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Anterior cingulate cortex causally supports flexible learning under motivationally challenging and cognitively demanding conditions

Kianoush Banaie Boroujeni, Michelle K. Sigona, Robert Louie Treuting, Thomas J. Manuel, Charles F. Caskey, Thilo Womelsdorf

PLOS Biology 2022, 20, e3001785 · 10.1371/journal.pbio.3001785

nonhuman primatehealthybehaviour

Abstract

Anterior cingulate cortex (ACC) and striatum (STR) contain neurons encoding not only the expected values of actions, but also the value of stimulus features irrespective of actions. Values about stimulus features in ACC or STR might contribute to adaptive behavior by guiding fixational information sampling and biasing choices toward relevant objects, but they might also have indirect motivational functions by enabling subjects to estimate the value of putting effort into choosing objects. Here, we tested these possibilities by modulating neuronal activity in ACC and STR of nonhuman primates using transcranial ultrasound stimulation while subjects learned the relevance of objects in situations with varying motivational and cognitive demands. Motivational demand was indexed by varying gains and losses during learning, while cognitive demand was varied by increasing the uncertainty about which object features could be relevant during learning. We found that ultrasound stimulation of the ACC, but not the STR, reduced learning efficiency and prolonged information sampling when the task required averting losses and motivational demands were high. Reduced learning efficiency was particularly evident at higher cognitive demands and when subjects experienced loss of already attained tokens. These results suggest that the ACC supports flexible learning of feature values when loss experiences impose a motivational challenge and when uncertainty about the relevance of objects is high. Taken together, these findings provide causal evidence that the ACC facilitates resource allocation and improves visual information sampling during adaptive behavior.

Abstract via europepmc.

Speciesmacaque
Subjects2 animals
Sessions per subject24
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesiaawake
Readoutsbehaviourtrials-to-criterion; fixational information sampling (gaze duration); reaction time; post-learning plateau accuracy
Direction of effectinhibitoryACC-TUS (but not STR-TUS) slowed learning, prolonged information sampling, and reduced plateau accuracy selectively in the gain-loss (loss-experience) motivational context, especially at higher cognitive load; STR-TUS had no effect.
Adverse eventsnot reported

Exposures

Exposure 1: TUS to ACC (area 24)

Target: dorsal anterior cingulate cortex — “ACC (area 24)
Device: Sonic Concepts · Sonic Concepts · H115MR

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)1,200✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

30-ms bursts of TUS were delivered every 100 ms over a duration of 80 seconds (40 seconds each hemisphere). We bilaterally sonicated or sham-sonicated the ACC or the STR in individual sessions immediately after monkeys had completed the first 6 learning blocks.

Exposure 2: TUS to anterior striatum (head of caudate)

Target: caudate nucleus — “anterior striatum (STR, head of the caudate nucleus)
Device: Sonic Concepts · Sonic Concepts · H115MR

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)1,200✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

30-ms bursts of TUS were delivered every 100 ms over a duration of 80 seconds (40 seconds each hemisphere). We bilaterally sonicated or sham-sonicated the ACC or the STR in individual sessions immediately after monkeys had completed the first 6 learning blocks.

Flags from extraction

  • exposures[0].unspecified_domain.pressure_kpa1.2 MPa pressure is stated for the stimulation protocol but the sentence does not explicitly say whether it is a free-field or in-situ value; the following sentences describe hydrophone calibration in water, so domain is ambiguous and the value is placed in unspecified_domain.
  • exposures[1].unspecified_domain.pressure_kpaSame 1.2 MPa value and domain ambiguity as exposures[0]; same protocol used for both targets.
  • exposures[0].timing.pulse_repetition_frequency_hzPRF (10 Hz) converted from the stated inter-burst interval of 100 ms; not stated directly as Hz in the text.
  • exposures[1].timing.pulse_repetition_frequency_hzPRF (10 Hz) converted from the stated inter-burst interval of 100 ms; not stated directly as Hz in the text.
  • exposures[0].timing.duty_cycle_pctDuty cycle not stated by the paper; leaving not_reported rather than computing from pulse duration (30 ms) and period (100 ms).
  • direction_of_effectDirection is inferred from behavioural impairment only; no direct neural recording of ACC activity was performed in this study.