Neurobiology of Wisdom

Dilip V. Jeste, M.D.Stein Institute for Research on Aging

Departments of Psychiatry & NeurosciencesUniversity of California, San Diego

Of all the pursuits opento men, the search forwisdom is most perfect, more sublime, more profitable, and more full of joy

— Thomas Aquinas (~1260)

OUTLINE

• Historical Perspective• Common Elements in Definition of Wisdom• Neurobiology of Wisdom• Aging and Wisdom• Neuroplasticity of Aging• Implications

Psychological Constructs Long Ignored by Biological Researchers

• Consciousness• Cognition• Emotion• Stress• Resilience• Wisdom

Sophia: The Greek Goddess of Wisdom

Saraswati:The Hindu Goddess of Wisdom

Gall’s Phrenology (circa 1820)

Modern Western Views• Erikson – Last stage of personality development• Baltes – Rare expertise in pragmatics of life• Sternberg – “Common sense” used to balance

intra-, inter-, & extra-personal factors for common good

• Brugman – Knowledge of and adapting to uncertainty

• Ardelt – Emotional regulation• Jason – Spirituality, Harmony & warmth

*

* Adapted from Meeks and Jeste (2009)

050

100150200250300350

1970s 1980s 1990s 2000-2010

Number of Publications on “Wisdom” in PubMed by Decade *

OUTLINE

• Historical Perspective

• Common Elements in Definition of Wisdom

• Neurobiology of Wisdom• Aging and Wisdom• Neuroplasticity of Aging• Implications

(I). Lit. Review: Common Elements of Wisdom in Modern Scientific Definitions

• Pragmatic knowledge of life / Social decision making

• Emotional Regulation• Pro-social attitudes & behaviors • Reflection / Self-understanding• Dealing effectively with uncertainty and

ambiguity• Value Relativism / Tolerance

(Meeks TW & Jeste DV: Arch Gen Psych, 66:355-365, 2009)

(II). Expert Consensus: Delphi Method Study

• 2-phase survey of 30 international experts on wisdom ---- Large consensus noted

• Wisdom is different from intelligence and spirituality on most relevant items

• Wisdom conceptualized as a complex, uniquely human trait, with advanced cognitive and emotional development, experience-driven, can be learned, and increases with age

(Jeste, Ardelt, Blazer, Kraemer, Vaillant, Meeks; J Gerontology, 2010, in press)

Expert Consensus:Items Characteristic of Wisdom

• Rich knowledge of life, Practical life skills• Social cognition, Social cooperation• Emotional regulation • Tolerance of ambiguity• Value relativism, Tolerance of diversity• Insight• (Openness to new experience)• (Successful coping strategies, Resilience)• (Sense of humor)

(III.) Wisdom in the Ancient East: The Bhagavad Gita

Wisdom in the Ancient East: The Bhagavad Gita

• The Bhagavad Gita: “The Song of the God or the Divine One”

• Concise guide to Hindu philosophy, written 200-500 years BC; Based on the Yogas, which date back to 2,000-5,000 years BC

• Business Week, 2007: The Gita has become the most influential ancient text as a guide for the western business community

(Jeste DV & Vahia IV: Psychiatry, 71:197-209, 2008)

Methods• Independent review of English translations by

Zaehner/Goodall, and Swami Nirmalananda Giri

• Translation & back translation using Oxford English Dictionary, Roget’s New Millennium Thesaurus, & Cologne Digital Sanskrit Lexicon

• Textalyser and NVivo software usd with electronic version of the Giri translation

• Inter-rater reliability

Components of Wisdom in the Gita

• General Knowledge of life• Emotional Regulation• Compassion/Sacrifice• Insight / Humility• Decisiveness • Duty and Work• Self-Contentedness• (Love of God)• (Renunciation of materialistic pursuits)

OUTLINE

• Historical Perspective• Common Elements in Definition of Wisdom

• Neurobiology of Wisdom• Aging and Wisdom• Neuroplasticity of Aging• Implications

Neurobiology of Wisdom?

