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week 12 Flashcards

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1
Q

Define Anxiety

A

An adaptive state of increased apprehension that helps an animal avoid potential danger, and it is associated with muscle tension and vigilance

An cautious or avoidant behaviours

Includes panic

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2
Q

Define Fear

A

Emotional response to real or perceived imminent threat

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3
Q

What does fear include?

A

surges of autonomic arousal necessary for fight or flight

Thoughts of immediate danger, and escape behaviours

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4
Q

What is anxiety related to?

A

Fear

It is not the same

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5
Q

What is anxiety a umbrella term for?

A

A variety of disorders

within DSM-5

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6
Q

What are the manifestations of anxiety disorder?

A

Both psychological and physical

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7
Q

What are examples of potential stressors?

A
  1. Failures
  2. Personal losses
  3. Frightening events
  4. Time precursors
  5. Insults
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8
Q

When the potential stressors are perceived as a threat, what is it subdivided into?

A
  1. Bodily effects

2. Upsetting thoughts

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9
Q

What are examples of bodily effects?

A
  1. Autonomic emergency response
  2. Shallow breathing
  3. Pounding heart
  4. Tense muscles
  5. Digestive problems
  6. Sleep disturbances
  7. Fatigue
  8. Psychosomatic illness
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10
Q

What are examples of upsetting thoughts?

A
  1. Anger
  2. Fears
  3. Preoccupations
  4. Self-doubts
  5. Negative self-talk
  6. Repeated ‘‘danger’’ thoughts
  7. Worry about body reactions and health
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11
Q

What does bodily effects and upsetting thoughts lead to?

A

Ineffective behaviour

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12
Q

What is an example of ineffective behaviour?

A
  1. Escape
  2. Avoidance
  3. Indecision
  4. Aggression
  5. Inflexible responses
  6. Poor judgement
  7. Inefficiency
  8. Drug use
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13
Q

What is ineffective behaviour’?

A

Behaviour you engage that has no actual purpose or produce no result

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14
Q

What is fear processing?

A
  1. Thalamus projects to amygdala
  2. Indirectly via the cortex (long pathway)
  3. Directly (short route)
  4. Amygdala connects hypothalamus: bodily manifestations of feat
  5. Output: run/freeze
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15
Q

Where is sensory stimulation interpreted in?

A

sensory thalamus

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16
Q

When do we respond very quickly to a stimulus?

A

When the stimulus evokes fear and bypasses the cortex

Engage in fear without thinking, simply start feeling very agitated

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17
Q

what are the main circuits involved in fear conditioning?

A
  1. sensory areas - process the conditioned and unconditioned stimuli
  2. certain regions of the amygdala that undergo plasticity
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18
Q

Where does fear reponse start in the brain?

A

Amygdala

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19
Q

What is amygdala dedicated to detecting?

A

Emotional salience of the stimuli

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20
Q

What does amygdala activate?

A

Areas involved in preparation for motor function involved in fight or flight

Triggers the release of stress hormone and sympathetic nervous system

leads to bodily changes that prepare us to be more efficient in a danger

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21
Q

What brain regions is closely connected to amygdala and what are their roles?

A
  1. Hippocampus
  2. Prefrontal cortex

Help brain interpret the perceived threat

Involved in higher processing of context

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22
Q

Where does the conditioned stimulus flow from?

A

The lateral amygdala to the central nucleus of the amygdala

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23
Q

What controls defensive behaviour i.e. freezing?

A

Pathways from central nucleus of amygdala to downstream areas

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24
Q

what does the hypothalamus ochestrate?

