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Investigating the neural correlates of location-specific fear learning in humans

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Benjamin Suarez-Jimenez

on 7 June 2017

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Transcript of Investigating the neural correlates of location-specific fear learning in humans

Investigating the neural correlates of location-specific fear learning in humans
Benjamin Suarez-Jimenez, James Bisby, Aidan J. Horner, John A. King, Daniel Pine, Neil Burgess
UCL Institute of Cognitive Neuroscience; National Institute of Health; UCL Dept of Clinical Psychology
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Learning about potential dangers in an environment is a vital adaptive behavior.


This process of learning to associate a stimuli with its proper context often goes wrong in anxiety disorders.


The amygdala and hippocampus are thought to support learning of associations between an aversive outcome and a predictive stimulus or context, respectively (
1, 2, 3, 4, 5
).


To date, little is know about the neural mechanisms supporting location-specific fear learning within a single environment.
Introduction
Materials and Methods
Participants:
21 healthy volunteers (12 males), average of 24 years.

Environment:

We created a circular virtual environment surrounded by distal cues and two local landmarks (one beehive on either side of the environment) to allow participants to orient themselves. Participants were told to explore the environment and collect flowers, which appeared one at a time.

Conditioning:

Each flower served as a conditioned stimulus (CS). Flowers collected in one half of the environment were paired with an electric shock (Danger; CS+) using a 50% reinforcement rate. Flowers collected in the opposite half of the environment were never paired with shock (Safe zone; CS-).

Data Analysis
FMRI

data were analyzed
SPM8
.

Preprocessing steps
included realignment, slice correction, unwarping, normalization and smoothing (i.e., correction for subtle head movement).


2x2 design
(Context and Time):

Safety / danger

Early / Late phases of learning
SCR Analysis:
SCR were log transformed (log [1+SCR]) to normalize the distribution and then range correction:

([SCR-SCRmin]/[SCRmax-SCRmin]) was applied to control for individual variation in responding (Lykken, 1972)

2x4 design (Context and Time)

Conclusions

Location specific fear learning was evidenced by greater SCRs to flowers approached in the dangerous part of the environment.


Increased vmPFC and anterior hippocampus activity at approach during the last half of learning may reflect the valuation of environmental information to predict the flowers associated outcome.


Once a flower is reached, midbrain areas and dACC may contribute to the behavioral response when threat is imminent.


During freezing, vmPFC may process information within the environment to inhibit fear responses within safe locations.


These have important implications for the way in which we learn about fearful situations in an environment. How these neural mechanisms break down in anxiety disorders?
Behavioral Results
Imaging Results
Active Approach
Freezing Period
[1]
Bach, D.R., Weiskopf, N., & Dolan, R.J. (2011). A stable sparse fear memory trace in human amygdala. J Neurosci. 31(25): 9383–9.
[2]
Buchel, C., Dolan, R.J., Armony, J.L., & Friston, K.J. (1999). Amygdala-hippocampal involvement in human aversive trace conditioning revealed through event-related functional magnetic resonance imaging. J Neurosci. 19(24):10869-76.
[3]
LeDoux, J. (1996). Emotional networks and motor control: a fearful view. Prog Brain Res. 107:437-46
[4]
Kim, J.J. & Fanselow, M.S. (1992). Modality-specific retrograde amnesia of fear. Science. 256(5057):675-7.
[5]
Kalisch, R., Korenfeld, E., Stephan, K.E., Weiskopf, N., Seymour, B., Dolan, R.J. (2996). Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. J Neurosci. 26(37):9503-11.

Skin conductance level was
higher when approaching flowers located in the dangerous zone

of the environment (F(1,21)=8.92, p<.01).

Skin conductance response was
higher when flowers were picked in the dangerous zone
of the environment (F(1,21)=7.76, p<.01). Also, SCR decrease over time across both conditions (F(3,63)=16.06, p<.01).

Expectancy ratings showed a clear effect of fear learning, as the
experiment progressed, participants reduced their expectancy ratings during trials within the safe zone
(F(3,63)=20.76, p<.01).
vmPFC
showed greater activity during the second half of learning as participants approached the flower.
Anterior hippocampus
showed greater activity during the second half of learning as participants approached the flower.
Dorsal ACC
showed greater activity during the approach to the flower in the dangerous zone.
Trial:

During each trial, participants approached the flower and, on collection, their movement was frozen. They were then required to make an expectancy rating (0-9) on whether they expected a shock. The participant was held still for further 4 sec with CS+ trials co-terminating with shock. Participants were then released and they could freely move to the next flower.
Periaqueductal gray
showed greater activity when flowers were picked in the dangerous zone.
vmPFC
showed greater activity when flowers were picked in the safe zone.
Insula
showed greater activity when flowers were picked in the dangerous zone.
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