The Role of the Locus Coeruleus in Age-related Distractibility

Losing Specificity: the Role of the Locus Coeruleus in Age-related Distractibility

A growing body of research has highlighted the importance of frontal regions, at both the functional and structural levels, in age-related declines in attentional and cognitive processing. However, the underlying neurobiological pathophysiological changes in the brain that contribute to these declines are still largely unclear. The objective of this proposal is to investigate neural mechanisms of age-related attentional distractibility, focusing on the neural circuit initiated from the locus coeruleus (LC). In the current proposal, the investigators will test the hypothesis that the neural dysconnectivity of LC with the salience network (SN) drives failures of ignoring distractors in older adults. The investigators will examine how LC-SN connectivity is associated with selective attention performance, and how improved LC-SN connectivity through a cognitive training program may lead to improved attentional performance.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Aging
• Intervention / Treatment: Behavioral: Tablet based adaptive multimodal attention practice program; Behavioral: Tablet based adaptive criterion task practice program

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tae-Ho Lee, PhD; Phone Number: 540-231-6174; Email: taehol@vt.edu
• Study Contact Backup: Name: Benjamin Katz, PhD; Phone Number: 540-231-9816; Email: katzben@vt.edu

Study Locations

• United States
  • Virginia
    • Blacksburg, Virginia, United States, 24061
      • Recruiting
      • Virginia Polytechnic Institute and State University
      • Contact: Tae-Ho Lee, PhD; Phone Number: 540-231-6174; Email: taehol@vt.edu
      • Contact: Benjamin Katz, PhD; Phone Number: 540-231-9816; Email: katzben@vt.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion:

• Healthy adult participants
• No younger than 18 and no older than 75 yrs of age
• Ability to provide written informed consent

Exclusion:

• History of surgery involving metal implants
• Possible metal fragments in the eyes
• Pacemaker
• A history of claustrophobia
• Braces
• Weighing over 250 pounds
• Pregnant or possibility of being pregnant.
• Severe medical or psychiatric conditions (e.g., blind or deaf, head trauma)
• Learning disabilities or developmental disabilities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Older adult participants; Older adult participants in the study will complete one of two variants of an attention practice program and that will be preceded by, and followed by, an fMRI scan session featuring an attention task	Behavioral: Tablet based adaptive multimodal attention practice program; An adaptive at-home tablet-based program that includes variants of the Flanker Task, the Stroop Task, and a Visual Tracking Task. Each session of practice will include up to ten minutes with each of these task types, and the tasks will increase in difficulty in a way that further taxes attention (such as through more distractors or more incongruent trials) as participant performance improves.; Behavioral: Tablet based adaptive criterion task practice program; An adaptive, at-home tablet-based variant of the criterion task, that is, the selective attention/distraction task used during the scanning portion of the human participant portions of the study, that takes up to 25 minutes to complete each session.
No Intervention: Younger adult participants; Younger adult participants in the study will complete one fMRI scan session featuring an attention task

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in accuracy on the place-face selective attention task after two weeks	During this task, participants will be presented to with target place stimuli overlaid on nonexpressive faces) and be asked to identify categories of place images ('building' to 'house') selectively as soon as possible while ignoring overlapped faces. The investigators will also include place only images to measure participants' baseline neural activation when there is no distractor. Each image condition will be presented in a mixed event related design that includes 15 blocks for each condition as a function of image type (overlaid vs. place-only). The block order will be counterbalanced and each block will be separated by a 10-s blank screen.	Scan before and after attentional practice (2 weeks between scans)
Change in fMRI LC-SN connectivity after two weeks	An fMRI measure of LC-SN connectivity	Scan before and after attentional practice (2 weeks between scans)

Collaborators and Investigators

• Sponsor: Virginia Polytechnic Institute and State University
• Investigators: Principal Investigator: Tae-Ho Lee, PhD, Virginia Polytechnic Institute and State University

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: September 13, 2022
• First Submitted That Met QC Criteria: October 6, 2022
• First Posted (Actual): October 10, 2022

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 19-514

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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