Craig Hassed Conference Presentation for Website 2

Neuroplasticity and the art of

using the brain wisely

Dr Craig Hassed

Senior Lecturer

Monash University

Department of General Practice

What is the brain? The human brain is

thought to be the most

complex thing in the

universe

Contains about 80-120

billion neurons each

connecting to thousands

of other neurons

Many supporting cells

Has roughly the

consistency of tofu

Brain cells talking to each other

Brain cells talk to each other

via chemicals

(neurotransmitters) released

in response to electrical

impulses sent along nerve

fibres (axons) which

stimulate receptors in the

next neuron

These messages activate

the target cells or organs,

e.g. muscles, gut, immune

cells, endocrine systems

Brain topography

Each part of the cerebral cortex (grey matter) has a

particular function e.g.

Broca‟s area is the language area for forming speech

Wernicke‟s area for understanding speech and remembering words

Motor cortex on each side for the capacity to move

Spiritual experiences and brain activation

During religious recitation religious subjects activate areas of the prefrontal and parietal cortex

Activity in temporal lobes of the brain associated with religious and psychological phenomena including blurring of interpersonal or ego boundaries

Azari NP, Nickel J, Wunderlich G et al. Eur J Neurosci. 2001;13(8):1649-52.

Persinger MA. Perceptual & Motor Skills. 1991;72(2):453-4.

Beauregard M, Paquette V. Neurosci Lett. 2006;405(3):186-90.

Image from

Mapping the Mind

Plato’s 3 aspects of the psyche

Three aspects of the psyche (soul)

Reason (intelligence)

Emotive element (passion, courage)

Appetitive element (instincts, pleasure)

According to Plato, justice is the right alignment of these elements and it leads to happiness, freedom and health and a cohesive community

The reasoning element governs (tempers / regulates) emotions and appetites

Botticelli’s “Pallas and the Centaur

Three regions of the brain

Frontal lobes (prefrontal cortex) centre for executive functioning

Attention regulation

Working memory

Reasoning and decision making

Emotional regulation

Appetite regulation

Impulse control

Directs immune system

Limbic system – emotion centre

Mesolimbic reward system – appetites

Neuroplasticity

“As a man thinketh, so he

becomes.”

James Allen

“Neurons that fire together, wire

together.”

Hebbes hypothesis

Maternal stress & schizophrenia

High levels of schizophrenia a/w stress during pregnancy (loss of husband, severe famine, unwanted pregnancies)

Women exposed to prenatal stress during the 1940 invasion of Holland c/w women who were pregnant in the previous year or following two years

Risk of schizophrenia in offspring increased by 2.8 times and worst for women in first trimester of pregnancy

British Journal of Psychiatry 1998;172:324-6

Happy bunnies (rats)

Lots of nurture

leads to more

brain serotonin

Stimulates brain to

make more of a genetic

enzyme to switch on

cortisol receptor

production

Higher level of cortisol receptors

leads to being less stress prone A happy

bunny

Child abuse

Experiencing child abuse leads to high levels of stress

chemicals (e.g. CTRH and cortisol) for the rest of

one‟s life even if no longer in a stressful situation

The brains of suicide victims with a history of child

abuse show the same effects on genes and brain

stress receptors as seen in the animal experiments

McGowan et al. Nature Neuroscience 2009;12:342-48.

Lee et al. Am J Psychiatry 2005;162:995-7.

Carpenter et al. Neuropsychopharm 2004;29:777-84.

Chronic pain and the brain

Chronic pain syndromes are common including in conditions where it is difficult to demonstrate somatic disease Burnout, epidemic fatigue, multiple chemical sensitivity, chronic

musculoskeletal pain, chronic low back pain, chronic fatigue syndrome, and fibromyalgia

Neural loops become sensitized and maintained by “sustained attention and arousal”

A high level of reactivity sensitises the brain to pain

This may be why reducing reactivity through mindfulness reduces chronic pain

Eriksen HR. J Psychosom Res. 2004;56(4):445-8.

