Abstract
Probing the brain structure–function relationship is at the heart of modern neuroscientific explorations, enabled by recent advances in brain mapping techniques. This study aimed to explore the anatomical blueprint of corticospinal excitability and shed light on the structure–function relationship within the human motor system. Using diffusion magnetic resonance imaging tractography, based on the spherical deconvolution approach, and transcranial magnetic stimulation (TMS), we show that anatomical inter-individual variability of the corticospinal tract (CST) modulates the corticospinal excitability and conductivity. Our findings show for the first time the relationship between increased corticospinal excitability and conductivity in individuals with a bigger CST (i.e., number of streamlines), as well as increased corticospinal microstructural organization (i.e., fractional anisotropy). These findings can have important implications for the understanding of the neuroanatomical basis of TMS as well as the study of the human motor system in both health and disease.
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The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
References
Ahdab R, Ayache SS, Brugières P et al (2016) The hand motor hotspot is not always located in the hand knob: a neuronavigated transcranial magnetic stimulation study. Brain Topogr 29:590–597. https://doi.org/10.1007/s10548-016-0486-2
Ammann C, Guida P, Caballero-Insaurriaga J et al (2020) A framework to assess the impact of number of trials on the amplitude of motor evoked potentials. Sci Rep 10:21422. https://doi.org/10.1038/s41598-020-77383-6
Barker AT, Jalinous R, Freeston IL (1985) Non-invasive magnetic stimulation of human motor cortex. The Lancet 325:1106–1107. https://doi.org/10.1016/S0140-6736(85)92413-4
Bastani A, Jaberzadeh S (2012) A higher number of TMS-elicited MEP from a combined hotspot improves intra- and inter-session reliability of the upper limb muscles in healthy individuals. PLoS ONE 7:e47582. https://doi.org/10.1371/journal.pone.0047582
Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system – a technical review. NMR Biomed 15:435–455. https://doi.org/10.1002/nbm.782
Benjamini Y, Hochberg Y (1995) Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B Methodol 57:289–300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.x
Bergmann TO, Karabanov A, Hartwigsen G et al (2016) Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives. Neuroimage 140:4–19. https://doi.org/10.1016/j.neuroimage.2016.02.012
Bestmann S, Krakauer JW (2015) The uses and interpretations of the motor-evoked potential for understanding behaviour. Exp Brain Res 233:679–689. https://doi.org/10.1007/s00221-014-4183-7
Brasil-Neto JP, Cohen LG, Panizza M et al (1992) Optimal focal transcranial magnetic activation of the human motor cortex: effects of coil orientation, shape of the induced current pulse, and stimulus intensity. J Clin Neurophysiol 9:132
Caminiti R, Carducci F, Piervincenzi C et al (2013) Diameter, length, speed, and conduction delay of callosal axons in macaque monkeys and humans: comparing data from histology and magnetic resonance imaging diffusion tractography. J Neurosci 33:14501–14511. https://doi.org/10.1523/JNEUROSCI.0761-13.2013
Cantone M, Lanza G, Vinciguerra L et al (2019) Age, height, and sex on motor evoked potentials: translational data from a large italian cohort in a clinical environment. Front Hum Neurosci 13:185. https://doi.org/10.3389/fnhum.2019.00185
Cavaleri R, Schabrun SM, Chipchase LS (2017) The number of stimuli required to reliably assess corticomotor excitability and primary motor cortical representations using transcranial magnetic stimulation (TMS): a systematic review and meta-analysis. Syst Rev 6:48. https://doi.org/10.1186/s13643-017-0440-8
