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Neuroimaging and intersubjectivity in psychiatry
Knut SchnellDep. Of General Psychiatry Translational Psychiatric Therapy Research
Mission: Illustrate the principles of experimental Psychopathology of intersubjective functions
Concepts of Intersubjective functions
Experimental psychopathology of ToM- and Empathy functions: ToM, Empathy
Experimental model of psychotherapy-effects on intersubjective functions in (chronic) Depression: Perceived functionality
Social brain Hypotheses (Brothers 1990, Dunbar 1998)
– Expansion of brain driven by social demands– Positive correlation of neocortex expansion and size of social groups in
primates
(Dunbar 2003, reprinted from Barrett et al. 2002)
(Adolphs 2003)
Mission
Proposed intersubjective functionsin humans
Imitation, Representation of Intentions Mirror Neurons
Sharing Feelings Empathy
Representing mental content Theory of Mind
Recognizing interpersonal effects Perceived Functionality
Joint attention …
Mirrorneurons in primates
Iacoboni & Dapretto NRN 2006adapted from Rizzolatti et al. 2001
ImitationRepresentation of Intentions
Mirror-Neurons in Humans
Iacoboni & Dapretto NRN 2006 adapted from Iacoboni et al. 1999
Intention, not movement or objects codedIacoboni & Dapretto NRN 2006 adapted from Iacoboni et al. 2005
Fig. 1. Experimental design. Subjects made sinusoidal movements with their right arm at the same time as observing movements that were either congruent or incongruent with their own movements. In each condition, the subject (S) was instructed to make sinusoidal movements of their right arm from the shoulder, which were either vertical or horizontal at a rate of 0.5 Hz. While making these arm movements, the subject observed movements made by another effector situated facing the subject, either the right arm of the experimenter (E) or a robotic arm (R), that were either congruent or incongruent with the executed movements. In addition, there were two baseline conditions in which the subject moved their arm either horizontally or vertically without watching anything.
Kilner, J. M., Paulignan, Y., & Blakemore, S. -J. Current Biology, (2003)
Interference with observed motion depends on self-reference (human/non-human)
Motor contagion
Theory of Mind
• Ability to understand, that other subjects have mental states (desires, beliefs, emotions), to recognize such mental states and to act on this basis
• Develops between 3. and 4. years of age
Imaging of ToM-functions in humans
Cartoons (Gallagher at al., 2000)
Stories (Fletcher et al., 1995)
Comic strips (Brunet et al., 2000)
mPFC
anterior medialPFC
TPJtemporoparietal junction
STSSulcus temporalis superior
Neuroanatomy of the ToM-network
OFCLateral Orbitofrontal Cortex
Empathie: Definition
For Basic Emotions like fear and happiness and complex emotions like guilt Restrains humans from aggressve behaviour, can motivate altruistic
behaviour
The Ability to share the feelings of another human being without direct Stimulation by affective stimuli
Hein & Singer define empathy “as an affective state, caused bysharing of the emotions or sensory states of another person” (Hein and Singer, 2008).
Empathy in mice?
In contrast to affective contagion, empathy is bound to the individual awareness that a specific emotion was primarily initiated in the other person (Hein and Singer, 2008).
Empathy in Humans
Shared activation for pain experienceof the partner
Singer et al. 2004
Empathy= Shared Pain?
In contrast to Hein & Singers restrictive definition of empathy, mentalizing is defined by Frith & Frith as “the process by which we make inferences about mental states” (Frith and Frith, 2006) and does not only include the inference about another persons’ motivational states and beliefs but also the immediate recognition and the cognitive inference about other persons’ emotional states.