• Loss of wisdom with localized brain injury (to prefrontal cortex)

• Loss of wisdom with disease affecting specific brain areas (prefrontal cortex)

• Review of literature focusing primarily on neuroimaging / brain localization of individual domains of wisdom: Balance between newest and oldest parts of brain (prefrontal cortex and limbic striatum)

(Meeks TW & Jeste DV, Arch Gen Psych, 66:355-365, 2009 )

Phineas Gage

Phineas Gage (1823-1860)• Railroad construction foreman in Vermont• “….. although untrained in the schools, he

possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent in executing all his plans of operation” – Dr. Harlow (his physician)

• 1848: A large iron rod went thru back of his left eye and came out thru top of his head; Physical recovery was almost complete

Phineas Gage

(Damasio H et al., Science,

1994; 264:1102-05)

Phineas Gage after the Injury“Fitful, irreverent, at times grossly profane, with

little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising .. and (then quickly) abandoning plans of future operations. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man. …. His mind was radically changed, so decidedly that his friends … said he was "no longer Gage.” – Dr. Harlow

•

Modern Day Phineas Gage• 26-year-old man with an exemplary academic

and professional (military) record • Penetrating head injury caused bilateral ventro-

medial prefrontal cortex damage, left > right• Precipitous decline in social functioning: Lost

job, followed by multiple temporary low-level jobs despite average to superior scores on most neurocognitive tests (e.g., Verbal IQ 19)

• 3 marital break-ups, estrangement from children

(Cato A., et al. J Int’l Neuropsychological Soc, 10, 453–465, 2004)

•

Fronto-Temporal Dementia (FTD)• Insidious onset of personality changes &

behavioral abnormalities before age 60• Pathology restricted to prefrontal (& anterior

temporal) lobes• Poor social decision making (Loss of personal

and social awareness)• Disinhibition, Impulsivitiy • Sociopathy, Lack of empathy • Emotional coldness, Apathy• Poor insight, Self-centeredness

Lit. Review: Brain Regions in WisdomAnt. Cing. Cortex (ACC)Conflict detection

Ventro-medial PreFrontal Cortex (vmPFC) Emotional & pro-social thinkingAmygdala

Strong emotions such as fear

Dorso-lateral PreFrontal Cortex (dlPFC)Cold cognition, Utilitarian choices

Lit. Review: Brain Regions in Wisdom• Dorso-lateral Prefrontal Cortex (dlPFC)

(= Proverbial Father): Rational, cold, calculating, competitive

• Ventro-medial Prefrontal Cortex (vmPFC)(= Proverbial Mother): Emotional, kind, supportive, social

• Anterior Cingulate Cortex (ACC) (=Proverbial Uncle): Detector of conflict

• Limbic striatum (= Proverbial Friend): Pleasure, reward

OUTLINE

• Historical Perspective• Common Elements in Definition of Wisdom• Neurobiology of Wisdom

• Aging and Wisdom• Neuroplasticity of Aging• Implications

Cognitive Abilities that Decline with Aging

• Speed of information processing• Reaction time• Working memory• Recall (Access to memory stores) • Some Aspects of Executive function• Some learning abilities

Data-Based Model of Cognitive Change Across Lifespan

(Craik & Bialystok, Trends in Cogn Sci 10:131-138, 2006)

Perf

orm

ance

Childhood Maturity Old age

Fluid mechanics

Crystallized pragmatics

Rome – Dr. Montalcini, a Nobel Laureate, on her 100th birthday: “My mind is sharper than when I was 20.” (Yahoo News 4-18-09)

Dr. Rita Levi Montalcini

Aging and Judgment

“I think I do science better now than I did when I was younger. In science, judgment is so important, and I now have a better understanding of which problems are important and which are not.”

--- Eric Kandel, age 77

(Wall Street Journal, Feb. 17, 2007)

Study Population• Total N > 3,000• Sites: Local retirement communities +

collaborations with other UCSD studies (e.g., Women’s Health Initiative or WHI)

• Non-institutionalized seniors• Most between 60 and 102 years of age• Representative of US seniors in physical &

mental health(Montross, et al., Am J Geriatric Psychiatry, 14:43-51, 2006)

(Jeste DV et al, World Psychiatry, in press, 2010)

Distribution of Self-Rated Successful Aging Scores in Older Women (N=1,979)

Least Successful

Most Successful

(Jeste DV et al, World Psychiatry, in press, 2010)

Successful Aging Using Non-Physical Criteria (1,957 women)

• Independent Living 94%• Positive Adaptation 81%• Active Engagement with Life 74%• Mastery / Growth 81%• Life Satisfaction 84%• Cognitive Function 71%

