Die Präsentation wird geladen. Bitte warten

Die Präsentation wird geladen. Bitte warten

Neuroimaging and intersubjectivity in psychiatry Knut Schnell Dep. Of General Psychiatry Translational Psychiatric Therapy Research.

Ähnliche Präsentationen


Präsentation zum Thema: "Neuroimaging and intersubjectivity in psychiatry Knut Schnell Dep. Of General Psychiatry Translational Psychiatric Therapy Research."—  Präsentation transkript:

1 Neuroimaging and intersubjectivity in psychiatry Knut Schnell Dep. Of General Psychiatry Translational Psychiatric Therapy Research

2 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

3 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)

4 Mission

5 Proposed intersubjective functions in humans Imitation, Representation of Intentions Mirror Neurons Sharing Feelings Empathy Representing mental contentTheory of Mind Recognizing interpersonal effects Perceived Functionality Joint attention…

6 Mirrorneurons in primates Iacoboni & Dapretto NRN 2006 adapted from Rizzolatti et al Imitation Representation of Intentions

7 Mirror-Neurons in Humans Iacoboni & Dapretto NRN 2006 adapted from Iacoboni et al Intention, not movement or objects coded Iacoboni & Dapretto NRN 2006 adapted from Iacoboni et al. 2005

8 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

9 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

10 Imaging of ToM-functions in humans Cartoons (Gallagher at al., 2000) Stories (Fletcher et al., 1995) Comic strips (Brunet et al., 2000)

11 mPFC anterior medialPFC TPJ temporoparietal junction STS Sulcus temporalis superior Neuroanatomy of the ToM-network OFC Lateral Orbitofrontal Cortex

12 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

13 Hein & Singer define empathy as an affective state, caused by sharing of the emotions or sensory states of another person (Hein and Singer, 2008).

14 Empathy in mice?

15 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).

16 Empathy in Humans Shared activation for pain experience of the partner Singer et al Empathy= Shared Pain?

17 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.

18 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 Relation between Self-Reported Empathy and Motor Identification with Imagined Agents Marzoli et al., 2011

19 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

20 14 Zielteilnehmer (7 w, mean age 26.5) 1. Schilderung der 4 positivsten und 4 negativsten autobiographischen Episoden, Skripterstellung. 2. Lesen des Skriptes, Videodreh: Schilderung der in der biographischen Situation erlebten Affekte 3. Rating des Videos durch Zielteilnehmer selbst: Welche Affekte wurden während der Schilderung erlebt (9 Punkte Likert Skala) kontinuierlich einschätzen 21 Wahrnehmende Teilnehmer (11 w, mean age 19.1) 1. Im MRT-Scanner: 6 Videos (M: 2,15 s) betrachten und Gefühle der Zielpersonen kontinuierlich einschätzen (9 Punkte Likert Skala), Methode

21 Empathic Accuracy: Correlation between rated timecourse of affective states from filmed target participants and perceivers (viewers)

22 Accuracy is correlated with brain activity during video pressentation

23 Diskussion Empathische Genauigkeit: Nützliches Konzept zur Erforschung der Grundlagen und Störungen sozialer Kognition z.B. bei ASD, Erforschung therapeutischer Prozesse Parallele Aktivierung von Hirnregionen der Mentalisierung / Mental State Attribution und des Shared Representation/ Spiegelneuronensystems Aber… Keine Korrelation mit AI, ACC, or SII Aktivierung: fehlende somatoviscerale Reizkomponmenten ? Keine Korrelation mit TPJ – Aktivierung: Abhängigkeit vom Kontext Inhalt sozialer Kognitionen ? Aufgabe zu leicht?

24 Brunet-Gouet & Decety, 2006 Theory of Mind regions overlap with emotion processing regions

25 Is there an overlap between ToM and Empathy? Does the term term cognitive empathy (Preston and de Waal, 2002) represent a meaningful neurofunctional concept What are the functions of STS, TPJ, OFC and mPFC? mPFC anterior medialPFC TPJ temporoparietal junction STS Sulcus temporalis superior OFC Lateral Orbitofrontal Cortex

26 Methods Subjects N=21 healthy subjects (9 female), all right-handed Data acquisition 3-Tesla Siemens Trio 462 whole brain scans TR =2060, TE =30, 32 slices, slice thickness =3.5mm, matrix =64 x 64 Data analysis: SPM5 with Matlab 7.1 1st level: 12 regressors of interest, 6 regressors of no interest 2nd level: Flexible-factorial Anova with 4 conditions

