Oxytocin and social adaptation: Insights from neuroimaging studies of healthy and clinical populations

Yina Ma1, Simone Shamay-Tsoory2, Shihui Han3, Caroline F. Zink4

1State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research

Beijing Normal University, Beijing, China

2Department of Psychology, University of Haifa, Israel

3Department of Psychology and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China

4Lieber Institute for Brain Development, USA

Address correspondence to:

Yina Ma Ph. D.State Key Laboratory of Cognitive Neuroscience and LearningIDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing, 100875, ChinaEmail: yinama01@gmail.com

Table S1 Summary of oxytocin-fMRI studies.

Studies examining OT effects on human brain function published before August 2015 were selected through a standard search in PubMed and Embase with keywords [‘oxytocin’] AND [‘fMRI’ OR ‘magnetic resonance imaging’]. The current review focused on fMRI studies, and excluded papers that used EEG, MEG, SPECT, PET or MRS, and those did not employ a double-blind, placebo-controlled procedure. Additional studies were collected by reviewing the reference list of relevant papers in the first step, or through the ‘related article’ function of the PubMed database. Table S1 provided details of all eligible studies, including the experimental paradigm/task/stimuli, participants' information and summary of the main OT neural effects of each study.

First Author,

year Paradigm/task Stimuli Male FemaleDose(IU)

Design

Main OT neural effect summary

Oxytocin-fMRI Studies Involved Patients

Pincus, 20101

RMET (affect, motor, gender task) Faces -

D (8)H (8) 40 1

OTSTG, Ins, IFG, SFG, MFG, ACC in D in affect attribution;CA, AMY, ACC, STG, IFG in H in affect attribution

Labuschagne,

20102Emotion/Shape

matchHappy/fearful/

angry/neutral facesSAD (18)

H (18) - 24 1AMY to fearful faces in SAD;No OT effect on AMY in H.

Labuschagne,

20123Emotional valence

identificationHappy/sad/neutral

facesSAD (18)

H (18) - 24 1

mPFC, ACC, SMA, SPL, VC, FFG to sad face; mPFC, ACC, CA, CB to happy face in SAD;ACC, MFG, SMA, SPL, Tha to sad face; mPFC, ACC, MFG, precu, FFG, CB, STG to happy face in H.

Domes, 20134

Face/house matching Faces, houses

ASD (14) H (14) - 24 1

AMY to faces in ASDAMY to faces in H.

Bertsch, 20135

Emotion classification

Happy/fearful/angry faces -

BP (41)H (38) 26 2

AMYto happy faces, to angry faces in BPD. AMYto angry faces, to happy faces in H

Gordon, 20136 RMET Eye/vehicles ASD (18) ASD (3) 24 1

OT x Social (eye>vehicles) interaction: striatum, NAcc, CB, PreCu, PCC, IPL, STS for eye, for vehicle

Watanabe, 20147

Foe/friend judgment

Positive/negative face/word ASD (33) - 24 1 dmPFC, ACC, SFG, STS; dmPFC-AI/ACC FC, AMY-ACC FC to face vs. word

Dodhia, 20148 Resting-state -

SAD (18) H (18) - 24 1 AMY-rostral ACC/mPFC FC, amygdala-frontal FC in SAD

Domes, 20149

Word/emotion judgment Eye/mouth/word

ASD (14)H (14) - 24 1

AMY, TP, STG, IFG, SMA, CB, dlPFC, Tha, SPL to Eye; AMY, TP, AI, STG, IFG, PCC, brainstem, precentral, ACC, SMA, CB, dlPFC, Tha, SPL to mouth

Aoki, 201410

First-order false belief task

Picture and sentence ASD (20) - 24 1 AI, cuneus, MT, IFG to social emotion inference

Gorka, 201511

Emotion/Shape match

Happy/fearful/angry/neutral faces

SAD (16) H (17) - 24 1

AMY activity to fearful faces in SAD. OT x Group interaction in FC between AMY and Ins, MCC, SMA, STG, PT to fearful faces in SAD, in H

Oxytocin-fMRI Studies Conducted on Healthy Volunteers

Kirsch, 200512

Emotion/Shape match

Fearful/threatening scenes and faces 15 - 27 1 AMY to threatening faces/scenes, AMY-brainstem FC

Domes, 200713 Morphed face

Happy/fearful/angry/neutral faces 13 - 24 1

AMY, ITG, MTG, MFG, CB to fear face; AMY, Tha, postcentral to angry face; AMY, ITG, MTG, paracentral to happy faces

Singer, 200814 Empathy for pain Experimental cues 20 - 32 1

AMY, striatum, midbrain, OFC to painful stimulation;OFC to empathy for other’s pain.

