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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cognitively intact older adults - ACTIVE tDCS | Experimental | Group receives active brain stimulation |
|
| MCI ACTIVE tDCS | Active Comparator | Group receives active brain stimulation |
|
| Cognitively intact older adults - SHAM tDCS | Sham Comparator | Group receives sham brain stimulation |
|
| MCI SHAM tDCS | Sham Comparator | Group receives sham brain stimulation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial direct current stimulation (tDCS) | Device | 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). |
| 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 |
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Inclusion Criteria:
General inclusion criteria (all participants):
MCI Inclusion Criteria:
Healthy older adults
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Benjamin M Hampstead, PhD | VA Ann Arbor Healthcare System, Ann Arbor, MI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Atlanta VA Medical and Rehab Center, Decatur, GA | Decatur | Georgia | 30033 | United States | ||
| VA Ann Arbor Healthcare System, Ann Arbor, MI |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25647757 | Result | England HB, Fyock C, Meredith Gillis M, Hampstead BM. Transcranial direct current stimulation modulates spatial memory in cognitively intact adults. Behav Brain Res. 2015 Apr 15;283:191-5. doi: 10.1016/j.bbr.2015.01.044. Epub 2015 Jan 31. | |
| 34602464 | Derived | Lengu K, Ryan S, Peltier SJ, Tyszkowski T, Kairys A, Giordani B, Hampstead BM. Effects of High Definition-Transcranial Direct Current Stimulation on Local GABA and Glutamate Levels Among Older Adults with and without Mild Cognitive Impairment: An Exploratory Study. J Alzheimers Dis. 2021;84(3):1091-1102. doi: 10.3233/JAD-201091. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cognitively Intact -Active Then Sham tDCS | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| FG001 | Cognitively Intact - Sham Then Active | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| FG002 | MCI - Active Then Sham | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| FG003 | MCI - Sham Then Active | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cognitively Intact Older Adults | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Computer errors caused missing data for a subset (n=4) of participants; those data have simply been omitted from analyses below. | Posted | Mean | Standard Deviation | Centimeters (cm) | Outcome assessed after each of 2 sessions (estimated within 1 week of each other) |
|
duration of each participant's study related activities (~2 weeks), with monitoring ending following the second tDCS session
All participants completed a standardized side effect questionnaire after every tDCS session.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cognitively Intact Active | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Headache |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Benjamin Hampstead | VA Ann Arbor Healthcare System; University of Michigan | 7347639259 | bhampste@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 20, 2018 | Mar 22, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
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Transcranial Direct Current Stimulation
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Double blinded
|
| Ann Arbor |
| Michigan |
| 48105 |
| United States |
| Patients With Mild Cognitive Impairment |
All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | MCI ACTIVE tDCS | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). |
| OG002 | Cognitively Intact SHAM tDCS | all participants received sham in a randomized order |
| OG003 | MCI SHAM tDCS | all participants received sham in a randomized order |
|
|
|
| Primary | 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. | Participants from each group were excluded due to movement artifact that invalidated fMRI data. | Posted | Mean | Standard Deviation | Percent signal change | change between active and sham tDCS sessions (<1month) |
|
|
|
|
| Primary | 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. | Participants from each group were excluded due to movement artifact that invalidated fMRI data. | Posted | Mean | Standard Deviation | arbitrary units | change between active and sham tDCS sessions (<1month) |
|
|
|
|
| Primary | Egocentric | Number of turns correctly recalled for each egocentric environment | Participants from each group were excluded due to movement artifact that invalidated fMRI data. | Posted | Mean | Standard Deviation | Correct turns | Outcome assessed after each of the 2 sessions |
|
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 13 |
| 21 |
| EG001 | Cognitively Intact Sham | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). | 0 | 22 | 0 | 22 | 17 | 22 |
| EG002 | MCI Active | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). | 0 | 20 | 0 | 20 | 15 | 20 |
| EG003 | MCI Sham | All participants received active and sham transcranial direct current stimulation (tDCS). Participants were randomized to order (i.e., half received active tDCS in the first session and sham in the second session; the other half received the opposite). | 0 | 20 | 0 | 20 | 12 | 20 |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Neck pain |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Scalp pain |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Tingling |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Itching |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Burning |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Skin redness |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Sleepiness |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | Concentration changes |
|
| Side effect questionnaire | Skin and subcutaneous tissue disorders | Systematic Assessment | mood changes |
|
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| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |
| <.001 |
| Superiority |
| .046 |
| Superiority |
| Superiority |