Objective: We aimed to modulate working memory (WM) in patients with MCI with Lewy bodies (MCI-LB) by non-invasive stimulation of the striatum with or without cerebellar stimulation.

Background: In prodromal stages of Lewy Body Dementia (LBD), working memory dysfunction is associated with impaired attentional filtering and reduced storage capacity, the former primarily due to the degeneration of dopaminergic terminals in the striatum. Transcranial temporal interference stimulation (tTIS) offers a promising solution to modulate deep brain structures. Given the cerebellum’s role in cognitive processes, we further investigated possible interactions of cerebellar TMS with striatal tTIS to modulate working memory in MCI-LB.

Method:

Twenty patients with MCI-LB, age 70.5 ± 6.8 years participated in a double-blind, randomized, sham-controlled crossover trial. The intermittent theta burst stimulation (iTBS) of the inferior cerebellum was followed by three blocks of theta-burst patterned tTIS targeting the striatum. The visual working memory task (vWMT) was administered before, during, and after each session to assess the impact of distraction while maintaining a constant WM load (distraction condition) and the additional costs of high WM load (high load condition). Statistical analysis was performed using linear mixed models (LMM).

Results: We  showed that the combined cerebellar iTBS and striatal tTIS approach significantly improved performance in the distraction condition of the vWMT task compared to both the control condition and striatal tTIS alone (p < 0.01). No significant differences were observed between stimulation protocols for reaction times.

Conclusion: The combined approach of cerebellar iTBS and striatal tTIS significantly enhanced performance in tasks requiring attentional filtering, demonstrating the potential of this dual-stimulation method to effectively target deep brain structures and improve cognitive function in MCI-LB patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/modulation-of-working-memory-in-prodromal-dlb-by-non-invasive-brain-stimulation-of-the-striatum-and-cerebellum/