Ruth Feldman Bar Ilan University

The Allegory of Charity

…….The roots of parenthood lie in the child's relations to his own parents in his earliest years. The love which a mother has for her children is a reflection of the love which she received when she was a little girl. The love which a father has for his children is a reflection of the love which he received when he was a little boy. It is in childhood that we learn to love"

Bowlby, The roots of parenthood, 1953 (p. 15).

Children Become Members of their Social World in the Context of Early Attachment

Bonds – “Selective and enduring attachments” – Attachment is a necessary process to insure survival

and social adaptation across mammalian species – Involves specific genetic, epigenetic, brain, hormonal,

behavioral, brain (and mental) components

– Parental, pair, and filial bonding share underlying mechanisms

– Bonding provides the basis for core social phenotypes including rules of social exchanges, capacity for empathy, emotion regulation, social cognition, and

symbol formation through processes of bio-behavioral synchrony

• What is the biological basis of the human capacity to build collaborative societies?

• Research in social animals (ants) beginning in the 1920s described the process of bio-behavioral synchrony among collaborative animals trying to accomplish a joint social goal

• The evolution of mammals - biobehavioral synchrony is learned within the “nursing dyad” and in the context of parent-infant proximity.

• Over time, partners become sensitized to each other’s biological and social cues leading to a unique bond of synchrony between physiology and behavior

• Synchrony is considered the cornerstone of adaptive social life and should be experienced in infancy.

Synchrony

- Postpartum maternal behavior - conserved species-specific

repertoire central for growth and adaptation

- Maternal behavior shapes the infant’s Oxytocin system (the

capacity to connect) and Cortisol system (the capacity to

handle stress)

• Gaze at infant face

• Positive affect

• “Motherese” vocalizations

• Affectionate touch

- Coordination of maternal behavior with infant readiness to

interact

- Touch is integrated into synchrony of visuo-affective cues

Maternal Post-Partum Behavior is the Mechanism upon which the Cross-

Generation Transmission Builds

Maternal Postpartum Behavior

Maternal Stress and Unvailability

Face-to-Face Synchrony

– At around 3 months infants become active participants in face-to-face interactions

– Coordination of gaze, affect, vocalization and touch – Dance-like quality: Matching of tempo, arousal

dynamics, and rhythms – Affords biological synchrony between mother and

child’s physiology (heart rhythms, hormone fit, brain-to-brain coupling)

– Predicts emotion regulation, symbol formation, stress management, and empathy across childhood and up to adolescence

Feldman, JCPP, 2007 Feldman, 2012, Hormones and Behavior

The Building Blocks

Synchrony as the Stable Component of the

Relationship

The Father Style

Fathers and Mothers Differ in Their Interactive Styles

Social gaze Social gaze

random random

Oxytocin Production and Receptor Distribution

15

Oxytocin: System that Supports the Formation of Social Bonds

• A nine-amino-acid neuropeptide synthesized in the hypothalamus has been known for its role in birth and lactation

• Recent studies implicated Oxytocin in a host of affiliative-related behavior including trust, social recognition, ToM, sexual behavior, and the formation of social bonds

• Closely linked with HPA, Dopamine, and immune systems. Receptors widely distributed throughout body and brain

• Strong epigenetic effects: shaped by early social experiences • Oxytocin functions as a biobehavioral feedback loop: More touch and

contact induce OT release and vice versa.

What have we Learned from Studies of Peripheral Oxytocin and Bonding

• High variability: range 11 – 4000 pg/ml • Highly stable within individuals (r = .60-.97) • No differences between men and women and between

mothers and fathers • Increases during periods of bond formation (pregnancy and

postpartum, falling in love) • Evidence for bio-behavioral synchrony between mothers and

fathers and between parents and infants • The provision of parent-specific touch (affectionate in mothers

and stimulatory in fathers) induces OT release • Peripheral levels are associated with behavioral synchrony

between attachment partners (parent-specific repertoire)

Central Unresolved Issues in Oxytocin Research on Human Affiliation

• Is peripheral OT release coordinated with activity of central oxytocinergiec neuropathways?

• Is there bio-behavioral synchrony in the effects of parental OT administration on infant physiology and behavior?

• Relations of OT to key circuits of the parental brain • OT in romantic and filial attachment • OT as biomarker for psychopathologies of social

functioning (autism) or bonding (PP depression) • OT as a potential therapeutic agent

• 352 individuals including 272 mothers and fathers and their 4-6 month old infants and 80 non-parents

• Risk alleles on OXTR (rs2254298, rs1042778) and CD38 (rs3796863) SNPs that have shown to be associated with autism in several large samples.

