I.P. Pavlov Journal of Higher Nervous ActivityI.P. Pavlov Journal of Higher Nervous ActivityЖурнал высшей нервной деятельности им. И.П. Павлова0044-46773034-5316The Russian Academy of Sciences65205010.31857/S0044467723010070GJGLQNФИЗИОЛОГИЯ ВЫСШЕЙ НЕРВНОЙ (КОГНИТИВНОЙ) ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКАФИЗИОЛОГИЯ ВЫСШЕЙ НЕРВНОЙ (КОГНИТИВНОЙ) ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКАASSOCIATION OF THE ZNF804A rs1344706 GENE POLYMORPHISM WITH THE INDUCED EEG RHYTHMS IN VISUAL PERCEPTION OF THE VERBAL STIMULI IN HEALTHY SUBJECTS AND IN SCHIZOPHRENIAАссоциация полиморфизма rs1344706 гена ZNF804A c индуцированными изменениями ритмов ЭЭГ при зрительном восприятии вербальных стимулов у здоровых испытуемых и больных шизофрениейGarakhZh. V.ГарахЖ. В.garakh@yandex.ruGolimbetV. E.ГолимбетВ. Е.garakh@yandex.ruLarionovaE. V.ЛарионоваЕ. В.garakh@yandex.ruLezheikoT. V.ЛежейкоТ. В.garakh@yandex.ruStreletsV. B.СтрелецВ. Б.garakh@yandex.ruZaytsevaYu.ЗайцеваЮ. С.garakh@yandex.ruInstitute of Higher Nervous Activity and Neurophysiology Russian Academy of ScienceФедеральное государственное бюджетное учреждение науки Институт Высшей Нервной Деятельности и Нейрофизиологии РАНMental Health Research CenterФедеральное государственное бюджетное научное учреждение “Научный центр психического здоровья”National Institute of Mental HealthНациональный центр психического здоровья3rd Faculty of Medicine, Charles University in Prague3-й лечебный факультет, Карлов университет в Праге01012023731385102022025Copyright ©; 2023, Ж.В. Гарах, В.Е. Голимбет, Е.В. Ларионова, Т.В. Лежейко, В.Б. Стрелец, Ю.С. ЗайцеваCopyright ©; 2023, Ж.В. Гарах, В.Е. Голимбет, Е.В. Ларионова, Т.В. Лежейко, В.Б. Стрелец, Ю.С. Зайцева2023Ж.В. Гарах, В.Е. Голимбет, Е.В. Ларионова, Т.В. Лежейко, В.Б. Стрелец, Ю.С. ЗайцеваЖ.В. Гарах, В.Е. Голимбет, Е.В. Ларионова, Т.В. Лежейко, В.Б. Стрелец, Ю.С. Зайцеваhttps://innoscience.ru/0044-4677/article/view/652050

We studied the relationship between the ZNF804A rs1344706 gene polymorphism and the parameters of event-related synchronization/desynchronization of EEG rhythms in visual perception of semantic and meaningless verbal information in patients with schizophrenia and schizophrenia spectrum disorders (n = 93) and mentally healthy subjects (n = 93). When reading verbal information regardless of psychiatric status, the theta rhythm synchronization was less pronounced in subjects with the AA genotype than in carriers of allele C. In healthy subjects, the carriers of the AA genotype, in comparison with carriers of allele C, the synchronization of theta rhythm in the posterior cortical areas of the left hemisphere was reduced, and there were no differences in the synchronization of gamma and desynchronization of mu rhythms when perceiving semantic and nonsensical verbal information. In patients with genotype AA, compared with carriers of allele C, the desynchronization of mu rhythm was smaller, which correlated with the severity of poverty of speech on the PANSS scale. The study results indicate a modulating effect of the rs1344706 polymorphism of the ZNF804A gene on the neurophysiological characteristics of the reading process and its contribution to the variability of clinically expressed language disorders.

