Neural regulation of human life processes

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processes – from the neuron to the behaviour. Interdisciplinary teaching

material concerning the structure, function and clinical aspects of the

nervous system for students of medicine, health and life sciences in

Hungary

Edited by Editors: János Kállai, Sámuel Komoly, Valér Csernus Ábrahám Hajnalka; Ács Péter; Albu Mónika; Balás István; Benkő András;

Birkás Béla; Bors László; Botz Bálint; Csathó Árpád; Cséplő Péter; Csernus Valér; Dorn Krisztina; Ezer Erzsébet; Farkas József; Fekete Sándor; Feldmann

Ádám; Füzesi Zsuzsanna; Gaszner Balázs; Gyimesi Csilla; Hartung István;

Hegedűs Gábor; Helyes Zsuzsanna; Herold Róbert; Hortobágyi Tibor; Horváth Judit; Horváth Zsolt; Hoyer Mária; Hudák István; Illés Enikő; Jandó Gábor;

Jegesy Andrea; Kállai János; Karádi Kázmér; Kerekes Zsuzsanna; Kereszty Éva; Koller Ákos; Komoly Sámuel; Kovács Bernadett; Kovács Norbert; Kozma Zsolt; Kövér Ferenc; Kricskovics Antal; Lenzsér Gábor; Lucza Tivadar; Mezősi

Emese; Mike Andrea; Montskó Péter; Nagy Alexandra; Nagy Ferenc; Pál Endre; Péley Iván; Pethő Gábor; Pethőné Lubics Andrea; Pfund Zoltán; Pintér Erika; Porpáczy Zoltán; Pozsgai Gábor; Reglődi Dóra; Rékási Zoltán; Schwarcz

Attila; Sebők Ágnes; Simon Gábor; Simon Mária; Sipos Katalin; Szapáry László; Szekeres Júlia; Szolcsányi Tibor; Tamás Andrea; Tényi Tamás;

Tiringer István; Tóth Márton; Tóth Péter; Trauninger Anita; Vámos Zoltán;

Varga József; Vörös Viktor, Dialóg Campus Kiadó

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students of medicine, health and life sciences in Hungary

by Editors: János Kállai, Sámuel Komoly, Valér Csernus and Ábrahám Hajnalka; Ács Péter; Albu Mónika;

Balás István; Benkő András; Birkás Béla; Bors László; Botz Bálint; Csathó Árpád; Cséplő Péter; Csernus Valér;

Dorn Krisztina; Ezer Erzsébet; Farkas József; Fekete Sándor; Feldmann Ádám; Füzesi Zsuzsanna; Gaszner Balázs; Gyimesi Csilla; Hartung István; Hegedűs Gábor; Helyes Zsuzsanna; Herold Róbert; Hortobágyi Tibor;

Horváth Judit; Horváth Zsolt; Hoyer Mária; Hudák István; Illés Enikő; Jandó Gábor; Jegesy Andrea; Kállai János; Karádi Kázmér; Kerekes Zsuzsanna; Kereszty Éva; Koller Ákos; Komoly Sámuel; Kovács Bernadett;

Kovács Norbert; Kozma Zsolt; Kövér Ferenc; Kricskovics Antal; Lenzsér Gábor; Lucza Tivadar; Mezősi Emese; Mike Andrea; Montskó Péter; Nagy Alexandra; Nagy Ferenc; Pál Endre; Péley Iván; Pethő Gábor;

Pethőné Lubics Andrea; Pfund Zoltán; Pintér Erika; Porpáczy Zoltán; Pozsgai Gábor; Reglődi Dóra; Rékási Zoltán; Schwarcz Attila; Sebők Ágnes; Simon Gábor; Simon Mária; Sipos Katalin; Szapáry László; Szekeres Júlia; Szolcsányi Tibor; Tamás Andrea; Tényi Tamás; Tiringer István; Tóth Márton; Tóth Péter; Trauninger Anita; Vámos Zoltán; Varga József; Vörös Viktor

Publication date 2016

Copyright 2016., Ábrahám Hajnalka; Ács Péter; Albu Mónika; Balás István; Benkő András; Birkás Béla; Bors László; Botz Bálint; Csathó Árpád; Cséplő Péter; Csernus Valér; Dorn Krisztina; Ezer Erzsébet; Farkas József; Fekete Sándor; Feldmann Ádám; Füzesi Zsuzsanna;

Gaszner Balázs; Gyimesi Csilla; Hartung István; Hegedűs Gábor; Helyes Zsuzsanna; Herold Róbert; Hortobágyi Tibor; Horváth Judit;

Horváth Zsolt; Hoyer Mária; Hudák István; Illés Enikő; Jandó Gábor; Jegesy Andrea; Kállai János; Karádi Kázmér; Kerekes Zsuzsanna;

Kereszty Éva; Koller Ákos; Komoly Sámuel; Kovács Bernadett; Kovács Norbert; Kozma Zsolt; Kövér Ferenc; Kricskovics Antal; Lenzsér Gábor; Lucza Tivadar; Mezősi Emese; Mike Andrea; Montskó Péter; Nagy Alexandra; Nagy Ferenc; Pál Endre; Péley Iván; Pethő Gábor;

Pethőné Lubics Andrea; Pfund Zoltán; Pintér Erika; Porpáczy Zoltán; Pozsgai Gábor; Reglődi Dóra; Rékási Zoltán; Schwarcz Attila; Sebők Ágnes; Simon Gábor; Simon Mária; Sipos Katalin; Szapáry László; Szekeres Júlia; Szolcsányi Tibor; Tamás Andrea; Tényi Tamás; Tiringer István; Tóth Márton; Tóth Péter; Trauninger Anita; Vámos Zoltán; Varga József; Vörös Viktor

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material concerning the structure, function and clinical aspects of the nervous system for students of medicine, health and life sciences in Hungary ... lxxvi

1. 1. Peripheral nervous system ... 1

1. 1.a. Development of the peripheral nervous system (ontogenesis, phylogenesis, neural crest, placod, biochemical features). – Judit Horváth [Translator-reviser: Andrea Pethőné Lubics] .. 1

1.1. 1. Summary ... 1

1.2. 2. Introduction ... 1

1.3. 3. Phylogenetics ... 2

1.4. 4. Ontogenetics of the neural crest, placodes, and peripheral nervous system ... 2

1.4.1. 4.1. Formation of the neural tube and molecular regulation ... 2

1.4.2. 4.2. Development of the spinal cord ... 6

1.4.3. 4.3. Similarity between the structure of the brainstem and the spinal cord .. 7

1.4.4. 4.4. Histological differentiation of the nerve cells in the neural tube ... 7

1.4.5. 4.5. Spinal nerves ... 8

1.4.6. 4.6. The innervation pattern of the spinal nerve ... 9

1.4.7. 4.7. Myelination ... 9

1.5. 5. Neural crest formation ... 10

1.5.1. 5.1. Placodes ... 12

1.5.2. 5.2. The rhombomeres and the cranial neural crest ... 12

1.6. 6. Molecular regulation ... 14

1.6.1. 6.1. Homeobox and hox genes ... 14

1.6.2. 6.2. The role of hox genes and other transcription factors in the differentiation of the neural tube ... 15

1.6.3. 6.3. Neaural crest induction – molecular biological aspects ... 16

1.6.4. Test questions ... 16

2. 1.b. The organization of the peripheral nervous system (cranial- and spinal nerves, plexuses, spinal segments, ganglions, motor nuclei). – Andrea Pethőné Lubics [Translator-reviser: Péter Kiss] ... 19

2.1. 1. About the peripheral nerves in general ... 19

2.1.1. 1.1. Fiber composition of peripheral nerves ... 19

2.1.2. 1.2. Localization of the cell bodies of neurons the axons of which run in the peripheral nerves ... 20

2.2. 2. Spinal nerves ... 21

2.2.1. 2.1. Spinal roots. Formation of spinal nerves (Figure 2) ... 21

2.2.2. 2.2. Spinal nerves, spinal cord segments ... 24

2.2.3. 2.3. Segmental and peripheral innervation ... 25

2.3. 3. Cranial nerves ... 28

2.3.1. 3.1. Fiber composition of the cranial nerves in general ... 29

2.3.2. 3.2. Localization of the cell bodies of neurons whose axons run in the cranial nerves ... 30

2.3.3. 3.3. Fiber composition of the individual cranial nerves, nuclei of the cranial nerves ... 30

3. 1.c. The light- and electronmicroscopic structure of the peripheral nerves (axons, sheets, terminals). – Judit Horváth [Translator-reviser: Dóra Reglődi] ... 37

3.1. 1. Summary ... 37

3.3. 3. Nervous tissue in general ... 39

3.3.1. 3.1. The nerve cell ... 39

3.3.2. 3.2. Glial cells ... 44

3.4. 4. Light and electron microscopic structure of neurons ... 45

3.4.1. 4.1. Perikaryon ... 45

3.4.2. 4.2. Dendrites ... 47

3.4.3. 4.3. Axon ... 48

3.4.4. 4.4. Sheaths of nerve fibers ... 51

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3.4.5. 4.5. Types of nerve fibers ... 54

3.5. 5. Peripheral nerve ... 54

3.5.1. 5.1. Light microscopic structure of the peripheral nerve ... 55

3.6. 6. Degeneration and regeneration of nerve fibers ... 56

3.7. 7. Nerve terminals ... 56

3.7.1. 7.1. Receptors ... 57

3.7.2. 7.2. Effectors ... 60

4. 1.d. The onset and propagation of the action potential (molecular mechanism, physiology). – Gábor Jandó [Translator-reviser: Mary Ann Alston] ... 64

