REF] Sbrockey | Large-Area MOCVD Growth of Ga2O3 in a Rotating Disc Reactor[END_REF][START_REF] Du | Characterization of Homoepitaxial β-Ga2O3 Films Prepared by Metal-Organic Chemical Vapor Deposition[END_REF] . MOCVD is an industrial technique which allows the growth of large-area, uniform semiconductor layers (e.g. III-V compounds) with excellent control of the purity. In the case of β-Ga2O3, we thus expect high resistivity of the grown material due to a very low concentration of impurities. In agreement with that point, Almena et al [START_REF] Alema | Fast Growth Rate of Epitaxial β-Ga2O3 by Close Coupled Showerhead MOCVD[END_REF] observed highly resistive electrical properties as no measurable conductivity was observed by Hall measurements, and Sbrockey el al [START_REF] Sbrockey | Large-Area MOCVD Growth of Ga2O3 in a Rotating Disc Reactor[END_REF] reported insulating films with sheet resistivity >10 [START_REF] Lee | Atomic Layer Deposited Gallium Oxide Buffer Layer Enables 1.2 v Open-Circuit Voltage in Cuprous Oxide Solar Cells[END_REF] Ohms/square, beyond the measurement range of their four-probe equipment.

Herein, a strongly compensated undoped β-Ga2O3 layer (~500 nm-thick) was grown (see experimental section) on c-sapphire substrates at T=775 0 C and PO2=5Torr (red dot in Fig. 1(a)X-ray Cu-Kα diffractograms, recorded between 2θ=10° and 130°, in θ/2θ configuration, exhibit a highly texture of gallium oxide in the β-Ga2O3 phase with monoclinic space group (C2/m) symmetry (Fig.

1(b))

. More intense peaks correspond to (0,0,0,6) and (0,0,0,12) Bragg reflections of c-Al2O3 substrates (with also tiny peaks at 2θ=17.07° and 37,60° associated to Cu-Kβ radiation). The more intense Bragg peaks of the film, at 2θ values of 18.91°, 38.33°, 58.98°, 82,01° and 110,21°, correspond to the family (-2n,0,n) planes. Their indexes in C2/m space group are (-201), (-402), (-603), (-804), (-1005) respectively, with a reticular distance d(-2,0,1) = 0.4690 nm, and intensity ratio in agreement with previous works for β-Ga2O3 films grown on csapphire [START_REF] Du | Characterization of Homoepitaxial β-Ga2O3 Films Prepared by Metal-Organic Chemical Vapor Deposition[END_REF][START_REF] Hu | Study on the Optical Properties of β-Ga2O3 Films Grown by MOCVD[END_REF][START_REF] Oda | Schottky Barrier Diodes of Corundum-Structured Gallium Oxide Showing on-Resistance of 0.1 MΩ•cm2 Grown by MIST EPITAXY®[END_REF][START_REF] Zhong | High-Performance Single Crystalline UV Photodetectors of β-Ga2O3[END_REF][42][START_REF] Seiler | Epitaxial Growth of Gallium Oxide Films on C-Cut Sapphire Substrate[END_REF] .The only additional detected Bragg peak at 2θ value of 48.71° might be indexed with (5 0 1) β-Ga2O3, with an intensity ratio lower than 0.5%, and may be negligible in term of crystallized volume. So we concluded that studied thin films are textured (-2 0 1) β-Ga2O3 crystalline phase. The film crystalline quality has also been analysed by Raman spectroscopy. Fig. 1(c) show the Raman spectra recorded using 514.5 nm excitation for: in red curve (-201) textured β-Ga2O3 thin film grown on c-cut sapphire substrates; in green curve a blank c-cut sapphire (0001) α-Al2O3; and in blue trace, a (100)-cut β-Ga2O3 single crystal. The primitive unit cell of β-Ga2O3 consists of 10 atoms which results in 30 phonon modes; of which 27 are optical modes. At the Γ -point, these belong to the irreducible representation [START_REF] Chen | The Lattice Distortion of β-Ga2O3 Film Grown on c-Plane Sapphire[END_REF] .

