- Email: [email protected]
Electrophysiological investigation of two monogenic disorders: RTT and FXS
Symposium abstracts / International Journal of Psychophysiology 69 (2008) 139–205
Electrophysiological investigation of two monogenic disorders: RTT and FXS N.L. Gorbachevskaya, V.Yu. Voinova, A.B. Sorokin, S.A. Tushkevich, N.V. Grigorieva, Yu.B. Yurov Mental Health Research Centre, Moscow University of Psychology and Education, Psychology Institute REA, Moscow, Russia Introduction RTT (Rett syndrome) and FXS (Fragile X syndrome) are severe neurodevelopmental disorders without neurodegenerative signs. FXS is caused by gene FMR1 mutation that leads to a deficiency of the FMR1 protein-translation suppressor that is involved in synaptic plasticity. The FXS associated with mental retardation, ADHD and autism. Rett syndrome is a complex progressive neurological disorder caused by mutations in the Xlinked methyl-CpG-binding protein gene (MECP2)-transcriptional repressor of brain-derived neurotrophic factor. RTT represents a leading cause of disability in females and associated with loss of speech and purposeful hand use, seizures and stereotypic hand movement. The current study examines phenotype–genotype and EEG correlations of RTT and FXS patients. Materials and method: We investigate clinical and QEEG findings of 63 RTT and 30 FXS children using EEG-mapping package “Brainsys” (Russia) and special clinical scale. Results: Clear dynamics of formation of pathological EEG pattern in RTT patients was demonstrated: significant deterioration of occipital and sensory–motor alpha-rhythms at the 2 stage of illness and increase of number EEGs with the bursts of theta activity (4–6 Hz) in central–frontal or central–parietal regions at the third stage. The positive correlation of thetaindex and deterioration of emotional communication and contact was revealed. General phenotype severity in RTT depends on gene MECP2 mutation type and mutation position. RTT patients with truncating mutations at the 3 disease stage demonstrated most severe alpha deterioration and greater number of slow activity then patients with missense mutation. In girl with extremely skewered X-inactivation (2/98) we observed clinical form “fruste” and nearly normal EEG. EEGs of FXS patients 3–19 years contain excessive theta activity (6–8 Hz) mostly in central and parietal regions. Alpha rhythm was significantly deteriorated. After 19 years flattering of EEG with decrease level of alphaactivity revealed. In female patients theta activity level was negatively correlated with IQ. Conclusion: Thus, similar EEG pattern which significantly deteriorates alpha rhythm and prevalence bursts of theta in central and frontal regions was revealed in RTT and FXS patients. This excessive theta rhythm was correlated with more severe illnesses course and may reflect synaptic plasticity deterioration and connections deficit in both disorders. Supported by RGNF grant № 06-06-00639a, Innovation Education Project MGPPU
191
evaluation of lapses in alertness. Tada will describe recent studies of eyeblink frequency patterns in humans and primates over the aging continuum. His research has led to the formulation of a two-factor theoretical model that has implications for the ontogenetic and phylogenetic development of eyeblinks. Andreassi will review the eyeblink component of the startle response as it provides information on activating physiological mechanisms related to attentional, emotional, and psychopathological states. He will describe a theoretical model that accounts for findings on eyeblink startle. Tecce will report on the accuracy of eyeblink rate in the prediction of outcomes of U. S. presidential elections held during the period 1960–2004. He will also describe ocular phenomena that might serve as useful predictor variables in the 2008 election. Rohrbaugh and Fukuda will be discussants.
doi:10.1016/j.ijpsycho.2008.05.512 The EYE: Reflector of attentional processes J.A. Stern, T.B. Brown, S. Kristjansson Washington University, St. Louis, MO. USA We have been studying ocular measures to index signs of alertness loss. Using a modification of the Psychomotor Vigilance Task involving presentation of information at three rather than one location and including a running memory component we have identified a number of bio-behavioral signs of loss of alertness as reflected in performance lapses. We find that blink timing is one such component. We generally inhibit blinking when we anticipate having to respond to events, the breakdown of such inhibition is associated with an attentional lapse. The occurrence of what we refer to as “long closure duration blinks” is another reflector of attentional loss. Saccade duration, the occurrence of slower than normal saccades indexes a period of lowered alertness. Pupil diameter change is yet another such reflector. On the behavioral side, we identify lapses not only by unusually long reaction times but also by the occurrence of responses not associated with the presentation of stimuli, the occurrence of partial responses, as well as changes in response duration. These signs of lapses in alertness generally occur infrequently and are preceded by as well as followed by “normal “responding. There are also marked individual differences in the ability to maintain alertness. The results of our current studies dealing with these issues will be reviewed. Our intent is the development of a bio-behavioral system allowing for the on-line identification of lapses in alertness and providing feedback to the operator about lapse occurrence.