Изучена ассоциация полиморфизма rs1344706 гена ZNF804A с параметрами синхронизации/десинхронизации ритмов ЭЭГ при зрительном восприятии смысловой и бессмысленной вербальной информации у больных шизофренией и расстройствами шизофренического спектра (n = 93) и психически здоровых испытуемых (n = 93). Установлено, что при чтении вербальной информации вне зависимости от психического статуса у испытуемых с генотипом АА синхронизация тета-ритма меньше, чем у носителей аллеля С. У здоровых испытуемых – носителей генотипа АА, по сравнению с носителями варианта С, снижена синхронизация тета-ритма в задних корковых областях левого полушария, а также отсутствуют различия синхронизации гамма- и десинхронизации мю-ритмов при восприятии смысловой и бессмысленной вербальной информацией. У пациентов – носителей варианта АА, по сравнению с носителями варианта С, меньше степень десинхронизации мю-ритма, что коррелирует с выраженностью речевых нарушений по шкале PANSS. Результаты исследования свидетельствуют о модулирующем эффекте полиморфизма rs1344706 гена ZNF804A на нейрофизиологические характеристики процесса чтения и его вкладе в вариативность клинически выраженных речевых нарушений.

gene ZNF804Atheta-rhythmgamma-rhythmmu-rhythmEEGschizophreniareadingген ZNF804Aтета-ритмгамма-ритммю-ритмЭЭГшизофрениячтениеГолимбет В.Е., Гарах Ж.В., Коровайцева Г.И., Лежейко Т.В., Зайцева Ю.С., Гурович И.Я., Шмуклер А.Б., Родионов Г.И., Стрелец В.Б. Связь генов нейротрофического мозгового фактора и переносчика серотонина с параметрами ранних компонентов вызванных потенциалов при пассивном восприятии слов. Журн. высш. нервн. деят. им. И.П. Павлова. 2016. 66 (5): 556–564.Ларионова Е.В., Гарах Ж.В., Зайцева Ю.С. Мю-ритм в современных исследованиях: теоретические и методологические аспекты. Журн. высш. нервн. деят. им. И.П. Павлова. 2022. 72 (1): 3–27.Лежейко Т.В., Габаева М.В., Колесина Н.Ю., Голимбет В.Е. Исследование влияния гена ZNF804А и родовых осложнений на клинические особенности шизофрении. Генетика. 2019. 55 (6): 701–706.Лежейко Т.В., Габаева М.В., Крикова Е.В., Голимбет В.Е. Полиморфизм гена ZNF804A rs1344706 и клиническая гетерогенность шизофрении. Научные результаты биомедицинских исследований. 2020. 6 (1): 51–62.Новотоцкий-Власов В.Ю. Анализ постстимульных изменений ЭЭГ, не выявляемых методом когерентного накопления. Диссертация к.б.н. 2000.Стрелец В.Б., Гарах Ж.В., Марьина И.В., Зайцева Ю.С., Гурович И.Я. Временны́е характеристики начальной стадии обработки вербальной информации в норме и при шизофрении. Журн. высш. нервн. деят. им. И.П. Павлова. 2012. 62 (2): 165–173.Agosta S., Magnago D., Tyler S., Grossman E. The pivotal role of the right parietal lobe in temporal attention. Journal of Cognitive Neuroscience. 2017. 29: 805–815.Alday P.M., Kretzschmar F. Speed-Accuracy Tradeoffs in Brain and Behavior: Testing the Independence of P300 and N400 Related Processes in Behavioral Responses to Sentence Categorization. Frontiers in Human Neuroscience. 2019. 13.Anitha A., Thanseem I., Nakamura K., Vasu M.M., Yamada K., Ueki T., Iwayama Y., Toyota T., Tsuchiya K.J., Iwata Y., Suzuki K., Sugiyama T., Tsujii M., Yoshikawa T., Mori N. Zinc finger protein 804A (ZNF804A) and verbal deficits in individuals with autism. Journal of psychiatry & neuroscience: JPN. 2014. 