Petrovic, 200815 Fear conditioning

Direct/averted gazed faces 27 - 32 2

AMY, subgenual ACC, right vlPFC, FG, left vlPFC to conditioned direct eye-gaze; vmPFC, OFC, left vlPFC to conditioned averted eye-gaze

Baumgar Trust and risk game Numbers 49 24 2 AMY, Postcentral, PT, Ins, CA, midbrain to negative feedback in trust game;

tner, 200816 no OT effect for negative feedback in risk gameGamer, 201017

Emotional valence identification

Happy/fearful/neutral faces 46 24 2

AMY to fearful faces; AMY to happy faces; AMY, SC, AMY-SC FC when shifting gazing to eye

Domes, 201018 Emotion arousal

Happy/fearful/angry/neutral faces - 16 24 1

MTL, AMY, Ins, FFG, STG, CB, brainstem; prefrontal to fearful face;IFG, vlPFC, dlPFC to angry face; MTL, FFG, Ins, STG, hippo, CB; dlPFC to happy faces

Rilling, 201119

Prisoner's Dilemma game Numbers 63 - 24 2

ACC, VC, vlPFC, SPL to defect; PT, Ins, AMY, CA, vlPFC, PCC, ITG, OFC, MFG, MTG, IFG; AMY-AI FC to cooperation

Riem, 201120

Passive listening infant cry Cry sounds - 42 24 2 AMY, Ins, IFG to infant cry

Sauer, 201221

Emotion/Shape match

fearful/threatening scenes and faces 55 - 25 1 FFG, MT, CB, MCC, angular, Ins (this OT effect: A- > A+ of rs3796863);

Exp. 221 Eye gaze Faces 55 - 25MFG, MO to eye-gaze (this OT effect: A- > A+ of rs3796863);CB, paracentral, PH to direct vs. averted eye-gaze (this OT effect: A- < A+);

Riem, 201222

Passive listening infant cry/laughter Cry/larghter sounds - 42 24 2 AMY; FC between AMY and OFC, hippo, angular, MTG to infant laughter

Striepens, 201223 Encoding/Retrieval

Aversive/neutral pictures 70 - 24 2

AMY; Ins;FC between AMY and AI, IFG

Lischke, 201224 Emotion arousal

Positive, negative, neutral scenes - 14 24 1 AMY, ITG, TP, postcentral to negative scenes; SMA to positive scenes

Wittfoth-Schardt, 201225 Passive view

Own/familar/unknown children 19 - 24 1

GP, CA viewing own child; GP, MTG viewing unknown child;FC between left GP and right GP, Hippcampus, MFG, SPG viewing own vs. familiar child

Montag, Eye gaze Faces 55 - 25 1 AMY to directed eye-gaze in both genotypes of rs401015;

201326 To averted eye-gaze: AMY in TC carriers; in TT of rs401015Sauer, 201327

Emotion/Shape match

Fearful/threatening scenes and faces 55 - 25 1

AMY to negative stimuli; no OT effect to positive stimuli;CD38 gene x COMT gene x OT interaction in AMY activity

Rupp, 201328 1 back Sexual/infant pic - 53 24 2 AMY to sexual arousal; AMY to infant arousal

Scheele, 201329 Passive view

Partner/familiar/unknown women 40 - 24 1

VTA, NAcc, PT, GP to partner’s face; to unfamiliar faces for heterosexual pair-bonded males

Sripada, 201330 Resting-State - 15 - 24 1 AMY-mPFC FC

Groppe, 201331

Social incentive delay Happy/angry faces - 28 26 2

MT, MO, VTA, MCC, NAcc, Ins to social reward anticipation;precentral, postcentral, cuneus

Riem, 201332 Resting-State - - 42 16 2 FC between PCC and brainstem, CBRupp, 201433 1 back

Negative/neutral pictures - 53 24 2 AMY to negative pictures

Grimm, 201434

Montreal Imaging stress task

Arithmetic numbers 32 - 24 1

PH, PCC, ACC, Ins; Tha, hippo (all subjects);Early-life stress x OT interaction in ACC, AMY, PH, Ins, PT, CA

Riem, 201435 RMET Faces - 50 16 2

Ins, STG (all subjects); Maternal love withdrawal x OT interaction in STG (for high love-withdraw; no OT effect for low love withdraw)

Voorthuis, 201436

emotion/gender judgment (Infant)

Infant picture/words - 50 16 2 STG, IFG, MT

Rilling, 201437

Prisoner's Dilemma game Numbers 60 45 24 2

Gender x OT interaction in NAcc, basal forebrain, CA, hippo, PT, Ins, PCC, Tha, OFC, CB, PH (stronger OT effect in male vs. female)

