Cover -- Title Page -- Copyright -- Dedication -- Contents -- Preface -- Acknowledgements -- 1 A brief evolutionary account of medical care -- 1.1 Simple organisms can take care of themselves -- 1.1.1 Unicellular organisms use simple strategies to protect themselves -- 1.1.2 The withdrawal reflex is present in both invertebrates and vertebrates -- 1.2 From the scratch reflex to grooming -- 1.2.1 The scratch reflex is a simple purposive behaviour -- 1.2.2 Grooming involves a complex behavioural repertoire -- 1.3 Scratching somebody else: a big evolutionary jump to social behaviour -- 1.3.1 Primates spend plenty of time in social grooming -- 1.3.2 From social grooming to altruistic behaviour -- 1.4 Taking care of the sick -- 1.4.1 From early forms of altruism to the emergence of the shaman -- 1.4.2 More rational treatments emerge slowly from prehistoric to historic medicine -- 2 Emergence and development of scientific medicine -- 2.1 Emerging knowledge and the problem of animal experimentation -- 2.1.1 Scientific medicine requires basic anatomical and physiological knowledge -- 2.1.2 Acquiring new medical and surgical skills -- 2.1.3 Effective treatments need not be understood, but they do need validation -- 2.1.4 Animal research impacts negatively on most people and raises many ethical concerns -- 2.2 Biological, psychological, and social factors all contribute to illness and healing -- 2.2.1 Modern scientific medicine includes a psychosocial component -- 2.2.2 Medical concepts vary across cultures but the psychosocial component stays the same -- 2.3 Medical practice meets neuroscience -- 2.3.1 Scientific medicine needs to include the study of the patient's and doctor's brain -- 2.3.2 To become and to be a patient involves four steps and relative brain processes -- 3 Feeling sick: a combination of bottom-up and top-down events.

3.1 The patient feels sick through bottom-up and top-down processes -- 3.1.1 What is a symptom? -- 3.1.2 Detection of a symptom is a combination of interoception and other factors -- 3.1.3 Different brain regions respond to interoceptive stimuli -- 3.1.4 The insula plays a crucial role in awareness -- 3.1.5 Interoceptive awareness undergoes a top-down modulation -- 3.2. Bottom-up and top-down processes contribute to the global experience of pain -- 3.2.1 Pain experience is built up from the periphery to the central nervous system -- 3.2.2 There is not a single pain centre but a distributed system -- 3.2.3 Pain experience changes across individuals and circumstances -- 3.2.4 A complex neural network is responsible for the top-down modulation of pain -- 3.3 Emotions influence the perception of symptoms -- 3.3.1 Feeling sick does not necessarily mean physical suffering -- 3.3.2 Positive and negative emotions are processed in the limbic system -- 3.3.3 Anxiety about pain activates brain circuits that increase the pain -- 3.3.4 Anger and depression influence pain perception -- 4 Seeking relief: the activation of motivational and reward circuits -- 4.1 Suppressing discomfort and seeking pleasure -- 4.1.1 Motivation is aimed at regulating internal states and at getting a reward -- 4.1.2 Suppressing discomfort from hunger, thirst, and thermal variations -- 4.1.3 Seeking pleasure from sex -- 4.1.4 Reward-seeking behaviours involve the mesolimbic dopaminergic system -- 4.2 Suppressing discomfort from sickness -- 4.2.1 Seeking relief from sickness is a motivated behaviour -- 4.2.2 Motivated behaviour varies according to cultural differences -- 4.2.3 The motivation/reward system is activated when seeking and expecting relief -- 5 Meeting the therapist: a look into trust, hope, empathy, and compassion mechanisms -- 5.1 Trusting the therapist.

