Value dynamics affect choice preparation during decision-making.

During decision-making, neurons in the orbitofrontal cortex (OFC) sequentially represent the value of each option in turn, but it is unclear how these dynamics are translated into a choice response. One brain region that may be implicated in this process is the anterior cingulate cortex (ACC), which strongly connects with OFC and contains many neurons that encode the choice response. We investigated how OFC value signals interacted with ACC neurons encoding the choice response by performing simultaneous high-channel count recordings from the two areas in nonhuman primates. ACC neurons encoding the choice response steadily increased their firing rate throughout the decision-making process, peaking shortly before the time of the choice response. Furthermore, the value dynamics in OFC affected ACC ramping-when OFC represented the more valuable option, ACC ramping accelerated. Because OFC tended to represent the more valuable option more frequently and for a longer duration, this interaction could explain how ACC selects the more valuable response.

Decoding cognition in real-time.

How can we study unobservable cognitive processes that cannot be measured directly? This has been an enduring challenge for cognitive scientists. In this essay we discuss advances in neurotechnology that could allow cognitive processes to be decoded in real-time and the implications that this may have for cognitive science and the treatment of neuropsychiatric disease.

Impaired discrimination of a subanesthetic dose of ketamine in a maternal immune activation model of schizophrenia risk.

BACKGROUND: Animal models of psychiatric diseases suffer from a lack of reliable methods for accurate assessment of subjective internal states in nonhumans. This gap makes translation of results from animal models to patients particularly challenging. AIMS/METHODS: Here, we used the drug-discrimination paradigm to allow rats that model a risk factor for schizophrenia (maternal immune activation, MIA) to report on the subjective internal state produced by a subanesthetic dose of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. RESULTS/OUTCOMES: The MIA rats' discrimination of ketamine was impaired relative to controls, both in the total number of rats that acquired and the asymptotic level of discrimination accuracy. This deficit was not due to a general inability to learn to discriminate an internal drug cue or internal state generally, as MIA rats were unimpaired in the learning and acquisition of a morphine drug discrimination and were as sensitive to the internal state of satiety as controls. Furthermore, the deficit was not due to a decreased sensitivity to the physiological effects of ketamine, as MIA rats showed increased ketamine-induced locomotor activity. Finally, impaired discrimination of ketamine was only seen at subanesthetic doses which functionally correspond to psychotomimetic doses in humans. CONCLUSION: These data link changes in NMDA responses to the MIA model. Furthermore, they confirm the utility of the drug-discrimination paradigm for future inquiries into the subjective internal state produced in models of schizophrenia and other developmental diseases.

Communication between the Anterior Cingulate Cortex and Ventral Tegmental Area during a Cost-Benefit Reversal Task.

The anterior cingulate cortex (ACC) is implicated in value-based decision making, anticipation, and adaptation; however, how ACC activity modulates these behaviors is unclear. One possibility is via the ACC's connections with the ventral tegmental area (VTA), a dopaminergic region implicated in motivation and feedback processing. We tested this by monitoring ACC and VTA local field potentials in rats performing a cost-benefit reversal task that elicited both value-based and anticipatory choices. Partial directed coherence analyses revealed that elevated 4-Hz ACC-to-VTA signaling accompanied decisions that appeared to be anticipatory. ACC-to-VTA signaling also occurred post-reversal, consistent with it being involved in the initiation of non-default behavior. An analysis of 4-Hz signals in the other direction (VTA-to-ACC) revealed that it was elevated when the rats committed errors and that this signal was followed by behavioral adaptation. Together, these findings suggest that bidirectional communication between the ACC and VTA supports behavioral flexibility.

Conflict and adaptation signals in the anterior cingulate cortex and ventral tegmental area.

The integration and utilization of feedback in order to determine which decision strategy to use in different contexts is the core of executive function. The anterior cingulate cortex (ACC) is central to these processes but how feedback is made available to the ACC is unclear. To address this question, we trained rats with implants in the ACC and the ventral tegmental area (VTA), a dopaminergic brain region implicated in feedback processing, in a spatial decision reversal task with rule switching occurring approximately every 12 trials. Following a rule switch, the rats had to shift and sustain responses to the alternative side in order to obtain reward. Partial directed coherence (PDC) models of signal directionality between the ACC and VTA indicated that VTA → ACC communication (near 4 Hz) increased immediately prior to incorrect choices and during post-error decisions. This increase did not occur during correct choices. These data indicate that the VTA provides a feedback-driven, bottom-up modulating signal to the ACC which may be involved in assessing, and correcting for, decision conflict.

Anterior Cingulate Cortex Modulation of the Ventral Tegmental Area in an Effort Task.

Information gained during goal pursuit motivates adaptive behavior. The anterior cingulate cortex (ACC) supports adaptive behavior, but how ACC signals are translated into motivational signals remains unclear. Rats with implants in the ACC and ventral tegmental area (VTA), a dopaminergic brain area implicated in motivation, were trained to run laps around a rectangular track for a fixed reward, where each lap varied in physical effort (a 30-cm climbable barrier). Partial directed coherence analysis of local field potentials revealed that ACC theta (4-12 Hz) activity increased as rats entered the barrier-containing region of the maze in trials when the barrier was absent and predicted similar changes in VTA theta activity. This did not occur in effortful, barrier-present trials. These data suggest that the ACC provides a top-down modulating signal to the VTA that can influence the motivation with which to pursue a reward.

Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.

There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.