Chen R, Gerloff C, Classen J et al (1997) Safety of different inter-train intervals for repetitive transcranial magnetic stimulation and recommendations for safe ranges of stimulation parameters. Electroencephalogr Clin Neurophysiol Mot Control 105:415–421. https://doi.org/10.1016/S0924-980X(97)00036-2
Conturo TE, Lori NF, Cull TS et al (1999) Tracking neuronal fiber pathways in the living human brain. Proc Natl Acad Sci 96:10422–10427. https://doi.org/10.1073/pnas.96.18.10422
Cuypers K, Thijs H, Meesen RLJ (2014) Optimization of the transcranial magnetic stimulation protocol by defining a reliable estimate for corticospinal excitability. PLoS ONE 9:e86380. https://doi.org/10.1371/journal.pone.0086380
Dell’Acqua F, Rizzo G, Scifo P et al (2007) A Model-based deconvolution approach to solve fiber crossing in diffusion-weighted MR imaging. IEEE Trans Biomed Eng 54:462–472. https://doi.org/10.1109/TBME.2006.888830
Dell’Acqua F, Scifo P, Rizzo G et al (2010) A modified damped Richardson-Lucy algorithm to reduce isotropic background effects in spherical deconvolution. Neuroimage 49:1446–1458. https://doi.org/10.1016/j.neuroimage.2009.09.033
Dell’Acqua F, Simmons A, Williams SCR, Catani M (2013) Can spherical deconvolution provide more information than fiber orientations? Hindrance modulated orientational anisotropy, a true-tract specific index to characterize white matter diffusion. Hum Brain Mapp 34:2464–2483. https://doi.org/10.1002/hbm.22080
Devanne H, Lavoie BA, Capaday C (1997) Input-output properties and gain changes in the human corticospinal pathway. Exp Brain Res 114:329–338. https://doi.org/10.1007/pl00005641
Di Lazzaro V, Rothwell JC (2014) Corticospinal activity evoked and modulated by non-invasive stimulation of the intact human motor cortex. J Physiol 592:4115–4128. https://doi.org/10.1113/jphysiol.2014.274316
Du X, Kochunov P, Summerfelt A et al (2017) The role of white matter microstructure in inhibitory deficits in patients with schizophrenia. Brain Stimulat 10:283–290. https://doi.org/10.1016/j.brs.2016.11.006
Dubbioso R, Madsen KH, Thielscher A, Siebner HR (2021) The myelin content of the human precentral hand knob reflects interindividual differences in manual motor control at the physiological and behavioral level. J Neurosci 41:3163–3179. https://doi.org/10.1523/JNEUROSCI.0390-20.2021
Dubois J, Hertz-Pannier L, Cachia A et al (2009) Structural asymmetries in the infant language and sensori-motor networks. Cereb Cortex 19:414–423. https://doi.org/10.1093/cercor/bhn097
Eichert N, Watkins KE, Mars RB, Petrides M (2021) Morphological and functional variability in central and subcentral motor cortex of the human brain. Brain Struct Funct 226:263–279. https://doi.org/10.1007/s00429-020-02180-w
Farzan F (2014) Single-pulse transcranial magnetic stimulation (TMS) protocols and outcome measures. In: Rotenberg A, Horvath JC, Pascual-Leone A (eds) Transcranial magnetic stimulation. Springer, New York, NY, pp 69–115
Faul F, Erdfelder E, Lang A-G, Buchner A (2007) G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39:175–191. https://doi.org/10.3758/BF03193146
Goldsworthy MR, Hordacre B, Ridding MC (2016) Minimum number of trials required for within- and between-session reliability of TMS measures of corticospinal excitability. Neuroscience 320:205–209. https://doi.org/10.1016/j.neuroscience.2016.02.012
Groppa S, Oliviero A, Eisen A et al (2012) A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee. Clin Neurophysiol 123:858–882. https://doi.org/10.1016/j.clinph.2012.01.010
Guder S, Frey BM, Backhaus W et al (2020) The influence of cortico-cerebellar structural connectivity on cortical excitability in chronic stroke. Cereb Cortex 30:1330–1344. https://doi.org/10.1093/cercor/bhz169
Guder S, Pasternak O, Gerloff C, Schulz R (2021) Strengthened structure–function relationships of the corticospinal tract by free water correction after stroke. Brain Commun. https://doi.org/10.1093/braincomms/fcab034