Empathie after social Interaction
Empathy for pain subsequent to social interaction in women and men
Activation of Nc. Acc.by pain of unfair players
in women and men
Singer et al. 2006
Relation between Self-Reported Empathy and Motor Identification with Imagined AgentsMarzoli et al., 2011
Simulation-Systems: Shared experience by isofunctional activation of limbic and sensorimotor regions (AI, ACC, or SII) during observation of a feeling, acting and perceiving human subject
Theory-Systems: Mental State Attribution/Mentalising by functional network of social inference: medialem PFC , inferior parietal and superior temporalem Cortex and esp. TPJ
Empathic Accuracy: Correlation between rated timecourse of affective states from filmed target participants and perceivers (viewers)
Accuracy is correlated with brain activity during video pressentation
Brunet-Gouet & Decety, 2006
Theory of Mind regions overlap with emotion processing regions
Is there an overlap between ToM and Empathy? Does the term term “cognitive empathy” (Preston and de Waal, 2002) represent a meaningful neurofunctional conceptWhat are the functions of STS, TPJ, OFC and mPFC?
mPFCanterior medialPFC
TPJtemporoparietal junction
STSSulcus temporalis superiorOFCLateral Orbitofrontal Cortex
Paradigm
A Paradigm:Distinction of perspective and affective contentNo immediately contagious affective contentRandomized stories/instructions
8.5 sec 8.5 sec 8.5 sec
Demands
difference?
- = +difference?
- = +
„Instruktion“ 32 stories
Design
6.5 sec
Nur für Bild 2 und 3 relevant!
- = +
- = +
Design (questions / stories randomised)
1st PP 3rd PP
( cognitive )
visuospatial
Affective
Nur für Bild 2 und 3 relevant!
- = +
- = +
Nur für Bild 2 und 3 relevant!
- = +
- = +
Nur für Bild 2 und 3 relevant!
- = +
- = +
Main effect of affective content:Activation of anteriorer parts of ToM network
Results
Main effect of 3rd Person PerspectiveActivation of posterior ToM Network, TPJ, FEF, Precuneus
Results
Results
Simple effectsV isuospatial; A ffective1. Person; 3. Person
InteraktionV isuospatial; A ffektiv1. Person; 3. Person
Results
Finally:„cognitive empathy“ can be renderered as a defined neurophysiological functional state, which is not „cold“ but rather linked to the activation of the amygdala.
Experimental psychopathology of ToM- and Empathy-functions
Impaired Inference on the mental states of others: in autism spectrum disorders (Baron-Cohen, 2001)in affective disorders (Inoue et al., 2006; Kerr et al., 2003)in schizophrenia (Brunet-Gouet and Decety, 2006; Walter et al., 2009) defined as an explicit target for psychotherapy (Bateman and Fonagy, 2008).
• Paranoid delusions associated mit Attributional Bias: Erklärung von aversiven Ereignissen durch den Einfluss anderer. Martin & Penn 2002
• Störung der mentalen Perspektivübernahme bei schizophrenen Patienten. Sprong et al. 2007, Bora et al. 2009
- = + - = +
Fühlt sich die Hauptperson besser, genauso oder schlechter als im Bild zuvor?
>
Sind mehr, gleichviele oder weniger lebende Wesen abgebildet als im Bild zuvor?
soziale Kognition
Störungen der selektiven sozialen Selbst-/Fremdreferenz
n=109 Gesunde
>>
Walter*, Schnell*, Erk* et al, 2010, Mol. Psychiatry
Genetically determinated functioanl impairment of selective Selbst-/Other-perspective taking as a mediator of schizophrenia risk?
Effect of a genetic Polymorphismu (rs1344706) associated with increased risk for schizophrenia during selective perspective taking
Main Effect
soziale Kognition
Experimental model of psychotherapyeffects on intersubjective functions in (chronic) Depression: Perceived functionality
An fMRI-Modell of learned helplessness in depression (Seligman 1978), preoperative causal thinking (McCullough 2000), derived from own experiences in CBASP practice…
Existential question :Does my behavior affect the affective state of others?
CD-patient: „I can‘t believe that it affects your mood if I tell you I was succesful in resolving the fight with my daughter !“
Basic ideas
S
Significant other /Traum
atic interpersonal experience
CBASP
Modify cognitiveschema
Interpersonal Discrimination/Perception of Functionality
SO
PatientTherapistSignificant other
S
R
C
We will improve the perception of interpersonal functionality!
Hmm, „perception of functionality“ … what am I supposed to do?