A
  1. Freezing or fleeing response and all the physical manifestation
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25
where is amygdala located in?
Medial temporal lobe | composed of number of different nuclei
26
What is lateral nucleus?
primary nucleus input of the amygdala It receives input from the thalamus and the cortex which provide it with information of the sensory stimuli the animal is experiencing
27
What is the primary output nuclei of the amygdala?
Central medial nucleus | Projects to a number of different structures
28
Where does the central medial nucleus project to?
1. Paraventricular nucleus of the hypothalamus and triggers release of stress hormone cortisol 2. Lateral hypothalamus - stimulating the autonomic nervous system 3. Periaqueductal grey matter - which in mice causes fear behaviours such as freezing
29
What happens when the downstream targets are coordinated?
The amygdala is able to produce many of the physiological changes associated with feeling of fear: 1. Increased heart rate 2. Sweating 3. Dilation of the pupils
30
What is fear conditioning?
When an animal learns to fear something
31
What happens in a typical fear conditioning experiment?
1. A mouse is given an unconditioned stimulus which is inherently negative such as a painful foot shock 2. causes a natural unconditioned response - the expression of fear 3. Also uses a neutral stimulus e.g. a sound which on its own produces no fear 4. When the neutral and unconditioned stimuli are presented , the animal learns the association between the sound and the shock 5. A neutral stimulus of the sound is then able to cause the fear behaviour itself without the shock
32
What is related to fear conditioning?
The concept of fear extinction
33
When does extinction occur?
When the conditioned stimulus of the tone is presented repeatedly without the unconditioned stimulus of the foot shock The animal gradually learns that the sound no longer predicts a shock The association is broken and the fear behaviour is no longer displayed
34
What is amygdala thought to be?
Primary area of the brain responsible for fear conditioning
35
How does amygdala participate in fear conditioning?
* The unconditioned stimulus of the foot shock travels to the spinal cord to the thalamus and cortex * Which both project to the lateral nucleus of the amygdala * The synaptic input from the unconditioned stimulus of the shock is strong enough to excite lateral amygdala neurons * Activation of neurons in the central medial nucleus and produces a fear response
36
What happens when the neuron encoding the shock and the neuron encoding the sound fire together?
Synaptic plasticity occurs This strengthens the synapse between the incoming neuron carrying information about the neutral stimulus of the sound and the lateral amygdala neurons
37
What does the lateral amygdala neuron do?
Excite central medial nucleus and produces feeling and fear
38
What are the neuroanatomical regions involved in anxiety disorders?
1. Amygdala: the central fear centre 2. Locus Coeruleus: Norepinphrine secretion - stimulated by active HPA axis 3. Septohippocampal GABAERGIC system
39
Amygdala: The central fear centre
1. Crucial for fear conditioning | 2. Lesion in humans demonstrated pivotal for storage and processing of emotional memories
40
Locus coeruleus: Norephinephrine secretion
LC stimulation generates panic attack LC blockade decreases panic attacks
41
Septohippocampal GABAERGIC system
1. Mediate anxiety and vigilance 2. High concentration of GABAergic neurons and receptors 3. Directly connected to LC
42
What does the stimulation of the stress response engage?
Locus Coeruleus Generating excessive response to a fear stimulus
43
Within a non-clinical population, where will there be differences in?
presentation of certain phenotypes
44
Who tends to have a larger amygdala?
Healthy children and adults with higher anxiety levels
45
What exhibits anxiety-related changes across the human adult lifespan?
Intrinsic functional connectivity between amygdala and multiple cortical networks
46
What is high-level trait anxiety predicted by?
Low-level global amygdala connectivity
47
What demonstrated anxiety-related changes of connectivity with left amygdala?
Somatomotor and dorsal attention networks
48
What had changes of connectivity with the right amygdala?
Frontoparietal control and ventral attention networks
49
What contributes to individual differences in anxiety behaviours?
Both low-level sensory networks and high-level associative network
50
What varies with individual's level of anxiety?
Amygdala response to threat-related stimuli located outside the current focus of spatial attention
51
What leads to differential activation of amygdala?
stimuli with different objective levels of threat
52
What is consistent with the most previous fMRI studies of conscious perception of threatening stimuli?
consciously processed fearful faces selectively activate the dorsal but not the basolateral amygdala.
53
Where is the activation of amygdala altered in?
Abnormal anxiety
54
What is the consequence of people with anxiety?
The amygdala will be much more rapidly reactive to fearful stimuli
55
What is associated with lifespan anxiety?
The number of synaptic connection of amygdala with neurons in the cortex
56
When is it more likely that an individual will experience anxiety?
The more connection that exist between amygdala neurons and cortical neurons
57
What showed a positive correlation between ipsilateral amygdala iFC and anxiety?
An area adjacent to left lateral occipital, parietal, and superior temporal cortex
58
Who had stronger iFC of the left amygdala correlated with higher level of trait anxiety
The right posterior central area Whereas an inverse correlational profile existed for the left dorsal lateral prefrontal cortex
59
What are the neurotransmitter thereoies of anxiety?
