One patient and one control were unable to complete the TOMM. An additional HC had abnormally low scores

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1 Ling et al Supplemental Methods Participants One patient and one control were unable to complete the TOMM. An additional HC had abnormally low scores on the TOMM only (T-score < 0), and was not included in analyses of that measure. Imaging Images were collected on a 3 Tesla Siemens Trio scanner. High resolution T 1 -weighted anatomic images were acquired with a 5-echo multi-echo MPRAGE sequence [TE (echo times) = 1.64, 3.5, 5.36, 7.22, 9.08 ms, TR (repetition time) = 2.53 s, TI=1.2 s, 7 flip angle, number of excitations (NEX) = 1, slice thickness = 1 mm, FOV (field of view) = 256 mm, resolution = 256 x 256] for a voxel size = 1 mm 3 ). T 2 -weighted images were collected with a fast spin echo sequence (voxel size = 1.15 x 1.15 x 1.5 mm). Finally, susceptibility weighted images (SWI) were collected using a gradient echo sequence [TR = 28 ms; TE = 20 ms; flip angle 15 ; bandwidth = 120 Hz/Px; FOV = 180 x 240 mm; matrix = 177 x 256; slice thickness = 1.5 mm; number of slices per slab = 88] on a smaller cohort of patients (N = 24) to better characterize petechial hemorrhages. Two diffusion tensor imaging scans (b = 800 s/mm 2 ) were acquired using a twice-refocused spin echo sequence with 30 diffusion gradients and the b = 0 experiment repeated 5 times [72 interleaved slices; TE = 8.4 s; TR = 9.0 s; 90 flip angle; NEX = 1; slice thickness = 2.0 mm; FOV = 256 x 256 mm; matrix size = 128 x 128; voxel resolution = 2 mm 3 ]. Image distortions caused by eddy currents or head motion were corrected by registering all diffusion weighted images to the first b = 0 s/mm 2 image using an affine correction with mutual information as the cost function. Supplemental Results Visit 1: To confirm that the complicated mtbi subjects were not uniquely responsible for significant group differences in FA at Visit 1 (left and right superior frontal gyri), two additional MANCOVAs were conducted on

2 Ling et al the mean FA data for these regions. Results did not indicate any significant differences in superior frontal FA for complicated mtbi patients relative to the rest of the patient cohort (p > 0.10).

3 Ling et al Supplementary Figure e-1. A flow-chart representing the principal analytic streams and their measures

4 Ling et al Supplementary Figure e-2. Depicts Cohen s d effect size maps for fractional anisotropy (FA) in the left (L) and right (R) hemispheres (Panel A), mean diffusivity (MD; Panel B), and cortical thickness (THK; Panel C). Small effect sizes (d = to 0.29) appear in grey. Moderate effect sizes (d = 0.30 to 0.59 ) appear in red (mtbi > HC) or blue (HC > mtbi), depending on the direction of effect. Large effect sizes appear in yellow (mtbi > HC; d >= 0.60) or cyan (HC > mtbi; d <= -0.60). For all maps, Cohen s d is adjusted for premorbid IQ.

5 Ling et al Supplementary Figure e-3. Subcortical Cohen s d effect size maps for fractional anisotropy (FA) and mean diffusivity (MD). Voxels with small effect sizes (d < 0.30) are not shown. Moderate effect sizes appear in red (mtbi > HC; d >= 0.30) and blue (HC > mtbi; d <= -0.30). Axial slice locations denote Talairach coordinate space.

