Induction of Synaptic Plasticity in the Human Brain by individualized biphasic repetitive I-wave Transcranial Magnetic Stimulation

• Applicants: Dr.-Ing. Bernhard Gleich; Dr. Nikolai Jung
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Electronic Semiconductors, Components and Circuits, Integrated Systems, Sensor Technology, Theoretical Electrical Engineering ; Pediatric and Adolescent Medicine
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398820493

• Final Report Year: 2023

Final Report Abstract

Synaptic plasticity in forms of long-term potentiation (LTP) and long-term depression (LTD) is considered to be the neurophysiological correlate of learning and memory. Impairments of these basal neurophysiological mechanisms (i.e. LTP and LTD) are thought to play a pivotal role in the development and phenotype of various medical conditions (e.g. developmental disorder). Repetitive transcranial magnetic stimulation (rTMS) – e.g. theta-burst stimulation (TBS) or quadri-pulse stimulation – is one of the most popular methods for non-invasive brain stimulation that can be used to induce and to investigate synaptic plasticity in humans. It becomes gradually more noticed in basic neuroscience as well as in the treatment of various neurological diseases such as drug resistant depression and rehabilitation after stroke. To reduce variability of after effects in this context, an individualized stimulation may be important. This variability may be triggered by individual oscillations so called I-waves. According to their individual latency, mainly three peaks have been discovered, termed I1-3 waves with a latency of app. 1.5 ms. They seem to contribute to and to modulate synaptic plasticity in human primary motor cortex (M1). I-waves are not only rigid oscillations with timely relation to TMS pulses but the recruitment pattern and latency of these descending volleys underlies inter-individual variability in latencies of around 1.5 ms. Here, we present a new technique with individual on I-wave adjustable TMS parameters. In a preliminary work, we demonstrate metaplastic effects of I-wave adapted rTMS with fixed interstimulus intervals (ISI). We then investigated the interand intraindividual variability of I-wave latencies to design an individual stimulation protocol, so called iqTBS. We demonstrate in our preliminary results a significant difference between the iqTBS and a stimulation with fixed ISI. The effect of an iqTBS stimulation on motor learning is currently under investigation. Our findings may help to better understand cortical learning mechanisms and help to enhance the therapeutical effects of TMS in clinical practice.

Publications

• Transcranial magnetic stimulation devices for biphasic and polyphasic ultra-high frequency protocols. Biology, Engineering and Medicine, 3(1).
  N. Gattinger; N.H. Jung; V. Mall & B. Gleich
  
• Individualisierte hochfrequente I-Wellen adaptierte quadri-pulse theta burst stimulation. Symposium DGKN 2020.
  Jung, N., Gleich, B., Brich, L., Heidsieck, A., Gattinger, N., Siebner, H. & Mall, V.
  
• Intra-individual variability of I- wave peaks – preliminary results. Posterpräsentation DGKN 2020.
  Brich, L., Gleich, B., Schaff, F., Mall, V. & Jung, N.
  
• Intra-individuelle Variabilität der I-Wellen-Latenzen am menschlichen primär-motorischen Kortex – vorläufige Ergebnisse. GNP 2020.
  Brich, L., Gleich, B., Schaff, F., Mall, V. & Jung, N.
  
• Individualized I- waves adapted TMS – preliminary results. Posterpräsentation DGKN 2021.
  Brich, L., Schaff, F., Gleich, B., Heidsieck, A., Mall, V. & Jung, N.
  
• Variabilität intrakortikaler Oszillationen am menschlichen Kortex und deren mögliche Bedeutung für eine individuelle nicht-invasive Hirnstimulation. Kongressvortrag GNP 2021.
  Brich, L., Gleich, B., Schaff, F., Heidsieck, A., Sandurkov, B., Mall, V. & Jung, N.
  
• Individualisierte quadri-theta-burst-Stimulation zur Induktion synaptischer Plastizität beim Menschen – vorläufige Ergebnisse. Posterpräsentation GNP & Neurowoche 2022.
  Brich, L., Gleich, B., Schaff, F., Heidsieck, A., Sandurkov, B. & Mall, V.
  
• Plasticity induction in humans by individualized quadri theta burst stimulation – preliminary results. Posterpräsentation DGKN 2022.
  Brich, L. Gleich, B., Schaff, F., Heidsieck, A., Sandurkov, B., Mall, V. & Jung, N.
  
• Bidirectional changes in corticospinal excitability following quadri-pulse theta burst stimulation with individually (I-wave) adapted and fixed interstimulus intervals – preliminary results. Posterpräsentation DGKN 2023.
  Brich, L., Schaff, F., Gleich, B., Gattinger, N., Sautter, K., Heidsieck, A., Sandurkov, B., Mall, V. & Jung, N.
  
• Changes in Cortico-Spinal Excitability by Individualized Quadri-Theta-Burst Stimulation. Posterpräsentation Brain Stimulation 2023.
  Schaff, F., Brich, L., Sautter, K., Heidsieck, A., Sandurkov, B., Gleich, B., Mall & V. & Jung, N.
  
• PLUSPULS: A transcranial magnetic stimulator with extended pulse protocols. HardwareX, 13, e00380.
  Staat, Christoph; Gattinger, Norbert & Gleich, Bernhard