Week 2 (Anxiety, Hearing, Alterations in Consciousness and Sleep) Flashcards

Question

Benzodiazepines

Answer 1

Bind **allosteric** site on **GABA-A** receptor-**chloride** **channel** complex (distinct from GABA binding site) Positive allosteric modulators: produce little or no effect on chrloride conductance in absence of GABA, but **enhance GABA-mediated** **increase** **in chloride conductance** (increase efficiency of GABAergic synaptic transmission by membrane **hyperpolarization** and **decrease firing** rate of neurons) All have **anxiolytic**, **sedative** and **hypnotic** properties

Answer 2

**Anxiolytics, sedatives, "tranquilizers"** cause **calm**, relaxation then drowsy, **sleepy**; also cause paradoxical disinhibition (inhibitory pathways themselves get turned off so excitation occurs) **Hypnotics** produce **sleep** **Anesthetics** cause **unconscious**

Answer 3

**Barbiturates** have **steep** response curve so **easy** to produce undesired effects (like drowsiness) **Benzodiazepines** have **shallow** curve so **wide safety margin** and takes **more** drug to produce undesired effects

Answer 4

Absorption: well absorbed after **oral** administration Distribution: very **lipid soluble**; distribute throughout body Metabolism: primarily **hepatic** **clearance**, oxidation and subsequent conjugation (**oxidation** can produce **active** **metabolites**)

Answer 5

**Diazepam**, **chlordiazepoxide** and **clonazepam** have **active** **metabolites** and long effective half-lives; accumulate with repeated daily administration **Oxazepam** and **lorazepam** are only conjugated (no CYP metabolism) and do **not** form active metabolites; accumulation is minor

Answer 6

Not if they have active metabolites! If drug has **active metabolites** (diazepam, chlordiazepoxide, clonazepam) then duration of action based on those active metabolites too!

Answer 7

CNS: **Anxiolytic** (treatment of GAD) **Sedative** (used before medical procedures like endoscopy) **Hypnotic** (promotes sleep) **Anesthetic** (note: benzos are not analgesic) **Anticonvulsant**, **muscle** **relaxant** (produces some degree of skeletal muscle relaxation (suppression of spinal and supraspinal motor reflexes))

Answer 8

Common adverse effects are extensions of their pharmacological actions: **sedation**, decreased intellectual function (**confusion**), **anterograde** **amnesia** (no memory acquisition or recall), **psychomotor** **impairment** (for days), withdrawal **seizures**; fatal OD rare unless combined with ethanol or other CNS depressant Abuse only in those with a history of abuse Few drug interactions due to wide safety margin (**high** **TI**) and no inhibition/induction of CYP450 Wide individual differences in sensitivity to benzodiazepines Elderly more sensitive to all effects In **liver** **disease**, increased sensitivity to those drugs that do CYP metabolism in liver (diazepam, etc) so use **oxazepam** or **lorazepam** instead for patients with liver disease

Answer 9

**Competitive** **antagonist** at benzodiazepine binding site; used clinically to **treat benzo OD**

Answer 10

**Tolerance** develops (pharmacodynamic, not pharmacokinetic) to benzos in general (not individual types) for **sedative** and **anticonvulsant** activity (**not** **anxiolytic** effects) Cross-tolerance between benzos and other CNS depressants Physical dependence occurs if chronic use and get withdrawal upon cessation **WIthdrawal** more apparent with **shorter** **acting** drugs (suddenly stop then immediately "off" drug as opposed to longer tapering built in to longer acting drugs) Symptoms of withdrawal may mimic anxiety (**jitteriness, insomnia, loss of appetite**) or may be different (**tremor, muscle twitching, paresthesias, seizures**)

Answer 11

Switch patient from short-acting to **long-acting benzo** and slowly reduce dosage of drug

Answer 12

Partial **agonist of 5HT1A** receptors Structurally different from benzodiazepines, does NOT interact with GABA receptors Best for previously untreated patients who might require **long-term** treatment of **GAD**, or who are abusers of CNS depressants Not effective in panic attacks Side effects: low incidence of headache, dizziness Response occurs only after **several** **weeks** of tretment **No bad side effects**: produces no sedation (just calming), no anticonvulsant or muscle-relaxant properties, little impairment of cognitive or psychomotor skills, no tolerance or withdrawal upon cessation, little or no abuse potential, no additive effect Used for **dyspepsia** or **IBS** because there are 5HT1A receptors in fundus of stomach

Answer 13

**TCAs**: effective in some patients with panic attacks MAOIs: effective in some patients with panic attacks **Beta blockers** (propranolol): prevent peripheral autonomic manifestations of anxiety (tremor, sweating, tachycardia and palpitations); don't prevent anxiety itself

Answer 14

Difficulty **falling** asleep, **staying** asleep, and/or too **early** awakening Caused by stress, emotional upset, aging, medical and psychiatric illness (sleep apnea, nocturnal myoclonus, depression), drugs, jet lag

Answer 15

Induce sleep rapidly Produce normal sleep Reduce number of awakenings Wake up refreshed (no hangover) Not cause tolerance or dependence Safe (high TI, few side effects, no drug interactions)

Answer 16

**Decrease latency** of sleep onset **Increase** duration of **stage 2, non-REM sleep** **Decrease** **slow-wave** sleep (stages 3 and 4) **Reduce REM** sleep (this is bad and can produce hangover the next day!) Prolong total sleep time

Answer 17

All benzos **can** be used as hypnotics but **don't** meet criteria for good hypnotic (have hangover effect, don't produce normal sleep, have tolerance so only good short-term, produce withdrawal effects (insomnia, REM rebound which can produce nightmares)) **Triazolam** (**Halcion**): short half life (1.5 - 5.5 hours), little hangover, less accumulation but can produce increased wakefulness during last 1/3 of night, daytime rebound anxiety and anterograde amnesia for some **Temazepam** (**Restoril**): half life between triazolam and flurazepam but slowly absorbed and sleep onset can be delayed

