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

Study Overview
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Brief Summary
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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.

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

Conditions
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Anxiety

Intervention / Treatment
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* Behavioral: Attention Bias Modification
* Behavioral: Attention Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Handedness (right handed) Normal Vision High Anxiety Preexisting Attentional Bias Exclusion Criteria: No MRI contraindications No History of Head Injury No Neurological History Psychological History Limited Recreational Drug Use, No Abuse Limited Prescription Drug Use, No Abuse No Claustrophobia Not Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Attention Bias Modification<br> | Behavioral: Attention Bias Modification<br>* Attention bias modification (ABM) sessions will consist of a modified dot-probe task that only contains incongruent trials (i.e., target-dot - neutral stimulus 100% pairing).<br>|
| Active Comparator: Attention Control<br> | Behavioral: Attention Control<br>* Attention control (AC) sessions, will consist of a standard dot-probe task (i.e., target-dot - neutral/threat stimulus 50% pairing). Thus, for AC participants, bias should remain the same, while ABM participants should show a reduced bias to threat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attentional Bias | Reaction time difference to congruent and incongruent trials in the dot-probe task, which measure heightened attentional bias to threat. | Baseline and after 6 weeks of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State and Trait Anxiety | Anxiety as measured by the Speilberger State-Trait Anxiety Inventory | Baseline and after 6 weeks of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Attentional Bias to Threat