How Neurosciences help us to How Neurosciences help us to understand some psychotherapeutic understand some psychotherapeutic

processes processes 

Bernadette Grosjean. MD.Bernadette Grosjean. MD.Harbor UCLA Harbor UCLA

Psychodynamic Psychotherapy Psychodynamic Psychotherapy Seminar 2012-2013Seminar 2012-2013

“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.

In 1936 Rosenzweig wondered:In 1936 Rosenzweig wondered:

Whether the factors Whether the factors alleged to be operatingalleged to be operating in a given therapy are identical with the in a given therapy are identical with the factors factors that actually arethat actually are operating operating

Whether the Whether the factors that actually are factors that actually are operatingoperating in several different therapies in several different therapies may may not have much more in commonnot have much more in common than have than have the factors alleged to be operatingthe factors alleged to be operating

Several Meta-analyses report no differences among Several Meta-analyses report no differences among different types of therapies, different types of therapies, although all are superior to although all are superior to no treatment.no treatment.Luborsky,L. 1975,1993,1999,2002; Smith & Glass 1977;Grissom 1996; Luborsky,L. 1975,1993,1999,2002; Smith & Glass 1977;Grissom 1996; Wampold et al 1997; Ahn and Wampold 2001; Prochaska and Norcross 2003.Wampold et al 1997; Ahn and Wampold 2001; Prochaska and Norcross 2003.

Common factorsCommon factors

Operation of Operation of implicitimplicit, non verbal, non verbal factors factors

Formal Formal consistency consistency of the therapeutic of the therapeutic ideology as a basis for reintegration.ideology as a basis for reintegration.

Alternative formulationAlternative formulation of of psychological eventspsychological events

Rosenzweig 1936.

Time travelTime travelFrom neuron to mirror neuronFrom neuron to mirror neuron

PlatoPlato

Athenes Athenes

(427-347 B.C.)(427-347 B.C.)

                  

St Thomas Aquinas

(1225-1274)

Saint Augustin ( 354 -430)

““SOUL IS DISTINCT FROM SOUL IS DISTINCT FROM THE BODY”THE BODY”

Hippocrates (460-377 B.C.)

René Descartes

(1596-1650)

                                               

                                                                

                                                                         

                                       

Santiago Ramon Y CajalSantiago Ramon Y Cajal1852-19341852-1934

““The nervous system is made The nervous system is made up of billions of separate nerve up of billions of separate nerve cells”cells”..

Nerve cells are polarized, Nerve cells are polarized, receiving information on their cell receiving information on their cell bodies and dendrites, and conducting bodies and dendrites, and conducting information to distant locations through information to distant locations through axons.axons.

"... mental exercise facilitates a greater development of the "... mental exercise facilitates a greater development of the protoplasmic apparatus and of the nervous collaterals in the protoplasmic apparatus and of the nervous collaterals in the part of the brain in use. In this way, pre-existing connections part of the brain in use. In this way, pre-existing connections between groups of cells could be reinforced by multiplication between groups of cells could be reinforced by multiplication

of the terminal branches of protoplasmic appendices and of the terminal branches of protoplasmic appendices and nervous collaterals". nervous collaterals".

CAJAL. Royal Society. London CAJAL. Royal Society. London 1894 1894

Donald Hebb Donald Hebb (1904-1985)(1904-1985)

The Organization of The Organization of Behavior Behavior

Hebb was fascinated by the way people Hebb was fascinated by the way people learned and the way they retained learned and the way they retained information. information.

In In 19491949, he suggested that the nervous , he suggested that the nervous system was encoding information by system was encoding information by strengthening strengthening activated neuronal activated neuronal connections.connections.

“ Cells that fire together wire together”

“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 1966. Timothy Bliss.London, 1973.

Terje Lomo- Timothy BlissLong Term Potentiation

Long-Term Potentiation

LTP

This phenomenon, which may persist for weeks, is

labeled long term potentiation

(LTP).”

Eric KandelEric Kandel

Nobel Prize in 2000.

In In 19651965 proposed that a form of proposed that a form of post-post-synaptic potentiation may synaptic potentiation may correspond to a simple form of correspond to a simple form of learning. learning.

how can you tell when a snail has learned something?

How can you tell when a snail has learned something?

