A Tradeoff in the Neural Code across Regions and Species.

Many evolutionary years separate humans and macaques, and although the amygdala and cingulate cortex evolved to enable emotion and cognition in both, an evident functional gap exists. Although they were traditionally attributed to differential neuroanatomy, functional differences might also arise from coding mechanisms. Here we find that human neurons better utilize information capacity (efficient coding) than macaque neurons in both regions, and that cingulate neurons are more efficient than amygdala neurons in both species. In contrast, we find more overlap in the neural vocabulary and more synchronized activity (robustness coding) in monkeys in both regions and in the amygdala of both species. Our findings demonstrate a tradeoff between robustness and efficiency across species and regions. We suggest that this tradeoff can contribute to differential cognitive functions between species and underlie the complementary roles of the amygdala and the cingulate cortex. In turn, it can contribute to fragility underlying human psychopathologies.

Shared yet dissociable neural codes across eye gaze, valence and expectation.

The direction of the eye gaze of others is a prominent social cue in primates and is important for communication1-11. Although gaze can signal threat and elicit anxiety6,12,13, it remains unclear whether it shares neural circuitry with stimulus value. Notably, gaze not only has valence, but can also serve as a predictor of the outcome of a social encounter, which can be either negative or positive2,8,12,13. Here we show that the neural codes for gaze and valence overlap in primates and that they involve two different mechanisms: one for the outcome and another for its expectation. Monkeys participated in the human intruder test13,14, in which a human participant had either a direct or averted gaze, interleaved with blocks of aversive and appetitive conditioning. We find that single neurons in the amygdala encode gaze15, whereas neurons in the anterior cingulate cortex encode the social context16, but not gaze. We identify a shared population in the amygdala for which the neural responses to direct and averted gaze parallel the responses to aversive and appetitive stimulus, respectively. Furthermore, we distinguish between two neural mechanisms-an overall-activity scheme that is used for gaze and the unconditioned stimulus, and a correlated-selectivity scheme that is used for gaze and the conditioned stimulus. These findings provide insights into the origins of the neural mechanisms that underlie the computations of both social interactions and valence, and could help to shed light on mechanisms that underlie social anxiety and the comorbidity between anxiety and impaired social interactions.

Irrelevant Threats Linger and Affect Behavior in High Anxiety.

Threat-related information attracts attention and disrupts ongoing behavior, and particularly so for more anxious individuals. Yet, it is unknown how and to what extent threat-related information leave lingering influences on behavior (e.g., by impeding ongoing learning processes). Here, human male and female participants (N = 47) performed probabilistic reinforcement learning tasks where irrelevant distracting faces (neutral, happy, or fearful) were presented together with relevant monetary feedback. Behavioral modeling was combined with fMRI data (N = 27) to explore the neurocomputational bases of learning relevant and irrelevant information. In two separate studies, individuals with high trait anxiety showed increased avoidance of objects previously paired with the combination of neutral monetary feedback and fearful faces (but not neutral or happy faces). Behavioral modeling revealed that high anxiety increased the integration of fearful faces during feedback learning, and fMRI results (regarded as provisional, because of a relatively small sample size) further showed that variance in the prediction error signal, uniquely accounted for by fearful faces, correlated more strongly with activity in the right DLPFC for more anxious individuals. Behavioral and neuronal dissociations indicated that the threat-related distractors did not simply disrupt learning processes. By showing that irrelevant threats exert long-lasting influences on behavior, our results extend previous research that separately showed that anxiety increases learning from aversive feedbacks and distractibility by threat-related information. Our behavioral results, combined with the proposed neurocomputational mechanism, may help explain how increased exposure to irrelevant affective information contributes to the acquisition of maladaptive behaviors in more anxious individuals.SIGNIFICANCE STATEMENT In modern-day society, people are increasingly exposed to various types of irrelevant information (e.g., intruding social media announcements). Yet, the neurocomputational mechanisms influenced by irrelevant information during learning, and their interactions with increasingly distracted personality types are largely unknown. Using a reinforcement learning task, where relevant feedback is presented together with irrelevant distractors (emotional faces), we reveal an interaction between irrelevant threat-related information (fearful faces) and interindividual anxiety levels. fMRI shows provisional evidence for an interaction between anxiety levels and the coupling between activity in the DLPFC and learning signals specifically elicited by fearful faces. Our study reveals how irrelevant threat-related information may become entrenched in the anxious psyche and contribute to long-lasting abnormal behaviors.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Neural Representations of Emotional Experiences Are More Similar Than Those of Neutral Experiences.