• Parent-infant interaction microcoded for phenotypes: Parent Touch and Gaze Synchrony

• Individuals reported on patterns of parental care in their own childhood

Study 1: Genetic Variability and Peripheral OT: Plasma OT, Variations in OXTR and CD38 Genes, and Core Social

Phenotypic Behavior

CD 38 mediates OT release

Salmina AB, Lopatina O, Ekimova MV, Mikhutkina SV, & Higashida H (2010) CD38/cyclic ADP-ribose system: a new player for oxytocin secretion and regulation of

social behaviour. J Neuroendocrinol 22(5):380-392.

Plasma OT Levels according to Risk Alleles on OXTR and CD38 Genes

200

250

300

350

400

450

Pla

sm

a O

T,

pg

/ml

AA

/AC

CC

AG

/AA

GG GG

/GT

TT

** * **

OXTR1042778OXTRrs2254298CD38rs3796863

20

25

30

35

40

Pa

ren

tal T

ou

ch

(F

req

ue

nc

y)

CD38rs3796863Plasma OT OXTR1042778

Hig

h O

T

Lo

w O

T AA

/AC

CC

GG

/GT

TT

****

**

Parental touch according to Risk Alleles on OXTR and CD38 Genes

Durations of Gaze Synchrony according to Plasma

OT and Risk Allele on CD38 Gene

4

6

8

10

12

Ga

ze

Syn

ch

ron

y D

ura

tio

ns

High Plasma OT Low Plasma OT

CD38rs3796863 AA/AC CD38rs3796863 CC

*

**

*

First evidence that peripheral OT is associated with genetic variability on the extended OT pathway, core social phenotypes and cross-generation transmission of parenting. OT underpins critical components of human attachment. No difference in gene x plasma x parenting memories in parents and non-parents. Allparenting in humans? Genetic markers indicating risk for ASD were found to correlated with core phenotypes (social gaze) (a) autism is on a continuum with normative social development in infancy (b) use of integrated genetic, endocrinological, and behavioral biomarkers for the early detection of ASD

Conclusions

Feldman, et al., 2012, Biological Psychiatry

Study 2: Oxytocin Administration to Parent Enhcnes Infant Physiological and Behavioral Readiness for Social

Engagement

• 35 fathers in double-blind placebo control within-subject design OT administration 45 minutes before interacting with their 6-months old infants.

• Salivary OT and cortisol were assayed from father (4 times) and child (3 times)

• Cardiac Vagal-Tone from father and child was collected during the free play, still-face, and reunion parts of the interaction.

• Interactions were micro-coded for father and child social behavior

Salivary OT in Father and Infant Following OT Inhaling

Father

5

6

7

Resting Free Play Still Face Reunion

Ca

rdia

c V

ag

al T

on

e

Oxytocin

Placebo

*

*

Infant

3

4

5

Free Play Still Face ReunionC

ard

iac

Va

ga

l T

on

e

Oxytocin

Placebo

*

RSA in Father and Infant Following OT Administration

Mean Duration of Father and Infant Behavior Following OT Administration

0

3

6

9

12

15

18

Touch Re-Engagement Social Gaze Object

Manipulation

Mea

n D

ura

tio

n

Placebo

Oxytocin

Father Infant

Weisman, Zagoory-Sharon, & Feldman, 2012, Biological Psychiatry

Study 3: The Neural Substrates of Parenting

• 30 Mothers and 15 fathers parents of 4-6 months old infants.

• Parent-own-child, parent standard-child, own infant alone, and standard infant alone as fMRI stimuli.

• Mothers divided into two groups based on micro-coding of interaction: synchronous – those who coordinate social behavior with infant signals, and intrusive – those who provide excessive parenting behavior while infant gaze averts and signals need for rest

• Plasma oxytocin and vasopressin measured from mother and father

Coordination of maternal behavior with infant social readiness

Synchrony: affect, gaze, mimicry

Intrusiveness: affect, gaze, touch

Provision of social behavior when infant signals a need for rest

Amygdala and Accumbens signal analysis Repeated measure GLM ANOVA: Interaction effect: F(3, 57)=3.8048, p=.01480

Intrusive, N=10

Synchronous, N=13

-2.0

-1.5

-1.0

-0.5

0.0

0.5

1.0

1.5

Right Amygdala Left NAcc

% s

ign

al c

han

ge ‘o

wn

-oth

er

infa

nt’

*

**

32

Iacoboni and Dapretto Redgrave Nature Reviews Neuroscience 7, 942–951 (December 2006) | doi:10.1038/ nrn2024

The mirror neuron system

Left Nucleus Accumbens Time Course 1. Intrusive 2. Synchronous 3. Intrusive 4. Intrusive 5. synchronous 6. Intrusive 7. synchronous 8. Intrusive 9. Intrusive 10. Intrusive 11. Intrusive 12. synchronous 13. synchronous 14. Synchronous 15. Synchronous 16. Synchronous 17. Synchronous 18. Synchronous 19. Synchronous 20. Synchronous 21. Synchronous

