Negative emotion

Question 1

Cognitive Appraisal Theory

Answer 1

Schacter and Singer, 1962 - the adrenaline and stooges experiment. A stimulus/event causes arousal (which determines intensity of emotion) and cognitive appraisal of that event (which determines quality of emotion)

Question 2

Emotions vs sensations

Answer 2

E.g. hunger is not an emotion, it is a physical sensation that does not require cognitive appraisal.
However, it can cause emotions - being hungry with no likelihood of getting food soon can cause anxiety, anger.

Question 3

Kluver-Bucy syndrome

Answer 3

Temporal lobe damage

Causes tameness, hypersexuality, inappropriate eating (e.g. copraphagia), visual agnosia

Question 4

Fear - what is it?

Answer 4

Anticipation of a negative stimulus elicits a ‘central fear state’, with similar signs for animals as for humans (increased heart rate, respiration changes, increased startle, frequent urination)

Question 5

Fear - neural pathways, evidence for amygdala involvement (7)

Answer 5

LeDoux lesioned auditory midbrain (effect on fear conditioning to auditory tone), auditory thalamus (effect), and auditory cortex (no effect).
Killcross et al 1997 - In rats, BLN lesions prevent conditioned punishment (but not general reduction in lever pressing), CeN lesions prevent conditioned suppression (but not specific avoidance of the lever paired with punisher)
Angrilli et al 1996 - a patient with extensive but specific right amygdala damage can decreased startle response, that failed to be potentiated by an presentation of aversive pictures (to produce an emotive background).
Bechara et al 1995 - Urbachs-Wiethe disease meant subject understood that CS predicted US, but didn’t show the autonomic SCR. Bilateral hippocampus damage gave the opposite pattern.
Other amygdala-damaged patients have shown no improvement of recall for emotional sections of films, despite both controls and amnesics showing this.
Adolphs, 1994, 1998 - Amygdala damaged patients impaired at recognising fear, and more likely to deem someone trustworthy
Herberlein and Adolphs 2004 - amygdala damaged subjects do not anthropomorphise when describing a line and shape animation

Question 6

Amygdala - inputs to BLN

Answer 6

Sensory thalamus and cortex, polymodal association areas, hippocampal and entorhinal cortex, PFC

Question 7

Amygdala - inputs to CeN

Answer 7

Viscero-sensory cortex, sensory brainstem, PFC

Question 8

Amygdala - outputs from BLN

Answer 8

Ventral striatum, polymodal association cortex, PFC, CeN via ITC

Question 9

Amygdala - outputs from CeN

Answer 9

Modulatory systems (NA, 5HT, DA, ACh), hypothalamus (sympathetic activation), dorsal motor nucleus of the vagus (parasympathetic activation), periaqueductal grey (freezing)

Question 10

Fear vs anxiety (1)

Answer 10

Fear - a response to the certain expectation or occurrence of an aversive event, e.g conditioned freezing
Anxiety - a response to the uncertainty in expectation of an aversive event, e.g. light-enhanced startle
Davis and Shi, 2006 - fear-potentiated startle (using a pavlovian-conditioned light) was blocked by glutamate antagonist in the CeN or BLN. Light-enhanced startle was blocked by glutamate antagonist in the BNST or BLN.

Question 11

Emotional regulation - what is it?

Answer 11

The process by which an emotional response is generated in accordance with the type of stimuli presented, the context it is presented in, and internal state.
Adaptable - to maintained environments/stimuli attributes
Flexible - to changes in environments/stimuli attributes

Question 12

Methods of emotional regulation

Answer 12

Adaptation to environment
Response suppression
Attentional refocus
Cognitive re-appraisal

Question 13

Adaptation to environment

Answer 13

Basically, extinction
This is not ‘forgetting’ the CS-US association, this is replacing is with a CS-no US association.
VMPFC lesions block recall of extinction - i.e. extinction itself is same as control, but then the next day they need extinguishing again!
Infralimbic cortex bursting predicts recall of extinction on day2, activity in prelimbic cortex predicts failed recall of extinction on day2

Question 14

Prefrontal cortex control of fear - model plus rat evidence (5)

Answer 14

Infralimbic cortex stimulates intercalated cell mass, which inhibits CeN and prevents entry into central fear state
Prelimbic cortex stimulates BLN, which stimulates CeN and promotes entry into central fear state
Prelimbic neurons show sustained activity to conditioned stimuli, whereas amygdala neurons show transient activity
Prelimbic activity fits timescale of freezing
Prelimbic activity to a CS is reduced after BLN lesion
VMPFC lesions block recall of extinction - i.e. extinction itself is same as control, but then the next day they need extinguishing again!
Infralimbic cortex bursting predicts recall of extinction on day2, activity in prelimbic cortex predicts failed recall of extinction on day2

Question 15

Prefrontal cortex control of fear - human evidence (1)

Answer 15

In humans, dorsal anterior cingulate cortex thickness and activity is correlated with fear acquisition. Ventromedial PFC thickness and activity is correlated with fear extinction

Question 16

Fear experiments - translational difficulties

Answer 16

Prelimbic in rats may not equal dACC in humans. Cytoarchitecture and functional neuroimaging both give different answers (and opposite to each other!). Looking at connectivity may help, but is in its infancy.
We measure fear in humans using autonomic response, but we measure in rats using freezing. Hence marmosets (with implanted sensors in aorta) are closer.

