1.Happiness and the brain Dick Swaab Netherlands Institute for Neuroscience, Amsterdam. .

2. Reward and Happiness

Sensory pleasuresare linked tofoodandsex(evolutionary importance, but also responsible for overpopulation and obesity).

Social pleasures :social interactions, romantic love, pair bonding, maternal love.

Higher-order pleasures : artistic, scientific monetary, musical, altru i stic and transcendental pleasures, may lead tohappiness .

Also transcendental pathology (TLE, mania)

Anhedonia:depression, schizophrenia, autism

Brain mechanisms : genetic and epigenetic factors

3. VMAT-2: associated withself-transcendence scaleof spirituality (Cloninger) 4. TLE A patient with ecstatic epileptic attacs saw Jesus. He had an astrocytoma of thetemporal lobe. The attacs diappeared after temporal lobectomy. 5.

The air was filled with a big noise, and I thought it had engulfed me. I have really touched God. He came into me myself; yes, God exists, I cried, and I don't remember anything else. You all, healthy people, he said, can't imagine the happiness we epileptics feel during the second before our attack. I don't know if this felicity lasts for seconds, hours, or months, but believe me, for all the joys that life may bring, I would not exchange this one.

(Dostoevsky, The Idiot).

6. Carmelite Nuns

Re-experience most mystic Christian experience in fMRI.

(i) activation midtemporal gyrus (~temp. lobe epilepsy; being one with God).

(ii) activation Caudate Nucleus (happiness and unconditional love).

(iii) activation brainstem, insula and PFC (emotional, somatoviscerale en autonomic reactions and cortical conciousness)

(iv) activation parital cortex (out of body experience: disturbed integration of somatic-visual-equilibrium information).

7. Yoga 8. 9. 10. 11.

Happiness is a physical state of the brain that can deliberately be induced, e.g. by meditation, ecstatic experiences of monks and nuns, meditation,

Pathology: TLE, mania .

12. 13. 2 times more martial problems, 2 times more unfaithful. 14. 15. OXT/AVP

OXT/AVP: - released during orgasm,

- reinforces social signals

- attachment and pair bonding (via DA).

.OXT:- mother-infant interaction

- maternal behavior via DA

- high levels related to intense romanticlove.

- increases trust, willingness to invest (viaAmygdala)

16. Coding versus causality

Pleasure codingin many brain areas (fMRI. PET): orbitofrontal cortex, anterior cingulate, insula, amygdala, nucleus accumbens, ventral pallidum, VTA,

- Cortex deactivated in romantic love and maternal love.

Some areas aresufficient :stimulation induces a pleasant feeling.

- Hedonic hotspots : Nucl. Accumbens, ventral pallidum and nucleus brachialis.

- Selfstimulation hotspots : laterallateral hypothalamus, septum, nucleus accumbens and medial forebrain bundle

Few areas arenecessary (reward function lost after lesion) :

- Ventral pallidum, extended amygdala and subst. innominata for sweet.

- Hypothalamus for sexual behavior, pairbonding, maternal behavior

17. Kent et al., Psychopharmacol. (2008) 199: 457-480 pleasantness odors water during thirst taste and smell monetary reward Medial OPFC 18. Kent et al.,OFC and pleasantness ratings of food 19. 20. 21. 22. Coding versus causality

Pleasure codingin many brain areas (fMRI. PET): orbitofrontal cortex, anterior cingulate, insula, amygdala, nucleus accumbens, ventral pallidum, VTA,

Some areas aresufficient :stimulation e.g. with opiates induces a pleasant feeling.

- Hedonic hotspots : Nucl. Accumbens, ventral pallidum and nucleus brachialis.

- Selfstimulation hotspots : laterallateral hypothalamus, septum, nucleus accumbens and medial forebrain bundle

Few areas arenecessary (reward function lost after lesion) :

-ventral pallidum, extended amygdala and subst. innominata for sweet,

- Hypothalamus for sexual behavior, pairbonding, maternal behavior

23. 24. 25. Hedonic hotspots : Nucl. Accumbens, ventral pallidum and nucleus brachialis.Kent et al., Psychopharmacol.,(2008) 199: 457-480 26. Coding versus causality

Pleasure codingin many brain areas (fMRI. PET): orbitofrontal cortex, anterior cingulate, insula, amygdala, nucleus accumbens, ventral pallidum, VTA,

Some areas aresufficient :stimulation induces a pleasant feeling.