Blank Anxious interaction

Stranger baby

self Depression interaction

Own baby Own interaction

Anxious baby

Stranger interaction

1. Intrusive

2. Intrusive

3. Intrusive

4. synchronous

5. Intrusive

6. Intrusive

7. Intrusive

8. synchronous

9. synchronous

10. Synchronous

11. synchronous

12. Intrusive

13. Intrusive

14. synchronous

15. synchronous

16. Synchronous

17. Synchronous

18. Synchronous

19. Synchronous

20. Intrusive

21. Synchronous

22. Synchronous Blank Anxious

interaction Stranger

baby

self Depression interaction

Own baby Own interaction

Anxious baby

Stranger interaction

37

Right Amygdala Time Course

Brain areas that show inter-parent correlations: pre motor and motor cortices,

temporal-parietal-junction (TPJ), inferior frontal gyrus (IFG) and insula.

Mother and father share online a socio-cognitive (Empathy,

ToM) network to their own infant

Mother-Father Brain Synchrony to

Infant Cues

Biology vs. Caregiving in the Parental Brain

I. 91 first-time parents including 48 homosexual fathers (in committed relationships), 21 heterosexual fathers, and 22 mothers.

II. Home visit, hormonal analysis, scanning III. Coding of Parent Sensitivity IV. Scanning

The ‘Attachment’ Network

Emotional Processing

Network • Amygdala

• VTA

• Insula

• dACC

• Hypothalamus

Mentalizing Network • mPFC

• Frontopolar Cortex

• STS

• Temporal Poles

Path Analysis of Brain, Hormones and Behavior In Primary and Secondary-Caregiving Parents

Maternal Depression - Juan Miro

Personage 1925 Head of a Woman 1938

Study 3: Building a Human Model of PPD

1983 Mothers

618 Mothers

Elimin

ate M

edica

l an

d

Psych

oso

cial R

isk

Low Depression High Depression

254 Mothers

Elimin

ate H

igh

Anxiety

2nd Post-Birth Day

6 Months 9 Months

182 Mothers

SCID Mother-Infant Interaction

Emotion Regulation HPA mother and child

6 Years Home Visit

155 Mothers

SCID, DAWBA DNA, Hormones

Parent-Child & Family Interactions Empathy

Symbolic Skills Neurocognitive, IQ

46 Depressed Mothers 92 Healthy Mothers

Maternal Depression

The Sequence of Interaction; Maternal MDD

Mother-Infant

Gaze Synchrony

Mother

gaze

brake

Infant no

Vocalization

Infant low Affect

Infant Gaze

Aversion

.69

.54

.37 .56 .22

.55 .78

.41

.43

.61

Maternal Depression and Child Disorder

0

20

40

60

80

100

Depressed Non-Depressed

Ch

ild

Ax

is I D

iso

rde

r %

Child Axis I Disorder

Child- No Disorder

Mothers

Maternal PPD and Child Social Outcomes

2

3

4

5

6

Social Engagement Empathy

Depressed Non-Depressed

Maternal PPD and OT in Mother, Father, and

Child

3

5

7

9

Mother Father Child

Sa

liv

ary

OT

(p

M)

Depressed Non-Depressed

**

*

Maternal and Child OT at Preschool

0

5

10

15

20

0 5 10 15 20 25

Mother - OT

Ch

ild

- O

T

r = 0.486

Maternal PPD and OXTR

0

10

20

30

40

50

60

70

Depressed Non-Depressed

OX

TR

22

54

29

8, n

GG

AA/AG

The Buffering Role of Oxytocin Depressed - N=46

29 = GG (63%)

17 = AA/AG (37%)

Of the OXTR GG

18 with disorder (62%)

11 without disorder (38%)

Of the OXTR AA/AG

6 with disorder (35%)

11 without disorder (65%)

Non-Depressed -

N=92 34 = GG (36%)

58 = AA/AG (64%)

Of the OXTR GG

9 with disorder (26%)

25 without disorder (74%)

Of the OXTR AA/AG

8 with disorder (13%)

50 without disorder (87%)

0

10

20

30

40

50

AA/AG GG AA/AG GG

Su

bje

cts

Child Axis I Disorder

Child- No Disorder

Depressed Mothers Non Depressed Mothers

Apter-Levy, Feldman, Vakart, Ebstein, & Feldman, AJP, 2013

Dyadic Video-Feedback Intervention for Post-Partum Depression: Before

After

Conclusions

• Maternal post-partum depression bears long-term negative effects on infant biology and behavior,

• Such disturbances interfere with the capacity to form social affiliation, including decreased social engagement, reciprocity, and the capacity for empathy and increased vulnerability for psychopathology

• The OT system appears to provide a buffer against the long-term effects of maternal post-partum depression on children’s mental health and social outcomes

