Cognitive neuroscience and psychotherapy認知神經科學與心理治療

Chau-Shoun LEE, M.D., Ph.D.

Senior attending psychiatrist and assistant professorDepartment of Psychiatrist, Mackay Memorial Hospital

Model of mental illness

stress x diathesis x time

Psychological trauma or stressor

FILTER

personality/coping skills

genetic vulnerability factors for psychological symptoms

4-3 Stahl S M, Essential Psychopharmacology (2000)

Developmental timing factor for emotional dysregulation: familial attachment and peer interaction

Developmental timing factor for nerve development: the microscopic aspect

• Neurogeneis– Production, migration, and development of distinct nerve or glia

from stem cells– An unavailable mother leads to smaller hippocampus due to

insufficient neurogenesis which results in over active HPA axis• Cell expansion

– Synaptogenesis, extensive growth of axons and dendrites to make synaptic connections

• Connection refinement– Pruning or synaptic elimination, maturing process of adolescents

is refinement and reduction of the gray matter and no growth• Apoptosis

– programmed cell death, a characteristic process with cell shrinkage, fragmentation, and phagocytosis of remnants

Psychological dysfunctions at various levels

RISK FACTOR 1

an enzyme is too slow ever since birth so it is hard to metabolize neurotransmitters when release is very fast

RISK FACTOR 2

some neurons migrated too far during development in utero

RISK FACTOR 3

some of the wrong synapses were eliminated in adolescence

RISK FACTOR 4

nerves fire too fast when you see your mother

1-3 are inherited genetic “hits” - 4 & 5 are environmental “hits” expressed through abnormal genetic responses

RISK FACTOR 5

nerves fire too fast when you take “speed”

4-2 Stahl S M, Essential Psychopharmacology (2000)

Molecular levels: genetics and epigenetics

Neurophysiological levels of emotional dysregulation:dysfuntion in the cellular signaling pathways –stahl, 2000

Clinical levels of emotional dysregulation:Treating the patient as a person not only a disorder

• Neuronal development– Neurogenesis- synaptogenesis- pruning- apoptosis

• Personality development– Familial attachment- peer interaction- intimate relationship

• Schizophrenic disorder– Cortical deficit- chemical sensitization- degeneration

• Mood disorder– Emotional dysregulation- biaxial dysfunction- cognitive

impairment

• Intracellular signaling– Long term potentiation v.s. depression– GABA v.s Glutamate- dopamine

Glutamate, NMDA and AMPA receptors

The process of LTP inducing a change at the synapse

---any difference from excito-toxicity?

Cognitive and emotional dysregulation during psychotherapy

Minding the Other and empathy:Simulation Theory and Social Neuroscience

• Mirror Neuron

– 鏡像神經元• http://www.youtube.com/w

atch?v=XzMqPYfeA-s

• How many persons do you need to empathize at interview?

– 舉杯邀明月，對影成三人

Adapted from: Seamans et al. J Neurosci 2001

Cognitive function and prefrontal Cognitive function and prefrontal cortex:cortex:

A cellular physiology of “efficient processing”A cellular physiology of “efficient processing”Optimal D1/D2-receptor signaling

(i.e. D-1 dominated state)Suboptimal D1/D2-receptor signaling

(ie. D-2 dominated state)

Optimum D1/D2 activation focuses and stabilizes the Optimum D1/D2 activation focuses and stabilizes the representational networkrepresentational network

(i.e. it enhances stability or signal-to-noise)(i.e. it enhances stability or signal-to-noise)

Prefrontal cortical neural regions implicated in emotion regulation--- Phillips ML et al, Molecular Psychiatry, 2008

• Prefrontal cortex (PFC) implicated in cognitive control processes, including decision-making and emotion regulation

– Orbitofrontal (OFC), dorsomedial prefrontal (MdPFC), anterior cingulate gyrus (ACG), dorsolateral prefrontal (DLPFC), ventrolateral prefrontal (VLPFC)

• Ventromedial areas (OFC, MdPFC and ACG) develop relatively early, involved in the control of emotional behaviors, whereas lateral prefrontal cortical regions (DLPFC and VLPFC) develop late, and are involved in higher executive functions.

• OFC, MdPFC and parts of ACG, are the most densely connected with amygdala, other subcortical limbic and paralimbic regions.

• Intrinsic cortico-cortical connections of OFC and MdPFC can reflect two distinct networks.

– ‘Orbital prefrontal network’ involves multisensory inputs into OFC and MdPFC and provides integration of information of an affective value.

– ‘Medial prefrontal network’ involves integration of visceromotor information.

