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Usefulness of the measurement of saccadic refixation in the diagnosis of attention-deficit hyperactivity disorder/hyperkinetic disorder in adults

Usefulness of the measurement of saccadic refixation in the diagnosis of attention-deficit... Background: The aim of the research is to evaluate the usefulness of the measurement of saccadic refixation in the diagnosis of attention-deficit hyperactivity disorder (ADHD)/hyperkinetic disorder (HKD) in adults. Methods: Seventy-eight individuals were examined: 40 with ADHD/HKD and 38 healthy ones. A noninvasive eye movement examination using the Saccadometer (Advanced Clinical Instrumentation, Cambridge, UK) was applied. Two saccadic tests, prosaccades task (PT) and antisaccades task (AT), were carried out. Results: Based on the results, we can assume that selected parameters, such as latency, standard deviation of latency, promptness, and correctness (directional errors), in individuals with ADHD/HKD differ statistically in the relevant parameters from the healthy ones. The latency and the standard deviation of latency in ADHD/HKD participants are greater when compared to healthy ones. ADHD/HKD participants have a greater number of directional errors in comparison to healthy ones. Conclusions: The standard deviation of latency prosaccades is a good parameter for distinguishing people from both groups. An important and innovative solution in this study in comparison to the studies of other authors, who reached similar results, is the use of an automatically calibrating system (autonomous) adapted Introduction An important goal of this neuropsychological research is to develop effective diagnostic tools, wherein a correct and precise diagnosis plays a crucial role in the process of choosing the most appropriate pharmacological and nonpharmacological management plan. This is particularly important because the accurate and early diagnosis improves the treatment effectiveness, thus increasing the likelihood of improving health outcomes. The better effectiveness of treatment depends also on the individualization of management and the evaluation of its progress with the application of neuropsychological tests. The aim of the research is to evaluate the usefulness of the measurement of physiological parameters of eye movement (i.e. saccadic refixation) in the diagnosis of attention-deficit hyperactivity disorder (ADHD) and hyperkinetic disorder (HKD). The choice of physiological parameters analyzed in this work is related to the pathogenesis of ADHD/HKD and to the neurophysiological substrate of these syndromes. The symptoms of ADHD/ HKD are associated with impaired cognitive function (attention and working memory) and behavioral disturbances (such as inter alia impulsivity or hyperactivity). Therefore, the evaluation of these functions based on the knowledge of the neuronal substrates of the disorders can be helpful in establishing the correct diagnosis. In questionnaire methods, the results are contaminated by subjective interpretation. In this work, a new method is proposed. The new method is based on the analysis of physiological parameters, which can increase the objectivity of the diagnosis of ADHD/HKD. However, the diagnostic method presented here should be considered complementary to psychological, psychiatric, and *Corresponding author: Piotr Krzysztof Walecki, Jagiellonian University Medical College, Kopernika 7e, Krakow 31-034, Poland, E-mail: piotr.walecki@gmail.com Edward Jacek Gorzelaczyk: Department of Theoretical Basis of Bio-Medical Sciences and Medical Informatics, Nicolaus Copernicus University Collegium Medicum, Bydgoszcz, Poland; Non-Public Health Care Center Sue Ryder Home, Bydgoszcz, Poland; MedsevenOutpatient Addiction Treatment, Bydgoszcz, Poland; and Kazimierz Wielki University, Bydgoszcz, Poland 106Walecki and Gorzelaczyk: Saccadic refixation in attention-deficit hyperactivity disorder in adults neurological examination [1]. The secondary objective of this study is to answer the question of whether the measurement of saccadic eye movements can take place in any hospital or clinic rather than in a specialized laboratory and whether the