Ursin H. Ann N Y Acad Sci. 2001 Mar;933:119-29.

Astin JA, et al. J Rheumatol. 2003;30(10):2257-62.

Musical training and neuroplasticity Musicians show significantly increased Grey Matter

volume in the language and sound production (Broca's)

area correlating with years of musical performance Abdul-Kareem IA, Stancak A, Parkes LM, Sluming V.J. Increased gray matter

volume of left pars opercularis in male orchestral musicians correlate

positively with years of musical performance. Magn Reson Imaging. 2011

Jan;33(1):24-32. doi: 10.1002/jmri.22391.

Brain regions activate differently in musicians and non-

musicians

Wan CY, Schlaug G. Music making as a tool for promoting brain plasticity across the

life span. Neuroscientist. 2010 Oct;16(5):566-77.

London Taxi drivers

London taxi drivers show

increased grey matter

density in the brain‟s

memory centres Acquiring "the Knowledge" of

London's layout drives

structural brain

changes.Woollett K, Maguire

EA.Curr Biol. 2011 Dec

20;21(24):2109-14.

Mental Practice and stroke

Mental practice (MP) of a motor skill activates the same musculature and neural pathways as physical practice of the same skill

RCT on stroke patients compared rehab +/- MP vs. a placebo intervention 30-minute MP sessions twice/wk for 6 weeks plus usual rehab

Subjects receiving MP showed: statistically and clinically significant reductions in impairment

significant increases in daily arm function

new ability to perform important activities of daily living Page SJ. Stroke. 2007;38(4):1293-7.

Neurogenesis

“For over 100 years a central assumption in the

field of neuroscience has been that new neurons

are not added to the adult mammalian brain.

This perspective examines the origins of this

dogma, its perseverance in the face of

contradictory evidence, and its final collapse.” Gross CG. Nature Reviews Neuroscience. 2000;1(1):67-73.

Neuronal stem cells persist throughout the entire

lifespan Arias-Carrion O. Revista de Neurologia. 2007;44(9):541-50.

Neurogenesis

Many factors enhance

hippocampal (memory

area) neurogenesis e.g.:

Physical exercise

Learning

Attention training

Other factors suppress

neurogenesis:

Aging

Stress / depression and

stress hormones (e.g.

cortisol/glucocorticoids)

Stimuli that activate the

stress response

Implications for

neurodegenerative

illnesses e.g. dementia

Elder GA. Mount Sinai Journal of Medicine. 2006;73(7):931-40.

Allostatic load

Prolonged stress leads to wear-and-tear on the body (allostatic load) Mediated through the Sympathetic Nervous System

Allostatic load leads to: Impaired immunity, atherosclerosis, metabolic syndrome,

bone demineralization

Atrophy of nerve cells in the brain Hippocampal formation: learning and memory

Prefrontal cortex: working memory, executive function

Growth of Amygdala mediates fear response

Many of these processes are seen in chronic depression and anxiety

McEwen BS. Ann N Y Acad Sci. 2004;1032:1-7.

Stress and the brain

Pro-inflammatory chemicals (cytokines) produced by immune cells in response to danger signals act on the brain (Central Nervous System)

Prolonged activation can: Precipitate development of depression

Trigger the „sickness response‟

Brain cytokine system can become sensitized early in life predisposing to mental illness later in life Dantzer R. Psychoneuroendocrinology.

2005;30(10):947-52.

Attention, leisure and dementia Brain regions active in

„default states‟ in young adults also show amyloid deposits in adults with AD Active tasks: tasks associated

with paying attention

Default states: when mind is inattentive, idle, recalling past

Early stages of AD prominent atrophy and metabolic abnormalities in these regions

Buckner RL et al. J Neurosci. 2005;25(34):7709-17.

Higher TV watching at 3 a/w higher ADHD at 7

Leisure and AD risk Lack of diversity

Less time on leisure activities

Passive leisure activities (principally TV)

Nearly four times as likely to develop dementia over 40-year f/up

Friedland RP et al. Proc Nat Acad Sci USA, 10.1073/pnas.061002998

Scarmeas N et al. Neurology 2001;57(12):2236-42.