4.1. 1. Ion channels ... 64

4.2. 2. Resting membrane potential ... 68

4.3. 3. Ionic movement across the membrane ... 69

4.4. 4. Gating of ion channels ... 71

4.5. 5. Membrane Potential ... 74

4.6. 6. Action Potential ... 76

4.7. 7. Operation and structure of single ion channel ... 82

5. 1.e. Mechanical and biochemical factors controling the onset and propagation of the stimulus (drugs affecting stimulus onset and propagation). – Gábor Jandó [Translator-reviser: Mary Ann Alston] ... 86

5.1. 1. Non-variable (constant) electrical properties of the membrane ... 86

5.2. 2. Extracellular electrical stimulation of the nerve ... 89

5.3. 3. Chronaxie: the excitability constant ... 94

5.4. 4. Refractoriness ... 96

5.5. 5. Propagation of action potentials in nerves and its determinants ... 97

5.5.1. 5.1. Compound action potential ... 97

5.5.2. 5.2. Measurement of conduction velocity of the nerve ... 98

5.5.3. 5.3. Unmyelinated axon ... 100

5.5.4. 5.4. Myelinated axon ... 101

5.5.5. 5.5. Demyelinated axon ... 102

5.6. 6. Channel blockers, neurotoxins ... 103

5.7. 7. Temperature ... 104

5.7.1. 7.1. Effect of decreased skin temperature on conduction velocity ... 104

5.8. 8. Ionic homeostasis and excitability ... 104

5.8.1. 8.1. Potassium ... 105

5.8.2. 8.2. Calcium ... 105

5.8.3. 8.3. Hyperventilation-induced hypocalcaemia (respiratory alkalosis) ... 106

5.8.4. 8.4. Sodium ... 106

5.8.5. 8.5. Paresthesia ... 107

6. 1.f. The pathology of the peripheral nerves (inflammations, degeneration, trauma, tumors). – Ágnes Sebők [Translator-reviser: Eszter Kurdiné Molnár] ... 109

6.2. 2. Patterns of damage of the peripheral nervous system (topological diagnosis) . 110 6.2.1. 2.1. Neuronopathy - sensory and motor (injury of the neuronal cell body) 110 6.2.2. 2.2. Radiculopathy and polyradiculopathy ... 110

6.2.3. 2.3. Mononeuropathy and mononeuritis multiplex ... 111

6.2.4. 2.4. Plexopathy ... 111

6.2.5. 2.5. Polyneuropathy ... 112

6.3. 3. Complaints and symptoms of peripheral neuropathy patients ... 112

6.3.1. 3.1. Motor complaints and symptoms ... 112

6.3.2. 3.2. Tendon reflexes ... 112

6.3.3. 3.3. Complaints and symptoms accompanying sensory loss ... 112

6.3.4. 3.4. Autonomic dysfunction ... 112

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6.4. 4. Mechanism of injury and regeneration of the peripheral nerves ... 113

6.4.1. 4.1. Basic mechanism of injury of the peripheral nerves ... 113

6.5. 5. Basic mechanisms of traumatic nerve injuries ... 114

6.5.1. 5.1. Stretch-related injuries ... 114

6.5.2. 5.2. Laceration ... 114

6.5.3. 5.3. Crush or compression injuries ... 114

6.6. 6. Grading systems for traumatic nerve injury ... 114

6.6.1. 6.1. Seddon’s grading system ... 115

6.6.2. 6.2. Sunderland’s grading system ... 116

6.7. 7. Regeneration of the peripheral nerve ... 116

6.8. 8. Common forms of peripheral nerve injury (from the roots to the nerves) ... 116

6.8.1. 8.1. Mononeuropathies ... 116

6.8.2. 8.2. Common nerve root lesions (See Table 1.) ... 123

6.8.3. 8.3. Plexus injuries ... 125

6.9. 9. Infectious neuropathies ... 126

6.9.1. 9.1. Bacterial diseases ... 126

6.9.2. 9.2. Viral infections ... 128

6.9.3. 9.3. Parasites ... 129

6.10. 10. Tumors of the peripheral nerves ... 129

6.10.1. 10.1. Signs and symptoms, evaluation ... 129

6.10.2. 10.2. Benign non-neoplastic nerve tumors ... 130

6.10.3. 10.3. Benign nerve sheath neoplasms ... 130

6.10.4. 10.4. Malignant peripheral nerve sheet tumors (MPNST) ... 130

6.10.5. 10.5. Malignant tumors affecting the peripheral nerves ... 131

7. 1.g. Dysimmune neuropathies. – Zoltán Pfund [Translator-reviser: Tünde Cecília Mátyusné Csépány] ... 134

7.1. 1. Acute inflammatory neuropathies: Guillain-Barré syndrome variants ... 135

7.1.1. 1.1. Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 135 7.1.2. 1.2 Acute motor axonal neuropathy (AMAN) ... 139

7.1.3. 1.3. Acute motor sensory axonal neuropathy (AMSAN) ... 140

7.1.4. 1.4. Miller Fisher syndrome (MFS) ... 140

7.1.5. 1.5. Pandysautonomia ... 141

7.1.6. 1.6. Pure sensory/ganglionopathy GBS ... 141

7.1.7. 1.7. Acute small fiber neuropathy ... 142

7.2. 2. Chronic inflammatory neuropathies ... 143

7.2.1. 2.1. Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) 144 7.2.2. 2.2. Distal acquired demyelinating sensorymotor neuropathy (DADS) ... 148

7.2.3. 2.3. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) ... 149

7.2.4. 2.4. Multifocal motor neuropathy (MMN) ... 149

7.2.5. 2.5. Multifocal acquired motor axonopathy (MAMA) ... 151

7.2.6. 2.6. Chronic relapsing axonal neuropathy (CRAN) ... 151

7.2.7. 2.7. Chronic sensory ataxic neuropathy (CSAN) ... 151

7.2.8. Summary ... 152

8. 1.h. Genetic neuropathies. – Endre Pál [Translator-reviser: Judit Hamarné Sávay] ... 157

8.1. 1. Charcot-Marie-Tooth (CMT) disease ... 158

8.1.1. 1.1. Epidemiology ... 158

8.1.2. 1.2. History ... 158

8.1.3. 1.3. Clinical-genetical classification ... 159

8.1.4. 1.4. Clinical features ... 160

8.1.5. 1.5. Pathomechanism of CMT ... 166

8.1.6. 1.6. Diagnostic tests in suspected CMT ... 167

8.2. 2. Hereditary sensory-autonomic neuropathies (HSAN) ... 170

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8.2.1. 2.1. HSAN I ... 171

8.2.2. 2.2. HSAN II ... 172

8.2.3. 2.3. HSAN III (Familial dysautonomia, Riley-Day syndrome) ... 172

8.2.4. 2.4. HSAN IV (CIPA: congenital insensitivity to pain with anhydrosis) . 172 8.2.5. 2.5. HSAN V ... 172

8.2.6. 2.6. HSAN VI ... 172

8.2.7. 2.7. Congenital absence of pain sensation ... 172

8.2.8. 2.8. Paroxysmal extreme pain disorder (PEPD) ... 172

8.2.9. 2.9. Pathomechanism of HSAN ... 172

8.3. 3. Hereditary motor neuropathies (HMN) ... 172

8.3.1. 3.1. HMN I ... 173

8.3.2. 3.2. HMN II ... 173

8.3.3. 3.3. HMN III ... 173

8.3.4. 3.4. HMN IV ... 173

8.3.5. 3.5. HMN V ... 173

8.3.6. 3.6. HMN VI ... 173

8.3.7. 3.7. HMN VII ... 173

8.3.8. 3.8. Pathomechanism ... 174

8.4. 4. Hereditary episodic neuropathies ... 174

8.4.1. 4.1. Hereditary neuropathy with liability to pressure palsies (HNPP) ... 174

8.4.2. 4.2. Familial brachial plexus neuropathy (hereditary neuralgic amyotrophy) 174 8.5. 5. Hereditary neuropathy in systemic diseases ... 174

8.5.1. 5.1. Mitochondrial diseases ... 174

8.5.2. 5.2. Hereditary ataxias ... 175

8.5.3. 5.3. Disorders of lipoprotein metabolism ... 175

8.5.4. 5.4. Peroxisomal disorders (See also in chapter 7d!) ... 175

8.5.5. 5.5. Lysosomal storage disorders (See also in chapter 7d!) ... 176

8.5.6. 5.6. Non-lysosomal Leukodystrophies (See also in chapter 7d!) ... 176

8.5.7. 5.7. Porphyrias ... 176

8.5.8. 5.8. Familial amyloid polyneuropathy (FAP) ... 176

8.5.9. 5.9. Chediak-Higashi's syndrome (CHS) ... 177

8.5.10. 5.10. Infantile neuroaxonal dystrophy (INAD, Seitelberger's disease) .. 177

8.6. 6. Differential diagnostics ... 177

8.7. 7. Therapy ... 178

8.7.1. 7.1. Drug therapy ... 178

8.7.2. 7.2. Symptomatic therapy ... 178

8.7.3. 7.3. Surgery ... 178

9. 1.i. The cell biology of remyelination. – Péter Ács [Translator-reviser: Éva Mészégetőné Halmos] ... 183

9.2. 2. Biology of oligodendrocyte cells and physiological myelination ... 184

9.2.1. 2.1. Origin of oligondendrocyte precursor cells ... 184

9.2.2. 2.2. OPC cell migration ... 184

9.2.3. 2.3. OPC cells’ differentiation and myelination ... 185

9.3. 3. Regulation of myelination ... 185

9.4. 4. Relationship between physiological myelin and neurons ... 186

9.4.1. 4.1. Demyelination ... 187

9.4.2. 4.2. Remyelination ... 188

9.5. 5. Cytokines ... 191

9.5.1. 5.1. Tumor necrosis factor-alpha (TNF-α) ... 191

9.5.2. 5.2. Interleukin-1β (IL-1β) ... 191

9.6. 6. Chemokines ... 192

9.6.1. 6.1. CXCL12 ... 192

9.6.2. 6.2. CXCL1/CXCL2/CXCR2 ... 192

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9.7. 7. Toll-like receptors (TLR) ... 193

