Frequency-specific neuromodulation of local and distant connectivity in aging & 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 (fMRI) with diffusion weighted imaging (DWI) and repetitive transcranial magnetic stimulation (rTMS) in order 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 prefrontal cortex or DLPFC) using 5Hz or 1Hz rTMS, respectively. We then assessed a region's local within-module degree (WMD), or the distributed between-module degree (BMD) between distant cortical communities. We predicted that (1) local stimulationrelated 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; 5Hz rTMS increased local success-related activity and local increases in PFC connectivity, while 1Hz 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. 2012), motor coordination (Heuninckx et al., 2008), and working memory (Reuter-Lorenz et al., 2000). This effect follows the more general observation of age-related reductions in core tasknetwork regions coupled with an increase in secondary task-network areas Nyberg et al., 2010), but may also be a specific example of adaptive efficiency in the aging brain. While the prevalence of this pattern in aging studies is widespread, the evidence that this effect benefits performance is mixed, and contralateral recruitment may only be effective if the additional cortical processors brought to bear on the task can play a complementary role in task performance (Colcombe et al., 2005). Such a model of the aging brain proposes that over the years, cortical messages are increasingly dominated by top-down predictions, and less by sensory inputs (Moran et al., 2014). This is consistent with the agerelated shift to PFC activation, and bilateral PFC activity is a likely consequence of this adaptive shift, given that every PFC region is connected to its contralateral homologue by at least one synapse (Aboitiz et al., 1992;Aboitiz and Montiel, 2003). Nonetheless, while correlational studies have observed that PFC regions over-recruited by OAs often show stronger long-ran...

Frequency‐specific noninvasive modulation of memory retrieval and its relationship with hippocampal network connectivity

“…Mechanisms for network‐level effects of TMS are not fully understood. Compensation‐oriented explanations propose that networks “compensate” against changes in local activity due to stimulation, such that local excitation of regions with positive connections to a network will result in network connectivity reductions, and vice versa for local inhibition (Cocchi et al, ; Davis, Luber, Murphy, Lisanby, & Cabeza, ; Eldaief et al, ; Fox et al, ; Steel et al, ). θ‐burst is considered inhibitory and iθ‐burst and β‐freq are both considered excitatory, based primarily on cortico‐motor effects (Chen et al, ; Huang et al, ; Pascual‐Leone et al, ), and the parietal area we stimulated has positive connectivity with the HCN.…”

“…will result in network connectivity reductions, and vice versa for local inhibition (Cocchi et al, 2015;Davis, Luber, Murphy, Lisanby, & Cabeza, 2017;Eldaief et al, 2011;Fox et al, 2012;Steel et al, 2016).…”

Older adults benefit from more widespread brain network integration during working memory

“…Where Ζ ̅ is the mean r-values between nodes of one partition, module, or system (similar to within-266 module degree or WMD), and Ζ ̅ is the mean of r-values between nodes of separate partitions (similar 267 to between-module degree or BMD, Davis et al, 2017). Accordingly, values greater than 0 reflect relatively lower between-system correlations in relation to within-system correlations (i.e., stronger 269 integration of systems), and values less than 0 reflect higher between-system correlations relative to 270 within-system correlations (i.e., diminished integration of systems).…”

Structural controllability predicts functional patterns and brain stimulation benefits associated with working memory

“…rTMS therefore provides an ideal means to test the assumption that a localized change in energy to a modal controller could affect a global change in brain states and concomitant behavior. The effects of neuromodulation are typically observed not only in the stimulated site, but also in distal connected regions (Bestmann et al, 2004;Davis et al, 2017;Ruff et al, 2008;Wang et al, 2014;Wang et al, 2018), and thus the controllability framework offers an opportunity to test the hypothesis that network-level activation due to exogenous neuromodulation can be estimated by the network properties of the stimulated site (Muldoon et al, 2016;Spiegler et al, 2016).…”