Measuring latency distribution of transcallosal fibers using transcranial magnetic stimulation

Zhen Ni, Giorgio Leodori, Felipe Vial, Yong Zhang, Alexandru V Avram, Sinisa Pajevic, Peter J Basser, Mark Hallett, Zhen Ni, Giorgio Leodori, Felipe Vial, Yong Zhang, Alexandru V Avram, Sinisa Pajevic, Peter J Basser, Mark Hallett

Abstract

Background: Neuroimaging technology is being developed to enable non-invasive mapping of the latency distribution of cortical projection pathways in white matter, and correlative clinical neurophysiological techniques would be valuable for mutual verification. Interhemispheric interaction through the corpus callosum can be measured with interhemispheric facilitation and inhibition using transcranial magnetic stimulation.

Objective: To develop a method for determining the latency distribution of the transcallosal fibers with transcranial magnetic stimulation.

Methods: We measured the precise time courses of interhemispheric facilitation and inhibition with a conditioning-test paired-pulse magnetic stimulation paradigm. The conditioning stimulus was applied to the right primary motor cortex and the test stimulus was applied to the left primary motor cortex. The interstimulus interval was set at 0.1 ms resolution. The proportions of transcallosal fibers with different conduction velocities were calculated by measuring the changes in magnitudes of interhemispheric facilitation and inhibition with interstimulus interval.

Results: Both interhemispheric facilitation and inhibition increased with increment in interstimulus interval. The magnitude of interhemispheric facilitation was correlated with that of interhemispheric inhibition. The latency distribution of transcallosal fibers measured with interhemispheric facilitation was also correlated with that measured with interhemispheric inhibition.

Conclusions: The data can be interpreted as latency distribution of transcallosal fibers. Interhemispheric interaction measured with transcranial magnetic stimulation is a promising technique to determine the latency distribution of the transcallosal fibers. Similar techniques could be developed for other cortical pathways.

Trial registration: ClinicalTrials.gov NCT03223636.

Keywords: Corpus callosum; Interhemispheric facilitation and interhemispheric inhibition; Latency distribution; Motor evoked potential; Primary motor cortex; Transcranial magnetic stimulation.

Conflict of interest statement

Declaration of competing interest All authors declare no conflict of interest. We further confirm that all subjects provided written informed consent and any aspect of the work covered in this study (clinical protocol, Clinicaltrials.gov Identifier NCT03223636) that has involved human subjects has been conducted with the ethical approval of the Combined NeuroScience Institutional Review Board at the National Institutes of Health.

Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Latency distribution of the transcallosal fibers tested with interhemispheric interaction. (A) Experimental setup. IHF and IHI from the right primary motor cortex to the left primary motor cortex tested with a paired-pulse transcranial magnetic stimulation paradigm were used to verify the latency distribution of transcallosal fibers with different diameters (color lines). The first CS was given to the right primary motor cortex. The second TS was given to the left primary motor cortex. The small arrows close to the coil show the induced current direction in the brain. (B) Hypothesis. CS activates multiple pyramidal neurons (triangles with different sizes) in the right primary motor cortex. These pyramidal neurons are connected to the transcallosal fibers with different diameters (color lines with different thickness). Pyramidal neurons (black triangle) in the left primary motor cortex are directly influenced by transcallosal inputs, leading to IHF. Local inhibitory interneurons (black rhombus) in the left cortex are also activated by transcallosal inputs, leading to IHI with longer latency. Dashed line indicates the mid-sagittal line. Facilitatory and inhibitory interactions are marked with small open and filled circles, respectively. (C) Example recordings. Average of 10 trials. All trials included a TS (vertical line). TS alone generated a MEP of about 0.5 mV in amplitude (first row). A preceding CS produced IHF at short ISIs (2–6 ms, second to sixth rows). IHI was induced at longer ISIs (8–14 ms, bottom rows). (D) IHF and IHI (N = 12) tested at ISIs of 1–15 ms with 1 ms resolution. Abscissa indicates the ISI. Ordinate indicates MEP amplitude induced by the paired-pulse stimulation. It is expressed as a percentage value of the mean MEP amplitude evoked by CS-TS to that evoked by TS alone (dashed line). Values above 100% indicate IHF (open circle) and values below 100% indicate IHI (filled circle). ∗P < 0.05, ∗∗P < 0.01, post hoc paired t-test with Bonferroni’s correction comparing MEP with paired-pulse stimulation to that with TS alone. CS = conditioning stimulus; IHF = interhemispheric facilitation; IHI = interhemispheric inhibition; IN = local inhibitory interneuron in the left primary motor cortex; ISI = interstimulus interval; MEP = motor evoked potential; TS = test stimulus. . (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 2
Fig. 2
Precise time courses of interhemispheric facilitation and inhibition. (A) IHF and (B) IHI (N = 12) tested at ISIs 1.5 ms before and 0.5 ms after the time points for maximal facilitation and inhibition with 0.1 ms resolution. Abscissa indicates the ISI. Time 0 was defined as the ISI with maximal IHF or IHI in each subject. Ordinate indicates the magnitude of IHF (open circle) or IHI (filled circle). It is expressed as a percentage difference between motor evoked potential amplitude induced by CS-TS paired-pulse stimulation and that induced by TS alone (defined as 100%). The value for IHF is positive and that for IHI is negative. ∗P < 0.05, ∗∗P < 0.01, post hoc paired t-test with Bonferroni’s correction comparing motor evoked potential with paired-pulse stimulation to that with TS alone. CS = conditioning stimulus; IHF = interhemispheric facilitation; IHI = interhemispheric inhibition; ISI = interstimulus interval; TS = test stimulus.
Fig. 3
Fig. 3
Latency distribution measurement. Latency distribution of transcallosal fibers measured with (A) IHF and (B) IHI in one subject. The ISI range from no IHF (or IHI) to the maximal IHF (or IHI) was shown. Abscissa indicates the ISI. Left ordinate (blue) in each panel indicates the magnitude of IHF (blue open circle) or IHI (blue filled circle). It is expressed as a percentage difference between motor evoked potential amplitude induced by CS-TS paired-pulse stimulation and that induced by TS alone (defined as 100%). The value for IHF is positive and that for IHI is negative. Right ordinate (red) in each panel indicates the proportion of the nerve fibers with certain conduction velocity in the whole bundle. The proportion for a group of nerve fibers (red curve) was represented by the percentage of the difference in IHF (or IHI) with the minimal increase in ISI (0.1 ms) divided by the maximal IHF (or IHI). The curve was smoothed with a two-point moving average. Note that the peak proportion of transcallosal fibers measured with IHF and that with IHI were similar. CS = conditioning stimulus, IHF = interhemispheric facilitation, IHI = interhemispheric inhibition, ISI = interstimulus interval, TS = test stimulus. . (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Fig. 4
Fig. 4
Correlation analysis for measurements with interhemispheric interaction. (A) Correlation between IHF and IHI at the peak interstimulus intervals. Abscissa indicates the magnitude of maximal IHF and ordinate indicates the magnitude of maximal IHI. They are expressed as a percentage difference between motor evoked potential amplitude induced by CS-TS paired-pulse stimulation and that induced by TS alone. The value for IHF is positive and that for IHI is negative. (B) Correlation between the proportion of the largest group of transcallosal fibers measured with IHF and that measured with IHI. Abscissa indicates the proportion of transcallosal fibers measured with IHF and ordinate indicate that measured with IHI. They are expressed as a percentage value of the largest change in IHF (or IHI) with the minimal increase in interstimulus interval (0.1 ms) divided by the maximal IHF (or IHI). The solid lines indicate significant correlation between two different variables with P < 0.05. CS = conditioning stimulus, IHF = interhemispheric facilitation, IHI = interhemispheric inhibition, TS = test stimulus.

