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  • Twenty-nine children diagnosed with ADHD, aged between 7 and 14 years (mean = 10.6 years; SD = 2.5), and a similar number (thirty-five) of sex/age matched healthy children participated in the experiment. Children with ADHD were classified as type Combined (N = 10), as Inattentive (N = 4) or as Hyperactive (N = 15). Twenty participants of the ADHD group were taking stimulant medication (Methylphenidate). The ADHD diagnosed children were all recruited through the Child and Adolescent Health Mental Center from Consorci Sanitari del Mareme, a public health consortium in Maresme (a nearly 400.000 inhabitant’s area in the North of Barcelona). Cases were diagnosed using the American Psychiatric Association's Diagnostic and Statistical Manual-IV-Text Revision criteria including a psychiatric and psychologist interview to assess the presence of symptoms of in-attention, hyperactivity and impulsivity during the last 6 months. Also the beginning of the symptoms before 7 years of age and the persistence of clinical dysfunction in at least two settings (school and home) were used as criteria [20]. Reasons for exclusion were mental retardation, other neurologic or mental disorder, or ophthalmologic problems. Part of the medical examination and psychiatric evaluation of all patients for diagnosing ADHD was the inquiry about visual problems. The survey included specific questions on strabismus and accommodation insufficiency. Patients with visual problems were discarded from the study. The children from the control group were recruited via two public schools showing no attention or conduct problems. All participants had normal or corrected-to-normal visual acuity. The children were given detailed instructions for the experiments. Before participating in the study written informed consent from the parents on behalf of the children enrolled in our study was obtained in accordance with the Helsinki Declaration. The study was approved by the Ethics Committee of the University of Barcelona and of Consorci Sanitari del Maresme. We used EventIDE (Okazolab Ltd, London, UK) for presenting the visual stimuli. The display resolution was 1024 x 768 pixels. The participants’ position of gaze was monitored using a binocular remote eye-tracking system at a sample rate of 120 Hz (T120, Tobii Technology AB, Sweden). Participants sat in a dimly lit room of the hospital or schools, in front of the PC monitor at a distance of 40–60 cm. To have similar conditions lights were switched off and curtains closed. The eye tracker was positioned in such a way that ambient lighting did not affect the recordings. The eye tracking equipment was calibrated (9 points, monocular) for each participant at the beginning of the experiment. Gaze fixations of at least 1000 ms within a region of 2°-3° around each calibration point were considered accurate. As subject needed only to fixate centrally during the task, mapping gaze position was secondary. Before starting the task, all participants practiced with some cue and no-cue trials (typically around 10–20 trials) to become familiar with the task. In both groups (ADHD and control) a similar number of practice trials were offered. When they confirmed that they understood the task we ran the experiment. To assess orienting visual attention we used a paradigm in which participants were required to discriminate the emotion (happy/sad) of a cartoon face placed in the periphery. During the task children had to maintain fixation at a central cross. On half of the trials participants were informed of the location of the face stimulus by a central cue stimulus (informative cue condition). On the other half they were unaware of the target location (uninformative cue condition). The experiment (Fig 1B) consisted of 4 sets with 32 trials each (128 trials in total) with 2 or 4 face images as possible targets. The 4 faces condition was introduced to make the task more difficult and was applied to the children older than 12 years of age. After eye calibration, observers were required to fixate a central cross with a size 0.7°x0.7° in the 2 face condition and 0.54°x0.54° in the 4 face condition. After 500 ms, 2 or 4 neutral face images (size of 4.1°x4.1° in the 2 face condition and 3.5°x3.5° in the 4 face condition) appeared in the periphery at an eccentricity of 4.8° or 6.4° for 2 or 4 faces, respectively. In the 2 face condition the faces were located on the left and right side of the fixation spot (Fig 1B). In the 4 face condition they were distributed, at an equidistant from each other, on an imaginary circle at angles of 45°, 135°, 225°, 315°. After 1000 ms, an informative cue stimulus or an uninformative cue stimulus appeared on top of the fixation cross. In both tasks the informative cue was an arrowhead with a size of 0.32° or 0.35° for 2 and 4 faces, respectively. The uninformative cue stimulus was a central cross with a size of 1.4°x1.4°. The informative cue was always valid. After an additional period of 1000 ms, one of the peripheral faces changed into a happy or sad face (= target; Fig 1C). In the 2 face condition the emotion of the face disappeared at the end of the trial, i.e. response time while in the 4 face condition, the face emotion disappeared after 300ms to make that task more demanding. Participants had to respond by pressing a button to indicate whether the face was happy or sad. Feedback was not given to the observers. After the end of the trial a new one started automatically. We calculated the angle of vergence by transforming the eye recordings (X and Y coordinates of both eyes) into angular units through algorithms designed to calculate 3-D components (Sx, Sy, Sz) of both eye gaze vectors. Sx,y,z are the three coordinates which represent the intersection point of the lines describing the line of sight of each eye. When these lines do not intersect this represents the midpoint of the smallest distance between them. The transformation was performed using a distance of the screen to the observer (DSD) of 50 cm and 5.5 cm for the inter-pupil distance (IPD). The angle of vergence is the angle at which the intersection of both eye gaze vectors made the least error. Sx,y,z are calculated as follow: Sx=IPD(IPD2(Yl-Yr)(Yl+Yr)+4IPD(-XrYl2-XlYr2−(Xr+Xl)DSD2)+4(Xr2(Yl2+DSD2)-Xl2(Yr2+DSD2)))2(-2XrYl+2XlYr+IPD(Yl+Yr))2+ 8((IPD+Xl-Xr)2+(Yl-Yr)2)DSD2(1) Sy=2IPD(YlYr(−2XlYr+2XlYr+IPD(Yl+Yr))+(IPD+Xl−Xr)(Yl+Yr)DSD2)(-2XrYl+2XlYr+IPD(Yl+Yr))2+ 4((IPD+Xl-Xr)2+(Yl-Yr)2)DSD2(2) Sz=IPD(Yl+Yr)(-2XrYl+2XlYr+IPD(Yl+Yr))DSD+4IPD(IPD+Xl-Xr)DSD3(-2XrYl+2XlYr+IPD(Yl+Yr))2+4((IPD+Xl-Xr)2+(Y1-Yr)2)DSD2(3) From these components we calculated the saccade amplitude by Eq (4) azimuth (horizontal component of the eye movement), Eq (5) latitude (vertical component of the eye movement) and the focalized distance by Eq (6) vergence angles: Azimuth(α)=arctan(SxSz)(4) Latitude(α)=arctan(SySx2+Sz2)(5) Vergence(β)=arctg(DIP/2‖S‖)(6) Where ||S|| was calculated as: ‖S‖=Sx2+Sy2+Sz2(7) Only correct trials were analyzed. Trials with blinks and in which the subject made a saccadic eye movement in the relevant data segment were filtered out. In total there were 4120 trials in the control group and 3112 trials in ADHD group. The final data set consisted of 884 (43%) cue and 1002 (47%) no-cue trials in the control group and 723 (46%) cue and 829 (53%) no-cue trials in the ADHD group. From the eye position data, saccades were detected by using a vector velocity threshold of approximately 200 degrees per second. For statistical analysis t-tests and a multi-comparison ANOVA test were used.
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