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;
durand.hoc *
groucho_gapbld.hoc *
groucho_gapbld_mix.hoc *
network_specification_interface.hoc *
serial_or_par_wrapper.hoc *
synaptic_compmap_construct.hoc *
synaptic_map_construct.hoc *
// groucho_gapbld_mix.hoc
****************************this is one big comment ************************
! 15 Nov. 2003, variation of groucho_gapbld.f to allow for gj
! between 2 cell populations, eg suppyrRS and suppyrFRB, or
! tuftRS and tuftIB.  Structure of gjtable as before, with col. 1
! giving cell of 1st type and col. 3 giving coupled cell of 2nd type.

      SUBROUTINE GROUCHO_gapbld_mix (thisno, numcells1, numcells2,
     & numgj, gjtable, allowedcomps, num_allowedcomps, display)
c       Construct a gap-junction network for groucho.f
$1 thisno double
$2 numcells1 = number of cells in 1st population.
$3 numcells2 = number of cells in 2nd population.
$4 numgj = total number of gj to be formed between these populations.
// this is the output: gjtable = table of gj's: each row is a gj.  
   Entries are: cell A, compartment on cell A; cell B, compartment on cell B
$o5 allowedcomps = a list of compartments where gj allowed to form
$6 num_allowedcomps = number of compartments in a cell on which a gj 
$7 display
c    might form.
c display is an integer flag.  If display = 1, print gjtable

        INTEGER thisno, numcells1, numcells2, numgj, gjtable(numgj,4),
     &    num_allowedcomps, allowedcomps(num_allowedcomps)
        INTEGER i,j,k,l,m,n,o,p, ictr /0/
c ictr keeps track of how many gj have been "built"
        INTEGER display

        double precision seed, x1(1), x2(1), y(2)
****************************this is one big comment ************************
objref gjtable,x1, x2, y1
obfunc groucho_gapbld_mix() { // see note above for arguments:
	thisno  = $1
	numcells1 = $2
	numcells2 = $3
	numgj = $4
	allowedcomps = $o5
	num_allowedcomps = $6
	display = $7
//	print "Arrived at groucho_gapbld_mix with display = ",display

	seed = new Vector()
	objref gjtable
	gjtable = new Matrix(numgj+1, 4+1) // FORTRAN-like indicies start at 1

	ictr = 0

// 2
	while (ictr < numgj) {
		k = 1
	    not_unique = 1
	    while (not_unique) {
		x1 = durand (seed, k, x1) // durand returns vec c-style indicies
		x2 = durand (seed, k, x2)
// c This defines a candidate cell pair
                k = 2
		y = durand (seed, k, y)
// c This defines a candidate pair of compartments

		i = int ( x1.x[0] * numcells1 ) + 1
		j = int ( x2.x[0] * numcells2 ) + 1

// c Is the ORDERED cell pair (i,j) in the list so far?
// superfluous but true           if (ictr.eq.0) goto 1

		not_unique = 0
		for eL = 1, ictr {
		  if ((gjtable.x(eL,1) == i) && (gjtable.x(eL,3) == j)) {not_unique = 1}
		if (one_tenth_ncell) {
			not_unique = 0
	    } // loop replaces  if (p.eq.1) goto 2

// c Proceed with construction
// 1
	    ictr = ictr + 1
	    m = int ( y.x[0] * num_allowedcomps ) + 1
	    n = int ( y.x[1] * num_allowedcomps ) + 1

	    gjtable.x[ictr][1] = i
	    gjtable.x[ictr][3] = j
	    gjtable.x[ictr][2] = allowedcomps.x[m]
	    gjtable.x[ictr][4] = allowedcomps.x[n]

	} // loop replacing if ( goto 2

// c Possibly print out gjtable when done.
//	print "at end of groucho_gapbld_mix display = ",display,", thisno = ",thisno
	if ((display == 1) && (thisno == 0)) {
		print " MIX GJTABLE"
		for i = 1, numgj {
	          printf("%6d, %6d %6d %6d \n",gjtable.x(i,1), gjtable.x(i,2), \
                                       gjtable.x(i,3), gjtable.x(i,4))
//	print "successfully printed or not"
	return gjtable