Dopamine is associated with prioritization of reward-associated memories in Parkinson’s disease

Patients with Parkinson’s disease have reduced reward sensitivity related to dopaminergic neuron loss, which is associated with impairments in reinforcement learning. Increasingly, however, dopamine-dependent reward signals are recognized to play an important role beyond reinforcement learning. In particular, it has been shown that reward signals mediated by dopamine help guide the prioritization of events for long-term memory consolidation. Meanwhile, studies of memory in patients with Parkinson’s disease have focused on overall memory capacity rather than what is versus what isn’t remembered, leaving open questions about the effect of dopamine replacement on the prioritization of memories by reward and the time-dependence of this effect. The current study sought to fill this gap by testing the effect of reward and dopamine on memory in patients with Parkinson’s disease. We tested the effect of dopamine modulation and reward on two forms of long-term memory: episodic memory for neutral objects and memory for stimulus-value associations. We measured both forms of memory in a single task, adapting a standard task of reinforcement learning with incidental episodic encoding events of trial-unique objects. Objects were presented on each trial at the time of feedback, which was either rewarding or not. Memory for the trial-unique images and for the stimulus-value associations, and the influence of reward on both, was tested immediately after learning and 2 days later. We measured performance in Parkinson’s disease patients tested either ON or OFF their dopaminergic medications and in healthy older control subjects. We found that dopamine was associated with a selective enhancement of memory for reward-associated images, but that it did not influence overall memory capacity. Contrary to predictions, this effect did not differ between the immediate and delayed memory tests. We also found that while dopamine had an effect on reward-modulated episodic memory, there was no effect of dopamine on memory for stimulus-value associations. Our results suggest that impaired prioritization of cognitive resource allocation may contribute to the early cognitive deficits of Parkinson’s disease.

Stable and dynamic representations of value in the prefrontal cortex

Optimal decision-making requires that stimulus-value associations are kept up to date by constantly comparing the expected value of a stimulus with its experienced outcome. To do this, value information must be held in mind when a stimulus and outcome are separated in time. However, little is known about the neural mechanisms of working memory (WM) for value. Contradicting theories have suggested WM requires either persistent or transient neuronal activity, with stable or dynamic representations, respectively. To test these hypotheses, we recorded neuronal activity in the orbitofrontal and anterior cingulate cortex of two monkeys performing a valuation task. We found that features of all hypotheses were simultaneously present in prefrontal activity, and no single hypothesis was exclusively supported. Instead, mixed dynamics supported robust, time invariant value representations while also encoding the information in a temporally specific manner. We suggest that this hybrid coding is a critical mechanism supporting flexible cognitive abilities.

Stopped cold: Motor-response inhibition reduces the capacity of sexually-explicit stimuli to elicit subjective and physiological sexual arousal

The motivational incentive of sexual stimuli can be a salient force in determining the focus of thought and behaviour. Here we show that the simple act of not pressing a key during the perception of sexual content reduces its motivational incentive and subsequent capacity to elicit sexual arousal. Undergraduate participants (N=116) completed a Go/No-go task that required them to inhibit responses to either sexual or non-sexual images. Later they watched sexually explicit videos and reported moment-to-moment changes in self-reported sexual arousal, while thermography was used to record changes in genital physiological arousal. Participants who previously inhibited sexual images experienced lower levels of both self-reported and physiological arousal than those who inhibited non-sexual images. These results extend prior research to suggest that a by-product of motor-response inhibition is a negative alteration of stimulus-value representations for associated items— the kind of value that drives even the most biologically-fundamental forms of motivated behaviour.

Механизмы перехода от ритмической активности к пачечной в модели ноцицептивного нейрона

The transitions from tonic spiking to bursting for the nociceptive neuron model have been studied with changing the external stimulus value. The presence of the fold limit cycle bifurcation in the structure of the bifurcation diagram of the fast subsystem and the torus bifurcation in the structure of the bifurcation diagram of the full system lead to the emergence of special solutions of the type torus canards in these transitions. This confirms the assumption that torus canards are an obligatory feature for transitions between rhythmic and burst discharges

Differential rapid plasticity in auditory and visual responses in the primarily multisensory orbitofrontal cortex

