Emotional Regulation and Dysregulation Experiments Flashcards
(55 cards)
What are the main experiments on Amygdala role in anxiety?
- Killcross et al 1997: Distinction between the role of BLA (goaldirection) and CeN (output)
- Mobbs et al 2010: Amygdala role in threat tracking (particularly right amyg.)
- Adolphs: amygdala damage in humans (HSV) causes reduced fear and no autonomic response to conditioned threat.
- Distinction between role of amygdala (CeN blocks short term response; BNST sustained response)
- BLA activates adBNST to induce anxiety (Kim et al 2013)
What were the key findings of Killcross experiments 1997?
Distinction between the BLA and CeN role:
* Set-up: rats trained to press two level for reward. One lever is coupled with a tone which proceeds a shock (CS+).
* Control rats bias response away frm CS+ lever
Results:
* CeN lesioned rats do not suppress pressing of CS+ lever as much as control (but still lower than CS-) (BLA had no effect on reducing supression of CS+ pressing).
* BLA lesioned rats show reduction in lever pressing to both but reduced ability to bias behaviour away from CS+ (avoidance rather than goal directed behaviour).
Probems:
* Used neurotoxic lesions (not very localised; may have off-target effects
* Not a complete change in behaviour seen (is this because full abolition did not occur or other structures are involved? e.g. mPFC)
What did Mobbs et al (2010) experiments show?
Set-up: participants view a tarantula being placed at different distances from their feet while in an fMRI scanner. This is an unavoidable threat changing in proximity (fear → anxiety)
Results:
* Amygdala activity increased with proximity
* PAG, BNST and striatum also increased
* Right amygdala particularly active when threat approaching (role in tracking?)
* mPFC activity increased with habituation
Comments:
* No distinction made between BLA and CeN (which are known to have different roles)
* Habituation occured over the experiment which was accounted for in a standardised way (not allowing for individual variation)
What is the effect of HSV encephalitis?
Adolphs 1998: patients with HSV encephalitis show localised amygdala damage.
- Causes reduced fear (to threat); inability to recognise fearful faces in others and lack of anthropomorphising.
- No autonomic response is learned to a CS+ (shock)., though concious recall of CS proceeding shock is present.
What is the role of Interoceptive feedback in fear/anxiety?
Set up: participants asked to say whether beat of music matches their heart beat.
Results: feedback feeds into anxiety circuits (amyg.) via Vagus and spinal cord
* Participants who were more successful show lower anxiety scores.
* Success correlated with right insula activity
* Severence of Vagus nerve or spinal cord reduces insula response and success
Which experiments show the distinction between fear and anxiety?
- Presenting stimulus for short or long time (showed difference in role between BLA, CeN and BNST)
- Mobbs et al tarantula experiment
Describe an experiment investigating the brain regions (bottom-up) involved in fear vs. anxiety responses:
Set-up: tone associated with shock (CS+) after ending. Tone played for short time (e.g. 2 secs) or long (>1min). Response measured by magnitude of startle reflex.
Results:
* Inactivation (using glutamate agnoist) of BLA blocked startle in short and long term
* Inactivation of CeN blocked short term but not long term
* Inactivation of BNST blocked long term but not short term. Also increased the short startle response magnitude (suggesting a role in CeN regulation usually).
* Provides evidence against idea that BNST is not involved in conditioned fear response
What are the main experiments on the role of PFC in emotional regulation?
Involved in many different types of regulation:
* Damasio et al: vmPFC lesioned patients show deficits in IOWA gambling task and inspire somatic marker hypothesis
* Ochsner et al 2004: Different PFC areas required for different forms of cognitive re-appraisal
* Delango et al 2008: attentional refocus is an effective form of emotional suppression
* Wallis et al 2017: vmPFC role in extincion behaviour
* Alexander et al 2020: vmPFC plays a causal role in anxiety in marmosets.
* Amat et al 2008: vmPFC activation provides stress resistance for an uncontrollable stressor
What is the somatic marker hypothesis?
Proposed by Damasio: Emotional processes bias decision making in complex/uncertain situations.
Significant critiques:
* No causal evidence (hard to investigate)
What is the evidence gained from vmPFC lesioned patients? What are the problems?
Damasio 1996 investigated vmPFC lesioned patients:
* vmPFC patients continue to choose disadvantageous decks (despite having normal IQ and WM
* Suggests they cannot integrate information across many trials
* Show no change in GSR to emotionally meaningful pictures
However:
* IOWA gambling task requires several executive functions including memory and 3/5 amygdala damaged patients also had hippocampal damage…
* Results have not been replicated
Give correlational evidence that different frontal lobe areas are required for different forms of cognitive re-appraisal
Ochsner et al 2004
Setup: fMRI used to measure regional PFC activation while participants asked to imagine scenario getting worse better as form of cognitive re-appraisal.
Results:
* Consciously imagining situation getting worse (‘increasing’) increases pCC
* Consciously imagining situation improving (‘decreasing’) increases OFC activation
* Decreasing down-modulates amydala activity (particularly left)
Cognitive re-appraisal is a valid form of emotional regulation
Evidence that attentional refocus is an effective form of emotional regulation:
Delango et al 2008
Set up: (human) participants learned to associated two coloured squares (Pavlovian) with shock (CS+) or no shock. Told to either attend to stimulus or focus on something else.
Results:
* Attentional refocus is a successful way of suppressing autonomic response to threat
* dlPFC activation correlated with vmPFC activation and left amygdala actiivty decrease leading to success of suppression (GSR)
* Right amygdala changes more during extinction, left during emotional suppression.
