Transient neuronal suppression for exploitation of new sensory evidence

In noisy but stationary environments, decisions should be based on the temporal integration of sequentially sampled evidence. This strategy has been supported by many behavioral studies and is qualitatively consistent with neural activity in multiple brain areas. By contrast, decision-making in the face of non-stationary sensory evidence remains poorly understood. Here, we trained monkeys to identify and respond via saccade to the dominant color of a dynamically refreshed bicolor patch that becomes informative after a variable delay. Animals’ behavioral responses were briefly suppressed after evidence changes, and many neurons in the frontal eye field displayed a corresponding dip in activity at this time, similar to that frequently observed after stimulus onset but sensitive to stimulus strength. Generalized drift-diffusion models revealed consistency of behavior and neural activity with brief suppression of motor output, but not with pausing or resetting of evidence accumulation. These results suggest that momentary arrest of motor preparation is important for dynamic perceptual decision making.

Multiplexed and flexible neural coding in sensory, parietal, and frontal cortices during goal-directed virtual navigation

We do not understand how neural nodes operate within the recurrent action-perception loops that characterize naturalistic self-environment interactions, nor how brain networks reconfigure during changing computational demands. Here, we record local field potentials (LFPs) and spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and dorsolateral prefrontal cortex (dlPFC) as monkeys navigate in virtual reality to “catch fireflies”. This task requires animals to actively sample from a closed-loop visual environment while concurrently computing latent variables: the evolving distance and angle to a memorized firefly. We observed mixed selectivity in all areas, with even a traditionally sensory area (MSTd) tracking latent variables. Strikingly, global encoding profiles and unit-to-unit coupling suggested a functional subnetwork between MSTd and dlPFC, and not between these areas and 7a, as anatomy would suggest. When sensory evidence was rendered scarce, lateral connectivity through neuron-to-neuron coupling within MSTd strengthened but its pattern remained fixed, while neuronal coupling adaptively remapped within 7a and dlPFC. The larger the remapping in 7a/dlPFC and the greater the stability within MSTd, the less was behavior impacted by loss of sensory evidence. These results highlight the distributed nature of neural coding during closed-loop action-perception naturalistic behaviors and suggest internal models may be housed in the pattern of fine-grain lateral connectivity within parietal and frontal cortices.

Enhanced learning and sensory salience in a cerebellar mouse autism model

Among the impairments manifested by autism spectrum disorder (ASD) are sometimes islands of enhanced function. Although neuronal mechanisms for enhanced functions in ASD are unknown, the cerebellum is a major site of developmental alteration, and early-life perturbation to it leads to ASD with higher likelihood than any other brain region. Here we report that a cerebellum-specific transgenic mouse model of ASD shows faster learning on a sensory evidence-accumulation task. In addition, transgenic mice showed enhanced sensitivity to touch and auditory cues, and prolonged electrophysiological responses in Purkinje-cell complex spikes and associative neocortical regions. These findings were replicated by pairing cues with optogenetic stimulation of Purkinje cells. Computational latent-state analysis of behavior revealed that both groups of mice with cerebellar perturbations exhibited enhanced focus on current rather than past information, consistent with a role for the cerebellum in retaining information in memory. We conclude that cerebellar perturbation can activate neocortex via complex spike activity and reduce reliance on prior experience, consistent with a weak-central-coherence account in which ASD traits arise from enhanced detail-oriented processing. This recasts ASD not so much as a disorder but as a variation that, in particular niches, can be adaptive.