The cells and their interconnections were always The cells and their interconnections were always the same. 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.

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. 2005.

BrainBrain

Human: genes around 35,000 Human: genes around 35,000 We share about 97% of our genes with We share about 97% of our genes with

chimpanzees. Our closest relative, the chimpanzees. Our closest relative, the bonobo, has about 98.4 % of the same bonobo, has about 98.4 % of the same genes that we do. (just 500 genes #)genes that we do. (just 500 genes #)

Human brains differ from those of other Human brains differ from those of other primates in three main areas- primates in three main areas- the frontal the frontal lobes, the hippocampus, and the cerebellum. lobes, the hippocampus, and the cerebellum.

Those three highly developed brain Those three highly developed brain structures allow humans to do all sorts of structures allow humans to do all sorts of amazing things. amazing things.

We can manipulate symbols and create We can manipulate symbols and create realities in our heads that can stand quite realities in our heads that can stand quite apart from the external reality that all other apart from the external reality that all other animals share.animals share.

The advanced processors that allow us to remember, The advanced processors that allow us to remember, imagine, plan, and create are still basically wired up to imagine, plan, and create are still basically wired up to emotional systems that are not too different from those emotional systems that are not too different from those

of our primate ancestors. of our primate ancestors.

We continue to be driven by the same instincts We continue to be driven by the same instincts and emotions. It is as though we have a super-and emotions. It is as though we have a super-

fast computer hooked up to a chimpanzee fast computer hooked up to a chimpanzee emotional system.emotional system.

HippocampusHippocampus“Puzzle Assembler”.“Puzzle Assembler”.

Facilitate the storage of Facilitate the storage of spatial, non verbal and spatial, non verbal and

semantic or verbal semantic or verbal memories that memories that involve

the encoding of experience into

powerful symbolic representation

facilitated by languagefacilitated by language

Rich in NMDA receptors

Hippocampus / Dente GyrusHippocampus / Dente Gyrus

The dentate gyrusdentate gyrus is a site of active neurogenesis neurogenesis .

I has been hypothesized that it ensure that new learned patterns do not interfere with the old ones and remain separable (Viamontes 2008)

AmygdalaAmygdala““EMOTIONAL BRAIN”EMOTIONAL BRAIN”

Key role in Key role in the emotions (fear, pleasure).the emotions (fear, pleasure). Key role in Key role in implicit, emotional memoriesimplicit, emotional memories:: interprets the emotional interprets the emotional

significance of the experience.significance of the experience.

Rich in glucocorticoid and NMDA receptors

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 CortexAnterior Cingulate Cortex““Conflict monitoring”Conflict monitoring”

NMDA receptor in the NMDA receptor in the prefrontal cortex are critically prefrontal cortex are critically involved in both LTP and involved in both LTP and contextual memory contextual memory (Zhao et al. (Zhao et al. 2005).2005).

CerebellumCerebellum

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

The cerebellum, along with our frontal lobes and The cerebellum, along with our frontal lobes and hippocampus, is much larger in humans than our hippocampus, is much larger in humans than our physical stature would predict. In fact this mysterious physical stature would predict. In fact this mysterious structure contains over half of the brain's neurons.structure contains over half of the brain's neurons.

The commonly recognized function of the cerebellum is The commonly recognized function of the cerebellum is the coordination and balance of muscle movements. Our the coordination and balance of muscle movements. Our talents in that area certainly would not explain the need talents in that area certainly would not explain the need for such enlarged cerebellums.for such enlarged cerebellums.

Ventral Pre-motor CortexVentral Pre-motor Cortex

...And MIRROR NEURONS                            Illustration © Marco Iacoboni

Mirror NeuronsMirror Neurons

A class of A class of neuronsneurons that discharge not only that discharge not only when a when a monkey executesmonkey executes goal-related hand goal-related hand action, but also action, but also when observingwhen observing other other individuals individuals executing similarexecuting similar actions. actions.

Gallese, Rizzolatti et al. Gallese, Rizzolatti et al. 1996.1996.

Mirror NeuronsMirror Neurons Empathy Empathy “Einfühlung”“Einfühlung”

To empathize, we need to invoke the To empathize, we need to invoke the representation of the actionsrepresentation of the actions associated associated with the emotions we are witnessingwith the emotions we are witnessing..

