PUBLISHED: 21 NOVEMBER 2016 | VOLUME: 1 | ARTICLE NUMBER: 0010

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NEUROSCIENCE

Hacking the brain to overcome fear

Confronting fears is a core component of cognitive behavioural therapies for anxiety disorders, but also a major
hurdle for patients. A new study introduces a method for reducing defensive responses without consciously
confronting the threatening cues, paving the way for fear-reducing therapies via unconscious processing.

Daniela Schiller

W
hat if instead of struggling up pattern was activated in the visual cortex
a mountain of fear there was a increased, so did the size of the disc and the
simple way around it? Exposure participants’ monetary gains.
therapy is the most successful treatment Put simply, from their perspective, the
we have right now for alleviating fear participants did something that somehow
and anxiety disorders1. During exposure enlarged the disc on the monitor and made
sessions, patients have to recall and describe them richer. This ‘something’ corresponded
their traumatic event again and again, to the neural expression of the target
until it blunts their emotional reactions. stimulus pattern in the visual cortex. In
For some, this could be an excruciating this way, participants were rewarded by
process; one they will choose to evade. In Koizumi et al.2 for unconsciously producing
this first issue of Nature Human Behaviour, neural responses representing a threatening
Koizumi and colleagues2 introduce a visual stimulus, without actually seeing it.
technique to reduce defensive responses Indeed, the participants gave no indication
ALBERTO RUGGIERI/ILLUSTRATION WORKS/GETTY
that avoids consciously recalling the of arousal responses during these sessions,
threatening memory. This may pave the they had no knowledge of the actual purpose
way for fear-reducing therapies by way of of the study, nor were they able to guess the
unconscious processing. identity of the target stimulus.
Koizumi et al.2 took advantage of The crucial test came on the fifth day,
a simple learning phenomenon called when the participants again saw all the
classical, or Pavlovian, threat conditioning, stimuli. The session started with a few
the process by which we learn to associate unsignalled electric shocks; a stressful
neutral stimuli in the environment with exposure that effectively brings up threat
dangerous outcomes. The entire study memories. When later confronted with
consisted of five sessions, run on consecutive the stimuli, participants’ conditioned
days, that were conducted during functional defensive reaction to the target stimulus was
magnetic resonance imaging (fMRI). On the significantly lower than their reaction to the
first day, the participants experienced threat control stimulus. Koizumi et al.2 observed
conditioning, during which they learned participants saw achromatic visual gratings. a similar pattern of results in the amygdala;
to associate a mild electric shock with two Using any mental technique, they were the brain region that mediates classical
different images (vertical gratings of red asked to increase the diameter of a disc conditioning and induces conditioned
and green circles, for example), but not two on the monitor in order to gain monetary defensive reactions4. The amygdala showed
other images (vertical gratings of blue and rewards. Unbeknownst to the participants, similarly heightened responses to the
yellow circles). Electrodes placed on the the experimenters monitored their brain target and control stimuli on day 1; but
participants’ fingers measured their skin responses and reinforced them, in real lower responses to the target compared
conductance response, indicating their level time, if the responses corresponded to with the control stimulus on day 5. Neural
of physiological arousal, one of the markers the conditioned stimulus. In order to do reinforcement, therefore, was effective
of fear. By the end of this procedure, this, an initial fMRI session preceded the in diminishing behavioural and neural
the participants showed heightened experiment, in which the experimenters reactions to the targeted threatening cue.
physiological arousal in response to the presented the visual stimuli to the The ability to reduce threat learning
red and green circles compared with the participants, and, in the fMRI signal of the via extinction training, the laboratory
non-reinforced blue and yellow circles. This visual cortex, identified a unique multi-voxel model of exposure therapy, depends on the
meant they were now ‘afraid’ of the images pattern for each stimulus3. Then, during integrity of the ventral medial prefrontal
that predicted an upcoming electric shock. the neural reinforcement sessions, they cortex5 (VMPFC). Would this region
The next three days were dedicated decoded the fMRI signal for each participant engage in diminishing threat responses via
to accessing the brain’s representation of and estimated how likely it was that the unconscious processing? To address this,
one of the conditioned stimuli, without observed patterns corresponded to the the authors searched the entire brain for the
participants’ awareness, and associating target stimulus (the red circle, for example, occurrence of target stimulus multi-voxel
it with a positive outcome. During these while the green circle served as the control). patterns that correlated with the likelihood
‘neural reinforcement’ sessions, the As the likelihood that the target stimulus of pattern occurrence in the visual cortex.

