A Mechanistic Study to Investigate tDCS and Working Memory in MCI Patients

The current study is a mechanistic study to evaluate working memory gains with transcranial direct current stimulation (tDCS) in older adults with mild cognitive impairments (MCI) compared to cognitively healthy control. This study is funded by a mentored career award (The University of Florida, Clinical and Translational Science Institute [CTSI] Pilot Award) and thus the mentors (Drs. Cohen, DeKosky, Woods, Fang) are listed as additional Principal Investigators in this study. The proposed study investigates the effects of acute (one-time) tDCS application on working memory gains (i.e., behavior and functional) by evaluating brain structure and cognitive function relationships. tDCS is a method of non-invasive brain stimulation that directly stimulates brain regions involved in active cognitive function and enhances neural plasticity when paired with a training task. A mechanistic, in-scanner, crossover design tDCS study (active and sham stimulation) with 2milliamps (mA) fixed dosing application will enroll 110 participants comprising 55 cognitively normal/healthy older adults and 55 older adults with MCI. The study will employ multi-modal neuroimaging (structural and functional data), person-specific computational models, and machine learning to elucidate acute tDCS effects on working memory. Change in cognitive function (i.e., working memory performance) will be quantified using working memory tasks and magnetic resonance imaging (MRI). The investigators will compare changes in working memory performance resulting from active tDCS versus sham tDCS during 2-back task compared to 0-back task.

The investigators will test the following hypotheses:

• Acute tDCS will increase working memory performance during active tDCS and larger degree of brain atrophy seen in MCI patients will significantly decrease current intensity in stimulated brain regions.
• Acute tDCS will significantly increase functional connectivity within the working memory network during active tDCS but not sham.

To date, no studies have examined acute tDCS application in MCI cohort and directly comparing results to cognitively healthy cohort. The present study will provide insight into mechanisms underlying tDCS application in MCI population for combating cognitive decline in a rapidly aging population in the United States. Information gathered from this study may guide future intervention strategies to combat cognitive decline and improve the quality of life of aging population.

Inclusion criteria

• Age 60-95 years
• Montreal Cognitive Assessment (MoCA) score 18 and above (scores will be adjusted for education)
• Able to receive electrical stimulation
• Ability to comprehend conversational voices
• Adequate motor capacity to operate computer mouse and click-button in-scanner
• Ability to participate in the intervention and attend training sessions Exclusion Criteria
• Failure to provide informed consent
• Contraindications to MRI recording (e.g., any kind of ferrous metallic stents or ferrous metal objects in the body, heart valve prosthesis, or other metal implants, claustrophobia, neurostimulation system, defibrillator, pacemaker, or other implanted device)
• Left-handed, or left hand dominant
• History of neurological, seizures, and psychiatric disorders, traumatic brain injury, incidence of stroke involving large vessel
• Terminal illness with life expectancy less than 12 months, as determined by physician
• Brain tumor or malformation or any foreign body known or previously identified in brain
• Cancer in active treatment, besides skin cancer
• Currently on GABAergic or glutamatergic medications, or on calcium or sodium channel blockers, which alter or block the ability of tDCS to facilitate tissue excitability
• Unable to communicate because of severe hearing loss or speech disorder
• Severe sensory impairment
• Inability to communicate in English
• Severe visual impairment, which would preclude completion of the assessment and/or intervention
• No physical impairment precluding motor response or lying still for an hour in the scanner that could confound study findings
• Moderate-to-severe depressive symptoms as defined by scoring 10 or above on the Geriatric Depression Scale (GDS)