Transcranial magnetic stimulation of the brain: What is stimulated? – A consensus and critical position paper

Copyright © 2022 The Author(s) and International Federation of Clinical Neurophysiology. Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.Aman S. Aberra was supported by a U. S. A. National Science Foundation Graduate Research Fellowship (No. DGF 1106401). Andrea Antal has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01GP2124B) and by a grant of the Lower Saxony Ministry of Science and Culture (Grant 76251-12-7/19 ZN 3456). Marco Davare has been supported by a BBSRC responsive mode grant. Klaus Funke has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01EE1403B) as part of the German Center for Brain Stimulation (GCBS) and by the Deutsche Forschungsgemeinschaft (DFG) (Grants FU256/3-2; 122679504–SFB874). Mark Hallett is supported by the NINDS Intramural Program. Anke N. Karabanov holds a 4-year Sapere Aude Fellowship which is sponsored by the Independent Research Fund Denmark (Grant Nr. 0169-00027B). The sponsor had no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Giacomo Koch has been supported by na EU grant H2020-EU.1.2.2. - FET Proactive (Neurotwin ID: 101017716). Sabine Meunier is Emeritus Research Director at INSERM, this has no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Carlo Miniussi has been supported by a grant of the Caritro Foundation, Italy. Walter Paulus received grants from the Deutsche Forschungsgemeinschaft and BMBF. Angel V. Peterchev was supported by grants from the U. S. A. National Institutes of Health (Grants Nos. R01NS117405, R01NS088674, RF1MH114268, R01MH111865). Traian Popa has been supported by the Defitech Foundation and NIBS-iCog grant from the Swiss National Science Foundation. Hartwig R. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186-2015-2138). The salary for Janine Kesselheim (PhD project) has been covered by a project grant “Biophysically adjusted state-informed cortex stimulation” (BASICS) funded by a synergy grant from Novo Nordisk Foundation (PI: Hartwig R Siebner, Interdisciplinary Synergy Program 2014; grant number NNF14OC001). Axel Thielscher has been supported by grants of the Lundbeck foundation (R118-A11308, R244-2017-196 and R313-2019-622). Yoshikazu Ugawa has been supported in part by grants from the Research Project Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (Grants 15H05881, 16H05322, 19H01091, 20K07866). Ulf Ziemann received grants from the German Ministry of Education and Research (BMBF), European Research Council (ERC), and German Research Foundation (DFG)

Weathering in the Lake Baikal watershed during the Kazantsevo (Eemian) interglacial: Evidence from the lacustrine clay record

The clay-mineralogical record of a piston core recovered on an elevated plateau in the northern basin of Lake Baikal has been investigated for the Kazantsevo interglacial period (i.e., Eemian s.s. equivalent in northern Europe). The age model (as inferred from palaeomagnetic intensity) suggests that this stage spans ca. 128 to 117 kyr BP. Relative clay mineral abundances and clay-mineral ratios are used to reconstruct the weathering conditions within the Baikal watershed at a sub-millennial resolution, and suggest that the clay record is highly variable. A bimodal clay-data distribution is in agreement with different clay sources and/or formation between the studied glacial and interglacial periods. High amounts of smectites in the Taz glacial samples (128.7-136.4 kyr BP) may be explained by an additional source of neoformed smectites during the glacial stage. In addition to the classically used smectite/illite ratio, the mineralogical results are integrated by the calculation of a hydrolysis index that takes into account the abundance of all clay species and their sensitivity to chemical weathering. A principal components analysis (PCA) of the Baikal clay minerals allows the comparison of the clay parameters with regard to weathering conditions. Clay data are further compared (i) with diatom and pollen profiles, (ii) with pollen-based quantitative reconstructions for the same core material, and (iii) with other climate reconstructions for the Lake Baikal region and Siberia. Several features of our record are highlighted here. During the early period of the Kazantsevo interglacial (128.4-125.2 kyr BP), weathering processes remain controlled by physical reworking for more than 2 kyr after the initial transition from cold to warm conditions. Inception of chemical weathering starts only after ca. 125 kyr BP, a period coincident with the warmest conditions according to both the pollen record and by the strongest chernozem development in Siberian soils. Within the interglacial interval, the hydrolysis index displays a two-step increase, punctuated by a minimum value ca. 122 kyr BP. The increasing but irregular trend persists after the transition from the Kazantsevo interglacial to the Zyryanka glacial (similar to 117 kyr BP). Peak chemical weathering, as inferred by clay changes, lags the interglacial/ glacial transition by at least 2 kyr. This suggests that pedogenesis remains active after the interval of surface stabilization. Lake Baikal clay minerals trace the nature of the main weathering conditions within the watershed. We note any increase in physical weathering is rapidly recorded in sedimentary clay assemblages but the mineral imprint to chemical weathering changes is more gradual, lagging reconstructed climate conditions over the lake by ca. 2 kyr. 0 2007 Elsevier B.V.. All rights reserved.Continen

Change in dust seasonality as the primary driver for orbital scale dust storm variability in East Asia

Glacial periods are recognized to be dustier than interglacials, but the conditions leading to greater dust mobilization are poorly defined. Here we present a new high-resolution dust record based on 230Th-normalized 4He flux from Ocean Drilling Program site 882 in the Subarctic North Pacific covering the last 170,000 years. By analogy with modern relationships, we infer the mechanisms controlling orbital-scale dust storm variability in East Asia. We propose that orbital-scale dust flux variability is the result of an expansion of the dust season into summer, in addition to more intense dust storms during spring and fall. The primary drivers influencing dust flux include summer insolation at subarctic latitudes and variable Siberian alpine glaciation, which together control the cold air reservoir in Siberia. Changes in the extent of the Northern Hemisphere ice sheets may be a secondary control

Holocene climate evolution of the Ugii Nuur basin, Mongolia

In order to evaluate the Holocene palaeoenvironmental evolution of the Ugii Nuur basin, central Mongolia, investigations on chemical and mineralogical properties of lacustrine sediments were carried out on a 630cm sediment core from lake Ugii Nuur. The interpretation of the record is based on a principal component analysis (PCA) of the elemental composition of the samples. The results show that lacustrine deposition started at 10.6 kyr BP. Low lake level conditions were identified during the Early Holocene (10.67.9ky BP). The Mid Holocene (7.94.2 kyr BP) was characterized by generally higher lake levels and thus higher moisture supply, but it experienced strong climatic fluctuations. Arid conditions prevailed from 4.22.8 kyr BP and were followed by a stable, more humid phase until today