Enhancing Spatial Navigation Using Non-Invasive Brain Stimulation

Study Overview
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Brief Summary
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Remembering how to travel from one location to another is critical in everyday life, yet this vital ability declines with normal aging and can be further affected by conditions that disproportionately affect the elderly, such as vision loss or progressive dementia. Human and animal research has shown that two distinct memory systems interact during navigation. The first, referred to as allocentric navigation, is very flexible and uses spatial knowledge of key features or landmarks to develop and use a mental map of the environment. This approach involves brain regions that are critical for new learning and memory but that decline with age. The second, referred to as egocentric navigation, is inflexible and relies on habit memories that link specific features with specific directions. This approach relies on brain regions that are critical for automatic responses and that are relatively unaffected by age. The main problem is that allocentric navigation declines with age and is accompanied increased dependence on egocentric navigation. This change increases the risk of becoming disoriented or lost when traveling in unfamiliar areas or even when traveling new routes in familiar areas. Therefore, the main goal of this project is to examine whether non-invasive brain stimulation, specifically transcranial direct current stimulation, can improve allocentric navigation in healthy older adults and patients with mild cognitive impairment. Participants will complete two functional magnetic resonance imaging sessions while learning new environments. Before one of these sessions, participants will receive active brain stimulation over the parietal cortex. Before the other session, participants will receive sham brain stimulation over the parietal cortex. The effects of this stimulation will be evaluated using both an allocentric and an egocentric memory test. Physiologic effects will be evaluated using both task-based and resting-state MRI.

Official Title
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Enhancing Spatial Navigation Using Non-Invasive Brain Stimulation

Conditions
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Mild Cognitive Impairment, Alzheimer's Disease

Intervention / Treatment
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* Device: Transcranial direct current stimulation (tDCS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General inclusion criteria (all participants): All medications stable for approximately 1-2 months; No history of severe mental illness; No current untreated alcohol or substance abuse/dependence; English as native and preferred language; MRI-compatible if taking part in fMRI studies Able to give informed consent. MCI Inclusion Criteria: Diagnosis of amnestic MCI based on criteria set forth by Petersen (2004). Additionally, other potential causes of cognitive deficit ruled out by the referring physician; Healthy older adults intact cognitive functioning as measured by neuropsychological testing Exclusion Criteria: History of neurological disease or injury History of severe mental illness Current untreated alcohol or substance abuse Other conditions may exclude; please discuss with contact

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 88 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: Crossover Assignment
Interventional Model Description: Transcranial Direct Current Stimulation
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitively intact older adults - ACTIVE tDCS<br>Group receives active brain stimulation | Device: Transcranial direct current stimulation (tDCS)<br>* Active and/or sham; All participants receive both stimulation condition. Groups will be counterbalanced (half receiving active tDCS in the first session and sham in the second session; the other half receiving the opposite).<br>|
| Active Comparator: MCI ACTIVE tDCS<br>Group receives active brain stimulation | Device: Transcranial direct current stimulation (tDCS)<br>* Active and/or sham; All participants receive both stimulation condition. Groups will be counterbalanced (half receiving active tDCS in the first session and sham in the second session; the other half receiving the opposite).<br>|
| Sham Comparator: Cognitively intact older adults - SHAM tDCS<br>Group receives sham brain stimulation | Device: Transcranial direct current stimulation (tDCS)<br>* Active and/or sham; All participants receive both stimulation condition. Groups will be counterbalanced (half receiving active tDCS in the first session and sham in the second session; the other half receiving the opposite).<br>|
| Sham Comparator: MCI SHAM tDCS<br>Group receives sham brain stimulation | Device: Transcranial direct current stimulation (tDCS)<br>* Active and/or sham; All participants receive both stimulation condition. Groups will be counterbalanced (half receiving active tDCS in the first session and sham in the second session; the other half receiving the opposite).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy in Centimeters From Target Location for Allocentric | 1 active tDCS; 1 sham tDCS for each measure. Participants touched a screen (using a ELO 19 touchscreen monitor) to document the location of the landmark. The distance between the actual vs. selected location served as the dependent measure. | Outcome assessed after each of 2 sessions (estimated within 1 week of each other) | 
| Hippocampal BOLD Signal During Task-based fMRI | BOLD signal change comparing active to sham tDCS during Allocentric navigation (i.e., active HD-tDCS > sham HD-tDCS). Activation maps thresholded at p<.01 with minimum cluster size of 5 voxels. | change between active and sham tDCS sessions (<1month) | 
| Dorsal Attention Network Connectivity During Resting-state fMRI | Change in resting state functional connectivity strength between active and sham tDCS sessions. Strength is measured by Pearson r correlations between nodes, which are z-transformed, and summated. | change between active and sham tDCS sessions (<1month) | 
| Egocentric | Number of turns correctly recalled for each egocentric environment | Outcome assessed after each of the 2 sessions | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aging, Alzheimer's Disease/Dementia, Cognitive Disorders, Imaging, Magnetic Resonance Imaging (MRI), Neurology, Physical Medicine & Rehabilitation, transcranial direct current stimulation