Γ opt = 10Ag + 5Bg + 4Au + 8Bu (2)
The modes with Ag and Bg symmetry are Raman active, while those with odd parity (index u) are infrared active.

The Raman spectrum for the (-201) textured β-Ga2O3 thin film grown on c-cut sapphire substrates is a combination of β-Ga2O3 (labelled using "#" in Fig. 1(c)) This journal is © The Royal Society of Chemistry 20xx

Please do not adjust margins Please do not adjust margins and α-Al2O3 phonon modes (labelled using "*" in Fig. 1c).

No , which is also in agreement with previous reports [START_REF] Chikoidze | P-Type β-Gallium Oxide: A New Perspective for Power and Optoelectronic Devices[END_REF] .

Electrical properties

Here, a detailed study of the electrical transport properties of strongly compensated β-Ga2O3 has been performed (while others were unsuccessful) thanks to home developed high temperature and high impedance set-up. Van der Pauw Hall Effect measurements were employed to determine the resistivity, carrier type, density and mobility. I-V characteristic for Ohmic contacts at 700K is shown in insert of Figure 2(a).Resistivity at T = 530 K (the lowest temperature for valid measurements) was found to be ρ = 2.9×10 5 Ω•cm.

By heating the sample up to T = 850K, the resistivity decreases down to ρ = 1.2×10 3 Ω•cm as shown in Fig.

2(a)

. The resistivity dependence on Tρ(T), shows the typical behaviour of semi-insulating material, with a hopping conductivity enhancement above 650K (see Fig. 2 (b)). The determination of the majority carrier type is not trivial in practice when the sample is of high resistance ( > 10 7 Ω) due to the difficulty in correctly extracting the Hall voltage (VH) from the total measured voltage. To further validate the sign of majority carriers, the Hall voltage dependence on the applied magnetic field was measured at different temperatures. Hall voltage measurements were carried out at varying magnetic fields (0-1.6 T) in the temperature range of 650K -850K. In a non-magnetic material, VH is linearly proportional to the applied magnetic field and a positive sign indicates that the majority charge carriers are ptype (holes). As shown in Fig. 2(c), the positive VH linearly increase with perpendicularly applied magnetic field. This confirms that the layer was p-type. The temperature dependence for Hall hole concentration is shown in Fig. 2(d). At the largest available temperature of 850 K, the free hole concentration is p = 5.6×10 14 cm - A carrier activation energy of Ea = 1.24 eV ±0.05 eV has been determined from the ln(p) versus 1/T plot. For a ptype semiconductor, the general description of the hole concentration at a temperature T (K) is given by the neutrality equation:

(

) 3
Where k is Boltzmann's constant (m 2 kg s -2 K -1 ), gD is the acceptor degeneracy, NA is the acceptor concentration (cm -3 ) and ND is the compensating donor concentration (cm -3 ). MV is the hole density of states in the valence band. If p << NA-ND and p << ND, in the strong compensation regime, the neutrality equation (2) becomes :

(4)

      - = - - + kT E p N N M p N p g i D A v D d exp ) ( ) (       -               - = kT E g M N N N p i d v D D A exp
Please do not adjust margins Please do not adjust margins Thus, the experimental activation energy of Ea = Ei = 1.24 eV should correspond to the ionization energy of the acceptor centre (Ei). This ionization energy value agrees well with two-times of the activation energy estimated (0.56 eV) for a previously reported arguably p-type weakly compensated Ga2O3 thin-films grown by pulsed laser deposition (PLD) [START_REF] Chikoidze | P-Type β-Gallium Oxide: A New Perspective for Power and Optoelectronic Devices[END_REF] . A gallium vacancy acceptor level VGa located at ~1.2 eV above the valence band has been already reported by several groups by deep-level transient spectroscopy (DLTS) [START_REF] Dohy | Raman Spectra and Valence Force Field of Single-Crystalline β Ga2O3[END_REF][START_REF] Polyakov | Point Defect Induced Degradation of Electrical Properties of Ga2O3 by 10 MeV Proton Damage[END_REF] .

