A Basal Forebrain-Cingulate Circuit in Macaques Decides It Is Time to Act
Nima Khalighinejad, Alessandro Bongioanni, Lennart Verhagen, Davide Folloni, David Attali, Jean-Francois Aubry, Jerome Sallet, Matthew F.S. Rushworth
Neuron 2020, 105, 370-384.e8 · 10.1016/j.neuron.2019.10.030
Abstract
The medial frontal cortex has been linked to voluntary action, but an explanation of why decisions to act emerge at particular points in time has been lacking. We show that, in macaques, decisions about whether and when to act are predicted by a set of features defining the animal's current and past context; for example, respectively, cues indicating the current average rate of reward and recent previous voluntary action decisions. We show that activity in two brain areas-the anterior cingulate cortex and basal forebrain-tracks these contextual factors and mediates their effects on behavior in distinct ways. We use focused transcranial ultrasound to selectively and effectively stimulate deep in the brain, even as deep as the basal forebrain, and demonstrate that alteration of activity in the two areas changes decisions about when to act.
Abstract via europepmc.
Exposures
Exposure 1: Bilateral ACC TUS
Target: anterior cingulate cortex — “anterior cingulate cortex (ACC)”
Device: Sonic Concepts · Sonic Concepts, Bothell, WA, USA · H115-MR (63.2 mm radius of curvature, 64 mm diameter) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | ⚑ |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 1,152, 1,292swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulation | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | ⚑ |
| In-situ Ispta (W/cm²) | not reported |
30 ms bursts of 250 kHz ultrasound were generated every 100 ms for a total duration of 40 s per hemisphere; each target was sonicated bilaterally for 80 s total (40 s per hemisphere, contralateral hemisphere immediately after). TUS was delivered immediately before the behavioural task; each of four stimulation conditions (ACC, BF, POp control, sham) was repeated five times on separate days, pseudo-randomized per animal, with a 48-hour gap between sessions.
Exposure 2: Bilateral BF (basal forebrain) TUS
Target: basal forebrain — “basal forebrain (BF), spanning anterior-medial BF/medial septum-diagonal band and posterior-lateral BF/nucleus basalis of Meynert”
Device: Sonic Concepts · Sonic Concepts, Bothell, WA, USA · H115-MR (63.2 mm radius of curvature, 64 mm diameter) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | 1,152, 1,292swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulation | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Same stimulation parameters as ACC TUS (30 ms bursts every 100 ms, 250 kHz, 40 s per hemisphere, 80 s bilateral total) but targeted at the basal forebrain (BF), defined from whole-brain peak activity for the actTime contrast; stimulation was also associated with activity change in the adjacent posterior-lateral BF subregion.
Flags from extraction
exposures[0].free_field.pressure_kpa— Source text prints the unit as 'MP' rather than 'MPa' (likely an OCR/typesetting artefact); recorded assuming MPa as stated elsewhere in the same methods (peak negative pressure in MPa is standard for this transducer/reference).exposures[1].target.terms— The basal forebrain (BF) target spans both the anterior-medial BF (~septal_nuclei/medial septum) and posterior-lateral BF (~nucleus basalis of Meynert), neither of which maps cleanly onto a single target-ontology term; coded as 'other' with the paper's own description in target.label.exposures[0].timing.duty_cycle_pct— Duty cycle is not stated directly; it would require dividing pulse duration (30 ms) by period (100 ms), which is arithmetic we must not perform, so left not_reported.exposures[0].in_situ.isppa_w_cm2— Paper describes an acoustic/thermal k-Wave simulation and an 'impact probability map' referencing a 10 W/cm^2 threshold from prior work (Verhagen et al., 2019), but does not state a specific simulated in-situ intensity value for the ACC/BF targets in this paper's main text.direction_of_effect— Effects are on a behavioural decision-timing measure and on resting-state functional connectivity, not on a simple excitatory/inhibitory neural readout; classified as mixed_or_unclear.