Supplementary materials

Methods

The vmPFC was a specifically hypothesized ROI; however, none of the vmPFC to

subcortical tracts passing through the aLIC had sufficient numbers of subjects with tracts

(<90%). As we were uncertain if this was due to the low SNR in this region or that these

tracts may be missed by limiting to tracts within the aLIC, we conducted a separate analysis

including both vmPFC and Brodmann Area 25 to the NAcc, thalamus and STN without

constraining to the aLIC.

Results

In the separate analysis for vmPFC (and BA 25) and NAcc without constraining in the aLIC,

89% of subjects showed tracts between this cortical-subcortical region (supplementary

figure 3). The number of individuals with tracts between vmPFC (and BA 25) and STN

(19%) and thalamus (65%) without constraining in the aLIC was still low with the latter

including multiple implausible connections on visualization. We showed lower FA in OCD

subjects compared to healthy controls (t(165)=2.87, p=0.005).

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Supplementary Tables

Supplementary Table 1. Distribution of OCD symptoms.

OCD individuals reporting each symptom (%)

Symmetry 24

Taboo thoughts 31

Checking 30

Contamination/Cleaning 41

Hoarding 3

Other 21

Note: Totals exceed 100% given that each subject was allowed to report multiple obsessions

and compulsions.

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Supplementary Table 2. Number of subjects with tractography results.

vlPFC dlPFC vmPFC dACC preSMA OFC

Thalamus 180 187 33 182 187 184

Caudates 161 182 33 163 105 135

Putamen 179 183 29 157 170 104

NAcc 0 0 10 0 0 2

STN 179 171 2 152 172 169

vlPFC: ventrolateral prefrontal cortex, dlPFC: dorsolateral prefrontal cortex, vmPFC:

ventromedial prefrontal cortex, dACC: dorsal anterior cingulate cortex, preSMA: anterior

portion of supplementary motor area, OFC: orbitofrontal cortex, NAcc: nucleus accumbens,

STN: subthalamic nucleus. The numbers in bold indicate tracts found in more than 90% of

subjects (>169).

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Supplementary Table 3. Center of gravity of thalamocortical connections.

Cortical targets of

thalamocortical connections

Min (mm) Max (mm) Mean (mm) SD (mm)

Left vlPFC (-22, -1, 2) (-15, 12, 17) (-17, 8, 8) (0.8, 1.7, 2.3)

Left dlPFC (-20, 4, 1) (-14, 11, 18) (-17, 8, 9) (0.8, 1.3, 2.7)

Left dACC (-21, -4, 8) (-16, 9, 17) (-18, 5, 12) (0.7, 1.7, 1.8)

Left preSMA (-22, -4, 13) (-17, 4, 17) (-20, 1, 15) (0.7, 1.5, 0.8)

Left OFC (-19, 7, 2) (-15, 11, 12) (-17, 10, 6) (0.6, 0.7, 1.6)

Right vlPFC (12, -3, -2) (22, 11, 17) (18, 8, 8) (1.1, 2.1, 2.7)

Right dlPFC (16, 5, 2) (20, 11, 15) (18, 9, 8) (0.7, 1.1, 2.1)

Right dACC (17, 1, 6) (22, 15, 18) (19, 6, 12) (0.8, 1.9, 2.3)

Right preSMA (19, -5, 11) (23, 4, 18) (20, 1, 15) (0.7, 1.9, 1.1)

Right OFC (14, 6, -2) (22, 21, 9) (17, 10, 4) (0.9, 1.2, 2.1)

Min: minimum, Max: maximum, SD: standard deviation. Note: Coordinates are in the MNI

space.

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Supplementary Table 4. Clusters with voxel-wise group differences in FA.

Cluster

#

Anatomical region Peak t-

stat.

p-values

(TFCE)

Size

(mm3)

X

(mm)

Y

(mm)

Z

(mm)

1 Anterior thalamic radiation -4.6320 0.0159 31 -28 28 25

2 Anterior thalamic radiation -4.3275 0.0229 23 -24 21 14

3 Forceps minor -4.0792 0.0001 3147 20 40 13

4 Forceps minor -4.8755 0.0001 1161 -19 47 9

5 Cerebral WM in IFG -5.0075 0.0001 760 -34 15 19

6 Inferior fronto-occipital

fasciculus

-5.1242 0.0176 21 -29 47 -4

7 Cerebral WM in insular cortex -5.9961 0.0001 372 -27 17 4

8 Cerebral WM in insular cortex -4.0820 0.0403 16 27 15 11

9 Cerebral WM in insular cortex -4.5232 0.0304 11 29 4 15

10 Cerebral WM in MFG -4.9230 0.0076 73 28 13 34

11 Cerebral WM in MFG -5.0323 0.0055 73 -26 14 34

12 Cerebral WM -4.1726 0.0069 250 27 -7 21

13 Cerebral WM -4.2759 0.0067 204 -26 -9 20

14 Subcortical WM -3.0231 0.0458 3 25 1 31

15 Subcortical WM near putamen -4.9229 0.0241 7 27 17 8

16 Superior longitudinal fasciculus -3.9833 0.0210 64 38 -40 25

17 Superior longitudinal fasciculus -4.2858 0.0235 24 39 -41 32

18 Superior longitudinal fasciculus -4.3635 0.0288 18 53 -46 -15

19 Superior longitudinal fasciculus -4.1833 0.0429 2 34 -22 33

20 Uncinate fasciculus -4.5199 0.0251 22 -32 31 -7

WM: white matter, IFG, inferior frontal gyrus, MFG, middle frontal gyrus. Coordinates are in

the MNI space. Note: T-statistics were computed for the contrast of healthy controls

subtracted from patients with OCD.

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Supplementary Figures

Supplementary Figure 1. Denoising using local PCA. Raw DSI data (upper row) and

denoised DSI data (lower row) using local PCA. B-values are marked.

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Supplementary Figure 2. Examples of registration of regions of interest. For randomly

chosen four subjects (two health controls, HC; two patients with OCD, OCD), regions of

interest (ROI) registered in the native diffusion-spectrum imaging (DSI) space are shown.

Color-coding (the same scheme as Figure 1 in the main text) marks integer labels: 1 =

ventrolateral prefrontal cortex, 2 = dorsolateral prefrontal cortex, 3 = ventromedial prefrontal

cortex, 4 = dorsal anterior cingulate cortex, 5 = anterior portion of supplementary motor area,

6 = orbitofrontal cortex, 7 = thalamus, 8 = caudate nucleus, 9 = putamen, 10 = nucleus

accumbens, 11 = subthalamic nucleus.

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Supplementary Figure 3. Clinical measures at baseline and follow-up. A: Yale-Brown

Obsessive-Compulsive Scale (Y-BOCS), B: Hamilton Anxiety Rating Scale (HAM-A), C:

Hamilton Depression Rating Scale (HAM-D).

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Supplementary Figure 4. Ventromedial prefrontal and nucleus accumbens connectivity.

A: tracts from a representative healthy control subject. B: group-averaged track-density

image. C: Group difference in fractional anisotropy of the tracts.

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