Oxygen Annealing

Annealing in an oxygen rich (i.e. Ga deficient) atmosphere should lead to an increase of acceptor VGa centres. As many other metal oxides, gallium oxide is a well-known material for gas sensing [START_REF] Zhang | Deep Level Defects throughout the Bandgap of (010) β-Ga2O3 Detected by Optically and Thermally Stimulated Defect Spectroscopy[END_REF] and, therefore, the effect of oxygen annealing at high temperatures on the conductivity of insulating bulk β-Ga2O3 have been intensively investigated previously [START_REF] Pearton | A Review of Ga2O3 Materials, Processing, and Devices[END_REF][START_REF] Fleischer | Sensing Reducing Gases at High Temperatures Using Long-Term Stable Ga2O3 Thin Films[END_REF] . For β -Ga2O3, it has been reported a conductivity activation temperature onset of around ~700 o C. Annealing above 700 o C in air or oxygen ambient would lead to the creation of oxygen vacancies (VO) due to the outdiffusion of oxygen atoms from the Ga2O3 lattice. This generation of VO leads to an additional source of freeelectrons and to a n-type conductivity enhancement. The ionization energy of VO in case of ceramic β-Ga2O3 samples has been estimated to be ~1.5 eV from the conduction band [START_REF] Fleischer | Electron Mobility in Single-and Polycrystalline Ga2O3[END_REF] . The effect of oxygen annealing leading decrease of background n type carrier concentrations for diodes annealed in O2 ambient and for annealed sabstrated have been demonstrated. [33-51-53] .

Therefore, to enhance hole conductivity while not creating additional oxygen vacancies, post annealing in pure oxygen atmosphere at a reduced temperature of 600° have been carried out in a condition of weak compensation (blue spot in Fig. 1(a)). It is worth to be mentioned that, after annealing, neither X-ray diffractograms nor Raman spectroscopy evidenced any change so the gallium oxide films would remain structurally unaffected. Electrical transport measurements showed that oxygen annealing leads the decrease of resistivity from ρ = 1.2x10 3 Ω•cm to ρ = 1.7 x10 2 Ω•cm at T= 850K while, at room temperature, the resistivity was determined to be ρ = 1x10 4 Ω•cm (Fig.

3(a)

). We have not detected any "electrical inhomogeneity" performing I-V characterization and resistivity measurements, which could be in case of surface conductivity resulting bi-layered structure. A double-slope conductivity curve with two different activation energies has been determined with (high temperature) Ea1 = 0.56 eV and (low temperature) Ea2 = 0.17 eV (Fig. 3(b)). In the high temperature range, the activation energy (Ea1 = 0.56eV) is similar to the half of the activation energy of the same acceptor centre but in highly compensated conditions (Ei = 1.24eV). The low temperature activation energy (Ea2 ) might be related with another shallow acceptor centre created after annealing in the oxygen atmosphere.

As in the as-grown samples, Hall Effect measurement methodology (measure Hall voltage with different applied magnetic field) the same as for grown sample, was applied showing that the annealed sample is p-type as well (See Fig. 3(c)). In this case, the Hall hole concentration was significantly increased up to p = 5.6x10 17 cm -3 (T = 850 K), when compared with available free-hole concentration before annealing (p = 5.6x10 14 cm -3 ). Nevertheless, the Hall mobility is lower, µ = 0.4cm 2 V/s (µ ~ 8.0 cm 2 /Vs before annealing), probably due to an increased number of scattering centers. It must be mentioned that to perform Hall Effect at entire This journal is © The Royal Society of Chemistry 20xx

