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 Sciences65200110.31857/S0044467723060059IDVTUVФИЗИОЛОГИЯ ВЫСШЕЙ НЕРВНОЙ (КОГНИТИВНОЙ) ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКАФИЗИОЛОГИЯ ВЫСШЕЙ НЕРВНОЙ (КОГНИТИВНОЙ) ДЕЯТЕЛЬНОСТИ ЧЕЛОВЕКАCORRELATION BETWEEN SUBTHALAMIC ALPHA RHYTHMIC ACTIVITY AND MOTOR CONTROL IMPAIRMENT IN PARKINSONIAN PATIENTSСвязь ритмической альфа-активности субталамического ядра с нарушениями двигательного контроля у пациентов с болезнью ПаркинсонаNezvinskiyA. A.НезвинскийА. А.nezvinskii@phystech.eduBelovaE. M.БеловаЕ. М.nezvinskii@phystech.eduSayfulinaK. E.СайфулинаК. Э.nezvinskii@phystech.eduGamaleyaA. A.ГамалеяА. А.nezvinskii@phystech.eduTomskiyA. A.ТомскийА. А.nezvinskii@phystech.eduSedovA. S.СедовА. С.nezvinskii@phystech.eduSemenov Federal Research Center for Chemical Physics, Russian Academy of ScienceФедеральное государственное бюджетное учреждение науки Федеральный исследовательский центр химической физики им. Н.Н. Семенова РАНBurdenko National Medical Research Center of NeurosurgeryНациональный медицинский исследовательский центр нейрохирургии им. Н.Н. Бурденко0111202373672573402022025Copyright ©; 2023, А.А. Незвинский, Е.М. Белова, К.Э. Сайфулина, А.А. Гамалея, А.А. Томский, А.С. СедовCopyright ©; 2023, А.А. Незвинский, Е.М. Белова, К.Э. Сайфулина, А.А. Гамалея, А.А. Томский, А.С. Седов2023А.А. Незвинский, Е.М. Белова, К.Э. Сайфулина, А.А. Гамалея, А.А. Томский, А.С. СедовА.А. Незвинский, Е.М. Белова, К.Э. Сайфулина, А.А. Гамалея, А.А. Томский, А.С. Седовhttps://innoscience.ru/0044-4677/article/view/652001

Increased oscillatory beta activity in basal ganglia is one of the main electrophysiological biomarkers of impaired motor control in Parkinson’s disease. However, the functional role of dynamical rhythmic processes during movements is still not investigated in detail. We used microelectrode recordings to investigate the subthalamic nucleus neuronal activity in 9 patients with Parkinson’s disease during deep brain stimulation surgery. We have shown that the amplitude of the subthalamic nucleus alpha (7–12 Hz) and low-beta (12–20 Hz) activity correlated with motor impairment indices in patients with Parkinson’s disease. Also, we have shown that, in contrast to beta rhythmic activity, the magnitude of alpha activity decreased significantly during motor tests execution. Moreover, the degree of rhythmic activity suppression in the alpha band correlated with the severity of bradykinesia. These results allow us to suppose that, along with beta activities, subthalamic nucleus neuronal alpha activity also participate in motor control of Parkinson’s disease patients.

Повышенная осцилляторная бета-активность в базальных ганглиях считается одним из основных электрофизиологических биомаркеров нарушения двигательного контроля при болезни Паркинсона. При этом функциональная роль динамических процессов ритмической активности при выполнении движений до сих пор не до конца изучена. Методом микроэлектродной регистрации мы исследовали ритмическую активность нейронов субталамического ядра у 9 пациентов с болезнью Паркинсона во время проведения нейрохирургических операций для установки систем глубинной стимуляции мозга. Мы показали значимую положительную корреляцию амплитуды альфа- (7–12 Гц) и низкой бета- (12–20 Гц) активности в субталамическом ядре с общими показателями двигательных нарушений у пациентов с болезнью Паркинсона. Также мы показали, что амплитуда ритмической альфа-активности, в отличие от бета-ритмов, значимо снижалась при выполнении пациентами двигательных тестов. Более того, степень снижения альфа-активности напрямую коррелировала с выраженностью симптома брадикинезии. Полученные результаты позволяют предположить, что наряду с бета-активностью в двигательном контроле пациентов с болезнью Паркинсона играет роль также альфа-ритмическая активность нейронов субталамического ядра.