9.8. 8. Growth Factors ... 193

9.9. 9. Signal transduction pathways ... 194

9.10. 10. MicroRNAs ... 195

9.11. 11. Transcription factors ... 196

9.12. 12. Clinical overview ... 198

9.12.1. 12.1. Therapeutic options stimulating remyelination ... 198

9.12.2. 12.2. Regenerative treatment options in MS ... 199

9.12.3. 12.3. Exogenous stem cell therapy ... 199

9.12.4. 12.4. Endogenous cell therapy ... 199

10. 1.j. The effects of the intrauterine hormonal environment on the development of the neural system. – Júlia Szekeres [Translator-reviser: János Hamar] ... 206

10.2. 2. The effect of Adrenocorticotropic hormone (ACTH) on the immature nervous system ... 206

10.3. 3. The effect of thyroid hormones on the developing nervous system ... 207

10.4. 4. Steroids ... 207

10.4.1. 4.1. Neurosteroids ... 208

10.4.2. 4.2. Steroids and sexual dimorphism ... 210

10.4.3. 4.3. Perinatal steroid exposure affects behavioural patterns in adulthood 212 10.5. 5. Neural Sexual Differentiation in Humans ... 213

10.6. 6. Summary and conclusions ... 214

11. 1.k. Metabolic-, endocrine- and other diseases associated neuropathies.– Emese Mezősi 90%, Sámuel Komoly 10% [Translator-reviser: Péter Ács] ... 220

11.1. 1. The structure and function of the peripheral nervous system (basic concepts) 220

11.2. 2. Causes of peripheral neuropathies ... 221

11.2.1. 2.1. Diabetic neuropathy (DN) ... 224

11.2.2. 2.2. Alcoholism ... 228

11.2.3. 2.3. Heavy metal poisoning ... 228

11.2.4. 2.4. Chemotheurapeutics ... 228

11.2.5. 2.5. Vitamin B12 (cobalamin) deficiency ... 229

11.2.6. 2.6. Neuropathy associated with thyroid dysfunction ... 229

11.2.7. 2.7. Chronic kidney diseases ... 230

11.2.8. 2.8. Liver disorders ... 230

11.2.9. 2.9. Critical illness neuropathy ... 231

11.2.10. 2.10. AIDS ... 231

11.2.11. 2.11. Porphyrias ... 231

2. 2. Somatomotoric system ... 236

1. 2.a. The development of the somatomotoric system (ontogenesis and phylogenesis), its structure and general functions. – Valér Csernus [Translator-reviser: Gábor Rébék-Nagy] ... 236

1.1. 1. The motion ... 236

1.2. 2. The mechanism of the motion of the living creatures ... 236

1.3. 3. The phylogeny of the somatomotoric system ... 238

1.3.1. 3.1. The invertebrates ... 238

1.3.2. 3.2. The vertebrates ... 239

1.3.3. 3.3. The mammals. The development of the cerebral cortex ... 240

1.3.4. 3.4. The human cortex ... 241

1.3.5. 3.5. The cerebellum ... 242

1.4. 4. The ontogeny of the somatomotoric system ... 243

1.5. 5. The principles of the functions of the somatomotoric system ... 246

1.5.1. 5.1. The pyramidal system ... 247

1.5.2. 5.2. The extrapyramidal system ... 247

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1.5.3. 5.3. The control of the muscle tone ... 248

2. 2.b. The structure, function, control and pathology of the myoneural junction. – Zoltán Pfund [Translator-reviser: Tünde Cecília Mátyusné Csépány] ... 251

2.1. 1. Structure and function of neuromuscular junction ... 252

2.1.1. 1.1. Neuromuscular junction ... 252

2.1.2. 1.2. Acetylcholine receptor ... 252

2.1.3. 1.3. Mechanism of action ... 252

2.2. 2. Presynaptic disorders ... 253

2.2.1. 2.1. Lambert-Eaton myasthenic syndrome ... 253

2.2.2. 2.2. Botulism ... 256

2.2.3. 2.3. Tick paralysis ... 258

2.2.4. 2.4. Congenital presynaptic disorders ... 259

2.3. 3. Synaptic disorders ... 260

2.3.1. 3.1. Endplate acetylcholinesterase deficiency ... 260

2.3.2. 3.2. Congenital myasthenic syndrome associated with β2-laminin deficiency 261 2.4. 4. Postsynaptic disorders ... 261

2.4.1. 4.1. Myasthenia gravis ... 261

2.4.2. 4.2. Congenital postsynaptic disorders ... 270

2.4.3. 4.3. Congenital myasthenic syndromes with defects in mechanisms governing endplate development and maintenance ... 273

2.4.4. 4.4. Familial limb-girdle myasthenia ... 274

2.5. 5. Summary ... 274

3. 2.c. Corticospinal system (structure, function and pathology). – Zoltán Rékási [Translator-reviser: Dóra Reglődi] ... 280

3.1. 1. Pyramidal tract ... 281

3.1.1. 1.1. Origin of the corticospinal tract ... 281

3.1.2. 1.2. Parts, course and termination of the voluntary motor pathway ... 283

3.2. 2. Non-pyramidal descending pathways from the brainstem ... 286

3.2.1. 2.1. Medial brainstem pathways ... 286

3.2.2. 2.2. Lateral brainstem pathway ... 287

3.3. 3. Lesions of upper and lower motor neurons ... 287

3.3.1. 3.1. Upper motor neuron system ... 287

3.3.2. 3.2. Lower motor neuron system ... 288

3.3.3. 3.3. Localization of lesions in the central motor system ... 289

3.3.4. 3.4. Lower motor neuron disease ... 290

4. 2.d. Extrapyramidal system (the complex control of somatomotoric system) – principles, structure, features of the building blocks. – Valér Csernus [Translator-reviser: Gábor Rébék-Nagy] 295 4.1. 1. Introduction – the basics of the body movements ... 295

4.2. 2. The systems controlling our skeletal muscles ... 295

4.2.1. 2.1. The pyramidal system ... 296

4.2.2. 2.2. The extrapyramidal system ... 296

4.2.3. 2.3. The control of the muscle tonus ... 296

4.3. 3. The structure and functions of the extrapyramidal system ... 296

4.4. 4. The components of the extrapyramidal system ... 298

4.4.1. 4.1. The initiation (command channel) ... 298

4.4.2. 4.2. The movement-pattern store ... 298

4.4.3. 4.3. The feedback system ... 300

4.4.4. 4.4. The output of the cerebellum ... 302

4.4.5. 4.5. The internal feedback loops of the extrapyramidal system. The basal ganglia 302 4.5. 5. The output of the extrapyramidal system ... 304

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4.6. 6. Other locomotor control structures – out of the core of the extrapyramidal system 305

4.6.1. 6.1. Fasciculus longitudinalis medialis ... 305

4.6.2. 6.2. The tractus tectospinalis (Löwenthal) ... 306

4.6.3. 6.3. The tractus vestibulospinalis (Held) ... 306

4.6.4. 6.4. Tractus reticulospinalis ... 306

4.7. 7. A functional overview of the extrapyramidal system ... 307

4.7.1. 7.1. The backbone of the system ... 307

4.7.2. 7.2. An alternative output ... 307

4.7.3. 7.3. Feedbacks from sensory organs ... 308

4.7.4. 7.4. The control circuits ... 308

4.8. 8. The disorders of the extrapyramidal system, clinical data ... 309

4.8.1. 8.1. Congenital and perinatal damage ... 309

4.8.2. 8.2. Diseases of the extrapyramidal system ... 310

4.8.3. 8.3. Extrapyramidal symptoms of various diseases ... 310

5. 2.e. Control of muscle tone. – Márton Tóth [Translator-reviser: Katalin Eklicsné Lepenye] 313 5.1. 1. Passive muscle tone ... 313

5.2. 2. Active muscle tone ... 314

5.2.1. 2.1. Striated muscle ... 314

5.2.2. 2.2. Muscle receptors ... 314

5.2.3. 2.3. Nerve fibres ... 315

5.2.4. 2.4. Motoneurons ... 316

5.3. 3. Gamma-loop ... 317

5.4. 4. Higher centres taking part in modulation of active muscle tone ... 318

5.4.1. 4.1. Nucleus Deiters and formatio reticularis ... 318

5.4.2. 4.2. Cortex, cerebellum, formatio reticularis of medulla oblongata and nucleus ruber ... 318

5.5. 5. Pathological tone distributions ... 319

5.5.1. 5.1. Decorticational rigidity ... 319

5.5.2. 5.2. Decerebrational rigidity ... 320

5.5.3. 5.3. Rigor ... 320

5.5.4. 5.4. Hypotonia ... 320

6. 2.f. The pathology and clinics of the extrapyramidal (involuntary motor) system. – Márton Tóth [Translator-reviser: János Hamar] ... 324

6.1. 1. Tremors ... 324

6.1.1. 1.1. Resting tremor ... 324

6.1.2. 1.2. Essential or action tremor ... 324

6.1.3. 1.3. Intention tremor ... 324

6.1.4. 1.4. Physiological (postural) tremor ... 325

6.2. 2. Idiopathic Parkinson disease and other Parkinson syndromes accompanied by unconscious movement disorders ... 325

