Advances in the Brain and Behavioral Sciences

Presented by

John Arden, Ph.D.

Disclosure Neither Dr. John Arden, the presenting speaker, nor the activity planners of this program are aware of any actual, potential or perceived conflict of interest

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Institute for Brain Potential

PO Box 2238 Los Banos, CA 93635

COURSE OBJECTIVES Participants completing the program should be able to identify evidence‐based approaches to: 1. Overcoming traumatic and posttraumatic stress related disorders including adverse childhood and adult experiences. 2. Understanding and managing generalized anxiety disorder, social anxiety disorder, and perfectionism. 3. Enhancing emotional resilience 4. Improving health‐related habits 5. Understanding and applying mind‐body approaches to improve the mind‐body connection as it affects the immune system and inflammation. 6. Understanding and improving interpersonal relationships including reasoning with unreasonable people and high‐conflict interactions. 7. Describing how food affects mental health 8. Understanding and improving memory and cognition and preventing dementia. 9. Adopting lifestyle modifications for improving physical activity, diet, meditation and sleep. 10. Applying positive psychology. Policies and Procedures 1. Questions are encouraged. However, please try to ask questions related to the topic being discussed. You may ask your question by clicking on “chat.” Your questions will be communicated to the presenter during the breaks. Dr. Arden will be providing registrants with information as to how to reach him by email for questions after the day of the live broadcast.

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In the unlikely event that you lose your certificate, please send your request in writing and a check for $20 payable to IBP at PO Box 2238, Los Banos, CA 93635, email [email protected], or call 866 -652-7414. IBP is a nonprofit scientific and educational organization dedicated to promoting advances in behavioral medicine. IBP is entirely supported by the tuition it charges for its seminars and the sale of educational materials. Neither IBP, its planning committee, nor any of its instructors has a material or financial interest with any entity, product, or service mentioned in the seminar unless such relationship is disclosed at the beginning of the program. The information presented is of a general nature. For specific advice, please consult a specialist in your area. Advances in the Brain and Behavioral Sciences The Ten Certificate Programs 1. Understanding and Overcoming Trauma 2. Understanding and Managing Anxiety 3. Developing Emotional Resilience 4. Improving Health-Related Habits 5. The Immune System, Inflammation and the Mind-Body Connection

The Ten Certificate Programs UNDERSTANDING AND OVERCOMING TRAUMA 6. Managing Interpersonal Conflicts A Certificate Program 7. How Food Affects Mental Health 8. Understanding Memory, Cognition and Earn 12 hours of CE and a Certificate: Dementia Lecture 1: Adverse Childhood Events 9. Lifestyle Modification to Create Lecture 2: Understanding and Treating PTSD Meaningful Change 10. Applying Positive Psychology

John Arden, PhD, ABPP John D. Preston, PsyD, ABPP Dr. Arden is the Chief Academic Officer for IBP. Dr. Preston has been Professor at Alliant The author of 15 books, he was previously the International University. He is the author Northern California Director of Training of numerous texts concerning brain and overseeing 24 Kaiser Permanente medical centers with 150 interns and postdoctoral behavior. residents. He received the Mental Health He has been instrumental in developing the Association’s President’s Award for certificate program and enabling IBP attendees exceptional contributions to the mental to receive graduate credit for taking IBP health community. He has taught for the lectures. For questions email him at: Institute since the 1990s. [email protected]

1 Categories of Adverse The ACE Study Childhood Experiences Abuse, by Category Category • Examined the health effects of ACE’s throughout the lifespan among 17, 421 Prevalence (%) members of Kaiser Permanente in San • Psychological (by parents) 11% Diego county • Physical (by parents) 11% • Sexual (anyone) 22% • What are Adverse Childhood Experience? Household Dysfunction, by Category • Substance Abuse in family 26% – Childhood abuse and neglect • Mental Illness in family 19% – Growing up with domestic violence, • Domestic Violence 13% substance abuse, parental discord, • Imprisoned Household Member 3% crime, or mental illness in the home • Loss of parent 23%

The ACE Score and the Prevalence of ACEs score percentages Severe Obesity (BMI>35)

Number of categories of childhood experiences ACE Score are summed Prevalence 0 48% 1 25% 2 13% 37% 47% Percent obese (%) • More than half have at least one ACE • Slightly more than one quarter have experienced ACE Score 2 – 4 ACE categories

The ACE Score and a History of Sexual Abuse of Male Children and Their Lifetime Depression Likelihood of Impregnating a Teenage Girl

1.8x

1.3x 1.4x

1.0 ref Percent depressed (%)

ACE Score Not 16-18yrs 11-15 yrs <=10 yrs abused Age when first abused

2 The ACE Score and the Prevalence of ACE Scores and Attempted Suicide History of STDs Percent attempted (%)

ACE Score

Childhood Sexual Abuse and the ACE Score and Hallucinations Number of Unexplained Symptoms

Abused Number of Symptoms Alcohol 0 1 2 3 4 5 6 7 8 or Drugs (%) Percent Abused Abused Percent Ever (%) Hallucinated* Ever History of Childhood Sexual Abuse ACE Score *Adjusted for age, sex, race, and education.

ACE Score and Indicators of ACE Score and Rates of Impaired Worker Performance Antidepressant Prescriptions

25 ACE Score approximately 50 years later 0 1 2 3 4 or more 20 4 5 or more 15 3

10 2 1 Performance Performance (%) 5 Prevalence Prevalence of Impaired

Prescription Prescription rate 0 per 100 person-years)

0 Absenteeism (>2 Serious Financial Serious Job ACE Score days/month Poblems Problems

3 Effect of ACEs on Death Rate

Death Age Group Early Death

Disease, Disability and Social Problems Adoption of Health-risk Behaviors

Social, Emotional, & Cognitive Impairment

Adverse Childhood Experiences

The Science has Changed Epigenetics

“Mental functions direct electrochemical traffic at the cellular level” Roger Sperry

“Psychotherapy works by producing changes in gene expression that alter the strength of synaptic connections…” Eric Kandel

Epigenetics and Increased Stress Epigenetics and Decreased Stress

• Increased methylation levels of cortisol receptor • Decreased methylation levels of cortisol gene: receptor gene: • In suicide victims with a family history of • In offspring who had good nurturing abuse and/or neglect • Also in preemies: produces more cortisol receptors on the • Can’t easily turn off the stress response hippocampus • Decreased methylation of the arginine • Lower levels of CRH, ACTH, and vasopressin gene cortisol • If stressed early in life: • More 5-HT • Resulting in increased vasopressin and stimulating the stress response • Stress tolerance (Good thermostat)

4 Cell Aging: Telomeres Length Stress and Telomeres * • “Psychobiomarker”: Linked to social status, perceived stress, depression, predictive of

mortality (Epel, 2009, Current Directions) • •Telomeres: non-coding sequences capping ends, serving as a  Chronic stress and perceived stress were associated with • “senescence clock” (Blackburn, 1978) shorter telomeres as well as reduced telomerase. • •Telomerase: enzyme that prevents  Women with the highest levels of perceived stress have shortest telomeres telomere shortening, promotes cell  Shorter on average by the equivalent of at least one resilience. decade of additional aging. • Psychobiomarker”: Linked to social status, perceived stress, • depression, predictive of mortality (Epel, 2009, Current Directions)  These findings may explain one way in which stress promotes earlier onset of age-related diseases. Epel, Blackburn et al , PNAS, 2004

Dopamine D2 Receptors in Drug The Epidemic Users And Food Addicts

• Drug Addiction • Obese

• DA D2 (Dopamine Receptors) • In the brains of controls, drug abusers, and obese subjects

• Bad Diet Obesity-Associated Adipose Tissue • Simple carbs Inflammation • Transfatty acids Di • Saturated fats • Food allergies • Bad oils • High dairy • High gluten •No exercise •Chronic illnesses • Autoimmune disorders •Chronic pain • Chronic stress • Being overweight • Apple shape • Leaky gut

5 Deprived Social Brain Networks

Epigenetics • 150,000 children found languishing in • Severe neglect: gene silencing: Romanian orphanages. They were emotionally neglected. excessive methylation interfering with access to genes • They missed human contact during critical periods (Kuhn & Schanberg, 1998). cortisol receptor gene: ?? Inter-generational transmission?? Sustained impairment if over one year • Size of hippocampus: – Increased Cortisol Size matters: smaller: • Impaired OFC less stress resistance • Cognitive impairments (i.e. ADD) Influence on the brain’s ability to regulate affect

SEVERE NEGLECT: “Normal” vs Romanian Brains Persistent Neurobiological Changes Decreased serotonin irritability; reduced emotional control Increased CRF: ↓ deep sleep; depression; anxiety Decreased Oxytocin: attachment problems

Child Abuse and Neuropathology “Normal” vs Abused Brains • Diminished left hemisphere and left hippocampal volume (Bremner et al., 1997).

• Accelerated loss of neurons (Simantov, et. al., 1996)

• Delays myelination (Dunlap, et. al., 1997) • Abnormalities in developmentally appropriate

pruning (Todd, 1992)

• Inhibition of neurogenesis (Gould, et. al., 1997) • Adults who were physically or sexually abused as children – high IL-6 & CRP

• diminished left hippocampal development (Howe, Roth, & Cicchetti, 2006).

6 Chronic, severe, inescapable Avoidance • The major factor in perpetuating PTSD • War Zones and contributing to a more chronic course • Rape But, severity of the traumatic event • Avoiding specific trauma • Child abuse is not predictive of triggers; Reminders outcome – People • Elder abuse – Situations – Conversations • Domestic violence – Media – Medical Treatment • POWs and refugees

Disordered Fear Regulation in PTSD Parallel Brain Circuits, Encoding , Memory, and Response

From: Mahan AL, Ressler KJ. Trends Neurosci, 2012, 35:24-35. Amygdala

Amygdala-Level Processing

• Rapid, Crude, Generalized • Many false alarms • Non-Responsive to new “Data” • Outside awareness & Automatic • Beneath the radar of consciousness

7 Impaired Information Processing in Post-Traumatic Stress Disorder

• Dissociation at time of trauma (encoding) • Fragmented, “jigsaw” memories images, emotions, bodily sensations, cognitions……… dis-integrated cont.