neuronal oscillationsbradykinesiamicroelectrode recordingssubthalamic nucleusParkinson’s diseaseнейронная ритмическая активностьбрадикинезиямикроэлектродная регистрациясубталамическое ядроболезнь ПаркинсонаAlegre M., Alonso-Frech F., Rodríguez-Oroz M.C., Guridi J., Zamarbide I., Valencia M., Manrique M., Obeso J.A., Artieda J. Movement-related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements. Eur J Neurosci. 2005. 22 (9): 2315–2324.Bate D., Mächler M., Bolker B., Walker S. Fitting Linear Mixed-Effects Models Using lme4. J Stat Soft. 2015. 67 (1): 1–48.Belova E.M., Semenova U., Gamaleya A.A., Tomskiy A.A., Sedov A. Is there a single beta oscillation band interfering with movement in Parkinson’s disease? Eur J Neurosci. 2021. 54 (1): 4381–4391.Bichsel O., Gassert R., Stieglitz L., Uhl M., Baumann-Vogel H., Waldvogel D., Baumann C.R., Imbach L.L. Functionally separated networks for self-paced and externally-cued motor execution in Parkinson’s disease: Evidence from deep brain recordings in humans. NeuroImage. 2018. 177: 20–29.Drebitz E., Schledde B., Kreiter A.K., Wegener D. Optimizing the Yield of Multi-Unit Activity by Including the Entire Spiking Activity. Front Neurosci. 2019. 13: 83. 745Eisinger R.S., Cagle J.N., Opri E., Alcantara J., Cernera S., Foote K.D., Okun M.S., Gunduz A. Parkinsonian Beta Dynamics during Rest and Movement in the Dorsal Pallidum and Subthalamic Nucleus. 2020. J. Neurosci. 40 (14): 2859–2867.Feldmann L.K., Lofredi R., Neumann W.-J., Al-Fatly B., Roediger J., Bahners B.H., Nikolov P., Denison T., Saryyeva A., Krauss J.K., Faust K., Florin E., Schnitzler A., Schneider G.-H., Kühn A.A. Toward therapeutic electrophysiology: beta-band suppression as a biomarker in chronic local field potential recordings. Npj Park Dis. 2022. 8 (1): 44.Galvan A., Wichmann T. Pathophysiology of Parkinsonism. Clin Neurophysiol. 2008. 119 (7): 1459–1474.Geng X., Xu X., Horn A., Li N., Ling Z., Brown P., Wang S. Intra-operative characterisation of subthalamic oscillations in Parkinson’s disease. Clin Neurophysiol. 2018. 129 (5): 1001–1010.Godinho F., Fim Neto A., Bianqueti B.L., Luccas J.B., Varjão E., Terzian Filho P.R., Figueiredo E.G., Almeida T.P., Yoneyama T., Takahata A.K., Rocha M.S., Soriano D.C. Spectral characteristics of subthalamic nucleus local field potentials in Parkinson’s disease: Phenotype and movement matter. Eur J. Neurosci. 2021. 53 (8): 2804–2818.Hammond C., Bergman H., Brown P. Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci. 2007. 30 (7): 357–364.Horn A., Neumann W.-J., Degen K., Schneider G.-H., Kühn A.A. Toward an electrophysiological “sweet spot” for deep brain stimulation in the subthalamic nucleus. Hum Brain Mapp. 2017. 38 (7): 3377–3390.Khawaldeh S., Tinkhauser G., Shah S.A., Peterman K., Debove I., Nguyen T.A.K., Nowacki A., Lachenmayer M.L., Schuepbach M., Pollo C., Krack P., Woolrich M., Brown P. Subthalamic nucleus activity dynamics and limb movement prediction in Parkinson’s disease. Brain. 2020. 143 (2): 582–596.Kuhn A.A., Kempf F., Brucke C., Gaynor Doyle L., Martinez-Torres I., Pogosyan A., Trottenberg T., Kupsch A., Schneider G.-H., Hariz M.I., Vandenberghe W., Nuttin B., Brown P. High-Frequency Stimulation of the Subthalamic Nucleus Suppresses Oscillatory Activity in Patients with Parkinson’s Disease in Parallel with Improvement in Motor Performance. J. Neurosci. 2008. 28 (24): 6165–6173.Kühn A.A., Kupsch A., Schneider G.-H., Brown P. Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease: STN activity and motor improvement. Eur. J. Neurosci. 2006. 23 (7): 1956–1960.Kühn A.A., Trottenberg T., Kivi A., Kupsch A., Schneider G.-H., Brown P. The relationship between local field potential and neuronal discharge in the subthalamic nucleus of patients with Parkinson’s disease. Exp Neurol. 2005. 194 (1): 212–220.Kühn A.A., Tsui A., Aziz T., Ray N., Brücke C., Kupsch A., Schneider G.