Covid-19, Funding ended

This is an administrative supplement to an existing project "Using fMRI-guided TMS to increase central executive function in older adults: NCT02767323" This award allows extending our existing fMRI-TMS paradigm to patients with a prodromal form of Alzheimer's Disease (AD) known as amnestic Mild Cognitive Impairment (MCI), and investigate the role of brain health factors in mediating the TMS-related memory performance benefits associated with communication between a network of frontoparietal brain regions in these populations.

The focus on focal neurostimulation at only a single site represents a fundamental gap in the approach of memory-based neurostimulation therapies. Neurostimulation affects multiple sites within a cortical network, but these global effects have not been used as targets for stimulation because of limited knowledge about what influence these localized sites have on global changes in brain state. To address this problem, multimodal neuroimaging tools and network modeling approaches developed though the parent U01 project will be used, to demonstrate how focal neurostimulation improves the efficacy of TMS for enhancing memory function. These goals will be addressed in the Administrative Supplement under our two specific aims. First, network-guided TMS will be applied to optimize memory success based in the frontoparietal network (FPN) in a new group of MCI patients. A new form of TMS targeting that involves modeling of the global network to understand how the controllability of a stimulation site evokes changes in widespread brain networks will be tested. Second, structural and functional factors affecting the efficacy of individualized network-guided TMS will be identified to ameliorate deficits in MCI. By creating a multimodal model of neural deficits related to MCI, network-guided TMS will be adjusted to demonstrate how the MCI brain might compensate for these neural deficits. The parent U01 project has made foundational advances towards these goals, as we have demonstrated the ability of to selectively enhance and reduce working memory performance in healthy older adults. In the current Administrative Supplement this paradigm will be extended to a group of MCI participants in order to test the hypothesis that excitatory rTMS to the working memory network can provide positive outcomes for patients with pre-clinical AD. The proposed work will provide an important tool for studying the stability and controllability of network connectivity of memory states in the aging brain, as well as new information on the effectiveness of brain stimulation technologies as a therapeutic approach for cognitive decline.

Inclusion Criteria:

• English Speaking
• willing to provide consent
• signed HIPAA authorization
• clinical consensus for MCI; and/or met inclusion criterial on MoCA, ApoE.

Exclusion Criteria:

• History of any I DSM IV disorder that is unstable or untreated
• current or past history of substance abuse or dependence (excluding nicotine)
• women who are pregnant or breast feeding
• intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes
• increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma greater than mild concussion (History of significant head trauma, including with loss of consciousness for ≥ 30 minutes, alteration of consciousness for up to 24 hours following the event, or post-traumatic amnesia) in the past 10yrs or head injury received after age 65
• Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; cerebral aneurysm , Dementia, Huntington chorea, multiple sclerosis
• Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that are on the strong potential hazard list for rTMS.
• Subjects taking medications with an ACB score of 3.

These participants only performed the behavioral task. No TMS was applied.

adverse event data are collected during rTMS and a few minutes after.

rTMS was not applied so no adverse event/ all cause mortality were monitored