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How Neurosciences help us to understand some psychotherapeutic processes How Neurosciences help us to understand some psychotherapeutic processes Bernadette.

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Presentation on theme: "How Neurosciences help us to understand some psychotherapeutic processes How Neurosciences help us to understand some psychotherapeutic processes Bernadette."— Presentation transcript:

1 How Neurosciences help us to understand some psychotherapeutic processes How Neurosciences help us to understand some psychotherapeutic processes Bernadette Grosjean. MD. Harbor UCLA Psychodynamic Psychotherapy Seminar

2 We must recollect that all our provisional ideas in psychology will presumably one day be based on an organic substructure Sigmund Freud On Narcissism 1914.

3 In 1936 Rosenzweig wondered: Whether the factors alleged to be operating in a given therapy are identical with the factors that actually are operating Whether the factors alleged to be operating in a given therapy are identical with the factors that actually are operating Whether the factors that actually are operating in several different therapies may not have much more in common than have the factors alleged to be operating Whether the factors that actually are operating in several different therapies may not have much more in common than have the factors alleged to be operating Several Meta-analyses report no differences among different types of therapies, although all are superior to no treatment. Luborsky,L. 1975,1993,1999,2002; Smith & Glass 1977;Grissom 1996; Wampold et al 1997; Ahn and Wampold 2001; Prochaska and Norcross 2003.

4 Common factors Operation of implicit, non verbal factors Operation of implicit, non verbal factors Formal consistency of the therapeutic ideology as a basis for reintegration. Formal consistency of the therapeutic ideology as a basis for reintegration. Alternative formulation of psychological events Alternative formulation of psychological events Rosenzweig 1936.

5 Time travel From neuron to mirror neuron

6 PlatoAthenes ( B.C.) St Thomas Aquinas ( ) Saint Augustin ( ) SOUL IS DISTINCT FROM THE BODY SOUL IS DISTINCT FROM THE BODY Hippocrates ( B.C.) René Descartes ( )

7 Santiago Ramon Y Cajal The nervous system is made up of billions of separate nerve cells. The nervous system is made up of billions of separate nerve cells. Nerve cells are polarized, receiving information on their cell bodies and dendrites, and conducting information to distant locations through axons. Nerve cells are polarized, receiving information on their cell bodies and dendrites, and conducting information to distant locations through axons.

8 "... mental exercise facilitates a greater development of the protoplasmic apparatus and of the nervous collaterals in the part of the brain in use. In this way, pre-existing connections between groups of cells could be reinforced by multiplication of the terminal branches of protoplasmic appendices and nervous collaterals". "... mental exercise facilitates a greater development of the protoplasmic apparatus and of the nervous collaterals in the part of the brain in use. In this way, pre-existing connections between groups of cells could be reinforced by multiplication of the terminal branches of protoplasmic appendices and nervous collaterals". CAJAL. Royal Society. London 1894

9 Donald Hebb ( ) The Organization of Behavior Hebb was fascinated by the way people learned and the way they retained information. In 1949, he suggested that the nervous system was encoding information by strengthening activated neuronal connections. Cells that fire together wire together

10 The stimulation of certain neuronal fibers by high frequency waves creates a significant and measurable increase in the inter-synaptic strength, insofar as it increases the ability to initiate post-synaptic potentials. Terje Lomo Norway Timothy Bliss.London, Terje Lomo- Timothy Bliss Long Term Potentiation

11 Long-Term Potentiation LTP This phenomenon, which may persist for weeks, is labeled long term potentiation (LTP).

12 Eric Kandel Nobel Prize in In 1965 proposed that a form of post- synaptic potentiation may correspond to a simple form of learning.

13 how can you tell when a snail has learned something?

14 How can you tell when a snail has learned something?

15 The cells and their interconnections were always the same. What changed in the learning process were changes in synaptic strength. Kandel and his team located and mapped the neural circuit in the gill- withdrawal reflex.

16 Psychotherapy, like medication, is ultimately mediated by neuro- anatomical structures Successful psychotherapy is correlated with discrete brain changes Etkin, Kandel et al. 2005; Roffman et al

17 Brain

18 Human: genes around 35,000 Human: genes around 35,000 We share about 97% of our genes with chimpanzees. Our closest relative, the bonobo, has about 98.4 % of the same genes that we do. (just 500 genes #) We share about 97% of our genes with chimpanzees. Our closest relative, the bonobo, has about 98.4 % of the same genes that we do. (just 500 genes #) Human brains differ from those of other primates in three main areas- the frontal lobes, the hippocampus, and the cerebellum. Human brains differ from those of other primates in three main areas- the frontal lobes, the hippocampus, and the cerebellum.

