Neuromodulation and fMRI in Neurodegenerative Diseases Study

Mild Cognitive Impairment, Neurodegeneration, Traumatic Brain Injury

Transcranial Alternating Current Stimulation, Neuromodulation, Functional Magnetic Resonance Imaging, Cognitive Assessment

In addition to neuronal loss, dysfunction in brain network connectivity has been identified as a correlate of cognitive deficits in neurodegenerative and post-traumatic brain injury states. Transcranial alternating current stimulation (tACS) has been suggested as a promising, non-invasive, method of normalizing network connectivity and hence improving cognition, notably memory. This study will examine the efficacy of tACS at improving working memory performance in patients with neurodegeneration and its correlation to changes in network connectivity, based on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) imaging data.

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.

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