6.2.1. 2.1. The origin of „extrapyramidal” nomenclature ... 325

6.2.2. 2.2. Functional anatomy of the tracts of basal ganglia: a short summary . 325 6.2.3. 2.3. Parkinson-disease ... 325

6.2.4. 2.4. Parkinson-plus syndromes ... 329

6.2.5. 2.5. Dystonias ... 333

6.2.6. 2.6. Drug-induced movement disorders (tardiv dyskinesias) ... 334

6.2.7. 2.7. Wilson–disease ... 335

7. 2.g. The body schema, initiation and inhibition of the movements. Target oriented locomotion. – János Kállai [Translator-reviser: József Varga] ... 339

7.2. 2. Definitions of body image, body schema ... 339

7.3. 3. Disorders of body image and body schema ... 341

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7.3.1. 3.1. The body as a schema ... 341

7.3.2. 3.2. Body schema disorders ... 342

7.3.3. 3.3. The unity, dissociation and neuropsychological disorders of body schema and body image, asomatognosis ... 345

7.4. 4. The neurocognitive model of one’s own body-experience, the body matrix .... 349

7.5. 5. Summary ... 351

8. 2.h. The motivation of the motoric control; reward- and punishment. – János Kállai [Translator- reviser: Tibor Szolcsányi] ... 354

8.1. 1. Preface ... 355

8.2. 2. Learning and motor organization ... 355

8.2.1. 2.1. Classical conditioning ... 355

8.2.2. 2.2. Operant conditioning ... 357

8.2.3. 2.3. The basic concepts of the organization of behaviour ... 358

8.3. 3. Reward ... 358

8.3.1. 3.1. The basic elements of reward control in neuroscience ... 360

8.4. 4. Punishment ... 363

8.5. 5. The elements of goal-directed behaviour ... 365

8.5.1. 5.1. Goals ... 366

8.5.2. 5.2. Behavioural planning and strategy ... 366

8.6. 6. Motivational and emotional components of the self: what joins and what separates 366 8.7. 7. Parkinson’s disease, deficiency of the basal ganglia ... 368

8.8. 8. Huntington’s disease ... 368

8.9. 9. The effects of cerebellar disorders on the motor system ... 369

8.10. 10. Summary ... 369

9. 2.i. The temper in children and adults (genetics, development and integration of the neutotransmitter systems. János Kállai [Translator-reviser: Mária Hoyer] ... 372

9.2. 2. The general view of personality, the definition of temperament and character 373 9.2.1. 2.1. Temperament and character ... 374

9.2.2. 2.2. Childhood temperament ... 374

9.2.3. 2.3. Easy, difficult and slow-to-warm-up temperament as the basic dimension of behaviour ... 375

9.2.4. 2.4. Interaction approach to temperament. Reactivity and self-regulation 376 9.2.5. 2.5. Temperament and adult personality ... 378

9.2.6. 2.6. Introduction of Cloninger’s temperament factors ... 378

9.3. 3. Character factors ... 380

9.3.1. 3.1. Self-Directedness ... 380

9.3.2. 3.2. Cooperativeness ... 381

9.3.3. 3.3. Self-Transcendence ... 381

9.4. 4. Psychopathological relevance of temperament and character ... 381

9.4.1. 4.1. Connection between temperament factors and personality disorders 381 9.4.2. 4.2. Relationship between character factors and personality disorders .... 381

9.5. 5. Summary ... 382

10. 2.j. The effects of the mother-child relationship on the development of the nervous system. Approach – avoidance. – János Kállai 50%, Krisztina Dorn 50% [Translator-reviser: József Varga] 386 10.1. 1. Introduction ... 386

10.2. 2. Early attachment ... 387

10.2.1. 2.1. Definition of attachment ... 387

10.2.2. 2.2. Attachment behaviour ... 387

10.2.3. 2.3. The attachment system ... 388

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10.2.4. 2.4. Internal Working Model ... 388

10.2.5. 2.5. The function of attachment ... 389

10.2.6. 2.6. Supplementing, substituting the primary caregiver ... 390

10.2.7. 2.7. The interaction of social relations and the development of the nervous system ... 390

10.2.8. 2.8. The gradual development of attachment ... 392

10.3. 3. Attachment theory ... 393

10.3.1. 3.1. Historical background ... 393

10.3.2. 3.2. The experimental research concerning attachment and its effects .. 394

10.3.3. 3.3. Attachment types ... 395

10.3.4. 3.4. Multiple attachments ... 396

10.4. 4. If the attachment breaks or loosens: the consequences of deprivation ... 396

10.4.1. 4.1. Deficiencies in attachment ... 396

10.4.2. 4.2. Clinical implications, children’s psychopathology ... 397

10.5. 5. Attachment and the adult social relationships ... 398

10.5.1. 5.1. The investigation of adult attachment (AAI, Adult Attachment Interview) 398 10.5.2. 5.2. Affect regulation in adulthood, realistic self-esteem ... 399

10.5.3. 5.3. Adult psychopathology ... 399

10.5.4. 5.4. Application of attachment theory in psychotherapy ... 399

10.6. 6. Summary ... 399

11. 2.k. Functional neurosurgery interventions in treatment of movement disorders. – Norbert Kovács 50%, István Balás 50% [Translated by Katalin Eklicsné Lepenye, Translator-reviser: Dóra Reglődi] ... 403

11.2. 2. Clinically significant movement disorders ... 403

11.2.1. 2.1. Parkinson's disease ... 403

11.2.2. 2.2. Essential tremor ... 410

11.2.3. 2.3. Dystonia ... 410

11.3. 3. Deep brain stimulation ... 413

11.3.1. 3.1. Historical review of functional neurosurgery interventions ... 413

11.3.2. 3.2. Functional disciplines of deep brain stimulation ... 413

11.3.3. 3.3. Surgical investigation ... 416

11.3.4. 3.4. Surgical indications and effectiveness ... 417

11.3.5. 3.5. Operation ... 418

11.3.6. 3.6. Post-operative care ... 419

11.4. 4. Summary ... 419

12. 2.l. Rehabilitation of motorial system and health psychological principle of the healing. – Péter Montskó 60%, János Kállai 40% [Translated by János Kállai, Translator-reviser: Árpád Csathó] 424 12.1. 1. General issues of locomotor rehabilitation ... 424

12.2. 2. Rehabilitation for patients with lower limb deficiency ... 426

12.3. 3. The immobilization syndrome ... 428

12.4. 4. Rehabilitation of patients with post-stroke hemiplegia ... 429

12.5. 5. Rehabilitation of patients with cranial injury ... 430

12.6. 6. Rehabilitation of patients with spinal cord injury and transverse lesion ... 432

12.7. 7. Psychosocial aspects of locomotor rehabilitation ... 433

12.8. 8. Summary ... 434

3. 3. Somatosensory system ... 439

1. 3.a. Development of the somatosensory system (ontogenesis and phylogenesis), its structure and general functions. – Dóra Reglődi [Translator-reviser: Zoltán Rékási] ... 439

1.1. 1. General structure of the two main somatosensory pathways ... 440

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1.2. 2. General structure of the two main somatosensory systems ... 440

1.2.1. 2.1. Dorsal column / medial lemniscus system ... 440

1.2.2. 2.2. Spinothalamic tract ... 447

1.3. 3. General structure of the brainstem somatosensory pathways ... 453

1.3.1. 3.1. Trigeminal nucleus in the medulla – nucleus of the spinal tract of the trigeminal nerve ... 453

1.3.2. 3.2. Trigeminal nuclei in the pons and midbrain: principal nucleus and mesencephalic nucleus of the trigeminal nerve ... 454

1.4. 4. Brief summary of the evolutionary perspectives of the somatosensory system 455 1.5. 5. Short summary of the embryonic development of the somatosensory system 461

1.5.1. 5.1. Regulation of the axonal growth of sensory neurons during development 462 1.6. 6. Ending of somatosensory pathways – thalamus – somatosensory cortex ... 462

1.6.1. 6.1. Thalamocortical projection – primary sensory cortex ... 463

2. 3.b. Skin receptors (structure, functions, pathology). – József Farkas [Translator-reviser: Dóra Reglődi] ... 469

2.1. 1. The function of sensory receptors ... 470

2.2. 2. Sensory transduction and receptor potentials ... 470

2.2.1. 2.1. Receptive fields ... 471

2.2.2. 2.2. Sensory coding ... 474

2.2.3. 2.3. Adaptation of sensory receptors ... 475

2.2.4. 2.4. Somatosensory pathways ... 476

2.2.5. 2.5. Classification of sensory receptors based on their structure ... 477

2.2.6. 2.6. Classification of sensory receptors, based on the source of the stimuli 477 2.2.7. 2.7. Classification based on the modality of the stimulus ... 478

3. 3.c. Receptors of the sensory organs (retina, stato-acustic system, smelling, tasting – structure, functions, pathology). – Gábor Jandó [Translator-reviser: Mary Ann Alston] ... 491