6 Ling et al Table e-1: Demographic and injury information for all mtbi patients. Age Gender Injury Mechanism AAN Rating Days postinjury MRI NP LOC (h:m:s) PTA (h:m:s) Number of Previous Injuries* Return Subject 19 F Fall :03:00 0:00:00 NA N 19 F MVA :12:30 24:00:00 NA Y 20 F MVA :00:00 0:00:03 NA Y 21 F MVA :05:00 NA NA Y 21 F Fall :01:20 0:00:00 NA N 21 F Fall :00:02 0:00:00 1 N 22 F Assault :00:00 0:03:30 0 N 22 F Fall :30:00 0:25:00 NA N 22 F MVA :02:30 2:10:00 0 N 22 F MVA :00:00 0:00:05 2 N 23 F Fall :00:30 0:00:00 0 Y 23 F Assault :00:00 0:01:00 NA Y 23 F Assault :00:00 0:30:00 NA N 24 F MVA :00:30 1:00:00 NA Y 24 F Assault :00:00 0:00:00 NA Y 25 F MVA :07:30 7:00:00 NA Y 26 F Fall :02:00 0:00:00 0 N 27 F Assault :00:00 NA NA Y 27 F MVA :00:00 NA NA N 28 F Fall :00:30 18:00:00 1 N 28 F Assault :00:00 0:05:00 NA N 37 F Fall :01:00 0:00:00 NA Y 41 F Fall :01:00 NA NA Y 48 F Fall :00:00 0:00:00 0 Y 50 F MVA :01:30 4:00:00 NA Y 18 M Fall :07:30 0:45:00 1 N 18 M Assault :00:05 0:00:00 1 N 18 M Assault :00:00 0:00:40 0 N 19 M Assault :00:03 0:00:00 0 Y 19 M Fall :00:05 0:00:45 1 Y 19 M MVA :02:00 0:02:00 6 N 22 M MVA :00:30 0:00:00 1 Y 23 M Fall 3 17 NA NA NA NA N 23 M Assault :17:30 0:00:00 NA Y 23 M Fall :00:00 0:00:00 NA Y 24 M Fall :00:03 0:30:00 NA Y 24 M Fall :02:30 0:30:00 NA N 28 M MVA :00:25 0:00:00 0 Y 30 M MVA :05:00 0:00:00 NA N

7 Ling et al M Assault :05:00 24:00:00 NA N 32 M Assault :01:00 5:00:00 NA Y 32 M MVA :00:30 0:00:00 0 Y 33 M Assault :00:02 0:03:00 1 N 33 M Fall :00:15 0:00:00 NA N 36 M MVA :00:00 2:00:00 1 N 40 M Assault :01:00 0:00:00 NA Y 41 M Fall :00:00 1:00:00 0 Y 45 M Assault :04:00 0:10:00 1 Y 49 M Assault :02:00 0:00:00 NA Y 51 M Fall :00:00 24:00:00 0 N Note: MVA = motor vehicle accident; AAN = American Academy of Neurology; NP = neuropsychological testing; LOC = Loss of consciousness; and PTA = Post traumatic amnesia. Duration of LOC and PTA are based on subjective self-report at initial assessment for the study. The assault category also includes injuries sustained from falling objects or during collisions (e.g., sports-related). *Previous injuries were documented using a modified version of the Rivermead scale, and data collection with this instrument began after the start of the study (not available; NA). Return Subject column indicates if this patient returned for longitudinal follow-up

8 Ling et al Table e-2: Effect sizes for cortical regions of interest. For reference, labels are derived directly from FreeSurfer. FA MD Cortical Label TBI HC Cohen's d TBI HC Cohen's d Effect sizes for a priori cortical regions of interest Caudal anterior L 0.15(0.02) 0.15(0.02) (0.05) 0.72(0.05) 0.05 cingulate gyrus R 0.15(0.02) 0.15(0.02) (0.04) 0.72(0.05) Entorhinal cortex L 0.13(0.03) 0.13(0.03) (0.19) 0.84(0.18) R 0.12(0.03) 0.12(0.03) (0.21) 0.85(0.22) 0.04 Inferior temporal L 0.14(0.02) 0.14(0.02) (0.06) 0.55(0.06) gyrus R 0.15(0.01) 0.14(0.01) (0.06) 0.57(0.06) 0.15 Lateral L 0.15(0.02) 0.16(0.02) (0.49) 0.57(0.35) orbitofrontal R cortex 0.17(0.02) 0.17(0.02) (0.23) 0.69(0.04) 0.30 Medial orbitofrontal cortex Middle temporal gyrus L 0.18(0.02) 0.18(0.02) (0.07) 0.71(0.07) R 0.17(0.02) 0.16(0.01) (0.06) 0.69(0.06) 0.03 L 0.14(0.01) 0.14(0.01) (0.05) 0.67(0.04) R 0.14(0.01) 0.14(0.01) (0.08) 0.70(0.06) Parsorbitalis L 0.13(0.02) 0.13(0.02) (0.06) 0.78(0.05) 0.18 R 0.14(0.01) 0.13(0.02) (0.05) 0.75(0.06) Parstriangularis L 0.14(0.02) 0.14(0.02) (0.05) 0.79(0.05) R 0.14(0.02) 0.14(0.02) (0.05) 0.76(0.05) 0.02 Rostral anterior L 0.14(0.02) 0.14(0.02) (0.07) 0.78(0.07) cingulate gyrus R 0.14(0.02) 0.14(0.02) (0.05) 0.77(0.05) Rostral middle L 0.13(0.02) 0.13(0.02) (0.06) 0.78(0.06) frontal gyrus R 0.15(0.02) 0.14(0.01) (0.06) 0.74(0.06) Superior temporal gyrus L 0.15(0.01) 0.15(0.01) (0.04) 0.73(0.04) R 0.14(0.01) 0.14(0.01) (0.04) 0.76(0.04) 0.05 Frontal pole L 0.09(0.05) 0.08(0.04) (0.24) 0.55(0.24) 0.19 R 0.10(0.05) 0.09(0.03) (0.22) 0.57(0.18) 0.32 Temporal pole L 0.18(0.02) 0.18(0.03) (0.06) 0.72(0.06) R 0.18(0.02) 0.18(0.02) (0.14) 0.89(1.62) Effect sizes for remaining cortical regions Bankssts L 0.14(0.01) 0.14(0.02) (0.04) 0.68(0.04) R 0.13(0.01) 0.13(0.02) (0.04) 0.69(0.05) 0.00 Caudal middle L frontal 0.15(0.02) 0.15(0.02) (0.05) 0.76(0.05) 0.08

