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Home , Inferior frontal gyrus, Precentral gyrus

Supplementary Materials Tetereva et al., Asymmetry of Resting-State Functional Connectivity in Healthy Human

Abbreviations: ACC – anterior AMYG – amygdala BDI – Beck depression inventory CAUD – caudate nuclei FC – functional connectivity fMRI – functional magnetic resonance imaging HIP – hippocampus, IFGorb – inferior frontal , pars orbitalis IFGtriang – , triangular part INS – insula MTG – PCC – posterior cingulate cortex PHG – preCG – PTSD – post-traumatic stress disorder ROI – region of interest SFG – , SFGmed – superior frontal gyrus, medial STAI – State-Trait Anxiety Inventory STP – superior temporal pole UNC – vlPFC – ventrolateral vmPFC – ventromedial prefrontal cortex.

Materials and methods Exclusion criteria for fMRI: We used general exclusion criteria such as prior head trauma, any contraindications against MRI, medication affecting the central nervous system, history of neurologic or psychiatric disorders, consumption of drugs, excessive consumption of alcohol and nicotine, and pregnancy. Preprocessing of MRI data Functional images were realigned with the mean functional image for motion correction. Magnitude and phase values from the field map images served for calculation of the voxel displacement map (VDM) and the subsequent mapping to the mean functional image. Next, each fMRI volume was unwrapped using VDM. After co-registration of the mean functional image with the anatomical image, all functional images were normalized into the standard template of Montreal Neurological Institute (MNI) space with a voxel size of 1.5 x 1.5 x 1.5 mm3 in two stages by the SPM New Segment tool: segmentation of anatomical images into grey and white

1 matter, cerebrospinal fluid, bones, and air, followed by deformation of fMRI volumes and anatomical image using deformation fields. After the normalization procedure, we smoothed the fMRI images using a Gaussian kernel with a full width at half maximum (FWHM) of 6 mm. Afterward, fMRI data were filtered by a fifth-order Butterworth band-pass filter with a frequency window from 0.01 Hz to 0.1 Hz. During the final stage of preprocessing, we performed a regressing-out procedure in order to exclude motion patterns and signals derived from ventricles from the fMRI data (Fox et al., 2009). The mask for ventricles was created in WFU PickAtlas 3.0.4 (Maldjian et al., 2003) and then deformed to the individual space via the procedure described in the previous section. The ventricles' time series and six motion parameters were extracted for each subject and used as regressors in the general linear model. The resulting regression residuals were used for further analysis of FC. Results Table S1. Demographic characteristics and state/trait anxiety scores of all participants collected in the first and second visit (in 1 week).

1 visit 2 visit

Gender Distribution 14 male, 6 female Age (Mean±SD) 25.9 ± 4.27 State Anxiety 28.6 ± 5.12 30.5 ± 6.89 Trait Anxiety 32.9 ± 7.43 34.3 ± 6.80 Depression 5.0 ± 2.77

2 Figure S1. Significant positive correlations of functional connectivity for (L) the left and (R) right amygdala with other brain regions overlapped for two scanning sessions (1 – first session and 2 – in 1 week). k-threshold for 1 session and left amygdala= 204 voxels, right amygdala = 185 voxels; for 2 session, left = 182 voxel, right = 173 voxels.

Table S2. FC of the left and right amygdala with other brain regions according to separate one- sample t-tests for the first and second sessions in one week (pFWE<0.05, T = 5.82, cluster threshold <113 voxels). R-in the right, L- in the left hemisphere; BA- . Anatomic region with the Number Scanning Regions included in the Peak MNI peak FC R/L BA of Session cluster (voxel size) coordinate in the cluster (voxel size) voxels Middle Temporal Gyrus L 21 (73) 117 -54 -18 -22.5 (44) Hippocampus (711); Superior temporal pole (164); Uncus (120); BA 34 (225); Amygdala (408) L 53 2149 -22.9 -3 -19.5 1st Session/ Amygdala (118); L Parahippocampal Gyrus (101) Parahippocampal Gyrus (186); Amygdala (91) R 53 256 21 1.5 -21 BA 34 (69); Hippocampus (46) Caudate (47) R 48 Thalamus (15) 115 10.5 -6 18 Superior Temporal Gyrus (152); Superior Temporal Pole R 38 BA 38 (98); 203 51 15 -12 (105) Inferior Orbitofrontal Gyrus (48) Parahippocampal Gyrus (1039); Hippocampus (597); BA 34 (226); Superior Temporal Gyrus (140); Amygdala (397) R 53 2223 24 -3 -19.5 1st Session/ Superior Temporal Pole Amygdala (137); R Uncus (70); BA 28 (68); Olfactory Cortex (61); Lentiform Nucleus (48); Inferior Frontal Gyrus (40) Parahippocampal Gyrus (327); Hippocampus (159) L 34 365 -16.5 -9 -19.5 Amygdala (130); BA 34 (124) Inferior Frontal Gyrus, BA 47 (69); R 47 145 52.5 33 -4.5 pars orbitalis (134) (55) Insula (113) R 13 Insula 119 39 1.5 -4.5