In human, fMRI study showed that the In human, fMRI study showed that the same brain region are activatedsame brain region are activated while while observingobserving an emotion or during the an emotion or during the imitationimitation of the emotional face expression of the emotional face expression

““Neural mechanisms of empathy in human: a relay from neural Neural mechanisms of empathy in human: a relay from neural systems for imitation in limbic area” Carr, Iacoboni et al 2003. systems for imitation in limbic area” Carr, Iacoboni et al 2003.

NEUROPLASTICITY

• 100 billion neurons

• Each develops between 1,000 to 10,000 connections with other neurons

Brain growth spurtBrain growth spurt in humans between the in humans between the last last 3 months of pregnancy3 months of pregnancy and extends and extends into the into the first 3 years of life. first 3 years of life.

Around 18 month Around 18 month dente gyrusdente gyrus (hippocampus) (hippocampus) starts to “create” episodic memory.starts to “create” episodic memory.

Around Around 4 y/o starts4 y/o starts developing developing autobiographic autobiographic memory.memory.

Major Pruning end around the end of puberty.Major Pruning end around the end of puberty. Adult brain remains plastic during the entire Adult brain remains plastic during the entire

life.life.

Timeline…

NEUROPLASTICITYNEUROPLASTICITY

Development shapes the brain by Development shapes the brain by altering the strength of synaptic altering the strength of synaptic connections within the brain.connections within the brain.

New synapses can be formed in response New synapses can be formed in response to experience.to experience.

Genetic information, toxic substance, and Genetic information, toxic substance, and stressful or absent experience can lead stressful or absent experience can lead to elimination of synapses.to elimination of synapses.

NN-methyl-D-aspartate -methyl-D-aspartate subtype glutamate subtype glutamate

receptorsreceptors

NMDARsNMDARs

Glutamate is recognized as a Glutamate is recognized as a neurotransmitter in 1972 (Watkins).neurotransmitter in 1972 (Watkins).

Primary excitatory neurotransmitter in the Primary excitatory neurotransmitter in the mammalian brain (60%). mammalian brain (60%).

Receptors for Glutamate are divided into Receptors for Glutamate are divided into NMDA and non NMDAr (AMPA, Kainate).NMDA and non NMDAr (AMPA, Kainate).

Glutamate

NMDA-receptor

Hippocampus, forebrain, amygdala, caudate, putamen and thalamus (rodents).Hippocampus, forebrain, amygdala, caudate, putamen and thalamus (rodents).

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

LTP is dependentLTP is dependent on the presence on the presence NMDA NMDA receptorsreceptors (NMDAR) (Collingridge(NMDAR) (Collingridge & al& al 1983 1983). ).

Glutamate and NMDAR are involved in many CNS Glutamate and NMDAR are involved in many CNS mechanisms of plasticity including those contributing mechanisms of plasticity including those contributing to to learning and memory.learning and memory.

The period when NMDAR function isThe period when NMDAR function is critical critical for for neuronal survivalneuronal survival in rats encompasses a period that in rats encompasses a period that in humans extends form the in humans extends form the third trimester of third trimester of pregnancy to several years after birthpregnancy to several years after birth. . Balâazs et al 2006

NMDA AntagonistNMDA Antagonist

Impair/block memory Impair/block memory Impair/block learning processes Impair/block learning processes

Produce selective loss of conscious function such Produce selective loss of conscious function such as dissociation, derealized and depersonalized as dissociation, derealized and depersonalized states.states.

Disturb the cognitive-evaluative pain componentDisturb the cognitive-evaluative pain component Modulate sensitivity to pain e.g., ketamine can Modulate sensitivity to pain e.g., ketamine can

prevent the experience of physical painprevent the experience of physical pain

Environment – Environment – NMDA neurotransmission NMDA neurotransmission

Stress...Stress...

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

Early maternal separation Early maternal separation appeared to exert a dramatic appeared to exert a dramatic suppressive effectsuppressive effect on synaptic on synaptic overproduction in the overproduction in the early early development of development of hippocampus.hippocampus.De Bellis et al.2001.De Bellis et al.2001.