The fundamental question:
McCulloughBrain
Bandura 1978
„If I (O) do this (R), the other person (S) will do that (C) “
(with a probality of E‘ %)
StimulusOrganism
Reaction
Consequence
Behavioral Model
Hypotheses I (Basic Study) Continuous update of predictive models of social partners, enables affective self-regulation through prediction of their affective reactions
Hypotheses II (Clinical Trial CBASP vs Escitalopram) Update of predictive models of others is impaired in chronic depression
Hypotheses
I : Basic Study
Simulation of an occasional conversation
n=21 Healthy Subjects, fMRI, 3Tesla Siemens Trio, TR 2,07s
I Basic Study
Event related fMRI design
Positiver?
Happy hour! Taxes raised!
predictedReaction?
Happy hour! Taxes raised!
E´=E?
Is my model congruent with the reaction?
12 incongruent12 congruent
12 incongruent12 congruent
12 congruent12 congruent
response response
Equal number of happy and aversive reactions for every partner,i.e. no classical conditioning !!! but operand contingencies differ !!!
How does the brain detect differences in operand contigencies ?
I Basic Study
How reliable is this person? (Whom can I trust?)
I Basic Study
pre training post training post fMRI
Training fMRI
n=21 Healthy Subjects
I Basic Study
How reliable is this person? (Whom can I trust?)
-40
-30
-20
-10
0
10
20
30
40
50
60
70
1 2 3
100% 50%
-
>0.001 >0.025
Perceived functionality
**
Identification of contingent partner
Diff
eren
ce in
trus
t rati
ngs
[mm
]
PreTraining
PostTraining
PostfMRI
Difference [mm]?
*
12
3
I Basic Study
unpredictable > predictable Partner
n=21 Healthy Subjects
Effect of contingencies of partners
p>0.001 uncorrected
100%50%
(neutral expression)Theory of Mind –network dmPFC, TPJ, ant. Insula/IFG
Schnell et al. in press
I Basic Study
Regulatory effect of interpersonal response prediction on affective reactions?
I Basic Study
Amygdala
unpredicted > predicted angry response
Predictions about affective responses modulate activation of limbic regions
Prediction effect: Angry response of unpredictable partners
Display p<0.001 uncorrected
50%
I Basic Study
Right Amygdala p<0.05 FWE coorected for ROI /AAL
Summary I:
i.) Update of interpersonal model- contingency associations in social interaction is represented in specific neural network and behaviour
ii.) Predictions about affective responses modulate activation of the amygdala
I Basic Study
Clinical Trial: CBASP vs EscitalopramPreliminary findings
II CBASP vs Escitalopram
Dual centre study
Bonn: Henrik Walter (Berlin), Dieter Schoepf (Bonn), Knut Schnell (Heidelberg)
Freiburg: Elisabeth Schramm, Ingo Zobel (Freiburg)
Hypotheses II (Clinical Trial CBASP vs Escitalopram) Update of predictive models of others is impaired in chronic depression
II CBASP vs Escitalopram
Comparison ofn=14 (11/2010: 18 ) CD Patients (Mean Age 40,2 years; SD 11,49; 11f) Acute treatment completed: 8 CBASP, 6 ADn=12 controls (Mean Age 38,4 years, SD 11,9, 7f)
II CBASP vs Escitalopram
Week 8 Week 28Baseline
acute continuation
CBASP
CM+Escitalopram
fMRI fMRI
100% 50%
-
Impaired perceived functionality in CD
Identification of contingent partner
Difference [mm]?1
23 Δ 2-1
Difference in trust ratings Pre-Post Training [mm]
?
II CBASP vs Escitalopram
-40
-30
-20
-10
0
10
20
30
40
50
60
70
1
HCCD patients
*
Before treatment: Impaired discrimination of contingent social partners in CD
100% 50%
-
Improvement of perceived functionality
Difference [mm]?
?
