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FEB 20 Flashcards

1
Q

paper: “fear learning modulates large-scale…”

A

“fear learning modulates large-scale BRAIN CONNECTIVITY”

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2
Q

extinction is disrupted in what?

A

anxiety disorders

like in PTSD

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3
Q

why is it important to learn about the neural mechanisms behind fear extinction being disrupted in anxiety disorders?

A

because it may lead to BETTER UNDERSTANDING

and IMPROVED TREATMENT

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4
Q

fear learning and extinction is well understood where?

A

in animal models

but work TRANSLATING from animals to humans has focused on limited ‘FEAR NETWORK’ involving vmPFC, dACC, insular cortex, hippocampus and amygdala

likely other brain regions are involved, esp in CONSCIOUS AWARENESS of fear

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5
Q

LeDoux’s 2 system model

A

(contrasts with the ‘FEAR CENTER’ MODEL)

threat >

sensory system >

COGNITIVE CIRCUIT and DEFENSIVE SURVIVAL CIRCUIT

cognitive circuit leads to FEAR (fearful feelings)

survival circuit leads to DEFENSIVE RESPONSES

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6
Q

fear center model

A

threat >

sensory system >

fear circuit (FEAR) >

fear responses

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7
Q

LeDoux major addition in his 2 system model

A

cognitive circuit

(working memory, appraisal etc)

leads to feelings

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8
Q

extinction memory and og fear memory interact to do what?

A

to control fear responding

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9
Q

where does the memory reside?

A

unlikely to reside in a single brain region

engrams are likely DISTRIBUTED ACROSS BRAIN

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10
Q

Karl Lashley

A

neuroscientist who was looking for the LOCUS of LEARNING and MEMORY

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11
Q

how did Lashley look for locus of fear memory?

A

trained rats in a maze

lesioned diff parts of cortex

SPECIFIC LOCATION of the lesion DIDN’T MATTER

ONLY THE SIZE OF THE LESION MATTERED

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12
Q

what did Lashley conclude about memories after his lesion studies?

A

memories (engrams) aren’t localized in specific parts of the brain

they’re highly distributed

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13
Q

what did this paper do and predict? (“fear extinction learning modulates large-scale brain connectivity”)

A

predict that extinction learning will engage BROADLY DISTRIBUTED BRAIN REGIONS

test this using fMRI in 137 Ps trained in fear conditioning and extinction

assess whole brain connectivity and activation in a trial-by-trial manner

predict that a LARGE NUMBER of BRAIN REGIONS will be RECRUITED

predict that the MAGNITUDE of increased network connectivity during extinction learning will be CORRELATED WITH EXTINCTION RECALL in a later recall session after a day

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14
Q

paper predicts what about the magnitude of increased network activity?

A

magnitude of increased network activity during extinction learning

will be CORRELATED

with EXTINCTION RECALL in a LATER SESSION after a delay

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15
Q

MRI

A

magnetic resonance imagining

uses large scale MAGNET to generate magnetic field that DIFFERENTIALLY ALIGNS the spin of HYDROGEN ATOMS

when this magnetic field = briefly disrupted, hydrogen atoms will show DIFFERENCES in the RATE OF REALIGNMENT to the magnetic field, depending on their local chemical environment

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16
Q

structural MRI is used to see what?

A

different in TISSUES in the brain

ie. grey and white matter diffs

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17
Q

fMRI

A

functional magnetic resonance imagining

exploits relationship between NEURAL ACTIVITY and BLOOD FLOW to infer an INDIRECT MEASURE OF NEURAL ACTIVITY

brain regions that are more active have higher blood flow

diffs in hydrogen atoms between OXYGENATED and DEOXYGENATED HEMOGLOBIN can be detected as changes in hydrogen atoms

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18
Q

is fMRI a direct measure of neural activity?

A

no, it’s indirect

it assess the BOLD signal - regions that are more active have HIGHER BLOOD FLOW

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19
Q

BOLD SIGNAL

A

blood-oxygen level dependent signals

detects diffs between hydrogen atoms between OXYGENATED and DEOXYGENATED hemoglobin

used to infer which brain regions are ACTIVE at a given time

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20
Q

fMRI strengths and weaknesses

A

STRENGTHS:

  1. non-invasive
  2. offers high temporal resolution (seconds)
  3. compatible with probing stimulus-evoked changes in brain activity (ie. viewing a picture)

WEAKNESSES:

  1. very noisy
  2. Ps must lie still in tiny environment for extended time period
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21
Q

paper methods

A

137 healthy Ps

2 day FEAR CONDITIONING and EXTINCTION in fMRI scanner

  1. conditioning
  2. extinction
  3. extinction recall

Ps set own level of electric stimulation to be used in conditioning (“highly annoying yet non-painful)