References

    1. Wedeen V.J., Rosene D.L., Wang R. The geometric structure of the brain fiber pathways. Science. 2012;335:1628–1634.
    1. Drakesmith M., Harms R., Rudrapatna S.U., Parker G.D., Evans C.J., Jones D.K. Estimating axon conduction velocity in vivo from microstructural MRI. Neuroimage. 2019;203:116186.
    1. Callaghan P.T., Coy A., MacGowan D., Packer K.J., Zelaya F.O. Diffraction-like effects in NMR diffusion studies of fluids in porous solids. Nature. 1991;351:467–469.
    1. Basser P.J., Pajevic S., Pierpaoli C., Duda J., Aldroubi A. In vivo fiber tractography using DT-MRI data. Magn Reson Med. 2000;44:625–632.
    1. Avram A.V., Sarlls J.E., Barnett A.S. Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure. Neuroimage. 2016;127:422–434.
    1. Assaf Y., Blumenfeld-Katzir T., Yovel Y., Basser P.J. AxCaliber: a method for measuring axon diameter distribution from diffusion MRI. Magn Reson Med. 2008;59:1347–1354.
    1. Komlosh M.E., Ozarslan E., Lizak M.J. Mapping average axon diameters in porcine spinal cord white matter and rat corpus callosum using d-PFG MRI. Neuroimage. 2013;78:210–216.
    1. Ni Z., Vial F., Avram A.V. Measuring conduction velocity distributions in peripheral nerves using neurophysiological techniques. Clin Neurophysiol. 2020;131:1581–1588.
    1. Gazzaniga M.S. Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain. 2000;123:1293–1326.
    1. Luders E., Thompson P.M., Toga A.W. The development of the corpus callosum in the healthy human brain. J Neurosci. 2010;30:10985–10990.
    1. Zarei M., Johansen-Berg H., Smith S., Ciccarelli O., Thompson A.J., Matthews P.M. Functional anatomy of interhemispheric cortical connections in the human brain. J Anat. 2006;209:311–320.
    1. Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007;55:187–199.
    1. Ni Z., Müller-Dahlhaus F., Chen R., Ziemann U. Triple-pulse TMS to study interactions between neural circuits in human cortex. Brain Stimul. 2011;4:281–293.
    1. Hanajima R., Ugawa Y., Machii K. Interhemispheric facilitation of the hand motor area in humans. J Physiol. 2001;531:849–859.
    1. Baumer T., Bock F., Koch G. Magnetic stimulation of human premotor or motor cortex produces interhemispheric facilitation through distinct pathways. J Physiol. 2006;572:857–868.
    1. Ferbert A., Priori A., Rothwell J.C., Day B.L., Colebatch J.G., Marsden C.D. Interhemispheric inhibition of the human motor cortex. J Physiol. 1992;453:525–546.
    1. Ni Z., Gunraj C., Nelson A.J. Two phases of interhemispheric inhibition between motor related cortical areas and the primary motor cortex in human. Cerebr Cortex. 2009;19:1654–1665.
    1. Boroojerdi B., Battaglia F., Muellbacher W., Cohen L.G. Mechanisms influencing stimulus-response properties of the human corticospinal system. Clin Neurophysiol. 2001;112:931–937.
    1. Rothwell J.C., Thompson P.D., Day B.L., Boyd S., Marsden C.D. Stimulation of the human motor cortex through the scalp. Exp Physiol. 1991;76:159–200.
    1. Oldfield R.C. The assessment and analysis of handedness: the Edingburgh inventory. Neuropsychologia. 1971;9:97–113.
    1. Kaneko K., Kawai S., Fuchigami Y., Morita H., Ofuji A. The effect of current direction induced by transcranial magnetic stimulation on the corticospinal excitability in human brain. Electroencephalogr Clin Neurophysiol. 1996;101:478–482.
    1. Di Lazzaro V., Oliviero A., Saturno E. The effect on corticospinal volleys of reversing the direction of current induced in the motor cortex by transcranial magnetic stimulation. Exp Brain Res. 2001;138:268–273.
    1. Wahl M., Lauterbach-Soon B., Hattingen E. Human motor corpus callosum: topography, somatotopy, and link between microstructure and function. J Neurosci. 2007;27:12132–12138.
