Could TCM be described in terms of affective neuroscience ?

1. Could TCM bedescribed in terms of affectiveneuroscience? • integrationinto a TCM clinical synopsis • ( ppt-presentation) • 1st Revision MMXIV • 05/05/2014 • J.P.Fossion, MD • Scientificcommission Brussels • BVGA • Bibliography • The humancentralnervous system; Nieuwenhuys, Voogd, van Huiyzen • Springer Verlag, 3d revisededition, ’88 • Chinese syndromes in terms of a coherent unifying model in neuroscience- • preliminary report 2005; J.P.Fossion (RG full text) • The psyche in Chinese Medicine; Giovanni Maciocia; • ChurchillLivingstone 2009 • - Manual of Acupuncture; P.Deadman;

2. Could TCM bedescribed in terms of affectiveneuroscience? integrationinto a clinical synopsis Af f e c t i v e d i sorde r s Clinical Synopsis TCM 1st revision MMXIV Jean Pierre Fossion MD Scientific commission Brussels

3. Affective Disorders integration TCM & affectiveneuroscience DeficiencySyndromes Full Syndromes StagnationLiver Qi SHEN Spirit or the awareness to Anticipate HUN ethereal soul or coping styles to Participate Hot Pole Cold Pole Full Fire Kidney-Yang Zhi Will-power or the drive to survive individually & as species Wind

4. Affective Disorders DeficiencySyndromes Full Syndromes frustration StagnationLiver Qi Thermogenesis Glu Full Fire Cold Pole Hot Pole Kidney-Yang DA (over)compensation l.&dl.PAG decompensation vl.PAG depression <- -> mania Wind

5. Deficiencies Premature responding hyperreflexia, easy startle, easily distracted def.Blood Dorsalstriatum Hyperaesthetic Emotional Syndrome Restless Organs/ Zang Zao restlessness (motor) unrest (mental) Organ: Lu, He Dizziness, ear-tingling Fear (Spl) <-> Anxiety (Ki) t°R restlessness (motor) unrest (mental) Iped striatum Three ttiers ventral striatum def.Yin Nucleus accumbens(core & shell) Impulsive choice impatience, immediate satisfaction

6. Deficiencies Heart palpitations β-blockers nebivolol He + Spl: Fear (XinJi) cardioexcitation BDZ tranquilizer anxiolytic, aversiveconditioning, sleep-induction def.Blood HES/ Restless Organs/ Zang Zao Medication side effects: asthenia -> concealed asthenia -> revealed asthenia BDZ tranquilizer anxiolytic, aversiveconditioning, sleep-induction propranolol He + Ki: Anxiety (ZhengChong) PanicThrobbing def.Yin Alprazolam Panicattack He + Lu Sorrow (Bai He Bing)

7. All deficiencies Heart palpitations β-blockers He + Spl: Fear (XinJi) cardioexcitation def.Blood HES/ Restless Organs/ Zang Zao Medication side effects: asthenia -> concealed asthenia -> revealed asthenia Asthenia Anorexia Anhedonia Antidepressant Activating (non-sedative!) YU (decompensation) Kidney-Y. Spl.(Y-Qi) Spleen-Qi 3 Yang-Qi deficiencies Decompensation Learned helplessness Porsolt-test Major depression cf. Cloninger: Harm Avoidance 5HT↑ & 5HTT↓ BDZ tranquilizer anxiolytic, aversiveconditioning, sleep-induction He + Ki: Anxiety (ZhengChong) PanicThrobbing def.Yin He + Lu Sorrow (Bai He Bing)

8. Limbic circuits of “deficiencies” in TCM Limbic computation medial forebrain: risk assessment He + Spl: Fear (XinJi) cardioexcitation def.Blood Fearconditioning Cue-related amygdala (Am.ce) HES/ Restless Organs/ Zang Zao He + Ki: Anxiety (ZhengChong) PanicThrobbing def.Yin Anxietyconditioning Context-related extendedamygdala (BNST)

9. limbic circuits of “deficiencies” in TCM subGenual subregion Rodent: PL Cx IL Cx Mammal: preGenual Cx subGenual Cx YU (decompensation) Side effects: Asthenia -> revealed - -> concealed - Major depression def.KidneyYang Spl.(Y-Qi) Spleen-Qi SNr↓: inhibition rewardpredictionerror aB 25↑ aB 32↓ Acc ↓ Apathy - anhedonia behaviouralinhibition, delayingreward LearnedHelplessness visceral motor cortex aB25 subGenual subregion ventral striatum: Nu. Accumbens SNc HES Zang Zao (restlessness) SNr def.Kidney Yin cf.A.Damasio somatic marker(s) InterPeduncular nucleus SNc↑: DAexpectation of reward aB 32↑ aB 25↓ Acc ↑ Impulsive choice impatience, immediate satisfaction exploratory behaviour actionreversal