Answer 18

Structure unrelated to benzodiazepines or barbiturates but still interact with **GABA-A** receptor! **Zolpidem** (**Ambien**): relatively short half life (1.5 - 4.5 hours), no active metabolites **Zaleplon** (**Sonata**): binds subtype of GABA-A receptor, very short duration of action, useful for patients who have difficulty falling asleep or awaken in the middle of the night **Eszopiclone** (**Lunesta**): binds to subtype of GABA-A receptor; intermediate duration of action

Answer 19

**5HT** is turned to **N-acetyl serotonin** by **NAT** in the pineal gland N-acetyl serotonin is turned to **melatonin** Note: synthesis under control of **postganglionic sympathetic fibers** that innervate the pineal gland

Answer 20

Lipophilic hormone Mainly produced and secreted at **night** by the **pineal gland** Stimulated by darkness and inhibited by light **Light** --\> eyes/retinohypothalamic tract --\> **SCN** of hypothalamus --\> **PVN** of hypothalamus --\> **spinal** **cord** --\> preganglionic cell bodies in intermediolateral horn project out **sympathetic** **ganglia** --\> **superior cervical ganglion** --\> postganglionic sympathetic neurons along internal carotid --\> **pineal gland** Synthesis and release decreases with age

Answer 21

**Melatonin** receptor **agonist** Targets MT1 and MT2 melatonin receptors (expressed in SCN and throughout brain) Does not show binding to GABA-A receptors Particularly for delayed sleep onset Not shown to produce dependence or potential for abuse **Augments** ongoing natural **melatonin release**

Answer 22

**Antidepressants** (given at bedtime to facilitate sleep) **Antihistamines** (doxylamine, diphenhydramine) NOT ethanol! Can cause REM rebound

Answer 23

**Early morning awakening** Rebound daytime **anxiety** **Amnesic** episodes

Answer 24

**Extracellular** pathogens (**bacteria**) activate **pro-inflammatory** gene program: IL1B, **IL6**, **TNF**, **NF-kB** **Intracellular** pathogens (**viruses**) elicit **antiviral** gene program: **IFN** genes, TFs such as **IRFs** (interferon regulatory factors)

Answer 25

1) **HPA** **axis**: CRH --\> ACTH --\> **GCs** from adrenal gland --\> GCs enter WBCs and (1) **decrease** expression of **antiviral** immune response genes (IFNA, IFNB) and (2) **decrease** expression of **pro-inflammatory** immune response genes (IL1B, IL6, TNF) and (3) **induces** transcription of **anti-inflammatory** NFKB1A and (4) **antagonizes** **pro-inflammatory** TFs (NF-kB and AP1) via protein-protein interactions 2) **Sympathetic** nervous system: **epi** from adrenal gland and **NE** from SNS nerve fibers act on **beta adrenergic receptors** on WBCs to (1) **decrease** expression of **antiviral** immune response genes (IFNA, IFNB) and (2) **increase** epression of **pro-inflammatory** immune response genes (IL1B, IL6, TNF) and (3) **stimulates** tx of **TH2-type cytokine** genes (IL4, IL5) and (4) **suppresses** expression of **TH1-type** genes (IFN, IL12) Summary: HPA suppresses antiviral and inflammatory response (yet inflam present because reduced levels of GC-mediated gene transcription?); SNS suppresses antiviral but activates inflammation

Answer 26

Yes! Tyrosine hydroxylase nerve terminal in direct contact with lymphocyte This allows quick regulation of immune cells by epi and NE?

Answer 27

Increased risk of infectious disease (viral?!) Increased risk of cardiovascular disease

Answer 28

In **MDD**, have increased sympathetic stimulation (?) so have increased **pro-inflammatory cytokines** and increased **cardiovascular** **mortality**

Answer 29

**Poor social ties** are associated with increased susceptibility to the **common cold** **Higher psychological stress** increases **susceptibility** and **severity** of common cold symptoms Remember, common cold is a **VIRAL** illness! **Decreased antiviral genes** in depression/stress!

Answer 30

Yes, **stress** and **depression** make viral **vaccines** (pneumococcal, herpes zoster, hepatitis) **less** **effective**!

Answer 31

Social inhibition (shyness) accelerates progression of HIV/AIDS!

Answer 32

Stress promotes metastasis! Beta blockers being studied in Israel to determine whether they can prevent metastasis

Answer 33

Third way to regulate innate immune system and antiviral gene programs CNS sensing what is going on externally and integrating info regarding general physiological conditions to lead to **changes** in **innate immune system** and **antiviral gene programs** This is critical because for example, when we're sleeping, CNS gives DIFFERENT signals to immune system than when we're awake

Answer 34

**SNS** is **fast** acting, so initially get **increased** **pro-inflammatory** cytokines **GCs** act **later** to **suppress pro-inflammatory** cytokines

Answer 35

Because GC response elements (receptors) are downregulated!

Answer 36

Insomnia and shift work upregulates inflammatory markers Sleep restriction activates pro-inflammatory cytokine genes and increased NF-kB activity

Answer 37

1) Interaction of **circulating** **cytokines** with cytokine receptors in the **brain circumventricular organs** that lack a functional BBB 2) Stimulation of **brain vascular endothelial cells** to release second messengers that stimulate subsequent **cytokine production within the brain** 3) **Active** **transport** of cytokines across the BBB via **carrier molecules** 4) **Peripheral** inflammatory stimulation of afferent nerves that subsequently **stimulate** **CNS** tissues to produce **cytokines**

Answer 38

Hypothalamus: key role in the regulation of systemic physiological function and organism-level biobehavioral dynamics (metabolism, sleep, feeding) Amygdala: mediates fear- or threat-related responses and processes social information Hippocampus: key role in learning and short-term memory, general information processing, spatial information processing, and navigation and mobility Pre-frontal cortex: complex information processing and planning Anterior cingulate cortex: involved in a diverse array of cognitive-emotional interactions Ventral striatum: involved in positive motivation and reward

Answer 39

Endotoxin causes inflammation and inflammatory cytokines increase **depression** Also inhibits reward activity in the brain (ventral striatum?)

