Causal Control
# Continue PAPER_TPL
BIO
Low-intensity tFUS targeted to the right hippocampus increased hippocampal glucose metabolism and improved recognition memory without detectable BBB opening.
"The PET analysis showed an increased level of rCMRglu in the right hippocampus (t = 4.74; z = 3.07; p = 0.001; cluster size = 46 voxels; coordinates = 28, −14, −26) (Figure 3). Other brain regions, including the left hippocampus, did not demonstrate significant changes in rCMRglu. In addition, increases in hippocampal glucose metabolism were positively associated with the improvement of recognition memory (Spearman’s ρ = 0.77, p = 0.02) (Figure 4)."
3. Results, p. 7
An exogenous causal intervention (tFUS) changed neural function (hippocampal metabolism) and behavior (recognition memory), demonstrating causal control over cognition-relevant circuitry in humans .
"Immediately after the intravenous injection of MB (Definity, Lantheus Medical Imaging Inc., North Billerica, MA, USA; 10 µL/kg over one minute), tFUS was delivered using the following parameters (7): fundamental frequency = 250 kHz; tone-burst duration = 20 ms; pulse repetition frequency = 2 Hz; duty cycle = 4%; treatment duration = 180 sec; in situ mechanical index = 0.30–0.88."
2.5. Application of tFUS, p. 4
The explicit stimulation parameters establish a controlled causal perturbation to hippocampal circuits, suitable for linking intervention to downstream neural and cognitive changes .
"Radiological evidence of contrast enhancement associated with BBB opening was found in neither the visual inspection nor the ICA of the DCE–MRI data."
3. Results, p. 6
The observed neural and cognitive changes followed tFUS without detectable BBB opening, strengthening the inference that neuromodulation itself causally altered neural function and behavior .
Figures
Figure 3 (p. 7)
: Shows localized increase of hippocampal rCMRglu after tFUS, evidencing causal impact on neural metabolism relevant to conscious cognition .
Figure 4 (p. 7)
: Demonstrates behavior–brain coupling (metabolism–recognition memory) after causal intervention, linking neural change to reportable performance .
Tables
Table 2 (p. 6)
: Table 2. Changes in neuropsychological test results after transcranial focused ultrasound.
Limitations: No sham control; small N; potential practice effects; multiple-comparison corrections not applied; severity skewed toward moderate–severe AD, limiting generalizability.