-H., Brown P. Pathological synchronisation in the subthalamic nucleus of patients with Parkinson’s disease relates to both bradykinesia and rigidity. Exp Neurol. 2009. 215 (2): 380–387.Kuznetsova A., Brockhof P.B., Christensen R.H.B. lmerTest Package: Tests in Linear Mixed Effects Models. J Stat Soft. 2017. 1 (13): 1–26.Little S., Pogosyan A., Neal S., Zavala B., Zrinzo L., Hariz M., Foltynie T., Limousin P., Ashkan K., FitzGerald J., Green A.L., Aziz T.Z., Brown P. Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 2013. 74 (3): 449–457.Lofredi R., Tan H., Neumann W.-J., Yeh C.-H., Schneider G.-H., Kühn A.A., Brown P. Beta bursts during continuous movements accompany the velocity decrement in Parkinson’s disease patients. Neurobiol Dis. 2019. 127: 462–471.Marmor O., Rappel P., Valsky D., Bick A.S., Arkadir D., Linetsky E., Peled O., Tamir I., Bergman H., Israel Z., Eitan R. Movement context modulates neuronal activity in motor and limbic-associative domains of the human parkinsonian subthalamic nucleus. Neurobiol Dis. 2020. 136: 104716.Moran A., Bar-Gad I. Revealing Neuronal Functional Organization through the Relation between Multi-Scale Oscillatory Extracellular Signals. J Neurosci Methods. 2010. 186 (1): 116–129.Neumann W.-J., Degen K., Schneider G.-H., Brücke C., Huebl J., Brown P., Kühn A.A. Subthalamic synchronized oscillatory activity correlates with motor impairment in patients with Parkinson’s disease: Correlation of Subthalamic B Oscillations and PD Symptoms. Mov Disord. 2016. 31 (11): 1748–1751.Neuville R.S., Petrucci M.N., Wilkins K.B., Anderson R.W., Hoffman S.L., Parker J.E., Velisar A., Bronte-Stewart H.M. Differential Effects of Pathological Beta Burst Dynamics Between Parkinson’s Disease Phenotypes Across Different Movements. Front Neurosci. 2021. 15: 733203.Oswal A., Beudel M., Zrinzo L., Limousin P., Hariz M., Foltynie T., Litvak V., Brown P. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease. Brain. 2016. 139 (5): 1482–1496.Oswal A., Brown P., Litvak V. Movement related dynamics of subthalmo-cortical alpha connectivity in Parkinson’s disease. NeuroImage. 2013. 70: 132–142.Rappel P., Grosberg S., Arkadir D., Linetsky E., Abu Snineh M., Bick A.S., Tamir I., Valsky D., Marmor O., Abo Foul Y., Peled O., Gilad M., Daudi C., Ben-Naim S., Bergman H., Israel Z., Eitan R. Theta-alpha Oscillations Characterize Emotional Subregion in the Human Ventral Subthalamic Nucleus. Mov Disord. 2020. 35 (2): 337–343.Scherer M., Steiner L.A., Kalia S.K., Hodaie M., Kühn A.A., Lozano A.M., Hutchison W.D., Milosevic L. Single-Neuron Bursts Encode Pathological Oscillations in Subcortical Nuclei of Patients with Parkinson’s Disease and Essential Tremor. Proc Natl Acad Sci USA. 2022. 119 (35).Sharott A., Gulberti A., Zittel S., Tudor Jones A.A., Fickel U., Munchau A., Koppen J.A., Gerloff C., Westphal M., Buhmann C., Hamel W., Engel A.K., Moll C.K.E. Activity Parameters of Subthalamic Nucleus Neurons Selectively Predict Motor Symptom Severity in Parkinson’s Disease. J Neurosci. 2014. 34 (18): 6273–6285.Steiner L.A., Neumann W.-J., Staub-Bartelt F., Herz D.M., Tan H., Pogosyan A., Kuhn A.A., Brown P. Subthalamic beta dynamics mirror Parkinsonian bradykinesia months after neurostimulator implantation: STN Beta Dynamics Mirror Parkinsonian Bradykinesia. Mov Disord. 2017. 32 (8): 1183–1190.Tinkhauser G., Pogosyan A., Tan H., Herz D.M., Kühn A.A., Brown P. Beta burst dynamics in Parkinson’s disease OFF and ON dopaminergic medication. Brain. 2017a. 140 (11): 2968–2981.Tinkhauser G., Pogosyan A., Little S., Beudel M., Herz D.M., Tan H., Brown P. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s disease. Brain. 2017б. 140 (4): 1053–1067.van Wijk B.C.M., Neumann W.-J., Kroneberg D., Horn A., Irmen F., Sander T.H., Wang Q., Litvak V., Kühn A.A. Functional connectivity maps of theta/alpha and beta coherence within the subthalamic nucleus region. NeuroImage. 2022. 257: 119320.