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20 Those three highly developed brain structures allow humans to do all sorts of amazing things. Those three highly developed brain structures allow humans to do all sorts of amazing things. We can manipulate symbols and create realities in our heads that can stand quite apart from the external reality that all other animals share. We can manipulate symbols and create realities in our heads that can stand quite apart from the external reality that all other animals share.

21 The advanced processors that allow us to remember, imagine, plan, and create are still basically wired up to emotional systems that are not too different from those of our primate ancestors. The advanced processors that allow us to remember, imagine, plan, and create are still basically wired up to emotional systems that are not too different from those of our primate ancestors. We continue to be driven by the same instincts and emotions. It is as though we have a super- fast computer hooked up to a chimpanzee emotional system. We continue to be driven by the same instincts and emotions. It is as though we have a super- fast computer hooked up to a chimpanzee emotional system.

22 Hippocampus Puzzle Assembler. Facilitate the storage of spatial, non verbal and semantic or verbal memories that facilitated by language Facilitate the storage of spatial, non verbal and semantic or verbal memories that involve the encoding of experience into powerful symbolic representation facilitated by language Rich in NMDA receptors

23 Hippocampus / Dente Gyrus dentate gyrus neurogenesis The dentate gyrus is a site of active neurogenesis. I has been hypothesized that it ensure that new learned patterns do not interfere with the old ones and remain separable (Viamontes 2008)

24 AmygdalaEMOTIONAL BRAIN Key role in the emotions (fear, pleasure). Key role in the emotions (fear, pleasure). Key role in implicit, emotional memories: interprets the emotional significance of the experience. Key role in implicit, emotional memories: interprets the emotional significance of the experience. Rich in glucocorticoid and NMDA receptors

25 Vital to cognitive functions, such as reward anticipation, decision-making, empathy, and emotion. ACC is involved in the processing of the affective dimension of pain responsible for rendering new memories permanent. Anterior Cingulate CortexConflict monitoring NMDA receptor in the prefrontal cortex are critically involved in both LTP and contextual memory (Zhao et al. 2005).

26 Cerebellum Cerebellum There is increasing recognition that the cerebellum contributes to cognitive processing and emotional control in addition to its role in motor coordination There is increasing recognition that the cerebellum contributes to cognitive processing and emotional control in addition to its role in motor coordination

27 The cerebellum, along with our frontal lobes and hippocampus, is much larger in humans than our physical stature would predict. In fact this mysterious structure contains over half of the brain's neurons. The cerebellum, along with our frontal lobes and hippocampus, is much larger in humans than our physical stature would predict. In fact this mysterious structure contains over half of the brain's neurons. The commonly recognized function of the cerebellum is the coordination and balance of muscle movements. Our talents in that area certainly would not explain the need for such enlarged cerebellums. The commonly recognized function of the cerebellum is the coordination and balance of muscle movements. Our talents in that area certainly would not explain the need for such enlarged cerebellums.

28 Ventral Pre-motor Cortex...And MIRROR NEURONS Illustration © Marco Iacoboni

29 Mirror Neurons A class of neurons that discharge not only when a monkey executes goal-related hand action, but also when observing other individuals executing similar actions. Gallese, Rizzolatti et al

30 Mirror Neurons EmpathyEinfühlung To empathize, we need to invoke the representation of the actions associated with the emotions we are witnessing. To empathize, we need to invoke the representation of the actions associated with the emotions we are witnessing. In human, fMRI study showed that the same brain region are activated while observing an emotion or during the imitation of the emotional face expression In human, fMRI study showed that the same brain region are activated while observing an emotion or during the imitation of the emotional face expression Neural mechanisms of empathy in human: a relay from neural systems for imitation in limbic area Carr, Iacoboni et al 2003.

31 NEUROPLASTICITY 100 billion neurons Each develops between 1,000 to 10,000 connections with other neurons

32 Brain growth spurt in humans between the last 3 months of pregnancy and extends into the first 3 years of life. Brain growth spurt in humans between the last 3 months of pregnancy and extends into the first 3 years of life. Around 18 month dente gyrus (hippocampus) starts to create episodic memory. Around 18 month dente gyrus (hippocampus) starts to create episodic memory. Around 4 y/o starts developing autobiographic memory. Around 4 y/o starts developing autobiographic memory. Major Pruning end around the end of puberty. Major Pruning end around the end of puberty. Adult brain remains plastic during the entire life. Adult brain remains plastic during the entire life. Timeline…

33 NEUROPLASTICITY Development shapes the brain by altering the strength of synaptic connections within the brain. Development shapes the brain by altering the strength of synaptic connections within the brain. New synapses can be formed in response to experience. New synapses can be formed in response to experience. Genetic information, toxic substance, and stressful or absent experience can lead to elimination of synapses. Genetic information, toxic substance, and stressful or absent experience can lead to elimination of synapses.

