Subcortical control of precision grip after human spinal cord injury.
The motor cortex and the corticospinal system contribute to the control of a precision grip between the thumb and index finger. The involvement of subcortical pathways during human precision grip remains unclear. Using noninvasive cortical and cervicomedullary stimulation, we examined motor evoked potentials (MEPs) and the activity in intracortical and subcortical pathways targeting an intrinsic hand muscle when grasping a small (6 mm) cylinder between the thumb and index finger and during index finger abduction in uninjured humans and in patients with subcortical damage due to incomplete cervical spinal cord injury (SCI). We demonstrate that cortical and cervicomedullary MEP size was reduced during precision grip compared with index finger abduction in uninjured humans, but was unchanged in SCI patients. Regardless of whether cortical and cervicomedullary stimulation was used, suppression of the MEP was only evident 1-3 ms after its onset. Long-term (∼5 years) use of the GABAb receptor agonist baclofen by SCI patients reduced MEP size during precision grip to similar levels as uninjured humans. Index finger sensory function correlated with MEP size during precision grip in SCI patients. Intracortical inhibition decreased during precision grip and spinal motoneuron excitability remained unchanged in all groups. Our results demonstrate that the control of precision grip in humans involves premotoneuronal subcortical mechanisms, likely disynaptic or polysynaptic spinal pathways that are lacking after SCI and restored by long-term use of baclofen. We propose that spinal GABAb-ergic interneuronal circuits, which are sensitive to baclofen, are part of the subcortical premotoneuronal network shaping corticospinal output during human precision grip.
University of Pittsburgh, Department of Physical Medicine and Rehabilitation, Center for the Neural Basis of Cognition, Systems Neuroscience Institute, Pittsburgh, Pennsylvania 15261, and.
Karen L
KL
Bunday
University of Pittsburgh, Department of Physical Medicine and Rehabilitation, Center for the Neural Basis of Cognition, Systems Neuroscience Institute, Pittsburgh, Pennsylvania 15261, and.
Toshiki
T
Tazoe
Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
John C
JC
Rothwell
University of Pittsburgh, Department of Physical Medicine and Rehabilitation, Center for the Neural Basis of Cognition, Systems Neuroscience Institute, Pittsburgh, Pennsylvania 15261, and perezmo@pitt.edu.
Monica A
MA
Perez
D000328:Adult; D000704:Analysis of Variance; D001418:Baclofen / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology*; D005260:Female; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D018737:Hand Strength / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*
D058786:GABA-B Receptor Agonists; D001418:Baclofen
Baclofen; corticospinal drive; primary motor cortex; spasticity; spinal motoneurons; voluntary drive