Please do not adjust margins Please do not adjust margins temperature range was complicated owing to this low mobility. Though still, it was actually measured in a narrower temperature range, it appears that the hole mobility does not change significantly with temperature. Therefore, it is concluded that the conductivity activation energy is mainly determined by the activation of free carriers with temperature (Fig. 3(d)). Therefore, we could assume that the conductivity activation energy of Ea2 = 0.17 eV is the acceptor level energy with an ionization energy of around this value. A potential origin of this shallow level may be further elucidated by considering several theoretical assumptions. It is well-known that, close to the stoichiometry, oxide's oxygen vacancies tend to be preferentially in a double charged (VO ++ ) state then as single charge(VO + ) state [START_REF] Zacherle | Ab Initio Calculations on the Defect Structure of β-Ga2O3[END_REF] . In off-stoichiometry state, when hole concentration are important, the compensating donor defects are expected to be even more abundant in double charged state. Taking this fact into account, we attribute the shallower acceptor centre with Ea2 = 0.17eV activation energy to be due to the creation of a VGa --VO ++ complexes. Indeed, the high probability of creation of such vacancy complexes has been studied in detail by Ingebrigtsen et al [START_REF] Wertheim | X-Ray Photoemission Band Structure of Some Transition-Metal Oxides[END_REF] . In the case of oxygen annealed strongly compensated β-Ga2O3, because of the Coulombic interactions between VGa -and VO ++ , the VO ++ donor centre has a tendency to be located in the vicinity of charged acceptor centre, forming VGa --VO ++ complexes. Consequently, the energy of electron localized on VGa' decreased by amount 𝒐𝒐𝒐𝒐 ∆𝑬𝑬 = 𝟐𝟐𝒆𝒆 𝟐𝟐 ε𝑹𝑹 ⁄ 𝑨𝑨𝑨𝑨 , where 𝑹𝑹 𝑨𝑨𝑨𝑨 is distance between VGa -and VO ++ ,ε is static dielectric constant of Ga2O3. If VO •• defect is located in the first coordination spheres, its proximity can reduce electronic level of VGa' (1.24eV) by ∼ 1 eV, which is in a good agreement with Ea2 = 0.17eV activation energy observed in experiment. Please do not adjust margins Please do not adjust margins X-ray photoelectron spectroscopy (XPS) is a fine chemical method to investigate a material's valence band characteristic and brings additional evidence of the presence of states within the bandgap 57-59 4, it was found a clear correlation within the amount of states in the lower half of the bandgap and the p-type character in the sequence, n-type (Si-doped) commercial reference, p-type (undoped) and p-type (annealed). The n-type control sample is a commercial (Novel Crystal Technology, Inc.) nominally n-type Si-doped β-Ga2O3 (ND-NA = 1.3 × 10 18 cm -3 ) epitaxy (500 nm) grown on a single crystal β-Ga2O3 (labelled "n-type (Si-doped)"). For our samples, the valence band edge is shifted towards more p-type using the Ga3d peak as the calibration peak (smaller Fermi level implies more p-type character), see Fig. 4(a) and (b). The numerical values of the energy levels are in agreement with those given by Hall. A zoom of the smallest binding energies further reveals the presence of states within the bandgap (Fig. 4(c),(d) and (e)). The counts per second (counts/s) are normalized to the maximum value in the range of 0-6 eV. The Fermi level is near the conduction band in the case of the commercial Si-doped Ga2O3 reference (~4.4 eV). For the Ga2O3 reference, there is no indication of further tail states within the bandgap. The Fermi level is shifted towards an intrinsic value (i.e., mid-gap) in our undoped as-grown Ga2O3, but a number of tail states arise at ~1.5-1.2 eV from the conduction band. In the annealed sample, the states further extend towards the lower part of the bandgap and hence, indicating a much larger p-type carrier density (and hence, conductivity), as the I-V and Hall experiments suggest. From the extrapolation of the valence band edge, the Fermi level is as low as ~0.2 eV for the annealed sample.

