Neuroscience Study Notes PDF

Neuroplasticity Brain Injury Mechanisms Coup/Contre-coup Injury ○ A French phrase that describes bruises that occur at two sites in the brain. ○ When the head is struck, the impact causes the brain to bump the opposite side of the skull. ○ Damage oc...

Neuroplasticity Brain Injury Mechanisms Coup/Contre-coup Injury ○ A French phrase that describes bruises that occur at two sites in the brain. ○ When the head is struck, the impact causes the brain to bump the opposite side of the skull. ○ Damage occurs at the area of impact and on the opposite side of the brain. Diffuse Axonal Injury ○ Brain injury does not require a direct head impact. ○ During rapid acceleration of the head, some parts of the brain can move separately from other parts. ○ This type of motion creates shear forces that can destroy axons necessary for brain functioning. These shear forces can stretch the nerve bundles of the brain. ○ The brain is a complex network of interconnections. ○ Critical nerve tracts can be sheared and stressed during an acceleration-type of injury. ○ Diffuse axonal injury is a very serious injury, as it directly impacts the major pathways of the brain. Epidural Hematoma ○ An epidural hematoma is a blood clot that forms between the skull and the top lining of the brain (dura). ○ This blood clot can cause fast changes in the pressure inside the brain. ○ When the brain tissue is compressed, it can quickly result in compromised blood flow and neuron damage. Subdural Hematoma ○ A subdural hematoma is a blood clot that forms between the dura and the brain tissue. ○ The clot may cause increased pressure and may need to be removed surgically. ○ When the brain tissue is compressed, it can quickly result in compromised blood flow and tissue damage. Recovery from Brain Injury Compensation – recruit new brain regions or increase activity Form new connections Reorganize E.g. Gabrielle Giffords E.g. Trevor Greene Brain Plasticity Experience can alter the brain by modifying existing circuitry or by creating novel circuitry. This happens at the level of the morphology of the synapse. In animals can count number of dendrites and if there is a change in number then clearly there has been a change in synaptic organization. New Neurons CAN Occur Dyes can be used and injected into areas of animals’ brains that are later shown to have moved into new neurons, thus showing new neuron growth. Can have the generation of new neurons in the hippocampus when an animal learns a new task e.g. Morris water maze. E.g. LTP It has also been shown that glial, vascular and metabolic processes can change in response to experience. Long Term Potentiation (LTP) The strengthening of a connection between two, already connected, neurons which lasts for minutes to months – activation to installation. The cellular basis of learning and memory. Glutamate is the key neurotransmitter in LTP and acts on two different types of receptors on the postsynaptic membrane ○ AMPA (alpha-amino-3-hydroxy-5-methylisoa-zole-4-proprionic acid) Normally responds to glutamate to release Na ions ○ NMDA (N-methyl-D-aspartate) Normally blocked by magnesium (Mg2+) ions Responds to glutamate Responds with an influx of Ca+2 ions glutamate → NMDA receptor → Mg+2 release → Ca+2 influx → depolarization and action potential (EPSP) = strengthening of synapse = LTP Calcium and LTP The Ca+2 ions are extremely important intracellular messengers that activate many enzymes by altering their conformation ○ e.g. calmodulin, which becomes active when four Ca+2 ions bind to it. It then becomes Ca+2/calmodulin = the main second messenger for LTP. Ca+2/calmodulin then in turn activates other enzymes that allow for a cascade of biochemical reactions that play key roles in LTP. ○ Increased responsiveness of AMPA receptors to glutamate ○ Formation of new AMPA receptors  ○ Retrograde messengers that trigger more glutamate release from presynaptic neuron\ Two Phases of LTP Establishment (or induction/activation) - lasts about an hour ○ Can be experimentally induced by a single, high-frequency stimulation. ○ It involves the activity of various enzymes that persist after the Ca+2 is eliminated, but no protein synthesis. Maintenance (or expression/installation) – can last for days/months ○ Triggered by a series of high-frequency stimuli. ○ Unlike the establishment phase of LTP, the maintenance phase requires the synthesis of new proteins e.g. the ones that form the receptors and contribute to the growth of new synapses. Activated mental states foster installed neural traits LTP Summary Rapid, intense stimulation of neurons depolarizes them. Binding of glutamate to their NMDA receptors opens them. Ca+2 ions flow into the cell through the NMDA receptors and activate second messenger (e.g. cAMP). AMPA receptors become more permeable to the inflow of Na+ ions and thus increase