diagnostic tool can be easily used as a psychiatrist's or physician's assistant device without prolonged training. The research results confirm the occurrence of movement eye disorders in ADHD/HKD. In several studies, significant differences in saccadic parameters of the eye movement between people with ADHD/HKD and healthy ones were observed [2­22]. In some studies, there were no statistically significant differences in saccadic parameters between people with ADHD/HKD and healthy ones [23­26]. Although most studies have been found statistically significant differences in parameters of eye movement, the results may vary and are not conclusive. To conduct the study, the consent of the Bioethics Commission at Jagiellonian University Medical College in Krakow was obtained (consent no. KBET/50/B/2008). Results A summary of the test results is shown in Tables 1 and 2. Based on the results, it is possible to assume that selected parameters such as latency, standard deviation of latency, promptness [27, 28], and correctness (directional errors) in individuals with ADHD/HKD differ statistically from the relevant parameters in healthy subjects. Latency is a good parameter for distinguishing people from both groups. In the PT, the latency in ADHD participants was greater by 30% when compared to the healthy subjects. In the AT, ADHD was greater by 26% in comparison to healthy subjects. In the PT, the standard deviation of latency in ADHD participants was greater by 150% when compared to healthy subjects. In the AT, ADHD was greater by 77% in comparison to healthy subjects. Also, statistically significant differences between the two groups in the promptness and correctness occurred. In the PT and AT, ADHD participants were characterized by smaller promptness by 11% when compared to healthy subjects. In the PT, ADHD participants had a greater number of directional errors by 178% in comparison to healthy subjects. In the AT, ADHD participants had a greater number of directional errors by 74% compared to healthy subjects. Materials and methods A noninvasive eye movement examination with the implementation of the Saccadometer (Advanced Clinical Instrumentation, Cambridge, UK) was applied. The Saccadometer System enables the easy and quick collection of saccadic response parameters with a minimal influence of the subject's fatigue. It records the position of the globes with the time resolution of 1 ms (1000 Hz). The eye movement measurement is automated and synchronized with the presentation of the stimuli. The examiner's participation is reduced to the role for checking correct sensor placement and giving instructions. The calibration of the eye movement relies on the fixed angular separation between targets and the vestibulo-ocular reflex cancellation response, which ensures that the head movements do not influence the target position in relation to the eyes (no head restraints needed). The device projects three laser spot targets with 10° separation. The target steps randomly to the left or right, with a randomized fore-period. When the resultant saccade is detected, the next trial begins automatically. The two following saccadic tests were carried out: prosaccades task (PT) and antisaccades task (AT). Each test consisted of 10 trials for calibration and 50 trials of the measurement. In total, 120 responses to stimuli were evoked in each person. The PT and AT tests were carried out in two distinguished research groups. Forty adults (age 22±7 years) with ADHD and 38 healthy controls matched in terms of demographic characteristics were examined. Table 1:Comparison of average values of PT in patients with ADHD/ HKD and healthy ones. Parameters Results ADHD/HKD C ADHD/HKD>C None ADHD/HKD>C None p=0.024080 p=0.016662 p=0.000001 ­ p=0.000000 ­ p=0.002499 ­ ­ ­ ­ ­ ­ ­ Number of correct saccades Number of incorrect saccades Latency of correct saccades Latency of incorrect saccades Standard deviation of latency of correct saccades Standard deviation of latency of incorrect saccades Promptness of correct saccades Promptness of incorrect saccades Duration of correct saccades Duration of incorrect saccades Amplitude of correct saccades Amplitude of incorrect saccades Peak