This project aims to elucidate further the
neurophysiological underpinnings of spasticity and abnormal
muscle coactivation patterns (synergies) that present following
stroke by using a combination of targeted pharmacological
probes and novel robotics.
Though the exact pathophysiological mechanisms responsible
for the development of spasticity and synergies have yet to
be determined conclusively, it is thought that these two emergent
abnormalities may share a common neurological substrate. Specifically,
these movement disorders may be attributable to an increased
reliance on descending monoaminergic motor pathways originating
in the brainstem following damage to corticospinal tracts.
Importantly, bulbospinal pathways can be distinguished from
corticospinal tracts both by their comparatively diffuse vertical
spinal projections and by their profound neuromodulatory effects
on spinal alpha motoneurons.
Holistically, these distinctions help to explain putatively
both abnormal muscle synergies and spasticity. The significant
branching exhibited by bulbospinal projections can lead to
simultaneous activation of multiple motoneuron pools, thereby
facilitating the expression of synergies, while the neuromodulatory
effects of monoamines can result in motoneuronal hyperexcitability,
which is thought to contribute to the development of spasticity.
By using highly specific pharmacological agents to facilitate
and suppress specific pathways and receptors implicated in
the development of post-stroke movement disorders, this project
aims to determine the exact cause of synergies and spasticity
while also reducing their expression. A novel robotic device
capable of generating virtual environments and allowing unrestrained
motion of the upper limb (the ACT-3D system) will be used
in conjunction with other quantitative metrics and clinical
scales to assess changes motor performance before, during
and after intervention.
Figure 1. Schematic representations of (a) the
neuroanatomical organization of select descending motor pathways,
and (b) the organization of descending information transfer
from cortex to brainstem to the spinal cord. Panel A adapted
from: http://thebrain.mcgill.ca/flash/a/a_06/a_06_cl/a_06_cl_mou/a_06_cl_mou.html;
Panel B adapted from Heckman: CJ, Lee, RH, Brownstone, RM
(2003) Hyperexcitable dendrites in motoneurons and their neuromodulatory
control during motor behavior. Trends in Neurosciences 26,
688-695.
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