Question 17

Prefrontal cortex control of fear - monkey evidence (6)

Answer 17

Klavir et al 2012 - used low frequency stimulation to inactivate the dACC in rhesus monkeys, found no effect on extinction but better extinction recall in inactivated dACC than in controls. So dACC impairs extinction, just like prelimbic cortex.
Agustin-Pavon et al 2012 - OFC and vlPFC lesions potentiated recovery from partial extinction in marmosets (i.e. potentiated reinstatement of conditioned fear response).
OFC and vlPFC lesions increased anxiety in response to human intruder (and innate fear in response to snake?)
Shiba et al 2017 - FDG-PET scans showed rincreased fearstate-minus-safestate amygdala and insula activity in the intact hemisphere when OFC and vlPFC have been lesioned - this suggests both OFC and vlPFC converge on the amygdala
Clarke et al 2015 - vlPFC lesions cause enhanced bias away from punishment
Dias et al 1996 - lateral PFC lesions impaired ability of monkeys to switch attention away from aversive stimulus (i.e. they couldn’t learn a new rule because they were fixated on the aversive stimulus)

Question 18

Attentional refocus (1)

Answer 18

Delgado et al 2008 - told subjects to either ‘attend’ to the aversive stimulus, or ‘regulate’ by thinking of something calming. Found decreased physiological responses, decreased amygdala activity, and increased ventromedial PFC activity in the ‘regulate’ condition.

Question 19

Cognitive re-appraisal (2)

Answer 19

Oschner et al 2004 - told subjects to ‘increase’ aversivity by imagining it was them in the film, neutral, or ‘decrease’ aversivity by putting a positive spin on the film outcome. Subjective surveys showed a bidirectional effect of this cognitive alteration, and amygdala activity was reduced in the ‘decrease’ condition. PFC activity increased in both ‘increase’ and ‘decrease’, but more on ‘decrease’.
Goldin et al 2008 - ‘think objectively’ decreased amygdala activity, increased PFC activity

Question 20

Response suppression (2)

Answer 20

Gross 1999 - suppressing visible, external emotion increased the autonomic response (pulse, ventilation rate)
Goldin et al 2008 - ‘keep face still’ increased amygdala and PFC activity

Question 21

Patients with damage to VMPFC - classic symptoms

Answer 21

Phineas Gage - became sexually inappropriate, foul-mouthed
In general - behaviour disadvantageous to themselves and socially inadequate, struggle to choose appropriate friends and partners, or to think about the future over the present, plan the work day. But learning, intellect, working memory, attention are all normal.

Question 22

Somatic marker hypothesis (2)

Answer 22

Damasio 1996 - when a problem is posed, we use cognitive appraisal (weighing up pros and cons) and somatic markers (bodily, emotional responses, processed in the VMPFC and amygdala).
Hypothesised because VMPFC patients can’t make quick sensible decisions, and can’t express and experience emotions normally. Cognitive processes are laborious, so we often rely on emotion to guide decision-making
Failed to generate raised SCR to aversive pictures
Bechara et al 1997 - Iowa gambling task - VMPFC damaged patients showed lower SCR than controls when they realised the game was rigged, and failed to choose the advantageous hand.

Question 23

Interoception and emotion (4)

Answer 23

Theory - interoceptive info, transmitted by vagal nerve and lamina I of dorsal horn, guides emotion
Schacter and Singer 1962 - stooges etc
Critchley et al 2004 - Heartbeat awareness correlated with insula activity and volume, insula activity correlated with anxiety, heartbeat awareness correlated with anxiety
Werner et al 2009 - people with good cardiac perception performed better at the Iowa gambling task, and showed stronger emotional response to aversive films, pictures and emotion-related adjectives
Werner et al 2013 - heartbeat detection correlated with insula and somatosensory cortex activity preceding disadvantageous decisions in Iowa gambling task. In accurate interoceptors, but not inaccurate interoceptors, insula activity correlated with performance on the Iowa gambling task.
Craig - insula important for subjective feelings, self-awareness
Damasio - anterior cingulate cortex important for mapping relationship between body and emotional object