Apter-Levi, Feldman, Vakart, Ebstin, & Feldman (2013). American Journal of Psychiatry

Oxytocin, Synchrony, and Emotion

Regulation in Preschoolers with ASD

F ree P lay – S till F ace P rocedure

E motion R egulation P roceduresWith P arent and S tranger

Mother OT

3

4

5

6

7

8

9

10

Basal Following

Play

Following

Contact

Post

Interaction

Sa

liv

ary

Ox

yto

cin

, P

M

ASD

TD

Father OT

5

6

7

8

9

10

11

12

Basal Following

Play

Following

Contact

Post

Interaction

Sali

vary

Oxyto

cin

, P

M

ASD

TD

Child OT

* * *

*

With Father

2

4

6

8

10

Basal Following

Play

Following

Contact

Post

Interaction

Sa

liv

ary

Ox

yto

cin

, P

M

TD

ASD

With Mother

2

4

6

8

10

Basal Following

Play

Following

Contact

Post

Interaction

Sa

liv

ary

Ox

yto

cin

, P

M

TD

ASD

Gaze Synchrony

0 0.4 0.8 1.2 1.6

ASD

TD

Seconds

Joint Attention

0 1 2 3 4 5 6 7

ASD

TD

Seconds

Gaze Synchrony

0 0.4 0.8 1.2 1.6 2 2.4 2.8 3.2

ASD

TD

Seconds

Joint Attention

0 2 4 6 8

ASD

TD

Seconds

With Father With Mother

Feldman, Golan, Hirshler, Ostfeld, & Zagoory-Sharon, British Journal of Psychiatry, 2014

Bonding and Oxytocin: Conclusions

• Bonding is a process through which the physiological and social signals of one partner synchronize with those of the attachment partner’s

• The extended OT pathway plays an important role in this process

• Like mammals, humans can impact the physiological systems of the attachment partner by means of social contact and the effects of two core social phenotypes: touch and social gaze.

• Conditions associated with early disruptions to social bonding, including autism, maternal post-partum depression (18%) premature birth (12%), are associated with dysfunctions in OT as well as core social behavior.

Bonding-Related Interventions

• Because the OT system is open to environmental influences interventions that increase tactile contact and facilitate social gaze synchrony may assist in conditions of early social dysfunction or disruptions to maternal-infant bonding

• Such interventions show promise in repairing the child’s physiological, social, and emotional growth.

Conceptual Implications

• Gerald Edelman and the question of the Subjectivity Gap and a potential for Brain Based Epistemology

• Husserl’s phenomenology and the question of Philosophy as a Rigorous Science (1911)

• Can the four-channel bio-behavioral synchrony conceptual framework provide a perspective of scientifically-valid Intersubjectivity to the central question in current neuroscience?

Feldman, 2012 Hormones and Behavior

“grant me the prayer that I may never lose the bliss of the touch of the

one in the play of the many”

(rabindranath tagore)

Thank You

Special Thanks to:

Orna Zagoory-Sharon, PhD

Ilanit Gordon, PhD

Shir Atzil, PhD

Inna Schneiderman

Omri Weisman

Magi Singer, PhD

Ari Levine, PhD

Dalia Silberstein, PhD

Adva Vangrober, PhD

Adam Vakart

Michal Feldman

Yael Apter

Yael Hirschler

Sharon Ostfeld-Etzion

Collaborators:

Richard P. Ebstein, PhD-Genetics

Talma Hendler, MD-Imaging

Avi Goldstein, PhD-ERP & MEG

Eyad Hallaq, PhD- PTSD

Arthur I Eidelman, MD – Preterms

Yoram Louzoun – Mathematics

Ofer Golan, PhD- Autism

Conclusions

• Synchrony is the process through which the physiological and behavioral systems of one human become coordinated with those of another and this process serves as the basis of social adaptation, emotion regulation, empathy, and stress management throughout life

• Educators and educational settings can provide the communities where synchrony, social reciprocity, and self-regulation can be mastered.

• Public awareness and community-based interventions are key to highlight the critical role of early parent-child attachment for children’s social and emotional development

Special Thanks to:

Orna Zagoory-Sharon, PhD

Ilanit Gordon, PhD

Shir Atzil, PhD

Inna Schneiderman, PhD

Eyal Avraham

Omri Weisman

Magi Singer, PhD

Ari Levine, PhD

Adva Vengrober, PhD

Adam Vakart

Michal Feldman, PhD

Yael Apter

Yael Hirschler

Sharon Ostfeld-Etzion

Ortal Shimon

Collaborators:

Richard P. Ebstein, PhD-Genetics

Talma Hendler, MD-Imaging

Avi Goldstein, PhD- MEG

Eyad Hallaq, PhD- PTSD

Yoram Louzoun – Mathematics