УДК 159.9ББК 88.25К57

Когнитивная наука в Москве: новые исследования. Материалы конференции 19 июня 2019 г. Под ред. Е. В. Печенковой, М. В. Фаликман. – М.: ООО «Буки Веди», ИППиП. 2019 г. — 656 стр.

ISBN 978-5-4465-2346-7

ISBN 978-5-4465-2346-7 ©Авторы статей, 2019

УДК 159.9ББК 88.25

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MNI NORMALIZATION OF TMS MOTOR MAPS: PROBING WITHIN-LIMB SOMATOTOPY OF THE PRIMARY HAND MOTOR CORTEX

M. Nazarova*♥ (1, 2), P. Novikov♥ (1), K. Kozlova (1, 3), E. Ivanina (4), V. Nikulin (1, 5)chantante@gmail.com♥ — The authors share the first authorship and have contributed equally to the study1 — Centre of Cognition and Decision Making, Institute for Cognitive Neuroscience, National Research University Higher School of Economics, Moscow, Russia; 2 — Federal State Budget Institution Federal Center for Cerebrovascular Pathology and Stroke of the Ministry of Healthcare of the Russian Federation, Moscow, Russia; 3 — Department of Psychology, Russian State Social University, Moscow, Russia; 4 — Department of Psychology, National Research University Higher School of Economics, Moscow, Russia; 5 — Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Abstract. A within-limb somatotopy of the motor cortex remains a highly debated research topic. Transcranial magnetic stimulation (TMS) is a promising approach of non-invasive motor cortex mapping which is suitable for studying this topic in humans. One of the problems for interpreting TMS mapping results is that MNI normalization, which is routinely used for other brain mapping techniques, is still quite rarely applied for TMS mapping results. Thus, the aim of this work was to develop an algorithm for MNI normalization of TMS maps and to assess the somatotopy gradient for intrinsic and extrinsic hand muscles both at the individual and averaged TMS motor maps. 17 healthy young male right-handed volunteers underwent a TMS motor mapping procedure that included an investigation of three upper limb muscles: abductor pollicis brevis (APB), abductor digiti minimi (ADM) and extensor digitorum communis (EDC). We developed a TMS map normalization algorithm based on SPM8 and implemented it into the TMSmap software. Comparison of the locations of the centers of gravity and hotspots for ADM and EDC TMS representations relative to the APB TMS-map in MNI space revealed a more medial location of ADM and EDC centers of gravity and hotspots: 3 and 8 mm, respectively. For weighted normalized cortical TMS-representations, the ADM area was equivalent to 81%, and the EDC area was equivalent to 115% of the APB area. Thus, in this work, we showed the presence of a within-limb somatotopic gradient in the upper limb primary motor cortex using MNI-normalized TMS motor maps.

Keywords: motor cortex, transcranial magnetic stimulation, MNI normalization, motor mapping

Acknowledgments. nTMS data were obtained in the Research Center of Neurology, Moscow while MN was working there in the years 2012 – 2016. Authors are grateful to I. Gusarovas

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and D. Pozdeeva for help with the experiments. The work of PN was supported by Russian Science Foundation under grant 18-79-00328. The work of MN, VVN was partly conducted within the framework of the Basic Research Program at the National Research University Higher School of Economics (HSE) and was partly supported within the framework of a sub-sidy by the Russian Academic Excellence Project 5-100.

Background

A within-limb somatotopy of the motor cortex remains a highly debated ques-tion until now (Omrani et al., 2017). Transcranial magnetic stimulation (TMS) is a promising approach of non-invasive motor cortex mapping which is suitable for studying this question in humans (Raffin et al., 2015; Raffin & Siebner, 2019; Ruo-honen & Karhu, 2010). Most commonly, to report within-limb interactions probed by TMS motor mapping, investigators use the distances between the hotspots and centers of gravity (CoG) or amplitude-weighted mean positions of cortical rep-resentations for different muscles (Raffin et al., 2015; Raffin & Siebner, 2019). Although there are clear arguments for the fact that there is a lateral-medial gra-dient for TMS maps of the hand (Raffin et  al., 2015; Raffin  & Siebner, 2019), the TMS within-limb mapping is not yet a commonly accepted procedure. For in-stance, it is not known whether there is a within-limb TMS somatotopy in aver-aged TMS motor map because MNI normalization, which is routinely used in other brain mapping techniques, is still quite rarely applied for TMS mapping results (Kraus & Gharabaghi, 2016; Säisänen et al., 2011; Weiss et al., 2013). Thus, the aim of this work was to develop an algorithm for MNI normalization of TMS maps and to assess somatopy gradient for intrinsic and extrinsic hand muscles both at the individual and averaged TMS motor maps.

