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The macaque anterior cingulate cortex translates counterfactual choice value into actual behavioral change

E Fouragnan, BKH Chau, D Folloni, N Kolling, L Verhagen, Miriam Klein-Flügge, L Tankelevitch, GK Papageorgiou, JF Aubry, J Sallet, MFS Rushworth

2018 · 10.1101/336917

nonhuman primatehealthybehaviour

Abstract

The neural mechanisms mediating sensory-guided decision making have received considerable attention but animals often pursue behaviors for which there is currently no sensory evidence. Such behaviors are guided by internal representations of choice values that have to be maintained even when these choices are unavailable. We investigated how four macaque monkeys maintained representations of the value of counterfactual choices – choices that could not be taken at the current moment but which could be taken in the future. Using functional magnetic resonance imaging, we found two different patterns of activity co-varying with values of counterfactual choices in a circuit spanning hippocampus, anterior lateral prefrontal cortex, and anterior cingulate cortex (ACC). ACC activity also reflected whether the internal value representations would be translated into actual behavioral change. To establish the causal importance of ACC for this translation process, we used a novel technique, Transcranial Focused Ultrasound Stimulation, to reversibly disrupt ACC activity.

Abstract via europepmc.

Speciesrhesus macaque (Macaca mulatta)
Subjects2 animals
Sessions per subject9
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesiaawake
Readoutsbehaviour
Direction of effectinhibitoryACC TUS abolished the significant influence of counterfactual (better vs. worse alternative) choice values on subsequent switching behavior that was present in the control condition, indicating disruption of ACC's role in translating counterfactual value into behavioral change; lOFC TUS (anatomical specificity control) had no such effect.
Adverse eventsnot reported

Exposures

Exposure 1: ACC TUS

Target: pregenual anterior cingulate cortex — “rACC
Device: Sonic Concepts · Sonic Concept, Bothell, WA, USA · H115-MR

Pulse timing
Waveformpulsed
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✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)1,152, 1,292swept✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatederatingmean or range across subjects
In-situ pressure (kPa)760, 850swept✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

30 ms bursts of ultrasound were generated every 100 ms (i.e., a pulse every 100 ms, converting to a 10 Hz pulse repetition rate) for an overall stimulation duration of 40 s, applied immediately prior to each of nine TUS testing sessions interleaved with nine sham sessions per monkey; sham sessions mirrored the TUS procedure except sonication was not triggered.

Exposure 2: lOFC TUS (anatomical specificity control)

Target: orbitofrontal cortex — “lateral orbitofrontal cortex (lOFC)
Device: Sonic Concepts · Sonic Concept, Bothell, WA, USA · H115-MR

Pulse timing
Waveformnot reported
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✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)1,152, 1,292swept✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)760, 850swept✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

A control experiment applying the same TUS technique (250 kHz, cigar-shaped focal spot) to lateral orbitofrontal cortex instead of ACC, to test anatomical specificity; other timing/pressure parameters are not restated separately in the text for this control.

Flags from extraction

  • exposures[0].free_field.pressure_kpaPaper writes 'MP' where MPa is presumably intended (unit abbreviation truncated/typo); value itself recorded as stated.
  • exposures[1].timing.pulse_duration_msTiming and pressure parameters for the lOFC control exposure are not restated separately from the ACC protocol in the main text; left not_reported rather than assuming identical values.
  • exposures[1].free_field.pressure_kpaNot explicitly restated for lOFC exposure; general TUS methods paragraph (pressure/timing) is written in the context of the ACC experiment.
  • direction_of_effectClassified as inhibitory based on behavioral disruption of counterfactual-value-guided switching; paper does not report a direct neural excitatory/inhibitory measure for the TUS effect itself.
  • n_subjectsOnly 2 of the 4 macaques used in the main fMRI task received TUS; n_subjects reflects those exposed to ultrasound.