TV, children & executive functioning

4-year-olds randomly assigned to watch a fast-paced TV

cartoon (Spongebob Squarepants), educational cartoon or

draw for 9 minutes, then 4 tasks on executive function

Children who watched the fast-paced TV cartoon

performed significantly worse on executive function tasks

“Just 9 minutes of viewing a fast-paced television cartoon

had immediate negative effects on 4-year-olds' executive

function. Parents should be aware that fast-paced

television shows could at least temporarily impair young

children's executive function.” Lillard AS, Peterson J. The Immediate Impact of Different Types of

Television on Young Children's Executive Function. Pediatrics

Published online September 12, 2011, (doi: 10.1542/peds.2010-1919)

Mental stimulation and brain health Healthy elderly (av. 76.1yrs) c/w patients with Alzheimer

Disease (74.8yrs) and young controls (24.5yrs)

„Brain health‟ (amyloid deposits) c/w participation in cognitive

activities (e.g. reading, writing, playing games)

Greater participation in cognitively stimulating activities

(particularly in early and middle life) associated with reduced

amyloid uptake

The top ¼ of older participants for cognitive activity had amyloid

uptake comparable to young controls

The lowest ¼ for cognitive activity had amyloid uptake comparable to

patients with AD

Landau SM, Marks SM, Mormino EC, Rabinovici GD, Oh H, O'Neil JP,

Wilson RS, Jagust WJ. Association of Lifetime Cognitive Engagement and

Low β-Amyloid Deposition. Arch Neurol. 2012 Jan 23. [Epub]

Mindfulness and the brain Mindfulness training improves functioning in

areas related to executive functioning,

attentional control, self-regulation, sensory

processing, memory and regulation of the

stress response Thickening of cortex in regions associated with

attention, self-awareness and sensory processing thicker in meditators

“The regular practice of meditation may have neuroprotective effects and reduce the cognitive decline associated with normal aging.” Hölzel BK, Carmody J, Evans KC, et al. Stress reduction correlates with

structural changes in the amygdala. Soc Cogn Affect Neurosci. 2010

Mar;5(1):11-7.

Hölzel BK, Carmody J, Vangel M, et al. Mindfulness practice leads to

increases in regional brain gray matter density. Psychiatry Res. 2011 Jan

30;191(1):36-43.

Kilpatrick LA, Suyenobu BY, Smith SR, et al. Impact of Mindfulness-Based

Stress Reduction training on intrinsic brain connectivity. Neuroimage. 2011

May 1;56(1):290-8.

Lazar SW, Kerr CE, Wasserman RH, et al. Neuroreport. 2005;16(17):1893-

1897.

Pagnoni G. Cekic M. Neurobiology of Aging. 2007;28(10):1623-7.

Mindfulness and the brain

Change in gray

matter concentration

(GMC) within the

cluster in the left

hippocampus from

the Pre to the Post

time-point in the

MBSR and the

control group; error

bars show 95%

confidence interval.

Hölzela BK, Carmody J, Vangela M, et al. Mindfulness practice leads to increases in

regional brain gray matter density. Psychiatry Research: Neuroimaging 2010.

Diet and Alzheimer’s Disease

Associated with lower odds of cognitive

deficits or reduced risk of AD

higher intake of fruits, vegetables, fish, nuts and

legumes

lower intake of meats, high fat dairy, and sweets

adequate vitamin D levels

Gu Y, Scarmeas N. Dietary patterns in Alzheimer's

disease and cognitive aging. Curr Alzheimer Res. 2011

Aug;8(5):510-9.

Lu'o'ng KV, Nguyên LT. The beneficial role of vitamin D

in Alzheimer's disease. Am J Alzheimers Dis Other

Demen. 2011 Nov;26(7):511-20.

