Dementia Care Research and Psychosocial Factors

Background: Repetitive transcranial magnetic stimulation enhances cognition in people with mild cognitive impairment (MCI). Whereas conventional treatment requires daily sessions for 4-6 weeks, accelerated intermittent theta burst stimulation (iTBS) shortens the treatment course to just 3 days, substantially improving feasibility of use in people with MCI. We conducted a Phase I safety and feasibility trial of iTBS in MCI, finding preliminary evidence of cognitive improvement. Here, we explore the neural mechanism of this effect by evaluating iTBS-related changes in functional connectivity in relation to the observed cognitive change.

Method: Twenty-two patients with amnestic MCI received iTBS to left dorsolateral prefrontal cortex (l-dlPFC) over 3 treatment days (with 8 stimulation sessions of 600 pulses per day) within 1 week. Nineteen had complete MRI and cognitive testing data. The primary cognitive outcome was the fluid cognition composite score from the NIH Toolbox Cognition Battery. We computed functional connectivity from resting-state fMRI and calculated participation coefficient for three regions of interest. Lower participation coefficient values indicate that a region is more selectively connected to its own network and higher values indicate that it is more widely connected across networks (i.e., a "hub"). We calculated change in participation coefficient from pre- to post-treatment for two regions belonging to the frontoparietal network (the l-dlPFC iTBS target and the contralateral right dlPFC) and a negative control (primary visual; V1).

Result: There was a significant, large effect-size (d = 0.98) improvement in fluid cognition from pre- to post-iTBS treatment. Improvements in cognition were significantly associated with increased participation coefficient of l-dlPFC (r = .52, p = .022), with a marginal effect in r-dlPFC (r = .41, p = .084) and a near zero effect in the negative control V1 (r = .03, p = .898).

Conclusion: This preliminary investigation suggests that iTBS-related cognitive improvement in MCI may be attributable to increased connectivity of the stimulated frontoparietal network. Specifically, a larger increase in "hubness" (i.e., connectivity across multiple networks) of the l-dlPFC target region is associated with greater cognitive gains. However, as these analyses are based on a limited number of regions and small sample, future studies are needed to further evaluate the neural mechanisms of iTBS in MCI.