Endophenotype of emotional dysregulation: Learning by

emotion instead of situation LeDoux JE, 1994

Integrating cortical control and emotional drive

• High sensitivityHigh sensitivity (sensitive alarm system)(sensitive alarm system)

– Immediate reactionsImmediate reactions

– Low threshold for emotional reactionLow threshold for emotional reaction

• High reactivityHigh reactivity (high amygdala reaction)(high amygdala reaction)

– Extreme reactionsExtreme reactions

– High arousal dysregulates cognitive processingHigh arousal dysregulates cognitive processing

• Slow return to baselineSlow return to baseline (low regulation from medial (low regulation from medial prefrontal cortex and hippocampus)prefrontal cortex and hippocampus)

– Long-lasting reactionsLong-lasting reactions

– Contributes to high sensitivity to next emotional Contributes to high sensitivity to next emotional stimulusstimulus

• High sensitivityHigh sensitivity (sensitive alarm system)(sensitive alarm system)

– Immediate reactionsImmediate reactions

– Low threshold for emotional reactionLow threshold for emotional reaction

• High reactivityHigh reactivity (high amygdala reaction)(high amygdala reaction)

– Extreme reactionsExtreme reactions

– High arousal dysregulates cognitive processingHigh arousal dysregulates cognitive processing

• Slow return to baselineSlow return to baseline (low regulation from medial (low regulation from medial prefrontal cortex and hippocampus)prefrontal cortex and hippocampus)

– Long-lasting reactionsLong-lasting reactions

– Contributes to high sensitivity to next emotional Contributes to high sensitivity to next emotional stimulusstimulus

Manifestations of Emotional VulnerabilityManifestations of Emotional Vulnerabilityin the Psychotherapyin the Psychotherapy

Manifestations of Emotional VulnerabilityManifestations of Emotional Vulnerabilityin the Psychotherapyin the Psychotherapy

What is the role of psychotherapy when we encounter the patient

during or after the adolescent stage?

“A key technical difference in psychodynamic psychotherapy in contrast to cognitive behavior therapy and interpersonal psychotherapy is its

emphasis on transference.”

Cutler JL et al., 2004 in AJP

Cognitive therapy (CT) and antidepressant (ADM): response rate after 8 and 16 weeks-- DeRubeis RJ et al.,2008

Limbic SystemLimbic System

PrefrontalPrefrontalCortexCortex LocusLocus

CoeruleusCoeruleus(NE source)(NE source)

Raphe NucleiRaphe Nuclei(5-HT source)(5-HT source)

Serotonin (5-HT) and norepinephrine (NE) pathways in the human brain

AmygdalaAmygdala

HippocampusHippocampus

Based on: Cooper JR, et al. The Biochemical Basis of Neuropharmacology. 8th ed. New York: Oxford University Press; 2003.

Descending 5-HT pathways

DescendingNE pathways

Time course of the changes to amygdala and prefrontal function associated with ADM and CT--

DeRubeis RJ et al.,2008

In comparison to other networks, DMN has unique patterns of activity (Gusnard et al., 2001; Raichle et al., 2001): both in terms of energy consumption and BOLD

signal, activation levels in this network were shown to descend below baseline during cognitively demanding tasks.

DMN shows high activation levels at rest compared to task.

Cortical and subcortical pathways for vision and emotion: primary visual cortex (V1) lateral geniculate nucleus (LGN) thalamus (Th) pulvinar (Pulv) superior colliculus (SC) amygdala (AMG) periaqueductal grey (PAG)

nucleus accumbens (NA) anterior cingulate cortex (ACC). orbitofrontal (OFC) substantia innominata (SI)

Bio-psycho-social interaction in performing a psychotherapy

Neuroanatomy and neurophysiology of sense and sensibility--Winstanley Ca, 2005; Carli M, 2005; Cardinal RN,2004; Meyer-Lindenberg et al, 2006; Pezawas et al, 2005

• Prefrontal cortex for cognition

(dorsolateral)

• COMT activity (val and met alleles)

• D 1

• Medial prefrontal cortex

• Anterior cingulate• Functional connectivity and 5-

HTTLPR (ll and s carrier)

S1A

• S2A

• Orbitofronal cortex for behavioral inhibition

• MAO-A VNTR-L

D2

• Neucleus accumbens for delayed and larger reward

• Amygadala/hippocampus

Changes in blood-oxygen-level-dependent (Bold) signal in response to cognitive and emotional tasks associated with

cognitive therapy --- DeRubeis RJ et al.,2008

The relation between BOLD response and self–other discrepancy for subregions of the MPFC: serotonergic v.s. dopaminergic therapy

Tamir D I , Mitchell J P PNAS 2010;107:10827-10832

©2010 by National Academy of Sciences

Mentalization or object representation (Lois W. Choi-Kain, M.D., M.Ed. & John G. Gunderson, M.D. 2008):

a major function of medial prefrontal cortex

Differential triggers in mental disorders: specific therapy module for specific precipitator

• Social encounter v.s. social phobia

• Panic context v.s. agorophbia

• Body cues v.s. panic disorder

• Spider or high places v.s. simple phobia

• Traumatic reminder v.s. PTSD

• Loss event v.s. major depressive disorder

Interventions from expressive to supportive psychotherapy

• Expressive dimension (unconscious, non-conscious, implicit, automatic, subliminal)

– Interpretation

– Observation

– Confrontation

– Clarification

– Encouragement to elaborate

– Empathic validation

– Psychoeducational interventions

– Advice and praise

• Supportive dimension

壓力因應模式

介入模式 (engagement) 迴避模式

理性(cognition)介入

感性 (Emotion)介入

解決問題

認知重構

傾訴

尋求支持

理性

感性

白日夢

鴕鳥

政策

自責

社交退縮

子曰：「學而時習之，不亦說乎？

有朋自遠方來，不亦樂乎？ 人不知而不慍，不亦君子乎？」