9 Ling et al R 0.15(0.02) 0.15(0.02) (0.06) 0.75(0.05) 0.21 Cuneus L 0.12(0.02) 0.12(0.03) (0.06) 0.77(0.06) R 0.12(0.02) 0.12(0.03) (0.05) 0.76(0.06) Fusiform L 0.14(0.01) 0.14(0.02) (0.04) 0.62(0.05) 0.19 R 0.14(0.01) 0.14(0.02) (0.06) 0.64(0.05) 0.13 Inferior parietal L 0.13(0.01) 0.12(0.02) (0.05) 0.72(0.05) R 0.12(0.01) 0.12(0.01) (0.05) 0.72(0.06) Isthmus cingulate L 0.17(0.02) 0.17(0.02) (0.05) 0.73(0.05) 0.10 R 0.17(0.02) 0.17(0.02) (0.05) 0.73(0.04) Lateral occipital L 0.12(0.01) 0.11(0.01) (0.05) 0.68(0.06) R 0.12(0.01) 0.12(0.01) (0.06) 0.65(0.05) Lingual L 0.13(0.01) 0.13(0.01) (0.05) 0.74(0.05) R 0.13(0.01) 0.13(0.02) (0.05) 0.75(0.05) Parahippocampal L 0.14(0.02) 0.14(0.02) (0.10) 0.88(0.09) 0.23 R 0.13(0.02) 0.13(0.02) (0.10) 0.88(0.09) 0.33 Paracentral L 0.16(0.03) 0.15(0.02) (0.08) 0.79(0.06) R 0.15(0.03) 0.15(0.02) (0.06) 0.78(0.06) Parsopercularis L 0.14(0.01) 0.14(0.02) (0.04) 0.77(0.05) 0.00 R 0.14(0.01) 0.14(0.01) (0.04) 0.75(0.04) 0.15 Pericalcarine L 0.12(0.01) 0.12(0.02) (0.05) 0.80(0.06) R 0.12(0.02) 0.12(0.02) (0.05) 0.80(0.06) Postcentral L 0.14(0.02) 0.14(0.02) (0.06) 0.84(0.06) 0.06 R 0.14(0.02) 0.13(0.02) (0.07) 0.88(0.07) Posterior L cingulate 0.16(0.02) 0.16(0.02) (0.05) 0.69(0.05) 0.18 R 0.16(0.02) 0.15(0.02) (0.04) 0.70(0.04) Precentral L 0.15(0.02) 0.15(0.02) (0.06) 0.80(0.05) 0.14 R 0.14(0.02) 0.14(0.02) (0.06) 0.80(0.06) 0.11 Precuneus L 0.14(0.02) 0.14(0.02) (0.07) 0.76(0.05) 0.03 R 0.14(0.02) 0.14(0.02) (0.05) 0.77(0.05) Superior frontal L 0.16(0.02) 0.16(0.02) (0.05) 0.75(0.05) 0.08 R 0.16(0.02) 0.16(0.02) (0.05) 0.75(0.04) 0.04 Superior parietal L 0.14(0.02) 0.13(0.02) (0.07) 0.82(0.06) R 0.13(0.02) 0.13(0.02) (0.07) 0.83(0.06) Supramarginal L 0.13(0.02) 0.13(0.01) (0.05) 0.75(0.05) R 0.12(0.01) 0.12(0.02) (0.06) 0.77(0.06) Transverse L temporal 0.15(0.02) 0.16(0.02) (0.06) 0.76(0.05) 0.13 R 0.14(0.03) 0.14(0.02) (0.07) 0.83(0.08) -0.04

10 Ling et al Insula L 0.16(0.01) 0.16(0.01) (0.04) 0.74(0.03) 0.16 R 0.16(0.01) 0.16(0.01) (0.04) 0.76(0.04) 0.12 Note: Parcellations determined through FreeSurfer software. Cohen s d values are adjusted for WTAR.

