A Computational Assessment of Target Engagement in the Treatment of Auditory Hallucinations with Transcranial Direct Current Stimulation

Abstract

We use auditory verbal hallucinations (AVH) to illustrate the challenges in defining and assessing target engagement in the context of transcranial direct current stimulation (tDCS) for psychiatric disorders. We defined the target network as the cluster of regions of interest (ROIs) that are consistently implicated in AVH based on the conjunction of multimodal meta-analytic neuroimaging data. These were prescribed in the New York Head (a population derived model) and head models of four single individuals. We appraised two potential measures of target engagement, tDCS-induced peak electric field strength and tDCS-modulated volume defined as the percentage of the volume of the AVH network exposed to electric field magnitude stronger than the postulated threshold for neuronal excitability. We examined a left unilateral (LUL) montage targeting the prefrontal cortex (PFC) and temporoparietal junction (TPJ), a bilateral (BL) prefrontal montage, and a 2 × 1 montage targeting the left PFC and the TPJ bilaterally. Using computational modeling, we estimated the peak electric field strength and modulated volume induced by each montage for current amplitudes ranging 1-4 mA. We found that the LUL montage was inferior to both other montages in terms of peak electric field strength in right-sided AVH-ROIs. The BL montage was inferior to both other montages in terms of modulated volume of the left-sided AVH-ROIs. As the modulated volume is non-linear, its variability between montages reduced for current amplitudes above 3 mA. These findings illustrate how computational target engagement for tDCS can be tailored to specific networks and provide a principled approach for future study design.

Keywords: auditory hallucinations; computational modeling; neuroimaging; schizophrenia; transcranial direct current stimulation.

Figure 1

(A) Spatial distribution of the coordinates from meta-analyses of studies of patients with auditory verbal hallucinations (AVH) derived from Table S11 in Supplementary Material. Red = during AVH, green = during auditory or language tasks, and blue = morphometric studies. (B) Three-dimensional rendering of the brain regions of interest associated with AVH in a representative model. L, left.

Figure 2

Electric field modeling of transcranial direct current stimulation (tDCS) for three montages: (A) left unilateral 1 × 1 montage with F3-FP1 as the anode and T3-P3 as the cathode, (B) bilateral prefrontal 1 × 1 montage with F3-FP1 as the anode and FP2 as the cathode, and (C) 2 × 1 montage with F3-FP1 as the anode and cathodes at T3-P3 and T4-P4. First column shows tDCS electrode placements representing anode (red) and cathode (blue) electrodes in the New York head model (Subject 1; S1). Rows from top to bottom show electric field magnitude (E) and electric field normal to the cortical surface (E_n) for the models of Subjects 1–5 (S1–S5) at current amplitude of 2 mA.

Figure 3

(A) Regional electric field strength and spatial distribution at a current of 2 mA generated by each transcranial direct current stimulation montage in a representative head model. (B) Peak electric field magnitude at a current of 2 mA in each auditory verbal hallucinations (AVH) region of interest (ROI). Bars show mean values, and error bars show SD across the five head models for each target AVH-ROI. (C) Spatial distribution of the coefficient of variation (CV) of peak electric field magnitude in each target AVH-ROI across the five head models for each montage. (D) CV of the peak electric field magnitude in target AVH-ROI across the five head models for each montage. LUL, left unilateral 1 × 1 montage with F3-FP1 as the anode and T3-P3 as the cathode; BL, bilateral prefrontal 1 × 1 montage with F3-FP1 as the anode and FP2 as the cathode; 2 × 1, montage with one anode at F3-FP1 and cathodes at T3-P3 and T4-P4. IFGo, inferior frontal gyrus (pars opercularis); IFGt, inferior frontal gyrus (pars triangularis); ACG, anterior cingulate gyrus; PreCG, precentral gyrus; PoCG, postcentral gyrus; HES, Heschl’s gyrus; STG, superior temporal gyrus; HIP, hippocampus; INS, insula; THA, thalamus.

Figure 4

Brain regions with electric field strength above the modulation threshold (0.2 V/m) in a representative model as a function of current amplitude. Spatial distribution of the electric field shown for the cortical surface and in a representative coronal slice for current amplitudes ranging from 1 to 4 mA for each montage. LUL, left unilateral 1 × 1 montage with F3-FP1 as the anode and T3-P3 as the cathode; BL, bilateral prefrontal 1 × 1 montage with F3-FP1 as the anode and FP2 as the cathode; 2 × 1, montage with one anode at F3-FP1 and cathodes at T3-P3 and T4-P4. R, right.

Figure 5

Percentage modulated volume in (A) left-sided and (B) right-sided auditory verbal hallucinations (AVH) regions of interest (ROIs) across all head models for each of the three montages as a function of current amplitude. Coefficient of variation in percentage-modulated volume in (C) left-sided and (D) right-sided AVH-ROIs across all head models for each of the three montages. LUL, left unilateral 1 × 1 montage with F3-FP1 as the anode and T3-P3 as the cathode; BL, bilateral prefrontal 1 × 1 montage with F3-FP1 as the anode and FP2 as the cathode; 2 × 1, montage with one anode at F3-FP1 and cathodes at T3-P3 and T4-P4.