Evaluating the Potential for Smoke from Stubble Burning to Taint Grapes and Wine

It has been well established that bushfire/wildfire smoke can taint grapes (and therefore wine), depending on the timing and duration of exposure, but the risk of smoke contamination from stubble burning (a practice employed by some grain growers to prepare farmland for sowing) has not yet been established. This study exposed excised bunches of grapes to smoke from combustion of barley straw and pea stubble windrows to investigate the potential for stubble burning to elicit smoke taint. Increased levels of volatile phenols (i.e., chemical markers of smoke taint) were detected in grapes exposed to barley straw smoke (relative to control grapes), with smoke density and the duration of smoke exposure influencing grape volatile phenols. However, the sensory panel did not perceive wine made from grapes exposed to low-density smoke to be tainted, despite the presence of low levels of syringol providing compositional evidence of smoke exposure. During the pea stubble burn, grapes positioned amongst the burning windrows or on the edge of the pea paddock were exposed to smoke for ~15–20 and 30–45 min, respectively, but this only resulted in 1 µg/kg differences in the cresol and/or syringol concentrations of smoke-affected grapes (and 1 µg/L differences for wine), relative to controls. A small, but significant increase in the intensity of smoke aroma and burnt rubber flavor of wine made from the grapes positioned amongst the burning pea stubble windrows provided the only sensory evidence of any smoke taint. As such, had vineyards been located immediately downwind from the pea stubble burn, it is unlikely that there would have been any smoke contamination of unharvested grapes.

Trial-by-trial fluctuations in amygdala activity track motivational enhancement of desirable sensory evidence during perceptual decision-making

People are biased towards seeing outcomes that they are motivated to see. For example, sports fans of opposing teams often perceive the same ambiguous foul in favor of the team they support. Here, we test the hypothesis that amygdala-dependent allocation of visual attention facilitates motivational biases in perceptual decision-making. Human participants were rewarded for correctly categorizing an ambiguous image into one of two categories while undergoing fMRI. On each trial, we used a financial bonus to motivate participants to see one category over another. The reward maximizing strategy was to perform the categorization task accurately, but participants were biased towards categorizing the images as the category we motivated them to see. Heightened amygdala activity preceded motivation consistent categorizations, and participants with higher amygdala activation exhibited stronger motivational biases in their perceptual reports. Trial-by-trial amygdala activity was associated with stronger enhancement of neural activity encoding desirable percepts in sensory cortices, suggesting that amygdala-dependent effects on perceptual decisions arose from biased sensory processing. Analyses using a drift diffusion model provide converging evidence that trial-by-trial amygdala activity was associated with stronger motivational biases in the accumulation of sensory evidence. Prior work examining biases in perceptual decision-making have focused on the role of frontoparietal regions. Our work highlights an important contribution of the amygdala. When people are motivated to see one outcome over another, the amygdala biases perceptual decisions towards those outcomes.Significance StatementForming accurate perceptions of the environment is essential for adaptive behavior. People however are biased towards seeing what they want to see, giving rise to inaccurate perceptions and erroneous decisions. Here, we combined behavior, modeling, and fMRI to show that the bias towards seeing desirable percepts is related to trial-by-trial fluctuations in amygdala activity. In particular, during moments with higher amygdala activity, sensory processing is biased in favor of desirable percepts, such that participants are more likely to see what they want to see. These findings highlight the role of the amygdala in biasing visual perception, and shed light on the neural mechanisms underlying the influence of motivation and reward on how people decide what they see.

Frontal but not parietal cortex is required for decisions under risk

Neurons in frontal and parietal cortex encode task variables during decision-making, but causal manipulations of the two regions produce strikingly different results. For example, silencing the posterior parietal cortex (PPC) in rats and monkeys produces minimal effects in perceptual decisions requiring integration of sensory evidence, but silencing frontal cortex profoundly impairs the same decisions. Here, we tested, for the first time, the causal roles of the rat frontal orienting field (FOF) and PPC in economic choice under risk. On each trial, rats chose between a lottery and a small but guaranteed surebet. The magnitude of the lottery was independently varied across trials and was indicated to the rat by the pitch of an auditory cue. As in perceptual decisions, both unilateral and bilateral PPC muscimol inactivations produced weak effects. FOF inactivations produced substantial changes in behavior even though our task had no working memory component. We quantified control and bilateral inactivation behavior with a multi-agent model consisting of a mixture of a 'rational' utility-maximizing agent (U=Vρ) with two `habitual' agents that either choose surebet or lottery. Silencing PPC produced no significant shifts in any parameters relative to controls. Effects of FOF silencing were best explained by a decrease in ρ, the exponent of the utility function. This effect was parsimoniously explained by a dynamical model where the FOF is part of network that performs sensory-to-value transformations.