Answer 40

Cognitive behavioral therapy Aerobic exercise Meditation Tai Chi Chih: boosts viral immunity and response to vaccination

Answer 41

Increased coping Reduced depression Increased natural killer activity Lower rates of recurrence and death

Answer 42

Deeply engrained Inflexible Maladaptive Stable Impairs function Distresses others Definition of personality disorder: PDs represent failure to develop a sense of **self-identity** and the **capacity for interpersonal functioning** that are adaptive in the context of the individual's cultural norms and expectations

Answer 43

Cluster A = Mad = odd or eccentric = paranoid, schizoid, schizotypal = social deficits, perceptual distortions, cognitive impairment = psychosis Cluster B = Bad = dramatic, emotional or erratic = histrionic, antisocial, borderline, narcissistic = impulsivity, aggression, affective instability, emotionality = substance misuse, sociopathy Cluster C = Sad = anxious or fearful = avoidant, dependent, obsessive-compulsive = anxiety/behavioral inhibition, compulsivity = depression, anxiety disorders, social phobia, somatoform disorders, eating disorders

Answer 44

Pervasive pattern of **detachment** from social relationships and a **restricted range of expression of emotions** in interpersonal settings Experience of illness: anxiety because of forced contact with others Problemati behaviors: delay seeking care, appears unappreciative Management strategies: provide clear explanations, avoid over involvement in personal and social issues

Answer 45

Pervasive pattern of **social** and **interpersonal** **deficits** marked by acute discomfort with, and reduced capacity for close relationships as well as by **cognitive** or **perceptual** **distortions** and **eccentricities** of behavior Prominent features: odd beliefs, socially isolative Experience of illness: odd interpretations of illness Problematic behaviors: delay seeking care, odd beliefs, odd behavior Management strategies: tolerate odd beliefs and behaviors, avoid over involvement

Answer 46

Pervasive **distrust** and **suspiciousness** **of others** such that their motives are **interpreted as malevolent**; this begins by early adulthood and is present in a variety of contexts Prominent features: distrust, suspicion Experience of illness: heightened sense of fear and vulnerability Problematic behaviors: feal that physician will harm leads to arguments and conflict Management strategies: adopt a professional stance, provide clear explanations, be empathetic to fears, avoid direct challenge to paranoid ideation

Answer 47

Pervasive pattern of **grandiosity**, **need for admiration**, and **lack of empathy** that begins by early adulthood and is present in a variety of contexts Experience of illness: anxiety caused by doubts of personal adequacy Problematic behaviors: demanding, attitude of entitlement, denial of illness, alternating praise and devaluation of physician Management strategies: validate concerts, give attentive and factual responses to questions, channel patient's skills into dealing with illness

Answer 48

Pervasive and excessive **emotionality** and **attention-seeking behavior** which begins by early adulthood and is present in a variety of contexts Problematic behaviors: overly dramatic, attention seeking behavior, inability to focus on facts and details, somatization Management strategies: avoid excessive familiarity, show professional concern for feelings, emphasize objective issues

Answer 49

Pervasive pattern of **instability** **of interpersonal relationships**, self-image, affects, and marked **impulsivity** that begins by early adulthood and is present in a variety of contexts Experience of illness: terrifying fantasies about illness Problematic behaviors: fear of rejection and abandonment of self-destructive acts, idealization and devaluation of physician Management strategies: avoid excessive familiarity; schedule regular visits; provide clear, non technical explanations; tolerate angry outbursts but set limits; maintain awareness of personal feelings; consult psychiatrist

Answer 50

Pervasive pattern of disregard for, and violation of, the rights of other that begins in childhood or early adolescence and continues into adulthood Experience of illness: anger, entitlement, fear Problematic behaviors: anger, impulsive behavior, deceit, manipulative Management strategies: set clear nonpunitive limits

Answer 51

Preoccupation with **orderliness**, **perfectionism**, and **mental** and **interpersonal** **control**, at the expense of flexibility, openness and efficiency which begins by early adulthood and is present in a variety of contexts Experience of illness: fear of losing control of bodily functions and emotions Problematic behaviors: fear of relinquishing control, excessive questioning and attention to details, anger about disruption of routines Management strategies: complete thorough history and examinations, provide thorough explanations, do not overemphasize uncertainty, encourage patient participation in treatment

Answer 52

Pervasive and excessive need to be taken care of that leads to submissive and clinging behavior and fears of separation which begins by early adulthood and is present in a variety of contexts; the dependent and submissive behaviors are designed to elicit care giving and arise from self-perception of being unable to function adequately without the help of others Management strategies: provide reassurance, schedule regular check-ups, set realistic limits on availability, enlist others to support patient, avoid rejection of patient Prominent features: excessive need to be taken care of, submissive and clinging behavior Experience of illness: fear of abandonment, helplessness

Answer 53

Pervasive pattern of **social** **inhibition**, feelings of **inadequacy**, and **hypersensitivity to negative evaluation** that begins by early adulthood and is present in a variety of contexts Experience of illness: heightened sense of inadequacy, low self-esteem Problematic behaviors: withholds information, avoids questioning or disagreeing with physician Management strategies: provide reassurance, validate concerns, encourage reporting of symptoms and concerns

Answer 54

Perception is **not** determined solely by what we **hear** (bottom-up processing) but by **higher-level processes** (top-down) **McGurk** **Effect**: hear "ba" but when **see**"ga" at the same time, then hear "da" (vision goes into what you "hear" because brain is **integrating** information!)