Hallett M (2000) Transcranial magnetic stimulation and the human brain. Nature 406:147–150. https://doi.org/10.1038/35018000
Haueisen J, Tuch DS, Ramon C et al (2002) The Influence of Brain Tissue Anisotropy on Human EEG and MEG. Neuroimage 15:159–166. https://doi.org/10.1006/nimg.2001.0962
Herbsman T, Forster L, Molnar C et al (2009) Motor threshold in transcranial magnetic stimulation: The impact of white matter fiber orientation and skull-to-cortex distance. Hum Brain Mapp 30:2044–2055. https://doi.org/10.1002/hbm.20649
Hübers A, Klein JC, Kang J-S et al (2012) The relationship between TMS measures of functional properties and DTI measures of microstructure of the corticospinal tract. Brain Stimulat 5:297–304. https://doi.org/10.1016/j.brs.2011.03.008
Jang SH, Seo YS (2019) Diagnosis of conversion disorder using diffusion tensor tractography and transcranial magnetic stimulation in a patient with mild traumatic brain injury. Diagnostics 9:155. https://doi.org/10.3390/diagnostics9040155
Jang SH, Kim DH, Kim SH, Seo JP (2017) The relation between the motor evoked potential and diffusion tensor tractography for the corticospinal tract in chronic hemiparetic patients with cerebral infarct. Somatosens Mot Res 34:134–138. https://doi.org/10.1080/08990220.2017.1343188
Jones DK (2008) Studying connections in the living human brain with diffusion MRI. Cortex 44:936–952. https://doi.org/10.1016/j.cortex.2008.05.002
Jones DK, Simmons A, Williams SCR, Horsfield MA (1999) Non-invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI. Magn Reson Med 42:37–41. https://doi.org/10.1002/(SICI)1522-2594(199907)42:1%3c37::AID-MRM7%3e3.0.CO;2-O
Kim H, Kim J, Lee H-J, et al (2021) Optimal stimulation site for rTMS to improve motor function: Anatomical hand knob vs. hand motor hotspot. Neurosci Lett 740:135424. https://doi.org/10.1016/j.neulet.2020.135424
Klöppel S, Bäumer T, Kroeger J et al (2008) The cortical motor threshold reflects microstructural properties of cerebral white matter. Neuroimage 40:1782–1791. https://doi.org/10.1016/j.neuroimage.2008.01.019
Kobayashi M, Pascual-Leone A (2003) Transcranial magnetic stimulation in neurology. Lancet Neurol 2:145–156. https://doi.org/10.1016/S1474-4422(03)00321-1
Kozel FA, Nahas Z, deBrux C et al (2000) How coil-cortex distance relates to age, motor threshold, and antidepressant response to repetitive transcranial magnetic stimulation. J Neuropsychiatry Clin Neurosci 12:376–384. https://doi.org/10.1176/jnp.12.3.376
Leemans A, Jeurissen B, Sijbers J, Jones DK (2009) ExploreDTI: a graphical toolbox for processing, analyzing, and visualizing diffusion MR data. Hawaii, USA, p 3537
McConnell KA, Nahas Z, Shastri A et al (2001) The transcranial magnetic stimulation motor threshold depends on the distance from coil to underlying cortex: a replication in healthy adults comparing two methods of assessing the distance to cortex. Biol Psychiatry 49:454–459. https://doi.org/10.1016/S0006-3223(00)01039-8
Mills KR, Boniface SJ, Schubert M (1992) Magnetic brain stimulation with a double coil: the importance of coil orientation. Electroencephalogr Clin Neurophysiol Potentials Sect 85:17–21. https://doi.org/10.1016/0168-5597(92)90096-T
Mirchandani AS, Beyh A, Lavrador JP et al (2020) Altered corticospinal microstructure and motor cortex excitability in gliomas: an advanced tractography and transcranial magnetic stimulation study. J Neurosurg 1:1–9. https://doi.org/10.3171/2020.2.JNS192994
Mollink J, Smith SM, Elliott LT et al (2019) The spatial correspondence and genetic influence of interhemispheric connectivity with white matter microstructure. Nat Neurosci 22:809–819. https://doi.org/10.1038/s41593-019-0379-2
Nathan PW, Smith MC, Deacon P (1990) The corticospinal tracts in man: Course and location of fibres at different segmental levels. Brain 113:303–324. https://doi.org/10.1093/brain/113.2.303
