Selective enhancement of fronto-temporal mechanisms for adaptive memory
Benjamin Slater, Timothy Griffiths, Hugo Caffaratti, Jérôme Sallet, Patrick Degenaar, Marcus Kaiser, Alexander Easton, Yukiko Kikuchi, Christopher Petkov
2025 · 10.64898/2025.12.19.695543
Abstract
There is substantial scientific interest in advancing knowledge on the control mechanisms supporting adaptive memory and improving approaches that can enhance cognition through brain stimulation. We implemented a non-invasive focal Transcranial Ultrasound Stimulation (TUS) approach with known longer-lasting post-stimulation effects in two rhesus macaques performing a novel context-dependent memory-sequencing task implemented on multiple touchscreens within their home units. Consistently in both monkeys, TUS to the anterior, but not posterior, medial temporal lobe enhanced performance under stable memory-sequencing contexts. TUS to the medial prefrontal cortex, on the other hand, selectively improved performance when contexts were unstable and the monkey needed to adapt to both a change in context and temporal sequence. These findings provide positive causal evidence of a functional dissociation within fronto-temporal memory circuits and pave the way for advancing non-invasive approaches to improve cognitive function and the study of neural circuits under focal enhancement across species. IMPACT STATEMENT Transcranial ultrasound stimulation of the prefrontal-hippocampal network selectively enhances context-guided memory in macaques, demonstrating that non-invasive brain stimulation can causally improve, rather than only disrupt, memory circuits.
Abstract via europepmc.
Exposures
Exposure 1: mPFC TUS
Target: ventromedial prefrontal cortex — “medial prefrontal cortex (mPFC)”
Device: Sonic Concepts · Sonic Concepts (Bothell, WA, USA) · H115-MR ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓⚑ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 580 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 11.5 | ✓✓✓⚑ |
| Free-field Ispta (W/cm²) | 3.45 | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
30 ms pulses delivered every 100 ms (30% duty cycle); pulse train of 40 s per hemisphere, bilaterally, delivered offline before the behavioural session; sham had the transducer in place but not activated.
Exposure 2: aMTL TUS
Target: hippocampus — “anterior medial temporal lobe (aMTL), primarily anterior hippocampus”
Device: Sonic Concepts · Sonic Concepts (Bothell, WA, USA) · H115-MR ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 580 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 11.5 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 3.45 | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
30 ms pulses delivered every 100 ms (30% duty cycle); pulse train of 40 s per hemisphere, bilaterally, delivered offline before the behavioural session; sham had the transducer in place but not activated.
Exposure 3: pMTL TUS
Target: hippocampus — “posterior medial temporal lobe (pMTL), primarily posterior hippocampus”
Device: Sonic Concepts · Sonic Concepts (Bothell, WA, USA) · H115-MR ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 580 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 11.5 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 3.45 | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
30 ms pulses delivered every 100 ms (30% duty cycle); pulse train of 40 s per hemisphere, bilaterally, delivered offline before the behavioural session; sham had the transducer in place but not activated.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— Discussion states intensity 10 W/cm2 while Methods free-field measurement gives Isppa 11.5 W/cm2; Methods value recorded.n_subjects— Only two animals; one male, one female, each serving as own control.exposures[0].timing.pulse_repetition_frequency_hz— PRF from the Discussion (10 Hz pulse frequency); Methods give a 100 ms pulse repetition interval.exposures[0].in_situ.method— Simulations with k-Plan were run for targeting but no in situ pressure or intensity values are reported in the main text.auditory_control— Earplugs worn during sonication; the paper notes these do not eliminate noise confounds fully.randomised— Sessions were counterbalanced; Monkey PL initially had a blocked design.