Stimuli that evoke the same feelings can nevertheless look different and have different semantic meanings. Although we know much about the neural representation of emotion, the neural underpinnings of emotional similarity are unknown. One possibility is that the same brain regions represent similarity between emotional and neutral stimuli, perhaps with different strengths. Alternatively, emotional similarity could be coded in separate regions, possibly those sensitive to emotional valence and arousal. In behavior, the extent to which people consider similarity along emotional dimensions when they evaluate the overall similarity between stimuli has never been investigated. Although the emotional features of stimuli may dominate explicit ratings of similarity, it is also possible that people neglect emotional dimensions as irrelevant to that judgment. We contrasted these hypotheses in (male and female) healthy controls using two measures of similarity and two picture databases of complex negative and neutral scenes, the second of which provided exquisite control over semantic and visual attributes. The similarity between emotional stimuli was greater than between neutral stimuli in the inferior temporal cortex, the fusiform face area, and the precuneus. Additionally, only the similarity between emotional stimuli was significantly represented in early visual cortex, anterior insula and dorsal anterior cingulate cortex. Intriguingly, despite the stronger neural similarity between emotional stimuli, the same participants did not rate them as more similar to each other than neutral stimuli. These results contribute to our understanding of how emotion is represented within a general conceptual workspace and of the overgeneralization bias in anxiety disorders.SIGNIFICANCE STATEMENT We tested differences in similarity between emotional and neutral scenes. Arousal and negative valence did not increase similarity ratings. When conditions were equated on semantic similarity, participants rated emotional stimuli as similar to each other as neutral ones. Despite this equivalence, the similarity among the neural representations of emotional compared with neutral stimuli was higher in regions, which also expressed similarity between neutral stimuli and in unique regions. We report a striking difference between behavioral and neural similarity; strong neural similarity between emotional pictures did not influence similarity judgements in the same participants in the behavioral rating task after the scan. These findings may have an impact on research about the neural representations of emotional categories and the overgeneralization bias in anxiety disorders.

A neural and behavioral trade-off between value and uncertainty underlies exploratory decisions in normative anxiety.

Exploration reduces uncertainty about the environment and improves the quality of future decisions, but at the cost of provisional uncertain and suboptimal outcomes. Although anxiety promotes intolerance to uncertainty, it remains unclear whether and by which mechanisms anxiety relates to exploratory decision-making. We use a dynamic three-armed-bandit task and find that higher trait-anxiety is associated with increased exploration, which in turn harms overall performance. We identify two distinct behavioral sources: first, decisions made by anxious individuals are guided toward reduction of uncertainty; and second, decisions are less guided by immediate value gains. These findings are similar in both loss and gain domains, and further demonstrate that an affective trait relates to exploration and results in an inverse-U-shaped relationship between anxiety and overall performance. Additional imaging data (fMRI) suggests that normative anxiety correlates negatively with the representation of expected-value in the dorsal-anterior-cingulate-cortex, and in contrast, positively with the representation of uncertainty in the anterior-insula. We conclude that a trade-off between value-gains and uncertainty-reduction entails maladaptive decision-making in individuals with higher normal-range anxiety.

Quantifying the excitatory-inhibitory balance: A comparison of SemiLASER and MEGA-SemiLASER for simultaneously measuring GABA and glutamate at 7T.