the sensitivity of the cell to depolarization. ○ may also increase the number of AMPA receptors at the synapse. Increased gene expression (i.e., protein synthesis) Structural changes in the synapse – dendritic spines, formation of synapses. Chemical, structural and functional changes occur. Neuroplasticity Examples Acquired Brain Injury – Greene and Giffords Stroke Recovery – cognitive rehabilitation study/physical therapy Learning Disability – Barbara Arrowsmith-Young (The woman who changed her brain) Mental Health – PTSD - Brunet Addiction – Mindfulness-Based Relapse Prevention (MBRP) Chronic Pain – mindfulness in breast cancer patients Football players – Amen Clinics Optimizing outcomes requires individualized medicine/practice Self Directed Neuroplasticity Neurobics ○ Brain exercise, several books 1. Involve one or more of your senses in a new context. 2. Involve your full attention, at least briefly. 3. Break your routine in some significant way. ○ Multimillion dollar industry Supplements for Smarts Brain Protex with Huperzine– herbs, nutrients and antioxidants ○ Improve brain function and memory. ○ Protect brain capacity. ○ Improve and protect nerves. ○ Rapidly pass through the blood-brain barrier. Chinese researchers recently discovered that a standardized extract of huperzine helps improve learning and memory in animals. Similar improvements were observed when the compound was given to humans with Alzheimer’s disease. Additional research shows that phosphatidyl serine can help improve cognitive measures in patients with Alzheimer’s disease. Ingredients: Huperzine, Ginkgo biloba, phos-phatidyl serine, choline, ethanolamine, inositol, lycopene, alpha lipoic acid and Rhododendron caucasicum. Neuroplasticity Mindfulness training is assisting with some of the complications of stress, disease, drug use and overall well-being. Sleep, exercise, nutrition, social connections, gratitude, new learning also can help us create the best brain possible. Humans Neuronal change is inferred by behaviour in humans. Post-mortems can tell something about the actual synaptic properties but these results are strictly correlative. Imaging helps with larger scale changes in brain properties. Human Cortical Plasticity Musicians who play string instruments have increased cortical representation of the fingers of the left hand. Braille readers have increased cortical representation of the reading finger. To Have a Healthy Brain 1. Healthy heart. 2. Incremental training. 3. Training needs to be taxing and systematically improving ie. Doable but hard. 4. Training needs to be interesting to engage motivation circuits. Psychopathy Myths about Psychopathy? Not Psychosis Not out of touch with reality Not only criminals Not only males Not only adults Brief History 1801 - Mania without delirium 1810 - Moral insanity 1818 - Psychopath 1930 - Cleckley’s primary psychopath 1941 - Cleckley’s Mask of Sanity - "They carry disaster lightly in each hand." 1940-1950s - Psychiatry couldn’t cure so dismissed it as something external – Sociopath 1958 - DSM sociopathic personality 1968 – Antisocial Personality Disorder (APD) 1993 – Hare’s Without Conscience 2006 - Snakes in Suits 2014 – The Psychopath Whisperer Cleckey’s Psychopath Imagine - if you can - not having a conscience, none at all, no feelings of guilt or remorse no matter what you do, no limiting sense of concern for the well-being of strangers, friends, or even family members. Imagine no struggles with shame, not a single one in your whole life, no matter what kind of selfish, lazy, harmful, or immoral action you had taken. And pretend that the concept of responsibility is unknown to you, except as a burden others seem to accept without question, like gullible fools. Characteristics Interpersonally- egocentric, manipulative, dominant, cold-hearted Affectively- labile emotions, no long lasting bonds to people or principles or goal, lack of empathy or guilt Behaviourally- impulsive, sensation-seeking, violate social norms Definitions “morally depraved individual who represents our society, an unstoppable and untreatable predator whose violence is planned, purposeful and emotionless.” “They are usually very charming and excellent with words. Therefore, they are able to manipulate and talk they’re way out of situations and fool people. Because they are void of emotion and empathy, they are able to mimic emotion and make their victims feel like they empathize with them.” “You may think that they are out of touch with reality, but that is not the case. Psychopaths know right from wrong and are able to calculate their crimes and plan out every single detail to ensure success. According to the article, “their motivation is power, gratification, personal gain and survival.” “One of their chief characteristics is a kind of glow or charisma that makes sociopaths more charming or