velocity of correct saccades Peak velocity of incorrect saccades ADHD/HKD<C None None None None None None None Walecki and Gorzelaczyk: Saccadic refixation in attention-deficit hyperactivity disorder in adults107 Table 2:Comparison of average values of AT in patients with ADHD/ HKD and healthy ones. Parameters Results ADHD/HKD C ADHD/HKD>C ADHD/HKD>C ADHD/HKD>C ADHD/HKD>C ADHD/HKD<C ADHD/HKD<C None ADHD/HKD 0.9) and in the proposed cutoff point of 116 ms (above this value; ADHD/HKD diagnosis) has high sensitivity (Sn; 82%), high specificity (Sp; 88%), low false-positives (FP; 12%), high accuracy (ACC; 87%), high positive predictive value Receiver operating characteristic (ROC) The proposed cut-off point: 116 1.0 116 0.8 True positive rate (sensitivity) 0.0 0.0 0.2 0.4 0.6 0.8 1.0 False positive rate (100-specificity) Figure 1:ROC analysis of the standard deviation of correct prosaccades latency. 108Walecki and Gorzelaczyk: Saccadic refixation in attention-deficit hyperactivity disorder in adults Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. 14. Karatekin C. Improving antisaccade performance in adolescents with attention-deficit/hyperactivity disorder (ADHD). Exp Brain Res 2006;174:324­41. 15. Rommelse NN, Van der Stigchel S, Witlox J, Geldof C, Deijen J-B, Theeuwes J, et al. Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers. J Neural Transm 2008;115:249­60. 16. Mahone EM, Mostofsky SH, Lasker AG, Zee D, Denckla MB. Oculomotor anomalies in attention-deficit/hyperactivity disorder: evidence for deficits in response preparation and inhibition. J Am Acad Child Adolesc Psychiatry 2009;48:749­56. 17. Goto Y, Hatakeyama K, Kitama T, Sato Y, Kanemura H, Aoyagi K, et al. Saccade eye movements as a quantitative measure of frontostriatal network in children with ADHD. Brain Dev 2010;32:347­55. 18. Walecki P, Gorzelanczyk EJ. Differences of saccadic refixations in ADHD/HKD and non-ADHD individuals. J Neurol 2011;258:128. 19. Walecki P, Gorzelaczyk EJ. P-349 ­ using saccadometry to enhance effectively diagnosis of ADHD. Eur Psychiatry 2012;27:1. 20. White T, Mous S, Karatekin C. Memory-guided saccades in youth-onset psychosis and attention deficit hyperactivity disorder (ADHD). Early Interv Psychiatry 2014;8:229­39. 21. Damyanovich EV, Baziyan BK, Sagalov MV, Kumskova GA. Saccadic movements of the eyes in children with attention deficit and hyperactivity syndrome. Bull Exp Biol Med 2013;156:25­8. 22. Lee Y-J, Lee S, Chang M, Kwak H-W. Saccadic movement deficiencies in adults with ADHD tendencies. Atten Defic Hyperact Disord 2015;7:271­80. 23. Rothlind JC, Posner MI, Schaughency EA. Lateralized control of eye movements in attention deficit hyperactivity disorder. J Cognit Neurosci 1991;3:377­81. 24. Karatekin C, Asarnow RF. Components of visual search in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder. J Abnorm Child Psychol 1998;26:367­80. 25. Aman CJ, Roberts RJ, Pennington BF. A neuropsychological examination of the underlying deficit in attention deficit hyperactivity disorder: frontal lobe versus right parietal lobe theories. Dev Psychol 1998;34:956­69. 26. Hanisch C, Radach R, Holtkamp K, Herpertz-Dahlmann B, Konrad K. Oculomotor inhibition in children with and without attention-deficit hyperactivity disorder (ADHD). J Neural Transm 2006;113:671­84. 27. Carpenter RH, McDonald SA. LATER predicts saccade latency distributions in reading. Exp Brain Res 2007;177:176­83. 28. Perneczky R, Ghosh BC, Hughes L, Carpenter RH, Barker RA, Rowe JB. Saccadic latency in Parkinson's disease correlates with executive function and brain atrophy, but not motor severity. Neurobiol Dis 2011;43:79­85. 29. Karatekin C. Eye tracking studies of normative and atypical development. Dev Rev 2007;27:283­348. 30. Rommelse NN, Van der Stigchel S, Sergeant JA. A review on eye movement studies in childhood and adolescent psychiatry. Brain Cognit 2008;68:391­414. 31. Gorzelaczyk EJ, Walecki P, Feit J, Kunc M, Fareed A. Improvement of saccadic functions after dosing with methadone in opioid addicted individuals. J Addict Dis 2016;35:52­7. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Bio-Algorithms and Med-Systems de Gruyter