Working the Physical & mental Health Benefits of Positive Psychology “Therapeutic Window” Posttraumatic Growth: Bonanno, Rennicke, & Dekel (2005): resilience is most common outcome of trauma, not PTSD! lessons from bamboo Predictive factors: early social support, early + meaning Appreciation for life, personal strength, identify and act on new life directions, improved relationships, spiritual deepening. Post Traumatic Growth Inventory (Tedeschi & Calhoun, 2006)

Post-Traumatic Growth UNDERSTANDING AND MANAGING ANXIETY Martin Seligman, 2012 A Certificate Program

•Compassion…altruism Earn 18 hours of CE and a Certificate •Capacity for empathy Lecture 1: Why We Worry Lecture 2: Shyness and Social Anxiety •Create a new identity Lecture 3: The Pathology of Perfectionism as a survivor

8 Physiology of GAD Martin Antony, PhD, ABPP • Less parasympathetic more Dr. Antony is an internationally sympathetic-- reduced vagal tone recognized expert in the assessment • Bed nucleus of the stria terminalis (BNST) and treatment of anxiety, past –Free-floating anxiety president of the Canadian • Amygdala—an intolerance for Psychological Association, and ambiguity leading author and speaker in the – Anxious individuals select more field of anxiety disorders. threatening interpretations of

ambiguous stimuli (e.g., Mathews & Mackintosh, 2000) •

Balancing the ANS Activating the PNS

• Diaphragmatic Breathing: Stretch • Yoga • Meditation • Cuddling • Orgasm • Pulling the Kegel

↑ Oxygen Breathing and Over-Breathing ↓↓ CO2 Variability is good • Most people breathe 9 to 16 breaths per minute. Panic attacks - Peak/valley differences 27 breaths Notice how heart rate = vagal tone when resp is in normal range • Over-breathing pulls in too much increases with inhale. oxygen forces down the carbon Heart rate decreases with stream. exhale. This pattern shows • Carbon dioxide helps maintain the critical acid base (pH) level in high vagal tone (high Respiration Heart blood. Lower pH level causes Rate nerve cells become more excitable PSNS activity) and a high and people associate the feelings amount of heart rate with a panic attack. variability. • Causing respiratory alkalosis Gevirtz 11/15/2017

9 CBT vs. Metacognitive Models Interrupting the Worry Loop (ACT, DBT, MBCBT, etc.)

CBT MC Models Rationale=control Rationale=relinquish control Cognitive restructuring Thought Diffusion Breathing retraining Observe & accept Interoceptive exposure to Interoceptive exposure with lessen fear & avoidance acceptance of internal cues Situational Situational exposure to lessen fear exposure to achieve fear and avoidance life values and goals

REAL not GAD Exposure-Based Treatments “R” is for relaxation, including deep breathing, stretching, self hypnosis, mediation, and prayer to activate your parasympathetic nervous system and increase vagal tone. “E” is for exposure such as in scheduling an hour of worry time, In-Vivo Exposure allowing focused exposure to all your worries, and giving your higher brain a chance to work on developing the capability of Imaginal Exposure dealing with the ambiguities inherent to life. “A” is for acceptance. Since there is no ultimate certainty with Interoceptive (Symptom) Exposure much of life, acceptance of uncertainties allows worries to fade into the texture of normal living. Prevention of Safety Behaviors “L” is for labeling. When you have an anxious thought you can label it as just “an anxious thought,” thereby detaching from Virtual Reality Exposure the feeling of anxiety.

Principles of Effective Exposure Is Acceptance Anything New? • Accepting the presence of anxiety is crucial Predictability and perceived control • The patient usually wants to avoid or fight anxiety symptoms. Graduated exposure versus flooding In cognitive therapy, he is encouraged instead to accept his Longer exposure practices work best symptoms Exposures should be spaced closely • Paradoxically, by giving up the idea of control, the patient can be taught to control his anxiety Reduce the use of safety behaviors and subtle • Acceptance is allowing what exists at the moment to be as it avoidance strategies is. Acceptance is acknowledging the existence of an event Vary the context of the exposure practices without placing a judgment or label on it (right/wrong, good/bad, Do not fight the fear safe/dangerous) • The patient is encouraged to stop "value-judging" his anxiety

10 Deceptively Simple but so Complex Interoceptive Exposure + • There are a variety of interoceptive exercises Exposure including: Techniques –Running in place--- to increase heart rate and hyperventilation and the Will –Holding your breath--- to simulate to face fears sensations of suffocation –Spinning--- leading to dizziness –Hyperventilation or breathing through a straw---leading to light- headedness

Neurodynamics of Anxiety Slow Track—Allostasis

• Two routes to the amygdala, the fast –Automatic thoughts—fast track and slow impulse—interrupt with curiosity and time • Right frontal bias in general for – Assumptions—from pessimism to anxiety disorders incremental optimism • Under-activation of the left • “I’m working on it and can tolerate frontal lobes and in Broca’s distress” area explains why some people feel “speechless” – Core beliefs—existential self descriptor

when they’re scared (Rauch et al., 1997). • “I’m a survivor.” • Global/Passive (R-PFC) vs. Detail/Action (L-PFC)

Shifting Perspective to Speed Up BEAT Panic the Slow Track “B” is for body. When you feel your heart race or breathe too • Labeling thoughts—”That is an anxiety provoking fast just ride it out. Say, “I can befriend my own body! thought” vs. “This makes me anxious!”—R-vlPFC “E” is for exposure. Through interceptive exposure exercises you can regain tolerance to body sensations. Say, “this is • Externalizing—”What would another person in this not a heart attack but just my own body sensations that I’ve situation say and how is s/he right?” felt many times before.” “A” is for the amygdala. With its fast and slow tracks. “I can • Temporal Distance—”How will I sensibly view this learn to slow down my fast track and speed up my slow situation in six months?” track.” “T” is for thinking. To speed up your slow track, remind • Humor—”What is funny about this?” yourself that what you think is happening has a dramatic effect on what you feel is happening. • Wisdom—”How can I grow from this?”

11 DEVELOPING EMOTIONAL RESILIENCE John D. Preston, Psy.D., ABPP A Certificate Program Dr. Preston has been Professor at Alliant International University. He is the author Earn 18 hours of CE and a Certificate of numerous texts concerning brain and Lecture 1: Developing Positive Emotional Habits behavior. Lecture 2: Mastering Sixteen Key Habits of He received the Mental Health Emotionally Resilient People Association’s President’s Award for Lecture 3: Understanding and Practicing Positive exceptional contributions to the mental Psychology health community. He has taught for the Institute since the 1990s.

Kateri McRae, PhD William Sieber, PhD Dr. McRae, an expert in the study of Dr. Sieber is a Clinical Professor in emotion regulation, is Associate Psychiatry and Family Medicine at the Professor of Psychology at the University of California, San Diego. University of Colorado, Denver. He coordinates the Collaborative Care Her work includes the role of brain program, and supervises primary care images to reveal how emotions are patients with chronic illnesses. His organized in the brain and clinical expertise includes the strategies to improve resilience. treatment of fatigue, stress, anxiety, and mood disorders.

Primary Care is the ‘De Facto’ Prevalence Mental Health System

Pie of all behavioral health needs

Sources: 1McGinnis JM et al. JAMA 1993; 270:2207-12. 2Mokdad AH, et 71 Source: Wang P et al. Arch Gen Psychiatry, 2005: 62. 72 al. JAMA 2004; 291:1230-1245. Adapted from Katon, Rundell, Unützer, Academy of PSM Integrated Behavioral Health 2014

12 The danger of downward spirals The reappraisal brain

Ochsner, Silvers & Buhle, 2012

Thoughts that control emotion Emotion regulation strategies

• It’s not as bad as I first thought Do more Do less • This won’t last forever • Situation modification • Avoidance • This will be better soon • Distraction • Distraction • This will be even better than before • Reappraisal • Suppression • Labeling • Rumination • This is worth it • Finding social support • This is normal • Problem‐solving • How will I feel about this tomorrow? Next year? 10 years? • Accepting • What would I tell a friend in this situation?

The reward circuit turns actions to habits But There’s Habituation… • Striatum: Basal Ganglia circuit –Also part of lower “animalistic” brain • Repeated stimulation decreases –Learns habits/responses without thought response of reward system –Activates habitual motor patterns –Learns reward‐seeking behaviors • Too much of a good thing: –“Stamps” actions that are followed by reward into memory –Good becomes neutral • This reward system increases the likelihood that a behavior will be repeated and “transfers” its response to the earliest reliable predictor of reward (cue) • Even more of a good thing: –Neutral becomes unpleasant

13 How to curtail habituation Delay of gratification predicts… • Higher SAT scores • Make pleasure last longer: savoring • Better social competence • Keep pleasure in mind: notice the • Self‐assuredness and self‐esteem experience, devote awareness to it • Fewer conduct disorders • Avoid repeating the experience right • Lower impulsiveness, aggressiveness, hyperactivity away • Less likely to have substance abuse problems, get –Food: the 10 minute rule divorced, be overweight

Mischel et al., 1989

Catch the upward spiral Optimism, Well‐Being and Mortality • Meta analysis: 70 studies • Optimistic people: 18% less likely to die from: almost all causes of mortality • Psychological well‐being is protective

Chida & Steptoe, 2008

Understanding Positive Beliefs about change Psychology • Fixed mindset: – people believe their basic qualities, like their Wanting Versus Liking: wanting is a intelligence or talent, are simply fixed traits. They dopamine-driven state that is identified with spend their time documenting their intelligence or talent instead of developing them. They also believe craving and addiction; liking is a state that that talent alone creates success—without effort. activates the endogenous opioid receptors of • Growth mindset: the brain and is associated with satisfaction, – people believe that their most basic abilities can be enjoyment, and liking. developed through dedication and hard work—brains and talent are just the starting point. This view creates Wanting without liking is the essence of a love of learning and a resilience that is essential for addiction; liking without wanting is the essence great accomplishment of happiness.

14 Managing cravings Executive Network: with increased dopamine? bilateral prefrontal cortex; When dopamine is low in the limbic system then immediate rewards (simple decision) wins out. When sufficient responsible for selection, planning, and dopamine is present, then prefrontal cortex (complexity, delayed gratification) will win out. decision-making toward goals; Memory, based in hippocampus, tends to lower firing of working memory that helps select, orient, dopamine neurons with expectation of a familiar non- gratifying activity, more firing of dopamine neurons with a and maintain an object in the mind; familiar pleasurable activity, whereas greater firing of dopamine neurons occur when ‘opportunity’ for pleasure is moment to moment monitoring of novel (encouraging exploration). experience (meta-cognition) Gratitude journal, self-care, massage, dance, play, novelty

Default Mode Network (DMN): Salience Network (SN): anterior and posterior midline and cingulate cortex; bilateral anterior insulae, dorsal anterior spontaneous thoughts or mind-wandering; cingulate, amygdala; activated during tasks of mentalizing, projecting oneself into the future & decision-making; detecting emotional and reward saliency;  activation when performing focused attention detecting and orienting toward external events meditation in bottom-up fashion; referred to as the ‘sentient self’ (meta- awareness)

Creating Positive States and The Limits of Positive Traits Psychology States and Traits: states are temporary Pathological Search For Happiness: the search for emotional experiences that can vary happiness does not make us happy — it is happiness- related experiences that underlies and helps sustain from moment-to-moment, from positive emotional states.

madness to mindfulness; traits are Half of people value money more than time, and this enduring characteristics such as a tends to be a fairly consistent trait both for daily interactions and major life events. Those who reported mindset that predisposes us to be fearful valuing time more than money reported greater happiness (Whillans, 2015) (study did not include or to be loving those in poverty!)

