Fig. 6. Functional connectivity is increased in HighF and LowF treated mice and correlates with memory performance in the APA test.

A A subcortical memory network was identified using ICA analysis involving the posterior hippocampus, thalamus and the retrosplenial-anterior congulate cortex which is involved in spatial learning. B In ultrasound treated mice, performance in the APA memory test was positively correlated with the subcortical memory network connectivity, particularly the connectivity between the anterior thalamus and the retrosplenial cortex. (Heat map indicates voxels with p < 0.05 correlation). C Linear regression of functional connectivity in the subcortical memory circuit (FC t-stat) and the learning index revealed a significant correlation in LowF treated mice (R² = 0.83, p = 0.0006), and a correlation in HighF treated mice (R² = 0.28, p = 0.1). D The magnitude of the improvement in learning and memory after ultrasound treatment is equivalent to those obtained in APP23 mice treated with ultrasound plus microbubbles that opens the BBB (SUS^+MB) reported in two earlier studies. E Graphical representation of the findings of this study: Improved memory, enhanced functional connectivity and an altered proteome were found in APP23 mice in the absence of Aβ reduction after repeated treatments with scanning ultrasound without microbubbles (SUS^only) at 1 MHz (HighF) and, to a lesser extent, at 286 kHz (LowF).