Answer 55

Sound waves are compressed air/rarefied air Pitch (**frequency**; period) Loudness (volume/**intensity**; amplitude) **Phase**

Answer 56

**External**/outer ear = pinna, external auditory canal **Middle** ear = tympanic membrane, stapes (ossicles), incus; middle ear is amplification device because tympanum larger than stapes/oval window **Inner** ear = oval window, round window, semicircular canals, cochlea, auditory nerve

Answer 57

Tympanum --\> malleus --\> incus --\> stapes --\> oval window --\> scala vestibuli --\> helicotrema --\> scala tympani --\> round window Note: scala media between 2 canals (scala vestibuli and scala tympani) and this is where mechanotransduction and cochlea proper sits

Answer 58

Hair cells transduce **mechanical** energy to **electrical** signals: **cillia** on inner hair cells embedded in gelatinous membrane (tectorial membrane) and when **perilymph** **vibrates**, it vibrates reissner (?) membrane and shears **tectorial** and **basilar** membrane to move cillia forward and backward which opens/closes K+ channels to **let K+ in** **Inner** hair cells are **single** row **Outer** hair cells are **3-5** rows **Inner** hair cells are primarily responsible for **hearing**

Answer 59

**Inner** hair cells: innervated by **many** **fibers** so most info comes from inner hair cells; only have 3,500 inner hair cells which is not very many and these **die** as you age! **Outer** hair cells: not innervated by many fibers; sensory neurons but receive **efferent** innervation from **CNS** so can **change** flexibility/**physical** **properties** of basilar membrane to help you hear (mechanical amplification/attenuation so contraction of outer hair cells changes physical properties/function of inner hair cells)

Answer 60

**Areas** **lined** **up** by which energy vibration (frequency) affects that area High levels of energy vibrate thicker end of membrane and low levels of energy vibrate thinner end of membrane (apex) Cochlea all the way to auditory cortex (entire auditory system) has tonotopy, or frequency map

Answer 61

**Decomposes** complex sounds to **component frequencies**

Answer 62

Hearing is the detection of the **vibration** of **air** molecules

Answer 63

**Single** nerve fiber has a **characteristic** **frequency** where it will fire the **highest** number of spikes With **higher** **intensity** (louder) sounds, still will have the same characteristic frequency but will fire **more spikes**

Answer 64

Auditory nerve (CNVII) Cochlear nerve Cochlear nuclei Olivary complex Nucleus of the lateral lemniscus Inferior colliculus (all in **brainstem**) Medial geniculate nucleus (in **thalamus**) A1 (primary auditory cortex: Broadmann's area 41) (in **cortex**)

Answer 65

**Both** sides! Information is bilateral, and becomes bilateral very early on

Answer 66

**Rostral** tip of primary auditory cortex has **low** frequency Caudal tip of primary auditory cortex has **high** frequency

Answer 67

**Left** auditory areas more responsive to **speech** **Right** auditory areas more responsive to **music** **Equally** responsive to **environmental** sound

Answer 68

1) **Horizontal** (azimuth) discrimination based on **interaural** **time** **delay** (20-2,000Hz; **low** **frequency**) 2) **Horizontal** (azimuth) discrimination based on **interaural level differences** (2,000-20,000Hz; **high frequency**) 3) **Vertical** (elevation) discrimination based on **shape of pinna**

Answer 69

**Up/down** is dramatically **altered** by **shape** of pinna Can still tell if sound is coming from left/right if pinna distorted

Answer 70

**Right** ear neurons fire at certain **point** in phase/cycle but **left** ear neurons fire slightly **later because** phase is off because took longer to get there **Compute** **difference** in firing in R vs. L ear and tell which direction sound is coming from

Answer 71

In a given fiber, the action potential tends to occur at the **same** **phase** (ie always at the **peak** of the sound wave) Note: this is how we can calculate interaural time delays!

Answer 72

Because if **complete** **cycle** or 2 cycles off, you **can't tell** which one came "first" This is why you have to use interaural level differences to tell difference in direction when high frequency waves

Answer 73

Sound reaches **L ear** and action potential travels **toward** **medial superior olive** (MSO) Sound reaches **R ear** a little **later** and action potential begins traveling toward MSO **APs** **converge** on an MSO neuron that responds most strongly if arrival is **coincident** In this way, based on **location** of AP convergence, can tell which one came first!

Answer 74

Used to detect horizontal location when you have **higher** **frequencies** 1) Get stronger stimulus to **L** lateral superior olive (**LSO**) of olivary complex 2) Stimulis **inhibits** **R** **LSO** via medial nucleus of trapezoid body (MNTB) interneuron 3) **Excitation** from **L** greater than inhibition from R so get net excitation to higher centers 4) Inhibition from L greater than excitation from R so get **net inhibition on R** and no signal to higher centers

Answer 75

**One month**

Answer 76

1) **Conductive** (mechanical): **otosclerosis** (ossification of bones or ligaments of middle ear); **otitis media** (scar tissue immobilize membrane) 2) **Sensorineural**: **hair** **cell** loss (aging, loud sounds, ototoxic drugs like gentamicin); **brainstem** **lesions** (trauma, tumors); more serious

Answer 77

**Gradual** **loss** of hearing in **high** **frequency** range

Answer 78

**Ringing** in the ear that can be produced by **ototoxic** **drugs** or **loud sounds** Permanent tinnitus can be due to a **phantom** sound (like phantom limb) generated in CNS Acute/permanent **damages** in **cochlea** trigger permanent lesion in **auditory** **cortex** which **decreases** amount of **input** so brain **reacts with plasticity** to **increase** **activity** of cells in auditory cortex so get **phantom sound**

Answer 79

An unpleasant **sensory** and **emotional** experience associated with actual or potential tissue damage, or described in terms of such damage

Answer 80

**Location** on the body **Duration**: acute, recurent, chronic **Intensity**: mild, moderate, severe **Etiology**: malignant, nonmalignant **Mechanism**: nociceptive, neuropathic