-40-30-20-10
010203040506070
1 2
CBASP
AD
HCt0 t1 (12 sessions, 8 weeks)
Difference in trust ratings Pre-Post Training [mm]
*
Identification of contingent partner
II CBASP vs Escitalopram
Amygdala
Predictions about affective responses modulate activation of amygdala
p<0.001 uncorrected
unpredicted > predicted angry response
Affective prediction effect: Angry response of unpredictable partner
II CBASP vs Escitalopram
BASIC STUDY
P<0.005 uncorrected
N=8 CBASP, n=6 AD
Interaction of time x treatment in regulatory prediction effect in right Amygdala: Increase of regulatory effect in CBASP group
II CBASP vs Escitalopram
unpredicted > predicted angry response
Affective prediction effectAngry response of unpredictable partner
MNI [18 0 -15]
Summary
Distinct intersubjective functions can be rendered by neuroimaging
Impaired intersubjective functions contribute to the emergence of disorders like schizophrenia
Intersubjective functions are promising targets to dismantle the mechanisms of psychotherapy
Thank you !
In contrast to affective contagion, empathy is bound to the individualawareness that a specific emotion was primarily initiated in the otherperson (Hein and Singer, 2008).
In contrast to the restrictive definition of empathy, mentalizing isdefined by Frith & Frith as “the process by which we make inferencesabout mental states” (Frith and Frith, 2006b) and does not only includethe inference about another persons’ motivational states and beliefsbut also the immediate recognition and the cognitive inference aboutother persons’ emotional states.
Modulation des Mentalisierungs-Netzerkes durch die Amygdalae mittels emotionaler Signale und kognitiven Fokus eine fMRT-Studie
Durch den affektiven
Zustand eines anderen
Verusrsacht
selbst einen Affekt haben
Affektive Isomorphie
kausale Beziehung der Affekte
Explizit Repräsentiert
Motiviert sein zu prosozialem
Verhalten
Prototypisches Beispiel
MimikrieLächeln weil jemand anderes lächelt
Emotionale AnsteckungSich amüsieren, weil jemand lacht
Persönliches Leidensich unentspannt fühlen, weil jemand leidet
Affektive (hot) EmpathieSich traurig fühlen, weil jemand traurig ist
Kognitive (cold) Empathie= Affektive Theory of Mind / Kognitive Empathie
Schließen, das jemand anderes glücklich ist
MitleidMitleid haben weil jemand deprimiert ist
SympathieEmpathische Betroffenheit
Mitleid haben und helfen wollen, weil jemand deprimiert ist
Table 1: Overview over different concepts related to empathy
92
Paradigma
7.5 sec 7.5 sec 7.5 sec
Antwort?
- = +
10
GeschichtenAntwort?
- = +
„Fühlt sich die Hauptperson schlechter, gleich oder besser als auf dem vorherigen Bild?“
93
Hypothesen
Kategorielle Effekte
• Emotionale Signale > keine emotionale Signale:
• TPJ erhöhte Aktivität; Erhöhte Aktivität im rechten posterioren STS→ Story, Kausalität und Intention verständlicherGallagher HL et al. (2003)
• Erhöhte Aktivität in Temporallappen-Polen→ Angemessenes Verhalten deutlicher erkennbarGallagher HL et al. (2003)
• Erhöhte Amygdala-Aktivität→ Emotionaler Zustand u.A. an Gesichtsausdruck erkennbarMorris JS et al. (1998)
• Weniger Aktivität im PFC → Aufgabe leichter
94
Hypothesen
Konnektivität
• Emotionale Signale > keine emotionale Signale:
• Verstärkte Konnektivität Amygdalae mit ToM-Arealen
Effekte auf das vegetative Nervensystem
• Veränderte Hautleitfähigkeit (SCR)→ Efferenzen der Amygdalae zum vegetativen Nervensystem
95
Methoden
Probanden• N=22 psychisch gesunde, rechtshändige Probanden (13 m) • 23,73 Jahre (SD=3,06).