Exercise and cognitive decline

Physical exercise, even if moderate, protective against cognitive decline and stimulates neuronal growth particularly in the hippocampus

Reduces risk of Alzheimer‟s disease by half

For patients already suffering from dementia, physical exercise, especially when combined with music, associated with improved cognitive function

Archives of Internal Medicine 2001;161:1703-8.

Laurin D, Verreault R, Lindsay J, et al. Arch Neurol. 2001;58(3):498-504.

Van de Winckel A, et al. Clin Rehabil. 2004;18(3):253-60.

Lautenschlager NT, et al. Curr Opin Psychiatry. 2006 Mar;19(2):190-3.

Buchman AS, Boyle PA, Yu L, et al. Total daily physical activity and the risk of

AD and cognitive decline in older adults. Neurology. 2012 Apr 18.

Lifestyle and MS

Study on 5-day residential retreat for people with MS

which promotes lifestyle modification within a patient-

centred model of care

Analysis of the health-related quality of life (HRQOL) of

the retreat participants was undertaken using the

MSQOL-54, prior to attendance, 1 and 5 years after the

retreat

274 retreat participants (71%) completed baseline

questionnaires Hadgkiss EJ, Jelinek GA, Weiland TJ, et al. Health-related quality of life

outcomes at 1 and 5 years after a residential retreat promoting lifestyle

modification for people with multiple sclerosis. Neurol Sci DOI

10.1007/s10072-012-0982-4

Lifestyle and MS

Participants demonstrated clinically and statistically

significant improvements in HRQOL

At 1 year median improvements of 11.3% in overall

QoL

At 5 years there was a 19.5% median improvement in

overall QoL compared to baseline

17.8% in the physical health

22.8% in the mental health

“Non-drug therapies should be considered as part of

any comprehensive treatment plan for people with MS.” Hadgkiss EJ, Jelinek GA, Weiland TJ, et al. Health-related quality of life

outcomes at 1 and 5 years after a residential retreat promoting lifestyle

modification for people with multiple sclerosis. Neurol Sci DOI

10.1007/s10072-012-0982-4

Exam stress and performance

High math anxiety led to smaller working

memory spans

Reduced working memory capacity led to

pronounced increase in reaction time and errors Ashcraft MH. J Exp Psychol Gen. 2001 Jun;130(2):224-37.

“Performance pressure harms individuals

most qualified to succeed by consuming the

working memory capacity that they rely on for

their superior performance.” Beilock SL. Psychol Sci. 2005;16(2):101-5.

Mobile phone use and motor vehicle

accidents

Driver's use of a mobile phone within 5 min

before a crash associated with fourfold

increased likelihood of crashing (OR 4.1) McEvoy SP, Stevenson MR, Woodward M.The contribution of passengers

versus mobile phone use to motor vehicle crashes resulting in hospital

attendance by the driver. Accid Anal Prev. 2007 Nov;39(6):1170-6. Epub 2007

Apr 9.

Mathers CD, Loncar D. Projections of global mortality and burden of disease

from 2002 to 2030. PLoS Med. 2006 Nov;3(11):e442.

Antidepressant trials and placebo

On brain scan, placebo response biologically similar to that in people receiving active drug

Mayberg HS, et al. Am J Psych. 2002;159(5):728-37.

Antidepressant drug–placebo differences: virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression Data on all clinical trials

submitted to the US FDA Kirsch I et al. PLoS Medicine

2008 Feb;5(2):e45 doi:10.1371/journal.pmed.0050045

Default mode network Active tasks: tasks associated with paying attention

Default states: mind is inattentive, idle, recalling past

Brain regions active in „default states‟ in young adults also show amyloid deposits in adults with AD

Buckner RL et al. J Neurosci. 2005;25(34):7709-17.

High default mental activity in psychopathology (e.g.

depression, anxiety, schizophrenia and autism)

Default activity decreased or deactivated when paying attention

(e.g. experienced mindfulness meditators)

In experienced meditators even when default network active,

regions associated with self-monitoring and cognitive control

are co-activated: reduced vulnerability to default thinking

Brewer JA, Worhunsky PD, Gray JR, et al. Meditation experience is

associated with differences in default mode network activity and

connectivity. Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20254-9.