1. Norepinephrine 2. Serotonin 3. GABA
60
What is norepinephrine?
Excess leads to excessive activation of cortex NE reuptake inhibitors such as tricyclic antidepressant that block NE are effective anti-anxiety treatments
61
What is NRI associated with?
down-regulation of beta adrenergic receptors
62
What are beta adrenergic agonist and antagonist?
Agonist - Anxiogenic Antagonist - Anxiolytic
63
What does stress paradigms generate?
Hypersecretion of NE
64
What is serotonin role?
1. Complex | 2. 5-HT can be anxiolytic and anxiogenic
65
For serotonin, what is effective anti-anxiety treatment across disorders?
SSRI
66
What are effective in some anxiety disorders?
Serotonin tricyclic antidepressant
67
What does Benzodiazepine (BZ) bind to?
GABA-A receptor enhance GABA activity potent anxiolytic
68
What does other GABA-receptor modulators (alcohol) have?
Anxiolytic effects
69
What is observed in brains of anxious disorders?
Reduction of BZ receptor
70
What enhanced anxious behaviours?
GABA-A/BZ receptor
71
What does benzodiazepine act as?
GABA-A allosteric modulator
72
What does BZ potentiate when it binds to its site?
Inhibitory action of GABA and produce: 1. Sedation 2. Sleep 3. Anxiolysis 4. Anticonvulsant activity
73
How is anxiety treated?
Anxiolytics
74
What are the drugs used to treat various anxiety disorder?
1. Benzodiazepine 2. Tricylic antidepressant 3. Monoamine oxidase inhibitors 4. Selective serotonin reuptake inhibitors 5. Buspirone
75
What are examples of benzodiazepine, what disorders?
1. Valium 2. Xanax 1. GAD 2. PTSD 3. Panic disorder
76
What are examples of tricyclic antidepressant?
1. Tofranil 2. Aventil 1. Panic disorder 2. GAD 3. OCD 4. PTSD
77
What are examples of monoamine oxidase inhibitors?
1. Nardil 2. Parnate 1. Social phobia 2. Panic disorder
78
What are examples of SSRI?
1. Prozac 2. Zoloft 3. Paxil 1. Social phobia 2. Panic disorder 3. OCD 4. PTSD
79
What are examples of Buspirone
1. BuSpar 1. GAD 2. Panic disorder 3. OCD
80
What does anxiety disorders have?
Heterogenous origin
81
Where did most of the abundant research on PTSD actually come from?
Vietnam veterans | 30% of veterans that came back from war experienced PTSD
82
What does PTSD have?
one of the highest incidence of suicide among all of the mental illness
83
What is PTSD?
A form of anxiety occurring after exposure to a traumatic event
84
What are examples of traumatic events?
1. War 2. Natural disaster 3. Terrorist attacks 4. Physical assault 5. Rape 6. Child abise 7. Car accidents
85
What is PTSD characterised by?
1. Increased physiological reactivity to reminders of trauma 2. Sleep disturbances/nightmares 3. Flashback to the traumatic event 4. Avoidance of cues associated with trauma 5. Numbing of emotional responses/detachment
86
What does imaging studies show?
High levels of responsiveness of amygdala to trauma cues 2. Less activity in anterior cingulate and medial prefrontal cortices
87
What does PTSD cause?
1. Dysregulation of HPA axis 2. Low cortisol 3. High CRH 4. High catecholamine
88
What are the current pharmacological approaches for PTSD therapy?
1. Use of benzodiazepine | 2. Beta-adrenoceptor blockers
89
What does behavioural therapy include (PTSD)?
1. Exposure based therapy in which an individual is exposed to a reimagining of the original trauma/ a cue associated with the original trauma in the absence of an aversive outcome
90
What is the therapeutic benefit in targeting epigenetic mechanism for PTSD therapy?
1. Infralimbic medial prefrontal cortex to improve strength and persistence of extinction
91
What is a region linked specifically with memory extinction?
Infralimbic medial prefrontal cortex
92
What does histone acetyltransferase add?
Acetyl groups of histones, generally associated with relaxing wound DNA
93
What does HDAC do?
Remove these acetyl groups
94
What histone methyltransferase (HMT) do?
Add methyl groups to histone, generally associated with tightening wound DNA
95
What does HDM do?
Remove those methyl groups
96
What does DNA methyltransferase (DNMT) do?
Add methyl groups to DNA, sometimes associated with DNA silencing
97
How does the animal learn to stop responding feafully to stimulus via sounds?
Accumulation of new memories
98
What can help PTSD sounds?
Extinction which is new learning
99
What can accelerates the process of new learning or extinction?
1. Ketamine | 2. Hallucinogenic
100
What requires de novo transcription?
Consolidation of emotional memories
101
What is required to convert transient short term memory into persistent long-term fear memory (CREB activation)?
New gene transcription in the amygdala
102
What does memory consolidation also require?
Epigenetic changes (acetylation)
103
What promotes memory consolidation?
Enhancing acetylation
104
What are the consequence of PTSD?
1. Lack of extinction of fear memories 2. Reduced size amygdala in PTSD sufferers 3. Hippocampus size predicts PTSD risk
105
What are the physiological reactions to PTSD?
1. Flashbacks - reliving trauma 2. Racing heart or sweating 3. Bad dreams 4. Having difficulty sleeping 5. Frightening thoughts 6. Feeling tense 7. Having angry outburst
106
What does virtual reality run on ?
Commodity-level personal computers and provide interactive, immersive experiences and scenarios that open many doors for psychological research and behavioural health applications
107
What can VR provide?
a way to immerse users in stimulations of the traumatic experience the clinician can precisely control the scene's emotional intensity and customize the pace and relevance of the exposure for the individual patient
108
What is the main role of virtual reality?
Re-learning to ''extinguish'' emotional memory as therapeutic strategy to treat PTSD
109
What mediates the formation of new memories?
The use of histone de-acetylase inhibitors (HDAC) such as: 1. Valproic acid 2. Lithium

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