Failure of spinal paired associative stimulation to induce neuroplasticity in the human corticospinal tract

J Spinal Cord Med. 2014 Sep;37(5):565-74. doi: 10.1179/2045772314Y.0000000267.


Context/objective: Paired associative stimulation (PAS) involves paired-stimulation pulses at both the head (via transcranial magnetic stimulation) and the periphery (via peripheral nerve stimulation). The purpose of PAS, when applied to the spinal cord, is to induce neuroplasticity and upregulate the corticospinal tract leading to effector muscles. While limited research has suggested that it is possible to produce neuroplasticity through spinal PAS, all such studies have provided stimulation at a fixed frequency of 0.1 or 0.2 Hz.

Design/interventions: The present study therefore sought to compare the effectiveness of a typical 0.1 Hz paradigm with a 1 Hz paradigm, and a paradigm which provided stimulation in 5 Hz "bursts". Two inter-stimulus intervals were tested: one which was expected to produce synchronous pre- and post-synaptic activation at the spinal synapse, and one which was not. The peripheral stimulation was applied at the wrist, to induce thumb adduction.

Results: None of the paradigms were able to successfully induce neuroplasticity in a consistent manner.

Conclusion: The high between-subject variability in this study suggests that responses to the spinal PAS treatment may have been highly individual. This serves to highlight a potential limitation of the spinal PAS treatment, which is that its effectiveness may not be universal, but rather dependent on each specific recipient. This may be a challenge faced by spinal PAS should it continue to be tested as a potential novel therapy.

Keywords: Electric stimulation therapy; Neuroplasticity; Spinal cord; Transcranial magnetic stimulation.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Combined Modality Therapy / methods
  • Evoked Potentials, Motor / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Contraction / physiology*
  • Neuronal Plasticity*
  • Pyramidal Tracts / physiology*
  • Reference Values
  • Transcranial Magnetic Stimulation / methods*
  • Transcutaneous Electric Nerve Stimulation / methods*
  • Treatment Failure
  • Treatment Outcome