Suggests attentional refocus may stimulate dlPFC to up-regulate vmPFC which suppresses fear.
Evidence for the role of vmPFC in extinction behaviour in rodents. How does this differ from NHPs?
Wallis et al 2017
Set-up: sound associated with punishment (shock) which induces freezing (innate behavioural fear response). Number of trials required to reach extinction measured.
Results:
* Increased PL activity increases time till extinction (stimulates fear)
* Increased IL activity decreases time until extinction (suppresses fear)
* Suggests similar role to vmPFC in humans
* Both cause changes to BP
BUT
* Shows IL and PL opposite in function though considered anatomically similar.
* A25 and A32 also not opposite for BP control (A32 overactivation has no effect but A25 inactivation dereases Bp and HR) - suggests dissociation between autonomic and behavioural response.
Also look at Delango study.
Evidence for the role of vmPFC in anxiety and stress:
Alexander et al 2020
Set-up: Rubber snake used as proximal but uncertain threat (anxiety) paired to tone. Excitation of A25 using microinfucion of DHK = glutamate re-uptake inhibitor).
Results:
* A25 overactivation increases anxiety (increased vigialant scanning)
* Overactivation of A25 blocks extinction of fear but does not effect cortisol levels (does not increase stress levels
* Increases cardiovascular arousal
* PET scan shows A25 overactivation increases amygdala activation, decreases OFC and dlPFC activtation (mutual inhibition?).
Why is it important to consider the degree of escapability (controlability) of a stressor?
Degree of peceived contorl over a stressor changes response.
Amat et al 2008 - exposure to an escapable stressor provides resistance to a later inescapable stressor through activation of vmPFC (sufficient and necessary)
Set-up:
* Exposure to an IS (FST) leads to overactivation of DRN, increased fear, difficulty learning.
* Exposure to an ES (e.g. tail shock) does not show this profile.
* Exposure to ES provides protection against future IS so that effects are not seen (=’immunisation’)
* Previous work shows vmPFC is necessary for this immunisation (i.e. inactivation of vmPFC during ES means IS shows normal response)
Results:
* Activating vmPFC mimics the effect of a previous ES so that response to IS is suppressed despite no previous ES exposure.
* This is mediated through vmPFC inhibition of 5-HT release (quantity and transience) in DRN
Describe investigations into brain regions involved in response to inescapable stressors
- Amat et al 2008 (see card) - vmPFC is necessary and sufficient for resistance to anxiety response in IS (via 5-HT suppression in DRN)
- Izquierdo et al 2006 - uncontrollable stressors induce morphological changes in IL and PL. Suggests impact of environmental conditions.
Give some evidence that environmental conditions change brain structure in IL/PL of mice.
Izquierdo et al 2006
* 3 FSTs a day used as uncontrollable stressors. Dendritic branching used as measure of morphological change.
Results:
* Exposure to brief stressor causes dendritic retraction in apical IL but not PL
* Reduces ability to extinguish fear
* Suggests IL neurons highly sensitive to uncontrollable stress and produces extinction resistance.
What are the main roles of OFC and which experiments determined these?
- OFC in cognitive re-appraisal (Oschner et al)
- Distal threat processing (Mobbs)
- Response to distal and proximal threat (Stawica et al): aOFC increases behavioural arousal but decreases cardiovascular arousal (BP) to a proxial threat (fear)
- Role in updating reward status in marmosets
- Conetext dependent decision making
How do the Amygdala and BNST interact (Give experiments)
Kim et al 2013
* Used optogenetics to determine BLA stimulates adBNST activity which is output for anxiety behaviour
Provide evidence that the OFC has a role in suppression of fear to a distal threat.
Stawica et al 2021
Set-up: inactivation of aOFC or pOFC (using muscimol) effect on response distal (HIT) or proximal (conditioned response) threat.
Results: aOFC has role in suppressing fear response to uncertain/distal threat (anxiety) but can upregulate response to proximal threats
* aOFC inactivation reduce anticipatory beavioural and cardiovascular arousal (BP) for a proximal threat (pOFC no effect)
* aOFC inactivation increased reseponsivity to a distal threat
Points to consider:
* Distinciton between proxial and distal threat
* Distinction between anticipation and response
* Heterogeneity of OFC
How can sadness (a major component of depression) be fractionated?
Negative biased bottom up emotional perception:
* Anticipatory anhedonia (reduced ‘wanting’)
* Consummatory anhedonia
Negative top down expectation:
* Increased sensitivity to -ve stimuli (including feedback)
Deficient top down control:
* Decisional anhedonia (deficits in learning/decision making)
Detail experiment showing increased response to -ve stimuli as a component of sadness
- Elliot et al 1996: MDD patients show reduced ability in probabilistic reversal learning task - huge increase in failure if task directly before gave -ve feedback (become worse over time
What evidence is there that A25/IL is implicated in sadness?
- Transient activation of A25 induces sadness
- Behavioural effect of DA depletion (using AMPT) correlates strongly with the decrease in DA metabolism in vmPFC
- Transient inactivation of IL reduces depression like symptoms in rodents
Detail evidence that DA is involved in reward processing.
Role in motivation:
* DA depletion reduces motivation : rodent eats easy to access poor food rather than pressing lever (work) for better reward.
* Loss of motivation seen in Parkinson’s disease (DA depletion)
* Chemically selective lesioning (6-OHDA) to kill DA synthesising cells shows intact liking but deficient motivation (measured using facial expression changes across species…)
* DA injection can induce mania states
