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.

Study Overview

• Status: Completed
• Conditions: Anxiety
• Intervention / Treatment: Behavioral: Attention Bias Modification; Behavioral: Attention Control

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Marquette, Michigan, United States, 49855
      • Northern Michigan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 37 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Attention Bias Modification	Behavioral: Attention Bias Modification; 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).
Active Comparator: Attention Control	Behavioral: Attention Control; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI measures of gray matter volume	T1-weighted MRI measures of gray matter volume	Baseline and after 6 weeks of the intervention
MRI measures of structural and functional connectivity	Diffusion-tensor weighted MRI based measures of structural connectivity and functional MRI based measures of functional connectivity.	Baseline and after 6 weeks of the intervention

Collaborators and Investigators

• Sponsor: Northern Michigan University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Joshua M Carlson, PhD, Northern Michigan University

Publications and helpful links

General Publications

• Carlson JM, Fang L, Koster EHW, Andrzejewski JA, Gilbertson H, Elwell KA, Zuidema TR. Neuroplastic changes in anterior cingulate cortex gray matter volume and functional connectivity following attention bias modification in high trait anxious individuals. Biol Psychol. 2022 Jul;172:108353. doi: 10.1016/j.biopsycho.2022.108353. Epub 2022 May 13.
• Carlson JM, Fang L. Attentional bias to threat and gray matter volume morphology in high anxious individuals. Cogn Affect Behav Neurosci. 2022 Jun;22(3):600-609. doi: 10.3758/s13415-021-00968-9. Epub 2021 Nov 9.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2017
• Primary Completion (Actual): March 14, 2020
• Study Completion (Actual): March 14, 2020

Study Registration Dates

• First Submitted: March 14, 2017
• First Submitted That Met QC Criteria: March 21, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Attentional Bias to Threat
• Other Study ID Numbers: HS13-555; R15MH110951 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be uploaded to the NIMH Data Archive

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No