27 Paradigm A Paradigm: Distinction of perspective and affective content No immediately contagious affective content Randomized stories/instructions 8.5 sec Demands difference? - = + difference? - = + Instruktion 32 stories Design 6.5 sec

28 Nur für Bild 2 und 3 relevant!

29

30 - = +

31

32 Design (questions / stories randomised) 1st PP3rd PP ( cognitive ) visuospatial Affective

33 Nur für Bild 2 und 3 relevant!

34

35 - = +

36

37 Nur für Bild 2 und 3 relevant!

38

39 - = +

40

41 Nur für Bild 2 und 3 relevant!

42

43 - = +

44

45 Main effect of affective content: Activation of anteriorer parts of ToM network Results

46 Main effect of 3rd Person Perspective Activation of posterior ToM Network, TPJ, FEF, Precuneus Results

47 Simple effects V isuospatial; A ffective 1. Person; 3. Person

48 Interaktion V isuospatial; A ffektiv 1. Person; 3. Person Results

49 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.

50 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).

51

52 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 = + 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

53 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 (rs ) associated with increased risk for schizophrenia during selective perspective taking Main Effect soziale Kognition

54 Experimental model of psychotherapy effects on intersubjective functions in (chronic) Depression: Perceived functionality

55 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 cant believe that it affects your mood if I tell you I was succesful in resolving the fight with my daughter ! Basic ideas

56 S Significant other / Traumatic interpersonal experience CBASP Modify cognitive schema Interpersonal Discrimination/ Perception of Functionality S O Patient Therapist Significant other S R C

57 We will improve the perception of interpersonal functionality! Hmm, perception of functionality … what am I supposed to do? The fundamental question: McCullough Brain

58 Bandura 1978 If I (O) do this (R), the other person (S) will do that (C) (with a probality of E %) Stimulus Organism Reaction Consequence Behavioral Model

59 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

60 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

61 Positiver? Happy hour! Taxes raised!

62

63 predicted Reaction? Happy hour! Taxes raised!

64

65 E´=E? Is my model congruent with the reaction? 12 incongruent 12 congruent 12 incongruent 12 congruent 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

66 How reliable is this person? (Whom can I trust?) I Basic Study

67 pre training post training post fMRI Training fMRI n=21 Healthy Subjects I Basic Study How reliable is this person? (Whom can I trust?)

68 100%50% - >0.001 >0.025 Perceived functionality ** Identification of contingent partner Difference in trust ratings [mm] Pre Training Post Training Post fMRI Difference [mm]? * I Basic Study

69 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

70 Regulatory effect of interpersonal response prediction on affective reactions? I Basic Study

71 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

72 p<0.001 uncorrected Prediction effect: Happy response of unpredictable partner unpredicted > predicted happy response 50% I Basic Study

73 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

74 Clinical Trial: CBASP vs Escitalopram Preliminary findings II CBASP vs Escitalopram

75 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

76 Comparison of n=14 (11/2010: 18 ) CD Patients (Mean Age 40,2 years; SD 11,49; 11f) Acute treatment completed: 8 CBASP, 6 AD n=12 controls (Mean Age 38,4 years, SD 11,9, 7f) II CBASP vs Escitalopram Week 8 Week 28 Baseline acute continuation CBASP CM+Escitalopram fMRI

77 100%50% - Impaired perceived functionality in CD Identification of contingent partner Difference [mm]? Δ 2-1 Difference in trust ratings Pre-Post Training [mm] ? II CBASP vs Escitalopram * Before treatment: Impaired discrimination of contingent social partners in CD

78 100%50% - Improvement of perceived functionality Difference [mm]? ? t0 t1 (12 sessions, 8 weeks) Difference in trust ratings Pre-Post Training [mm] * Identification of contingent partner II CBASP vs Escitalopram

79 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

80 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 effect Angry response of unpredictable partner MNI [ ]

81 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

82 Thank you !

83

84

85

86

87

88

89 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). In contrast to the restrictive definition of empathy, mentalizing is defined by Frith & Frith as the process by which we make inferences about mental states (Frith and Frith, 2006b) 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.