3 Superior Temporal Gyrus Middle Temporal Gyrus (200); R 22 374 64.5 -31.5 0 (205) BA 22 (117); Middle Frontal Gyrus (55) Inferior Frontal Gyrus, R 45 BA 45 (39) 170 58.5 30 9 pars triangularis (170) Superior Frontal Gyrus, L 10 BA 10 (130) 292 -6 60 28.5 Medial (231) Parahippocampal Gyrus (1274); Hippocampus (730); BA 28 (87) Amygdala (458) L 53 Uncus (278); BA 34 (239); 2664 -24 -3 -19.5 Superior Temporal Pole nd 2 Session/ (203); Amygdala Superior Temporal Gyrus L (140) Middle Temporal Gyrus BA 21 (52); L 21 129 -57 -1.5 -22.5 (86) Superior Temporal Pole (39)

Parahippocampal Gyrus BA 34 (91); Amygdala (91); L 53 269 16.5 -3 -18 (239) Hippocampus (59)

Middle Temporal Gyrus BA 21 (114); R 22 332 57 -4.5 -13.5 (289) Superior Temporal Gyrus (39) Parahippocampal Gyrus (1007); Hippocampus (566); Superior Temporal Gyrus Amygdala (459) R 53 (367); 2615 24 -3 -18 Uncus (243); BA 34 (234); BA 38 (134); BA 28 (83); 2nd Session/ Inferior Frontal Gyrus (109); Amygdala (94) R Uncus (53); BA 34 (41); Parahippocampal Gyrus Superior Temporal Pole (49); L 34 109 -16.5 1.5 -19.5 (47) Parahippocampal Gyrus (37); Amygdala (21) Inferior Frontal Gyrus, Middle Frontal Gyrus (48); R 47 112 42 36 -16.5 pars orbitalis (95) BA 11 (30) Inferior Frontal Gyrus, R 47 BA 47 (41) 164 51 33 -4.5 pars orbitalis (143) BA 4 (40); Precentral Gyrus (112) R 4 113 28.5 -28.5 63 (29)

Table S3. Z-scores of Pearson correlation coefficients and interclass correlation coefficients (ICC) only for the left and right amygdala’ connections with regions of interest (R-in the right, L- in the left hemisphere). Values are given in descending order for ICC. z-score for z-score for Mean z-score Regions of interest ICC 1st Session 2nd Session for 2 sessionsa

4 AMYG R - preCG R 0.66 0.19* 0.17* 0.18

AMYG L - HIP L 0.59 0.20* 0.16* 0.18 AMYG R - preCG L 0.57 0.18* 0.17* 0.18

AMYG R - IFGorb R 0.56 0.20* 0.21* 0.21 AMYG R - INS L 0.54 0.15* 0.12 0.14

AMYG R - HIP R 0.51 0.16 0.14 0.15

AMYG R - Caud R 0.5 0.09 0.12 0.11 AMYG R - INS R 0.49 0.17 0.19* 0.18

AMYG R - IFGtriang L 0.49 0.14 0.1 0.12 AMYG L - IFGorb L 0.47 0.11 0.13 0.12

AMYG L - MTG L 0.46 0.08 0.12 0.1

AMYG R - PHG R 0.44 0.17* 0.12* 0.14 AMYG R - MTG R 0.43 0.23* 0.23* 0.23

AMYG R - SFGmed R 0.43 0.14 0.12 0.13 AMYG L - BA38 L 0.4 0.1 0.14* 0.12

Table values are sorted according to the decreasing mean z-scores for both sessions and limited to z > 0.1; ** p < 0.05 after FWE correction.