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22
Q

experimental paradigm

A

contextual stimuli PICTURES of either a LIBRARY or OFFICE

with an UNLIT LAMP

presented for 3 seconds before LAMP turned on to BLUE, RED or YELLOW for 6 seconds = three different CS

electrical stimulation to the hand = the US

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23
Q

CS, US and contexts in the experiment

A

US = electrical stimulation to the hand

CS = the blue, red, yellow lamps

contexts: the library and office pictures

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24
Q

experimental paradigm: conditioning

A

during conditioning, 2 of the coloured lights were PARTIALLY REINFORCED by shock (62.5% of trials)

this happened 500 ms after light onset

THESE ARE THE CS+

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25
CS+
the 2 coloured lights that were partially reinforced they went on 500 ms before shock and were reinforced on 62.5% of trials
26
CS-
one of the coloured lights was never reinforced by shock
27
experimental paradigm - extinction
after conditioning, extinction occurred in DIFF CONTEXT (ie. either library or office) during extinction, one of the CS+ was presented 16 times with no shock, and the CS- was also presented 16 times
28
experimental paradigm - extinction recall
next day - extinction memory recall was tested in the SAME CONTEXT as the EXTINCTION LEARNING all 3 coloured lamps were presented 8 times CS+E 8 times CS+U 8 times CS-
29
measure of learning
skin conductance response (SCR) measured with electrodes ^ measure of the conditioned response
30
SCR
measure of the conditioned response INDIRECT MEASURE of sympathetic autonomic activity - AMPLITUDE of SCR is associated with arousal level for each phase (conditioning, extinction, recall), conditioned response calculated as: (MAX SCR DURING CS) - (AVERAGE SCR FINAL 2 SEC CONTEXT)
31
fMRI data acquisition
structural and functional data (preprocessed prior to data analysis)
32
fMRI data analysis - broadly, they explored what?
explored WHOLE BRAIN CONNECTIVITY to measure the relative difference in connectivity FOR EACH SINGLE TRIAL ^ compared to all other trials
33
fMRI data analysis - parcellated...
parcellated the brain into 400 cortical regions and 32 subcortical regions for each region, they estimated pair-wise FUNCTIONAL CONNECTIVITY among BRAIN REGIONS
34
what does a region with high connectivity on a trial indicate?
indicates the activity of this region is STRONGLY CORRELATED to the REST OF THE BRAIN compared to other trials
35
what did network-based statistical analyses identy?
networks! default mode network, salience network showed SIGNIFICANT DIFFERENCES in the CS+ versus the CS- comparison across early to late extinction learning
36
network-based statistical analyses identified significant differences where?
between the CS+ and CS- comparisons ACROSS EARLY to LATE EXTINCTION learning
37
main takeaway result
brain connectivity changes during fear conditioning, extinction and extinction recall (changes in brain connectivity induced by extinction learning are different for the CS+ versus the CS-) (because extinction is happening to the CS+, but nothing is happening to the CS-)
38
133 brain regions generally exhibited larger connections with other regions in late extinction learning during what processing?
during CS+ processing (as opposed to during CS- processing) later analyses looked at average activity of the 133 regions and IDENTIFIED THEM AS IMPORTANT FOR LATE EXTINCTION
39
within the CS+ type, what did they observe about connectivity?
significant change in connectivity for CS+ from EARLY CONDITIONING to EXTINCTION (NO SUCH DIFFERENCE WAS OBSERVED FOR CS-)
40
fact that there was significant change in connectivity in CS+ processing from conditioning to extinction (but no change for CS-) shows that...
extinction learning induced changes in brain connectivity that are specific to CS+
41
when assessing differences in connectivity between CS+ and CS-, when do differences in connectivity first emerge?
after ~8 trials of extinction (mid-late extinction)
42
was there a significant change in connectivity for CS+ during fear conditioning?
no but in LATE CONDITIONING, CS+ connectivity was LOWER than CS- connectivity this is the OPPOSITE to the observed connectivity INCREASE for CS+ across extinction
43
what was consistent with the finding that regions important for fear extinction have decreased neuronal activity during fear conditioning?
tracking brain regions that were modulated during extinction they see that these regions had REDUCED CONNECTIVITY to the CS+ DURING CONDITIONING (also find that 4 other brain regions were modulated during fear conditioning, and that these are different than the regions modulated in extinction)
44
opposing process in brain connectivity
1. during extinction, there's higher functional connectivity in CS+ processing than CS- processing (and there's changes in connectivity between early conditioning to late extinction - whereas no such diff was observed for CS-) 2. during fear conditioning, there wasn't a sig diff in connectivity for CS+ but in later conditioning, CS+ connectivity was lower than CS- connectivity
45