The importance of the excitatory-inhibitory (E/I) balance in a wide range of cognitive and behavioral processes has prompted a commensurate interest in methods for reliably quantifying it. Proton Magnetic Resonance Spectroscopy (1H-MRS) remains the only method capable of safely and non-invasively measuring the concentrations of the brain's major excitatory (glutamate) and inhibitory (γ-aminobutyric-acid, GABA) neurotransmitters in-vivo. MRS relies on spectral Mescher-Garwood (MEGA) editing techniques at 3T to distinguish GABA from its overlapping resonances. However, with the increased spectral resolution at ultrahigh field strengths of 7T and above, non-edited spectroscopic techniques become potential viable alternatives to MEGA based approaches, and also address some of their shortcomings, such as signal loss, sensitivity to transmitter inhomogeneities and temporal resolution. We present a comprehensive comparison of both edited and non-edited strategies at 7T for simultaneously quantifying glutamate and GABA from the dorsal anterior cingulate cortex (dACC), and evaluate their reproducibility and relative bias. The combined root-mean-square test-retest reproducibility of Glu and GABA (CVE/I) was as low as 13.3% for unedited MRS at TE=80 ms using SemiLASER localization, while edited MRS at TE=80 ms yielded CVE/I=20% and 21% for asymmetric and symmetric MEGA editing, respectively. An unedited SemiLASER acquisition using a shorter echo time of TE=42 ms yielded CVE/I as low as 24.9%. Our results show that non-edited sequences at an echo time of 80 ms provide better reproducibility than either edited sequences at the same TE, or non-edited sequences at a shorter TE of 42 ms. This is supported by numerical simulations and is driven in part by a pseudo-singlet appearance of the GABA multiplets at TE=80 ms, and the excellent spectral resolution at 7T. Our results uphold a transition to non-edited MRS for monitoring the E/I balance at ultrahigh fields, and stress the importance of using a properly-optimized echo time.

Neurons in the Nonhuman Primate Amygdala and Dorsal Anterior Cingulate Cortex Signal Aversive Memory Formation under Sedation.

BACKGROUND: Anesthetics aim to prevent memory of unpleasant experiences. The amygdala and dorsal anterior cingulate cortex participate in forging emotional and valence-driven memory formation. It was hypothesized that this circuitry maintains its role under sedation. METHODS: Two nonhuman primates underwent aversive tone-odor conditioning under sedative states induced by ketamine or midazolam (1 to 8 and 0.1 to 0.8 mg/kg, respectively). The primary outcome was behavioral and neural evidence suggesting memory formation. This study simultaneously measured conditioned inspiratory changes and changes in firing rate of single neurons in the amygdala and the dorsal anterior cingulate cortex in response to an expected aversive olfactory stimulus appearing during acquisition and tested their retention after recovery. RESULTS: Aversive memory formation occurred in 26 of 59 sessions under anesthetics (16 of 29 and 10 of 30, 5 of 30 and 21 of 29 for midazolam and ketamine at low and high doses, respectively). Single-neuron responses in the amygdala and dorsal anterior cingulate cortex were positively correlated between acquisition and retention (amygdala, n = 101, r = 0.51, P < 0.001; dorsal anterior cingulate cortex, n = 121, r = 0.32, P < 0.001). Neural responses during acquisition under anesthetics were stronger in sessions exhibiting memory formation than those that did not (amygdala median response ratio, 0.52 versus 0.33, n = 101, P = 0.021; dorsal anterior cingulate cortex median response ratio, 0.48 versus 0.32, n = 121, P = 0.012). The change in firing rate of amygdala neurons during acquisition was correlated with the size of stimuli-conditioned inspiratory response during retention (n = 101, r = 0.22 P = 0.026). Thus, amygdala and dorsal anterior cingulate cortex responses during acquisition under anesthetics predicted retention. Respiratory unconditioned responses to the aversive odor anesthetics did not differ from saline controls. CONCLUSIONS: These results suggest that the amygdala-dorsal anterior cingulate cortex circuit maintains its role in acquisition and maintenance of aversive memories in nonhuman primates under sedation with ketamine and midazolam and that the stimulus valence is sufficient to drive memory formation.

Prestimulus Activity in the Cingulo-Opercular Network Predicts Memory for Naturalistic Episodic Experience.

Human memory is strongly influenced by brain states occurring before an event, yet we know little about the underlying mechanisms. We found that activity in the cingulo-opercular network (including bilateral anterior insula [aI] and anterior prefrontal cortex [aPFC]) seconds before an event begins can predict whether this event will subsequently be remembered. We then tested how activity in the cingulo-opercular network shapes memory performance. Our findings indicate that prestimulus cingulo-opercular activity affects memory performance by opposingly modulating subsequent activity in two sets of regions previously linked to encoding and retrieval of episodic information. Specifically, higher prestimulus cingulo-opercular activity was associated with a subsequent increase in activity in temporal regions previously linked to encoding and with a subsequent reduction in activity within a set of regions thought to play a role in retrieval and self-referential processing. Together, these findings suggest that prestimulus attentional states modulate memory for real-life events by enhancing encoding and possibly by dampening interference from competing memory substrates.