10. Addiction DA↑ ↓ l.Hab degeneration pos.symptoms psychosis (phlegm-heat) Smoking Nicotin ↓ m.Hab degeneration relaxing (settling E ffect) • Med.forebrain: • risk assesment • approach • breaking point • avoidance • + memory • m.S->Hc epi- thalamus • Affective neuroscience • stress coping styles • hardwired • reinforcement learning • plasticity Passiveavoidancel.Hab: Glu Inescapableorunavoidable stress coping style YU (decompensation) Major depression Kidney-Ya Spl.(Y-Qi) Spleen-Qi SNr↓inhibition of DA rewardpredictionerror prox.Raphe: cf. Cloninger l. DRN: passiveavoidance Apathy - anhedonia learnedhelplessness, behaviouralinhibition Contextualanxiety: Kidney extendedamygdala sub- lenticular . amygdala HES Zang Zao (restlessness) activeavoidance Kidney Yin SNc↑: DA↑expectation of reward Approachbehavior: Yang ApproachinhibitedifnegativerewardpredictionerrorYin -> devaluation -> omission Impulsive choice impatience, immediate satisfaction Active avoidancem.Hab.→IPed Escapableoravoidable stress coping “flightpattern”

11. med.fB -  rVLM: visceral alert 86% SLEA shifts in pos.& neg.salience 77% Am.ce fear encoding 59% BNST anxiety encoding 56% IPAC (non-fundus striati/putamini) fear TAN cholinergic interneurons Procedural memory -> stroma sensorimotor reflexes salinecy -> striosome patches limbic functions relevancy Concept of “Blood” = stroma -> sensorimotorreflexes -> + sensorimotorgating(OCD) Concept of Yin = TAN pauze & Yang = TAN: -> limbicfunctions = patches -> oppositeoutcome -> neg.&pos.psychosis = Phl

12. CART mapping rodent

13. Neurosis pattern configurations150 BC: stress coping styles Full syndromes Deficiencies Frustration Dysphoria BDZ tranquilizer anxiolytic, aversiveconditioning, sleep-induction St.Liver Qi St.Blood def.Blood Gb irritability HES/ Restless Zang YU (stagnation) Defensive aggression Antidepressant activating YU (decompensation) Ascending Yang Full Fire def. KiYang Spl.(Y-Qi) Spleen-Qi anger 3 Y -Qi DEFICIENCIES Liv.Fire indignation St Fire Gb39 reproduction Deficient Fire P.Deadman def.Yin BDZ Alprazolam Panicattack Ki.Fire Liv.Fire Wind St Fire Gb39 BDZ Clonazepam (anticonvulsive) e.g. neck pain Ki.Fire

14. Dian-Kuang soft-hard madness Frustration Dysphoria St.Liver Qi St.Blood def.Blood postpartum psychosis HES/ Restless Zang Defensive aggression 3 Y-Qi DEFICIENCIES Full Fire Kidney-Y. Spl.(Y-Qi) Spleen-Qi TAN occludes (mental) “Heartopenings” Phlegm-Cold Phlegm - Heat PSYCHOSIS exception def.Yin Wind

15. St.Liver Qi def.Blood YU reactional depression atypical depression boulimic Monopolar depression YU Learned helplessness Full Fire Kidney-Y. Spl.(Y-Qi) Spleen-Qi BipolardepressionDian Congenitalpredisposition TAN: Ming dynasty 15th century ManiaKuang 5HT2-R + blocker D2-R Phlegm-Cold Dian Phlegm -Heat Kuang DA↓ 5HT1A-R– naturalligand • mental retardation • physicalhyporeflexia • weightgain PSYCHOSIS negative signs positive signs def.Yin def.Yin 5HT↑ typical =D1-R&D2-R neuroleptic atypical SSRI OCD D1-R 5HT = subtypical effect dependsonreceptor subtype Wind tardivedyskinesia (extrapyramidal)