interesting than the other people around them. They’re more spontaneous, more intense, more complex, or even sexier than everyone else, making them tricky to identify and leaving us easily seduced. Fundamentally, sociopaths are different because they cannot love. Sociopaths learn early on to show sham emotion, but underneath they are indifferent to others’ suffering. They live to dominate and thrill to win.” Importance Psychopaths make up 25% of male prison population but perform > 50% of violent crime Psychopaths recidivate 3 - 4x more than non-psychopaths following release from prison Psychopaths are not all in jail and are not all criminals. “Successful” psychopaths use the system and people to get what they want Knowledge is power! Hare Psychopathy Checklist – Revised (PCL-R) Uses ○ assessing and diagnosing psychopathy for research and clinical purposes ○ parole board hearings / dangerous offender verdicts ○ best predictive tool for recidivism / risk assessments The Checklist  ○ 20 characteristics ○ semi-structured interview and collateral information ○ childhood, relationships, work experience, family history, criminal history, general view of life and people Neurobiology of Psychopathy Background ○ 1) “Pseudopsychopaths” and “acquired sociopaths” ○ 2) EEG – startle, conditioning, lexical decision task ○ 3) Functional and Structural MRI studies The Lexical Decision Task They know the words but not the music – only word deep understanding They can learn to use ordinary words...and to reproduce the pantomime of feeling...but the feeling itself does not come to pass e.g. "I'm really sorry I hurt you baby, but, hey... life goes on, right?“ A powerful technique for investigation of the semantic and affective components of language = lexical decision task Words have both denotative (explicit, literal) and connotative (implicit, implied) meanings The impact of the affective connotations of words can be evaluated by recording: ○ – Lexical decision times ○ – Brain activity associated with the decisions (EEG)  Neutral & emotional words, and pronounceable nonwords, briefly presented in random order on a computer screen ○ eg. RAPE, EPRA TREE, ETER Was what you saw a word? fMRI in Psychopaths Go/No Go test of response inhibition ○ Psychopaths showed no significant dorsolateral prefrontal cortex activation during response inhibition Emotional Word Task of emotional processing ○ Psychopaths showed reduced activation of several limbic structures while viewing emotional words and increased activation of the anterior temporal lobe when compared with noncriminal individuals First fMRI study of well-defined psychopaths showing significant neural differences between psychopaths and control subjects in dorsolateral prefrontal cortex during response inhibition and limbic structures during emotional processing. Combined with the Neuroanatomy of prefrontal cortex and its connections Conclusions for image → Inefficient neural communication and integration between dorsolateral PFC, OFC and limbic structures may be compensated for over time and alternate neural systems may be used.>en the left anterior insula and left dorsal anterior cingulate cortex is reduced in psychopaths. The group difference map (bottom row) indicates an area in dorsal anterior cingulate where non-psychopaths have significantly greater connectivity with anterior insula than psychopaths. Psychopaths reported feeling regret when they saw how much they won or could have won on the game. However, psychopaths were unable to use the information about the choices they were given to anticipate how much regret they were going to experience in the future, and to adjust their decision-making accordingly. They have a deficit in prospective regret, not retrospective regret.”  ○ The inability to learn from their mistakes also predicted the number of times the participants had been incarcerated. Sleep A Clock for All Seasons Zeitgebers ○ Zeitgeber Cues from the environment that entrain the biological rhythms; a “time giver” Example: Light resets the biological clock ○ Entrainment Determination or modification of the period of a biorhythm – e.g. daylight savings time kicks in. ○ Jet lag Fatigue and disorientation from rapid travel through time zones and exposure to a changed light-dark cycle Biological Clocks ○ Chronobiology = the study of biological rhythms ○ Behaviour is not simply driven by external cues from the environment ○ Rhythms are endogenous (control comes from within) ○ Biological Clock Neural system that times behaviour Allows animals to anticipate events before they happen Example: Birds migrate before it gets cold Neural Basis of the Biological Clock Suprachiasmatic Nucleus (SCN) ○ Main pacemaker of circadian rhythms located just above the optic chiasm ○ Richter – stimulated brain with electrodes to show that circadian rhythms could be stalled by