## 4 Discussion  
In this experimental work, we clearly demonstrate an efficiency of a novel method of stimulation of clearance of F\(\alpha\beta\) from mouse brain using noninvasive music-induced OBBB. The A\(\beta\) is present in the brain fluids and is regarded as a metabolic waste product [45]. For the last three decades, the A\(\beta\) hypothesis, which posits A\(\beta\) deposition as a key initial step in the pathogenesis of AD, has been the dominant theory driving treatment development [46]. While the role of A\(\beta\) burden in the development and progression of clinical symptoms remains unclear and is under active investigation, the A\(\beta\) plaque clearance has been a key target of numerous clinical trials. Results to date have largely been disappointing [47; 48], although one recent trial linked a significant reduction in A\(\beta\) to the stabilization of cognitive decline at 1 year [49]. Therefore, strategies that prevent A\(\beta\) accumulation in the brain could promote healthy brain aging and be useful in preventing AD. We revealed here that music-induced OBBB stimulates endogenous drainage and clearing processes in the mouse brain. Indeed, using in vivo and ex vivo fluorescence microscopy, we observed that spreading of F\(\alpha\beta\) in CSF was higher in mice with OBBB vs. IBBB. Using an MRI analysis of the distribution of Omniscan in the mouse brain, we also found that the distribution of the tracer was higher in mice with OBBB vs. IBBB. Our results are consistent with human data suggesting that OBBB by FUS stimulates an effective clearance of soluble A\(\beta\) from the brain of patients with AD that is associated with a significant improving of their cognitive status [14]. The mouse models of amyloidosis also show that FUS reduced the level of A\(\beta\) in the brain, triggered neural plasticity, and prevented spatial memory deficit [17; 18; 19]. The mechanisms by which A\(\beta\) is cleared from the brain are not fully understood, although there is evidence that MLVs play an important role in removing A\(\beta\) from the brain of humans and animals [7; 11]. We investigated removing of A\(\beta\) from the mouse brain via the meninges into dcLNs, which are the first anatomical station of CSF exit and the place of accumulation of molecules excreted from the brain [5; 23]. Our results revealed that the level of the fluorescent signal from F\(\alpha\beta\) in both the meninges and dcLNs was significantly higher in mice with OBBB compared with mice with IBBB. These data suggest that OBBB is associated with an activation of lymphatic clearance of F\(\alpha\beta\) from the mouse brain. In our previous investigations, we showed that music-induced OBBB is accompanied by fast removing of fluorescent dextran 70 kDa after its crossing of OBBB [23]. We hypothesize that OBBB contributes to changes in PVS and in the extracellular spaces due to a transport via OBBB soluble molecules and fluids (Figure 2). Similar scenario is observed during sleep when the volume of PVSs increases in 60% [50]. These changes are strongly associated with the activation of clearance of A\(\beta\) from the brain [50]. Opposite, wakening dramatically reduces the volume of PVS that is accompanied by the accumulation of A\(\beta\) in the brain [50,51]. We assume that OBBB-induced changes in drainage of the brain tissues contributes lymphatic clearance of A\(\beta\) from the brain. Further studies of this hypothesis will shed light on the mechanisms by which A\(\beta\) is cleared from the brain. In our recent review, we discussed that the EEG dynamics can be a potential biomarker of BBB integrity [25]. Here, we propose the EDFA analysis of EEG data and show that OBBB can be identified based on the EEG data using long-range power-law correlations. Our data concur with our previous results demonstrating a successful application of a nonlinear analysis of EEG patterns in the evaluation of OBBB [26, 27, 28, 29, 30, 31].