16. OS - -> PS visceral alert m.fB->rVLM postprandialdistension m.fB->DVC fear (a.o.) guilt St.Liver Qi St.Blood def.Blood YU reactional depression anorexia (adHD) hyperkinetic disorder atypical depression boulimic YU Major depression anhedonia seasonalaffective disorder Full Fire Kidney-Y. Spl.(Y-Qi) Spleen-Qi DA↓ 5HT2A/C-R block HES/ Restless Organs: Zang Zao Phlegm - Heat anxiety def.Yin 5HT↑ MEL (a)typical neuroleptic sleep phase shift extrapyramidal (ADhd) attention deficit disorder Wind SSRI OCD acroparesthesia pruritus urticaria tremor Agomelatine Lighttherapy

17. St.Liver Qi def.Blood reactional depression atypical depression boulimic Monopolar depression Learned helplessness Full Fire Kidney-Y. Spl.(Y-Qi) Spleen-Qi Bipolardepression Congenitalcondition Mania Phlegm-Cold Phlegm - Heat DA↓ PSYCHOSIS negative signs positive signs def.Yin 5HT↑ (a)typical neuroleptic St40 Liv5 Ki6 Plumpit Qi SSRI OCD He7 Gb37 Spl1, St45, Gb44 Parasomnia He7 Ki4 Dementia

18. Transormations between pattern configurations Wind: Xian (fever) convulsions epilepsy Consumes Blood & Yin: PS hypo-activity Full Fire defensiveaggression deficiency of Yin: HyperaestheticEmotionalSyndrome Irritation-> anger PAG: NK1 -> CCK def. Fire: Zang Zao OS-hyper-activity Stagnation of LiverQi: Frustrationdysphoria

19. Liv3 Gb41 Bl18 Liv13 Liv14 Chinese transformationsbetweenpatternconfigurations (5HT- & NA-) RUI SNRI (venlafaxine) (5HT- & NA-) RUI - Fear (cue-related) • frustration dysphoria • irritation • impatience He5 St.Liver Qi def.Blood Liv.Blood: Liv3,Ki5 NA • frequent sighing • postprandial distension • photophobia • phonophobia • postmenopauzal dysph. • premenstrual tension • Late luteal phase/ PMDD: 02g-R, COMT-gene, 5HT↓ Liv 1, 2, 3, 4 Liv4, St41 • hyperreflexia, easy startle • cold fingertips (& -toes) Gb41 Spl2, Liv2, St44 Liv3, Gb41, Gb37 • mental unrest • motor unrest • asthenia (concealed form) HyperaestheticEmotionalSyndrome RestlessOrgans St37, St44 He7, He6, He5, He4 SI7, Pc8 Spl6, Pc6, RM6 Gb37, Gb41 • impatience • hot fingertips & toes Gb44 Ki6, Spl2,4,6 BDZ tranquilizer anxiolytic, aversive conditioning, sleep-induction First choice needling suggested by P.Deadman def.Yin Liv.Yin: Liv3, Bl18 5HT - Anxiety (context-related) Gb39 (5HT- & NA-) RUI LC: NA -> sensorimotor “attention”: easilydistracted Raphe: 5HT -> risk assesment (cf. Cloninger: avoidance) Anxiolytic SSRI (paroxetin/ sertralin)

20. VTA: DA +->Acc.: mesolimbic DA (5HT- & NA-) RUI Curcumine Passifloraincarnata Panax Ginseng • frustrationdysphoria • generalizedindifference St.Liver Qi frustration dysphoria The 3 Yang-Qi deficiencies OS - -> PS Major Depression (monopolar) Burn out syndrome Learned Helplessness Liver dominating Spleen reactional depression reversible IMAO-A (5HT-NA-DA) TCA: Amitryptilin (75mg?) Sedative/ insomnia • anorexia • postprandial distension • sighing • constipation (dry stools) • cold fingertips & toes Kidn.Yang Spl.(Y-Qi) Spleen-Qi 5HT-RUI/ SSRI S-NA RI/ SNRI • - daytime somnolence • genital anhedonia • abdominal distension • undigested food • internal cold • oedema • Asthenia (revealed form) • Anorexia/nausea • Anhedonia Liv2 Liv3 TCA ? Imipramin/ activating alternating • postprandial distension • loose stools • dyspnea • cold fingers & toes • memory loss Spl9 - fluid stagnation (sweating)