doi:10.1016/j.ijpsycho.2008.05.513 Age and species related differences in blink rate
doi:10.1016/j.ijpsycho.2008.05.511 SYMPOSIUM 34: Psychophysiology of Ocular Phenomena Symposium Chair: Joseph J. Tecce (USA); Co-Chair: John L. Andreassi (USA) Psychophysiology of ocular phenomena J.J. Tecce a, J.L. Andreassi b, J.A. Stern c, H. Tada d, J.W. Rohrbaugh e, K. Fukuda f Boston College, Psychology Department, Chestnut Hill, USA b Baruch College, City University of New York, Psychology Department, New York, USA c Washington University, Department of Psychology, St. Louis, USA d Hakuoh University, Department of Psychology, Oyama-City, Tochigi, Japan e Washington University School of Medicine, Department of Psychiatry, St. Louis, USA f Fukuoka Prefectural University, Department of Human Development & Education, Tagawa-City, Fukuoka, Japan
H. Tada a, Y. Omori b, T. Sugiyama c, K. Hirokawa d, H. Ohira e, M. Tomonaga f Hakuoh Univ., Department of Psychology, Oyama, Japan b Jinai Univ., Department of Psychology, Fukui, Japan c Tohoku Univ., Department of Health Science, Sendai, Japan d Fukuyama Univ., Department of Psychology, Fukuyama, Japan e Nagoya Univ., Department of Psychology, Nagoya, Japan f Kyoto Univ., Primate Research Institute, Inuyama, Japan
a
a
An understanding of the psychophysiology of ocular phenomena depends largely on the study of eye movements from a variety of methodological approaches. In this symposium, participants will provide diverse vantage points to assess the value of ocular research over the past three decades. Stern proposes to deal with the issue of monitoring alterations in alertness using oculomotor parameters. He will touch on how aspects of blinking, saccadic eye movements, and pupil diameter changes can be used for the on-line
To understand the detailed mechanism underlying endogenous eyeblinks, it is necessary to know the course of its development, both ontogeny and phylogeny. We have found few studies dealing with these issues, with much disagreement across studies. We have not, as yet, established standards for blink rate in different age groups, though it has long been known that there are such differences. Thus we conducted two studies to determine average blink rate in specific age groups of humans and other primates searching for psychological and biological origins of the large interindividual differences in blink rate within species. We have collected blink rate information on 1401 human subjects ranging in age from 3 months to 93 years under similar condition of observation. The results are as follows: 1) Blinking was virtually absent at birth, increases steadily until adolescence. It reaches a plateau at about 9 years, and that level is maintained throughout adult life; 2) the distribution of blinks across time differed in each age group; 3) the developmental curves of closing and reopening of the eyes during a blink were similar to that of blink rate, with the exception of 3 months old infants;
Electrophysiological investigation of two monogenic disorders: RTT and FXS N.L. Gorbachevskaya, V.Yu. Voinova, A.B. Sorokin, S.A. Tushkevich, N.V. Grigorieva, Yu.B. Yurov Mental Health Research Centre, Moscow University of Psychology and Education, Psychology Institute REA, Moscow, Russia Introduction RTT (Rett syndrome) and FXS (Fragile X syndrome) are severe neurodevelopmental disorders without neurodegenerative signs. FXS is caused by gene FMR1 mutation that leads to a deficiency of the FMR1 protein-translation suppressor that is involved in synaptic plasticity. The FXS associated with mental retardation, ADHD and autism. Rett syndrome is a complex progressive neurological disorder caused by mutations in the Xlinked methyl-CpG-binding protein gene (MECP2)-transcriptional repressor of brain-derived neurotrophic factor. RTT represents a leading cause of disability in females and associated with loss of speech and purposeful hand use, seizures and stereotypic hand movement. The current study examines phenotype–genotype and EEG correlations of RTT and FXS patients. Materials and method: We investigate clinical and QEEG findings of 63 RTT and 30 FXS children using EEG-mapping package “Brainsys” (Russia) and special clinical scale. Results: Clear dynamics of formation of pathological EEG pattern in RTT patients was demonstrated: significant deterioration of occipital and sensory–motor alpha-rhythms at the 2 stage of illness and increase of number EEGs with the bursts of theta activity (4–6 Hz) in central–frontal or central–parietal regions at the third stage. The positive correlation of thetaindex and deterioration of emotional communication and contact was revealed. General phenotype severity in RTT depends on gene MECP2 mutation type and mutation position. RTT patients with truncating mutations at the 3 disease stage demonstrated most severe alpha deterioration and greater number of slow activity then patients with missense mutation. In girl with extremely skewered X-inactivation (2/98) we observed clinical form “fruste” and nearly normal EEG. EEGs of FXS patients 3–19 years contain excessive theta activity (6–8 Hz) mostly in central and parietal regions. Alpha rhythm was significantly deteriorated. After 19 years flattering of EEG with decrease level of alphaactivity revealed. In female patients theta activity level was negatively correlated with IQ. Conclusion: Thus, similar EEG pattern which significantly deteriorates alpha rhythm and prevalence bursts of theta in central and frontal regions was revealed in RTT and FXS patients. This excessive theta rhythm was correlated with more severe illnesses course and may reflect synaptic plasticity deterioration and connections deficit in both disorders. Supported by RGNF grant № 06-06-00639a, Innovation Education Project MGPPU
191
evaluation of lapses in alertness. Tada will describe recent studies of eyeblink frequency patterns in humans and primates over the aging continuum. His research has led to the formulation of a two-factor theoretical model that has implications for the ontogenetic and phylogenetic development of eyeblinks. Andreassi will review the eyeblink component of the startle response as it provides information on activating physiological mechanisms related to attentional, emotional, and psychopathological states. He will describe a theoretical model that accounts for findings on eyeblink startle. Tecce will report on the accuracy of eyeblink rate in the prediction of outcomes of U. S. presidential elections held during the period 1960–2004. He will also describe ocular phenomena that might serve as useful predictor variables in the 2008 election. Rohrbaugh and Fukuda will be discussants.