Methods

Seventeen young healthy male right-handed volunteers completed the study (19 – 33  y.o.). MRI-navigated TMS motor mapping sessions of three right-hand muscles were performed. Sessions consisted of multi-muscle nTMS mapping of the cortical representations of the three upper limb muscles: abductor pollicis bre-vis (APB), abductor digiti minimi (ADM) and extensor digitorum communis (EDC). Each TMS session consisted of 50 – 60 points stimulated in a pseudo-random or-der five times each. The analysis was performed using custom-made TMSmap software (http://tmsmap.ru/) (Novikov et al., 2018). Spatial filter for the points lay-ing closer than 2 mm apart was used, ABOS approach for interpolation between stimulation points for TMS maps construction was applied. Transformation to MNI space of TMS motor maps and weighted average map construction was done us-ing custom-made algorithm using SPM8 and TMSmap software.

Results

We have developed TMS maps normalization algorithm based on SPM8 and implemented it in the TMSmap program allowing group comparison of the TMS mapping data. Thus, we were able to compare the somatotopy gradient in the in-

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dividualized MNI TMS-maps and averaged MNI-normalized weighted TMS-maps. For individualized MNI TMS maps we found a lateral-medial gradient for the hand muscles compared to one that was reported earlier for a so called linear sulcus shape-informed TMS mapping revealed of the first dorsal intercrosses and ADM

Figure 1. MNI normalized individual TMS motor maps of APB, ADM and EDC muscles of a representative subject in TMSmap software interface. CoGs are shown with white crosses; hotspots are shown with blue stars. Red square — the same spot in the MNI space. Color scale is reflecting the motor evoked potential amplitude in microvolts in a stimulation point.

Figure 2. MNI normalized and weighted TMS motor maps of APB, ADM and EDC in TMSmap software interface (17 volunteers). CoGs are shown with white crosses; hotspots are shown with blue stars. Red square — the same spot in the MNI space. Color scale is reflecting the mean weighted motor evoked potential in a stimulation point.

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muscles (Raffin et al., 2015; Raffin & Siebner, 2019). Thus, medial shift of the ADM and EDC compared to APB cortical representations was 5.9 mm and 8.1 mm for hotspots and 1.9 mm and 2.2 mm for CoGs, correspondingly (Figure 1). In case of the averaged MNI-normalized weighted TMS cortical motor map medial to lateral distances were substantially smaller: 1 mm (APB-ADM) and 2.5 mm (APB-EDC) for hotspots and 2 mm (APB-ADM) and 3.5 mm (APB-EDC) for CoGs, corresponding-ly (figure 2). As for the MNI-normalized areas, ADM area was equivalent to 81 % of APB area, while EDC area was equivalent to 115 % of APB area.

Conclusions

In this work, we demonstrated that a within-hand somatotopy gradient using normalized TMS motor maps is substantially smaller than the distances between hotspots and CoGs of different muscles cortical representation at the individual-ized level. These results need further elaboration for consideration of the novel topography parameters additionally to the among-channel CoGs and hotspots dif-ferences and for checking the test-retest reliability of TMS metrics of within-limb somatotopy.

References

Kraus D., Gharabaghi A. Neuromuscular plasticity: Disentangling stable and variable motor maps in the human sensorimotor cortex // Neural Plasticity. 2016. Vol. 2016. P. 1 – 13. doi:10.1155/2016/7365609

Novikov P. A., Nazarova M. A., Nikulin V. V. TMSmap — software for quantitative analysis of TMS mapping results // Frontiers in Human Neuroscience. 2018. Vol. 12. P. 239. doi:10.3389/fnhum.2018.00239

Omrani M., Kaufman M. T., Hatsopoulos N. G., Cheney P. D. Perspectives on classical con-troversies about the motor cortex  // Journal of Neurophysiology. 2017. Vol. 118. No. 3. P. 1828 – 1848. doi:10.1152/jn.00795.2016