15 IMPROVING HEALTH-RELATED HABITS George F. Koob, PhD A Certificate Program Dr. Koob is an expert on how the brain forms new habits. He is Director of the National Earn 24 hours of CE and a Certificate Institute of Drug Abuse and Alcoholism of Lecture 1: How the Brain Forms New Habits the NIH. Lecture 2: Calming an Overactive Brain He Chairs the Committee on the Lecture 3: Substance and Addictive Disorders Neurobiology of Addictive Disorders at Lecture 4: How to Adopt Healthful Habits Scripps and teaches at UCSD where he received five “Outstanding Faculty Teaching Awards.”

Jodie Trafton, PhD Bill M. Kelley, PhD.

Dr. Trafton is a neuroscientist and affiliated the Stanford Dr. Kelley is a Professor of Center for Health Policy. She is responsible for national evaluation of mental health programs concerning the Psychological and Brain Sciences at treatment of addictive disorders, the behavioral Dartmouth College. Dr. Kelley is an management of chronic conditions and Directors VA expert in the study how people Evaluation and Resource Center. learn to control their thoughts, She directs the Publication Division of the Institute for behaviors, emotions, and desires Brain Potential including the Best Practice Series and the and how people form new habits. text Training Your Brain To Adopt Healthful Habits. She has taught for the Institute for over a decade.

Features of Addiction Three Types of Habits Key Elements • Automatic Thoughts (blue) • Compulsive bad habits • Automatic Actions (green) – Repeated reward‐seeking despite negative consequences • Cravings, Fears, and Emotions (orange) – Craving for reward – Loss of control in limiting intake • Become normal with the substance on board -- Tolerance • Withdrawal when abstaining – Can be drug-specific or global -- Characterized by negative emotional states • Habits have triggers, learned contexts where rewards are available for seeking

16 Dependence Cycles Addiction Cycle to Motivation for Drug Seeking

• Lead not only to compulsively repeated responses, but also increasingly negative emotional states, and dysregulation of affective and stress systems – For example, decreases in dopamine function and increases in CRF function • Downward spiral – Chasing relief with a response that maintains From: Koob GF. Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit disorder. In: Spanagel R, Sommer W (eds) Behavioral Neurobiology of Alcohol Addiction (series title: the distress Current Topics in Behavioral Neuroscience), Springer, New York, in press.

Theoretical Framework Relating Addiction Habits are Learned and Maintained by Cycle to Motivation for Drug Seeking Reinforcement Circuits • Reinforcement is not always pleasure – It increases the likelihood of repetition – Not always associated with positive affect • Reinforcement takes you from an immediate state of: OK to good = positive reinforcement – Reinforcement- focused habits Bad to OK (or less bad) = negative reinforcement – Threat‐based habits – You can reinforce a response without ever having felt good or euphoric

From: Koob GF. Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit disorder. In: Spanagel R, Sommer W (eds) Behavioral Neurobiology of Alcohol Addiction (series title: • Partial relief of an ongoing pain stimulus Current Topics in Behavioral Neuroscience), Springer, New York, in press.

Neurobiology of Addiction: Binge-Intoxication Stage Preoccupation/Anticipation (“Craving”) Stage

From: Koob, G. F. and Volkow. N. D. Neurocircuitry of Addiction, Neuropsychopharmacology From: Koob, G. F. and Volkow. N. D. Neurocircuitry of Addiction, Neuropsychopharmacology Reviews reviews 35 (2010) 217-238 35 (2010) 217-238

17 Withdrawal-Negative Affect Stage Neurobiology of Addiction

From: Koob, G. F. and Volkow. N. D. Neurocircuitry of Addiction, Neuropsychopharmacology Reviews From: Koob, G. F. and Volkow. N. D. Neurocircuitry of Addiction, Neuropsychopharmacology Reviews 35 (2010) 217-238 35 (2010) 217-238

Conceptual Framework for Neurobiological Bases of the Transition to Compulsive Drug Seeking Cognitive Overvaluation

• Our conscious beliefs and expectations change our dopamine neuron function – Example: Placebo effects – Being given a placebo “painkiller” increased release of dopamine in persons who were anticipating a painful stimulus in proportion to the anticipated analgesic effects (Scott et al., 2007) – A placebo “analgesic cream” decreased self‐reported pain and activation of brain circuits that detect pain in

response to a heat stimulus (Wager et al., 2004)

Secondary Gain Associational Overvaluation • Rewards that are linked in time to behaviors can amplify reward • Doting, rescuing, or attending primarily to negative estimates responses can reinforce bad habits in others – Example: Pictures of attractive faces activate dopaminergic • Providing attention, relief, or rescuing people when they reward circuits and arbitrary pictures that had been shown at the respond inappropriately can reward bad responses and same time as the attractive faces were preferred following the make them habitual viewing session (Bray & O’Doherty, 2007) – Advertising uses this principal • These rewards can turn a maladaptive response into a • We will overvalue habits that have been linked to other rewards, habit like pretty faces, symbols of power, successes, or relief • If we are rewarded for doing things that make us feel bad, • Experience by observation will train these circuits then we will tend to feel bad – Seeing someone else benefit can change our estimates

18 Decreased Dopamine D Receptor Activity Reward Transmitters Implicated in the Motivational Effects of 2 in a Cocaine Abuser Drugs of Abuse

Positive Hedonic Effects Negative Hedonic Effects of Withdrawal Dopamine Dopamine … “dysphoria”

Opioid peptides Opioid peptides ... pain

Serotonin Serotonin … “dysphoria”

GABA GABA … anxiety, panic attacks

From: Volkow ND, Fowler JS, Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey S and Wolf AP, Synapse, 1993, 14:169-177.

CRF, Stress, and Bad Habits Cravings: Neurobiology • Reward and punishment processing (negative affect) – Addictions reduce aversive states – Impaired prefrontal functioning

• Stress will make you more likely to do bad habits • Cue-reactivity and attentional bias – Attention is directed unconsciously to stimuli associated with • Activation of these neurons also facilitates fear substance abused – Attentional bias  enhanced sensitivity to drug-related rewards  risk conditioning and prevents fading of these associations for cue-reactivity  craving and relapse – Higher activity of limbic system, or anterior cingulate cortex, or PFC – – Learning of fear cues by the amygdala • Impulsivity – Motor: impulsive action or disinhibition – Chronic activation of these circuits can lead to – Cognitive: impulsive choice generalized anxiety and exaggerated fear responses – Associated with prefrontal dysregulation • Decision making and executive function • Fear can prevent behavior change and maintain bad – Maladaptive decision making or cognitive inflexibility – Contrary results: majority found decreased dlPFC activation, coupled habits with activation of OFC, parietal cortex, putamen, and postcentral gyrus

From: Crunelle et al. 2012 Brain and Behavior 2: 499-523

Anti-Reward Transmitters Implicated in the Motivational Effects of Addictive Features of Comfort Foods Drugs of Abuse • Compulsive Eating Disorders – A disorder of compulsive overeating – Food dependence: Hunger leads to eating which in the absence of additional eating is followed by hunger Dynorphin … “dysphoria” – Short‐cutting this cycle can lead to overeating CRF … stress • Eating carbohydrates may increase reward neurotransmitters and improve Norepinephrine … stress mood • Eating to feel better and weight‐related stigma can produce a dependence cycle • If you eat for relief when you feel bad but feel bad about yourself when you eat, then you will chronically overeat

– Compulsive overeating is associated with decreased D2 receptors in the basal ganglia in human and animal studies, and increases in CRF activity

19 Non Drug “Process” Addiction Cycles Drug AddictionCompulsive Exercise Compulsive Shopping Substance Use Disorders

• Core problem: – Over‐trained, over‐triggered, over‐valued, easily‐induced, punishment‐resistant drug‐seeking behaviors • Additional common issues: Compulsive GamblingCompulsive Eating Compulsive Sex – Dependence – Tolerance – Harmful effects of acute or repeated drug ingestion

Cingulate

Training the Brain’s Reward Learning System Frontal Cortex Striatum

Substantia Nigra • Circuit designed to train in automatic habits of thought, Dopamine emotion and behavior that produce quick gains in well‐being motor neurons • Detects opportunities for quick benefit or relief (i.e. recognizes potential rewards) – Dopaminergic neurons signal opportunities

• Learns and encourages return to context in which the Nucleus opportunity was experienced Accumbens

• Hippocampus Addictive drugs pharmacologically disrupt this circuit and Extended Amygdala process in a consistent way & VTA Dorsal Raphe Nucleus Dopamine reward neurons Serotonin neurons

Do drugs activate reward pathways differently than What does this system normally do? natural rewards? • Involved in prediction of reward • On first exposure to a novel reward, get dopamine – Emotionally salient stimuli such as food, water, sex, neuron firing at time of reward receipt. Same with social reward, pain, threats, and so forth, all release drugs. dopamine in the nucleus accumbens. • With repeated exposure to the same natural reward, • Nucleus Accumbens is situated between the the dopamine neuron signal gets shifted to the systems involved in detecting emotionally earliest predictive cue, and there is no longer dopamine neuron firing at the time of reward important situations (the Amygdala) and those receipt. If the reward does not arrive, dopamine that initiate habitual behavior (the striatum) neuron firing will decrease below baseline levels. – This system helps determine when you need to react to • Dopaminergic VTA neurons provides an error signal potential rewards, either by seeking positive rewards about reward predictions. or escaping harm.

