Frequency‐specific neuromodulation of local and distant connectivity in aging and episodic memory function

Abstract

A growing literature has focused on the brain's ability to augment processing in local regions by recruiting distant communities of neurons in response to neural decline or insult. In particular, both younger and older adult populations recruit bilateral prefrontal cortex (PFC) as a means of compensating for increasing neural effort to maintain successful cognitive function. However, it remains unclear how local changes in neural activity affect the recruitment of this adaptive mechanism. To address this problem, we combined graph theoretical measures from functional MRI with diffusion weighted imaging and repetitive transcranial magnetic stimulation (rTMS) to resolve a central hypothesis: how do aged brains flexibly adapt to local changes in cortical activity? Specifically, we applied neuromodulation to increase or decrease local activity in a cortical region supporting successful memory encoding (left dorsolateral PFC or DLPFC) using 5 or 1 Hz rTMS, respectively. We then assessed a region's local within-module degree, or the distributed between-module degree (BMD) between distant cortical communities. We predicted that (1) local stimulation-related deficits may be counteracted by boosting BMD between bilateral PFC, and that this effect should be (2) positively correlated with structural connectivity. Both predictions were confirmed; 5 Hz rTMS increased local success-related activity and local increases in PFC connectivity, while 1 Hz rTMS decreases local activity and triggered a more distributed pattern of bilateral PFC connectivity to compensate for this local inhibitory effect. These results provide an integrated, causal explanation for the network interactions associated with successful memory encoding in older adults. Hum Brain Mapp 38:5987-6004, 2017. © 2017 Wiley Periodicals, Inc.

Network Models Predict That Pyramidal Neuron Hyperexcitability and Synapse Loss in the dlPFC Lead to Age-Related Spatial Working Memory Impairment in Rhesus Monkeys

“…How do age-related changes in synaptic plasticity, discussed below, affect DRT performance? Might neuromodulation (Arnsten et al, 2012;Davis et al, 2017;Wang et al, 2019) during working memory task performance reduce the pyramidal neuron hyperexcitability observed in vitro? Computational models provide an essential means for testing and refining hypotheses as future data become available.…”

Mapping the organization and dynamics of the posterior medial network during movie watching

“…Connectomes were generated by using FLIRT to apply a linear registration to a 471-region subparcellated version of the Harvard-Oxford atlas (HOA) (Davis et al, 2017) to register it to each subject's native diffusion space. The sub-parcellated HOA has the advantage of full cortical and subcortical coverage and relatively uniform, isometric ROI sizes.…”

A Systematic Review of Non-invasive Brain Stimulation Applications to Memory in Healthy Aging

“…Davis et al (53) used rTMS at lower frequencies of either 1 or 5 Hz in the left DLPFC and did not identify any subsequent changes in word-pair association memory. Using functional Magnetic Resonance Imaging (fMRI), Davis et al did however find changes in neural activity following differing stimulation conditions.…”

“…A final 2 studies examined the effects of rTMS on associative memory performance (53,60). Manenti et al (60) applied rTMS (20 Hz) to either the left or right DLPFC during encoding or recalling of word-pairs and found that stimulation significantly impeded word-pair recall accuracy.…”