High frequency deep brain stimulation (DBS) of the
subthalamic nucleus (STN) suppresses parkinsonian motor symptoms and
modulates cortical activity.
Cortical evoked potentials (cEP) generated by STN DBS reflect
the response of cortex to subcortical stimulation, and the goal was to
determine the neural origin of cEP using a two-step approach.
we recorded cEP over ipsilateral primary motor cortex during different
frequencies of STN DBS in awake healthy and unilateral 6-OHDA lesioned
Second, we used a biophysically-based model of the
thalamocortical network to deconstruct the neural origin of the
cEP. The in vivo cEP included short (R1), intermediate (R2) and
long-latency (R3) responses. Model-based cortical responses to
simulated STN DBS matched remarkably well the in vivo responses.
was generated by antidromic activation of layer 5 pyramidal neurons,
while recurrent activation of layer 5 pyramidal neurons via excitatory
axon collaterals reproduced R2. R3 was generated by polysynaptic
activation of layer 2/3 pyramidal neurons via the
Antidromic activation of the
hyperdirect pathway and subsequent intracortical and
cortico-thalamo-cortical synaptic interactions were sufficient to
generate cEP by STN DBS, and orthodromic activation through basal
ganglia-thalamus-cortex pathways was not required. These results
demonstrate the utility of cEP to determine the neural elements
activated by STN DBS that might modulate cortical activity and
contribute to the suppression of parkinsonian symptoms."