20 Dopamine Firing Dopamine Firing

First exposure to natural reward: First exposure to drug reward:

After repeated exposure to same reward and predictor: Next exposure to drug and predictor:

First time a better reward is received: After repeated exposure to drug:

If expected reward isn’t received:

Cue Reward Cue Reward

Treatment Implications Treatment Implications • Cognitive/behavioral interventions can also reduce • Reducing dopamine neuron firing and/or dopamine neuron reward estimates dopamine release in response to drug cues or • 1) Change beliefs about the effects of drug use/seeking. This drug use will decrease the drive to drug seek. will alter PFC feedback to dopamine neurons. • – Example: Helping a weight‐conscious patient recognize Several effective SUD pharmacotherapies the connection between marijuana smoking and binge reduce dopamine neuron firing in response to eating. drug use • 2) Change experienced effects of drug seeking/use. This will – Naltrexone for Alcohol and Opioid Use Disorders alter limbic reward circuit feedback about the actual reward – Opioid Agonist Treatment with methadone or value. buprenorphine – Example: Helping patient get engaged in a social network – Varenicline and nicotine replacement therapy that values abstinence from substance use

Nucleus Accumbens Medium Spiny Nucleus Accumbens Medium Spiny Neurons Neurons • Two subtypes • Listen to dopamine neuron reward value – Direct pathway – D1 receptor, excited by dopamine estimates • Dopamine makes them more likely to trigger reward seeking • But also express dynorphin which can cause dysphoria and aversion • Choose and trigger reward‐seeking behaviors – Indirect pathway D2 receptor, inhibited by dopamine when dopamine neuron estimates are large • Dopamine makes it harder to trigger reward seeking • D2 activation increases inhibition so that it takes larger or more sustained activation enough to trigger reward seeking • Big spikes in dopamine internalize D2 receptors, removing this inhibition • Low D2R favors large and immediate rewards, potentially to the exclusion of smaller and more distal rewards

21 When dopamine signals are huge Summary and Take Home

• Activate reward‐seeking and reinforcement via direct D1 pathway • All drugs of abuse, when rapidly absorbed, will: – But also release dynorphin producing dysphoria – Lead to over‐valuation of drugs and drug seeking • Internalize D2 receptors on indirect D2 pathway behaviors, and bias habit‐driven decisions toward drug – Takes D2 receptors off of the surface of the cell so that they can not signal use • Prevents the reduction in starting activation resulting from D2 receptor – Lead to dependence and withdrawal symptoms with activation • Reward opportunities don’t decrease tendency to reward‐seek as much chronic use – Reduces the brakes on reward seeking • This includes dysregulation of stress response systems and • Makes reward seeking easier and faster to trigger facilitation of dysphoria and negative affect • Will make you feel lousy, but more likely to repeat the thoughts, – Lead to down‐regulation of D2R dopamine receptors, feelings and behaviors that lead to drug use, and more likely to and thus dopamine deficiency compulsively use when an opportunity arises • Leads to impulsive behavior and bias towards immediate • Observed with drugs of abuse, and processed food (i.e. food with gratification over long‐term goals concentrated levels of fat, sugar and salt that are not found in nature)

Summary and Take‐homes THE IMMUNE SYSTEM, INFLAMMATION, AND THE MIND-BODY CONNECTION • Core strategies to facilitate recovery include: A Certificate Program – Increasing opportunities for natural rewards with long‐term benefits • Social support Earn 18 hours of CE and a Certificate • Social skills training • Coping skills Lecture 1: The Immune System • Problem‐solving skills Lecture 2: Mind‐Body Interactions and Inflammation • Exercise and other recreation Lecture 3: Understanding the Gut Brain • Employment

Margaret Kemeny, PhD Lisa E. Goehler, Ph.D.

Dr. Kemeny has been Professor of Dr. Goehler is an expert in the study of the Psychiatry and Director of Health mind‐immune system connection including Psychology at the University of the role of stress, inflammation, and mood. California, San Francisco. She is a Research Associate Professor of Nursing at the University of Virginia. She is one of the leading scientists to She helped discover how chronic GI advance the field of psychoneuro‐ inflammation produces depression and immunology. She has taught for the anxiety. Institute since the 1980s.

22 Psychoneuroimmunology: Merrily Kuhn, RN, PhD, ND Investigations of the bidirectional linkages between the CNS, the endocrine system and the immune Dr. Kuhn is an expert in complementary system, and the clinical implications of these linkages. medicines. In her first career, Dr. Kuhn received her doctoral degree in Physiology (SUNY, Buffalo). Drawing upon her background in nursing, medicine, and physiology, she presents best practices in complementary medicines. Dr. Kuhn has taught for the Institute since the 1990s.

Where Does the Action Take Place? • Lymph vessels and lymph nodes — filtering system for the lymph. WBCs lie in wait for foreign substance to destroy

• Bone marrow — origin of WBCs

• Thymus — where T cells differentiate into functioning cells from precursors

• Spleen — filtering system for the blood

• Other organs — gastrointestinal tract has Peyer's patches with high density of WBCs, respiratory tract has tonsils, skin, etc.

Inflammation Cytokines • A complex set of events to bring immune cells into damaged areas so they can destroy or inactivate foreign Most of the action takes place via communication substances invaders and set stage for tissue repair. called cytokines (lymphokines if it comes from lymphocytes, monokines if it comes from monocytes). • Vasodilation so increased blood flow  Cytokines: Proteins released by immune cells that act on • Increased vascular permeability target cells to regulate immune response • Fever  Proinflammatory cytokines: coordinate inflammatory • Edema or swelling as fluid enters tissues responses in the body; produced by activated macrophages • Chemotaxis: chemical attraction of immune cells like neutrophils in response to microbes; mediates acute inflammation • Immune cells into the tissues • IL‐1 • Destruction of invader • Tumor Necrosis Factor (TNF • Wall off injured area to delay exit of organism • IL‐6 • Wound healing

23 On the other hand: C Reactive Protein (CRP)

• C‐reactive protein (CRP) test = blood test that measures the amount of C‐reactive protein in your blood. • Reflects general levels of inflammatory activity in your body. • Very high levels of CRP are caused by infections. • Moderately high levels of CRP are associated with long‐ term immune based diseases. • But a CRP test cannot show where the inflammation is located or what is causing it.

An overactive immune system can lead to ongoing inflammatory activity and disease

Inflammatory Diseases

The Immune system as a sensory system : How do What brain systems does immune‐related signals the influence the brain? inflammation influence? • Viscerosensory and • Part of “interoception” (aka viscerosensory) autonomic pathways for • Via nerves: immune chemicals (such as controlling physiology cytokines & prostaglandins) interact with • Pathways that detect receptors on sensory nerve fibers, signaling pain, stress, and coping the presence of inflammation and infection responses • Pathways that are • Via circulation: cytokines (etc.) travel in the involved in emotion and blood to the brain memory • Directly by interacting with receptors in or • Networks involved in around the brain decision‐making and sense of self

24 The brain is a master regulator of the immune The Brain Controls the Stress Pathways • Under certain forms of distress, the cortex and limbic system system signal to the hypothalamus. • Via the Hypothalamo‐Pituitary‐Adrenal (HPA) axis and Autonomic Nervous System (ANS) • The hippocampus (memory) also • The immune system major player in homeostasis/physiological has inputs to the hypothalamus. regulation • The hypothalamus maintains • Immune cells have receptors for hormones (cortisol, epinephrine etc.), homeostasis by regulating visceral and neurotransmitters (norepinephrine, acetyl choline, GABA, and many activities: heart rate, blood more) pressure, body temperature, • Too much of the stress hormone cortisol can suppress the immune thirst, hunger, weight, system and have other deleterious effects sleep/wakefulness. • Too little cortisol reactivity can impair the ability of this system to • It also controls the body’s stress constrain inflammation in the body, since cortisol is the body’s own anti‐ response systems: the inflammatory. hypothalamic pituitary adrenal axis and the autonomic nervous system.

Short Term Stress Can Suppress Immune System Stress • Examination stress* (Kiecolt‐Glaser/Glaser): Activation of corticotropin • Suppress T cell function releasing factor (CRF): • Suppress natural killer cell function  Contributes to delayed gastric • Suppress lymphocyte proliferation emptying • Suppress production of interferon  Increased colonic activity • Reactivate latent viruses (herpes simplex  Functional bowel disease (IBS) virus; Epstein Barr virus) •  Increase in gut permeability decreased ability of cell to repair broken DNA.  Leaky gut – antigens leaking out • Lower antibody response when vaccinated.  Toxic liver overload  Systemic disease T cells attack a virus *effects also seen in bereavement, divorce, and other stressors

But Stress Can Enhance Inflammation Sooooo The Immune System Can Affect Your Emotions: Implications  Too early to test patients for cytokine levels but • Brief laboratory stresses can increase production of pro‐ awareness that PIC can contribute to depression is inflammatory cytokines important (underlying inflammatory condition) • Short term real‐life stressors like exams can also increase  Stressors may contribute to depression or production of these cytokines depression exacerbation via PIC • Chronic stressors (caregiving for a child with cancer) can  Findings provide a way of understanding also have this effect‐prolonged depression in medical conditions involving inflammation

 Provides a link between depression and vulnerability to medical diseases (CVD, autoimmune)

25 Inflammation and Dementia Do Cytokines Contribute to • Dementing conditions may be exacerbated by chronic Depression? inflammation. • Obesity and diabetes as risk factors  Depressed patients have increased levels of • Small strokes may be caused by inflammation. proinflammatory cytokines (PIC) • Inflammation may play a role in deterioration of brain cells, formation of plaques. Some of the protein in  Inflammatory diseases are often associated plaques are products of inflammation. with depression • Inflammatory mediators can cross into the brain and influence learning and memory.  Injections of PIC can increase depressive • Frequent use of non‐steroidal anti‐inflammatory drugs symptoms (dysphoria, anhedonia, fatigue, may prevent or delay Alzheimer’s Disease. • In a study conducted at Johns Hopkins, those who took such medications apathy, helplessness, which regresses) for two years had a decreased chance of developing Alzheimer’s Disease  PICs cause a depression‐like Sickness Behavior (60% less chance). • Stress may influence the onset and course of dementia via these inflammatory pathways

Peripheral nerves are also involved in How does stress affect inflammation? inflammation • Bidirectional: nerves sense • Stress effects are complex inflammation, and contribute to it • Chronic stress‐ leads to increased inflammation (via several • Both pro‐inflammatory and anti‐ mechanisms including glucocorticoid resistance‐ immune cells inflammatory effects don’t respond) • C‐fibers modulate pain and • Stress can disrupt balance within the immune system inflammation • Chronic stress cause epigenetic changes in the expression of • Sympathetic and pro‐inflammatory cytokine genes in immune cells parasympathetic nerves reduce inflammation (especially vagus) • ‐Peripheral inflammation induces neuroinflammation

Other aspects of stress “Developmental Programming” of stress responses Ability to meet challenges is key‐ stress from not meeting them dysregulates immune • Experiencing trauma or stress in infancy or childhood leads to system, increases inflammation and impairs impaired regulation of HPA axis, behavioral responses to brain function challenge/stress • Acute or chronic: acute stress can potentiate • Elevated levels of inflammation, especially in gut immune responses, but chronic stress can impair • them Increased incidence of pain conditions including fibromyalgia & irritable bowel syndrome, and pre‐term birth • Controllable vs. uncontrollable • Epigenetic changes to genes involved in inflammation

• Social stress and loneliness

26 Communication in the immune system happens via What is the Gut Brain? chemicals

 Cytokines: Proteins released by immune cells that act on target cells to regulate immunity, and signal the brain

 Proinflammatory cytokines: coordinate inflammatory responses in the body; produced by activated macrophages in response to microbes; mediates acute Enteric inflammation (e.g. IL‐1b, TNFa, IL‐6)

 Anti‐inflammatory cytokines: controls the pro‐inflammatory response (e.g. IL‐10)

 Chemokines: recruit cells to affected tissues

 Prostaglandins: recruit immune cells, and signal the brain

Microbiome Enteric Nervous System

Enteric – meshwork of nerve fibers that innervate the viscera (gastrointestinal • The GOOD: may be necessary; helps digest certain foods the stomach/small tract, pancreas, intestine doesn’t, can combat invading microorganisms. Our own microbes generally do not cause disease unless they grow abnormally; they exist in harmony and symbiotically with us. In a germ free environment animals can gall bladder) have an exaggerated HPA response to psychological stress, which normalizes when certain bacteria colonize again.