Age-related response speed deficits arise from specific impairments in sensory evidence accumulation rate

Older adults exposed to enriched environments (EE) maintain relatively higher levels of cognitive function, even in the face of compromised markers of brain health. Response speed (RS) is often used as a simple proxy to measure the preservation of global cognitive function in older adults. However, it is unknown which specific sensory, decision, and/or motor processes provide the most specific indices of neurocognitive health. Here, using a simple decision task with electroencephalography (EEG), we found that the efficiency with which an individual accumulates sensory evidence was a critical determinant of the extent to which RS was preserved in older adults. Moreover, the mitigating influence of EE on age-related RS declines was most pronounced when evidence accumulation rates were shallowest. Our results suggest that EEG metrics of evidence accumulation may index neurocognitive vulnerability of the ageing brain.

Flexible neural coding in sensory, parietal, and frontal cortices during goal-directed virtual navigation

We do not understand how neural nodes operate within the recurrent action-perception loops that characterize naturalistic self-environment interactions, nor how brain networks reconfigure during changing computational demands. Here, we record local field potentials (LFPs) and spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and dorsolateral prefrontal cortex (dlPFC) as monkeys navigate in virtual reality to catch fireflies. This task requires animals to actively sample from a closed-loop visual environment while concurrently computing latent variables: the evolving distance and angle to a memorized firefly. We observed mixed selectivity in all areas, with even a traditionally sensory area (MSTd) tracking latent variables. Strikingly, global encoding profiles and unit-to-unit coupling suggested a functional subnetwork between MSTd and dlPFC, and not between these are 7a, as anatomy would suggest. When sensory evidence was rendered scarce, lateral connectivity through neuron-to-neuron coupling within MSTd strengthened but its pattern remains fixed, while neuronal coupling adaptively remapped within 7a and dlPFC. The larger the remapping in 7a/dlPFC and the greater the stability within MSTd, the less was behavior impacted by loss of sensory evidence. These results highlight the distributed nature of neural coding during closed-loop action-perception naturalistic behaviors and suggest internal models may be housed in the pattern of fine-grain lateral connectivity within parietal and frontal cortices.

Toward the unity of pathological and exertional fatigue: A predictive processing model

Fatigue is a common experience in both health and disease. Yet, pathological (i.e., prolonged or chronic) and transient (i.e., exertional) fatigue symptoms are traditionally considered distinct, compounding a separation between interested research fields within the study of fatigue. Within the clinical neurosciences, nascent frameworks position pathological fatigue as a product of inference derived through hierarchical predictive processing. The metacognitive theory of dyshomeostasis (Stephan et al., 2016) states that pathological fatigue emerges from the metacognitive mechanism in which the detection of persistent mismatches between prior interoceptive predictions and ascending sensory evidence (i.e., prediction error) signals low evidence for internal generative models, which undermine an agent’s feeling of mastery over the body and is thus experienced phenomenologically as fatigue. Although acute, transient subjective symptoms of exertional fatigue have also been associated with increasing interoceptive prediction error, the dynamic computations that underlie its development have not been clearly defined. Here, drawing on the metacognitive theory of dyshomeostasis, we extend this account to offer an explicit description of the development of fatigue during extended periods of (physical) exertion. Accordingly, it is proposed that a loss of certainty or confidence in control predictions in response to persistent detection of prediction error features as a common foundation for the conscious experience of both pathological and nonpathological fatigue.