Answer 81

**Nociceptive** pain: experienced when injury or irritation is detected by receptors that respond to **heat, cold, vibration, stretch** and **chemicals** released from **damaged** **cells**; note that you can be so focused at another task that you don't notice nociceptive pain until later **Neuropathic** pain: experienced when **peripheral**, **autonomic** or **central** **nervous** **system** structures are injured, irritated and/or overactive causing **dysfunction in pain signaling**

Answer 82

Pain does not subside even despite healing of the injury **Spontaneous** pain **Hyperpathia**: more pain than would be expected after a painful event **Hyperalgesia**: increased intensity of pain to further noxious stimulus **Secondary hyperalgesia**: spreading of sensitivity or pain to nearby uninjured tissue **Allodynia**: sensation of pain from a normally innocuous stimulus

Answer 83

**Biological** processes related to pain perception include **prior pain experiences** and nervous system reactivity and recovery in response to stress and symptoms **Psychological** processes include **temperamental** tendencies, such as **attentional** **biases** toward symptom-related stimuli and coping strategies employed **Social** environmental factors include **chronic** **stressors** and responses of others to symptom behavior

Answer 84

Yes! Sensory receptors can **become sensitized** to repeated stimulation, thereby causing a decreased threshold for AP firing and **allodynia** Prior medical illness, physical injury, trauma and hospitalizations have been found to be related to **increased pain sensitivity** Adverse nature of prior pain experiences appears to be more important than the number of past pain episodes **Newborns** are **more sensitive** to pain than older infants/children/adults, repetitive or prolonged pain in neonatal period can **cause long-term changes in neural pathways** involved in pain processing (including pain sensitivity) and pain does not have to be **remembered** for it to have had an impact on current pain processing :(

Answer 85

Definition: **personality** **traits**; the tendency to respond to and cope with stimuli in predictable ways Ex: activity level, habit regularity (eating, sleeping), tendency to approach or withdraw from novel situations, adaptability, emotional intensity/reactivity, mood (tendency to be optimistic or pessimistic), persistence, distractibility and sensory sensitivity **Behaviorally inhibited children** (restrained, wary, fearful) are more likely to **activate** **distress** **responses** to novel stimuli, and to d**evelop anxiety disorders** and **somatic symptoms** (ie anxious child having stomach ache when starting new school)

Answer 86

Tendency to **fixate** on pain is related to **greater** levels of pain and disability Those with tendency to interpret anxiety-related bodily sensations as **dangerous** (anxiety sensitivity) and those who **catastrophize** are more likely to develop **anxiety disorders** and **chronic pain**

Answer 87

**Coping** **inefficacy** is associated with increased distress, autonomic arousal, plasma catecholamine secretion (stress hormones) **Accommodative** **coping** (distraction, acceptance, positive thinking, challenging unhelpful irrational thoughts) is correlated with **less** **pain** **Passive coping** strategies (denial, cognitive avoidance, behavioral avoidance, wishful thinking) are correlated with **increased** levels of pain **Active coping** strategies (problem solving, emotional expression, emotional modulation, decision making) aimed at **reducing** **pain** or a specific stressor are helpful, however, active problem-solving behaviors that are not focused on a changeable problem may be ineffective and **frustrating**

Answer 88

**Denial** **Regression**: reversion to earlier developmental stage **Acting out** **Dissociation**: losing track of time, self, and/or usual thought processes and memories **Compartmentalization**: parts of oneself are separated from awareness of other parts **Projection**: misattribution of a person's undesired thoughts, feelings or impulses onto another person who does not have those thoughts, feelings or impulses **Reaction formation**: converting of unwanted or dangerous thoughts, feelings or impulses into their opposites

Answer 89

**More mature:** **Repression**: unconscious blocking of unacceptable thoughts, feelings and impulses **Displacement**: redirecting of thoughts, feelings and impulses directed at one person, but taken out upon another person or object **Intellectualization**: overemphasis on thinking when confronted with an unacceptable impulse, situation or behavior **Rationalization**: reframing a situation to reduce cognitive dissonance **Undoing**: attempt to take back an unconscious behavior or thought that is unacceptable or hurtful **Mature:** **Sublimation**: channeling of unacceptable impulses, thoughts and emotions into more acceptable ones (humor, imagining a different future) **Compensation**: psychologically counterbalancing perceived weakness by emphasizing strength in other arenas to reinforce a person's self-esteem and self-image **Assertiveness**

Answer 90

**Sympathetic nervous system** activated after stressful/traumatic event **Cortisol** released to cause **increased** **BP** and **blood** **sugar** which **reduces** immune system's ability to **heal** **Beta receptors** cause production of **pro-inflammatory cytokines**, influencing **increased pain response**

Answer 91

**80%** of people with chronic pain have anxiety symptoms (including 15-30% with PTSD) **Anxiety** is associated with **greater** **pain**, **emotional distress** and **disability**

Answer 92

Process whereby **somatic** (**physical**) symptoms are expressed in response to **stress** and is **not intentional**; is an automatic response to stress Can control symptoms with training and practice, but somatization is **not falsifying** symptoms Most frequently reported symptoms are **pain**, **GI** and/or **neurological** but can also include tension headache **Underlying** **illness** or injury can be significant stressor that triggers or **exacerbates somatization** (child with epilepsy can have non-epileptic seizures)

Answer 93

**Distress** **Disability** **Interference with recovery**

Answer 94

**One or more** somatic symptoms that are distressing and/or disrupting daily life Chronic = 6 months **At least 2** of the following: 1) **Disproportionate** and **persistent** **concerns** about medical seriousness of one's symptoms 2) High level of **health-related anxiety** 3) **Excessive** **time** and **energy** devoted to these symptoms or health concerns

Answer 95

**Illness falsification**: malingering, factitious disorder **Adjustment** **disorder**: clinically significant psychological response to an identifiable stressor **Psychological factors** affecting medical condition