- Hedonic hotspots : Nucl. Accumbens, ventral pallidum and nucleus brachialis.

- Selfstimulation hotspots : laterallateral hypothalamus, septum, nucleus accumbens and medial forebrain bundle

Few areas arenecessary (reward function lost after lesion) :

-ventral pallidum, extended amygdala and subst. innominata for sweet,

- Hypothalamus for sexual behavior, pair bonding, maternal behavior

27. 28. 29. OCD 30. Does DBS produce pure wanting rather than liking? 31. Coding versus causality

Pleasure codingin many brain areas (fMRI. PET): orbitofrontal cortex, anterior cingulate, insula, amygdala, nucleus accumbens, ventral pallidum, VTA,

Some areas aresufficient :stimulation induces a pleasant feeling.

- Hedonic hotspots* : Nucl. Accumbens, ventral pallidum and nucleus brachialis.

- Selfstimulation hotspots : laterallateral hypothalamus, septum, nucleus accumbens and medial forebrain bundle

Few areas arenecessary (reward function lost after lesion) :

-ventral pallidum, extended amygdala and subst. innominata for sweet,

- Hypothalamus for sexual behavior, pair bonding, maternal behavior

32. * * 33. 2003:no tuber cinereum,no infundibulum,no pituitary stalk,no corp. mamill., no bottom of 3 rd ventricle(concirmed byendoscopy) TEMP, CLOCK and MEMORY DIET AGRRESION Not: sex, attention,sleep Craniopharyngioma,operation, 1990 (than 18 years old 34. Neurotransmitters and reward systems

VTA-NA: DA inhibited by cortisol

Opiates (Stimulation hotspots)

OXT, vasopressin: (social brain, pair bonding, romantic love, deficient in autism).

OXT inhibits amygdala (via GABA) and reduces fear. AVP has reverse effects.

5HT: appetite and mood, decreased in beginning of romantic love and (other) compulsive disorders.

35. 36. 37. 38. 39. 40. 41. Anhedonia

Depression* (cortisol inhibits DA release in VTA)

Schizophrenia

Addiction

42. 43. 44. A.Kalsbeek 45. 46. Anhedonia

Depression

Schizophrenia

Addiction*

47. 48. Makris et al., 49. 50. RR >2 for depression, schizophreniaand obesity, 1.6 for addiction. 51. 52. 53. Conclusions

Reward/happiness: genetic & epigenetic factors (e.g. dysmaturity)

Pleasure coding: PFC etc etc

Sufficient for reward: hedonic and selfstimulation hotspots

Necessary for reward (Ventr. Pall for sweet, Hypothalamus for sex and pair bonding)

Neurotransmitters- VTA-NA: DA, inhibited by cortisol

- Opiates Stimulation hotspots)

- Oxytocin, vasopressin (social brain, deficient in autism

Risk: polymorphisms and environmental factors

New therapy: DBS

54. 55. 56. Biol.Psych. 2008, 64, 192-2002. 57. Glucocorticoid hypothesis (Atypical depression)

hypercortisolemia in MD (Gold and Chrousos, 2002)

Glucocrticoid treatment: 33% (Mitchell and OKeane)(O)

Cushing syndrome (Gold et al., 1995) (O)

*SNPs GR gene NR3C1 (West et al., 2006)

*SNP MR gene (Kuningeas et al., 2007)

*Inhibitors of cortisol production as anti-depressants(O) (metyrapone, aminoglutethamide, ketoconazole) Reus et al. 1997; Murphy, 1997)

*GR-antagonist (mifepristone (RU486)) for psychotic(I) depression (Gold 2002, Belanoff et al 2002)

GR/MR receptor imbalance (Wang et al., 2008) (I)

Corticosteroids affect DA-system (anhedonia) (Dunlop and Nemeroff, 2007) (O)

58. 59. Happiness and the brain Dick Swaab Netherlands Institute for Neuroscience, Amsterdam. 60. Makris et al., 61. Neurotransmitters and reward systems

VTA-NA: DA, inhibited by cortisol

Opiates Stimulation hotspots)

Oxytocin, vasopressin (social brain, deficient in autism

62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. The neurobiology of depression Dick Swaab Netherlands Institute for Neuroscience, Amsterdam. Depression as a multi-causal networksyndrome 76. L-Dopa 77. 78. 79. 80. 81. 82.