Mechanisms and Modulation of Motor Skill learning in the healthy and injured Brain

• Antragstellerin: Dr. Janine Reis
• Fachliche Zuordnung: Klinische Neurologie; Neurochirurgie und Neuroradiologie
• Förderung: Förderung von 2012 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 210366290

• Erstellungsjahr: 2018

Zusammenfassung der Projektergebnisse

The central hypothesis of this Emmy Noether project is that after brain injury, aside from the cerebral lesion itself, motor skill learning promotes a plastic environment that is beneficial to enhance recovery of motor function. We hypothesized that anodal tDCS, a form of noninvasive neuromodulation, can further augment this process. Moreover, we assumed that the neurotrophic factor BDNF plays a key role in promoting neuroplastic effects induced by injury, training and brain stimulation within the early time window after stroke. We investigated the process of motor skill learning in acute stroke patients and age-matched elderly controls. We found that motor skill deteriorates as a function of age and is further compromised by an acute stroke. Despite poor skill of the paretic hand, the possibility to undergo skill learning, i.e. to demonstrate behavioral improvements of motor function through training is preserved in acute stroke patients. While the learning magnitude is similar to agematched controls, the alteration of subcomponents of learning suggests that an acute stroke particularly disturbs motor memory consolidation. Subsequently, we investigated if anodal tDCS applied to the motor cortex, known to improve motor skill learning in healthy subjects and chronic stroke patients, can enhance motor skill learning in acute stroke patients. This clinical trial is ongoing and will exceed the Emmy Noether program. In translational experiments in rodents, we determined safety limits for anodal tDCS and attenuated current concerns of negative effects of tDCS on stroke lesion size. The similar temporal dynamics of BDNF tissue protein contents in the affected hemisphere as well the course of spontaneous recovery of fine motor function in the first fourteen days post stroke support the concept of an early “plastic window”. We showed that BDNF secretion in the injured brain can be modified by anodal tDCS applied to the affected hemisphere. Moreover, tDCS positively interacted with the physiological recovery process when combined with plasticity-inducing interventions such as motor training. Taken together, noninvasive electrical brain stimulation may hold the potential to optimize plasticity within an early critical time period after acute stroke.

Projektbezogene Publikationen (Auswahl)

• Effects of different electrical brain stimulation protocols on subcomponents of motor skill learning. Brain Stimulation 2014;7(4):532-40
  Prichard G, Weiller C, Fritsch B, Reis J
  
• Cerebellar direct current stimulation enhances on-line motor skill acquisition through an effect on accuracy. Journal of Neuroscience 2015; 35(7), 3285-3290
  Cantarero G, Spampinato D, Reis J, Ajagbe L, Thompson T, Kulkarni K, Celnik P
  
• Time- but not sleep dependent consolidation of tDCS-enhanced visuomotor skills. Cereb Cortex 2015;25(1):109-17
  Reis J, Fischer JT, Prichard G, Weiller C, Cohen LG, Fritsch B
  
• Glia: A Neglected Player in Non-invasive Direct Current Brain Stimulation. Frontiers in Cellular Neuroscience 2016; 10:188
  Gellner AK, Reis J, Fritsch B
  
• Non-invasive electrical brain stimulation montages for modulation of human motor function. J. Vis. Exp 2016; 108
  Curado MR, Fritsch B, Reis J
  
• Pre-Trial EEG-Based Single-Trial Motor Performance Prediction to Enhance Neuroergonomics for a Hand Force Task. Frontiers in Human Neuroscience 2016;10:170
  Meinel A, Castaño-Candamil S, Reis J, Tangermann M
  
• Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimulation 2016, 9(5), 641–61
  Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, …. Reis J,… Woods AJ
  
• Anodal Transcranial Direct Current Stimulation enhances Survival and Integration of Dopaminergic Cell Transplants in a Rat Parkinson Model. eNeuro 2017;19:4(5)
  Winkler C, Reis J, Hoffmann N , Gellner AK, Münkel C, Curado MR, Furlanetti L, Garcia J, Dobrossy M, Fritsch B
  
• Effects of tDCS on motor learning and memory formation: a consensus and critical position paper. Clin Neurophysiol. 2017;128(4):589-603
  Buch ER, Santarnecchi E, Antal A, Born J, Celnik PA, Classen J, Gerloff C, Hallett M, Hummel FC, Nitsche MA, Pascual-Leone A, Paulus WJ, Reis J, Robertson EM, Rothwell JC, Sandrini M, Schambra HM, Wassermann EM, Ziemann U, Cohen LG
  
• Transcranial Electrical Brain Stimulation in Alert Rodents. J Vis Exp. 2017;(129)
  Fritsch B, Gellner AK, Reis J