Eckstein, 201438

Montreal Imaging stress task

Arithmetic numbers 60 - 24 2 Precu, PCC, ACC

Scheele, 201439

Pleasantness rating of touch

A male or female faces 40 - 24 1

Ins, OFC, Precu, cuneus, ACC to female touch; OFC to male touch; Precu, ACC to female vs. male touch

Scheele, 201440 Arousal rating Faces 23 - 24 1 ACC, MCC, Precu, Ins to disgust arousalRiem, 201441

Passive listening of infant crying

Infant cry labeled as sick or bored - 50 16 2

Ins, IFG to sick infant crying; Ins IFG to bored crying;AMY to 500 Hz crying, but to 700 Hz crying.

Fan, 201442

Resting-State;Montreal Imaging

stress taskArithmetic numbers 18 - 24 1

ACC-amygdala rest-task interaction, especially in subjects with low early life stress scores

Kanat, 201543 Emotion detection

Angry/happy/neutral faces 46 - 24 2

AMY, FFG, CB, midbrain, Tha, hippo, MFG, striate, IP, CA, IFG to angry eye; AMY, Ins, dmPFC, pallidum, ITG, PT, hippo, dlPFC to happy mouth; AMY-FFG FC

Zunhammer,

201544

Intensity/unpleasantness

rating Experimental cues 36 - 32 1angular, frontal pole, postcentral with stimulation regressor;hippo, OFC, Precu, calcarine, lingual with temperature regressor;

Preckel, 2015

Exp. 145Imagery of partner

infidelity Sentences 22 - 24 1 ventral ACC to sexual infidelity imagery

Exp. 245Moral/non-moral

dilemma Stories 48 - 24 2 ACC, PCC, PreCu, MCC, OFC to moral vs. non-moral judgmentEckstein,

201546Fear Conditioning

extinction Faces/houses 62 - 24 2mid-PFC, mPFC to early fear extinction; AMY to early and later extinction; AMY-PreCu, PFC-PCC FC to later vs. early extinction

Hu, 201547

Reinforcement learning task

Smiling/angry faces or cartoon faces 15 -

241 AMY, hippo, PH, PT during social feedback; FC between AMY and Ins, CA

Bos, Empathy for pain Painful/non-painful 54 - 24 2 SII, MCC, Ins to empathy for other’s pain (Black + White hands)

201548 black or white handGregory, 201549

One-back matching task

Cry/smile infant, sexual photos - 59

242 VTA to crying infant and sexual images; no OT effect to smiling infant

Feng, 201550

Fan, 201551

Kanat, in press52

Gender judgment on eyes Happy/fearful eyes 43 -

242 AMY, olfactory cortex, SMA, ACC, paracentral, MT to fear vs. happy eyes

Kumar, in press53 Resting-State - 15 - 24 1 the degree centrality of Precu; Precu-AMY FCFeng, in press54

Prisoner's Dilemma game Numbers 104 100

242

Gender x OT interaction in CA, PT, dmPFC (stronger OT effect in male vs. female)

Chen, in press55

Note:Column 2 - RMET= Read mind in the eyes test;Column 4, 5 – Male/Female: SAD = Social anxiety disorder; ASD = Autism spectrum disorder; D = Depression; H = Healthy volunteers; BP = Border line personality disorder;Column 7 - Design: 1 = Oxytocin vs. Placebo sessions, within-subject design; 2 = Oxytocin vs. Placebo groups, between-subject design;Column 8 –STG=superior temporal gyrus; IFG=inferior frontal gyrus; SFG=superior frontal gyrus; MFG=middle frontal gyrus; ACC=anterior cingulate cortex; AMY=amygdala; mPFC=medial prefrontal cortex; SMA=supplementary motor area; SPL=superior parietal lobe; VC=visual cortex;FFG=fusiform gyrus; ITG=inferior temporal; TP=temporal pole; MCC=mid-cingulate cortex; PT=putamen; PreCu=precuneus; NAcc=Nucleus accumbens; PCC=posterior cingulate cortex; IPL=inferior parietal lobe; dlPFC=dorsal lateral prefrontal cortex; AI= anterior insula;

MTG=medial temporal gyrus; Tha=thalamus; vlPFC=ventral lateral prefrontal cortex; SC=superior colliculi; CA=caudate; CB=cerebellum; FC=functional connectivity; Ins=insula; AI=anterior insula; PH=parahippocampal; GP=globus pallidus; VTA=ventral tegmental area; MO=middle occipital; hippo=hippocampus; SII= secondary somatosensory cortex; FC=functional connectivity.

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