Daten Aquirierung• 3-Tesla Siemens Trio• 334 whole brain scans (funktioneller Lokalisator: 235 whole brain
scans)• TR =2070, TE =30, slice thickness =3.5 mm, matrix =64 x 64
Datenanalyse• SPM5 mit Matlab 7.1 und Matlab 7.6• 2nd level: One Sample T- Tests• SEM; PPI
96
Ergebnisse• TomFeel > SelfNum zeigt typische ToM-Regionen
→ Funktioneller Lokalisator des ToM-Netzwerkes
p < 0,001 (uncorr.)
p < 0,05 (FWE)
97
ErgebnisseFace > NoFace
• Erhöhte Aktivität: FFA, Haxby JV et al. (2002)Temporallappen-Pol (rechts) außerdem pSTS (rechts)
p < 0,05 (FDR)
98
ErgebnisseNoFace > Face
• erhöhte Aktivität in frontalen Bereichen → Größere kognitive Leistung nötig
• Anteriores Cingulum (Empathie)Singer T et al. (2004)
p < 0,001 (uncorr.)
99
Ergebnisse
Face > NoFace; parametrisch moduliert
• Zusätzliche Aktivierung in rechter Amygdala
p < 0,001 (uncorr.)
100
Ergebnisse
NoFace > Face; parametrisch moduliert• Aktivierung in okzipitalen Bereichen
p < 0,05 (FDR)
101
Ergebnisse
Effektive Konnektivität (SEM)• Erstellen eines Pfadmodells mittels CoCoMac und berechnen des „best fitting” Modells
102
ErgebnisseEffektive Konnektivität (SEM)• Erstellen eines Pfadmodells mittels CoCoMac und berechnen des „best fitting” Modells
103
ErgebnisseEffektive Konnektivität (SEM)• Erstellen eines Pfadmodells mittels CoCoMac und berechnen des „best fitting” Modells• T-Test über die Gruppe, ob sich Verbindungen von 0 unterscheiden
PPI
105
Ergebnisse
PPI• Rechte Amygdala zeigt veränderte Konnektivität
mit rechtem orbitofrontalem Cortex und linkem BA 10 in Abhängigkeit der Condition
p < 0,001 (uncorr.); k = 8 Voxel
PPI
• Rechte Amygdala zeigt veränderte Konnektivität mit rechtem orbitofrontalem Cortex und linkem BA 10 in Abhängigkeit der Condition
106
Ergebnisse
p < 0,001 (uncorr.); k = 8 Voxel
107
ErgebnissePPI
• Rechte Amygdala zeigt veränderte Konnektivität mit rechtem orbitofrontalem Cortex und linkem BA 10 in Abhängigkeit der Condition
p < 0,001 (uncorr.); k = 8 Voxel
108
ErgebnissePPI
• Rechte Amygdala zeigt veränderte Konnektivität mit rechtem orbitofrontalem Cortex und linkem BA 10 in Abhängigkeit der Condition
p < 0,001 (uncorr.); k = 8 Voxel
109
ErgebnissePPI
• Linke Amygdala zeigt veränderte Konnektivität mit linkem BA 10 und linkem ACC in Abhängigkeit der Condition
p < 0,001 (uncorr.); k = 5 Voxel
110
ErgebnisseVergleich der Reaktionszeiten bei Face und NoFace• Signifikant längere Reaktionszeit bei NoFace als bei Face
(p = 3,9866 * 10-4)
Einfluss der Condition auf SCR• Kein signifikanter Unterschied in der Höhe der SCR in Bezug auf die Condition (p = 0,1294)
111
Vielen Dank für die Aufmerksamkeit
Fragen?
Anmerkungen?
CBASP
Being caused by an other’s affective
state1
Being in anaffective
state oneself
Affective isomorphy
Explicit repre-
sentation of causal
affective relations2
Being motivated
for prosocial behavior
Prototypical example
MimicrySmiling because someone else is smiling
Emotional Contagion
Feeling amused, because others are laughing
Personal distressFeeling uneasy, because someone suffers
Affective (hot) Empathy
Feeling sad, because someone else is sad
Cognitive (cold) Empathy= Affective Theory of Mind
Inferring that someone feels happy
CompassionFeeling pity, because someone is depressed
SympathyEmpathic concern
Feeling pity and wanting to help, because someone is depressed and wanting to help
Table 1: Overview over different concepts related to empathy
Soziale Kognition: Versuch einer Schematisierung