Usefulness of the measurement of saccadic refixation in the diagnosis of attention-deficit hyperactivity disorder/hyperkinetic disorder in adults

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de Gruyter
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Abstract

Background: The aim of the research is to evaluate the usefulness of the measurement of saccadic refixation in the diagnosis of attention-deficit hyperactivity disorder (ADHD)/hyperkinetic disorder (HKD) in adults. Methods: Seventy-eight individuals were examined: 40 with ADHD/HKD and 38 healthy ones. A noninvasive eye movement examination using the Saccadometer (Advanced Clinical Instrumentation, Cambridge, UK) was applied. Two saccadic tests, prosaccades task (PT) and antisaccades task (AT), were carried out. Results: Based on the results, we can assume that selected parameters, such as latency, standard deviation of latency, promptness, and correctness (directional errors), in individuals with ADHD/HKD differ statistically in the relevant parameters from the healthy ones. The latency and the standard deviation of latency in ADHD/HKD participants are greater when compared to healthy ones. ADHD/HKD participants have a greater number of directional errors in comparison to healthy ones. Conclusions: The standard deviation of latency prosaccades is a good parameter for distinguishing people from both groups. An important and innovative solution in this study in comparison to the studies of other authors, who reached similar results, is the use of an automatically calibrating system (autonomous) adapted Introduction An important goal of this neuropsychological research is to develop effective diagnostic tools, wherein a correct and precise diagnosis plays a crucial role in the process of choosing the most appropriate pharmacological and nonpharmacological management plan. This is particularly important because the accurate and early diagnosis improves the treatment effectiveness, thus increasing the likelihood of improving health outcomes. The better effectiveness of treatment depends also on the individualization of management and the evaluation of its progress with the application of neuropsychological tests. The aim of the research is to evaluate the usefulness of the measurement of physiological parameters of eye movement (i.e. saccadic refixation) in the diagnosis of attention-deficit hyperactivity disorder (ADHD) and hyperkinetic disorder (HKD). The choice of physiological parameters analyzed in this work is related to the pathogenesis of ADHD/HKD and to the neurophysiological substrate of these syndromes. The symptoms of ADHD/ HKD are associated with impaired cognitive function (attention and working memory) and behavioral disturbances (such as inter alia impulsivity or hyperactivity). Therefore, the evaluation of these functions based on the knowledge of the neuronal substrates of the disorders can be helpful in establishing the correct diagnosis. In questionnaire methods, the results are contaminated by subjective interpretation. In this work, a new method is proposed. The new method is based on the analysis of physiological parameters, which can increase the objectivity of the diagnosis of ADHD/HKD. However, the diagnostic method presented here should be considered complementary to psychological, psychiatric, and *Corresponding author: Piotr Krzysztof Walecki, Jagiellonian University Medical College, Kopernika 7e, Krakow 31-034, Poland, E-mail: piotr.walecki@gmail.com Edward Jacek Gorzelaczyk: Department of Theoretical Basis of Bio-Medical Sciences and Medical Informatics, Nicolaus Copernicus University Collegium Medicum, Bydgoszcz, Poland; Non-Public Health Care Center Sue Ryder Home, Bydgoszcz, Poland; MedsevenOutpatient Addiction Treatment, Bydgoszcz, Poland; and Kazimierz Wielki University, Bydgoszcz, Poland 106Walecki and Gorzelaczyk: Saccadic refixation in attention-deficit hyperactivity disorder in adults neurological examination [1]. The secondary objective of this study is to answer the question of whether the measurement of saccadic eye movements can take place in any hospital or clinic rather than in a specialized laboratory and whether the diagnostic tool can be easily used as a psychiatrist's or