Effects of in-Scanner Bilateral Frontal tDCS on Functional Connectivity of the Working Memory Network in Older Adults

Abstract

Working memory is an executive memory process essential for everyday decision-making and problem solving that declines with advanced age. Transcranial direct current stimulation (tDCS) is a non-invasive form of brain stimulation that has demonstrated potential for improving working memory performance in older adults. However, the neural mechanisms underlying effects of tDCS on working memory are not well understood. This mechanistic study investigated the acute and after-effects of bilateral frontal (F3/F4) tDCS at 2 mA for 12-min on functional connectivity of the working memory network in older adults. We hypothesized active tDCS over sham would increase frontal connectivity during working memory performance. The study used a double-blind within-subject 2 session crossover design. Participants performed an functional magnetic resonance imaging (fMRI) N-Back working memory task before, during, and after active or sham stimulation. Functional connectivity of the working memory network was assessed within and between stimulation conditions (FDR < 0.05). Active tDCS produced a significant increase in functional connectivity between left ventrolateral prefrontal cortex (VLPFC) and left dorsolateral PFC (DLPFC) during stimulation, but not after stimulation. Connectivity did not significantly increase with sham stimulation. In addition, our data demonstrated both state-dependent and time-dependent effects of tDCS working memory network connectivity in older adults. tDCS during working memory performance produces a selective change in functional connectivity of the working memory network in older adults. These data provide important mechanistic insight into the effects of tDCS on brain connectivity in older adults, as well as key methodological considerations for tDCS-working memory studies.

Effects of Transcranial Direct Current Stimulation Paired With Cognitive Training on Functional Connectivity of the Working Memory Network in Older Adults

“…No improvements in behavior were observed after sham stimulation on either task difficulty level. Nissim et al (2019) identified significantly increased functional connectivity between two frontal working memory ROIs during an acute single session of active stimulation while participants performed a 2-Back task (Nissim et al, 2019). Both the prior study and the current study only demonstrated significant changes in connectivity during the more challenging 2-Back and not the less challenging 0-Back task with active stimulation.…”

“…A growing body of evidence demonstrates that 2 mA produces a net increase in excitability under the anode and cathode electrodes (Batsikadze et al, 2013;Mosayebi et al, 2019;Nissim et al, 2019). We chose this montage to elicit excitability under both the anode and cathode electrodes which is supported by prior behavioral and connectivity findings with tDCS using this same montage (Nissim et al, 2019;Soyata et al, 2019). Figure 2 demonstrates a computational model of expected current flow for the bilateral frontal montage that was used in this study.…”

“…Conventional 1 × 1 tDCS (Soterix Medical, tDCS-CT for clinical trials) was applied at 2 mA intensity using two 5 × 7 cm 2 saline-soaked Soterix sponge electrodes (0.9% NaCl; 4 mls per side, 8 ml total/sponge) at F3 (cathode) and F4 (anode) location, approximately over left and right DLPFC, respectively. A growing body of evidence demonstrates that 2 mA produces a net increase in excitability under the anode and cathode electrodes (Batsikadze et al, 2013;Mosayebi et al, 2019;Nissim et al, 2019). We chose this montage to elicit excitability under both the anode and cathode electrodes which is supported by prior behavioral and connectivity findings with tDCS using this same montage (Nissim et al, 2019;Soyata et al, 2019).…”

“…While tDCS paired with cognitive training has shown promise for enhancing working memory function in older adults, the underlying neural mechanisms of these effects are not yet well understood (Jones et al, 2015;Stephens and Berryhill, 2016). In a recent study, we demonstrated that tDCS delivered bilaterally to the frontal lobes (F3/F4) increases functional connectivity between left ventrolateral prefrontal cortex (VLPFC) and left DLPFC in older adults during performance on a working memory task (Nissim et al, 2019). However, these effects were only evident during active stimulation and not immediately after stimulation was stopped (i.e., after-effects).…”

“…Declines in working memory are commonly observed in older adults and, consequently, may cause significant negative impacts to activities of daily living and functional independence (Mograbi et al, 2014). Structural and functional changes of brain regions within the working memory network are known to occur with advanced age and have been associated with working memory decline (Cabeza et al, 2002;Nissim et al, 2017Nissim et al, , 2019. Thus, there is a strong need to identify targeted interventions that can enhance working memory processes in older adults.…”