TMS for Investigating Memory Facilitation

The aim of this study is to investigate the effects of Transcranial Magnetic Stimulation (TMS) following a Paired Associative Stimulation (PAS) protocol on the memorization capacity of elderly individuals. For this purpose, we will apply TMS synchronized with a working memory (WM) task and assess its effects on cortical connectivity and memorization capacity by Magnetic Resonance Imaging (MRI) and WM task learning. This study will be carried out in an older population of healthy participants. We will use the study results to refine the task related PAS protocol towards enhancing memory performance and brain connectivity.

The fundamental objective is to evaluate the changes derived from the specific Paired Associative Stimulation (PAS) protocol applying Transcranial Magnetic Stimulation (TMS) towards the hippocampus to enhance memory in an older population. We will evaluate the following effects: 1) Changes in memory capacity using task performance of the working memory (WM) task and calculating the correctly memorized items; and 2) Changes in brain connectivity using resting state functional Magnetic Resonance Imaging (rs-fMRI) and comparing the correlated activity between areas related to the process of memorization.

In order to understand the memory and brain connectivity changes derived from the PAS intervention more specifically, we will characterize the stimulation localization, the Inter Stimulus Interval (ISI) timing and rule out training and placebo effects. To research if the PAS effects are specific to the stimulated brain area, we will conduct a control group in which stimulation will be delivered to the primary motor area (M1). Then, we will compare the outcome measures (changes in memory capacity and brain connectivity) between the different brain areas. To characterize the ISI, our goal is to calculate the synchronization timing that triggers cortical plastic changes. Thus, we will test two different ISI between the TMS pulse delivery and memorization task. Finally, to differentiate the effects that are derived from the PAS versus the effects from repetition of the task or placebo effects, we will conduct another control group with Sham TMS stimulation and reproduce the same experimental procedures as the group that receives the TMS stimulation. Sham TMS is used in this study to compare if brain stimulation (active TMS) can help improve memory compared to receiving no brain stimulation (sham TMS).

Eligibility Criteria:
Inclusion Criteria for Older Healthy Participants:

* Age from 60 to 85 years, inclusive (For piloting purposes, this inclusion criteria may vary).
* No history of a brain and/or skull lesion (e.g., stroke)
* Normal vision (can be corrected)
* Able to understand and give informed consent
* No neurological disorders
* Able to understand and speak English

Exclusion Criteria for Healthy Participants:

* Cardiac pacemaker or pacemaker wires; neurostimulators; implanted pumps
* Metal in the body (rods, plates, screws, shrapnel, dentures, IUD) or metallic particles in the eye
* Surgical clips in the head or previous neurosurgery
* Any magnetic particles in the body
* Cochlear implants
* Prosthetic heart valves
* Epilepsy or any other type of seizure history
* History of significant head trauma (i.e., extended loss of consciousness, neurological sequelae)
* Significant claustrophobia
* Ménière's disease
* Pregnancy or breast feeding
* Non prescribed drug use
* History of current substance abuse (exception: current nicotine use is allowed)
* Marijuana
* Any neurological diagnoses
* Dementia; severe depression; or prior neurosurgical procedures
* Tremor or parkinsonism, or psychiatric disease that would interfere with study procedures for TMS, or MRI.
* Significant other disease (cardiological or heart disease, renal, hepatic, malignant tumors, mental or psychiatric disorders) that would prevent participants from fully engaging in study procedures
* Prisoners
* Medications contraindicated for TMS: antipsychotic and antidepressant medications.