Answer 96

Education, physical, behavioral, psychological, academic or work interventions, complementary/alternative therapies, pharmacological **Relaxation** **Distraction** **Hypnotherapy** **Biofeedback**: controlled breathing, relaxation or hypnotic techniques with a mechanical device that provides visual or auditory feedback when desired action is approximated **Psychotherapy** **Physical therapy** **Acupuncture** **Yoga** **Massage therapy**

Answer 97

**Mechanical** sound: sound to eardrum, **hearing** **bones** and delivered to **cochlea**; problems in mechanical sound transmission is **conductive hearing loss** **Conversion** of **mechanical** sound waves to **electrical** signals: occurs by **hair cells** within the cochlea; problems with hair cell conversion termed **sensory hearing loss** **Electrical** transmission: occurs by **cochlear** **nerve** (**CN** **VIII**); carries current generated by **hair cells to brain**; problems with cochlear nerve are **neural hearing loss** **Auditory** **perception**: occurs by the **brain**; problems with auditory sound perception are **central hearing loss**

Answer 98

**Top** part of eardrum in both posterior-superior and anterior-superior area **Natural weak spot** Critical to assess pars flaccida

Answer 99

Ear canal lesion: **foreign** **bodies** (occlusive ear wax, batteries?), **otitis** **externa** Ear drum: **tympanosclerosis** (healing after trauma), **perforations**, **atelectasis** (TM thin and drawn in), **cholesteatoma** Middle ear: **effusion**, **otitis media** Ossicles: **fixation**, **erosion**, **trauma** (fracture, dislocation)

Answer 100

AKA swimmer's ear **Infection** of **skin** **lining** ear canal Can close ear canal entirely Treated with **antibiotics** (orally, ear drops) but may need ear canal stent if completely swollen closed

Answer 101

Trapped squamous epithelium (skin) due to flaky dead skin **folding** onto itself, usually at **top** part of ear drum Eardrum becomes retracted into middle ear and folds on itself Secretes lytic enzymes **eroding bone** (ossicles, facial nerve canal, skull base, labyrinth) Locally **invasive** **Recurrence** common (comes back if you don't get it all out!) **Intracranial** complications: **meningitis**, **encephalocele**, epidural, subdural or intracerebral **abscess**, lateral sinus **thrombosis**, otitic **hydrocephalus**, **cerebrospinal fluid leak** **Extracranial** complications: **conductive** hearing loss, **sensorineural** hearing loss, **facial paralysis**, vertigo, subperiosteal **abscess**, petrous apicitis, labyrinthine fistula, Bezold's abscess, cutaneous fistula **Treatment**: no medical treatment, must be **surgically** removed (tympanomastoidectomy: postauricular incision, drill out mastoid cortex exposing cholesteatoma, 10% risk of recurrence)

Answer 102

**Inflammation** of middle ear space longer than **6 weeks** Usually **bacterial**, but often **culture negative** Presentation: **otalgia** (less severe than acute otitis media, may be ear fullness only), **otorrhea** (concurrent TM perforation), **conductive** hearing loss

Answer 103

**Ototoxic** **exposures**: chemotherapy (cisplatin, carboplatin, vincristine, bleomycin), antibiotics (aminoglycosides/gentomycin, vancomycin, biaxin, chloramphenicol), heavy metals (mercury, lead, arsenic, gold), diuretics (loop), opiates (high doses only); medications have **synergistic** effects so don't be on 2 of these! **Genetic** causes: non-syndromic (connexin-26), syndromic (Usher's, Pendred's, Alport's, Waardenberg's) **Infections**: prenatal (TORCH, syphilis), postnatal (meningitis: Strep pneumoniae, H. influenzae, N. meningitis) **Neoplasms**: acoustic neuromas/vestibular schwannomas **Sudden sensorineural** **Presbycusis** **Noise induced**

Answer 104

**Connexin-26** 50% of all patients with genetic hearing loss **Autosomal recessive** Gene is **GJB-2**: produces connexin-26 which is gap junction protein important in cell-cell ion exchange Variable severity and progression of hearing loss Treatment: **hearing aids** or **cochlear** **impant** if profound hearing loss

Answer 105

Sensorineural **hearing** loss and **visual** loss due to **retinitis pigmentosa** Leading cause of **deaf-blindness** Autosomal recessive (several subsets) Visual loss usually detected by 10yo (visual field, night blindness) Variable **vestibulopathy** **Early cochlear implantation** for auditory rehabilitation

Answer 106

Sensorineural **hearing** loss and **thyroid** dysfunction Defect in **peroxidase** (cannot incorporate iodine into thyroid hormone) **Goiter** Thyroid hormone deficiencies SNHL is typically **progressive** Autosomal recessive

Answer 107

**Sensorineural** hearing loss and **kidney** dysfunction Defect in **type IV collagen** Kidney failure in **teen** years **X-linked**, so male predominance

Answer 108

Sensorineural hearing loss Defect in **neural crest** development **Dystopia canthorum** Disorders in skin and hair pigmentation (**white forelock**) **Autosomal dominant**

Answer 109

**Benign** neuromas (more accurately called **vestibular schwannomas**) Very **rare** (1 in 100,000) Benign growth of **schwann cells** lining the **vestibular nerve** Occurs wihtin **cerebello-pontine angle** and into the **internal auditory canal** Presentation with unilateral sensorineural hearing loss, **tinnitus**, and variable **dizziness** **T1 MRI with contrast** is best for diagnosing vestibular schwannoma

Answer 110

Fairly **common** (1 in 1,000) Acute **unilateral** sensorineural hearing loss: will have ear **fullness** and tinnitus, variable **vestibular** symptoms Need to rule out other causes (neoplasms) Presumed **viral** **infection** (can be from vascular or other issues) but not totally known Treatment is high dose **corticosteroids** (better to do this within days), now doing injection through TM and pills Can be **noise induced** (volume of sound combined with duration)

Answer 111

Hearing loss with **increased** **age** Quite **common** Cannot predict stability vs. progression Treatment: **hearing aid**, cochlear **implant** if severe