lesions to the suprachiasmic nucleus (SCN) of hypothalamus = biological clock. ○ If the SCN are damaged in rodents, eating, drinking, exercise, and sleep occur a normal amount, but at haphazard times. ○ Neurons in the SCN maintain their rhythmic electrical activity even when all the pathways into and out of the SCN are cut ie. Intrinsic cues are also important ○ Metabolic activity of the SCN is higher during the light period of the day-night cycle than it is during the dark period of the cycle Retinohypothalamic Pathway  ○ Neural route from a subset of cone receptors in the retina to the suprachiasmatic nucleus of the hypothalamus; uses glutamate as the primary neurotransmitter; allows light to entrain the rhythmic activity of the SCN Other pacemakers exist in the retina and pineal gland, but the SCN is the main one What Ticks? ○ At least half a dozen genes and the proteins they make form two interlocking loops that produce the circadian rhythm of SCN cells in mammals ○ Mechanism is not fully understood ○ One Model for Circadian Timing System Light entrains the SCN pacemaker SCN pacemaker drives a number of “slave oscillators,” each of which controls the rhythmic occurrence of one behaviour (e.g., body temperature) SCN pacemaker may drive the slave oscillators via hormones (e.g. melatonin), proteins, or neurotransmitters Sleep Stages Sleep is very organized and cyclical. Sleep has five stages: stage 1-4 (non-REM – shallow to deep) and REM. Once REM sleep is achieved, the cycle reverses itself and goes back through stages II, III, IV and again to IV, III, II and REM. Throughout the night, this cycle occurs at 90-to-100 minute intervals. Sleep Stages and Dreaming NREM Sleep ○ Large range of activities take place Examples: decrease in body temperature and increase in growth hormone release ○ Dreaming does occur in NREM sleep, but dreams are not as vivid as in REM sleep ○ Inconsistent with NREM sleep being a quiet, inactive period Sleeptalking Sleepwalking Night terrors Dreaming ○ Vivid dreams occur during REM sleep Everyone dreams a number of times each night  Dreams appear to take place in real time, dream sessions get longer throughout a sleep session You remember dreams and are alert if you awake during REM Importance of Sleep The "average" human sleeps about 8 hours every day. That's one third of your life! That’s about 122 days every year. A 75 year old person would have spent a total of about 25 years asleep. What Does Sleep Accomplish? 1. Sleep As a Passive Process ○ Early explanation that sleep is a passive process that takes place as a result of a decrease in sensory stimulation ○ Does not account for the complexity of sleep ○ No direct evidence Sensory deprivation research has shown that people actually sleep less, not more, when placed in isolated environments (contrary to what one would expect) 2. Sleep As a Biological Adaptation ○ Sleep is an energy-conserving strategy Gather food at optimal times and sleep to conserve energy the rest of the time Animals with nutrient-rich diets spend less time foraging for food and more time sleeping ○ Predators sleep more than animals that are prey ○ Nocturnal or diurnal animals will sleep during those times in which they cannot travel easily Example: bears cannot see well at night 3. Sleep As a Restorative Process ○ Chemical events that provide energy to cells may be reduced during waking and are replenished during sleep We need to sleep so we can function – if not…. Sustained attention reduced Irritable and sluggish Reaction time is slower REM rebound Brain’s use of glucose is attenuated significantly after being awake 24 hours. 4. Sleep and Memory Storage  ○ Sleep plays a role in solidifying and organizing events in memory ○ Place cell Hippocampal neuron that fires when a rat is in certain location in an environment Wilson and McNaughton Groups of place cells that fired during a food-searching task also fired during the subsequent sleep period Importance of NREM sleep for memory storage ○ Maquet and colleagues Used PET imaging to record brain activity while human subjects performed a serial reaction time task PET imaging during subsequent sleep revealed that the same brain regions that were active during the task were also active during REM sleep Subjects were dreaming about their learning experience REM sleep strengthened the memory of the task ○ Dreams store events in memory in NREM or REM ○ Stickgold and Walker study of procedural memory for motor skills. right handers asked to type a sequence of numbers with left hand as fast as possible improved 60-70% over 6 minutes practice after 12 hours of break = no further improvement BUT if learned at night and then slept = 15%-20% faster and 30-40% more accurate. ○ Fogel studies of naps, sleep, age, motor learning, etc. Neural Bases of Sleep Moruzzi and Magoun (1949) named the Reticular Activating System (RAS) as neurons that produce the waking EEG = diffuse network of fibers and nuclei in the center of the brainstem. ○ Reticular activating system gets input from a) spinal cord b) all sensory modalities c) cortex d) visceral sources e) cerebellum ○ Then sends information back to each, plus most cranial nerves (e.g. salvation, swallowing, facial expressions). ○ Damage to RAS can result in sleep or coma. Two brainstem systems influence waking  ○ E.g. Specific cells from the ascending pathways activate awake EEG ○ 1) basal forebrain Ach cells project to neocortex – are active when animal is alert but immobile ○ 2) median raphe 5-HT cells project to neocortex – when animal is moving. ○ Lesion both and rat can still walk but EEG looks like sleep and can’t learn anything. ○ When you are sleepy, move around and 5-HT is released so stay awake more easily. Neural Bases of REM 1. Atonia – inhibition of motor neurons 2. Waking EEG pattern 3. Eye movements 4. Dreams 5. Sharp EEG spikes from pons, lateral geniculate nucleus and visual cortex (PGO waves). Related to peribrachial area in dorsal brainstem (pons) whereas NREM is more the reticular formation. Peribrachial Area Peribrachial area = cholinergic neurons in the dorsal brainstem that activate REM. ‘REM’ on cells start firing 80 seconds before the onset of REM sleep. These neurons connect directly to brainstem regions that control eye movements and with limbic and cortical areas involved in emotion and learning = initiation of the fast eye movements and the emotional aspects of dreaming that occur during REM sleep. Medial Pontine Reticular Formation Lesioning MPRF has same effect on REM as lesioning peribrachial area ie. Reduced sleep. Also releases Ach to activate EEG. Atonia is produced by MPRF through a pathway that sends input to the subcoeruleus nucleus that excites the magnocellular nucleus of the medulla which projects to the spinal motor neurons to inhibit them = paralysis. PGO Waves Phasic electrical bursts of neural activity that travel from the Pons to the Lateral Geniculate Nucleus of the thalamus into the Occipital Visual Cortex. Occur shortly before the onset of REM sleep.  PGO waves = visual information and visual processing of information, particularly in dreams and the rapid eye movements typical of REM sleep. Other Neurotransmitters DA - from the substantia nigra connecting with frontal cortex affects wakefulness and alertness. Glutamate and Aspartate – excitatory neurotransmitters released during wakefulness in cortex and brainstem. Histamine - receptors in hypothalamus project to cerebral cortex and indirectly activates Ach ‘REM on cells’. Keeps us awake and aroused. Blocking H1 (antihistamines) can cause drowsiness. 5-HT – raphe nuclei in reticular formation targeting thalamus, hypothalamus, hippocampus, basal ganglia and the neocortex. Stimulation produces arousal but during SWS firing reduces and in REM stops. Norepinephrine (NE) - locus coeruleus in brainstem connecting to the cerebral cortex, areas involved in memory, temperature regulation, hormonal regulation and brainstem areas. The rate of firing of NE cells of the locus coeruleus almost stops during REM sleep and increases radically when awoken. Disorders of NREM Insomnia and narcolepsy. Disorders of slow wave sleep (stages 3,4). Anxiety and depression can account for a significant amount of insomnia ~35%. Narcolepsy - May be due to mutations in the gene that produces hypocretin/orexin peptides as few orexin neurons in hypothalamus of animals with narcolepsy. Ritalin is used to help narcolepsy. Disorders of REM Sleep paralysis = atonia and dread or fear, awake but can’t move or talk – inhibition of motor neurons. Cataplexy = form of narcolepsy linked to strong emotional stimulation in which an animal loses all muscle activity or tone, as if in REM sleep, while awake and alert. Genetic component to each E.g. of cataplexy in dogs – neurons in magnocellular layer of medulla become active as in REM. Treated with Ritalin. Parasomnias Parasomnias are undesirable motor, verbal, or experiential events that occur during sleep. Not pathologic necessarily. Thought of as a response to CNS activation that results in sleep-wake or REM-NREM state confusion or when a person is caught in a mixed state of transition from 1 sleep cycle to the next (eg, NREM-wakefulness). Sleep Walking Somnambulism is a disorder of arousal = a parasomnia. Sleepwalkers appear to have an abnormality in SWS regulation especially during the first sleep cycle, and the whole NREM-REM sleep cycle is more fragmented. Perhaps a sign of CNS immaturity as mostly in children. Stress, fatigue, anxiety, alcohol, drugs all can be linked to sleep walking. Consciousness Definitions of Consciousness  Conducting an investigation with the very instrument being investigated makes both the definition of the problem and the approach