The Role of the Locus Coeruleus in Age-related Distractibility

Study Overview
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Brief Summary
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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.

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

Conditions
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Aging, Alzheimer Disease

Intervention / Treatment
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* Behavioral: Tablet based adaptive multimodal attention practice program
* Behavioral: Tablet based adaptive criterion task practice program


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Older adult participants<br>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<br>* 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.<br>Behavioral: Tablet based adaptive criterion task practice program<br>* 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.<br>|
| No Intervention: Younger adult participants<br>Younger adult participants in the study will complete one fMRI scan session featuring an attention task | |

What is the study measuring?
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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) |