Answer 112

Externally worn processor picks up sound and codes it into a "map" Signal sent across the skin by FM radio waves Computer chip under skin behind the ear sends signals to **electrodes in cochlea** Electrodes **stimulate auditory nerve** Cochlear implant takes over the **mechanical sound transmission** (ear drum, hearing bones) and conversion into **electrical** **signals** done by the **hair cells** to stimulate the cochlear nerve directly Cochlear implants have been around since 1970s

Answer 113

**Conductive** hearing loss | (Same as Weber test)

Answer 114

Treat **nerve** hearing loss right away! Can wait before treating conductive hearing loss

Answer 115

Endogenous Period close to, but a little **longer than 24 hours** Synchronized by **light** and other environmental cues Impact almost **all** biological processes Strong **genetic control**

Answer 116

1) At dawn, **light** activates transcription of **Per** and **Cry** (clock genes) 2) Message translated into **proteins**, they **dimerize** 3) Then at dusk are **translocated** back into **nucleus** where they **inhibit** their own transcription (**negative feedback!**)

Answer 117

You could **lose rhythmicity** altogether You could have a **shorter** endogenous rhythm (like family in Utah that woke up at 3-4am every morning)

Answer 118

If **longer** cycle length, then a **"night person"** because can stay up later If **shorter** cycle length, then a **"morning person"** because can wake up earlier

Answer 119

**Retinal ganglion cells** (below photoreceptors in the retina) contain a novel photopigment, **melanopsin**, which is the circadian photoreceptor Melanopsin measures only light and dark (NOT image-forming; is a new sensory system!) and sensitive to blue/green wavelength light, and even blind people have functioning circadian rhythm! Melanopsin is a vitamin A-based opsin photopigment Melanopsin expressing ganglion cells **target the SCN** and give the SCN light/dark information

Answer 120

Photoreceptors usually shut off activity when light shines on them **RGCs depolarize** and generate APs when stimulated by **light**

Answer 121

In the **suprachiasmatic nucleus (SCN)**

Answer 122

Individual neurons generate autonomous rhythm (**active** during **day** and **silent** at **night**) Oscillations in SCN circuit more robust than single neurons thought (larger amplitude rhythm that is more precise)

Answer 123

Don't know much about this SCN targets **SON**, **PVN**, **ARC** which target **anterior** and **posterior pituitary** However, most **behavioral** and **physiological** **parameters** exhibit circadian oscillations: melatonin, core temperature, cortisol

Answer 124

**Melanopsin**-containing **RGCs** directly synapse onto **clock cells in SCN** then go out through **spinal cord** then **superior cervical ganglion** then **sympathetic** innervation of **pineal gland** regulates rate limiting enzyme **NAT** which takes 5HT to produce **melatonin**

Answer 125

Yes, they're **everywhere**! **Lung, liver, fibroblasts, etc** **Different** genes in different tissues are rhythmically regulated though

Answer 126

**RGCs** sense light via **melanopsin** --\> projections to central **clock/SCN** --\> **HPA** and **ANS** --\> separate clocks in each different organ system control genes important in each organ

Answer 127

You get **oxidative** **stress** and **inflammation** This is because **NF-kB pathway** is regulated by circadian timing system

Answer 128

**No purposeful response** to environment **No conscious arousal** **No speech** **No purposeful movements**

Answer 129

**EEG** **Muscle tone** **Eye movements** **HR** (and variability) **RR** (and variability) **Hormonal release** **Body temp** **Visceral motility**

Answer 130

EEG = **brain** electrical activity EOG = **eye** movements EMG = **muscle** tension

Answer 131

Duration of **REM** **increases** across a night and **quiet sleep** duration **decreases** **Fewer large slow waves** during quiet sleep across the night

Answer 132

**Core temperature** is **low during** sleep **Cortisol** is **low at midnight** and increases a few hours before waking up

Answer 133

Increased **eye** **movement** **Muscle atonia** **Autonomic** **storm** (erection, transient hyper and hypotension, substantial HR changes)

Answer 134

Infants have **compliant chest walls** because ribs not calcified and its muscle tension that provides thoracic wall rigidity During REM sleep, no muscle tension so **thoracic walls become "floppy"** and can be **sucked in** by negative pressure from descending diaphragm Infants have dangerously **low residual oxygen** reserves in REM sleep (chest sucked in instead of air!)

Answer 135

**Collapsed upper airway** but continued **diaphragmatic efforts** **Short term memory, spatial orientation deficits, elevated sympathetic levels** (even during waking) thus elevated BP Injury in **hypothalamus**, **cerebellum** (CV and breathing coordination, cognition), **medial midbrain**, **cingulate cortex** (depression, anxiety), **hippocampus** and **mammillary body** (memory), **insula cortex** (CV, pain, depression, anxiety) **Obese** **males** higher risk, high sensitivity to alcohol intake, upper airway malformations (**micrognathia**) or functional increased resistance (chronic **upper airway inflammation**), neural injury/cereballar injury/**stroke** higher risk

Answer 136

Abnormal pattern of breathing where you get progressively deeper/faster breaths then decreased and **temporary** **stop** in breathing (apnea) and pattern repeats every **30 sec to 2 min** A coordination issue: matching peripheral CO2 sensing with central chemoreception Found in half of **heart failure patients** and sometimes accompanies OSA Heart failure patients also show substantial **brain** **injury**, possibly resulting from **hypoxic damage** during apneic periods of Cheyne-Stokes breathing in sleep

Answer 137

3-fold risk for **hypertension**, even with moderate OSA High incidence of **stroke** Increased incidence of **atrial fibrillation**

Answer 138

Can't consider diabetes without considering the potential for OSA! **Interrupt sleep** with 2 hours of waking and get **elevated glucose by 50 mg/dl** **86%** of **obese** **T2DM** have moderate-to-severe **OSA** and remainder have mild OSA