ROI-FC changes and reproducibility of resting-state functional connectivity between two scanning sessions at a one-week interval Additionally, we analyzed pair-wise FC values of the brain areas that showed the increased connectivity with either the left or right AMYG in at least one of the two sessions. Figure S2 illustrates correlation matrices for 24 bilateral ROIs, including the left and right AMYG. Across 276 paired correlation coefficients, only 69 passed through FDR correction for multiple comparisons (p < 0.05) of the ICC reproducibility index computed for the two sessions. Of these, 21 pairs had some level of Pearson correlation r > 0.5 (Table S4), with steady bilateral coupling between CAUD, Ins, and SFGmed. We observed a predominance of the stable connections in the right hemisphere (Figure S2). The majority of reproducible FC values were obtained for the right IFGorb and IFGtriang, with other ROIs in both hemispheres. The bilateral parts of preCG had an almost equal number of stable FC values, but with the dominance of the right preCG. Additionally, we examined the within-subject reliability of the ROI-FC values for each session separately, using a more rigorous FWE threshold. Some instability of FC across one week was found: 53 FC values were significant for the first session but only 44 ROI-FC values passed the significance threshold for the second session (Table S5). FC between bilateral areas of SFGmed and INS was the highest for both sessions.

5 Figure S2. Cross-correlation maps of functional connectivity between regions of interest for two scanning sessions (A – first session, B – after a week). Each first row or column for region corresponds values in the right hemisphere, each second – in the left hemisphere. Points mark significant differences. Matrix C shows the most stable FC across a week with ICC > 0.4, FDR = 0.05.

Figure S3. Stable functional connectivity between regions of interest with interclass correlation coefficients ICC < 0.7 (p < 0.05, FDR corrected) for two scanning sessions in a one-week interval. Table S4. Regions of interest (ROI) with the most stable values of functional connectivity (z- scores of Pearson correlation coefficients) for the first and second sessions across a week, according to interclass correlation coefficients (ICC) (R-in the right, L- in the left hemisphere).

z-score for z-score for Mean z-score Regions of interest ICCa 1st Sessionb 2nd Sessionb for 2 sessionsc SFGmed L - SFGmed R 0.67 1.25 1.26 1.26 INS L - INS R 0.70 0.66 0.81 0.74 IFGorb R - SFGmed R 0.75 0.69 0.67 0.68 IFGorb R - MTG R 0.74 0.66 0.66 0.66 Caud L - Caud R 0.65 0.62 0.68 0.65 IFGorb R - SFGmed L 0.67 0.65 0.62 0.64

6 INS L - preCG L 0.82 0.59 0.62 0.61 SFGmed L - preCG L 0.72 0.59 0.62 0.61 IFGtriang R - preCG R 0.78 0.61 0.60 0.60 INS R - preCG R 0.74 0.58 0.59 0.59 IFGtriang R - INS R 0.74 0.56 0.59 0.58 IFGtriang R - preCG L 0.66 0.56 0.57 0.57 IFGorb R - MTG L 0.65 0.57 0.55 0.56 INS L - preCG R 0.82 0.52 0.59 0.56 SFGmed L - preCG R 0.68 0.52 0.59 0.56 BA38 R - MTG R 0.73 0.56 0.55 0.56 IFGtriang R - INS L 0.74 0.51 0.60 0.55 SFGmed R - preCG L 0.71 0.51 0.59 0.55 BA38 R - IFGorb R 0.72 0.51 0.54 0.53 SFGmed R - preCG R 0.68 0.47 0.57 0.52 IFGorb R - preCG R 0.76 0.53 0.50 0.52 a p < 0.05 after FDR correction; b p < 0.05 after FWE correction; c Table values are sorted according to the decreasing mean z-scores for both sessions and limited to z > 0.5.

Table S5. Pairs of regions of interest with higher values of interclass correlation coefficients (pFDR<0.05) and mean z-scores of functional connectivity coefficients for two sessions (pFWE<0.05).

ICC Z score Z score Mean Z pFWE pFWE< ROI ICC pICC (pFDR 1st 2nd for both <0.05 0.05 <0.05) Session Session session