5.1.1 Trust in doctors can be measured -- 5.1.2 The amygdala is a key region in trustworthiness decisions -- 5.1.3 Oxytocin enhances trust -- 5.1.4 Admiration for virtue and skills involves two separate neural systems -- 5.2. Sensory inputs can make the difference -- 5.2.1 Subtle differences in verbal communication may lead to different outcomes -- 5.2.2 Visual stimuli are the basis for nonverbal communication -- 5.2.3 Being touched by a beloved makes the pain more bearable -- 5.3 The patient wants the future to be better than the present -- 5.3.1 Hope and hopelessness may impact on health -- 5.3.2 Hopelessness/helplessness involve serotoninergic and noradrenergic systems -- 5.4 A look into the doctor's brain -- 5.4.1 Face expressions of pain are likely to have evolved for eliciting medical attention from others -- 5.4.2 Empathy and compassion have different meanings and mechanisms -- 5.4.3 There are two different neural systems for empathy -- 5.4.4 Compassion for social and physical pain engages two separate neural systems -- 5.4.5 Doctors can regulate their emotional responses to others' suffering -- 5.5 The doctor-patient interaction may have both positive and negative effects -- 5.5.1 A positive interaction may lead to positive outcomes -- 5.5.2 A negative interaction may lead to negative outcomes -- 6 Receiving the therapy: the activation of expectation and placebo mechanisms -- 6.1 The ritual of the therapeutic act changes the patient's brain -- 6.1.1 The patient is deluged with social stimuli during the therapeutic act -- 6.1.2 The placebo effect helps understand how social stimuli may be therapeutic -- 6.1.3 How the ritual of the therapeutic act changes brain chemistry and circuitry -- 6.1.4 Placebo effects can be completely unconscious -- 6.1.5 Different genetic variants may alter placebo responsiveness.

6.2 The global effect of drugs is influenced by cognition and emotions -- 6.2.1 Knowledge and non-knowledge about treatments affect the therapeutic outcome -- 6.2.2 The patient's psychological state interferes with the action of drugs -- 6.2.3 It is not possible to fully understand how therapies work -- 6.3 A closer look into unconscious conditioning and conscious expectation -- 6.3.1 Pavlovian conditioning is due to the temporal contiguity of the stimuli -- 6.3.2 Cognition may be at work during conditioning -- 6.3.3 Both conscious expectation and unconscious conditioning take place in the patient's brain -- 7 The brain of the demented patient -- 7.1 Many patients cannot communicate their discomfort -- 7.1.1 Who cannot communicate -- 7.1.2 Dementia is a major medical problem -- 7.2 How the demented patient feels sick -- 7.2.1 The lateral and medial pain systems are affected differently in Alzheimer's disease -- 7.2.2 Vascular dementia may be associated to hyperalgesia -- 7.2.3 Frontotemporal dementia leads to reduced pain responses -- 7.3. The demented patient cannot seek relief -- 7.3.1 Purposive behaviour is impaired in dementia -- 7.4. The demented patient meets the therapist -- 7.4.1 There is no real interaction between the demented patient and the doctor -- 7.5 How the demented patient responds to treatments -- 7.5.1 Demented patients are often undertreated for their symptoms such as pain -- 7.5.2 Placebo and expectation effects are reduced in Alzheimer's disease -- 7.6 If there is no prefrontal control, there is no placebo response -- 7.6.1 Blocking opioidergic transmission in the prefrontal cortex abolishes the placebo response -- 7.6.2 Inactivating the prefrontal cortex with transcranial magnetic stimulation abolishes the placebo response -- 8 Defence mechanisms of the body in the course of evolution: from cellular to social responses.

8.1 A variety of defence mechanisms are present in living organisms -- 8.1.1 Cells respond to invaders and to damage -- 8.1.2 Living organisms protect themselves from a variety of dangers -- 8.2 Defence mechanisms can also involve cultural and social aspects -- 8.2.1 Thermoregulation as an example of physiological and cultural mechanism -- 8.2.2 Social groups can be advantageous to health in a number of ways -- 8.3 The doctor-patient interaction is a social mechanism of defence -- 8.3.1 The system works regardless of effective therapies -- 8.3.2 Why does the system work this way? -- 8.3.3 The doctor himself belongs to the system -- Index.