Answer 139

**Fetus** has periods of **activity and rest**--should not be considered quiet sleep **Neonates** spend more time in **REM** (and more time asleep) **Adolescents** spend more time in **QS** and are **difficult to arouse** **Elderly** sleep **less** (and sleep is less continuous)

Answer 140

**Cholinergic** **Serotonergic** (raphe) **Adrenergic** (Locus coeruleus) **Histaminergic** (TM nucleus) **Orexin** (hypocretin)

Answer 141

Promote **arousal** Lost in nacrolepsy Located in hypothalamus Interact with other systems

Answer 142

**QS** in **basal forebrain** **REM** in **dorsolateral pons**

Answer 143

**Excessive daytime sleepiness** **Sleep attacks** at inappropriate times: can be triggered by **affective** **stimuli** (laughter, excitement) **Cataplexy**: sudden and transient episode of **loss of muscle tone**; distinct from sleepiness, unique to narcolepsy **Sleep paralysis** (similar, but occurs in normals) Hypnagogic hallucinations **REM sleep at sleep onset** (short REM latency) **Disrupted nighttime sleep** Orexin (hypocretin) involved (**loss of hypocretin cells**)

Answer 144

**Depression** **Inappropriate sleep habits** **Nocturnal myoclonus** **Circadian shift** **Other issues...**

Answer 145

**Tracheostomy** **Mandibular advancement devices** **Surgical advancement**, removal of excess tissue **Hypoglassal stimulation** Nasal continuous positive airway pressure (**CPAP**)

Answer 146

Release of **pro-inflammatory cytokine** interferon (**IFN-gamma)** as well as cytokine **TNF-alpha** as part of body's response to infection

Answer 147

Expose yourself to **sunlight** in the **morning** (but not before 5am) **Avoid blue/green** light during the **night**

Answer 148

Chronic jet lag could **reduce hippocampal volume**, cause **high cortisol**, performance deficits Jet lag increases mortality in mice

Answer 149

Difficulty with **quality** and **duration of sleep** Shift to **earlier** bedtime and wake up Fragmentation Difficulty with **daytime alertness** Difficulty with shifting to **changes** in LD cycle

Answer 150

**Cognitive** dysfunction including **memory** problems Trigger **affective disorders** **Metabolic** dysfunctions including increased risk of T2DM **CV** disease **GI** disturbances Increased risk for certain **cancers**

Answer 151

Form the largest endocrine organ even though they make up less than 1% of the total **GI epithlial cells** EE cells contain **20** different **hormones**/signaling molecules EE cells **sense** nutrients, bile salts, short chain fatty acids, bitter and sweet tastants, bacterial products and quorum sensing molecules

Answer 152

Nutrient related chemical and physical info **encoded** in the **gut** **Afferent** info transmitted to **CNS** via **vagal**, **spinal** and **endocrine** pathways Info integrated in **hypothalamus** Integration of various food related into in brain and generation of sensations of **hunger** and **satiingestive** behavior

Answer 153

95% in the **gut**! Sequestered in **neurons**, **enterochromaffin** cells, enteric **mast** **cells**, **platelets**

Answer 154

Gut related interoceptive signals inform CNS about **homeostatic** (satiety) and **non-homeostatic** (inflammation, mucosal irritation, lack of nutrients) events = **"gut sensations"** if require a **response** of the organism Activation of brain circuits created by these things can occur on just thought/**remembering** of particular situation --\> create **disgust** or **craving**, even in absence of actual gut signal

Answer 155

Only one study showed gut **microbes** affecting **brain** **circuits** in humans **Stress** induces changes in microbial environment: **Direct**: **NE** signaling to the gut can influence behavior of intestinal pathogens to **increase** their **virulence**; other stress-induced signaling molecules **released** into gut lumen (5HT, dynorphin, beta endorphin, etc) **Indirect**: **gastric** **acid** production, GI **motility**, intestinal **fluid** and **mucus** secretion, intraintestinal **pH**

Answer 156

**ANS, SNS, HPA axis** influence behavior of **macrophages, DCs, mast cells** Macrophage secretory products (**cytokines**) activate **vagus** to affect **brain**

Answer 157

**HPA axis** response **Anxiety**-like behavior **Neuroplastic** changes in emotion regulation regions (BDNF, PSD-95, synaptophysin, NR2B subunit, 5HT1A) Lack of inflammation induced somatic hyperalgesia

Answer 158

**Ecology of intestinal flora early in life** may play important role in shaping **stress response** **Compromised** intestinal microbiota = **decreased** **diversity, neonatal antibiotics, infections**

Answer 159

So far, **no**! Humans that ate probiotics did not have different response to viewing faces with negative affect (anger, fear)

Answer 160

**Interoceptive** **signals** related to the chemical, mechanical, and immune related context of our **inner** **environment** are encoded by different **cell types in the gut**. Gut **microbiota** in the intestinal lumen are likely to contribute to this information. Encoded info reaches **CNS** via **vagal** and **spinal** **afferent** **pathways**. CNS, including spinal cord and brain responds to this input in various **reflex** **pathways** to **adjust the body** in an optimal way. **Brain** responds to these interoceptive inputs via the **HPA** **axis** and the **ANS**, which in turn modulate the **activity** and **sensitivity** of the **target cells in the gut.** **Chronic** **overstimulation** of this gut brain axis by **intestinal** **factors** (e.g. chronic inflammation), or by **CNS** **factors** (chronic stress) can result in **neuroplastic** changes at multiple levels, changing the gain and responsiveness of the entire system. Future studies should explore if activity within the gut brain axis plays a role in **cognitive function, mood** and **affect** (currently no evidence for this in humans)

Answer 161

GI: functional **GI** disorders, cyclical **vomiting** syndrome, **IBD**, **celiac**, **obesity**, **metabolic** **syndrome** Non-GI (microbiota): **autism, anxiety, depression, coronary vascular disease**