    1. Hofer S., Frahm J. Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. Neuroimage. 2006;32:989–994.
    1. Aboitiz F., Scheibel A.B., Fisher R.S., Zaidel E. Fiber composition of the human corpus callosum. Brain Res. 1992;598:143–153.
    1. Avanzino L., Teo J.T., Rothwell J.C. Intracortical circuits modulate transcallosal inhibition in humans. J Physiol. 2007;583:99–114.
    1. Chen R., Yung D., Li J.-Y. Organization of ipsilateral excitatory and inhibitory pathways in the human motor cortex. J Neurophysiol. 2003;89:1256–1264.
    1. Kukaswadia S., Wagle-Shukla A., Morgante F., Gunraj C., Chen R. Interactions between long latency afferent inhibition and interhemispheric inhibitions in the human motor cortex. J Physiol. 2005;563:915–924.
    1. Daskalakis Z.J., Christensen B.K., Fitzgerald P.B., Roshan L., Chen R. The mechanisms of interhemispheric inhibition in the human motor cortex. J Physiol. 2002;543:317–326.
    1. Lemon R.N. Descending pathways in motor control. Annu Rev Neurosci. 2008;31:195–218.
    1. Müller-Dahlhaus F., Liu Y., Ziemann U. Inhibitory circuits and the nature of their interactions in the human motor cortex a pharmacological TMS study. J Physiol. 2008;586:495–514.
    1. Lee H., Gunraj C., Chen R. The effects of inhibitory and facilitatory intracortical circuits on interhemispheric inhibition in the human motor cortex. J Physiol. 2007;580:1021–1032.
    1. Fame R.M., MacDonald J.L., Macklis J.D. Development, specification, and diversity of callosal projection neurons. Trends Neurosci. 2011;34:41–50.
    1. Tomasi S., Caminiti R., Innocenti G.M. Areal differences in diameter and length of corticofugal projections. Cerebr Cortex. 2012;22:1463–1472.
    1. Hursh J.B. Conduction velocity and diameter of nerve fibers. Am J Physiol. 1939;127:131–139.
    1. Sherman D.L., Brophy P.J. Mechanisms of axon ensheathment and myelin growth. Nat Rev Neurosci. 2005;6:683–690.
    1. Hopf H.C. Electromyographic study on so-called mononeuritis. Arch Neurol. 1963;9:307–312.
    1. Stalberg E., van Dijk H., Falck B. Standards for quantification of EMG and neurography. Clin Neurophysiol. 2019;130:1688–1729.
    1. Ingram D.A., Davis G.R., Swash M. Motor nerve conduction velocity distributions in man: results of a new computer-based collision technique. Electroencephalogr Clin Neurophysiol. 1987;66:235–243.
    1. Di Lazzaro V., Profice P., Ranieri F. I-wave origin and modulation. Brain Stimul. 2012;5:512–525.
    1. Di Lazzaro V., Oliviero A., Profice P. Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation. Exp Brain Res. 1999;124:520–524.
    1. Ni Z., Charab S., Gunraj C. Transcranial magnetic stimulation in different current directions activates separate cortical circuits. J Neurophysiol. 2011;105:749–756.
    1. Di Lazzaro V., Rothwell J.C. Corticospinal activity evoked and modulated by non-invasive stimulation of the intact human motor cortex. J Physiol. 2014;592:4115–4128.
    1. Harris-Love M.L., Perez M.A., Chen R., Cohen L.G. Interhemispheric inhibition in distal and proximal arm representations in the primary motor cortex. J Neurophysiol. 2007;97:2511–2515.
    1. Basser P.J., Mattiello J., LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J. 1994;66:259–267.
    1. Koch G., Cercignani M., Bonni S. Asymmetry of parietal interhemispheric connections in humans. J Neurosci. 2011;31:8967–8975.
    1. Komlosh M.E., Özarslan E., Lizak M.J. Mapping average axon diameters in porcine spinal cord white matter and rat corpus callosum using d-PFG MRI. Neuroimage. 2013;78:210–216.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir