Understanding Brain Mechanisms Involved in Autobiographical Memory

Study Overview
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Brief Summary
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The overall objective of this project is to characterize the spatiotemporal dynamics of brain oscillations underpinning autobiographical memory (ABM) and the modulation of the memory network using non-invasive brain stimulation.

Detailed Description
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Accumulating evidence suggests that activity in distributed networks supporting ABM is altered even decades before the expected onset of clinical symptoms in Alzheimer's disease (AD). Robust network alterations associated with age-related memory and cognitive decline have been linked to abnormal oscillatory brain rhythmic activity and functional dysconnectivity. However, the detailed neural mechanisms are still poorly understood. The investigators propose to precisely characterize the underlying neurophysiological mechanisms that lead to behavioral and cognitive disturbances in ABM of MCI patients. Specifically, hdEEG will be used to characterize the sources and spatiotemporal dynamics of the neuronal activity involved in the ABM network of 40 mild cognitive impairment (MCI) patients and compare it to 40 age-matched, older healthy participants and 40 healthy young participants. The investigators will then apply non-invasive brain stimulation in the form of transcranial alternating current stimulation (tACS) to gain novel insights into the causal role of brain oscillations in the ABM network of MCI patients.

Official Title
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Understanding Brain Mechanisms Involved in Autobiographical Memory Using High-density Electroencephalography and Transcranial Alternating Current Stimulation

Conditions
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Mild Cognitive Impairment, Alzheimer Disease, Memory Loss

Intervention / Treatment
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* Device: high-density electroencephalography (hdEEG)
* Device: Transcranial alternating current stimulation (tACS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cognitively-Unimpaired Younger and Older Adults Age 18 to 35 years old (younger adults) Age 55+ years old (older adults) without any cognitive impairment (based on the Montreal Cognitive Assessment: MoCA) willing and capable to give informed consent for participation in the study after it has been thoroughly explained able willing to comply with all study requirements informed consent form was signed Mild Cognitive Impairment (MCI) patients Age 55+ years old Clinical Diagnosis of MCI Confirmation of diagnosis will be made by the study MD based on a holistic consideration of the participant's cognitive evaluation and history Mini-Mental State Examination (MMSE) ≥ 18 (Mild AD ≥ 21) CDR ≥ .5 Demonstration or history of autobiographical memory impairments On a stable dose of medications for memory loss including cholinesterase inhibitors (e.g. donepezil, rivastigmine) or memantine as defined as 6 consecutive weeks of treatment at an unchanging dose Minimum of completed 8th-grade education willing and capable to give informed consent for participation in the study after it has been thoroughly explained - note that to ensure this in the case of the MCI participants, a cut-off of MOCA score >18 will be applied able and willing to comply with all study requirements informed consent form was signed Exclusion Criteria: Cognitively-Unimpaired Younger and Older Adults any cognitive impairment captured by the Montreal Cognitive Assessment (MoCA) - score < 26 major psychiatric co-morbidity including major depressive disorder, schizophrenia, or psychosis blindness or other disabilities that prevent task performance Contraindication for undergoing MRI Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement) Mild Cognitive Impairment (MCI) patients Age < 55 years old Any current diagnosis of a major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depressive disorder) Other than MCI, any history of other progressive or genetic neurologic disorder (e.g. Parkinson's disease, multiple sclerosis, tubular sclerosis) or acquired neurological disease (e.g. stroke, traumatic brain injury, tumor), including intracranial lesions History of head trauma resulting in prolonged loss of consciousness Current history of poorly controlled headaches including chronic medication for migraine prevention History of fainting spells of unknown or undetermined etiology that might constitute seizures History of seizures, diagnosis of epilepsy, or immediate (1st-degree relative) family history of epilepsy with the exception of a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist Any unstable medical condition or chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) or study complication contraindications to tACS, as recorded on a standardized screening questionnaire, which include a reported seizure within the past two years, use of neuroactive drugs, self-reported presence of specific implanted medical devices (e.g., deep brain stimulator, medication infusion pump, cochlear implant, pacemaker, etc.), or the presence of any active dermatological condition, such as eczema, on the scalp Contraindication for undergoing MRI or receiving tACS Any metal in the brain or skull (excluding dental fillings) or elsewhere in the body unless cleared by the responsible covering MD (e.g. MRI compatible joint replacement) Any devices such as a pacemaker, medication pump, nerve stimulator, TENS unit, ventriculoperitoneal shunt unless cleared by the responsible covering MD

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: neurophysiological measurements<br>40 cognitively-unimpaired healthy young adults (age 18-35 years old), 40 cognitively-unimpaired healthy older adults (age 55+ years old), and 40 age-matched patients with mild cognitive impairment (MCI) (age 55+ years old) will be assessed using high-density electroencephalography (hdEEG) to characterize the spatiotemporal dynamics of brain oscillations during personalized, autobiographical memory (ABM) tasks. | Device: high-density electroencephalography (hdEEG)<br>* EEG will be recorded with a 257-channel EEG system (Geodesic Sensor Net, MegStim). An EEG net is applied at once on the head with evenly spaced sensors that provide full scalp coverage, including the cheek, Ag/Ag-Cl electrodes that are interconnected by thin rubber bands and contain small sponges soaked with saline water that touches the participant's scalp surface directly. Net application takes about 10 min to derive impedances to <30 kOhms. EEG is recorded with 1 kHz and band-pass filtered between 0.1-200 Hz. Vertex electrode Cz is used as an acquisition reference.<br>|
| Experimental: neuropsychological examination<br>40 MCI patients (age 55+ years old) will undergo 20min multi-channel protocols of transcranial alternating current stimulation; tACS (either gamma, beta, or ActiSham stimulation randomized across the three laboratory sessions) to modify cognitive functioning (MoCA score), and oscillatory brain activity during performing personalized, autobiographical memory (ABM) tasks and resting-state EEG. | Device: Transcranial alternating current stimulation (tACS)<br>* tACS will be delivered by a battery-driven current stimulator Starstim SS32 (Neuroelectrics) through surface Ag/AgCl electrodes placed into holes of a neoprene cap corresponding to the international 10/20 EEG system. Gel (Parker Lab, Inc.) will be applied to optimize signal conductivity and lower impedance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spatiotemporal dynamic changes measured with electroencephalography (hdEEG) | Changes in spatiotemporal dynamics in different frequency bands (theta, alpha, beta, gamma) will be assessed with hdEEG | up to 30 minutes | 
| Cognitive Assessment | The Montreal Cognitive Assessment (MOCA) will be administered to characterize the cognitive status | baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autobiographical memory (ABM), high-density electroencephalography (EEG), magnetic resonance imaging (MRI), non-invasive brain stimulation (NIBS), transcranial alternating current stimulation (tACS)