39 (5): 294–303.Araki T., Hirata M., Yanagisawa T., Sugata H., Onishi M., Watanabe Y., Ogata S., Honda C., Hayakawa K., Yorifuji Sh. Language-related cerebral oscillatory changes are influenced equally by genetic and environmental factors. Neuroimage. 2016. 142: 241–247.Bastiaansen M., Hagoort P. Oscillatory neuronal dynamics during language comprehension. Progress in brain research. 2006. 159: 179–196.Becker J., Czamara D., Hoffmann P., Landerl K., Blomert L., Brandeis D., Vaessen A., Maurer U., Moll K., Ludwig K.U., Müller-Myhsok B., Nöthen M.M., Schulte-Körne G., Schumacher J. Evidence for the involvement of ZNF804A in cognitive processes of relevance to reading and spelling. Translational psychiatry. 2012. 2 (7): e136.Benjamini Y., Hochberg Y. Controlling the false discovery rate – a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B. 1995. 57: 289–300.Brem S., Bach S., Kucian K., Guttorm T.K., Martin E., Lyytinen H., Brandeis D., Richardson U. Brain sensitivity to print emerges when children learn letter-speech sound correspondences. Proc. Natl. Acad. Sci. USA. 2010. 107 (17): 7939–7944.Carreiras M., Armstrong B.C., Perea M., Frost R. The what, when, where, and how of visual word recognition. Trends Cogn. Sci. 2014. 18 (2): 90–98.Chang H., Xiao X., Li M. The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms and neuronal functions. Mol Psychiatry. 2017. 22: 944–953.De Boer J.N., van Hoogdalem M., Mandl R.C.W., Brummelman J., Voppel A.E., Begemann M.J.H., Voppel A.E., Begemann M.J.H., van Dellen E., Wijnen F.N.K., Sommer I.E.C. Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts. npj Schizophrenia. 2020. 6 (1): 1–10.Dehaene S., Cohen L. The unique role of the visual word form area in reading. Trends in Cognitive Sciences. 2011. 15 (6): 254–262.DeLisi L.E. Historical pursuits of the language pathway hypothesis of schizophrenia. npj Schizophr. 2021. 7: 53.Dias E.C., Sheridan H., Martínez A., Sehatpour P., Silipo G., Rohrig S., Hochman A., Butler P.D., Hoptman M.J., Revheim N., Javitt D.C. Neurophysiological, Oculomotor, and Com-putational Modeling of Impaired Reading Ability in Schizophrenia. Schizophrenia bulletin. 2021. 47 (1): 97–107.Du J., Palaniyappan L., Liu Z., Cheng W., Gong W., Zhu M., Feng J. The genetic determinants of language network dysconnectivity in drug-naïve early stage schizophrenia. npj Schizophr. 2021. 7(1): 1–10.Ford J. Schizophrenia: The broken P300 and beyond. Psychophysiology. 1999. 36 (6): 667–682.Fraga González G., Van der Molen M.J.W., Žarić G., Bonte M., Tijms J., Blomert L., Stam C.J., Van der Molen M.W. Graph analysis of EEG resting state functional networks in dyslexic readers. Clin Neurophysiol. 2016. 127 (9): 3165–3175.Garagnani M., Lucchese G., Tomasello R., Wennekers T., Pulvermüller F. A Spiking Neurocomputational Model of High-Frequency Oscillatory Brain Responses to Words and Pseudowords. Frontiers in Computational Neuroscience. 2017. 10: 145.Garakh Z., Novototsky-Vlasov V., Larionova E., Zaytseva Y. Mu rhythm separation from the mix with alpha rhythm: Principal component analyses and factor topography. Journal of Neuroscience Methods. 2020. 346: 108892.Golimbet V., Garakh Zh., Zaytseva Y., Alfimova M., Lezheiko T., Kondratiev N., Shmukler A., Gurovich I., Strelets V.B. The Dopamine Receptor D2 C957T Polymorphism Modulates Early Components of Event-Related Potentials in Visual Word Recognition Task. Neuropsychobiology. 2018. 