Visual Aversive Learning Compromises Sensory Discrimination.

Aversive learning is thought to modulate perceptual thresholds, which can lead to overgeneralization. However, it remains undetermined whether this modulation is domain specific or a general effect. Moreover, despite the unique role of the visual modality in human perception, it is unclear whether this aspect of aversive learning exists in this modality. The current study was designed to examine the effect of visual aversive outcomes on the perception of basic visual and auditory features. We tested the ability of healthy participants, both males and females, to discriminate between neutral stimuli, before and after visual learning. In each experiment, neutral stimuli were associated with aversive images in an experimental group and with neutral images in a control group. Participants demonstrated a deterioration in discrimination (higher discrimination thresholds) only after aversive learning. This deterioration was measured for both auditory (tone frequency) and visual (orientation and contrast) features. The effect was replicated in five different experiments and lasted for at least 24 h. fMRI neural responses and pupil size were also measured during learning. We showed an increase in neural activations in the anterior cingulate cortex, insula, and amygdala during aversive compared with neutral learning. Interestingly, the early visual cortex showed increased brain activity during aversive compared with neutral context trials, with identical visual information. Our findings imply the existence of a central multimodal mechanism, which modulates early perceptual properties, following exposure to negative situations. Such a mechanism could contribute to abnormal responses that underlie anxiety states, even in new and safe environments.SIGNIFICANCE STATEMENT Using a visual aversive-learning paradigm, we found deteriorated discrimination abilities for visual and auditory stimuli that were associated with visual aversive stimuli. We showed increased neural activations in the anterior cingulate cortex, insula, and amygdala during aversive learning, compared with neutral learning. Importantly, similar findings were also evident in the early visual cortex during trials with aversive/neutral context, but with identical visual information. The demonstration of this phenomenon in the visual modality is important, as it provides support to the notion that aversive learning can influence perception via a central mechanism, independent of input modality. Given the dominance of the visual system in human perception, our findings hold relevance to daily life, as well as imply a potential etiology for anxiety disorders.

Inhibitory and excitatory mechanisms in the human cingulate-cortex support reinforcement learning: A functional Proton Magnetic Resonance Spectroscopy study.

The dorsal anterior cingulate cortex (dACC) is crucial for motivation, reward- and error-guided decision-making, yet its excitatory and inhibitory mechanisms remain poorly explored in humans. In particular, the balance between excitation and inhibition (E/I), demonstrated to play a role in animal studies, is difficult to measure in behaving humans. Here, we used functional magnetic-resonance-spectroscopy (1H-fMRS) to measure the brain's major inhibitory (GABA) and excitatory (Glutamate) neurotransmitters during reinforcement learning with three different conditions: high cognitive load (uncertainty); probabilistic discrimination learning; and a control null-condition. Participants learned to prefer the gain option in the discrimination phase and had no preference in the other conditions. We found increased GABA levels during the uncertainty condition, potentially reflecting recruitment of inhibitory systems during high cognitive load when trying to learn. Further, higher GABA levels during the null (baseline) condition correlated with improved discrimination learning. Finally, glutamate and GABA levels were correlated during high cognitive load. These results suggest that availability of dACC inhibitory resources enables successful learning. Our approach helps elucidate the potential contribution of the balance between excitation and inhibition to learning and motivation in behaving humans.

Self-monitoring of social facial expressions in the primate amygdala and cingulate cortex.

Keeping track of self-executed facial expressions is essential for the ability to correctly interpret and reciprocate social expressions. However, little is known about neural mechanisms that participate in self-monitoring of facial expression. We designed a natural paradigm for social interactions where a monkey is seated in front of a peer monkey that is concealed by an opaque liquid crystal display shutter positioned between them. Opening the shutter for short durations allowed the monkeys to see each other and encouraged facial communication. To explore neural mechanisms that participate in self-monitoring of facial expression, we simultaneously recorded the elicited natural facial interactions and the neural activity of single neurons in the amygdala and the dorsal anterior cingulate cortex (dACC), two regions that are implicated with decoding of others' gestures. Neural activity in both regions was temporally locked to distinctive facial gestures and close inspection of time lags revealed activity that either preceded (production) or lagged (monitor) initiation of facial expressions. This result indicates that single neurons in the dACC and the amygdala hold information about self-executed facial expressions and demonstrates an intimate overlap between the neural networks that participate in decoding and production of socially informative facial information.