to a solution especially complicated. Self awareness A constellation of thoughts, emotions, perceptions, sensations and dreams An alert cognitive state Concept of Attention The subjective, inner life of the Mind Your definition goes here! Levels of Consciousness Dependent on a person’s responsiveness to stimuli from the environment: 1) conscious (alert, aware of self and surroundings), 2) confused (disoriented), 3) delirious (disoriented but including hallucinations) 4) stuporous (sleep like state, still respond to pain), 5) persistent vegetative state or comatose (no response to stimuli, no pupil response). Glasgow Coma scale: a) eye-opening, b) verbal, c) motor responding) Localizing Consciousness? Acute bilateral loss of function in the intralaminar nuclei of the thalamus widely and reciprocally connected to the basal ganglia and cerebral cortex leads to immediate coma or profound disruption in arousal and consciousness. Similarly, damage to the reticular activating system needed for sleep, arousal, attention, memory can also lead to alterations in consciousness. Destruction of circumscribed parts of the cerebral cortex of patients can eliminate very specific aspects of consciousness, such as the ability to be aware of motion or to recognize objects as faces, without a concomitant loss of vision in general. Role of Claustrum? fMRI of Vegetative State Language areas active when sentences read. Motor areas active when asked to imagine playing tennis. Visual spatial navigation areas active when asked to go through her home from room to room. Theories of Consciousness Quantum physicist Ramachandran Blindsight Gazzanigan – consciousness is an emergent property, not a process in and of itself – a singular feeling of consciousness emerges from the chaos of 100 trillion neural connections. How? Investigating Consciousness; Historical Approaches within Psychology ○ Introspection  ○ Behaviourism Modern Approaches within Psychology ○ Deficits caused by stroke, lesions, injury ○ Dementia, schizophrenia – is it essential to be in touch with reality? What can this tell us about consciousness? Two Problems (Easy and Hard) Easy = How can a human subject discriminate sensory stimuli and react to them appropriately? How does the brain integrate information from many different sources and use this information to control behaviour? How is it that subjects can verbalize their internal states? = objective mechanisms of the cognitive system. Hard = How physical process in the brain gives rise to subjective experience. This involves the inner aspect of thought and perception: the way things feel for the subject. Neuroscience According to Crick & Koch, the neural correlates of consciousness can be defined as “the minimal neuronal mechanisms jointly sufficient for any one specific conscious percept” Visual Perception as Evidence Many researchers use ambiguous visual stimuli to understand consciousness. Neurotransmitter Correlates of Consciousness All neurotransmitter systems influence and regulate each other, and only a sensible balance between makes correct functioning possible. The whole brain is more than just the sum of its parts, and each part is of equal importance. Identifying a single part as being more important than the others has to be seen as a mistake. Conscious Thoughts Understanding how the brain works mechanically may not elucidate how it works conceptually.  Perhaps the mystery of the human brain is a good thing to some degree; self privacy. Consciousness and the Brain ‘Our brains have not evolved the equipment to resolve this mystery. They go blank when they try to understand how they produce the awareness that is our prized essence’. Colin McGinn (philosopher) Reward The Three Brains Primitive Brain – Limbic and Brainstem ○ Avoid harm, satisfy essential needs (food, water, sex, safety), fight/flight/freeze, survival Newer Brain - PFC ○ Imagine, plan, self-monitor, rationalize, create, decision making Brain Development Striatum = Older Brain – reward, motivation PFC = Newer Brain – Executive functioning Sex and the Brain Dreher and Sescousse conducted an original experiment in the form of a game that rewarded 18 volunteers with money or erotic images, during fMRI. Shared cerebral regions = the ventral striatum, insula, midbrain and anterior cingulate cortex. Dissociation between primary and secondary rewards in the orbitofrontal cortex. Posterior (more primitive) = erotic images (primary). Anterior (more recent) = monetary gain (secondary). ○ The more abstract and complex the reward, the more its representation stimulates the anterior regions of the orbitofrontal cortex – evolution? Also drugs, exercise, food, gambling, video games, coffee, work, thoughts, shopping and social media Reward Based Learning Trigger (ex. i’m bored or sad) → behavior → reward → repeat Addiction Hijacks the Brain Turns off