Mechanisms underlying atDCS-effects in patients with recurrent traumatic brain injury - a multi-modal analysis using electrophysiology, MR-spectroscopy and functional MRI

• Applicant: Professorin Dr. Agnes Flöel
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 240331393

Around 270,000 people in Germany sustain a concussion (traumatic brain injury, TBI) each year. In sports like ice hockey and American football the probability of suffering a TBI is particularly high (up to 5% / year). Recurrent TBI often lead to persistent cognitive and motor deficits. Epidemiological studies identified recurrent TBI as an independent risk factor for the development of Alzheimer´s dementia.Repeated TBI lead to a lifelong increase of Gamma aminobutyric acid (GABA) in the brain. GABA inhibits the formation of synaptic plasticity like long term potentiation (LTP). Increased GABA-activity and reduced LTP could already be demonstrated in athletes with a history of recurrent TBI, and may be responsible for the cognitive deficits in these individuals.A promising method to reduce both GABA and to increase learning ability and cortical plasticity is transcranial direct current stimulation (tDCS). Anodal tDCS (atDCS) over the primary motor cortex (M1) has been shown to reduce GABA concentration, as detected by magnetic resonance spectroscopy (MRS). Moreover, a positive effect of atDCS over M1 is known to improve LTP-like plasticity (as measured by transcranial magnetic stimulation, TMS) and motor learningIn a multimodal approach, we want to explore the effects of atDCS over M1 on behavioral, neurophysiological, neurochemical and functional and connectivity parameters in athletes with a history of recurrent TBI, and compare these results to a healthy control group. We will evaluate changes of GABA-concentration and GABA-activity (as measured by MRS and specific TMS paradigms), motor learning, LTP-like plasticity, as well as functional connectivity (using functional MRI), after atDCS and after sham stimulation (control condition).We expect that atDCS will significantly decrease GABA-concentration and GABA-activity , and will enhance LTP-like plasticity, motor learning and functional connectivity, as compared to sham stimulationIn addition to important insights into the mechanisms atDCS in the healthy and the injured brain, the study will yield a more thorough understanding of the mechanisms underlying cognitive deficits after recurrent TBI. In a proof-of-principle approach, we also want to explore the therapeutic potential of atDCS in patients after TBI. In the future, atDCS could be an important tool to improve TBI-associated memory impairment and may help to prevent neurodegenerative dementias.

• DFG Programme: Research Grants