Safety signals in the primate amygdala.

The ability to distinguish danger from safety is crucial for survival. On the other hand, anxiety disorders can result from failures to dissociate safe cues from those that predict dangerous outcomes. The amygdala plays a major role in learning and signaling danger, and recently, evidence accumulates that it also acquires information to signal safety. Traditionally, safety is explored by paradigms that change the value of a previously dangerous cue, such as extinction or reversal; or by paradigms showing that a safe cue can inhibit responses to another danger-predicting cue, as in conditioned-inhibition. In real-life scenarios, many cues are never paired or tested with danger and remain neutral all along. A detailed study of neural responses to unpaired conditioned-stimulus (CS-) can therefore indicate whether information on safety-by-comparison is also acquired in the amygdala. We designed a multiple-CS study, with CS- from both visual and auditory modalities. Using discriminative aversive-conditioning, we find that responses in the primate amygdala develop for CS- of the same modality and of a different modality from that of the aversive CS+. Moreover, we find that responses are comparable in proportion, sign (increase/decrease), onset, and magnitude. These results indicate that the primate amygdala actively acquires signals about safety, and strengthen the hypothesis that failure in amygdala processing can result in failure to distinguish dangerous cues from safe ones and lead to maladaptive behaviors.

The neurobehavioral correlates of exploration without learning: Trading off value for explicit, prospective, and variable information gains.

Exploration is typically motivated by gaining information, with previous research showing that potential information gains drive a "directed" type of exploration. Yet, this research usually studies exploration in the context of learning paradigms and does not directly manipulate multiple levels of information gain. Here, we present a task that isolates learning from decision-making and controls the magnitude of prospective information gains. As predicted, participants explore more with larger future information gains. Both value gains and information gains, at a trial-by-trial level, engage the ventromedial prefrontal cortex (vmPFC), the ventral striatum (VStr), the amygdala, the dorsal anterior cingulate cortex (dACC), and the anterior insula (aINS). Moreover, individual sensitivities to value gains and information gains modulate the vmPFC, dACC, and aINS, but the amygdala and VStr are modulated only by individual sensitivities to information gains. Overall, we identify the neural circuitry of information-based exploration and its relationship with inter-individual exploration biases.

Inhibitory mechanisms in the prefrontal-cortex differentially mediate Putamen activity during valence-based learning.

Learning from appetitive and aversive stimuli is important for survival. It involves interactions between the prefrontal cortex and subcortical structures, with inhibition playing a crucial role. However, direct evidence for this in humans is limited. Here, we overcome the difficulty of measuring inhibition in the human brain and find that GABA, the main inhibitory neurotransmitter, affects how the dACC interacts with subcortical structures during appetitive and aversive learning differently. We used 7T magnetic resonance spectroscopy (MRS) to track GABA levels in the dACC alongside whole-brain fMRI scans while participants engaged in appetitive and aversive learning tasks. During appetitive learning, dACC GABA levels were negatively correlated with learning performance and BOLD activity measured from the dACC and the Putamen. While under aversive learning, dACC GABA concentration negatively correlated with the functional connectivity between the dACC and the Putamen. Our results show that inhibition in the dACC mediates appetitive and aversive learning in humans through distinct mechanisms.

Aversive-bias and stage-selectivity in neurons of the primate amygdala during acquisition, extinction, and overnight retention.

