Neuromodulation and fMRI in Neurodegenerative Diseases Study

The participants will first be scanned on a 3T MRI system (at Sunnybrook Health Sciences Centre) using a multi-channel receive head coil.

The MRI protocol will comprise a T1-weighted structural scan to provide anatomical information and guide prescription of the geometry of subsequent functional scans and subsequent tACS montage (stimulation electrode geometry). Next, a Chemical Exchange Saturation Transfer (CEST) sequence will be run. CEST is a non-invasive alternative to positron emission tomography (PET) imaging that will allow us to make measurements of cerebral metabolism. Glucosamine will be used as an orally administered contrast agent. The next sequence of the MRI protocol will be the resting state blood-oxygenation level dependent (BOLD) fMRI, examining brain function while the patient is idle (i.e., not performing a specific task). Finally, a pseudo-continuous arterial spin labeling (pCASL)/BOLD fMRI sequence will be acquired during which participant may intermittently hear a variety of sounds and be asked to perform a simple memory task, inducing stimulus/task processing related neuronal activations in the brain. The pCASL sequence uses radiofrequency (RF) fields to magnetically "tag" blood in the carotid arteries, thus allowing estimation of cerebral blood flow.

EEG recordings will be performed after the MRI scan. Participants will have electrodes affixed to their scalp with a water soluble paste. After electrode application, participants will be escorted to a sound-attenuating chamber for testing. The participant will be seated in a comfortable reclining chair. Instructions will be given to the subject and testing started shortly after. Testing procedures will include monitoring brain responses to sounds or during performance of the aforementioned simple memory task. Sounds will be presented at a comfortable listening level though headphones or speakers.

After the initial baseline MRI and EEG have been acquired, participants will receive 20 minutes of tACS. The tACS will be delivered via a high definition-tACS system (Soterix Medical, New York, NY). The system is currently approved by US Federal Law as an investigational device. The system includes a cap with 32 electrodes that can be used to deliver stimulation. The electrodes will be chosen through finite head modelling to best stimulate the occipitoparietal cortex. The intensity of stimulation delivered through each electrode will not exceed 3 mA, as prescribed by the hardware-based safety limits.

The participants will undergo post-tACS imaging, on the first and final days of treatment administration and at a 1-month follow up visit, using the same sequences as in the baseline scans described above.

Inclusion criteria

• Be at least 25 years of age;
• Have no contraindications to MRI
• Have received 8 or more years of formal education
• Be fluent in English
• Cohort a. must be followed at Sunnybrook Health Sciences Center

Cohort a:

• Have been diagnosed with a suspected neurodegenerative disorder or traumatic brain injury (TBI) with memory deficits impacting functional status
• In case of TBI, cognitive impairment has persisted at least three months post-injury
• Received score of 16 or lower on the Mini Mental State Examination (MMSE)

Cohort b:

• Have no prior diagnosis of a neurodegenerative disorder or post-traumatic brain injury cognitive deficits
• Be experiencing healthy aging and be age and sex matched to Cohort a.

Exclusion criteria

• Have any contraindications to MRI
• Be pregnancy
• Have any major comorbid medical conditions (as determined by investigators - e.g., comorbid neurological diseases, uncontrolled hypertension or diabetes, malignancy) or major comorbid psychiatric conditions (as determined by investigators - e.g., schizophrenia or bipolar disorder)