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

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.