Superior Frontal Medial Gyrus L - 0.67 0.01 0.67 1.25 1.25 1.26 1.26 1.26 Superior Frontal Medial Gyrus R Insula L - Insula R 0.70 0.01 0.70 0.66 0.66 0.81 0.81 0.74 Inferior Frontal Gyrus, pars orbitalis R 0.75 0.00 0.75 0.69 0.69 0.67 0.67 0.68 - Superior Frontal Medial Gyrus R Inferior Frontal Gyrus, pars orbitalis R 0.74 0.00 0.74 0.66 0.66 0.66 0.66 0.66 - Middle Temporal Gyrus R Caudate L - Caudate R 0.65 0.01 0.65 0.62 0.62 0.68 0.68 0.65 Inferior Frontal Gyrus, pars orbitalis R 0.67 0.01 0.67 0.65 0.65 0.62 0.62 0.64 - Superior Frontal Medial Gyrus L Insula L - Precentral Gyrus L 0.82 0.00 0.82 0.59 0.59 0.62 0.62 0.61 Superior Frontal Medial Gyrus L - 0.72 0.00 0.72 0.59 0.59 0.62 0.62 0.61 Precentral Gyrus L Inferior Frontal Gyrus, pars triangularis 0.78 0.00 0.78 0.61 0.61 0.60 0.60 0.60 R - Precentral Gyrus R Insula R - Precentral Gyrus R 0.74 0.00 0.74 0.58 0.58 0.59 0.59 0.59

7 Inferior Frontal Gyrus, pars triangularis 0.74 0.00 0.74 0.56 0.56 0.59 0.59 0.58 R - Insula R Inferior Frontal Gyrus, pars triangularis 0.66 0.01 0.66 0.56 0.56 0.57 0.57 0.57 R - Precentral Gyrus L Inferior Frontal Gyrus, pars orbitalis R 0.65 0.01 0.65 0.57 0.57 0.55 0.55 0.56 - Middle Temporal Gyrus L Insula L - Precentral Gyrus R 0.82 0.00 0.82 0.52 0.52 0.59 0.59 0.56 Superior Frontal Medial Gyrus L - 0.68 0.01 0.68 0.52 0.52 0.59 0.59 0.56 Precentral Gyrus R BA38 R - Middle Temporal Gyrus R 0.73 0.00 0.73 0.56 0.56 0.55 0.55 0.56 Inferior Frontal Gyrus, pars triangularis 0.74 0.00 0.74 0.51 0.51 0.60 0.60 0.55 R - Insula L Superior Frontal Medial Gyrus R - 0.71 0.00 0.71 0.51 0.51 0.59 0.59 0.55 Precentral Gyrus L BA38 R - Inferior Frontal Gyrus, pars 0.72 0.00 0.72 0.51 0.51 0.54 0.54 0.53 orbitalis R Superior Frontal Medial Gyrus R - 0.68 0.01 0.68 0.47 0.47 0.57 0.57 0.52 Precentral Gyrus R Inferior Frontal Gyrus, pars orbitalis R 0.76 0.00 0.76 0.53 0.53 0.50 0.50 0.52 - Precentral Gyrus R Insula R - Precentral Gyrus L 0.71 0.00 0.71 0.48 0.48 0.52 0.52 0.50 Inferior Frontal Gyrus, pars orbitalis R 0.77 0.00 0.77 0.51 0.51 0.49 0.49 0.50 - Precentral Gyrus L Inferior Frontal Gyrus, pars orbitalis R - Inferior Frontal Gyrus, pars 0.66 0.01 0.66 0.46 0.46 0.49 0.49 0.48 triangularis L Inferior Frontal Gyrus, pars orbitalis L 0.72 0.00 0.72 0.48 0.48 0.46 0.46 0.47 - Precentral Gyrus L BA38 L - Insula L 0.70 0.01 0.70 0.41 0.41 0.42 0.42 0.42 Insula R - Middle Temporal Gyrus R 0.70 0.01 0.70 0.42 0.42 0.40 0.40 0.41 BA38 R - Inferior Frontal Gyrus, pars 0.74 0.00 0.74 0.40 0.40 0.40 0.40 0.40 triangularis R Caudate L - Middle Temporal Gyrus R 0.71 0.00 0.71 0.38 0.38 0.42 0.42 0.40 Caudate L - Precentral Gyrus L 0.70 0.01 0.70 0.34 0.34 0.41 0.41 0.37 Caudate L - Precentral Gyrus R 0.71 0.00 0.71 0.34 0.34 0.38 0.38 0.36 BA38 L - Precentral Gyrus L 0.66 0.01 0.66 0.35 0.35 0.34 0.34 0.35 Insula R - Middle Temporal Gyrus L 0.68 0.01 0.68 0.33 0.33 0.33 0.33 0.33 BA38 L - Inferior Frontal Gyrus, pars 0.71 0.00 0.71 0.34 0.34 0.31 0.31 0.33 triangularis R BA38 L - Inferior Frontal Gyrus, pars 0.74 0.00 0.74 0.35 0.35 0.30 0.30 0.32 triangularis L Caudate L - Middle Temporal Gyrus L 0.70 0.01 0.70 0.31 0.31 0.33 0.33 0.32 BA38 L - Insula R 0.71 0.01 0.71 0.28 0.28 0.34 0.34 0.31 Parahippocampal Gyrus L - Uncus L 0.76 0.00 0.76 0.33 0.33 0.25 0.25 0.29 BA38 L - Caudate L 0.65 0.01 0.65 0.22 0.22 0.25 0.25 0.24 Hippocampus L - Middle Temporal 0.70 0.01 0.70 0.24 0.24 0.21 0.00 0.22 Gyrus L