physician's assistant device without prolonged training. The research results confirm the occurrence of movement eye disorders in ADHD/HKD. In several studies, significant differences in saccadic parameters of the eye movement between people with ADHD/HKD and healthy ones were observed [2­22]. In some studies, there were no statistically significant differences in saccadic parameters between people with ADHD/HKD and healthy ones [23­26]. Although most studies have been found statistically significant differences in parameters of eye movement, the results may vary and are not conclusive. To conduct the study, the consent of the Bioethics Commission at Jagiellonian University Medical College in Krakow was obtained (consent no. KBET/50/B/2008). Results A summary of the test results is shown in Tables 1 and 2. Based on the results, it is possible to assume that selected parameters such as latency, standard deviation of latency, promptness [27, 28], and correctness (directional errors) in individuals with ADHD/HKD differ statistically from the relevant parameters in healthy subjects. Latency is a good parameter for distinguishing people from both groups. In the PT, the latency in ADHD participants was greater by 30% when compared to the healthy subjects. In the AT, ADHD was greater by 26% in comparison to healthy subjects. In the PT, the standard deviation of latency in ADHD participants was greater by 150% when compared to healthy subjects. In the AT, ADHD was greater by 77% in comparison to healthy subjects. Also, statistically significant differences between the two groups in the promptness and correctness occurred. In the PT and AT, ADHD participants were characterized by smaller promptness by 11% when compared to healthy subjects. In the PT, ADHD participants had a greater number of directional errors by 178% in comparison to healthy subjects. In the AT, ADHD participants had a greater number of directional errors by 74% compared to healthy subjects. Materials and methods A noninvasive eye movement examination with the implementation of the Saccadometer (Advanced Clinical Instrumentation, Cambridge, UK) was applied. The Saccadometer System enables the easy and quick collection of saccadic response parameters with a minimal influence of the subject's fatigue. It records the position of the globes with the time resolution of 1 ms (1000 Hz). The eye movement measurement is automated and synchronized with the presentation of the stimuli. The examiner's participation is reduced to the role for checking correct sensor placement and giving instructions. The calibration of the eye movement relies on the fixed angular separation between targets and the vestibulo-ocular reflex cancellation response, which ensures that the head movements do not influence the target position in relation to the eyes (no head restraints needed). The device projects three laser spot targets with 10° separation. The target steps randomly to the left or right, with a randomized fore-period. When the resultant saccade is detected, the next trial begins automatically. The two following saccadic tests were carried out: prosaccades task (PT) and antisaccades task (AT). Each test consisted of 10 trials for calibration and 50 trials of the measurement. In total, 120 responses to stimuli were evoked in each person. The PT and AT tests were carried out in two distinguished research groups. Forty adults (age 22±7 years) with ADHD and 38 healthy controls matched in terms of demographic characteristics were examined. Table 1:Comparison of average values of PT in patients with ADHD/ HKD and healthy ones. Parameters Results ADHD/HKD C ADHD/HKD>C None ADHD/HKD>C None p=0.024080 p=0.016662 p=0.000001 ­ p=0.000000 ­ p=0.002499 ­ ­ ­ ­ ­ ­ ­ Number of correct saccades Number of incorrect saccades Latency of correct saccades Latency of incorrect saccades Standard deviation of latency of correct saccades Standard deviation of latency of incorrect saccades Promptness of correct saccades Promptness of incorrect saccades Duration of correct saccades Duration of incorrect saccades Amplitude of correct saccades Amplitude of incorrect saccades Peak velocity of correct saccades Peak velocity of incorrect saccades