MBCT and depression

RCT investigated the effects of Mindfulness-based

cognitive therapy (MBCT) on the relapse in depression,

time to first relapse and the quality of life

106 recovered depressed patients with a history of at least 3

depressive episodes

Treatment as usual (TAU) vs MBCT plus TAU 1 year f/up

Relapse/recurrence significantly reduced and the time until

first relapse increased in the MBCT plus TAU c/w TAU

MBCT plus TAU group also showed a significant reduction

in both short and longer-term depressive mood, better

mood states and quality of the life Godfrin KA, van Heeringen C. The effects of mindfulness-based cognitive

therapy on recurrence of depressive episodes, mental health and quality of life:

A randomized controlled study. Behav Res Ther. 2010 Aug;48(8):738-46.

Godfrin KA, van Heeringen C. Behav Res Ther. 2010 Aug;48(8):738-46.

Godfrin KA, van Heeringen C. Behav Res Ther. 2010 Aug;48(8):738-46.

Mindfulness, depression and the

stress response Mindfulness negatively correlates with

depressive symptoms and reactivity of the

amygdala Way BM., Creswell JD., Eisenberger, NI., Lieberman MD.

Dispositional mindfulness and depressive

symptomatology: Correlations with limbic and self-

referential neural activity during rest. Emotion. Vol 10(1),

Feb 2010, 12-24.

Mindfulness, brain and immunity

Effects on brain and immune function of an 8-week clinical training program in mindfulness

At the end of course subjects vaccinated with influenza vaccine Significant increases in left-

sided anterior (prefrontal) activation (associated with positive mood)

Increase in antibody levels Davidson RJ Psychosom

Med. 2003;65(4):564-70.

Sleep, health and depression

Poor sleep associated with poor health – e.g. immunity, hypertension, cardiovascular disease, accidents, poor performance and memory…

Detailed histories from depressed patients reveal that it is common for sleep disturbance to precede lowered mood i.e. chronically poor sleep is a major risk factor for mood

disorders

Chronic insomnia trebles the chance of depression

Increased risk four times greater for women and twice as great for men

Insomnia second to bereavement as a risk factor for depression: more significant than a previous episode of depression

Holsboer-Trachsler E, Seifritz E. World J Biol Psychiatry. 2000;1(4):180-6.

Buysse DJ. Geriatrics 2004;59(2):47-51.

Riemann D, Voderholzer U. Journal of Affective Disorders 2003;76(1-3):255-9.

Cole MG. Dendukuri N. American Journal of Psychiatry. 2003;160(6):1147-56.

Mallon L, Broman J, Hetta J. Int Psychogeriatr. 2000;12(3):295-306.

Enhanced sleep and depression

Melbourne-based study on people with clinical depression Non-drug “Sleep Better – without drugs” program

75-80% significantly improved their sleep over the following 2 months

Of those who improved sleep, depression resolved in 57% and improved (by >40%) in another 13%

Findings replicated in other studies on other behavioural interventions for insomnia in those with depression

Morawetz, David. Sleep Research Online 5(2): 77-81, 2003. http://www.sro.org/2003/Morawetz/77/ .

Germain A, Moul DE, Franzen PL, et al. J Clin Sleep Med. 2006;2(4):403-6.

Meditation and compassion

Limbic brain regions implicated in empathic response to another's pain

Meditators have more active empathic response

Activation in insula greater in expert than novices

Empathy w/o stress reduces carer fatigue Lutz A, Brefczynski-Lewis J, Johnstone T, Davidson RJ.

PLoS ONE. 2008 Mar 26;3(3):e1897.

Caring for the brain

1. Learn to manage stress and difficult

emotions and cultivate healthy emotions

and attitude

2. Lead a healthy lifestyle

3. Sleep well

4. Take care choosing what to practice

What we practice we will get good at

5. Choose carefully the food we feed the mind

6. Cultivate mindfulness