do brain regions showing INCREASED CONNECTIVITY in EXTINCTION belong to known functional networks?
they assigned each brain region to one of eight established networks computed the percentage of regions within each subnetwork that showed increased connectivity networks that had the largest percentage of brain regions that were modulated by extinction: 1. default mode network 2. fronto-parietal network 3. ventral attention network
46
networks that had the largest percentage of brain regions that were modulated by extinction
1. default mode network 2. fronto-parietal network 3. ventral attention network
47
what do they conclude about the brain connectivity changes induced by extinction learning?
conclude that these changes induced by extinction learning TARGET BRAIN NETWORKS INVOLVED IN: 1. emotion regulation 2. memory storage 3. conscious attention processing
48
in the 133 brain regions showing increased connectivity in extinction, was there a sig diff in activity between CS+ and CS- trials across conditioning and extinction?
EARLY IN CONDITIONING: increased overall activity in extinction-associated regions in the CS+ EARLY EXTINCTION: this activity further increases EXTINCTION RECALL: this activity increases again
49
changes in activity seem to occur when?
seems like brain activity modulation MAINLY OCCURRED during EARLY EXTINCTION and EXTINCTION RECALL whereas connectivity changes were more prominent in LATE EXTINCTION
50
what shows the dissociation between activity and connectivity?
activity increased from early conditioning, to early extinction and extinction recall connectivity increased in late extinction (patter of activity shows altered connectivity in late extinction which reflects increases in activity in early extinction, that DISSIPATE and then RETURN at extinction recall)
51
what could the changes in either connectivity or activity be related to?
could be related to CONSOLIDATION OF THE EXTINCTION MEMORY ie. high activity during early conditioning, early extinction, then it drops off and increases again during extinction recall ie. connectivity increases in late extinction
52
how did they test to see if changes in connectivity and activity were related to consolidation of the extinction memory?
by looking at the CORRELATION between 1. changes in brain connectivity and 2. extinction memory recall (higher ERI = better extinction learning)
53
looking at the ERI, they showed that what correlates with extinction?
CONNECTIVITY but not activity CORRELATES WITH EXTINCTION (overall increase in mean connectivity across extinction-associated regions from early to late extinction was positively correlated with ERI for the CS+E)
54
findings suggest that what is more relevant to understanding extinction?
changes in CONNECTIVITY rather than activity
55
were neural signals predictive of the magnitude of extinction memory recall?
yes also further shows that changes in connectivity and activity are dissociated across extinction learning (distribution of correlations in CONNECTIVITY-change shifted towards MORE POSITIVE VALUES across extinction, and distributions of ACTIVITY-change to MORE NEGATIVE VALUES across extinction)
56
T/F: changes in connectivity and activity are dissociated across extinction learning
true (connectivity change correlations shifted towards more positive values across extinction) (activity change correlations shifted to more negative values across extinction)
57
summary of main findings
1. whole brain activity and connectivity is altered by fear extinction and recall 2. these changes extend BEYOND the canonical fear network 3. changes in connectivity can be dissociated from changes in activity 4. changes in connectivity during extinction learning predict extinction memory recall the next day
58
results show that broader brain circuits are involved in fear extinction - so...
it may be important to consider the role of ADDITIONAL brain networks authors suggest this is consistent with the LeDoux two-systems view of fear ^ there's cortical involvement too
59
what do they note about their measure of fear?
measure of fear is LIMITED to SCR would be informative to also have a CONSCIOUS MEASURE OF FEAR to see how this may relate to altered brain activity/connectivity (more research is needed to understand how distributed changes relate to conscious and unconscious measures of fear)
60
what does the dissociation between connectivity and activity suggeest?
suggests that these phenomena may REFLECT DIFF PROCESESES
61
how may connectivity and activity reflect diff processes?
ACTIVATION may reflect LOCAL PROCESSING whereas brain CONNECTIVITY may reflect NEURAL PLASTICITY and connectivity changes may be important for MEMORY CONSOLIDATION
62
commentary
1. paper shows that changes are BROAD and GO BEYOND canonical fear circuits 2. but there's a LACK OF SPECIFICITY in how they report their findings - and this is ULTIMATELY UNINFORMATIVE 3. analyses of changes in activation was constrained to consider brain regions that were found to have altered extinction-association functional connectivity - would they have found DIFF EFFECTS FOR ACTIVATION had they looked at OTHER BRAIN REGIONS?

Psyc 443 (20 decks)

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