90 Modulation des Mentalisierungs-Netzerkes durch die Amygdalae mittels emotionaler Signale und kognitiven Fokus eine fMRT-Studie

91 Durch den affektiven Zustand eines anderen Verusrsacht selbst einen Affekt haben Affektive Isomorphie kausale Beziehung der Affekte Explizit Repr ä sentiert Motiviert sein zu prosozialem Verhalten Prototypisches Beispiel Mimikrie L ä cheln weil jemand anderes l ä chelt Emotionale Ansteckung Sich am ü sieren, weil jemand lacht Pers ö nliches Leiden sich unentspannt f ü hlen, weil jemand leidet Affektive (hot) Empathie Sich traurig f ü hlen, weil jemand traurig ist Kognitive (cold) Empathie = Affektive Theory of Mind / Kognitive Empathie Schlie ß en, das jemand anderes gl ü cklich ist Mitleid Mitleid haben weil jemand deprimiert ist Sympathie Empathische Betroffenheit Mitleid haben und helfen wollen, weil jemand deprimiert ist Table 1: Overview over different concepts related to empathy

92 92 Paradigma 7.5 sec Antwort? - = + 10 Geschichten Antwort? - = + Fühlt sich die Hauptperson schlechter, gleich oder besser als auf dem vorherigen Bild?

93 93 Hypothesen Kategorielle Effekte Emotionale Signale > keine emotionale Signale: TPJ erhöhte Aktivität; Erhöhte Aktivität im rechten posterioren STS Story, Kausalität und Intention verständlicher Gallagher HL et al. (2003) Erhöhte Aktivität in Temporallappen-Polen Angemessenes Verhalten deutlicher erkennbar Gallagher HL et al. (2003) Erhöhte Amygdala-Aktivität Emotionaler Zustand u.A. an Gesichtsausdruck erkennbar Morris JS et al. (1998) Weniger Aktivität im PFC Aufgabe leichter

94 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 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 96 Ergebnisse TomFeel > SelfNum zeigt typische ToM-Regionen Funktioneller Lokalisator des ToM-Netzwerkes p < 0,001 (uncorr.) p < 0,05 (FWE)

97 97 Ergebnisse Face > NoFace Erhöhte Aktivität: FFA, Haxby JV et al. (2002) Temporallappen-Pol (rechts) außerdem pSTS (rechts) p < 0,05 (FDR)

98 98 Ergebnisse NoFace > Face erhöhte Aktivität in frontalen Bereichen Größere kognitive Leistung nötig Anteriores Cingulum (Empathie) Singer T et al. (2004) p < 0,001 (uncorr.)

99 99 Ergebnisse Face > NoFace; parametrisch moduliert Zusätzliche Aktivierung in rechter Amygdala p < 0,001 (uncorr.)

100 100 Ergebnisse NoFace > Face; parametrisch moduliert Aktivierung in okzipitalen Bereichen p < 0,05 (FDR)

101 101 Ergebnisse Effektive Konnektivität (SEM) Erstellen eines Pfadmodells mittels CoCoMac und berechnen des best fitting Modells

102 102 Ergebnisse Effektive Konnektivität (SEM) Erstellen eines Pfadmodells mittels CoCoMac und berechnen des best fitting Modells

103 103 Ergebnisse Effektive Konnektivität (SEM) Erstellen eines Pfadmodells mittels CoCoMac und berechnen des best fitting Modells T-Test über die Gruppe, ob sich Verbindungen von 0 unterscheiden

104 PPI

105 105 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

106 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

107 107 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

108 108 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

109 109 Ergebnisse PPI Linke Amygdala zeigt veränderte Konnektivität mit linkem BA 10 und linkem ACC in Abhängigkeit der Condition p < 0,001 (uncorr.); k = 5 Voxel

110 110 Ergebnisse Vergleich der Reaktionszeiten bei Face und NoFace Signifikant längere Reaktionszeit bei NoFace als bei Face (p = 3,9866 * ) Einfluss der Condition auf SCR Kein signifikanter Unterschied in der Höhe der SCR in Bezug auf die Condition (p = 0,1294)

111 111 Vielen Dank für die Aufmerksamkeit Fragen? Anmerkungen?

112

113 CBASP

114

115 Being caused by an other s affective state 1 Being in an affective state oneself Affective isomorphy Explicit repre- sentation of causal affective relations 2 Being motivated for prosocial behavior Prototypical example Mimicry Smiling because someone else is smiling Emotional Contagion Feeling amused, because others are laughing Personal distress Feeling 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 Compassion Feeling pity, because someone is depressed Sympathy Empathic 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


Herunterladen ppt "Neuroimaging and intersubjectivity in psychiatry Knut Schnell Dep. Of General Psychiatry Translational Psychiatric Therapy Research."

Ähnliche Präsentationen


Google-Anzeigen