34 N-methyl-D-aspartate subtype glutamate receptors NMDARs

35 Glutamate is recognized as a neurotransmitter in 1972 (Watkins). Glutamate is recognized as a neurotransmitter in 1972 (Watkins). Primary excitatory neurotransmitter in the mammalian brain (60%). Primary excitatory neurotransmitter in the mammalian brain (60%). Receptors for Glutamate are divided into NMDA and non NMDAr (AMPA, Kainate). Receptors for Glutamate are divided into NMDA and non NMDAr (AMPA, Kainate). Glutamate

36 NMDA-receptor Hippocampus, forebrain, amygdala, caudate, putamen and thalamus (rodents).

37 NMDAR, can detect the coincidence of 2 events, so called associativity.

38 LTP is dependent on the presence NMDA receptors (NMDAR) (Collingridge & al 1983). LTP is dependent on the presence NMDA receptors (NMDAR) (Collingridge & al 1983). Glutamate and NMDAR are involved in many CNS mechanisms of plasticity including those contributing to learning and memory. Glutamate and NMDAR are involved in many CNS mechanisms of plasticity including those contributing to learning and memory. The period when NMDAR function is critical for neuronal survival in rats encompasses a period that in humans extends form the third trimester of pregnancy to several years after birth. The period when NMDAR function is critical for neuronal survival in rats encompasses a period that in humans extends form the third trimester of pregnancy to several years after birth. Balâazs et al 2006

39 NMDA Antagonist Impair/block memory Impair/block memory Impair/block learning processes Impair/block learning processes Produce selective loss of conscious function such as dissociation, derealized and depersonalized states. Produce selective loss of conscious function such as dissociation, derealized and depersonalized states. Disturb the cognitive-evaluative pain component Disturb the cognitive-evaluative pain component Modulate sensitivity to pain e.g., ketamine can prevent the experience of physical pain Modulate sensitivity to pain e.g., ketamine can prevent the experience of physical pain

40 Environment – NMDA neurotransmission

41 Stress... Stress... Continuation of, or re-exposure to, stress results in unregulated excitation of glutamate neurons (Farb et al 1992), and a growing body of data have implicated glutamatergic neurotransmission in stress- induced hippocampal atrophy and death (Mc Ewen 1999).

42 Early maternal separation appeared to exert a dramatic suppressive effect on synaptic overproduction in the early development of hippocampus. Early maternal separation appeared to exert a dramatic suppressive effect on synaptic overproduction in the early development of hippocampus. De Bellis et al Neonatal isolation impairs hippocampal-dependent context conditioned fear in adult rats. Neonatal isolation impairs hippocampal-dependent context conditioned fear in adult rats. Kosten et al 2007 Neglect... Neglect...

43 It is impossible to cancel some memories related to fear once those have been written at the amygdala level (rodents). Ledoux 1996 Neocortex is indispensable for the extinction of the reflex associated to fear once it has been created through conditioning. Animal studies show that important forms of learning in both the conditioning and extinction of fear are dependent upon proper function of NMDA neurotransmission in the amygdala (Miserendino et al. 1990; Rodriguez et al. 2001; Pietersen et al. 2006). Fear... Fear...

44 Recent research on changing fears has examined targeting reconsolidation. (2010) Recent research on changing fears has examined targeting reconsolidation. (2010) During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Changing fear…. ive/memory/index.html ive/memory/index.html ive/memory/index.html

45 Through a non-invasive technique to target the reconsolidation of fear memories in humans, Schiller et al provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. Through a non-invasive technique to target the reconsolidation of fear memories in humans, Schiller et al provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. Changing fear…. ive/memory/index.html ive/memory/index.html ive/memory/index.html

46 As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear. Schiller D, Monfils M, Raio CM, Johnson D, LeDoux JE, Phelps EA (2010) Blocking the return of fear in humans using reconsolidation update mechanisms. Nature 463: Schiller D, Monfils M, Raio CM, Johnson D, LeDoux JE, Phelps EA (2010) Blocking the return of fear in humans using reconsolidation update mechanisms. Nature 463: Changing fear….

47 About the good enough environment... Reduced maternal care effect on cognitive function can be reversed with peripubertal environmental enrichment. Bredy et al 2003, Reduced maternal care effect on cognitive function can be reversed with peripubertal environmental enrichment. Bredy et al 2003, 2004.