• The BAD: the human microbiome may have a role in auto‐immune diseases (e.g., diabetes, rheumatoid arthritis, multiple sclerosis, fibromyalgia) and possibly some cancers. A poor mix of microbes in the gut may also aggravate obesity.

Our microbes are like an organ Gut bacteria • Produce nutrients, e.g. short chain fatty acids and vitamins Play a key role in nutrition • Control each other’s behavior Production of neutransmitters • Collaborate with our immune system in host defense Synthesize: vitamins thiamine (B1), • Program phenotypes/activity states of immune cells folic acid (B9), pyridoxine (B6), • Diet influence our microbial populations and vitamin K • Link of inflammation and disease Produce digestive enzymes to • Influence brain development absorption calcium, magnesium, • Influence our behavior and iron.

27 Stress/Depression and the Gut Microbiome Language of Gut  Stress can induce increased permeability of the gut  Visceral sensations include: nausea, allowing bacteria to cross the epithelial barrier (thin bloating tissue that lines the internal/external surfaces of the  All arrive at Insular Cortex in brain body) and activate a mucosal immune response, which  Plays role in alters the microbiome and leads to enhanced HPA emotions & body activity. homeostasis  In irritable bowel syndrome (IBS; cramping, abdominal  Regulates the immune pain, bloating etc) and depression there can be an system alteration of the HPA axis induced by increased gut  Conscious desires – food, permeability drugs  In IBS, the increased permeability can respond to probiotic therapy (live microorganisms (bacteria) that may provide health benefit when consumed.

TG Dinan, JF Cryan, Psychoneuroindocriology, 2012, vo 37(9), 1369‐1378

Inflammation, microbes and anxiety • Anxiety is common in illness, and inflammatory signals from the body contribute, e.g. TNF, vagal activation • A signal that something is not right • Special role of dysbiosis (imbalance in microbes)

“Leaky gut”: the consequences of stress and Dysbiosis and Microbial Diversity: the Importance inflammation and link between diet and health of Balance • AKA “increased intestinal permeability” • Diversity is good‐ a hallmark of disease is • Increased intestinal permeability is associated with many disorders reduced microbial diversity (diabetes, metabolic syndrome NAFL, allergies, neurological etc.) • Low diversity is associated with DYSBIOSIS • Single layer of cells between us and outside • Absorbs nutrients‐ increased permeability allows more absorption of nutrients, but also • Dysbiosis is when there is an imbalance in toxins and lets fluid out e.g. during inflammation and infection microbes, leading to overgrowth of some (diarrhea) • Many factor regulate this: immune species cells and molecules, microbes, stress

28 Cardo‐Metabolic Syndrome What drives inflammation in cardio‐metabolic syndrome? • Diabetes, cardiovascular • Obesity‐ fat releases pro‐inflammatory mediators, and disease, obesity contains pro‐inflammatory immune cells • Reduced • Gut barrier dysfunction microbial diversity • Dysbiosis • Leptin • Inflammatory diet (high intake of saturated fats, refined resistance sugar, processed foods, additives, lack of anti‐oxidants) • Mood disorders • Inflammation • AGEs/RAGE • Pro‐inflammatory insulin family members

How does inflammation affect the brain: Diet, inflammation and Pre‐diabetes Sickness behavior ‐increased markers of inflammation e.g. cytokines, CRP • *a symptom cluster also seen in chronic stress ‐increased fasting blood glucose, elevated • Depressed and/or anxious ‐weight loss improves inflammation mood and metabolic markers • * increased sensitivity to pain ‐dietary changes can help: • *loss of interest in food Fruits and nuts, berries, fish, whole grains, omega‐3 polyunsaturated • * social withdrawal fatty acids, red wine in moderation • * disordered sleep ‐avoiding trans‐fat and saturated fats, sugary foods, red meat • *fatigue, “cognitive fuzziness”

‐probiotics‐ diets low in probiotics are associated with type‐II diabetes

Depression Has A Very Interesting and Important Depression and fatigue in illness Relationship to Inflammation ‐Depressed patients ‐‐ increased levels of • Common symptoms proinflammatory cytokines (PIC)—strong of both acute and finding chronic illnesses ‐Chronic inflammatory diseases are often • Both caused by associated with depressive symptoms inflammation ‐‐Depression is associated with inflammation • Involves suppression in the brain of brain arousal So‐ does depression cause the increase in systems these cytokines or do these cytokines cause depression? Or is it a nasty positive‐feedback loop?

29 The Right Ways to Protect the Brain from Pre‐Diabetes MANAGING INTERPERSONAL CHALLENGES and Metabolic Syndrome A Certificate Program

Earn 24 hours of CE and a Certificate Lecture 1: Noxious People Lecture 2: Reasoning With Unreasonable People Lecture 3: Passive‐Aggression Lecture 4: Communicating to Create Meaningful Change

Joseph Shannon, PhD W. Robert Nay, PhD

Dr. Shannon, psychologist and Dr. Nay is Clinical Associate Professor researcher, has appeared on the CBS at Georgetown University School of Morning Program and PBS Medicine and an expert in the Viewpoint. He has presented treatment of anger‐related disorders. throughout the United States and In addition to over 30 research Canada. His uses film excerpts to papers and chapters, Dr. Nay is illuminate how to resolve author of leading texts in the field interpersonal conflicts. He has taught drawing on three decades of clinical for the Institute since the 1990s. experience.

Arousal and Anger Paula Butterfield, Ph.D. • Heart Rate and Breathing: Chest Breathing/Shallow, Dr. Butterfield is the winner of four Increased Heart Rate awards for distinguished teaching. • Musculoskeletal Tightening/Tension: Headaches, Back Pain, She has developed national training Jaw Discomfort programs for over two decades. • Vasodilation of Blood Vessels in the Face (Warmth) She integrates evidence‐based research • Gastrointestinal: Butterflies, Acid Stomach, Discomfort or in the brain and behavioral sciences with Pain, Nausea, Irritable Bowel essential communication strategies. • Senses Become More Acute • Blood Changes: Faster Clotting/Release of Cortisol

30 Precursors of Anger Arousal and Performance • Early Trauma and Insecure Attachment • Anger Scripts: Underlying belief about self, others and the world—role in anger arousal • Proximal Precursors: the “Five Ss” –Sleep –Stress –Sustenance –Substances –Sickness

Important brain structures in Anger Resilience • Respond with tenacity and determination versus feeling helpless and overwhelmed with anger/resignation. • Greater activity in the LPF (up to 30 times greater) versus the RPFC. Strong relationship between prefrontal cortex and amygdala. LPFC activity seems to inhibit the amygdala and facilitate rapid recovery from emotional breakdown. • Related to degree of white matter connections between the prefrontal cortex and amygdala. • Rx: Mindfulness training strengthens connections between the prefrontal cortex and the amygdala. Cognitive restructuring or reframing negative events reduces threat and anger.

Developing Social Intuition Self‐Awareness • One's ability to read body language and tone of voice, • To regulate emotions, awareness of personal thoughts and feelings accurately inferring what social behavior is required. Type: versus lack of recognition/understanding of why you are anxious, socially intuitive versus puzzled. angry or impatient. Type: self‐aware versus self‐opaque. • Low levels of activation in the fusiform portion of the visual • Directly related to activity in the insula (located between temporal cortex and high levels of activation in the amygdala. and frontal lobes), which receives signals from the visceral organs. • Rx: Practice paying attention to social cues‐‐both obvious Extremely high levels of insula activity = panic disorder and and subtle: voice, body language, facial expression (e.g., sit hypochondria. in a public place observing others, trying to predict how they • Rx: Mindfulness training to non‐judgmentally focus on your will react, talk or touch one another). thoughts, feelings and sensations moment to moment. Self‐ monitoring/keeping a diary/log.

31 Attention/Attending Insecure Attachment and Anger • “Selective attention” to important details and “non‐judgmental • Role of Early Developmental Factors. attention” (necessary for mindfulness). Type: focused versus –Disruptions in predictable, caring and safe environment = unfocused. Example: Focus on the most rewarding stimulus, missing poor ability to be intimate (e.g., withdrawal, avoidance, important social cues to effectively interact. intimidation, aggression). • Increased activity in the PFC bilaterally, particularly dorsal lateral PFC. –Impact is dysfunctional affective regulation, insecure • Rx: Improving focus requires increasing activity in the prefrontal attachments (e.g., from exposure to shaming or and parietal cortices. Achieved with mindfulness in two forms: experiencing outright physical abuse). focusing on one object, excluding other stimulation increases –Leads to hypervigilance, and oversensitivity to threats selective attention. Open‐presence monitoring of all impinging which can result in rage reactions and difficulty stimuli enhances non‐judgmental attention. modulating aggression.

Avoidant Attachment Anxious‐preoccupied Attachment • Strategy is to deactivate, because anger implies emotional • Tendency to intensify distress and ruminate about provocative experiences. investment (not congruent with avoiding other people and • Fear of separation, desperate desire for love and high dependency may instigate anger expression as well as cause them to direct it toward distancing oneself = self‐reliant). themselves. • Anger expressed an indirect, passive ways (passive‐aggression), • Associated with more anger, hostility and distress while discussing issues and hateful attitudes and generalized hostility. interacting with object of attachment. • Denies neediness or anger but reacts with hostility, hatred and • Men who score high on attachment anxiety engage in more severe and physiological arousal. frequent acts of abuse during couple conflicts. • Engage in antisocial behavior to distance themselves • Also increases risk of being abused or does the abuse increase attachment anxiety? interpersonally (e.g., parents) and to demonstrate by breaking rules and laws their lack of concern for others. • Leads to delinquent or criminal behavior as a way of crying out for attention/nurturance or expressing anger and resentment.