Neonatal isolation Neonatal isolation impairs impairs hippocampal-dependent context hippocampal-dependent context conditioned fear in adultconditioned fear in adult rats. rats. Kosten et al 2007Kosten et al 2007

Neglect...Neglect...

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...

Recent research on changing fears has examined Recent research on changing fears has examined targeting reconsolidation. (2010)targeting reconsolidation. (2010)

During reconsolidation, stored information is rendered During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological labile after being retrieved. Pharmacological manipulations at this stage result in an inability to manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that retrieve the memories at later times, suggesting that they are erased or persistently inhibited. they are erased or persistently inhibited. Unfortunately, the use of these pharmacological Unfortunately, the use of these pharmacological manipulations in humans can be problematic.manipulations in humans can be problematic.

Changing fear….Changing fear…. http://www.nature.com/nature/videoarchive/memory/index.html

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

Changing fear….Changing fear…. http://www.nature.com/nature/videoarchive/memory/index.html

As a consequence, fear responses are no longer expressed, As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to an effect that lasted at least a year and was selective only to reactivated memories without affecting others. reactivated memories without affecting others.

These findings demonstrate the adaptive role of These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear.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 Schiller D, Monfils M, Raio CM, Johnson D, LeDoux JE, Phelps EA (2010) Blocking the return of fear in humans using reconsolidation update mechanisms. of fear in humans using reconsolidation update mechanisms. Nature Nature 463:49-53 .463:49-53 .

Changing fear….Changing fear….

About the good enough About the good enough environment...environment...

Reduced maternal care effect on Reduced maternal care effect on cognitive function cognitive function can be reversedcan be reversed with with peripubertal environmental peripubertal environmental enrichmentenrichment. . Bredy et al 2003, 2004.Bredy et al 2003, 2004.

In rodents, iIn rodents, in comparison with animals reared n comparison with animals reared by low licking ⁄ grooming mothers, by low licking ⁄ grooming mothers, the offspring the offspring of of “good” (high licking)“good” (high licking) mothers showed: mothers showed:

- - increased hippocampal NMDA subunit mRNA increased hippocampal NMDA subunit mRNA expression,expression,

- - enhanced synaptogenesisenhanced synaptogenesis and improved and improved hippocampal-dependent spatial learning. hippocampal-dependent spatial learning.

Bredy et al 2004Bredy et al 2004

Nature AND Nature AND NurtureNurture

Nurse-visited children born to mothers with low Nurse-visited children born to mothers with low psychological resourcespsychological resources compared with control- compared with control-group counterparts had :group counterparts had : --at 6 monthsat 6 months of age were of age were less less likely to exhibit likely to exhibit emotional vulnerability in response to fearemotional vulnerability in response to fear stimuli stimuli-at -at 9y/o9y/o have have better grade-point averagesbetter grade-point averages and and achievement test scores in math and reading in achievement test scores in math and reading in grades 1 through 3grades 1 through 3--as a trend, as a trend, were less likely to diewere less likely to die from birth from birth through age 9, an effect accounted for by deaths through age 9, an effect accounted for by deaths that were attributable to potentially preventable that were attributable to potentially preventable causes.causes.

Home Visiting by Paraprofessionals and by Nurses: a Randomized, Home Visiting by Paraprofessionals and by Nurses: a Randomized, controlled Trialcontrolled Trial. Olds et al; Pediatrics 2002,2004,2007, 2010. . Olds et al; Pediatrics 2002,2004,2007, 2010.

Human StudiesHuman Studies

www.nursefamilypartnership.org

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. 2010 Eckenrode J, Campa M et al. Arch Pediatr Adolesc Med. 2010

MAIN POINTSMAIN 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 Neuronal damage mediated by NMDA neurotransmission may vary depending on the may vary depending on the timingtiming and the and the intensityintensity, , durationduration and type of stress. and type of stress.

Appropriate Appropriate NMDA NMDA stimulation stimulation maymay enhance enhance learning learning abilitiesabilities

……so how does so how does neuroscience apply to neuroscience apply to psychotherapy work?psychotherapy work?

Brain circuitry is the Brain circuitry is the final common pathway for the final common pathway for the ever-expanding set of methodsever-expanding set of methods that can be used that can be used to alleviate psychological distress. to alleviate psychological distress.