NATURE HUMAN BEHAVIOUR 1, 0010 (2016) | DOI: 10.1038/s41562-016-0010 | www.nature.com/nathumbehav 1

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This form of ‘information transmission’ strong and complex, as well as the stability of system would affect the other. The gateway
was mostly confined to the visual cortex the change. for unconscious threat processing that
and did not extend to the VMPFC. In fact, When facing the mountain of fear, Koizumi et al.2 have opened up is an
less information transmission between the then, which path would you choose? Will important step forward in understanding
visual cortex and VMPFC during neural you take the uphill battle of confronting how the two systems interact. ❐
reinforcement related to greater reduction your fears or the unconscious way around
in defensive reactions to the target stimulus it? This may not be a matter of choice but Daniela Schiller is in the Department of Psychiatry,
on day 5. This suggests that during neural rather a question of compatibility. When the Department of Neuroscience and the Friedman
reinforcement, unlike extinction methods, we use the term ‘fear’, we interchangeably Brain Institute, Icahn School of Medicine at
VMPFC disengagement rather than refer to the defensive behavioural and Mount Sinai, New York, New York 10029, USA.
engagement allows for threat reduction6. physiological responses to immediate e-mail: [email protected]
The results of Koizumi et al.2 are the first threats, as well as the conscious feelings of
demonstration that reduction of defensive fear. The ‘two-system’ framework8 posits References
reactions may be possible not only without that separate neural circuits control these 1. McLean, C. P. & Foa, E. B. Expert Rev. Neurother.
11, 1151–1163 (2011).
consciously confronting the threatening two consequences of threat detection. 2. Koizumi, A. et al. Nat. Hum. Behav. 1, 0006 (2016).
cues7 but even without physiological Malfunction of the circuits may affect 3. Amano, K., Shibata, K., Kawato, M., Sasaki, Y. & Watanabe, T.
arousal. Changing fear may simply require either system and require differential Curr. Biol. 26, 1861–1866 (2016).
4. Johansen, J. P., Cain, C. K., Ostroff, L. E. & LeDoux, J. E. Cell
‘neurohacking’ — decoding the neural treatment. For those with aberrant cortical
147, 509–524 (2011).
identity of threatening stimuli in the visual circuits that underlie cognitive functions 5. Quirk, G. J. & Mueller, D. Neuropsychopharmacology
cortex and counter-conditioning them and feelings states, behavioural therapy 33, 56–72 (2008).
with rewards. To translate this into clinical and direct confrontation may work best. 6. Schiller, D., Kanen, J. W., LeDoux, J. E., Monfils, M. H. &
Phelps, E. A. Proc. Natl Acad. Sci. USA 110, 20040–20045 (2013).
treatment, the next steps should assess Those with abnormal defensive circuits 7. Weinberger, J., Siegel, P., Siefert, C. & Drwal, J. Conscious Cogn.
the efficacy of the technique for real-life may benefit from unconscious processing. 20, 173–180 (2011).
memories, especially those that are old, It is also possible that treatment in one 8. LeDoux, J. E. & Pine, D. S. Am. J. Psychiat.173, 1083–1093 (2016).

2 NATURE HUMAN BEHAVIOUR 1, 0010 (2016) | DOI: 10.1038/s41562-016-0010 | www.nature.com/nathumbehav

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