Question 24

Factors increasing risk of anxiety development

Answer 24

Low resilience
High trait anxiety
Low controllability
Stress during development and adulthood
Individual genetic differences

Question 25

Low resilience and anxiety - evidence

Answer 25

Tugade and Frederickson 2004 - Sorted people into ‘low’ and ‘high’ resilience using a survey with questions like ‘I recover quickly after being startled’. Low resilience people had longer duration of raised cardiovascular activity after being shown an aversive stimulus
Waugh et al 2008 - Cue, then aversive picture (50% of the time) or neutral picture (50%). High resilience individuals had more raised insula activity in recovery period for cue-aversive than cue-neutral. Low resilience were equal for cue-aversive as cue-neutral. SO insula activity did not recover when the threat had been removed in low resilience people.

Question 26

High trait anxiety and anxiety - evidence

Answer 26

Fox et al 2008 - In rhesus monkeys, high trait anxious individuals had increased activity in amygdala, BNST, hippocampus and periaqueductal gray. This reflected phenotypic variation in how anxiety manifested itself (altering vocal expressions, freezing, and raised cortisol). Most high AT monkeys had altered activity in hippocampus or amygdala (changes which were heritable), but only those that froze had decreased motor cortex activation, and only those that increased cortisol had increased anterior hippocampus activity
Indovina et al 2011 - used context-predicted US and cue-predicted US. High trait anxiety correlated with increased amygdala activity in cue-predicted, and reduced vPFC recruitment in context-predicted. But these two did not correlate with each other, so trait anxiety comes from one or the other mechanism.
Bishop 2008 - High trait anxiety makes people more likely to detect fear in ambiguous faces. They have normal results in fear conditioning though, perhaps because they overgeneralise the CS.
High trait anxiety is associated with decreased neurodevelopment and neuroplasticity related genes in AT-related areas
Mikheenko et al 2015 - High AT monkeys (more freeing to human intruder, model snake) had lower 5-HT in amygdala when SSRI citalopram was administered via microdialysis (i.e. when you’re really seeing cumulative spontaneously released 5-HT).
Duvarci et al 2009 - Sham lesioned rats were on a continuum of poor to good discriminators (of CS vs unrelated cue). Poor discriminators did more contextual freezing and were more anxious on elevated plus maze. BNST lesioned rats all behaved like sham lesioned rats at the good discriminator end of the spectrum. So individual variation in fear generalisation and anxiety phenotype may depend on BNST influences on the amygdala and/or other targets.
Walker et al 2003 review - BNST mediates contextual rather than CS-associated fear, and slowly developing and long-lasting responses to diffuse threats

Question 27

Controllability and stress in anxiety - evidence

Answer 27

When giving rats mildly aversive tail shocks, those that can’t escape them (i.e. the group yoked to those that could escape the shocks by running on a wheel) showed higher corticosterone, more gastric ulceration, and poorer learning and memory performance afterwards.
In rats subject to inescapable stress, more 5-HT release near the dorsal raphe nucleus is seen. (counterintuitive given SSRIs… perhaps it’s about control of release).
Amat et al 1998 - more serotonin in ventral hippocampus in inescapably stressed, more in PAG in escapably stressed, increased 5-HT response to two brief footshocks afterwards in both
Izquierdo et al 2006 - In inescapably stressed rats, there’s decreased dendritic arborisation in the infralimbic cortex, but increased arborisation in the amygdala
Hartley et al 2014 - humans that underwent inescapable stress had poorer extinction to conditioning afterwards
Baram et al 2012 - Pups that had poorer mum-pup bonding during key developmental period performed worse at Morris water maze and had reduced dendritic arbor in CA1 of hippocampus at 4 months and a year old

Question 28

BNST and anxiety

Answer 28

BNST has comparable connectivity to the CeN - both receive inputs from BLA, both project to similar areas of brainstem. Yet amygdala lesions abolish fear responses to a CS, and BNST lesions leave it intact.
There are reciprocal connections between the two, so interaction is thought to balance the important fear response to threat against longer-term disadvantageous avoidance behaviour mediated by anxiety.
Duvarci et al 2009 - Sham lesioned rats were on a continuum of poor to good discriminators (of CS vs unrelated cue). Poor discriminators did more contextual freezing and were more anxious on elevated plus maze. BNST lesioned rats all behaved like sham lesioned rats at the good discriminator end of the spectrum. So individual variation in fear generalisation and anxiety phenotype may depend on BNST influences on the amygdala and/or other targets.
Walker et al 2003 review - BNST mediates contextual rather than CS-associated fear, and slowly developing and long-lasting responses to diffuse threats