Chemical analysis: XPS p-type valence band

Comparison with the state-of-the-art

In any case, for the majority of oxides, to achieve sizable p-type conductivity is challenging because their valence band maximum consists of strongly localized O 2pderived orbitals. In other words, the valence band of most oxides is rather flat, resulting in deep acceptor levels (lower free hole concentration at room temperature) and larger hole effective masses (lower mobilities) [START_REF] Hautier | Identification and Design Principles of Low Hole Effective Mass P-Type Transparent Conducting Oxides[END_REF][START_REF] Zhang | P-Type Transparent Conducting Oxides[END_REF], During many years the possibility of doping p-type Ga2O3 has been considered "out of question" due to the particular flatness of the computed valence band resulting in a high hole effective mass (see e.g. [START_REF] Sasaki | MBE Grown Ga2O3 and Its Power Device Applications[END_REF] ). A Ga2O3 valence band being governed by O 2p orbitals with arguably very low hole mobility and having very small dispersion in the wave vector-energy space has been routinely reported [START_REF] Varley | Oxygen Vacancies and Donor Impurities in β-Ga2O3[END_REF], [START_REF]Brillouin zone and band structure of β-Ga2O3 -Peelaers -2015 -physica status solidi[END_REF][START_REF] Varley | Role of Self-Trapping in Luminescence and $p$-Type Conductivity of Wide-Band-Gap Oxides[END_REF] . In addition, a strong localization of holes at specific sites in bulk Ga2O3 by a self-trapping effect, has also been predicted by firstprinciples calculations [START_REF] Mock | Band-to-Band Transitions, Selection Rules, Effective Mass and Exciton Binding Energy Parameters in Monoclinic \beta-Ga2O3[END_REF] Nevertheless, it has been also recently reported that the hole conduction mass in Ga2O3 is, indeed, fairly anisotropic and can be as low as ~0.4 m0 for certain orientations (while larger than 10 m0 in others) [START_REF] Yim | Computational Discovery of P-Type Transparent Oxide Semiconductors Using Hydrogen Descriptor[END_REF] . Fig. 5 (a,b).Thus, challenging current thinking, we have found experimentally a sizable hole mobility of at least ~10 cm as shown in Fig. 5(c).

Conclusions

In this work, we corroborate, via electrical Hall effect and chemical XPS measurements, that the ultra-wide band gap Ga2O3 oxide is an "native" ptype semiconductor oxide even in the case of strong compensation by donor defects. This unusual native p-type nature is due to the Ga2O3 particular point defects chemistry, mainly the large formation energy of oxygen donor vacancies, allowing the realization of a p-type. This confirms, in practice, that Ga2O3 is the p-type TSO with the largest band gap and also is potentially bipolar. The corroboration of this fact might have deep implications in optoelectronic, thanks to the shifting the optical band gap onset, and in power electronics in regard of the device's breakdown voltage range. Notably, the p-type nature was determined in samples grown by MOCVD, differently to the only previously reported native ptype conductivity for the samples grown by PLD [START_REF] Chikoidze | P-Type β-Gallium Oxide: A New Perspective for Power and Optoelectronic Devices[END_REF] . Such reproducibility reinforces our claim of possible realization of native hole conductivity in Gallium Oxide. Annealing in oxygen results in much improved (three-orders of magnitude) free hole concentration p(Ox-anneal) = 5.6x10 17 cm -3 vs. p(as-grown) = 5.6x10 14 cm -3 ) (T = 850 K) and resistivity ρ (Ox-anneal) =1.7 Ω•cm vs. ρ (as-grown) = ρ = 1.2×10 3 Ω•cm (T = 850 K). However, the mobility µ = 0.4cm 2 V/s (µ ~ 8.0 cm 2 /Vs before annealing) is reduced probably due to a greater number of acceptor scattering centres. The origin of such improved p-type conductivity is preliminary ascribed to the formation of VGa --VO ++ complexes, as a shallow acceptor centre.

