Verstärkung der SMA-M1 Verbindung des menschlichen Motorkortex durch neuartige nicht-invasive Hirnstimulation zur Verbesserung motorischer Leistungen und Lernprozesse

• Antragsteller: Professor Dr. Ulf Ziemann
• Fachliche Zuordnung: Klinische Neurologie; Neurochirurgie und Neuroradiologie ; Kognitive, systemische und Verhaltensneurobiologie
• Förderung: Förderung von 2014 bis 2019
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 259105706

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

The proposed project aimed at modulating physiological dynamic connectivity states of a specific cortico-cortical projection, i.e., between the supplementary motor area (SMA) and the primary motor cortex (M1) of the human brain, by timing- and site-specific non-invasive focal brain stimulation, using a novel combination of paired-associative stimulation (PAS) and transcranial direct current stimulation (tDCS). We sought to verify the hypothesis that posterior-anterior (PA) but not anterior-posterior (AP) tDCS of M1 produces cooperative effects with corticospinal plasticity induced by PAS of the SMA to M1 projection (PASSMAM1) in a highly controlled experimental design. Only the first experiment (PAS SMA->M1 with concurrent anodal M1-tDCS) was carried out within the originally planned project. This resulted in nil findings. The main hypothesis could not be verified. Since this main experiment was negative with respect to the primary hypothesis of this project, we concluded that it was unreasonable to continue with any of the other planned experiments within the project, as all of these experiments hinged on verification of the primary hypothesis (cooperative effect of anodal tDCS and PAS SMA->M1 induced plasticity). We decided to re-direct this project to pursue a similar purpose: improvement of inter-subject variability and effect size of TMS-induced plasticity, but with a novel alternative technique: real-time analysis of brain-state by electroencephalography (EEG) to trigger TMS only at specific states, i.e., phases of ongoing endogenous brain oscillations. The new technique has been termed EEG-TMS. We found that the EEG negative vs. positive peak of the endogenous sensorimotor gamma-rhythm represent high- vs. low-excitability states of corticospinal neurons, i.e. motor evoked potentials were larger when TMS pulses were given at the negative compared to positive peak. More importantly, otherwise identical repetitive high-frequency burst-TMS protocols triggered consistently at this high excitability vs. low-excitability state led to long-term potentiation (LTP)-like vs. no change in corticospinal excitability. Furthermore, low-frequency regular repetitive TMS resulted in a switch from long-term depression-like to LTP-like plasticity when triggered at the high- rather than low-excitability state. Findings raise the intriguing possibility that real-time information of instantaneous brain state can be used to control efficacy of plasticity induction in humans. This may result in a paradigm shift of therapeutic brain stimulation from open-loop fixed non-personalized stimulation protocols to individualized brain-state-dependent or even closed-loop adaptive stimulation protocols.

Projektbezogene Publikationen (Auswahl)

• (2017) Polarity-independent effects of tDCS on paired associative stimulation-induced plasticity. Brain Stimul 10:1061-1069
  Faber H, Opitz A, Müller-Dahlhaus F, Ziemann U
  
• (2018) Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex. Brain Stimul 11:1322-1330
  Gordon PC, Desideri D, Belardinelli P, Zrenner C, Ziemann U
  
• (2018) Modulation of cortical responses by transcranial direct current stimulation of dorsolateral prefrontal cortex: A resting-state EEG and TMS-EEG study. Brain Stimul 11:1024-1032
  Gordon PC, Zrenner C, Desideri D, Belardinelli P, Zrenner B, Brunoni AR, Ziemann U
  
• (2018) mu-Rhythm Extracted With Personalized EEG Filters Correlates With Corticospinal Excitability in Real-Time Phase-Triggered EEG-TMS. Front Neurosci 12:954
  Schaworonkow N, Caldana Gordon P, Belardinelli P, Ziemann U, Bergmann TO, Zrenner C
  
• (2018) Nil effects of mu-rhythm phase-dependent burst-rTMS on cortical excitability in humans: A resting-state EEG and TMS-EEG study. PLoS One 13:e0208747
  Desideri D, Zrenner C, Gordon PC, Ziemann U, Belardinelli P
  
• (2018) Real-time EEG-defined excitability states determine efficacy of TMS-induced plasticity in human motor cortex. Brain Stimul 11:374-389
  Zrenner C, Desideri D, Belardinelli P, Ziemann U
  
• (2019) EEG-triggered TMS reveals stronger brain state-dependent modulation of motor evoked potentials at weaker stimulation intensities. Brain Stimul 12:110-118
  Schaworonkow N, Triesch J, Ziemann U, Zrenner C
  
• (2019) Phase of sensorimotor muoscillation modulates cortical responses to TMS of the human motor cortex. J Physiol
  Desideri D, Zrenner C, Ziemann U, Belardinelli P