Neuroplasticity in an Extended Amygdala Network as a Target Mechanism for Attention Bias Modification Outcome

Anxiety disorders are one of the most common psychological disorders. Underlying anxiety is
an increased attentional bias to threat, which has been identified as a causal contributor in
the development of anxiety. Given this causal relationship, attention bias modification was
introduced as a treatment option where anxiety is reduced by training individuals to direct
their attention away from threat and thereby decreasing anxiety. Over a decade of research
using this approach, called attention bias modification (ABM), suggests that overall the
approach is effective in reducing anxiety. Although ABM appears to be a very promising
treatment option for anxiety, there are several factors limiting the effectiveness of ABM.
These include the recognition of individual-level needs and a known underlying mechanism of
action by which ABM is effective. Neuroimaging evidence suggests that attentional bias to
visual threat is associated with a network of brain regions including the amygdala, anterior
cingulate cortex, and visual cortex. In human participants, experience-dependent
neuroplasticity is visible in voxel-based morphometry based measures of gray matter volume
following training. Recently, voxel-based morphometry measures of gray matter volume have
been linked to dendritic spine density—a known cellular mechanism for learning-related
neuroplasticity. Thus, voxel-based morphometry measures are ideally suited to measure
learning-related neuroplasticity following attention bias modification. In this proposal
participants' level of attentional bias, anxiety, and gray matter volume will be measured
before and after completing six weeks of attention bias modification training (N = 50) or
attention control training (N= 50). The proposal aims to (1) establish that pre-treatment
bias predicts variability in gray matter volume in the extended amygdala and anterior
cingulate cortex, (2) assess the extent to which reduced extended amygdala and anterior
cingulate cortex gray matter volume following ABM underlies reductions in attentional bias
and anxiety, and (3) Establish pre-treatment bias as a predictor of successful ABM as
measured by reduced bias, reduced anxiety, and reduced gray matter volume in the extended
amygdala and anterior cingulate cortex. Consistent with the objectives of the AREA grant and
NIMH's focus on identifying and validating new targets for treatment development that
underlie disease mechanisms, the current proposal plans to involve students at a rural
primarily undergraduate university in a research project aimed at establishing
neuroplasticity in the extended amygdala and anterior cingulate cortex as a target mechanism
for ABM training outcome, which could be used to objectively track training-related outcomes
in anxiety treatment.