76: 143–150.Goto T., Hirata M., Umekawa Y., Yanagisawa T., Shayne M., Saitoh Y., Kishima H., Yorifuji S., Yoshimine T. Frequency-dependent spatiotemporal distribution of cerebral oscillatory changes during silent reading: a magnetoencephalograhic group analysis. Neuroimage. 2011 54 (1): 560–567.Hald L.A., Bastiaansen M., Hagoort P. EEG theta and gamma responses to semantic violations in online sentence processing. Brain and Language. 2006. 96 (1): 90–105.Hauk O., Pulvermuller F. Neurophysiological distinction of action words in the fronto-central cortex. Hum. Brain Mapp. 2004. 21: 191–201.Hederih J., Nuninga J.O., van Eijk K., van Dellen E., Smit D.J.A., Oranje B., Luykx J.J. Genetic underpinnings of schizophrenia-related electroencephalographical interme-diate phenotypes: A systematic review and meta-analysis. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2021. 104: 110001.Hess J.L., Glatt S.J. How might ZNF804A variants influence risk for schizophrenia and bipolar disorder? A literature review, synthesis, and bioinformatic analysis. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2014. 165B: 28–40.Huang Y., Huang J., Zhou Q.X., Yang C.X., Yang C.P., Mei W.Y., Ding Y.Q. ZFP804A mutant mice display sex-dependent schizophrenia-like behaviors. Molecular psychiatry. 2020. 1–19.Jeon Y.W., Polich J. Meta-analysis of P300 and schizophrenia: Patients, paradigms, and practical implications. Psychophysiology. 2003. 40 (5): 684–701.Kay S.R., Fizbein A., Opler L.A. The Positive and Negative Symptom Scale (PANSS) for schizophrenia. Schizophr. Bull. 1987. 13: 261–276.Lewis A.G., Wang L., Bastiaansen M. Fast oscillatory dynamics during language comprehension: Unification versus maintenance and prediction? Brain Lang. 2015. 148: 51–63.Linden D.E., Lancaster T.M., Wolf C., Baird A., Jackson M.C., Johnston S.J., Thome J. ZNF804A genotype modulates neural activity during working memory for faces. Neuropsychobiology. 2013. 67 (2): 84–92.Meyer L., Grigutsch M., Schmuck N., Gaston P., Friederici A.D. Frontal-posterior theta oscillations reflect memory retrieval during sentence comprehension. Cortex. 2015. 71: 205–218.Moreno I., de Vega M., León I. Understanding action language modulates oscillatory mu and beta rhythms in the same way as observing actions. Brain Cogn. 2013. 82 (3): 236–242.Murphy E., Benítez-Burraco A. Language deficits in schizophrenia and autism as related oscillatory connectomopathies: an evolutionary account. Neuroscience & Biobehavioral Reviews. 2017. 83: 742–764.Murphy E., Benítez-Burraco A. Toward the Language Oscillogenome. Frontiers in psychology. 2018. 9: 1999.Nicodemus K.K., Elvevåg B., Foltz P.W., Rosenstein M., Diaz-Asper C., Weinberger D.R. Category fluency, latent semantic analysis and schizophrenia: a candidate gene approach. Cortex. 2014. 55: 182–191.O’Donovan M.C., Craddock N., Norton N., Williams H., Peirce T., Moskvina V., Nikolov I., Hamshere M., Carroll L., Georgieva L. Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nat Genet. 2008. 40 (9): 1053–1055.Oliveira D.S., Saltuklaroglu T., Thornton D., Jenson D., Harkrider A.W., Rafferty M.B., Casenhiser D.M. Mu rhythm dynamics suggest automatic activation of motor and premotor brain regions during speech processing. Journal of Neurolinguistics. 2021. 60: 101006.Palaniyappan L., Du J., Zhang J., Feng J. Reply to: “Historical pursuits of the language pathway hypothesis of schizophrenia”. NPJ schizophrenia. 