Extensive evidence implicates the amygdala as a major station for acquisition, extinction, and consolidation of emotional memories. Most of this work relies on fear-conditioning in rodents and imaging in humans. Few studies have explored coding of value in the primate amygdala, but the circuitry that underlies extinction and overnight retention remains largely unexplored. We developed a learning paradigm for nonhuman primates (macaca fascicularis) and recorded the activity of single neurons during the different stages of acquisition, extinction, and overnight consolidation of pleasant and aversive tone-odor associations. We find that many neurons become phase-locked to respiratory cycles in a stage-dependent manner, emphasizing the flexibility of amygdala neurons to represent the current state and change their spontaneous activity accordingly. We suggest that these changes can serve to increase neuronal sensitivity to an upcoming event and facilitate learning mechanisms. We further show formation of aversive-bias during the acquisition of associations and during overnight retention, in the sense that neurons preferentially code for the aversive conditioned stimuli, even if they initially homogenously represent value of the reinforcer. Our findings show flexible representations in the primate amygdala during the different cycles of learning and memory, and suggest selective potentiation of aversive information.

Monetary loss alters perceptual thresholds and compromises future decisions via amygdala and prefrontal networks.

The influence of monetary loss on decision making and choice behavior is extensively studied. However, the effect of loss on sensory perception is less explored. Here, we use conditioning in human subjects to explore how monetary loss associated with a pure tone can affect changes in perceptual thresholds for the previously neutral stimulus. We found that loss conditioning, when compared with neutral exposure, decreases sensitivity and increases perceptual thresholds (i.e., a relative increase in the just-noticeable-difference). This was so even when compared with gain conditioning of comparable intensity, suggesting that the finding is related to valence. We further show that these perceptual changes are related to future decisions about stimuli that are farther away from the conditioned one (wider generalization), resulting in overall increased and irrational monetary loss for the subjects. We use functional imaging to identify the neural network whose activity correlates with the deterioration in sensitivity on an individual basis. In addition, we show that activity in the amygdala was tightly correlated with the wider behavioral generalization, namely, when wrong decisions were made. We suggest that, in principle, less discrimination can be beneficial in loss scenarios, because it assures an accurate and fast response to stimuli that resemble the original stimulus and hence have a high likelihood of entailing the same outcome. But whereas this can be useful for primary reinforcers that can impact survival, it can also underlie wrong and costly behaviors in scenarios of contemporary life that involve secondary reinforcers.

Low-frequency stimulation depresses the primate anterior-cingulate-cortex and prevents spontaneous recovery of aversive memories.

Functional abnormalities in the dorsal-anterior-cingulate-cortex (dACC) underlie anxiety disorders and specifically post-traumatic stress disorder (PTSD). Promising and common behavioral approaches have limited effectiveness and many subjects exhibit spontaneous recovery of fear, as also evident in animal models following extinction training. Here, we use low-frequency stimulation (LFS), a protocol shown to induce long-term depression, with the aim of affecting synaptic plasticity induced by fear acquisition and extinction. We use aversive conditioning of either tone or visual stimuli paired with an aversive air-puff to the eye in a trace-conditioning paradigm. We find that LFS in the nonhuman primate (Macaca fascicularis) dACC, when combined with extinction training, was successful in preventing spontaneous recovery of the memory 24-72 h following extinction. We simultaneously record single-units and local-field-potentials across the dACC, and show that LFS gradually depressed evoked responses. Moreover, this decrease in neural excitability predicted the successful reduction of overnight spontaneous recovery on a day-by-day basis. Finally, we show that this effect occurs when using either visual or auditory modality as the conditioned stimulus, and that the reduction was specific to the conditioned modality. Our results suggest that the primate dACC is actively involved in maintaining the original aversive memory, and propose that a combination of LFS with behavioral therapy might significantly improve treatment in severe cases.

A Bayesian approach for characterizing direction tuning curves in the supplementary motor area of behaving monkeys.

Neural responses are commonly studied in terms of "tuning curves," characterizing changes in neuronal response as a function of a continuous stimulus parameter. In the motor system, neural responses to movement direction often follow a bell-shaped tuning curve for which the exact shape determines the properties of neuronal movement coding. Estimating the shape of that tuning curve robustly is hard, especially when directions are sampled unevenly and at a coarse resolution. Here, we describe a Bayesian estimation procedure that improves the accuracy of curve-shape estimation even when the curve is sampled unevenly and at a very coarse resolution. Using this approach, we characterize the movement direction tuning curves in the supplementary motor area (SMA) of behaving monkeys. We compare the SMA tuning curves to tuning curves of neurons from the primary motor cortex (M1) of the same monkeys, showing that the tuning curves of the SMA neurons tend to be narrower and shallower. We also show that these characteristics do not depend on the specific location in each region.