Experimental Details

Ga2O3 growth details. Undoped β-Ga2O3 sample was grown in a RF-heated horizontal MOCVD reactor with separate inlets to avoid premature reactions in the manifold between oxygen and organometallics precursors. The reactor can operate at low pressure, between 30 and 760 torr, and at high growth temperature, up to 1000°C. Trimethylgallium (TMGa) and 5.5N pure oxygen were used as gallium and oxygen sources, respectively. Argon was used as carrier gas. The TMGa bubbler temperature was fixed at -15°C in order to obtain a low vapour pressure, and consequently a moderate growth rate near 5nm/min. The β-Ga2O3 layer was grown on C-oriented sapphire substrate using Ga/O ratio, growth temperature and reactor pressure set at 1.4×10 -4 , 775°C, and 30 torr respectively. The layer's thickness was measured at 450nm. X-ray diffraction profiles were recorded in θ/2θ configuration, using Rigaku SmartLab equipped with Cu-Kα1 source (λ=0,1541nm). Optical transmission spectra were measured in 200-2000 nm spectral range with a Perklin Elmer 9 spectrophotometer.

Raman spectra were recorded using a Renishaw Invia Reflex micro-Raman spectrometer at room temperature. The samples were excited using a cw Modu-Laser Stellar-REN laser emitting at 514.5nm with a power of 2-4mW. The reflecting microscope objective was 50X with a NA 0.75; the excitation spot diameter was 1μm. The back-scattered light was dispersed by a Please do not adjust margins Please do not adjust margins monochromator with a spectral resolution of 1.4cm -1 . The light was detected by a charge coupled device. The typical accumulation time was 30s. Raman shifts were calibrated using an optical phonon frequency (520.5 cm - 1 ) of silicon monocrystal. Several reference Raman spectra for beta-Ga2O3 single crystal substrates and sapphire c-cut substrates have been also measured.

Hall Effect measurement set-up. Ohmic contacts were prepared by silver paint at the four corners of the sample. Hall Effect measurements were performed in a Van der Pauw configuration in the temperature range of 300K to 850K and for magnetic fields perpendicular to the film plane varying from -1.6 T to 1.6 T, using a high impedance measurement set-up which was custom designed for measurement of high resistance.

X-ray photoemission spectroscopy (XPS) measurements were performed with a Phoibos 150 analyzer (SPECS GmbH, Berlin, Germany) in ultra-high vacuum conditions (base pressure 3×10 -10 mbar). XPS measurements were performed with a monochromatic Al KaX-ray source (1486.74 eV). This journal is © The Royal Society of Chemistry 20xx

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  , V. R. Dhanak, and T. D. Veal, APL Materials, 7, 022528 (2019) https://doi.org/10.1063/1.5054091

Fig. 1 .

 1 Fig. 1. (a) The dependence of growth pressure when hole conductivity appears, on growth temperature. The red point corresponds to our growth conditions, while blue point corresponds to post annealing conditions, T=600°C, 1atm. Pressure. b) The X-ray diffractogram of β-Ga2O3 film grown on (0001) sapphire (intensity in log scale); the peaks labelled by "*" indicates the XRD reflection corresponding to the sapphire substrate; c) The Raman spectra recorded using 514.5nm excitation for: Red trace:(-201) β-Ga2O3 thin film grown on c-cut sapphire substrates ; green trace :blank c-cut sapphire Blue trace: (100) β-Ga2O3 single crystal. The phonon

  Raman phonon modes belonging to other Ga2O3 polymorphs have been detected thus demonstrating that we have a single β-Ga2O3 phase. The Ga2O3 thin film Raman phonon modes Full width at half maximum (FWHM) of the β-Ga2O3 is closed to that of single crystal β-Ga2O3 and this is indicative for a very good crystallinity. Fig. 2(d) shows transmission spectrum T[%] in 200-2500 nm range. The Ga2O3 thin-films are highly transparent, with T~80% in UV-VIS-NIR. The optical band gap determined as Eg = 4.7±0.1 eV, from classical Tauc's plot extrapolation (see the insert in Fig.2 (d))