Secure Attachment Anger Flowchart

Outcome

Behavior

Emotions/Sensations

Self-talk

Expectations

Belief

32 Awareness Wheel HOW FOOD AFFECTS MENTAL HEALTH Sensing see, hear, A Certificate Program experience Earn 18 hours of CE and a Certificate Doing Thinking words & actions, self-talk, Lecture 1: Food For Thought non-verbal interpretations, behavior meaning Lecture 2: Medicinal Effects of Plant‐Based Nutrients Lecture 3: Medical and Medicinal Foods

Needing Feeling emotions & behaviors physical required of other sensations

Michael E. Lara, MD Merrily Kuhn, RN, PhD, ND

Dr. Lara, a Psychiatrist, completed his Dr. Kuhn is an expert in complementary residency at Stanford University. medicines. In her first career, Dr. Kuhn received her doctoral degree in He is recognized for his use of evidence‐ Physiology (SUNY, Buffalo). Drawing based approaches through lifestyle upon her background in nursing, prescriptions including to reduce medicine, and physiology, she presents anxiety, elevate mood, improve memory best practices in complementary and enhance wellbeing. He has taught medicines. Dr. Kuhn has taught for the for IBP for over a decade. Institute since the 1990s.

197 198

33 Nutrition and Inflammation FIBERS Protective Fibers: insoluble cellulose, hemicellulose and lignin and types of vegetables, fruits and grains and soluble gums (e.g. oat bran, legumes) and pectin (apples, citrus fruits). Cellulose: . Long chain of linked sugar molecules that gives wood its remarkable strength . Main component of plant cell walls Hemi‐Cellulose: • Collective term for non‐digestible polysaccharides found in plant cell walls; a dietary fiber, which can be either soluble or insoluble and more or less fermentable [1]. 200 • Used in foods as an added fiber, thickener, emulsifier or stabilizer. 199

SUGAR & SALT

INTERESTINGLY, OUR BODIES CALIBRATE TO THE EXISTING ENVIRONMENT: THE SWEETER YOUR DIET, THE SWEETER YOU WANT THINGS; CHILDREN INTRODUCED TO SALT EARLY ON DEVELOP BIGGER CRAVINGS FOR IT. MEANWHILE, NEW RESEARCH IS POINTING TO HIGH SUGAR DIETS INCREASING THE RISK OF ALZHEIMER'S DISEASE.

Diets styles for longevity: Mediterranean and Okinawa

34 UNDERSTANDING MEMORY, COGNITION, Mike Yassa, PhD AND DEMENTIA A Certificate Program Dr. Yassa is Associate Professor of Neurobiology Earn 18 hours of CE and a Certificate and the Director of the Center for the Neurobiology of Learning and Memory at UC, Lecture 1: Memory Irvine. Lecture 2: Preventing Cognitive Decline He is an expert in how the brain acquires and Lecture 3: The Habits of People Least Likely retrieves long‐term memory. He has received to Develop Alzheimer’s Disease multiple awards including the NSF, NIA, NIMH related to aging brain.

Craig E. L. Stark, PhD Stuart Zola, PhD

Dr. Stark is Director of the Center for the Dr. Zola is a leading neuroscientist and an expert in Neurobiology of Learning and Memory at the study of Alzheimer’s disease and how the brain UC Irvine and is a Professor in the forms new memories. He has codirected the Department of Neurobiology and Alzheimer’s Disease Research Center at Emory Behavior. University and has developed a brief test that accurately predicts who will and will not develop Alzheimer’s disease. His research specializes in studying normal memory, how memory changes with age, The American Association for the Advancement of amnesia or Alzheimer’s disease. Dr. Stark Science honored Dr. Zola for his “distinguished has frequently appeared on NPR. contributions in neuroscience.”

The aging world

35 Memory loss occurs in aging Area 46 of the prefrontal cortex

• Problems with: • In general there is no volumetric loss • Episodic memories (Craik and Simon, 1980) across the PFC with some exceptions,

• Source memory (Schacter et al., 1991) e.g. area 46.

• Recollection (Jennings and Jacoby, 1997) • Critical role in executive function and • Contextual memory (Henkel et al., 1998) working memory. • Spatial memory (Newman and Kaszniak, 2000) • Not neuronal loss, but rather… • Increase in false memories (Schacter et al., 1997) • Working memory • there is a 30% decrease in synaptic density. • Fine on:

• Skill and habit memory • similar loss in dendritic spines

• Vocabulary averaging 33%.

• Working memory maintenance

Successful aging is possible! What can we do to prevent AD?

• Exercise

• Physical activity linked to reduced risk for AD in epidemiological studies

• Small benefits in clinical trials, most notably in executive function

• Aerobic as well as strength training show positive effects

• Sessions longer than 30 minutes “I took pleasure when I could. I show larger effects than shorter acted clearly and morally and without regret. I’m very lucky.” sessions

• Need more studies!

What can we do to prevent AD? Neurodegeneration in Alzheimer’s Disease

Healthy Aging Alzheimer’s Disease • Social and leisure activities

• Engaging in mentally stimulating activities such as reading, playing board games, playing musical instruments, knitting, gardening, and dancing lower dementia risk

• Maintaining a larger social network has protective effects.

• High educational level and occupational attainment (high cognitive reserve) associated with decreased dementia incidence.

36 Alzheimer’s Disease

Tangles and Plaques

Risk Factors for Alzheimer’s Impact of Alzheimer’s Disease •Age • it is mainly after the age of 60‐65 that proportion of AD patients becomes •Over 4 million people currently sizable • Genetics and Family History •Age is biggest risk factor and there is a dramatic • presence of ApoE4, the gene coding for apolipoprotein increase in life expectancy • first‐degree relative with AD •The group over 85 ‐ the group with the highest risk • Gender • seem to be more women than men affected of AD ‐ is the fastest growing group in our • could be artifact because life expectancy longer in women population. •Head Trauma • even brief period of unconsciousness •By the year 2050, 14 million Americans will have • Education AD, if no treatments available. • dementia is greater among illiterate subjects • education may increase synaptic density

Differences between men and women and race At Least 27 Genetic Variations Underlying Alzheimer’s in Alzheimer’s • Genome‐wide association studies (GWAS) and whole exome sequencing (WES) and whole genome sequencing (WGS) • Almost 2/3 of Americans with Alzheimer’s are women • Identified 27 susceptibility genes or loci • Women live longer than men, and older age is a prime risk factor • • New evidence suggests higher risk is due to genetic or biological variations or Genetically complex disease: each variant has a small effect on even different life experiences disease risk • Type and amount of education • Amyloid pathway • Occupational choices • Immune system/inflammation • Possible links between APOEe4 and estrogen • Tau pathology • Older African‐Americans and older Hispanics more likely than older Whites to • Hippocampal synaptic function have Alzheimer’s • Microglial and myeloid cell function • Variables such as cardiovascular disease, education, social engagement • Phosphorylation‐dependent ubiquitination

37 Glycemic Index Is Alzheimer’s Diabetes of the Brain? • One way to choose fruits and other high‐carbohydrate foods is to check the glycemic index (GI). The GI is a ranking of foods on a scale from 1 to 100, • Unclear exactly how type 2 diabetes makes you vulnerable to with their score indicating how quickly they raise blood sugar levels. Alzheimer’s • High GI foods are absorbed faster than medium or low GI foods. Low GI foods are best for helping control blood sugar levels. • Clue: The two disorders have a similar genealogy of causes: • It may be a surprise to learn that most fruits have a low glycemic index. • Obesity, highblood pressure, high cholesterol, high triglycerides, Starchy vegetables like potatoes and grains are more rapidly digested and have a higher GI index. high‐fat diet, high‐sugar diet • Low GI fruits (GI less than 55) • Low physical activity • Apples • High blood sugar and dysfunctional insulin • Avocados • All can lead to brain damage • High‐GI fruits (GI Index of 70 or greater) • Dates • Destroying neurons • Watermelon • Increasing inflammation • Increasing risk of stroke

Poor Sleep May be Linked to Alzheimer’s Sleep deprivation impairs memory

•Lack of sleep or waking up several times during the • 36 hours of sleep deprivation night may be bad for the brain and may increase the • Word-pair test risk of Alzheimer’s disease •Researchers found that getting less sleep or sleeping poorly was tied to an increase in brain levels of beta‐ amyloid •70 older adults, average age 76; those who said they got the least sleep, under five hours a night, or who slept fitfully had higher levels of beta‐amyloid in the

brain than those who slept over seven hours a night Walker (2006)

Alzheimer’s: Not a homogeneous disease? LIFESTYLE MODIFICATION TO CREATE • Drug trials have been disappointing MEANINGFUL CHANGE • Current treatment strategies for AD have only minimal effect A Certificate Program • Ad is considered a homogeneous disease Earn 24 hours of CE and a Certificate • Risk profiles and molecular profiles of persons with AD show Lecture 1: Pumped: Building a Better Brain considerable variation Lecture 2: What Is In Our Food • Grouping patients with different risk profiles into a single Lecture 3: Meditation entity could mask the potential of small subgroups to be Lecture 4: Sleep and the Brain responsive to particular treatments • Precision medicine needs to take all of this into account

38 Michael E. Lara, MD Merrily Kuhn, RN, PhD, ND

Dennis Marikis, PhD Typical Activities of Hunter-Gatherer Dr. Marikis is a researcher in using meditation Physical activities of our paleolithic ancestors have correlates in modern day forms of exercise and neurofeedback to treat a wide range of disorders. Slow Cardio: 5-10 miles/day of low intensity walking Hunter gatherers cover 5-15 miles per days. Persistence hunters cover in excess of 30 miles/day. His teaching methods include the use of film Resistance Training: Lifting, Throwing, and Carrying Objects and the opportunity to practice and Encompass functional movements such as pushing, pulling, sprinting, and jumping experience different meditative practices. He Interval Training: Periodic bursts of high-intensity activity has presented training programs for the Brief bouts of sprinting alternating with walking or jogging in pursuit of Institute since the 1990s. prey

O'Keefe JH, Vogel R, Lavie CJ, Cordain L. Achieving Hunter-gatherer Fitness in the 21st Century: Back to the Future. AJM. 2012:1–5.

Americans Move Less Cerebellum and Movement

Cerebellum (Latin for “little brain”) is responsible Japanese for coordination, precision and accurate timing of movement Swiss Contains 50-80% of total neurons in brain

Australians Cerebellum is dysfunctional in movements of attention (ADHD) and movement (Parkinson

Americans Disease) Moving to rhythm or cadence is an established 0 2000 4000 6000 8000 10000 12000 treatment for both ADHD and PD Steps/day; 1 mile=2,000 steps Bassett DR JR.,Wyatt HR, Thompson H, Peters JC, Hill JO. Pedometer-measured physical activity and Bledsoe J, Semrud-Clikeman M, Pliszka SR. A magnetic resonance imaging study of the cerebellar vermis in health behaviors in United States adults. Med Sci Sports Exerc. 2010;42(10):1819. chronically treated and treatment-naive children with attention-deficit/hyperactivity disorder combined type. Biol. Psychiatry. 2009;65(7):620–624.

