Dementia is a leading cause of disability among people over 65 years in modern aging world and has become a major public health concern as the world population ages (Jia et al., 2020; Toyama et al., 2019). Vascular dementia (VD) is a prevalent form of dementia, second only to Alzheimer's disease (AD) (Kalaria et al., 2023; O'Brien and Thomas, 2015). Long-term chronic cerebral hypoperfusion (CCH) is a fundamental pathophysiological feature of VD, contributing to cognitive dysfunction through complex molecular and signaling pathways mechanisms (Song et al., 2023; Yu et al., 2022). Despite significant progress has been made in the research of treatment for VD over past decades, there remains a lack of licensed treatment strategies for VD in clinic (Eguchi et al., 2018; Linh et al., 2022; Song et al., 2023). Therefore, adopting novel and effective treatment strategies for VD is a major public health problem to be solved urgently.

In addition to traditional pharmacological therapy, recent studies have found significant potential for non-invasive brain stimulation techniques serving as effective therapeutic approaches to VD. Low-intensity focused ultrasound stimulation (LIFUS), an emerging non-invasive brain stimulation technique, has rapidly developed in treating neurological diseases due to its advantage of excellent targeting, penetration depth and spatiotemporal resolution (Darmani et al., 2022; Hu et al., 2023; Kim et al., 2021; Qin et al., 2024; Trenado et al., 2023). LIFUS has shown promise in the exploration of novel treatments for VD, and several preclinical studies have found that LIFUS has a certain improvement effect on VD models (Eguchi et al., 2018; Huang et al., 2017; Pei et al., 2024; Song et al., 2023; Wang et al., 2022). However, the regulatory effects of LIFUS on neural activities in the stimulation target brain region, as well as in the upstream and downstream brain regions of the VD model remain unclear. Currently, research on the treatment of neurological diseases using LIFUS, relies on behavioral indicators to assess therapeutic effects, often in the absence of objective measures. The two limitations mentioned above may hinder the clinical translation and application of LIFUS in the future. Therefore, further investigation into the neural network mechanisms underlying LIFUS treatment for VD, as well as the identification of objective indicators to assess its therapeutic effects, is significant.

Hippocampal neural oscillation modes are associated with cognitive function and the perturbation of them underlies cognitive dysfunctions in VD (Wang et al., 2017a; Xu et al., 2015; Xu et al., 2013; Zheng et al., 2020). Changes in the neural oscillation modes of hippocampus CA3-CA1 pathway, which plays a crucial role in learning and memory, contribute to memory deficits induced by cerebral ischemia (Wang et al., 2017a; Xu et al., 2015; Zheng et al., 2020). Recent studies have shown that neural oscillation modes can be non-invasively modulated by rhythmic light flicker and attenuate cognitive dysfunctions in rodent models of AD and VD (Adaikkan et al., 2019; Etter et al., 2019; Iaccarino et al., 2016; Martorell et al., 2019; Zheng et al., 2020). These findings suggest that modulating neural oscillation modes can recover cognitive dysfunctions. Currently, LIFUS have be found that can modulate the neural oscillation in in different brain regions of both health animal and disease models including AD, depression, Parkinson's disease (PD) (Tufail et al., 2010; Wang et al., 2023; Wang et al., 2020; Wang et al., 2019a; Wang et al., 2019b; Yang et al., 2024; Yuan et al., 2016). However, the role of neural oscillation modes between CA3-CA1 pathway in LIFUS treating VD is unclear. Therefore, the present study aimed to determine changes of neural oscillation modes between CA3-CA1 pathway in LIFUS treating VD.

In addition to the hippocampus, the neural oscillation modes of medial prefrontal cortex (mPFC) are also crucial for various cognitive functions including working memory and long-term memory (Abubaker et al., 2021; Xu et al., 2019). Moreover, the synchronized activity between the hippocampus and mPFC, driven by neural oscillation patterns, is equally important in learning and memory processes (Cohen, 2011; Eichenbaum, 2017; Shin and Jadhav, 2016). Aberrant dynamics in the hippocampus-mPFC circuit are observed in a range of neurological disorders, but these changes can be effectively reversed after noninvasive brain stimulation or drug therapy (Peng et al., 2023; Shing et al., 2022; Wang et al., 2023). Although the neural oscillation modes in hippocampus-mPFC are important in the cognitive process, the role in cognitive dysfunction induced by VD is not clear. Consequently, the second aim of this study is to explore changes of neural oscillation modes between hippocampus-mPFC pathway in LIFUS treating VD. Additionally, neural oscillation modes in different brain regions, which have been applied in the clinical diagnosis and monitoring of various neurological diseases, may serve as a suitable indicator for objectively evaluating the therapeutic effects of LIFUS in treating VD (Darmani et al., 2022; Moradi et al., 2023; Sarica et al., 2022). Therefore, the third aim of the present study is to explore the feasibility of using neural oscillation patterns as an objective indicator of the effectiveness of LIFUS in treating VD.