2021. 7 (1): 1–3.Pfurtscheller G., Lopes da Silva F.H. Event-related EEG/MEG synchronization and desynchronization: Basic principles. Clinical Neurophysiology. 1999. 110 (11): 1842–1857.Pinel P., Lalanne C., Bourgeron T., Fauchereau F., Poupon C., Artiges E., Dehaene S. Genetic and environmental influences on the visual word form and fusiform face areas. Cerebral Cortex. 2015. 25 (9): 2478–2493.Poeppel D., Emmorey K., Hickok G., Pylkkänen L. Towards a new neurobiology of language. J. Neurosci. 2012. 32 (41): 14125–14131.Revheim N., Corcoran C.M., Dias E., Hellmann E., Martinez A., Butler P.D., Lehrfeld J.M., DiCostanzo J., Albert J., Javitt D.C. Reading deficits in schizophrenia and individuals at high clinical risk: relationship to sensory function, course of illness, and psychosocial outcome. The American journal of psychiatry. 2014. 171 (9): 949–959.Rommers J., Dijkstra T., Bastiaansen M. Context-dependent semantic processing in the human brain: Evidence from idiom comprehension. Journal of Cognitive Neuroscience. 2013. 25 (5): 762–776.Saville C.W., Lancaster T.M., Davies T.J., Toumaian M., Pappa E., Fish S., Feige B., Bender S., Mantripragada K.K., Linden D.E., Klein C. Elevated P3b latency variability in carriers of ZNF804A risk allele for psychosis. Neuroimage. 2015. 116: 207–213.Smit D.J., Boersma M., van Beijsterveldt C.E., Posthuma D., Boomsma D.I., Stam C.J., de Geus E.J. Endophenotypes in a dynamically connected brain. Behav Genet. 2010. 40 (2): 167–177.Takashima A., Ohta K., Matsushima E., Toru M. The event-related potentials elicit-ed by content and function words during the reading of sentences by patients with schizophrenia. Psychiatry Clin Neurosci. 2001. 55 (6): 611–618.Tang Y., Wang J., Zhang T., Xu L., Qian Z., Cui H., Niznikiewicz M.A. P300 as an index of transition to psychosis and of remission: data from a clinical high risk for psychosis study and review of literature. Schizophrenia research. 2020. 226: 74–83.Tao R., Cousijn H., Jaffe A.E., Burnet P.W., Edwards F., Eastwood S.L., Shin J.H., Lane T.A., Walker M.A., Maher B.J., Weinberger D.R., Harrison P.J., Hyde T.M., Kleinman J.E. Expression of ZNF804A in human brain and alterations in schizophrenia, bipolar disorder, and major depressive disorder: a novel transcript fetally regulated by the psychosis risk variant rs1344706. JAMA Psychiatry. 2014. 71 (10): 1112–1120.Uhlhaas P.J., Singer W. Oscillations and neuronal dynamics in schizophrenia: the search for basic symptoms and translational opportunities. Biological psychiatry. 2015. 77 (12): 1001–1009.Vanova M., Aldridge-Waddon L., Jennings B., Puzzo I., Kumari V. Reading skills deficits in people with mental illness: A systematic review and meta-analysis. Eur Psychiatry. 2021. 64 (1): e19.Vukovic N., Shtyrov Y. Cortical motor systems are involved in second-language comprehension: evidence from rapid mu-rhythm desynchronization. NeuroImage. 2014. 102: 695–703.Xu T., Stephane M., Parhi K.K. Multidimensional analysis of the abnormal neural oscillations associated with lexical processing in schizophrenia. Clinical EEG and neuroscience. 2013. 44 (2): 135–143.Zhang Y., Yan H., Liao J., Yu H., Jiang S., Liu Q., Yue W. ZNF804A Variation May Affect Hippocampal-Prefrontal Resting-State Functional Connectivity in Schizophrenic and Healthy Individuals. Neurosci Bull. 2018. 34 (3): 507–516.