48 In rodents, in comparison with animals reared by low licking grooming mothers, the offspring of good (high licking) mothers showed: - increased hippocampal NMDA subunit mRNA expression, - enhanced synaptogenesis and improved hippocampal-dependent spatial learning. Bredy et al 2004 Nature AND Nurture

49 Nurse-visited children born to mothers with low psychological resources compared with control- group counterparts had : -at 6 months of age were less likely to exhibit emotional vulnerability in response to fear stimuli -at 6 months of age were less likely to exhibit emotional vulnerability in response to fear stimuli -at 9y/o have better grade-point averages and achievement test scores in math and reading in grades 1 through 3 -as a trend, were less likely to die from birth through age 9, an effect accounted for by deaths that were attributable to potentially preventable causes. Home Visiting by Paraprofessionals and by Nurses: a Randomized, controlled Trial. Olds et al; Pediatrics 2002,2004,2007, Human Studies

50 Long-term effects of prenatal and infancy nurse home visitation on the life course of youths: 19-year follow-up of a randomized trial.Eckenrode J, Campa M et al. Arch Pediatr Adolesc Med Long-term effects of prenatal and infancy nurse home visitation on the life course of youths: 19-year follow-up of a randomized trial.Eckenrode J, Campa M et al. Arch Pediatr Adolesc Med Long-term effects of prenatal and infancy nurse home visitation on the life course of youths: 19-year follow-up of a randomized trial. Long-term effects of prenatal and infancy nurse home visitation on the life course of youths: 19-year follow-up of a randomized trial.

51 MAIN POINTS NMDA neurotransmission: influences and is influenced by experience. has a clear impact on cognition (specifically emotion, affect, motivation, appraisal and evaluation of environmental stimuli). Neuronal damage mediated by NMDA neurotransmission may vary depending on the timing and the intensity, duration and type of stress. Appropriate NMDA stimulation may enhance learning abilities

52 …so how does neuroscience apply to psychotherapy work?

53 Brain circuitry is the final common pathway for the ever-expanding set of methods that can be used to alleviate psychological distress. One of them, psychotherapy, can be describe as an interpersonal process designed to bring about modifications of feelings, cognitions, attitudes and behavior which have proved troublesome. Strupp Background…

54 Neuronal plasticity is affected by environment not only at the initial establishment of neuronal circuitries of a developing brain, but during our entire life through memory retrieval, (re)- consolidation and rewiring connections. Background…

55 This potential of neuroplasticity has considerable implications when it comes to rehabilitation processes such as psychotherapy. Background…

56 During psychotherapy the attachment quality of the therapeutic relationship is critical. Experimental evidence suggests that secure attachment, is associated with reduction in amygdala firing (lessening anxiety) and increases in nucleus accumbens activity (possibly related to enhanced reward representations). Bartels and Zeki 2000,2004.

57 Within the secure attachment achieved through basic psychotherapeutic engagement The new learning is verbal (symbolic) and non verbal (emotional). There is activation of circuits involving explicit and implicit memory & (past) learning (priming, reflex). Mirror Neurons maybe crucial player in -our ability for empathy -our emotional learning and mentalization processes

58 In a secure, coherent therapeutic context: Reactivated schemes are given new implicit (mostly emotional) and explicit (mostly semantic) valences and a new recording of new associations (circuits activation) may take place in a new context. Experiences turns on the genetic machinery and through the synthesis of new proteins, change and create new brain internal connections.

59 Common factors ? Common factors ? Rosenzweig Operation of implicit, non verbal factors? Operation of implicit, non verbal factors? Formal consistency of the therapeutic ideology as a basis for reintegration? Formal consistency of the therapeutic ideology as a basis for reintegration? Alternative formulation of psychological events Alternative formulation of psychological events Neuroplasticity, quality of attachment, mirror neurons qualities, ability to teach new emotional and cognitive (symbolic learning)...

60 From the perspective of neuroscience, psychotherapy can be understood as a specific kind of enriched environment designed to enhance the growth of neurons and the integration of neural networks From the perspective of neuroscience, psychotherapy can be understood as a specific kind of enriched environment designed to enhance the growth of neurons and the integration of neural networks Cozolino, 2010

61 1.Establishment of a safe and trusting relationship 2.Gaining new information and experiences across the domains of cognition, emotion, sensation, behaviour 3.Simultaneous or alternating activation of neural networks, that are inadequately integrated 4.Moderate levels of stress or emotional arousal alternating with periods of calm and safety. 5.Integration of conceptual knowledge with emotional and bodily experience.

62 When brains talk…. In contrast to the prevailing privileged status of verbal, conscious cognition, it is more and more evident that emotional communications between therapist and patient lie at the psychobiological core of the therapeutic alliance In contrast to the prevailing privileged status of verbal, conscious cognition, it is more and more evident that emotional communications between therapist and patient lie at the psychobiological core of the therapeutic alliance (Schore, 1994, 2012). Trust in doctors is very much interpersonal trust

63 A fragile ego left alone remains fragile. Medication or superficial support alone is not a substitute for the feeling that one is understood by another human being. Anonymous Thank you ! atry.com


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