8 Hippocampus L - Middle Temporal 0.72 0.00 0.72 0.23 0.23 0.21 0.00 0.22 Gyrus R Parahippocampal Gyrus R - Middle 0.68 0.01 0.68 0.22 0.22 0.20 0.20 0.21 Temporal Gyrus R BA38 L - Caudate R 0.75 0.00 0.75 0.18 0.18 0.23 0.23 0.21 Inferior Frontal Gyrus, pars orbitalis R 0.66 0.01 0.66 0.22 0.22 0.18 0.18 0.20 - Hippocampus L Parahippocampal Gyrus R - Precentral 0.78 0.00 0.78 0.22 0.22 0.17 0.00 0.19 Gyrus R Parahippocampal Gyrus L - Middle 0.69 0.01 0.69 0.18 0.18 0.19 0.00 0.18 Temporal Gyrus L Inferior Frontal Gyrus, pars orbitalis L 0.65 0.01 0.65 0.16 0.16 0.20 0.20 0.18 - Hippocampus R Amygdala R - Precentral Gyrus R 0.66 0.01 0.66 0.19 0.19 0.17 0.17 0.18 Inferior Frontal Gyrus, pars orbitalis L 0.68 0.01 0.68 0.21 0.21 0.15 0.00 0.18 - Hippocampus L Inferior Frontal Gyrus, pars triangularis 0.70 0.01 0.70 0.18 0.18 0.13 0.00 0.16 R - Hippocampus L Superior Frontal Medial Gyrus R - 0.66 0.01 0.66 0.18 0.00 0.13 0.00 0.16 Hippocampus L BA38 R - Parahippocampal Gyrus R 0.69 0.01 0.69 0.16 0.00 0.15 0.00 0.16 Superior Frontal Medial Gyrus L - 0.70 0.01 0.70 0.18 0.00 0.13 0.00 0.16 Hippocampus L Parahippocampal Gyrus R - Precentral 0.70 0.01 0.70 0.16 0.00 0.14 0.00 0.15 Gyrus L Precentral Gyrus R - Uncus L 0.75 0.00 0.75 0.16 0.00 0.13 0.00 0.15 BA38 L - Parahippocampal Gyrus R 0.71 0.00 0.71 0.15 0.15 0.14 0.00 0.14 Insula L - Parahippocampal Gyrus R 0.68 0.01 0.68 0.13 0.00 0.15 0.00 0.14 Hippocampus L - Insula R 0.69 0.01 0.69 0.15 0.15 0.12 0.00 0.14 Caudate L - Parahippocampal Gyrus R 0.76 0.00 0.76 0.14 0.14 0.13 0.00 0.14 Caudate L - Hippocampus L 0.75 0.00 0.75 0.12 0.00 0.14 0.00 0.13 Precentral Gyrus L - Uncus l 0.71 0.00 0.71 0.13 0.00 0.12 0.00 0.13 Caudate R - Hippocampus L 0.76 0.00 0.76 0.14 0.00 0.11 0.00 0.12 Insula R - Parahippocampal Gyrus R 0.68 0.01 0.68 0.16 0.00 0.08 0.00 0.12 Inferior Frontal Gyrus, pars triangularis 0.69 0.01 0.69 0.16 0.00 0.07 0.00 0.12 L - Hippocampus L Inferior Frontal Gyrus, pars orbitalis R 0.68 0.01 0.68 0.11 0.00 0.11 0.00 0.11 - Parahippocampal Gyrus R Inferior Frontal Gyrus, pars triangularis 0.68 0.01 0.68 0.12 0.00 0.10 0.00 0.11 R - Uncus L Superior Frontal Medial Gyrus L - 0.72 0.00 0.72 0.10 0.00 0.09 0.00 0.09 Uncus L Insula R - Uncus L 0.72 0.00 0.72 0.08 0.00 0.10 0.00 0.09 Hippocampus L - Uncus R 0.73 0.00 0.73 0.04 0.00 0.03 0.00 0.03

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