Raffin E., Pellegrino G., Lazzaro V. D., Thielscher A., Siebner H. R. Bringing transcranial mapping into shape: Sulcus-aligned mapping captures motor somatotopy in human pri-mary motor hand area  // NeuroImage. 2015. Vol. 120. No. 4. P. 164 – 175. doi:10.1016/j.neuroimage.2015.07.024

Raffin E., Siebner H. R. Use-dependent plasticity in human primary motor hand area: Syn-ergistic interplay between training and immobilization  // Cerebral Cortex. 2019. Vol. 29. No. 1. P. 356 – 371. doi:10.1093/cercor/bhy226

Ruohonen J., Karhu J. Navigated transcranial magnetic stimulation  // Neurophysiol-ogie Clinique  / Clinical Neurophysiology. 2010. Vol. 40. No. 1. P. 7 – 17. doi:10.1016/j.neucli.2010.01.006

Säisänen L., Julkunen P., Niskanen E., Hukkanen T., Mervaala E., Karhu J., Könönen M. Short- and intermediate-interval cortical inhibition and facilitation assessed by navigated tran-scranial magnetic stimulation  // Journal of Neuroscience Methods. 2011. Vol. 195. No. 2. P. 241 – 248. doi:10.1016/j.jneumeth.2010.11.022

Weiss C., Nettekoven C., Rehme A. K., Neuschmelting V., Eisenbeis A., Goldbrunner R., Grefkes C. Mapping the hand, foot and face representations in the primary motor cortex — Retest reliability of neuronavigated TMS versus functional MRI // NeuroImage. 2013. Vol. 66. P. 531 – 542. doi:10.1016/j.neuroim

MNI Normalization of TMS Motor Maps: Probing of Within-Limb Somatotopy...

MNI НОРМАЛИЗАЦИЯ ТМС-КАРТ: ОЦЕНКА СОМАТОТОПИЧЕСКОГО ГРАДИЕНТА ВНУТРИ ЗОНЫ РУКИ В ПЕРВИЧНОЙ ДВИГАТЕЛЬНОЙ КОРЕ

М. А. Назарова♥* (1, 2), П. А. Новиков♥ (1), К. Д. Козлова (1, 3), Е. О. Иванина (4), В. В. Никулин (1, 5)chantante@gmail.com♥ — разделенное первое авторство1 — Центр нейроэкономики и когнитивных исследований, Институт когнитивных нейронаук, Национальный исследовательский университет «Высшая школа экономики», Москва, Россия; 2 — Федеральное государственное бюджетное учреждение «Федеральный центр цереброваскулярной патологии и инсульта» Минздрава РФ, Москва, Россия; 3 — Факультет психологии, Российский Государственный Социальный Университет; 4 — Департамент психологии, Факультет социальных наук, Национальный исследовательский университет «Высшая школа экономики», Москва, Россия; 5 — Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

Аннотация. Вопрос организации первичной двигательной коры внутри зоны предста-вительства конечности остается открытым до настоящего времени. Перспективным подходом для его изучения является картирование коры с использованием метода МРТ-навигируемой транскраниальной магнитной стимуляции (нТМС). Однако, MNI нор-мализация функциональных ТМС-карт, позволяющая производить сравнение между испытуемыми, которая рутинно используется при работе с методами функциональной МРТ или МЭГ, применяется на настоящий момент крайне редко. Целью работы было создание алгоритма нормализации ТМС-карт и оценка соматотопической организации корковых репрезентаций мышц руки, полученных при нТМС картировании в норме. У 17 здоровых праворуких мужчин была проведена процедура моторного нТМС кар-тирования трех мышц правой руки: abductor pollicis brevis (APB), abductor digiti minimi (ADM) и extensor digitorum communis (EDC). Нами был разработан и имплементирован в программу TMSmap алгоритм нормализации ТМС-карт. Сравнение расположений цен-тров тяжести и горячих точек для репрезентаций мышц ADM и EDC относительно APB в пространстве MNI выявило их более медиальное расположение на 3 и 8 мм соответ-ственно. Для взвешенных нормированных корковых ТМС-репрезентаций площадь ADM была эквивалентна 81 %, а площадь EDC — 115 % площади APB. Таким образом, в этой работе мы показали наличие соматотопического градиента в первичной двигательной коре внутри зоны руки на нормализованных моторных ТМС-картах.

Ключевые слова: моторная кора, транскраниальная магнитная стимуляция, MNI, про-странственная нормализация, моторное картирование