the PFC and leaves you in the Older brain (reward system). Judgment becomes distorted and the brain starts to treat the substance as necessary for survival. It is not a failure of moral judgement or poor will power – the brain IS hijacked Where and How? Olds and Milner, in 1954, discovered intracranial self stimulation (ISS) of the brain. Certain brain regions will keep an animal pressing a button or performing a behaviour to get the stimulation. Examples are the hypothalamus and the Medial Forebrain Bundle (MFB). Medial Forebrain Bundle (MFB) originates in the reticular formation, crosses the ventral tegmental area (VTA) and the lateral hypothalamus and continues into the nucleus accumbens, amygdala, septum and prefrontal cortex. MFB is the basis of the reward circuit as it encompasses the dopaminergic axons projecting from the VTA to the nucleus accumbens and amygdala in the Mesolimbic reward pathway (and from the VTA to the prefrontal cortex (Mesocortical pathway)). ↑ DA = reinforces the behaviours being performed. Increases in DA 1. DA increases with brain stimulation (ISS) 2. Drugs that increase DA increase ISS 3. Feeding and sex increase DA in nucleus accumbens 4. Nicotine and cocaine and other drugs increase DA in nucleus accumbens (opiates also increase DA among other things). 5. Anticipation of reward – leads to craving 6. Stimuli related to reward – paraphernalia, cues Other Brain Regions OFC receives direct inputs from primary taste and olfactory cortices as well as from higher order visual and somatosensory areas, thus storing reward value of all sensory stimuli. OFC responds in conditions that require both approach behaviour (medial) and response inhibition (lateral). Necessary for generating appropriate reward-directed behavioural responses.  Amygdala seems to be activated when positive or negative reinforcers are presented – the stronger the reinforcer the more amygdala activity there is. Ventral striatum (nucleus accumbens and olfactory tubercle) – stimulation is highly rewarding and plays a role in predicting rewards and biasing actions that seek rewards. Model of Addiction Newton’s 3rd Law of Physics For every action there is an equal and opposite reaction. The high transforms into a corresponding low…and with each succeeding drug or alcohol event, tolerance is built up and one needs more and more to get less and less of an effect. The high continues falling further and further until a person is no longer using to get high but just to get normal. "just keep me out of the quicksand" — prepared to do anything to avoid the withdrawal, the misery. More than just Dopamine Interplay of Neurotransmitters Endogenous Opiates: Endorphins in the VTA act on mu receptors on the dendrites of GABAergic interneurons. Normally, these interneurons inhibit the dopaminergic neurons that project from the VTA to the nucleus accumbens. But if natural endorphin levels increase (sports, drugs), it suppresses the release of GABA and thus removes the GABAergic inhibition on these dopaminergic neurons. = increase DA Consequently, the nucleus accumbens is even more stimulated by the dopamine from the dopaminergic neurons of the VTA, which creates a positive reinforcement. Heroin and morphine have a similar structure to endogenous endorphins and enkephalins and attach to the same receptors. In response to this artificial surplus, the endorphin/enkephalin-producing neurons reduce their activity and with no more drug, a person with a substance use disorder experiences displeasure and physical distress = drug dependency. Drivers of Habits of Thinking 1. Living on “automatic pilot” (rather than with awareness and conscious choice). 2. Relating to experience through thought (rather than directly sensing). 3. Dwelling on and in the past and future (rather than being fully in the present moment). 4. Trying to avoid, escape, or get rid of unpleasant experience (rather than approach it with interest). 5. Needing things to be different from how they are (rather than allowing them to be just as they already are). 6. Seeing thoughts as true and real (rather than as mental events that may or may not correspond to reality). 7. Treating yourself harshly and unkindly (rather than taking care of yourself with kindness and compassion). Drugs and Reward Caffeine Adenosine = neuromodulator that reduces neural activity. Caffeine acts as an adenosine antagonist. Speeding up neural activity causing the pituitary gland to secrete hormones that increase adrenaline = attention and energy burst. Caffeine also increases DA from VTA to nucleus accumbens. Drugs of Abuse Substance Use Disorder Impact on Society Drugs of abuse Technology Sex Food Gambling Shopping Exercise Work We Can’t Ignore This Why do people use? Why do some people get addicted while others do not? https://www.youtube.com/watch?feature=share&v=66cYcSak6nE&app=desktop