Altered bidirectional plasticity and reduced implicit motor learning in concussed athletes

Cereb Cortex. 2012 Jan;22(1):112-21. doi: 10.1093/cercor/bhr096. Epub 2011 May 13.

Abstract

Persistent motor/cognitive alterations and increased prevalence of Alzheimer's disease are known consequences of recurrent sports concussions, the most prevalent cause of mild traumatic brain injury (TBI) among youth. Animal models of TBI demonstrated that impaired learning was related to persistent synaptic plasticity suppression in the form of long-term potentiation (LTP) and depression (LTD). In humans, single and repeated concussive injuries lead to lifelong and cumulative enhancements of gamma-aminobutyric acid (GABA)-mediated inhibition, which is known to suppress LTP/LTD plasticity. To test the hypothesis that increased GABAergic inhibition after repeated concussions suppresses LTP/LTD and contributes to learning impairments, we used a paired associative stimulation (PAS) protocol to induce LTP/LTD-like effects in primary motor cortex (M1) jointly with an implicit motor learning task (serial reaction time task, SRTT). Our results indicate that repeated concussions induced persistent elevations of GABA(B)-mediated intracortical inhibition in M1, which was associated with suppressed PAS-induced LTP/LTD-like synaptic plasticity. This synaptic plasticity suppression was related to reduced implicit motor learning on the SRTT task relative to normal LTP/LTD-like synaptic plasticity in unconcussed teammates. These findings identify GABA neurotransmission alterations after repeated concussions and suggest that impaired learning after multiple concussions could at least partly be related to compromised GABA-dependent LTP/LTD synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Athletic Injuries / complications
  • Athletic Injuries / genetics
  • Brain Concussion / complications*
  • Brain Concussion / etiology
  • Brain Concussion / genetics
  • Brain-Derived Neurotrophic Factor / genetics
  • Electric Stimulation
  • Electromyography
  • Evoked Potentials, Motor / physiology*
  • Football
  • Humans
  • Learning Disabilities / etiology*
  • Learning Disabilities / pathology*
  • Male
  • Methionine / genetics
  • Motor Activity / genetics
  • Motor Activity / physiology*
  • Motor Cortex / physiopathology*
  • Neural Inhibition / genetics
  • Neuronal Plasticity / physiology*
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide / genetics
  • Psychomotor Performance / physiology
  • Reaction Time / genetics
  • Severity of Illness Index
  • Statistics as Topic
  • Transcranial Magnetic Stimulation / methods
  • Valine / genetics
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • Methionine
  • Valine