ADHD/HKD<C None None None None None None None Walecki and Gorzelaczyk: Saccadic refixation in attention-deficit hyperactivity disorder in adults107 Table 2:Comparison of average values of AT in patients with ADHD/ HKD and healthy ones. Parameters Results ADHD/HKD C ADHD/HKD>C ADHD/HKD>C ADHD/HKD>C ADHD/HKD>C ADHD/HKD<C ADHD/HKD<C None ADHD/HKD 0.9) and in the proposed cutoff point of 116 ms (above this value; ADHD/HKD diagnosis) has high sensitivity (Sn; 82%), high specificity (Sp; 88%), low false-positives (FP; 12%), high accuracy (ACC; 87%), high positive predictive value Receiver operating characteristic (ROC) The proposed cut-off point: 116 1.0 116 0.8 True positive rate (sensitivity) 0.0 0.0 0.2 0.4 0.6 0.8 1.0 False positive rate (100-specificity) Figure 1:ROC analysis of the standard deviation of correct prosaccades latency. 108Walecki and Gorzelaczyk: Saccadic refixation in attention-deficit hyperactivity disorder in adults Research funding: None declared. Employment or leadership: None declared. Honorarium: None declared. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication. 14. Karatekin C. Improving antisaccade performance in adolescents with attention-deficit/hyperactivity disorder (ADHD). Exp Brain Res 2006;174:324­41. 15. Rommelse NN, Van der Stigchel S, Witlox J, Geldof C, Deijen J-B, Theeuwes J, et al. Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers. J Neural Transm 2008;115:249­60. 16. Mahone EM, Mostofsky SH, Lasker AG, Zee D, Denckla MB. Oculomotor anomalies in attention-deficit/hyperactivity disorder: evidence for deficits in response preparation and inhibition. J Am Acad Child Adolesc Psychiatry 2009;48:749­56. 17. Goto Y, Hatakeyama K, Kitama T, Sato Y, Kanemura H, Aoyagi K, et al. Saccade eye movements as a quantitative measure of frontostriatal network in children with ADHD. Brain Dev 2010;32:347­55. 18. Walecki P, Gorzelanczyk EJ. Differences of saccadic refixations in ADHD/HKD and non-ADHD individuals. J Neurol 2011;258:128. 19. Walecki P, Gorzelaczyk EJ. P-349 ­ using saccadometry to enhance effectively diagnosis of ADHD. Eur Psychiatry 2012;27:1. 20. White T, Mous S, Karatekin C. Memory-guided saccades in youth-onset psychosis and attention deficit hyperactivity disorder (ADHD). Early Interv Psychiatry 2014;8:229­39. 21. Damyanovich EV, Baziyan BK, Sagalov MV, Kumskova GA. Saccadic movements of the eyes in children with attention deficit and hyperactivity syndrome. Bull Exp Biol Med 2013;156:25­8. 22. Lee Y-J, Lee S, Chang M, Kwak H-W. Saccadic movement deficiencies in adults with ADHD tendencies. Atten Defic Hyperact Disord 2015;7:271­80. 23. Rothlind JC, Posner MI, Schaughency EA. Lateralized control of eye movements in attention deficit hyperactivity disorder. J Cognit Neurosci 1991;3:377­81. 24. Karatekin C, Asarnow RF. Components of visual search in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder. J Abnorm Child Psychol 1998;26:367­80. 25. Aman CJ, Roberts RJ, Pennington BF. A neuropsychological examination of the underlying deficit in attention deficit hyperactivity disorder: frontal lobe versus right parietal lobe theories. Dev Psychol 1998;34:956­69. 26. Hanisch C, Radach R, Holtkamp K, Herpertz-Dahlmann B, Konrad K. Oculomotor inhibition in children with and without attention-deficit hyperactivity disorder (ADHD). J Neural Transm 2006;113:671­84. 27. Carpenter RH, McDonald SA. LATER predicts saccade latency distributions in reading. Exp Brain Res 2007;177:176­83. 28. Perneczky R, Ghosh BC, Hughes L, Carpenter RH, Barker RA, Rowe JB. Saccadic latency in Parkinson's disease correlates with executive function and brain atrophy, but not motor severity. Neurobiol Dis 2011;43:79­85. 29. Karatekin C. Eye tracking studies of normative and atypical development. Dev Rev 2007;27:283­348. 30. Rommelse NN, Van der Stigchel S, Sergeant JA. A review on eye movement studies in childhood and adolescent psychiatry. Brain Cognit 2008;68:391­414. 31. Gorzelaczyk EJ, Walecki P, Feit J, Kunc M, Fareed A. Improvement of saccadic functions after dosing with methadone in opioid addicted individuals. J Addict Dis 2016;35:52­7.

Journal

Bio-Algorithms and Med-Systemsde Gruyter

Published: Sep 1, 2016

References