Test-retest reliability of a stimulation-locked evoked response to deep brain stimulation in subcallosal cingulate for treatment resistant depression

Abstract

Deep brain stimulation (DBS) to the subcallosal cingulate cortex (SCC) is an emerging therapy for treatment resistant depression. Precision targeting of specific white matter fibers is now central to the model of SCC DBS treatment efficacy. A method to confirm SCC DBS target engagement is needed to reduce procedural variance across treatment providers and to optimize DBS parameters for individual patients. We examined the reliability of a novel cortical evoked response that is time-locked to a 2 Hz DBS pulse and shows the propagation of signal from the DBS target. The evoked response was detected in four individuals as a stereotyped series of components within 150 ms of a 6 V DBS pulse, each showing coherent topography on the head surface. Test-retest reliability across four repeated measures over 14 months met or exceeded standards for valid test construction in three of four patients. Several observations in this pilot sample demonstrate the prospective utility of this method to confirm surgical target engagement and instruct parameter selection. The topography of an orbital frontal component on the head surface showed specificity for patterns of forceps minor activation, which may provide a means to confirm DBS location with respect to key white matter structures. A divergent cortical response to unilateral stimulation of left (vs. right) hemisphere underscores the need for feedback acuity on the level of a single electrode, despite bilateral presentation of therapeutic stimulation. Results demonstrate viability of this method to explore patient-specific cortical responsivity to DBS for brain-circuit pathologies.

Keywords: cortico-cortical evoked potential; deep brain stimulation; forceps minor; stimulation evoked potential; subcallosal cingulate cortex; treatment resistant depression; white matter tractography.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1

Cortical response to unilateral stimulation of the left subcallosal cingulate. (a) Grand average of recorded voltages in the 10–10 array (n = 4; 15 sessions) following stimulation from left lead. Gray traces show maximum voltage at FP1 (bold) and Pz (hatched). x‐axis = time (ms); y‐axis = amplitude (μV). (b) Distribution of peak latencies (from 15 sessions). (c) Topography of grand average scalp voltages following stimulation from left lead at peak maxima/minima. Topography shown as if looking down on the head surface with nose oriented to the top of the page. Saturated color indicates higher amplitude (red = positive; blue = negative). Gray circle at 40 ms indicates channel FP1; and white circle at 100 ms indicates channel Pz. (d) Neural source model of grand average at peak latencies, including: the locus of stimulation in the SCC (blue circle), mesial temporal lobes and mesial temporal pole (25 ms); anterior ventral medial and orbital frontal dipoles (40 ms); frontal medial BA10 (70 ms); anterior ventral dipoles, including SCC, orbital, and medial frontal pole (100 ms), relative contribution of PCC is maximal at 100 ms (blue arrow)

Figure 2

Topography of evoked response at 25 ms reflects the location of unilateral DBS from left or right hemisphere. Topography of grand average scalp potentials (average of 15 sessions, n = 4) 25 ms following stimulation from A. Left hemisphere and C. Right hemisphere. Topography shown as if looking town on the head surface with nose oriented to the top of the page. Saturated color indicates higher amplitude (red = positive; blue = negative). B. CT showing DBS electrodes implanted in bilateral SCC

Figure 3

Reliability of the SCC DBS evoked response. A. Repeated measures in four patients shown at channel FP1. Patient‐level average across recording sessions shown in bold. Single session averages: T1 (blue), T2 (red), T3 (orange), T4 (yellow). x‐axis = time (ms), y‐axis = amplitude (μV) B. Minimum number of trials (p = .05. C. Topography of patient 1 scalp potentials at 40 ms (row 1) and 100 ms (row 2). Results shown for each of four sessions (columns). Topography shown as if looking town on the head surface with nose oriented to the top of the page. Saturated color indicates higher amplitude (red = positive; blue = negative). Gray circle at T1 indicates location of channel FP1

Figure 4

Amplitude of p100 is greater following left versus right hemisphere stimulation. (a) Topography of grand average scalp potentials (average of 15 sessions, n = 4) following stimulation from left hemisphere (left) and right hemisphere (right) at 100 ms. topography shown as if looking town on the head surface with nose oriented to the top of the page. Saturated color indicates higher amplitude (red = positive; blue = negative). (b) Means comparison within subjects. Corrected statistical threshold: *p = .0125, **p < .001

Figure 5

Divergent cortical response to left versus right SCC DBS at 40 ms. (a) Topography of grand average scalp potentials (average of 15 sessions, n = 4) on spherical head surface at 40 ms following stimulation from left hemisphere (left) and right hemisphere (right). Saturated color indicates higher amplitude (red = positive; blue = negative). (b) Differences observed in ventral medial frontal dipoles at p40 maximum: Greater following stimulation from left (left) compared with right (right) hemisphere. Lighter color indicates greater current source density (nA); yellow threshold at 50% of total range. (c) Whole‐brain probabilistic tractography of shared fiber tract maps from left and right unilateral SCC DBS target suggests additional contralateral connectivity from the left SCC target in this sample. Target in left SCC (blue); target in right SCC (orange)