Closed-Loop Brain Stimulation as a Potential Intervention for Cognitive Decline

Closed-Loop Brain Stimulation as a Potential Intervention for Cognitive Decline

The goal of this clinical study is to investigate the effectiveness of non-invasive stimulation to enhance cognitive control abilities in cognitively healthy adults and older adults diagnosed with mild cognitive disorder (MCI). The main questions it aims to answer are:

• whether it is possible to restore various cognitive functions in older adults diagnosed with MCI by delivering theta burst stimulation (TBS), a form of transcranial magnetic stimulation, and
• whether closed-loop TBS is able to induce therapeutic benefits that outperform open-loop TBS.

Participants play a cognitive video game while a brain-computer interface (BCI) analyzes their electroencephalogram (EEG) signals and decodes the presence or absence of the contingent negative variation (CNV) potential, a marker of cognitive control. The BCI triggers TBS when its outputs indicate that the participant is not engaged properly in the video game.

Researchers will compare the effects of sham, closed-loop, and open-loop TBS using the outcome metrics described below to see how much cognitive restorations is achievable with each stimulation modality.

Inclusion Criteria:

• Cognitively normal younger adults

  1. Ages between 18 to 35 years
  2. Good general health
  3. Normal or corrected vision
  4. Completed elementary school education or able to understand middle school level experiment instructions

• Cognitively normal older adults

  1. Ages between 60 to 90 years
  2. Good general health
  3. Normal or corrected vision
  4. Completed elementary school education or able to understand middle school level experiment instructions
  5. Score of 23 or higher on the Montreal Cognitive Assessment, a brief formal cognitive screening test, which is used to indicate absence of cognitive impairment

• Older adults with mild cognitive impairment (MCI)

  1. Ages between 60 to 90 years
  2. Diagnosis of MCI according to the National Institute on Aging - Alzheimer's Association (NIA-AA) criteria
  3. Good general health
  4. Normal or corrected vision
  5. Completed elementary school education or able to understand middle school level experiment instructions

Exclusion Criteria:

1. Neurological or psychiatric diseases (e.g., personal history of epilepsy/seizure brain damage, multiple sclerosis, schizophrenia, substance use disorder, etc.).
2. Current use of psychotropic medications with cognitive side effects (e.g., benzodiazepines, anticonvulsants, antipsychotics, etc.)
3. Current use of cognitive enhancing medications (e.g., Adderall, Memantine, etc.)
4. Factors hindering EEG acquisition and TMS delivery (e.g., skin infection, wounds, dermatitis, etc.)
5. Factors hindering MRI acquisition (e.g., implants, metallic tattoos, etc.)