Physical Health Criteria of Successful Aging

• Freedom from Disability 38%• Absence of Disease 20%

Paradox of Aging

• Generally, physical health and some cognitive abilitiess decline with aging, while mental health and psychosocial functioning tend to improve

Psychological Well Being and Aging • Gallup phone survey of > 340,000 Americans age

18-85 in 2008 re. global (one question) and hedonic (questions about yesterday’s affect) WB

• Global & Positive Hedonic WBs had U-shaped age profiles showing increased WB after age 50

• Negative Hedonic WBs: Stress and Anger - steeply declined from 20s; Worry - elevated thru midlife & then declined; Sadness - essentially flat

(Stone AA, et al., PNAS, 2010, in press)

Self-Rated Global Well Being by Age

(Stone et al. PNAS 2010)

Wisdom & Life Satisfaction in Old Age • Study of 81 women and 39 men, age 58-82, using

structural equation models with latent variables (LISREL models)

• Wisdom (defined as a composite of cognitive, reflective, and affective qualities) had a profoundly positive influence on life satisfaction independent of objective circumstances (physical health, social / financial situation), more in women than in men

(Ardelt, M: J Gerontol: Psychol Sci, 528:15-27, 1997)

Greater Wisdom with Aging?• Participants read stories about social conflicts,

and predicted how these conflicts would unfold • Coding scheme validated by a group of

professional counselors & wisdom researchers• Older people made greater use of higher-order

reasoning schemes that emphasized need for multiple perspectives, allowed for compromises, and recognized limits of knowledge

• Conclusion: Social reasoning seemed to improve with age despite decline in fluid intelligence

(Grossman I, et al., PNAS, 2010 epub)

OUTLINE

• Historical Perspective• Common Elements in Definition of Wisdom• Neurobiology of Wisdom• Aging and Wisdom

• Neuroplasticity of Aging• Implications

Plasticity of Aging Brain• Compensation may involve enhanced recruitment of alternate brain networks &/or more efficient utilization of same brain networks • Neurogenesis and Synaptogenesis continue to occur in old age, and can be stimulated by living in an enriched environment• “Bio/Socio-stasis”: Reduced emotional negativity due to reduced amygdala response

(Cabeza et al, 2002)

fMRI Prefrontal cortex activation during a source memory task in 3 Groups:

1) Successful Young

2) Unsuccessful Old

3) Successful Old

COMPENSATION?

Neurogenesis and Synaptogenesis

(Gage et al., Science)

Juggling-induced Changes in Grey Matter

(Draganski B. et al., Nature 427:311-312, 2004)

Juggling-induced Changes in Grey Matter

(Draganski B. et al., Nature 427:311-312, 2004)

Per

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ay m

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MRI studies in patients with schizophrenia show Grey matter density increases with Cognition Enhancement therapy compared to supportive therapy at 1 year

(Keshavan and colleagues, Arch Gen Psychiatry, in press )

Bio/Socio- static Changes with Aging?

• Positivity Effect of Aging: Lower level of experiencing, paying attention to, and remembering negative than positive emotional stimuli in older adults

• Reduced emotional negativity due to reduced amygdala response (Mather et al., 2004)

OUTLINE

• Historical Perspective• Common Elements in Definition of Wisdom• Neurobiology of Wisdom• Aging and Wisdom• Neuroplasticity of Aging

• Implications

Evolutionary Role for Human Aging-Associated Wisdom?

• In the absence of predators and natural disasters, the average life span equals the maximum life span in most species (but not in humans)

• The prolonged aging period in man is associated with physical & cognitive deterioration

• Age-associated increase in wisdom, facilitated by neuroplasticity, may enable humans to reach maximum life span

(Jeste DV, Harris JC: JAMA, in press, 2010)

Can the Wisdom of Aging be Activated and Make a Difference Societally?

• Experience Corps: A program based in public elementary schools in which trained older adult volunteers serve (> 15 hours/week) as mentors & tutors in areas such as literacy development & behavioral management skills to help enhance the children’s academic success

• Such programs may activate and promote the wisdom of aging and benefit the rest of the society simultaneously(Parisi, JM, et al., Educat’l Gerontol, 35, 867-879, 2009)

Summary• The basic concept of wisdom has remained

largely similar across temporal and geographic boundaries

• Wisdom is a complex human trait with a neurobiological basis

• Positive aging, with increase in wisdom, may have evolutionary significance

• Methodologically rigorous empirical research on biological aspects of wisdom and on wisdom-based therapies is warranted