39 Too Much Sitting: An Important Type 2 diabetes, cardiovascular The Consequences of a diseases, colon cancer, breast cancer, Predictor of Chronic Disease? Sedentary Lifestyle dementia and depression constitute a cluster of diseases, which are Increased participation in physical activity is a central tenet of mediated by inflammation. strategies for preventing major chronic diseases (type 2 Chronic inflammation is involved in diabetes, cardiovascular disease, breast and colon cancer). the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration Recent findings also suggest that physical activity, in the and tumor growth. context of otherwise sedentary lifestyles, is unlikely to be sufficient to prevent increasing rates of chronic disease. Evidence suggests that the protective effect of exercise may due to the anti- We spend an average of 9.3 hours/day sitting--even more time than inflammatory effect of regular we spend sleeping (7.7 hours) exercise

Owen N, Bauman A, Brown W. Too much sitting: a novel and important predictor of chronic disease risk? Pedersen BK. The diseasome of physical inactivity - and the role of myokines in muscle-fat cross talk. Journal British Journal of Sports Medicine. 2009;43 (2):81–83. of Physiology. 2009;587(23):5559–5568.

Myokines and Inflammation Exercise Improves Sleep Exercise improves sleep quality and normalizes circadian rhythms. Exercise increases slow wave sleep and total rest time. Also decreases the amount of time to fall asleep and Inactive muscle could contribute to pathological consequences decreases the amount of time spent in non-restorative. Lack of restorative sleep increases inflammatory cytokines Myokines are recently recognized as potential candidates for treating metabolic diseases and is associated with chronic disease A single night of sleep deprivation results in higher levels Exercise-induced myokines appear to be involved in mediating both of interleukin-6 and tumor necrosis factor systemic as well as local anti-inflammatory effects Uchida S, Shioda K, Morita Y, Kubota C, Ganeko M, Takeda N. Exercise Effects on Sleep Physiology.

Pedersen BK. The disease of physical inactivity - and the role of myokines in muscle-fat cross talk. The Journal of Physiology. 2009;587(23):5559–5568. doi:10.1113/jphysiol.2009.179515. Frontiers in Neurology. 2012;3.

Exercise Increases Neurotransmitters Beta-Endorphin and The Runner’s High

Exercise has both short and long-term effects on neurotransmitters that regulate attention, mood, and movement Exercise, a form of voluntary stress, activates the hypothalamic-pituitary- adrenal axis Norepinephrine (NE) increases abruptly at exercise intensities that exceed 50% of VO2 max Beta-endorphin is released from anterior pituitary NE turnover is increased in the frontal cortex and is helpful in alleviated symptoms of ADHD Subjective feelings of euphoria are mediated by rising levels of beta-endorphin Serotonin (5-HT) is modulated by exercise in specific brain regions and is also affected by intensity and duration of exercise. Naloxone, an opioid antagonist, attenuates the subjective feelings of joy and High-intensity interval training increases 5-HT synthesis in the hippocampus via interaction with euphoria associated with running brain derived neurotrophic factor (BDNF). Beta-endorphin increases in prefrontal and limbic regions of the brain after Dopamine (DA) is also increased in pathways involved in regulation and control of movement 2 hours of endurance running and levels correlate with euphoria ratings. Higher levels of moderate to vigorous activities are associated with a lower risk of developing Parkinson disease

Mattson MP, Maudsley S, Martin B. BDNF and 5-HT: a dynamic duo in age-related neuronal Janal MN, Colt EWD, Clark WC, Glusman M. Pain sensitivity, mood and plasma endocrine levels plasticity and neurodegenerative disorders. Trends in Neurosciences. 2004;27(10):589–594. in man following long-distance running: Effects of naloxone. Pain. 1984;19(1):13–25.

40 Aerobic Exercise Training Increases Brain Volume Benefits of Aerobic Training In Aging Adults The majority of scientific literature supports a general benefit of aerobic fitness on childhood cognitive performance. Interventional studies in adults suggest that previously sedentary older adults improve in executive functioning, attention, and memory after as little as 5-6 months of regular aerobic exercise. Aerobic training associated with increases in brain-derived neurotrophic factor (BDNF) and vascular endothelial growth Blue regions: Gray matter volume was increased for aerobic exercisers factor (VEGF). Yellow regions: White matter was increased for aerobic exercisers

Colcombe SJ, Erickson KI, Scalf PE, et al. Aerobic exercise training increases brain volume in aging Voss MW, Nagamatsu LS, Liu-Ambrose T, Kramer AF. Exercise, brain, and cognition across humans. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. the life span. Journal of Applied Physiology. 2011;111(5):1505–1513. 2006;61(11):1166–1170.

Fitness Correlates with Academic Achievement Cardiovascular Fitness and Cortical Plasticity in Aging Adults

Colcombe SJ. Cardiovascular fitness, cortical plasticity, and aging. PNAS. 2004;101(9):3316–3321

Understanding Meditation Open Awareness (Mindfulness) • Mindfulness (Open Monitoring): awareness of thoughts, feelings, and • Open-awareness Meditation (Wide Angle Lens) sensations without judgment as a present-centered, non-judgmental state to manage habitual cravings, fears, and anxiety. – Open-awareness is our wide angle, panoramic lens of consciousness. • Focused Attention (Closed Monitoring): present-centered states – This type of meditation can also be called "open monitoring" or attained by attention to the breath, an image, sound, sensation, or idea. "non-directive" meditation. Here, the practitioner is encouraged to • The Mindful Brain: mindfulness, anxiety reduction and calming the observe and be present. amygdala (part of the habit brain); from mind wandering to sustained – It is resting in awareness itself without boundary or guidance. It is focus and the prefrontal cortex; compassion, loving kindness and the self- relaxed, without the practitioner having to exert any particular aware brain. effect or to focus on any object at all. Open-awareness meditation • Minding the Body By Embodying the Mind: how the relaxation is often associated with the idea of the mind being an open sky. response calms the adrenaline fight-or-flight response and the cortisol The practitioner is to observe the clouds (or thoughts), that pass response to chronic stress; reducing oxygen consumption, respiratory along their field of awareness. Another popular view is that of rate, blood pressure; improving blood flow and immune function. observing a flowing river and noticing what drifts past the observer, carried by currents. Examples of formal types of open- awareness meditation are in Zen Buddhism.

41 Closed Monitoring Mindful Meditation • Concentrative meditation is our macro lens of • If concentrative meditation is our macro lens and open-awareness is our wide angle lens, mindfulness meditation would most consciousness. certainly be our standard lens. – In this type of meditation, the practitioner is asked to place his or her attention on an object; a single subject of focus. • Mindfulness is the happy medium between concentrative and open- awareness. It is the balanced merging of the two. With mindfulness, – Traditionally this has been a sound or mantra, the breath, or a we employ techniques from both concentrative and open- physical object, such as a candle. This meditation is very awareness meditations. We can choose an object of focus, perhaps deliberate. All extraneous thought and emotion is filtered away. the breath, but we can focus on this object with the same non- The concentration is entirely fixed on the object of focus. This judgment and acceptance of open-awareness. We can focus but type of meditation helps form mental acuity, focus and application. remain aware: aware of sensory input and perception, as well as It aids in overcoming distraction and builds patience. emotion and thought. Without being carried away by our thoughts or lost in the stories of our sensations and emotions, we can remain attentive to our object of focus and accepting of our whole experience.

Meditative Traditions of the East Meditative Adaptations of the West (cont’d) • Thinking Without Judging: the Indian origin of mindful • Zen: practicing sitting and walking meditations; focusing on the awareness. eternal moment of the here and now to appreciate the timelessness. • Thinking In the Here And Now: Yoga breathing (Pranayama), • Mindfulness-Based Stress Reduction: practicing nonjudgmental postures (Asanas), deep state of focused awareness (Samadhi) awareness and its benefits for patients with chronic pain, heart disease, cancer, depression, anxiety, and for healthy people. • Thinking without Suffering: suffering is linked to habit-based desire and cravings; meditative pathways through serenity and • Mindfulness-Based Cognitive and Acceptance-Based Therapy: insight. benefits of adding mindfulness to psychological interventions for major depression, bipolar disorder and anxiety disorders. • Tibetan Self-Aware Positive Emotions: compassionate mental • Neurofeedback: awareness of one’s brain wave activity and states including loving kindness and how this alters brain wave benefits for ADHD, anxiety, autism, depression, epilepsy, coherence. headaches and insomnia; states of awareness associated theta, • Zen: Thinking About Not Thinking: counting one’s breaths up to alpha, beta and gamma feedback. ten repeatedly, full absorption in what we experience; sitting meditation and Zazen.

Thinking Without Judging Yoga breathing (Pranayama) • Think of something good that happened to you recently, and how it affected your mindset. Now think of something bad that happened, • Several researchers have reported that pranayama and what that did to your mindset. techniques are beneficial in • Now imagine that neither event was good, and neither was bad. • Treating a range of stress-related disorders, They simply happened, existed. • Improving autonomic functions, • How does that change how you would have felt as a result of those events? How does it change your happiness, your mood? How • Teachers say that the practice develops a steady mind, does it change what you do in reaction? strong will-power and sound judgement; that sustained practice extends life and enhances perception, • When you stop judging things as good or bad, you are no longer burdened by the emotions of this judgment, and can live lighter, • A systematic review on the symptomatic relief of asthma freer. by breathing exercises did not find substantial evidence for improvement.

42 Benefits of Asana Postures Tibetan Self-Aware Positive Emotions

• reduce stress and anxiety • reduce symptoms of lower back pain • “Matthieu Ricard, a Tibetan Buddhist monk and • be beneficial for asthma and chronic obstructive pulmonary scientist, named ‘the happiest man in the world’ in disease (COPD) the interview said that positive emotions replace • increase energy and decrease fatigue negative destructive emotions. He says that • improve diabetes management 40,000 hours of meditation has enabled his brain • reduce sleep disturbances to produce more positive emotions.” • reduce hypertension • improve blood circulation

Tibetan Self-Aware Positive Emotions INSULA • The anterior insular cortex (AIC) is believed to be responsible for emotional feelings, including maternal and romantic love, anger, • When engaged in compassionate meditation, the fear, sadness, happiness, sexual arousal, disgust, aversion, brain region known as the insula burst into action unfairness, inequity, indignation, uncertainty. when the expert meditators heard the sound of a • A number of functional brain imaging studies have shown that the woman in distress. (The insula—a part of the insular cortex is activated when drug abusers are exposed to limbic system—has been associated with the environmental cues that trigger cravings. visceral feeling of emotion, a key part of • The insular cortex also is where the sensation of pain is judged as empathizing with another's emotional state.) to its degree. Further, the insula is where a person imagines pain when looking at images of painful events while thinking about their happening to one's own body. Those with irritable bowel syndrome have abnormal processing of visceral pain in the insular cortex related to dysfunctional inhibition of pain within the brain.

