<p>Supplementary Material</p><p>BRAIN IMAGING AND BEHAVIOR</p><p>Brain alterations in low-frequency fluctuations across</p><p> multiple bands in obsessive compulsive disorder</p><p>Mònica Giménez, PhD, Andrés Guinea-Izquierdo, MSc, Victoria Villalta-Gil,</p><p>PhD, Ignacio Martínez-Zalacaín, MSc, Cinto Segalàs, MD, PhD, Marta Subirà,</p><p>MD, Eva Real, MD, PhD, Jesús Pujol, MD, PhD, Ben J Harrison, PhD, Josep</p><p>Maria Haro, MD, PhD, Joao R Sato, PhD, Marcelo Q Hoexter, MD, PhD, Narcís</p><p>Cardoner, MD, PhD, Pino Alonso, MD, PhD, José Manuel Menchón, MD, PhD,</p><p>Carles Soriano-Mas*, PhD</p><p>*Corresponding author: Carles Soriano-Mas</p><p>Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical</p><p>Research Institute (IDIBELL). Feixa Llarga s/n, 08907, L'Hospitalet de</p><p>Llobregat, Barcelona, Spain.</p><p>Telephone: +34 2607500 (ext. 2864)</p><p>Fax: +34 932607658</p><p>E-mail: [email protected]</p><p>Three supplementary figures and four tables are included. Figure S1 shows the correlation between fALFF signal in the OFC of OCD patients at slow-5 and slow-3 bands. Figure S2 shows the between-group fALFF comparison at the 0.01-0.08Hz frequency range. Figure S3 shows the correlation between fALFF values and the DY-BOCS Current Impairment score at the slow-4 band. Table S1 shows details about the pharmacological treatment of the OCD sample. Table S2 displays between-group fALFF differences for the 0.01-0.08Hz frequency band.</p><p>Table S3 displays between-group ALFF differences across bands. Table</p><p>S4 shows the correlations between OCD clinical features and ALFF. Supplementary Figures</p><p>Figure S1. Relationship between fALFF signal at the Slow-5 and Slow-3 frequency bands in the OFC of OCD patients. Correlation was not significant</p><p>(p>0.05). Figure S2. Between-group fALFF comparisons at the 0.01-0.08Hz frequency band. Top, temporal representation of the 0.01-0.08Hz frequency band mean.</p><p>Bottom, T-statistic maps between patients with OCD (P) and normal controls</p><p>(C). Hot colors represent increased fALFF values in patients (positive T scores) compared to controls (P>C). Cold colors represent decreased fALFF values in patients (negative T scores) compared to controls (P<C). In axial and coronal views, the left hemisphere is displayed on the right (radiological convention). Figure S3. Correlation between fALFF values and the DY-BOCS Current</p><p>Impairment score in OCD patients at the slow-4 band. Top, correlation map, showing a cluster of positive correlation in the right fusiform gyrus. Bottom, correlation graph showing the relationship between both variables. Supplementary Tables</p><p>Table S1. Pharmacological treatment of the OCD sample: range and mean dose for treatment strategies other than one SSRI</p><p> n (%) Range Mean dose (mg/d) (mg/d)</p><p>SSRI with Clomipramine 23 (35.4) Clomipramine + Fluoxetine 7 (30.4) 75-300 + 40-80 203.6 + 57.1 Clomipramine + Fluvoxamine 9 (39.1) 75-225 + 200-300 191.7 + 233.3 Clomipramine + Escitalopram 3 (13.0) 150-187.5 + 20 162.5 + 20 Clomipramine + Paroxetine 2 (8.7) 300 + 60 300 + 60 Clomipramine + Sertraline 2 (8.7) 75-150 + 200 112.5 + 200 SSRI combinationsa 4 (6.1) Fluvoxamine + Fluoxetine 1 (25) 300 + 40 Fluvoxamine + Escitalopram 1 (25) 200 + 20 Fluoxetine + Paroxetine 1 (25) 60 + 60 Sertraline + Paroxetine 1 (25) 200 + 20 Antipsychotic augmentation 13 (20) Risperidone 5 (38.5) 1 1 Aripiprazole 4 (30.8) 5-15 10 Olanzapine 4 (30.8) 5-15 10 a For N=1, only dose is provided. Table S2. Regions showing significant between-group fALFF differences at the</p><p>0.01-0.08Hz frequency band</p><p>Brain Region Peak coordinates Peak T KE (voxels)</p><p> x y z (MNI space) value</p><p>Patients>Controls L Sup Med Frontal Gyrus -6 22 40 5.0377 359 Patients<Controls L Mid Occipital Gyrus -42 -70 4 -4.6369 732 L Sup Orb Frontal Gyrus -14 32 -16 -4.5182 388 R Fusiform /Inf Occipital Gyrus 40 -42 -4 -5.0276 1204 R Postcentral Gyrus 48 -26 52 -4.883 