3.1. 1. Vision ... 491

3.1.1. 1.1 Examination of the visual system ... 492

3.1.2. 1.2. The eye ... 498

3.1.3. 1.3. Retina ... 501

3.1.4. 1.4. Visual pathways ... 504

3.2. 2. Hearing ... 507

3.2.1. 2.1. Hearing tests ... 507

3.2.2. 2.2. Outer and middle ear ... 508

3.2.3. 2.3. Organ of Corti ... 509

3.2.4. 2.4. Auditory pathways ... 510

3.3. 3. The vestibular system ... 512

3.3.1. 3.1. Examination of the vestibular system ... 512

3.3.2. 3.2. Hair cells are the receptors of hearing and balance ... 513

3.3.3. 3.3. Semicircular canals ... 514

3.3.4. 3.4. Utricle and the saccule ... 515

3.3.5. 3.5. Vestibular nuclei ... 515

3.4. 4. Sense of taste ... 516

3.4.1. 4.1. Examination of taste ... 516

3.4.2. 4.2. Taste receptors ... 517

3.4.3. 4.3. Central taste pathways ... 518

3.5. 5. Sense of smell ... 518

3.5.1. 5.1. Examination of smell ... 519

3.5.2. 5.2. Receptors of smell ... 519

3.5.3. 5.3. Olfactory pathways ... 519

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4. 3.d. Anatomy of pain (receptors, pathways, processing, roles). – Valér Csernus [Translator-

reviser: Gábor Rébék-Nagy] ... 525

4.1. 1. The evolution of the pain sensory system ... 525

4.2. 2. The pain sensing receptors – the nociceptors ... 526

4.2.1. 2.1. Mechanical nociceptors ... 526

4.2.2. 2.2. Temperature sensing nociceptors ... 526

4.2.3. 2.3. Chemical nociceptors ... 526

4.2.4. 2.4. Silent nociceptors ... 526

4.2.5. 2.5. Polymodal nociceptors ... 526

4.3. 3. The afferentation of the pain sensation ... 526

4.3.1. 3.1. Sensory neurons of the spinal cord ... 527

4.3.2. 3.2. Pain sensory neurons of the cranial nerves ... 527

4.4. 4. The primary pain processing ... 528

4.4.1. 4.1. The substantia gelatinosa and its environment ... 529

4.4.2. 4.2. The function of the substantia gelatinosa ... 530

4.5. 5. The tractus spinothalamicus (Edinger) ... 532

4.6. 6. The pain-sensory pathways of the cranial nerves ... 534

4.7. 7. The visceral pain ... 534

4.8. 8. The sensory function of the thalamus. Somatosensory cortical areas ... 535

4.8.1. 8.1. Radiatio media (superior) thalami ... 535

4.8.2. 8.2. Radiatio anterior thalami ... 536

4.8.3. 8.3. Autonomic connections ... 537

4.8.4. 8.4. An overview of the central pain processing ... 538

4.9. 9. Other services and connections of the nociceptive system ... 538

4.9.1. 9.1. The nociceptive reflex ... 538

4.9.2. 9.2. The Head zones ... 539

4.9.3. 9.3. Muscle tone, reticular formation ... 541

4.10. 10. Medical relations of the pain ... 542

5. 3.e. Neuropathic and phantom pain. Influencing pain. – Zsuzsanna Helyes, Bálint Botz [Translator-reviser: Ian O'Sullivan] ... 544

5.1. 1. Introduction, etiology, symptomatology ... 544

5.1.1. 1.1. The definition of neuropathic pain, the classification of neuropathies 544 5.1.2. 1.2. The epidemiology of neuropathic pain ... 547

5.1.3. 1.3. The symptoms of neuropathic pain ... 547

5.1.4. 1.4. Special remarks on phantom limb pain ... 548

5.2. 2. Pathogenesis ... 548

5.2.1. 2.1. About the etiology of neuropathic pain in general ... 548

5.3. 3. Pathomechanisms ... 552

5.3.1. 3.1. The sensitization of sensory nerve endings (peripheral sensitization) 552 5.3.2. 3.2. The abnormal, ectopic excitation of the sensory nerve endings ... 553

5.3.3. 3.3. Pro-nociceptive (pain sensation-increasing) changes in the spinal dorsal root (central sensitization) ... 553

5.3.4. 3.4. The blockade of the spinal inhibitory system ... 553

5.3.5. 3.5. Pain maintained by sympathetic activation ... 553

5.3.6. 3.6. Central reorganization ... 554

5.3.7. 3.7. The characteristics of the development of phantom limb pain ... 554

5.4. 4. Pharmacotherapeutic management of neuropathic pain ... 554

5.4.1. 4.1. Drug groups used in the treatment of neuropathic pain ... 555

5.4.2. 4.2. The management of neuropathies caused by lesions of the central nervous system ... 556

5.4.3. 4.3 About the therapy of phantom limb pain ... 556

5.5. 5. EBM (Evidence Based Medicine) data ... 556

5.5.1. 5.1. Clinical studies in neuropathic pain ... 556

5.5.2. 5.2. Monotherapy vs. combinations ... 557

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5.5.3. 5.3. Clinical recommendations about the drugs currently on the market . 557

5.5.4. 5.4. Practical remarks on the therapy ... 558

5.5.5. 5.5. About the effectiveness of treatment ... 558

5.6. 6. Potential new therapeutic modalities (clinical and preclinical data) ... 559

6. 3.f. Other protopathic systems (extreme temperature, elementary touch). – Dóra Reglődi [Translator-reviser: Zoltán Rékási] ... 565

6.1. 1. Other protopathic sensory modalities ... 568

6.1.1. 1.1. Temperature ... 568

6.1.2. 1.2. Touch ... 568

6.1.3. 1.3. Crude touch ... 569

6.1.4. 1.4. Itch ... 572

6.1.5. 1.5. Ticklishness ... 573

6.2. 2. The central part of the protopathic system ... 573

6.2.1. 2.1. Spinal cord level: spinothalamic tract ... 573

6.2.2. 2.2. Brainstem level – nucleus of the spinal tract of the trigeminal nerve 574 6.3. 3. Some details to the spinothalamic system ... 575

6.4. 4. Ending of the spinothalamic tract: thalamus – somatosensory cortex ... 576

6.4.1. 4.1. Thalamocortical projection – primary sensory cortex ... 577

6.4.2. 4.2. Somatosensory cortex ... 578

6.4.3. 4.3. Sensory association areas ... 582

6.5. 5. Some interesting further reading on the other protopathic systems ... 583

6.5.1. 5.1. Lesion of the spinothalamic tract ... 583

6.5.2. 5.2. Plasticity of the somatosensory system ... 583

6.5.3. 5.3. Phantom sensation ... 583

6.5.4. 5.4. When only the somatosensory system remains – the story of Helen Keller 583 6.5.5. 5.5. Barrel cortex ... 584

6.5.6. 5.6. Crude touch and brain development ... 584

6.5.7. 5.7. Congenital analgesia and its relations to other protopathic systems . 584 6.5.8. Test questions ... 585

7. 3.g. Epicritic sensory system (receptors, pathways, processing, roles in motoric control). – Valér Csernus [Translator-reviser: Gábor Rébék-Nagy] ... 589

7.1. 1. The evolution of the sensory system ... 589

7.2. 2. An overview of the epicritic system ... 590

7.3. 3.Epicritic skin receptors ... 590

7.3.1. 3.1. Vater-Paccini corpuscle ... 590

7.3.2. 3.2. The Meissner body ... 591

7.3.3. 3.3. The Merckel body ... 592

7.3.4. 3.4. The Ruffini receptor ... 592

7.3.5. 3.5. Krause body ... 592

7.4. 4. Receptors of the locomotor system ... 593

7.4.1. 4.1. Muscle spindles ... 593

7.4.2. 4.2. Tendon organs ... 593

7.5. 5. Sensory neurons, sensory nerves ... 594

7.5.1. 5.1. Epicritic sensory neurons of the cranial nerves ... 594

7.5.2. 5.2. Spinal epicritic sensory neurons ... 594

7.6. 6. Epicritic sensory pathways ... 595

7.6.1. 6.1. Cranial epicritic sensory pathways ... 595

7.6.2. 6.2. Spinal epicritic sensory pathways ... 595

7.6.3. 6.3. Epicritic diencephalic and cortical areas ... 597

7.6.4. 6.4. Radiatio media (centralis) thalami ... 597

7.6.5. 6.5. The anterior thalamic radiation ... 598

7.6.6. 6.6. The autonomic irradiation ... 599

7.6.7. 6.7. An overview of the central processing of our epicritic sensations .... 599

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7.7. 7. The “services” of the epicritic sensory systems ... 599

7.7.1. 7.1. The proprioceptive reflex arch ... 599

7.7.2. 7.2. Pain analysis ... 600

7.7.3. 7.3. The spinocerebellar pathways ... 601

8. 3.i. Cognitive interpretation of somatosensory experiences. – Árpád Csathó 50%, Ádám Feldmann 50% [Translator-reviser: János Kállai] ... 606

8.1. 1. The problem of perception ... 606

8.2. 2. Somatosensory hallucinations ... 606

8.3. 3. Somatosensory illusions ... 607

8.3.1. 3.1. The Aristotle illusion (tactile diplopia) ... 607

8.3.2. 3.2. Mislocalizations in the somatosensory system ... 608

8.3.3. 3.3. Somatosensory illusions in size and weight perception ... 611

8.3.4. 3.4. Tactile variants of geometric illusions ... 612

8.3.5. 3.5. Illusions of the self-body perception ... 615

8.3.6. 3.6. A neurocognitive model of tactile information processing ... 618

9. 3.j. Mechanisms of pain of somatic-, neural- and mental origin. – Enikő Illés 60%, Sámuel Komoly 40% [Translated by Lilla Horváth, Translator-reviser: Dóra Reglődi] ... 623

9.2. 2. The pain phenomenon ... 625

9.2.1. 2.1. Definitions ... 625

9.2.2. 2.2. Components of pain ... 625

9.2.3. 2.3. Chronic Pain syndrome ... 626

9.3. 3. Somatoform disorders ... 629

9.3.1. 3.1. Pathogenesis of somatoform disorders: body-language instead of words is the language of pain ... 630

9.3.2. 3.2. Forms of somatic disorders ... 630

9.3.3. 3.3. Explanatory models of somatoform disorders ... 633

10. 3.k. Experience and memories of pain. – Zsuzsanna Kerekes [Translated by Lilla Horváth, Translator-reviser: Zsuzsanna Kerekes] ... 641