Meditation Interventions & Gene Expression Temporal Parietal Junction 2 small, randomized controlled trials of meditation (Cole et al). 45 stressed caregivers and 40 lonely adults. • This part of the brain also plays a role in emotional In both studies: meditation intervention shifted gene processing. People use the connections at the expression profiles in leukocytes away from an temporoparietal junction to understand their own inflammatory gene profile. emotions, and this structure plays a role in moral The expression of genes in immune cells can be influenced judgments as well. Ethical and moral decisions can by meditation. rely on information from this region. The temporoparietal junction also allows people to discern and process the emotions of others, attributing emotions to specific events or information known about other people.

43 APPLYING POSITIVE PSYCHOLOGY William Sieber, PhD A Certificate Program Dr. Sieber is a Clinical Professor in Psychiatry and Family Medicine at the Earn 12 hours of CE and a Certificate University of California, San Diego. Lecture 1: Practicing Positive Psychology Lecture 2: The Habits of Happy People He coordinates the Collaborative Care program, and supervises primary care patients with chronic illnesses. His clinical expertise includes the treatment of fatigue, stress, anxiety, and mood disorders.

Jaime L. Kurtz, PhD Neuroscience of Mindfulness: Dr. Kurtz is an expert in the application of Gratitude Your attitude plays a large role in determining whether you can feel grateful Positive Psychology. She is Associate in spite of life’s challenges. Gratitude is just happiness that we recognize Professor of Psychology at James Madison after-the-fact to have been caused by the kindness of others. Gratitude doesn’t just make us happier; it is happiness in and of itself! University. Her research has practical Gratitude is defined by your attitude towards both the outside world and strategies to enhance positive emotions in yourself; those who are more aware of the positives in their lives tend to focus their attention outside of themselves. Gratitude is a key to happiness and people with mood disorders and in healthy contributes to a healthier mind, body, and spirit. By practicing gratitude, we individuals. are celebrating what brings us joy, directs our actions, and influences our outcomes. Expressing gratitude fosters a greater sense of purpose.

She is co‐author of Positively Happy, a Practicing gratitude can increase happiness in general, strengthen the immune system, lower blood pressure, relax the body, increase energy levels, handbook providing key activities to facilitate healthy sleep, and foster better interpersonal relationships. The increase wellbeing. simple act of acknowledging things to be grateful for can influence our thoughts, action and mood.

Joy is contagious. Researchers of the Framingham Heart Unsustainable Sources of Happiness: why improving Study who investigated the spread of happiness over 20 life circumstances (e.g., income or one’s appearance) years found that those who are surrounded by happy does not make us sustainably happier due to hedonic people “are more likely to become happy in the future.” adaptation. This is reason enough to dump the Debbie Downers and spend more time with uplifting people. Dawber 5200

44 Resilience, not happiness, is the opposite of Causal analysis: the ability to completely and depression: Happy people know how to bounce back accurately identify causes of the problems and prevent replication. from failure. Resilience is like a padding for the inevitable hardship human beings are bound to face. Self‐efficacy: sense of mastery and competence. Realistic optimism: the ability to look realistically at As the Japanese proverb goes, “Fall seven times and what is, as well as what is possible, and choose a perspective that enhances one's ability to make the best stand up eight.” of the moment and bring one's best to life.

1) Maintaining good relationships with close family members,  6) Look for opportunities of self‐discovery after a struggle with loss

friends and others 7) Developing self‐confidence

 2) Avoid seeing crises or stressful events as unbearable 8) Keep a long‐term perspective and consider the stressful event in a problems broader context

 3) Accept circumstances that cannot be changed 9) Maintain a hopeful outlook, expecting good things and visualizing what is wished  4) Develop realistic goals and move towards them 10) Take care of one's mind and body, exercising regularly, paying  5) Take decisive actions in adverse situations attention to one's own needs and feelings

First, grateful thinking promotes the savoring of positive life Change Your Verbs. experiences.

Use “won't” instead of “can't” Second, expressing gratitude bolsters self‐worth and self ‐ esteem. When you realize how much people have done for you Use “want” instead of “need” or how much you have accomplished, you feel more confident Use “choose to” instead of “have to”  and efficacious.

Use “could” instead of “should.” Third, gratitude helps people cope with stress and trauma.

45 Fourth, the expression of gratitude encourages moral behavior. Grateful people are more likely to help others Fifth, expressing gratitude tends to inhibit invidious (e.g., you become aware of kind and caring acts and feel comparisons with others. If you are genuinely thankful compelled to reciprocate) and less likely to be and appreciative for what you have ( e.g., family, health, materialistic (e.g., you appreciate what you have and home), you are less likely to pay close attention to or become less fixated on acquiring more stuff ). envy what the Jones’ have.

Sixth, the practice of gratitude is incompatible with negative emotions and may actually diminish or deter such feelings as anger, bitterness, and greed. Self‐compassion entails being warm and understanding Last but not least, gratitude helps us with hedonic adaptation. toward ourselves when we suffer, fail, or feel inadequate, If you recall, hedonic adaptation is illustrated by our rather than ignoring our pain or flagellating ourselves remarkable capacity to adjust rapidly to any new circumstance with self‐criticism. or event.

Lyubomirsky, Sonja (2007‐12‐27).

Common humanity. Frustration at not having things exactly Therefore, self‐compassion involves recognizing that as we want is often accompanied by an irrational but suffering and personal inadequacy is part of the shared pervasive sense of isolation –as if “I” were the only person human experience ‐ something that we all go through suffering or making mistakes. All humans suffer, however. rather than being something that happens to “me” The very definition of being “human” means that one is alone. mortal, vulnerable and imperfect.

46 Laughter relaxes the whole body. A good, hearty laugh Forgiveness does not necessarily mean reconciliation with relieves physical tension and stress, leaving your muscles the person that hurt you, or condoning of their actions. relaxed for up to 45 minutes after. What you are after is to find peace. Forgiveness can be defined as the “peace and understanding that come from Laughter boosts the immune system. Laughter decreases blaming that which has hurt you less, taking the life stress hormones and increases immune cells and infection‐ experience less personally, and changing your grievance fighting antibodies, thus improving your resistance to story.” disease.

Humor The Neural Funny Bone: fMRI Study while Viewing Sitcoms • Humor is a significant component of what makes us unique as human beings; we are perhaps alone among animals in Humor detection engaging in behavior designed to encourage humorous increased activity in Humor appreciation responses. inferior frontal cortex increased activity in • Without humor, much of the color and variety inherent in and temporal cortex amygdala and insula human social discourse would be lost (Brownell and Gardner, 1988). Indeed, the absence of a sense of humor can have distressing interpersonal consequences. • Humor can be therapeutic, producing beneficial effects on the immune and central nervous system (Fry, 1992), and can provide coping mechanisms for life’s tribulations (Lefcourt et al., 1997).

Brownell, H.H., Gardner, H., 1988. Neuropsychological insights into humour. In: Durant, J., Miller, J. (Eds.), Laughing Matters: A Serious Look at Humour. Longman Scientific and Technica, Harlow, UK, pp. 17–34 Fry,1992 JAMA. 267:1857-1858 Lefcourt,, Davidson, Prkachin, Mills, 1997. J. Res. Pers. 31, 523–542. From: Moran JM, Wig GS, Adams RB Jr, Janata P, Kelley WM. Neuroimage, 2004, 21:1055-1060.

Increased Brain Activation (ventral and dorsal Increased Brain Activation striatum, anterior cingulate, auditory association (hippocampus/amygdala and auditory association areas) during Listening to Happy Classical Music areas) during Listening to Sad Classical Music

Hippocampus/Amygdala

Ventral Striatum

From: Mitterschiffthaler, Fu, Dalton, Andrew , and Williams. Hum Brain Mapp, 2007, From: Mitterschiffthaler MT, Fu CHY, Dalton JA, Andrew CM, Williams SCR. Hum Brain Mapp, 2007, 28:1150-1162. 28:1150-1162.

47 “Happiness is when what you think, what you say, and what you do are in harmony.” Enhancing Resilience To Stress: how mastering positive physical and psychological challenges facilitates coping with major physical illness and psychological stressors.

Fulfillment: substituting dopamine‐related sources of craving and everyday addictions to endorphin‐related sources joy and fulfillment.

Applying Positive Psychology: empowering the proactive, social, and self‐ aware prefrontal cortex to form positive habits, adding variety and flexibility to help make positive habits become automatic.

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Self‐Test

1) What was the ACE Study? a. A poker game study of pro players b. A study rating the categories of adverse childhood experiences and measuring them against the prevalence rates for poor health outcome. c. A study measuring the prevalence rates of disabilities matched against socio‐economic status d. Landmark research on the Advanced Cognitive Explorations 2) Post‐Traumatic Stress Disorder is associated with: a. All traumatic experiences b. Fragmented memory systems c. The severity of the traumatic incident(s) d. People of weak ego structures 3) Anxiety disorders are best addressed with: a. Medication b. Deep analysis c. Exposure‐based paradigms d. Relaxation 4) The three mental operating systems are: a. Go, stop, and idle b. Fast, slow, and still c. Thinking, feeling, and doing d. The executive, salient, and default mode network 5) What role does dopamine play in addictions: a. Wanting but not liking b. Liking but not wanting c. Pleasure d. Sedation 6) Chronic inflammation is associated with: a. Energy b. Sharp thinking c. Cognitive fog, dementia, and depression d. Decreased immune function 7) Gut bacteria: a. Must be balanced and if not can potentially lead to inflammation b. Should be cleansed periodically with antibiotics or enemas c. Optimally should be feed with simple carbohydrates d. Represent a symptom of illness 8) Alzheimer’s disease is associated with: a. Too much education b. Inflammation, glycation, poor sleep, and many other factors c. One gene d. The Mediterranean diet 9) Meditation can contribute to: a. A good distraction from a hectic life b. Overall improved wellbeing, including decreased anxiety and depression. c. Perpetuating a fad d. An opportunity to reflect on the things that really worry you 10) Positive Psychology has: a. Offered nothing more than a sugar coated pop psychology b. Has contributed to a diversion from what is really important c. Research backing the practices of compassion, gratitude, and forgiveness d. Just offered the flipside to clinical psychology