One of them, One of them, psychotherapy,psychotherapy, can be describe as can be describe as an an interpersonal process designed to bring interpersonal process designed to bring about modifications of feelings, cognitions, about modifications of feelings, cognitions, attitudes and behaviorattitudes and behavior which have proved which have proved troublesome.” troublesome.” Strupp 1978.Strupp 1978.

Background…Background…

Neuronal plasticityNeuronal plasticity is is affected by affected by environmentenvironment not only at the not only at the initial initial

establishment of neuronal circuitries of a establishment of neuronal circuitries of a developing brain, but developing brain, but during our entire lifeduring our entire life

through memory retrieval, (re)- through memory retrieval, (re)- consolidation and rewiring connections.consolidation and rewiring connections.

Background…Background…

This potential of This potential of neuroplasticityneuroplasticity has has

considerable implications considerable implications when it comes to when it comes to

rehabilitation processes rehabilitation processes such as such as psychotherapy.psychotherapy.

Background…Background…

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.

Within the secure attachment achieved through basic psychotherapeutic

engagement

The new learning is verbal (symbolic) and non verbal The new learning is verbal (symbolic) and non verbal (emotional).(emotional).

There is activation of circuits involving explicit and implicit There is activation of circuits involving explicit and implicit memory & (past) learning (priming, reflex).memory & (past) learning (priming, reflex).

Mirror Neurons maybe crucial player inMirror Neurons maybe crucial player in-our ability for empathy-our ability for empathy-our emotional learning and -our emotional learning and

mentalization processesmentalization processes

In a secure, coherent therapeutic In a secure, coherent therapeutic context:context:

Reactivated schemes are given new implicit (mostly Reactivated schemes are given new implicit (mostly emotional) and explicit (mostly semantic) valences emotional) and explicit (mostly semantic) valences and a and a new recording of new associationsnew recording of new associations (circuits (circuits

activation) may take place in a new context.activation) may take place in a new context.

Experiences Experiences turns on the genetic machineryturns on the genetic machinery and through the and through the synthesis of new proteins, change and create new brain synthesis of new proteins, change and create new brain

internal connections.internal connections.

Common factors ?Common factors ?Rosenzweig 1936.

Operation of Operation of implicitimplicit, non verbal, non verbal factors? factors?

Formal Formal consistency consistency of the therapeutic of the therapeutic ideology as a basis for reintegration?ideology as a basis for reintegration?

Alternative formulationAlternative formulation of psychological of psychological eventsevents

Neuroplasticity, quality of attachment, mirror neurons Neuroplasticity, quality of attachment, mirror neurons qualities, ability to “teach” new emotional and cognitive qualities, ability to “teach” new emotional and cognitive (symbolic learning)...(symbolic learning)...

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

Cozolino, 2010Cozolino, 2010

1.1. Establishment of a safe and trusting relationshipEstablishment of a safe and trusting relationship2.2. Gaining new information and experiences across Gaining new information and experiences across

the domains of cognition, emotion, sensation, the domains of cognition, emotion, sensation, behaviourbehaviour

3.3. Simultaneous or alternating activation of neural Simultaneous or alternating activation of neural networks, that are inadequately integratednetworks, that are inadequately integrated

4.4. Moderate levels of stress or emotional arousal Moderate levels of stress or emotional arousal alternating with periods of calm and safety.alternating with periods of calm and safety.

5.5. Integration of conceptual knowledge with Integration of conceptual knowledge with emotional and bodily experience. emotional and bodily experience.

When brains talk….When brains talk….

In contrast to the prevailing privileged In contrast to the prevailing privileged status of verbal, conscious cognition, it is status of verbal, conscious cognition, it is more and more evident that more and more evident that emotional emotional communicationscommunications between therapist between therapist and patient and patient lie at the psychobiological lie at the psychobiological core of the therapeutic alliancecore of the therapeutic alliance

(Schore, 1994, 2012).

“Trust in doctors is very much interpersonal trust”

““A fragile ego left alone remains A fragile ego left alone remains fragile. Medication or superficial fragile. Medication or superficial

support alone is not a substitute for support alone is not a substitute for the feeling that one is understood by the feeling that one is understood by

another human being.”another human being.”AnonymousAnonymous

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