Fig. 2 a

 2 Fig.2 a) show the resistivity versus temperature change for β-Ga2O3 thin films, from 530-850 K; Insert: I-V characteristics of 2-point contacts measurements at 700K. b) ln(σ) versus T dependence: two regime of conductivity, band activation above T > 625 K and at bellow temperature when hopping conduction starts to be more important . activation energy of conductivity estimated as Ea = 1.24 eV c) Hall voltage versus magnetic field at different temperatures; d)Temperature dependence for Hall hole concentration.

Fig. 3 a

 3 Fig.3 a) Resistivity temperature dependence b) ln(σ) versus T dependence c)Hall voltage VH versus applied external magnetic field at T=850K d) Hall hole concentrations versus temperature for as grown and annealed in O2 at 600°C β-Ga2O3 thin films.

Fig. 4 (

 4 Fig.4 (a) X-ray photoelectron spectroscopy of the Ga2O3 valence band for a commercial Si-doped (n-type) reference and the p-type as-grown/annealed of this work (calibrated with respect to Ga3d). (b) A zoom of the valence band region, which in the case of stoichiometric Ga2O3, has a O2p character. Investigation of the valence band tail states for (c) n-type (Si-doped), (d) p-type (as-grown) and (e) p-type (annealed) evidencing the presence of states in the lower part of the bandgap.

Fig. 5 .

 5 Fig. 5. a) Unit cell of β-Ga2O3 detailing crystallographic coordinate systems. b) β-Ga2O3 effective mass parameters for conduction and valence bands as indexed for lowest transition along directions a, b and c (in units of m0). c) Comparison of the predicted effective mass of the ultra-wide bandgap β-Ga2O3 compared with other wide-bandgap oxides [62], [63], [70], 71] . The figures a) and b) here are reproduced or adapted with permission from A. Mock et al., Band-to-band

  57.[ https://journals.aps.org/prl/pdf/10.1103/PhysRevLet t.28.1028], 58.[https://www.nature.com/articles/srep32457], 59.[https://www.nature.com/articles/ncomms14482.p df?origin=ppub]. When used in high resolution in the valence band vicinity (i.e., for the lowest binding energies), it is possible to directly detect whether there are states in the lower part of the bandgap (those responsible of the p-type character)[START_REF] Ingebrigtsen | Impact of Proton Irradiation on Conductivity and Deep Level Defects in β-Ga2O3[END_REF] 60.[https://iopscience.iop.org/article/10.1088/1757-899X/34/1/012002/meta]. As shown in Fig.

2 /Vs together with an outstanding transparency in the visible of above 80%. What is more important is the significant "shift of the native p-type conductivity" up to the ~5 eV region (~250 nm) when compared with previous p-type conductive oxides such as NiO, SnO, Cu-based delafossites (CuAlO2, CuGaO2, SrCu2O2) or oxychalcogenides, all of them lying in the range of ~2.5-3.7 eV [62-63],, [70],[62-72] 72 .

	72.
	Perez-Tomas, A., Functional Oxides for Photo-
	Neuromorphic Engineering: toward a Solar Brain.
	Advanced Materials Interfaces, 2019 (in press).

This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 9

Acknowledgements

Hagar Mohammed would like to acknowledge Cultural Affairs and Massion Sector, Egyptian Ministry for Higher Education for her fellowship giving possibility work in France. We express our thanks to Guillaume Bouchez (GEMaC) for his assistance for optical measurements. APT acknowledges Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) under contract ENE2015-74275-JIN. The ICN2 is funded by the CERCA programme / Generalitat de Catalunya and by the Severo Ochoa Centres of Excellence programme, funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706).

Conflicts of interest

There are no conflicts to declare.