10.2. 2. Definition of pain and its main components ... 642

10.3. 3. Experience of pain and its signalling function ... 644

10.3.1. 3.1. Pain threshold and pain tolerance ... 644

10.3.2. 3.2. Pain as psychic experience and influencing factors ... 645

10.3.3. 3.3. Components of pain ... 647

10.3.4. 3.4. The context of pain experience ... 648

10.4. 4. Pain behaviour ... 650

10.5. 5. Types of pain ... 651

10.6. 6. Pain models ... 653

10.6.1. 6.1. Loeser’s pain model ... 653

10.6.2. 6.2. Gate control theory of pain ... 654

10.6.3. 6.3. The neuromatrix theory of pain ... 655

10.7. 7. Pain memory ... 656

10.8. 8. Summary ... 656

11. 3.l. Chronic pain experience and the cognitive therapy of analgesia. – Zsuzsanna Kerekes [Translated by Tímea Bencsik, Translator-reviser: Zsuzsanna Kerekes] ... 660

11.2. 2. Chronic pain ... 661

11.2.1. 2.1. Epidemiology ... 662

11.2.2. 2.2. Division of chronic pains ... 662

11.3. 3. Chronic pain and emotional control ... 664

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11.3.1. 3.1. The biological background of the emotional control in general ... 664

11.3.2. 3.2. Emotion regulation and strategies in chronic pain ... 664

11.3.3. 3.3. Relationship between negative and positive emotions and chronic pain 665 11.3.4. 3.4. Alexithymia and chronic pain ... 666

11.4. 4. Chronic pain and distress ... 666

11.4.1. 4.1. Chronic pain as a stressor ... 667

11.4.2. 4.2. Chronic pain caused by distress ... 667

11.5. 5. Chronic pain and anxiety ... 667

11.6. 6. Chronic pain and depression ... 668

11.7. 7. When acute pain becomes chronic ... 669

11.7.1. 7.1. Iatrogenic risk factors in the process of pain becoming chronic ... 669

11.8. 8. Development of chronic pain ... 670

11.8.1. 8.1. Psychosocial background of the process of acute pain becoming chronic 670 11.8.2. 8.2. Physiological background of development of chronic pain ... 673

11.9. 9. Results of chronic pain and disability caused by chronic pain ... 675

11.9.1. 9.1. Deconditioning syndrome ... 675

11.9.2. 9.2. Social exclusion and pain ... 676

11.9.3. 9.3. Chronic pain and cognitions ... 676

11.9.4. 9.4. Chronic pain and suffering ... 678

11.9.5. 9.5. Disability ... 678

11.10. 10. Acceptance of pain ... 678

11.11. 11. Examination of pain ... 679

11.11.1. 11.1. Questionnaires ... 680

11.11.2. 11.2. Interview ... 681

11.11.3. 11.3. Pain diary ... 682

11.11.4. 11.4. Observation ... 683

11.11.5. 11.5. Study protocol ... 683

11.12. 12. Management of pain ... 683

11.12.1. 12.1. Medicinal treatment ... 685

11.12.2. 12.2. Non-medicinal biological, surgical analgesia ... 685

11.12.3. 12.3. Cognitive therapies ... 685

11.12.4. 12.4. Other psychotherapies ... 689

11.12.5. 12.5. Pain clinics ... 689

11.13. 13. Summary ... 689

12. 3.m. Significance of the pain experience in actions for damages. – Andrea Jegesy [Translated by Anita Hegedűs, Translator-reviser: Andrea Tamás] ... 695

12.2. 2. Legal aspects ... 695

12.2.1. 2.1. Aspects related to criminal law ... 695

12.2.2. 2.2. Aspects related to civil law ... 697

12.3. 3. Assessment of the pain experience from the forensic medical expert's point of view 699 12.3.1. 3.1. Difficulties in determining entitlement to compensation ... 702

12.3.2. 3.2. The role of the medical practitioner in actions for damages ... 702

12.4. 4. Set of examples of judging compensation for pain in foreign countries (in this section the author relies on data obtained by Ágnes Dósa, with her permission) ... 703

13. 3.n. Headaches and other pain syndromes. – Ferenc Nagy [Translator-reviser: Sámuel Komoly] 709 13.1. 1. The diagnosis of headache ... 710

13.2. 2. The significance of history ... 710

13.2.1. 2.1. Age at Onset ... 711

13.2.2. 2.2. Localization ... 711

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13.2.3. 2.3. Frequency ... 711

13.2.4. 2.4. Intensity ... 711

13.2.5. 2.5. The character of pain ... 712

13.2.6. 2.6. Cousre ... 712

13.2.7. 2.7. The duration of headaches ... 712

13.2.8. 2.8. Prodrome ... 712

13.2.9. 2.9. Accompanying symptoms ... 712

13.2.10. 2.10. Precipitating factors ... 713

13.2.11. 2.11. Relieving factors ... 713

13.2.12. 2.12. Family history ... 713

13.2.13. 2.13. Neurological and physical examination ... 713

13.3. 3. Headaches that require urgent care ... 713

13.4. 4. Idiopathic headache syndromes ... 715

13.4.1. 4.1. Migraine ... 715

13.4.2. 4.2. Cluster Headache ... 718

13.4.3. 4.3. Paroxysmal hemicrania ... 719

13.4.4. 4.4. Tension-type headache ... 720

13.4.5. 4.5. Headache caused by the overuse of drugs (“medication overuse headache”, “medication-induced headache”) ... 721

13.4.6. 4.6. Atypical facial pain ... 722

13.4.7. 4.7. Trigeminal neuralgia (tic douloureux) ... 722

13.4.8. 4.8. Headache developed after lumbar puncture ... 723

14. 3.o. Pharmacological principles of analgesia. – Gábor Pethő [Translated by Gábor Pozsgai, Translator-reviser: Balázs Fülöp] ... 726

14.2. 2. Groups of drugs suitable for analgesia ... 726

14.3. 3. General principles of the application of analgesics ... 727

14.4. 4. Non-steroidal anti-inflammatory drugs (NSAIDs) ... 727

14.4.1. 4.1. Mechanism of the analgesic effect of NSAIDs ... 727

14.4.2. 4.2. Unwanted effects of NSAIDs ... 729

14.4.3. 4.3. Contraindications, pharmacokinetics and most important interactions of the NSAIDs ... 729

14.4.4. 4.4. Characteristics of the subgroups of NSAIDs ... 730

14.5. 5. Opioid analgesics ... 732

14.5.1. 5.1. Effects of the opioids and their receptorial background ... 732

14.5.2. 5.2. Main side effects of the opioids ... 734

14.5.3. 5.3. Acute opioid intoxication ... 734

14.5.4. 5.4. Contraindications of opioids ... 735

14.5.5. 5.5. Tolerance and dependence to opioids ... 735

14.5.6. 5.6. Subgroups of opioids ... 735

14.5.7. 5.7. Factors increasing clinical efficacy and therapeutic range of opioids 737 14.5.8. 5.8. Basic principles regarding therapeutic use of opioids ... 737

15. 3.p. Spinal cord stimulation as a neurosurgical treatment for pain. – István Balás [Translated by Eszter Kurdiné Molnár, Translator-reviser: Dóra Reglődi] ... 740

15.2. 2. Mechanism of Action ... 743

15.3. 3. SCS Operation Indications ... 743

15.3.1. 3.1. Complex Regional Pain Syndrome (CRPS) ... 744

15.3.2. 3.2. Post-laminectomy Syndrome ... 744

15.3.3. 3.3. Angina Pain ... 745

15.3.4. 3.4. Chronic Pain and Ischemia in the Extremities ... 746

15.3.5. 3.5. Abdominal and Visceral Pain Syndromes ... 747

15.4. 4. Relevant Anatomy ... 747

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15.5. 5. Devices used During the Operation ... 747

15.6. 6. Complications ... 748

15.7. 7. Conclusion ... 749

16. 3.q. The mental dissociation of experiences and posttraumatic somatosensory experiences. – Zsuzsanna Kerekes [Translated by Brigitta Hajnal, Translator-reviser: Zsuzsanna Kerekes] 757 16.1. 1. Introduction ... 757

16.2. 2. Consciousness, alertness ... 757

16.2.1. 2.1. Consciousness ... 757

16.2.2. 2.2. Alertness ... 759

16.2.3. 2.3. The Preconscious ... 759

16.2.4. 2.4. The Unconscious ... 760

16.2.5. 2.5. Divided Consciousness ... 760

16.3. 3. States of Consciousness ... 760

16.3.1. 3.1. Wakefulness ... 761

16.3.2. 3.2. Sleep ... 761

16.3.3. 3.3. Altered States of Consciousness ... 764

16.4. 4. Stress, Trauma, Development and Somatosensory Experiences ... 766

16.4.1. 4.1. Stress ... 766

16.4.2. 4.2. Attachment, development and the connection between dissociation and trauma ... 767

16.5. 5. Dissociation and Dissociative Phenomena ... 770

16.5.1. 5.1. Development of Dissociative States ... 771

16.6. 6. Trauma ... 773

16.7. 7. The Therapy of PTSD ... 775

16.8. 8. Summary ... 776

17. 3.r. Mirror-neurons, intentionality, empathy and alexithymia. Differentiation of self and the other. – Róbert Herold 33%, Mária Simon 33%, János Kállai [Translated by János Kállai, Translator-reviser: Mária Simon] ... 781