1137 L Precentral-Postcentral Gyrus -34 -30 66 -4.2672 431</p><p>T values correspond to the maximum peak level difference between patients and controls in a two-sample T test comparison, AlphaSim corrected for multiple comparisons. Abbreviations: Inf, Inferior; KE, Cluster Extend (number of voxels); L, left; Med, Medial; Mid, Middle; MNI, Montreal Neurological Institute;</p><p>Orb, Orbital; R, right; Sup, Superior. Table S3. Regions showing significant between-group ALFF differences across the different bands (masked by significant fALFF results) </p><p>Brain Region Peak Peak T value KE coordinates (voxels) x y z (MNI space)</p><p>Slow-5 frequency band (0.01-0.027Hz) Patients<Controls Bil OFC -20 36 -12 -4.8065 1642 Slow-4 frequency band (0.027-0.073Hz) Patients>Controls L Sup Temp Cortex /Insula -50 0 -4 3.3516 58 L Dorsal Med Prefrontal 8 22 40 4.418 109 Cortex Patients<Controls R Sensorimotor Cortex 48 -26 58 -4.196 297 Slow-3 frequency band (0.073-0.198Hz) Patients>Controls L Med Temp Gyrus -30 -8 -26 5.1776 269 L Fusiform Gyrus -26 -40 10 3.9391 95 R Lingual Gyrus 4 -96 16 -4.7132 597 Patients<Controls R Precuneus 6 -80 44 -4.1464 211 L Dorsal Med Prefrontal 2 16 42 -3.1317 37 Cortex Slow-2 frequency band (0.198-0.25Hz) Patients>Controls L Thalamus -6 -10 2 4.2812 147 R Sensorimotor Cortex 42 -14 46 3.3905 61</p><p>0.01-0.08Hz frequency band</p><p>Patients>Controls</p><p>L Dorsal Med Prefrontal -10 22 38 4.5953 54 Cortex Patients<Controls</p><p>L Mid Occipital Cortex -44 -70 2 -3.1864 40</p><p>L OFC -20 36 -12 -4.8065 350</p><p>R Sensorimotor Cortex 50 -22 48 -4.6408 223</p><p>L Sensorimotor Cortex -16 -28 78 -3.5951 123 T values correspond to the peak level differences between patients and controls in a two sample T test comparison, AlphaSim corrected for multiple comparisons. Abbreviations: Bil, Bilateral; KE, Cluster Extend (number of voxels); L, left; Med, Medial; Mid, Middle; MNI, Montreal Neurological Institute;</p><p>OFC, Orbitofrontal Cortex; R, Right; Sup, Superior; Temp, Temporal. Table S4. Whole-brain correlations between OCD clinical features and ALFF values (masked by fALFF significant results) </p><p>Brain region Peak Peak r KE</p><p> coordinates value (voxels)</p><p> x y z (MNI</p><p> space) Y-BOCS Total Score Slow-4 frequency range (0.027-0.073Hz) R Ventral Striatum (Putamen) 18 8 -10 -0.30645 18* 46 18 54 0.4807 64</p><p>R Mid Sup Frontal Cortex 28 22 64 0.3949 16</p><p>30 8 68 0.4173 9 DY-BOCS Current Impairment Slow-5 frequency range (0.01-0.027Hz) R Rostral ACC 8 40 12 0.5295 339 Slow 4 frequency range (0.027-0.073Hz) R Inf Temp Cortex /Fusiform 32 -14 -42 0.3839 35 Gyrus DY-BOCS Symptom Severity Aggression (harm-related)/Checking Slow-5 frequency range (0.01-0.027Hz) R Supp Motor Cortex/Mid 6 -2 44 -0.5497 200</p><p>Cingulate Cortex 10 -10 66 -0.4292 57 Slow-3 frequency range (0.073-0.198Hz) R Supp Motor Cortex/Mid 4 -10 48 0.3436 5*</p><p>Cingulate Cortex 4 -12 54 0.3312 5* Symmetry/Ordering Slow-5 frequency range (0.01-0.027Hz) R Mid OFC 28 40 -16 0.5261 210 Slow-4 frequency range (0.027-0.073Hz) R Sup OFC 24 48 -10 0.4543 344 Slow-2 frequency range (0.198-0.25Hz) R Mid OFC 22 42 -20 -0.4147 29 Sexual/ Religious Slow-5 frequency range (0.01-0.027Hz) L Rolandic Operculum/Sensori- -54 -10 8 0.4387 206 motor Cortex -54 -10 50 0.4066 66 Hoarding Slow-4 frequency range (0.027-0.073Hz) L OFC -4 54 -14 0.3916 20 -64 -24 30 -0.4540 68</p><p>L Sensorimotor Cortex -46 -32 36 -0.4296 25</p><p>-52 -40 50 -0.3744 12 Slow-3 frequency range (0.073-0.198Hz) R Mid Inf Frontal Cortex 50 28 16 -0.3711 7 r value corresponds to the peak correlation between clinical variables and ALFF values, AlphaSim corrected for multiple comparisons. *Clusters significant at p</p><p><0.05. Abbreviations: Inf, Inferior; KE, Cluster Extend (number of voxels); L, left;</p><p>Mid, Middle; MNI, Montreal Neurological Institute; OFC, Orbitofrontal Cortex; R,</p><p>Right; Sup, Superior; Supp, Supplementary; Temp, Temporal.</p>