11 Ling et al Table e-3: Subcortical diffusion effect sizes. For reference, labels are derived directly from FreeSurfer. FA TBI HC Cohen s d MD TBI HC Cohen s d Effect sizes for a priori subcortical regions of interest Hippocampus L 0.19(0.02) 0.19(0.01) (0.04) 0.79(0.05) 0.13 R 0.18(0.02) 0.19(0.01) (0.04) 0.83(0.04) 0.08 Thalamus L 0.36(0.02) 0.36(0.02) (0.03) 0.63(0.03) 0.14 R 0.33(0.02) 0.34(0.02) (0.03) 0.67(0.03) 0.26 Effect sizes for remaining subcortical regions Caudate L 0.27(0.04) 0.27(0.04) (0.07) 0.72(0.08) 0.15 R 0.24(0.04) 0.24(0.03) (0.09) 0.78(0.07) 0.00 Putamen L 0.27(0.02) 0.26(0.02) (0.03) 0.55(0.03) 0.15 R 0.25(0.03) 0.24(0.02) (0.03) 0.58(0.03) 0.10 Pallidum L 0.44(0.05) 0.43(0.05) (0.04) 0.53(0.04) R 0.37(0.04) 0.37(0.04) (0.03) 0.59(0.03) 0.03 Amygdala L 0.19(0.02) 0.19(0.02) (0.06) 0.75(0.07) 0.06 R 0.17(0.02) 0.18(0.02) (0.05) 0.8(0.07) 0.10 Accumbens L 0.24(0.04) 0.24(0.04) (0.04) 0.63(0.04) 0.04 R 0.26(0.04) 0.26(0.04) (0.03) 0.62(0.03) 0.10 Ventral L 0.47(0.03) 0.47(0.02) (0.04) 0.69(0.03) 0.09 diencephalon R 0.45(0.02) 0.44(0.02) (0.04) 0.74(0.03) Note: Parcellations determined through FreeSurfer software. Volume normalized by intracranial volume and scaled by 100. Cohen s d values are adjusted for WTAR.

12 Ling et al Table e-4: Radiological findings derived directly from patient chart information. Patient Findings 1 CT: small amount of subdural blood along the falx and tentorium, with punctate subarachnoid hemorrhage within the vertex. nasal bone fractures. 2 MRI: Slight asymmetry of the temporal horn of the right lateral ventricle. Probably, anatomic variant. Subtle T1 hypointensity in the central/left paracentral upper pons. Not well seen on the T2WI's. Question of artifact vs. subtle finding. Consider clinical correlation and possible diagnostic MR. 3 CT: small amount of subarachnoid hemorrhage layering w/n the right sylvian fissure w/o significant mass effect or shift of midline structures. 4 CT: thin right supratentorial subdural hematoma. right posterior parietal scalp swelling extending to the vertex. 5 CT: left ZMC fracture pattern. intermediate attenuation fluid within left maxillary sinus, likely hemorrhage. Acute intracranial hemorrhage. 6 MRI: Left maxillary sinus mucous retention cysts. A cluster of small oval fluid signal areas can be found involving the right periatrial/parietal white matter. Largest area measuring about 4 mm. Nonspecific. Could represent dilated virchow robin spaces as other smaller areas of similar signal can be found in the left parietal lobe. 7 MRI: subtle, non-specific white matter lesion in the right centrum semiovale. may be posttraumatic in nature. 8 MRI: CSF or fluid signal is seen in the left anterior middle cranial fossa, anterior to the temporal lobe. This could represent CSF associated with volume loss of the left temporal lobe. Any history of prior trauma or vascular insult. This CSF signal area could also represent a small arachnoid cyst (2.3 cm x 1.5cm) 9 CT: posterosuperior intracranial soft tissue lacerations, and extracranial lacerations closed w/ surgical skin staples & associated w/ soft tissue swelling & hematomas