17.1. 1. Preface ... 781

17.2. 2. Components of empathy ... 781

17.2.1. 2.1. Mimicry ... 782

17.2.2. 2.2. ‘Contagious’ emotional states ... 784

17.2.3. 2.3. Sympathy, compassion, sorrow ... 784

17.3. 3. ‘The Self and the Other’: the organization of body experience ... 784

17.4. 4. Relations between empathy and the mirror neuron system ... 786

17.4.1. 4.1. Imitation, facts and beliefs: the mirror neuron system ... 789

17.5. 5. Summary ... 794

4. 4. Autonomic nervous system ... 801

1. 4.a. Development of the autonomic nervous system (ontogenesis and phylogenesis), its structure and functions. – Andrea Tamás [Translator-reviser: Zoltán Rékási] ... 801

1.1. 1. General function and structure of the vegetative nervous system ... 801

1.1.1. 1.1. General structure of the vegetative nervous system ... 801

1.1.2. 1.2. The general physiological function of the autonomic nervous system 802 1.2. 2. Structure of the parasympathetic nervous system (efferent fibers) ... 803

1.2.1. 2.1. General structure of the parasympathetic nervous system (efferent fibers) 803 1.3. 3. Structure of the sympathetic nervous system (efferent fibers) ... 804

1.3.1. 3.1. General structure of the sympathetic nervous system (efferent fibers) 804 1.4. 4. Afferent autonomic pathways ... 807

1.5. 5. Plexuses of the autonomic nervous system ... 808

1.5.1. 5.1. Plexuses of the thoracic cavity ... 809

1.5.2. 5.2. The plexuses of the abdominal cavity ... 810

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1.5.3. 5.3. The plexuses of the pelvis ... 812

1.6. 6. The phylogenesis of the autonomic nervous system - development of sympathetic and parasympathetic pathways ... 813

1.7. 7. Development of the vegetative nervous system in humans ... 814

2. 4.b. Sympathetic nervous system (anatomy, biochemistry, physiology and pathology). – Andrea Tamás 25%, Gábor Pozsgai 75% [Translator-reviser: Zoltán Rékási] ... 818

2.1. 1. General description of the sympathetic nervous system ... 818

2.2. 2. Cervical part of the sympathetic system ... 819

2.2.1. 2.1. The superior cervical ganglion ... 820

2.2.2. 2.2. The middle cervical ganglion ... 821

2.2.3. 2.3. The cervicothoracic ganglion (stellate ganglion) ... 821

2.3. 3. Thoracic part of the sympathetic system ... 821

2.4. 4. Lumbar part of the sympathetic system ... 822

2.5. 5. Pelvic part of the sympathetic system ... 822

2.6. 6. Prevertebral ganglia ... 822

2.7. 7. Biochemistry ... 822

2.7.1. 7.1. Neurotransmission of sympathetic preganglionic neurons ... 822

2.7.2. 7.2. Biosynthesis of noradrenaline ... 822

2.7.3. 7.3. Degradation of noradrenaline ... 826

2.7.4. 7.4. Storage of noradrenaline ... 827

2.7.5. 7.5. The release of noradrenaline ... 828

2.7.6. 7.6. Reuptake of noradrenaline into nerve terminals ... 829

2.8. 8. Physiology ... 830

2.8.1. 8.1. Adrenergic receptors ... 830

2.8.2. 8.2. Ocular effects of the sympathetic nervous system ... 831

2.8.3. 8.3. Effects of the sympathetic nervous system on salivary secretion ... 831

2.8.4. 8.4. Cardiac effects of the sympathetic nervous system ... 832

2.8.5. 8.5. Effects of the sympathetic nervous system on resistance vessels ... 832

2.8.6. 8.6. Effects of the sympathetic nervous system on the airways ... 832

2.8.7. 8.7. Gastrointestinal effects of the sympathetic nervous system ... 832

2.8.8. 8.8. Urogenital effects of the sympathetic nervous system ... 833

2.8.9. 8.9. Effects of the sympathetic nervous system on skeletal muscles ... 833

2.8.10. 8.10. Metabolic effects of the sympathetic nervous system ... 833

2.9. 9. Pathology ... 833

2.9.1. 9.1. Diseases affecting central structures of the sympathetic nervous system 833 2.9.2. 9.2. Diseases affecting peripheral structures of the sympathetic nervous system 834 2.9.3. 9.3. Pheochromocytoma ... 834

2.9.4. 9.4. The role of drugs acting on the sympathetic nervous system in pharmacotherapy ... 834

3. 4.c. Parasympathetic nervous system (anatomy, biochemistry, physiology and pathology). – Andrea Tamás 25%, Gábor Pozsgai 75% [Translator-reviser: Zoltán Rékási] ... 838

3.1. 1. Anatomy ... 838

3.1.1. 1.1. General description of the parasympathetic nervous system ... 838

3.1.2. 1.2. The efferent cranial fibers of the parasympathetic nervous system .. 839

3.1.3. 1.3. The efferent sacral fibers of the parasympathetic nervous system .... 845

3.2. 2. Biochemistry ... 846

3.2.1. 2.1. Biosynthesis of acetylcholine ... 846

3.2.2. 2.2. Storage of acetylcholine ... 847

3.2.3. 2.3. Acetylcholine release ... 850

3.2.4. 2.4. Degradation of acetylcholine ... 851

3.3. 3. Physiology ... 853

3.3.1. 3.1. Receptors of acetylcholine ... 853

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3.3.2. 3.2. Ocular effects of the parasympathetic nervous system ... 856

3.3.3. 3.3. Effects of the parasympathetic nervous system on glandular secretion 857 3.3.4. 3.4. Acetylcholine and perspiration ... 857

3.3.5. 3.5. Cardicac effects of the parasympathetic nervous system ... 857

3.3.6. 3.6. Effects of the parasympathetic nervous system on the airways ... 858

3.3.7. 3.7. Effects of acetylcholine on resistance blood vessels ... 858

3.3.8. 3.8. Effects of the parasympathetic nervous system on gastrointestinal smooth muscle ... 858

3.3.9. 3.9. Urogenital effects of the parasympathetic nervous system ... 858

3.4. 4. Pathology ... 859

3.4.1. 4.1. Diseases affecting central nervous system structures of the parasympathetic nervous system ... 859

3.4.2. 4.2. Diseases affecting peripheral structures of the parasympathetic nervous system ... 859

3.4.3. 4.3. The role of the parasympathetic nervous system in the pharmacotherapy of some diseases ... 859

4. 4.d. Main features of the gastro-intestinal nervous system. – Norbert Kovács [Translated by Gabriella Nagy, Translator-reviser: Dóra Reglődi] ... 863

4.2. 2. Overview of the Gastrointestinal Nervous System ... 864

4.2.1. 2.1. Structural Organization of the Enteric Nervous System ... 864

4.2.2. 2.2. Functions between the Enteric and the Central Nervous System ... 864

4.2.3. 2.3. Rectal Innervations and Functional Disorders of the Rectum ... 865

4.3. 3. Neurourological Pathological Pictures ... 865

4.3.1. 3.1. Neuroanatomical Relations ... 865

4.3.2. 3.2. Common Characteristics of Urinary Disorders from Neurogenic Damage 868 4.3.3. 3.3. Algorithms for Examinations of Neurourological Disorders ... 868

4.3.4. 3.4. Major Neurological Pathologies ... 876

4.3.5. 3.5. Urination Disorders in Neurological Pathologies ... 880

4.4. 4. Conclusions ... 882

5. 4.e. Neural control of the endocrine system. – Balázs Gaszner [Translator-reviser: Dóra Reglődi] 885 5.1. 1. Definition of the endocrine system and its role in the maintenance of homeostasis 885 5.2. 2. Neuroendocrinology ... 885

5.3. 3. The hypothalamo-hypophyseal system ... 885

5.3.1. 3.1. The pituitary gland (hypophysis) ... 885

5.3.2. 3.2. The endocrine functions of the hypothalamus ... 888

5.4. 4. The neural control of pineal functions ... 896

6. 4.f. Central control of the autonomic function. – Balázs Gaszner [Translator-reviser: Dóra Reglődi] ... 900

6.1. 1. Anatomy of the hypothalamus ... 900

6.2. 2. Afferent connections of the hypothalamus ... 902

6.3. 3. The main efferent connections of the hypothalamus ... 903

6.4. 4. Functional neuroanatomy of the hypothalamic nuclei ... 904

6.4.1. 4.1. The paraventricular nucleus of the hypothalamus ... 904

6.4.2. 4.2. The suprachiasmatic nucleus ... 906

6.4.3. 4.3. The arcuate nucleus (infundibular nucleus) ... 909

6.4.4. 4.4. The role of the hypothalamus in the regulation of the body temperature 910 6.4.5. Test questions ... 912

7. 4.g. Dysfunctions of the autonomic nervous system. Anxiety related vulnerability. – János Kállai [Translator-reviser: József Varga] ... 916

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7.2. 2. Theoretical context and diagnosis of anxiety ... 916

7.3. 3. The effect of fear and anxiety on memory processes ... 917

7.3.1. 3.1. Reconstruction of experiences in dangerous situations ... 918

7.4. 4. Psychological and biological vulnerability ... 919

7.4.1. 4.1. Vulnerability with panic and agoraphobia ... 920

7.4.2. 4.2. Neuroscientific approach ... 921

7.5. 5. Summary ... 923

8. 4.h. Coordination and expectancy. Placebo phenomena. False interpretation of somatosensory experiences. – Tibor Szolcsányi [Translator-reviser: János Kállai] ... 928

8.2. 2. A brief history of placebo ... 928

8.2.1. 2.1. The history of placebo treatments ... 928

8.2.2. 2.2. The origin of placebo ... 929

8.3. 3. The placebo effect and medical research ... 930

8.3.1. 3.1. Placebo treatments in medical research ... 931

8.3.2. 3.2. The placebo effect and the methodology of medical research ... 931

8.4. 4. What is placebo effect? ... 933

8.4.1. 4.1. Specific and non-specific effect, the effectiveness of open and hidden therapies ... 933

