Deconstruction of cortical evoked potentials generated by subthalamic DBS (Kumaravelu et al 2018)

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"... 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. First, we recorded cEP over ipsilateral primary motor cortex during different frequencies of STN DBS in awake healthy and unilateral 6-OHDA lesioned parkinsonian rats. 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. R1 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 cortico-thalamic-cortical pathway. 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."
1 . Kumaravelu K, Oza CS, Behrend CE, Grill WM (2018) Model-based deconstruction of cortical evoked potentials generated by subthalamic nucleus deep brain stimulation. J Neurophysiol 120:662-680 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex; Thalamus;
Cell Type(s): Neocortex M1 L6 pyramidal corticothalamic GLU cell; Neocortex M1 L5B pyramidal pyramidal tract GLU cell; Neocortex M1 L4 stellate GLU cell; Hodgkin-Huxley neuron; Neocortex layer 4 neuron; Neocortex fast spiking (FS) interneuron; Neocortex primary motor area pyramidal layer 5 corticospinal cell;
Channel(s): I Na,p; I K; I Sodium; I_KD; I Calcium; I T low threshold; I L high threshold; I_AHP;
Gap Junctions: Gap junctions;
Receptor(s): AMPA; Gaba; NMDA;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Deep brain stimulation; Evoked LFP;
Implementer(s): Kumaravelu, Karthik [kk192 at];
Search NeuronDB for information about:  Neocortex M1 L6 pyramidal corticothalamic GLU cell; Neocortex M1 L5B pyramidal pyramidal tract GLU cell; Neocortex M1 L4 stellate GLU cell; AMPA; NMDA; Gaba; I Na,p; I L high threshold; I T low threshold; I K; I Sodium; I Calcium; I_AHP; I_KD; Gaba; Glutamate;
balcomp.hoc *
defvar.hoc *
lbcreate.hoc *
mscreate.hoc *
parlib2.hoc *
traubcon.hoc *
traubcon_net.hoc *
proc load_balanced_create() {local host, gid, usx, sx, si, sb, c, cc, ptree \
  localobj cell, sr
	host =[$1]
	gid = load_balance_.gid.x[$1]
	sx = load_balance_.splitx.x[$1]
	usx = load_balance_.unsplitx.x[$1]
	si = load_balance_.spliti.x[$1]
	sb = load_balance_.splitb.x[$1]

	cell = cells.object(cells.count-1)

	if (sx < 0) { // entirely on this cpu
		c = load_balance_.cell_complexity(cell)
		sr = ldbal_reconnect(si, abs(sb))
// following tests must be carried out with point process complexities in mcomplex.dat = 0
//sr.sec printf("%d a split %s %g %g    %g %g   %d %d %d %d\n",, secname(), usx, c, sx, usx - sx, host, gid, si, sb)
		ptree = 0 if (sb < 0) { ptree = 1 }
		ldbal_split(sr, host, gid, ptree, cell)
//c = load_balance_.cell_complexity(cell)
//if (host == { cc = sx } else { cc = usx - sx }
//ptree = 0 if (!pc.gid_exists(gid)) ptree = 1
//printf("%d split %s %d %d %g %g\n",, cell, gid, ptree, c, cc)

//reconnect so a split at the returned
// SectionRef corresponds to the complexity desired
// ptree = 1 means the parent tree will go on the host
obfunc ldbal_reconnect() {local i  localobj sp, bs, sr, sc
	ip = load_balance_.parent_vec_.x[$1]
	if (ip  == -1) {
		execerror("cannot split at original root", "")
	sp = load_balance_.secref(ip)
	// the branch set (in the proper order)
	bs = load_balance_.parent_vec_.indvwhere("==", ip)
	// disconnect all the children
	// assume all children effectively connected at their 0 end to the trueparent
	// at the 1 end
	for i=0, bs.size-1 {
		sr = load_balance_.secref(bs.x[i])
		sr.sec { disconnect() }
	if ($2 <= bs.size) { // is it an individual?
		// then all get connected to the trueparent and return
		// the individual
		for i=0, bs.size-1 {
			sr = load_balance_.secref(bs.x[i])
			sp.sec connect sr.sec (0), 1
		sc = load_balance_.secref(bs.x[$2-1])
	}else{ // it is a sum
		sc = load_balance_.secref(bs.x[0])
		sp.sec connect sc.sec (0), 1
		n = $2 - bs.size // 1 means 0+1
		for i=1, n { // connect to the 0 child
			sr = load_balance_.secref(bs.x[i])
			sc.sec connect sr.sec (0), 0
		for i=n+1, bs.size-1 { // connect to the trueparent
			sr = load_balance_.secref(bs.x[i])
			sp.sec connect sr.sec (0), 1
	return sc

proc ldbal_split() {
	if ($4 == 0) {
		$o1.sec pnm.splitcell($2, $2+1)
		$o1.sec pnm.splitcell($2+1, $2)
	if (section_exists("comp", $o5.presyn_comp ,$o5)) {
		pc.set_gid2node($3 + splitbit,
		gidvec.append($3 + splitbit)