21. St.Liver Qi - frustration dysphoria He5 The 3 Yang-Qi deficiencies Major Depression (neurotic) Reward Deficiency Syndrome Learned Helplessness • reactional depression • Liver dominating Spleen Liv4 • anorexia (eating delayed) • sighing • postprandial distension • constipation • cold fingertips & toes Kidney-Y. Spl.(Y-Qi) Spleen-Qi • Asthenia (revealed ) • Anorexia (vitalistic) • Anhedonia • daytime somnolence • genital anhedonia • abdominal distension • undigested food • internal cold • oedema St36 Spl3 Spl6 TB6, Ki6 Liv2 Liv3 Spl6 • nausea • loose stools • dyspnea • cold fingers & toes Pc6 Spl9 Lu7, Ki4 Spl2, Ki3 Bl23, DM4, Ki2 -stagnation of fluids Lu5

22. Affective Disorders DeficiencySyndromes Full Syndromes Dian “soft madness” Kuang “hard meadness” StagnationLiver Qi Glu-ergict°-geneticaxis POHA/ AV3V: Glu -> DM/ hT: Glu -> RPa (cold-induced) Heat production Glu Full Fire Cold Pole Hot Pole Kidney-Yang DA DA-ergic (meso)limbicaxis VTA: DA -> Acc.: Rewardexpectancy VTA: DA -> striatum :Exploratorybeh. Wind

23. Dynorphine Carlezon/ CREB “runners’ high” (5HT- & NA-) RUI κ-OR - frustration dysphoria St.Liver Qi • postprandial distension • anorexia • constipation • cold fingertips (& toes) • postprandialdistension • anorexia • constipation • coldfingertips & toes irritation μ-OR • hypersthenia • mania (overdrive) anger LiverFire CCK • acid regurgitation • boulimia • constipation • hot fingers & toes Insomnia Sedative TCA/ amitryptiline tryptizol

24. (5HT- & NA-) RUI - frustration dysphoria St.Liver Qi • postprandialdistension • anorexia • constipation • coldfingertips (& toes) • hypersthenia • mania St36 Full Fire animal models of experimental agression Liv2, St41 - defensive agression Liver Gb39, St37 - predatory agression Stomach Ki9, Ki1 - reproductive agression Kidney

25. Herman van Praag (Netherlands): anxiety/aggressiondrivendepression 5HT-deficiency depression R/ SSRI + -> 5HT1A-R What is fuelling the angriness? ASCENDING YANG Full Fire Liver - defensive agression Stomach DEF.FIRE - predatory agression Liver - defensive agression KidneyYin deficiency Kidney • reproductive agression • (PO/dimorphic) Stomach - predatory agression anxiety Kidney • reproductive agression

26. 5HT = subtypical 1R-- Fire 2R ++ Trigeminovascular headache Cave: central hyperthermia anger βB 5HT1A-R -- ASCENDING YANG LiverFire 5HT1B/D-R -- DA2-R ++ blocker 5HT2A/C-R ++ Cave: serotonine syndrome Anxiolytic SSRI paroxetin/ sertralin migraine Propranolol Inderal/ non-selectiveBetaBlocker DEF.FIRE 5HT atypicalAntipsychotic (olanzapine > risperidone) multiple GABA-agonist KidneyYin Wind anxiety trigeminal neuralgia Triptans tryptaminefamily: vasoconstriciton Carbamazepine anticonvulsant = “moodstabilizer” Surrenal Adrenalin: He Fire

27. Bl67 Bl64 Gb44 Gb37, Gb38, Gb40 • identicalanatomicalsubstratepostulation • pharmacology • needling varia wind fire alcohol Lu7 Pc7 DM22 SI3 TW3 eye pain Bl60 He9 DV1 Pc9 visual aura Ki6 Gb20 anger βB 5HT1A-R ASCENDING YANG LiverFire 5HT1B/D-R DA2-R blocker 5HT2A/C-R Serotonine syndrome Anxiolytic SSRI paroxetin/ sertralin migraine Propranolol Inderal/ non-selectiveBetaBlocker DEF.FIRE atypicalAntipsychotic (olanzapine > risperidone) multiple GABA-agonist 5HT KidneyYin Wind anxiety trigeminal neuralgia Triptans tryptaminefamily: vasoconstriciton Carbamazepine anticonvulsant = “moodstabilizer” SurrenalAdrenalin Heart Fire

28. Af f e c t i v e d i sorde r s Thankyou ! TCM Clinical Synopsis 1st review MMXIV Jean Pierre Fossion MD Scientific commission Brussels