8.4.2. 4.2. Contextual effect, meaning response ... 934

8.5. 5. How does placebo effect work? ... 936

8.5.1. 5.1. Psychological mechanisms ... 936

8.5.2. 5.2. Neurochemical mechanisms ... 938

8.5.3. 5.3. The interaction between personality traits and therapeutic context ... 940

8.5.4. Test question ... 940

9. 4.i. Mental states and disorders. – Andrea Mike [Translator-reviser: Péter Ács] ... 947

9.1. 1. Neuroanamtomical correlates of consciousness ... 948

9.2. 2. Disorders of consciousness ... 948

9.3. 3. Clinical features of altered states of consciousness ... 949

9.3.1. 3.1. Coma ... 950

9.3.2. 3.2. Brain death ... 950

9.3.3. 3.3. Vegetative state ... 951

9.3.4. 3.4. Minimally conscious state ... 952

9.3.5. 3.5. Locked-in syndrome ... 952

9.3.6. 3.6. Delirium/acute confusional state ... 953

9.3.7. 3.7. Abulia and akinetic mutism ... 953

9.3.8. 3.8. Psychogenic unresponsiveness/Catatonia ... 953

9.3.9. 3.9. Epileptic seizures ... 954

9.4. 4. Bedside assessment of the unresponsive patient ... 954

9.4.1. 4.1. Behavioral scales ... 955

9.4.2. 4.2. Glasgow Coma Scale (GCS) ... 955

10. 4.j. Evaluation of mental distress in the forensic medicine – opinion on accountability. – István Bajnóczky [Translated by Éva Kereszty, Translator-reviser: Péter Sótonyi] ... 965

10.1. 1. Abnormality ... 966

10.1.1. 1.1. Organic brain syndromes ... 967

10.2. 2. Mental disease and criminal responsibility ... 967

10.3. 3. Fitness to stand trial ... 968

10.4. 4. The insanity defense (NGRI) ... 968

10.5. 5. Guilty but mentally ill (GBMI) ... 968

10.6. 6. Civil law – incompetency and guardianship ... 969

10.7. 7. Testamentary capacity ... 969

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11. 4.k. Stress and coping. – István Tiringer [Translated by Katalin Eklicsné Lepenye, Translator- reviser: István Tiringer] ... 973

11.1. 1. Introduction ... 973 11.2. 2. Stress triggering factors (stressors) ... 973 11.3. 3. Acute, severe stress and life strains ... 973 11.4. 4. Chronic stress ... 974 11.5. 5. Specific stress-responses ... 976 11.6. 6. Physiology of stress ... 976 11.6.1. 6.1. Locus coeruleus-hypothalamic-sympatho-adreno-medullary axis .. 976 11.6.2. 6.2. Hypothalamic-pituitary-adrenocortical axis ... 977 11.6.3. 6.3. Allostasis, allostatic load ... 977 11.7. 7. Impact of stress on the central nervous system ... 977 11.8. 8. Early experiences that determine stress responses ... 978 11.9. 9. How does stress endanger health? ... 979 11.9.1. 9.1. Unused mobilized energy ... 979 11.9.2. 9.2. Chronic stress response ... 979 11.9.3. 9.3. Impairment of the organism’s defense system ... 980 11.9.4. 9.4. Health hazardous behavioral patterns ... 980 11.10. 10. Effects of chronic stress on functions of particular organ systems ... 980 11.11. 11. Cognitive factors in stress response ... 981 11.12. 12. Coping ... 982 11.13. 13. Stress management ... 983 11.13.1. Test questions ... 984 12. 4.l. Assessment of mourning in actions for immaterial damages. – Andrea Jegesy [Translated by Katalin Eklicsné Lepenye, Translator-reviser: Gábor Simon] ... 987

12.1. 1. Legal aspects of mourning ... 987 12.2. 2. Medical and psychological judgment of grief reaction ... 988 12.3. 3. Assessment of compensation for losing a close relative ... 991 12.3.1. 3.1. Examples from the Hungarian forensic practice ... 992 12.3.2. 3.2. Hungarian judicial practice ... 993 12.3.3. 3.3. Foreign examples for compensations for damages due to mourning 995 12.4. 4. The practicing doctor’s duty in the case of mourning ... 997 12.5. 5. The role of the media in coping with grief, or making it complicated ... 997 12.6. 6. Psychological theoretical discussions about grief (Ágnes Riskó) ... 998 12.6.1. Test questions ... 998 13. 4.m. Principles of affective neuroscience – emotion, limbic- and paralimbic system, cognitive approaches. – Árpád Csathó 50%, Ádám Feldmann 50% [Translator-reviser: János Kállai] 1001

13.1. 1. Introduction ... 1001 13.2. 2. James–Lange theory ... 1002 13.3. 3. Cannon–Bard theory ... 1002 13.4. 4. Papez–circuit ... 1002 13.5. 5. Maclean and the limbic system ... 1002 13.6. 6. Neuroanatomical basics of affective functions ... 1003 13.6.1. 6.1. Lateralization ... 1003 13.6.2. 6.2. Thalamus and hypothalamus ... 1003 13.6.3. 6.3. Amygdala ... 1004 13.6.4. 6.4. Medial prefrontal lobe ... 1005 13.6.5. 6.5. Anterior cingulate cortex ... 1007 13.6.6. 6.6. Insula ... 1007 13.7. 7. Summary ... 1008 13.7.1. Test questions ... 1008 14. 4.n. The nature, basic mechanisms and concomitant syndromes of the mental conflicts. – Béla Birkás [Translated by Éva Mészégetőné Halmos, Translator-reviser: János Kállai] ... 1013

14.1. 1.Definition of the conflict ... 1013 14.2. 2. Psychodynamic aspects of intrapersonal conflicts ... 1014

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14.2.1. 2.1. Freud’s Personality Model ... 1014 14.2.2. 2.2. Unconscious conflicts and anxiety ... 1015 14.2.3. 2.3. Limitations of the structural model and the concept of unconscious conflict 1016

14.3. 3. Intrapersonal conflicts and cognition ... 1016 14.3.1. 3.1. Conflicts presenting in the course of cognitive development ... 1016 14.3.2. 3.2. Cognitive dissonance ... 1016 14.3.3. 3.3. Our roles and internal conflicts ... 1017 14.3.4. 3.4. Evaluation of situations and intrapsychic conflicts ... 1018 14.3.5. 3.5. Biological dimension of the cognitive evaluation of the conflict .. 1019 14.4. 4. Forms of manifestation of internal conflicts: neurosis and anxiety ... 1020 14.4.1. 4.1. Neurosis ... 1020 14.4.2. 4.2. Neuroticism ... 1021 14.4.3. 4.3. Anxiety ... 1022 14.4.4. 4.4. Biological foundations of anxiety and neuroticity ... 1022 14.5. 5. Psychic conflict and behavior ... 1024 14.5.1. 5.1. Self-regulation, self-control ... 1024 14.5.2. 5.2. Ontogenesis of self-regulation ... 1025 14.5.3. 5.3. Biological foundations of our self-regulatory functions ... 1025 14.6. 6. Summary ... 1026 14.6.1. Test questions ... 1026 15. 4.o. Conceptions of health and disease. – Zsuzsanna Füzesi 50%, József Varga 50% [Translated by Éva Mészégetőné Halmos, Translator-reviser: Zsuzsanna Füzesi] ... 1029

15.1. 1. Introduction ... 1029 15.2. 2. The concept of health and disease - as everyone knows it ... 1030 15.2.1. 2.1. The concept of health ... 1030 15.3. 3. The concept of health and disease – viewed by practising professionals ... 1031 15.3.1. 3.1. Classical biomedical theory ... 1031 15.3.2. 3.2. The naturalistic health concept ... 1032 15.3.3. 3.3. The normativist approach ... 1033 15.3.4. 3.4. Dynamic health approach ... 1033 15.4. 4. Concept of health and disease – the functional approach ... 1034 15.4.1. 4.1. Sociocultural model ... 1034 15.4.2. 4.2. Wolinsky’s three-dimensional health-illness model ... 1034 15.5. 5. The concept of health and illness – from laymen’s point of view ... 1036 15.5.1. 5.1. Lay health philosophies ... 1037 15.5.2. 5.2. Lay disease philosophies ... 1038 15.6. 6. Theories affecting the health concept ... 1038 15.6.1. 6.1. The theory of health capital ... 1038 15.6.2. 6.2. The health field theory (Lalonde Report) ... 1039 15.6.3. 6.3. The Ottawa Charter ... 1039 15.6.4. 6.4. The theory of salutogenesis ... 1039 15.6.5. 6.5. The experience of flow and the autoteleologic personality ... 1041 15.7. 7. Risks of the interpretation of health/illness ... 1041 15.7.1. 7.1. Healers’, nurses’ and other health care workers’ health risks ... 1042 15.8. 8. Limits of the health/illness concept ... 1042 15.8.1. Test questions ... 1042 5. 5. Complex brain functions. The mind (cognitive system). Mind-altering drugs ... 1049 1. 5.a. Structure and functions of the cognitive system (ontogenesis and phylogenesis, structure, functions). – Árpád Csathó 50%, Ádám Feldmann 50% [Translator-reviser: János Kállai] 1049

1.1. 1. Evolutionary considerations of the structure of the cognitive system ... 1049 1.2. 2. The functionality and connections of the frontal lobe ... 1050 1.3. 3. The structures and functions of the main neurocognitive systems ... 1051 1.3.1. 3.1. The fronto-striatal system ... 1051 1.3.2. 3.2. The structure and function of the fronto-parietal system ... 1057