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Ultrasound modulation of macaque prefrontal cortex selectively alters credit assignment–related activity and behavior

Davide Folloni, Elsa Fouragnan, Marco K. Wittmann, Lea Roumazeilles, Lev Tankelevitch, Lennart Verhagen, David Attali, Jean-François Aubry, Jerome Sallet, Matthew F. S. Rushworth

Science Advances 2021, 7 · 10.1126/sciadv.abg7700

nonhuman primatehealthyfmribehaviour

Abstract

Credit assignment is the association of specific instances of reward to the specific events, such as a particular choice, that caused them. Without credit assignment, choice values reflect an approximate estimate of how good the environment was when the choice was made—the global reward state—rather than exactly which outcome the choice caused. Combined transcranial ultrasound stimulation (TUS) and functional magnetic resonance imaging in macaques demonstrate credit assignment–related activity in prefrontal area 47/12o, and when this signal was disrupted with TUS, choice value representations across the brain were impaired. As a consequence, behavior was no longer guided by choice value, and decision-making was poorer. By contrast, global reward state–related activity in the adjacent anterior insula remained intact and determined decision-making after prefrontal disruption.

Abstract via europepmc.

Speciesrhesus macaque (Macaca mulatta)
Subjects4 animals
Sessions per subject5
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer, active control site
Auditory controlnot reported
Readout timingoffline
Anaesthesiaawake
Readoutsfmri, behaviourwin-stay/lose-shift probabilistic reward-guided choice task; reinforcement-learning model fits
Direction of effectinhibitoryTUS to area 47/12o reduced win-stay/lose-shift-related neural activity in 47/12o and choice-value-related activity in ACC, disrupting credit assignment and behavioral use of choice values; global-reward-state-related activity in anterior insula and its influence on behavior were unaffected by 47/12o TUS.
Adverse eventsnot reported

Exposures

Exposure 1: TUS to area 47/12o (bilateral)

Target: orbitofrontal cortex — “area 47/12o (lateral orbitofrontal cortex, at border of orbital/ventral prefrontal cortex)
Device: Sonic Concepts · Sonic Concept · H115-MR

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)250✓✓
Pulse duration (ms)30✓✓
Pulse repetition frequency (Hz)10✓✓
Duty cycle (%)30pulse duration × PRF gives 30%✓✓
Sonication duration (s)40✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)1,170, 1,290swept✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatesimulationmean or range across subjects
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)42.6, 34.6swept✓✓
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Offline TUS protocol: bilateral stimulation of area 47/12o applied several minutes before the behavioral/fMRI testing session, using a single-element transducer with a coupling cone, applied once for 40 s per session; five 47/12o TUS sessions and five interleaved sham sessions per animal in experiment 1 (counterbalanced order).

Flags from extraction

  • exposures[0].in_situ.isppa_w_cm2Reported as an approximate range (35-40 W/cm2) across the two bilateral target hemispheres (left 42.6, right 34.6 W/cm2 from simulation), not a range across subjects; reported_as vocabulary has no exact match for this case.
  • sham_typeStudy used both a no-stimulation sham condition (transducer procedures mirrored but sonication not triggered) and a genuine active-stimulation control at a different site (aPFC); both are recorded.
  • randomisedSham/TUS days were counterbalanced and interleaved but the paper does not use the word 'randomised' for session order.