doi:10.1016/j.ijpsycho.2008.05.512 The EYE: Reflector of attentional processes J.A. Stern, T.B. Brown, S. Kristjansson Washington University, St. Louis, MO. USA We have been studying ocular measures to index signs of alertness loss. Using a modification of the Psychomotor Vigilance Task involving presentation of information at three rather than one location and including a running memory component we have identified a number of bio-behavioral signs of loss of alertness as reflected in performance lapses. We find that blink timing is one such component. We generally inhibit blinking when we anticipate having to respond to events, the breakdown of such inhibition is associated with an attentional lapse. The occurrence of what we refer to as “long closure duration blinks” is another reflector of attentional loss. Saccade duration, the occurrence of slower than normal saccades indexes a period of lowered alertness. Pupil diameter change is yet another such reflector. On the behavioral side, we identify lapses not only by unusually long reaction times but also by the occurrence of responses not associated with the presentation of stimuli, the occurrence of partial responses, as well as changes in response duration. These signs of lapses in alertness generally occur infrequently and are preceded by as well as followed by “normal “responding. There are also marked individual differences in the ability to maintain alertness. The results of our current studies dealing with these issues will be reviewed. Our intent is the development of a bio-behavioral system allowing for the on-line identification of lapses in alertness and providing feedback to the operator about lapse occurrence.
doi:10.1016/j.ijpsycho.2008.05.513 Age and species related differences in blink rate
doi:10.1016/j.ijpsycho.2008.05.511 SYMPOSIUM 34: Psychophysiology of Ocular Phenomena Symposium Chair: Joseph J. Tecce (USA); Co-Chair: John L. Andreassi (USA) Psychophysiology of ocular phenomena J.J. Tecce a, J.L. Andreassi b, J.A. Stern c, H. Tada d, J.W. Rohrbaugh e, K. Fukuda f Boston College, Psychology Department, Chestnut Hill, USA b Baruch College, City University of New York, Psychology Department, New York, USA c Washington University, Department of Psychology, St. Louis, USA d Hakuoh University, Department of Psychology, Oyama-City, Tochigi, Japan e Washington University School of Medicine, Department of Psychiatry, St. Louis, USA f Fukuoka Prefectural University, Department of Human Development & Education, Tagawa-City, Fukuoka, Japan
H. Tada a, Y. Omori b, T. Sugiyama c, K. Hirokawa d, H. Ohira e, M. Tomonaga f Hakuoh Univ., Department of Psychology, Oyama, Japan b Jinai Univ., Department of Psychology, Fukui, Japan c Tohoku Univ., Department of Health Science, Sendai, Japan d Fukuyama Univ., Department of Psychology, Fukuyama, Japan e Nagoya Univ., Department of Psychology, Nagoya, Japan f Kyoto Univ., Primate Research Institute, Inuyama, Japan
a
a
An understanding of the psychophysiology of ocular phenomena depends largely on the study of eye movements from a variety of methodological approaches. In this symposium, participants will provide diverse vantage points to assess the value of ocular research over the past three decades. Stern proposes to deal with the issue of monitoring alterations in alertness using oculomotor parameters. He will touch on how aspects of blinking, saccadic eye movements, and pupil diameter changes can be used for the on-line
To understand the detailed mechanism underlying endogenous eyeblinks, it is necessary to know the course of its development, both ontogeny and phylogeny. We have found few studies dealing with these issues, with much disagreement across studies. We have not, as yet, established standards for blink rate in different age groups, though it has long been known that there are such differences. Thus we conducted two studies to determine average blink rate in specific age groups of humans and other primates searching for psychological and biological origins of the large interindividual differences in blink rate within species. We have collected blink rate information on 1401 human subjects ranging in age from 3 months to 93 years under similar condition of observation. The results are as follows: 1) Blinking was virtually absent at birth, increases steadily until adolescence. It reaches a plateau at about 9 years, and that level is maintained throughout adult life; 2) the distribution of blinks across time differed in each age group; 3) the developmental curves of closing and reopening of the eyes during a blink were similar to that of blink rate, with the exception of 3 months old infants;