Oldfield RC (1971) The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia 9:97–113. https://doi.org/10.1016/0028-3932(71)90067-4
Porter R, Lemon R (1995) Corticospinal function and voluntary movement. Oxford University Press
Rojkova K, Volle E, Urbanski M et al (2016) Atlasing the frontal lobe connections and their variability due to age and education: a spherical deconvolution tractography study. Brain Struct Funct 221:1751–1766. https://doi.org/10.1007/s00429-015-1001-3
Rossini PM, Barker AT, Berardelli A et al (1994) Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 91:79–92. https://doi.org/10.1016/0013-4694(94)90029-9
Rossini PM, Burke D, Chen R et al (2015) Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee Clin Neurophysiol 126:1071–1107. https://doi.org/10.1016/j.clinph.2015.02.001
Rosso C, Perlbarg V, Valabregue R et al (2017) Anatomical and functional correlates of cortical motor threshold of the dominant hand. Brain Stimulat 10:952–958. https://doi.org/10.1016/j.brs.2017.05.005
Sanes JN, Donoghue JP (2000) Plasticity and Primary Motor Cortex. Annu Rev Neurosci 23:393–415. https://doi.org/10.1146/annurev.neuro.23.1.393
Sartori L, Betti S, Castiello U (2013) Corticospinal excitability modulation during action observation. J vis Exp JoVE. https://doi.org/10.3791/51001
Seidl AH (2014) Regulation of conduction time along axons. Neuroscience 276:126–134. https://doi.org/10.1016/j.neuroscience.2013.06.047
Siebner HR, Hartwigsen G, Kassuba T, Rothwell JC (2009) How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition. Cortex 45:1035–1042. https://doi.org/10.1016/j.cortex.2009.02.007
Stokes MG, Chambers CD, Gould IC et al (2005) Simple metric for scaling motor threshold based on scalp-cortex distance: application to studies using transcranial magnetic stimulation. J Neurophysiol 94:4520–4527. https://doi.org/10.1152/jn.00067.2005
Sun ZY, Klöppel S, Rivière D et al (2012) The effect of handedness on the shape of the central sulcus. Neuroimage 60:332–339. https://doi.org/10.1016/j.neuroimage.2011.12.050
Tobimatsu S, Sun S-J, Fukui R, Kato M (1998) Effects of sex, height and age on motor evoked potentials with magnetic stimulation. J Neurol 245:256–261. https://doi.org/10.1007/s004150050215
Tranulis C, Guéguen B, Pham-Scottez A et al (2006) Motor threshold in transcranial magnetic stimulation: comparison of three estimation methods. Neurophysiol Clin Neurophysiol 36:1–7. https://doi.org/10.1016/j.neucli.2006.01.005
Tuch DS, Wedeen VJ, Dale AM et al (2001) Conductivity tensor mapping of the human brain using diffusion tensor MRI. Proc Natl Acad Sci 98:11697–11701. https://doi.org/10.1073/pnas.171473898
van den Heuvel MP, Stam CJ, Boersma M, Hulshoff Pol HE (2008) Small-world and scale-free organization of voxel-based resting-state functional connectivity in the human brain. Neuroimage 43:528–539. https://doi.org/10.1016/j.neuroimage.2008.08.010
Zhao EY, Vavasour IM, Zakeri M et al (2019) Myelin water imaging and transcranial magnetic stimulation suggest structure-function relationships in multiple sclerosis. Front Phys. https://doi.org/10.3389/fphy.2019.00141
Ziemann U (2004) TMS and drugs. Clin Neurophysiol 115:1717–1729. https://doi.org/10.1016/j.clinph.2004.03.006
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The study was supported by a grant from MIUR (Dipartimenti di Eccellenza DM 11/05/2017 n. 262) to the Department of General Psychology.
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Betti, S., Fedele, M., Castiello, U. et al. Corticospinal excitability and conductivity are related to the anatomy of the corticospinal tract. Brain Struct Funct 227, 1155–1164 (2022). https://doi.org/10.1007/s00429-021-02410-9
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DOI: https://doi.org/10.1007/s00429-021-02410-9