In a dynamic environment with rapidly changing contingencies, the orbitofrontal cortex (OFC) guides flexible behavior through coding of stimulus value. Although stimulus-evoked responses in the OFC are known to convey outcome, baseline sensory response properties in the mouse OFC are poorly understood. To understand mechanisms involved in stimulus value/outcome encoding it is important to know the response properties of single neurons in the mouse OFC, purely from a sensory perspective. Ruling out effects of behavioral state, memory and others, we studied the anesthetized mouse OFC responses to auditory, visual and audiovisual/multisensory stimuli, multisensory associations and sensory-driven input organization to the OFC. Almost all, OFC single neurons were found to be multisensory in nature, with sublinear to supralinear integration of the component unisensory stimuli. With a novel multisensory oddball stimulus set, we show that the OFC receives both unisensory as well as multisensory inputs, further corroborated by retrograde tracers showing labeling in secondary auditory and visual cortices, which we find to also have similar multisensory integration and responses. With long audiovisual pairing/association, we show rapid plasticity in OFC single neurons, with a strong visual bias, leading to a strong depression of auditory responses and effective enhancement of visual responses. Such rapid multisensory association driven plasticity is absent in the auditory and visual cortices, suggesting its emergence in the OFC. Based on the above results we propose a hypothetical local circuit model in the OFC that integrates auditory and visual information which participates in computing stimulus value in dynamic multisensory environments.Significance StatementProperties and modification of sensory responses of neurons in the orbitofrontal cortex (OFC) involved in flexible behavior through stimulus value/outcome encoding are poorly understood. Such responses are critical in providing the framework for the encoding of stimulus value based on behavioral context while also directing plastic changes in sensory regions. The mouse OFC is found to be primarily multisensory with varied nonlinear interactions, explained by unisensory and multisensory inputs. Audio-visual associations cause rapid plastic changes in the OFC, which bias visual responses while suppressing auditory responses. Similar plasticity was absent in the sensory cortex. Thus the observed intrinsic visual bias in the OFC weighs visual stimuli more than associated auditory stimuli in value encoding in a dynamic multisensory environment.

Stable and dynamic representations of value in the prefrontal cortex

The ability to associate positive and negative outcomes with predictive stimuli allows us to make optimal decisions. These stimulus-value associations are kept up to date by comparing an expected value with the experienced outcome. When a stimulus and its outcome are separated by a delay, the value associated with the stimulus must be held in mind for such comparisons to be possible, however little is known about the neural mechanisms that hold value representations online across delays. Temporarily remembering task-relevant information has been extensively studied in the context of item-specific working memory, and different hypotheses have suggested this ability requires either persistent or transient neuronal activity, with stable or dynamic representations respectively. To test these different hypotheses in the context of value representations, we recorded the spiking activity of neurons in the orbitofrontal and anterior cingulate cortex of two monkeys performing a task in which visual cues predicted a reward delivered after a short delay. We found that features of all hypotheses were simultaneously present in prefrontal activity and therefore no single hypothesis was exclusively supported. Instead, we report mixed dynamics that support robust, time invariant value representations while also encoding the information in a temporally specific manner. We suggest that this hybrid coding is important for optimal behavior and might be a critical mechanism supporting flexible cognitive abilities.

Dynamic perceptual feature selectivity in primary somatosensory cortex upon reversal learning

ABSTRACTNeurons in primary sensory cortex encode a variety of stimulus features upon perceptual learning. However, it is unclear whether the acquired stimulus selectivity remains stable when the same input is perceived in a different context. Here, we monitored the activity of individual neurons in the mouse primary somatosensory cortex in a reward-based texture discrimination task. We tracked their stimulus selectivity before and after changing reward contingencies, which allowed us to identify various classes of neurons. We found neurons that stably represented a texture or the upcoming behavioral choice, but the majority was dynamic. Among those, a subpopulation of neurons regained selectivity contingent on stimulus-value. These value-sensitive neurons forecasted the onset of learning by displaying a distinct and transient increase in activity, depending on past behavioral experience. Thus, stimulus selectivity of excitatory neurons during perceptual learning is dynamic and largely relies on behavioral contingencies, even in primary sensory cortex.

Single-response appetitive Pavlovian to instrumental transfer is suppressed by aversive counter-conditioning

Environmental stimuli, when paired with reward, can influence behaviour in maladaptive ways, for example, by encouraging overeating or addiction. Such behaviour can be sensitive to reward value manipulations, under circumscribed conditions, but whether reward-seeking is also sensitive to stimulus value manipulations remains unclear. Thus, the current experiment investigated whether reducing the hedonic value of a reward-paired stimulus would reduce reward-seeking behaviour. In total, 36 participants successfully completed a single-response Pavlovian-instrumental transfer (PIT) task with a counter-conditioning procedure. The Pavlovian phase associated three conditioned stimuli (CSs) with money at 100%, 50%, or 0% contingency. Counter-conditioning then followed for the experimental group, who saw the 100% CS paired with unpleasant pictures, while the control group saw only neutral images. Instrumental training required participants to learn a button-pressing response to win money. The transfer phase contrasted instrumental responding during baseline and CS presentation. Both experimental and control groups liked the 100% CS more than the other CSs after Pavlovian training, but counter-conditioning reduced this 100% CS liking. In transfer, the experimental group showed an abolition of appetitive PIT, while the control group showed maintenance of appetitive PIT. However, this group difference was only evident in response vigour, not response initiation. In summary, CS hedonic value influences cue-potentiated instrumental responding. More specifically, hedonic value of a reward-paired cue influences the vigour of instrumental responses, but not the decision to initiate a response. These data may have relevance to smoking cessation policies, where the introduction of health warnings may be viewed as a real-world example of counter conditioning.

Occipital Alpha and Gamma Oscillations Support Complementary Mechanisms for Processing Stimulus Value Associations

Selective attention is reflected neurally in changes in the power of posterior neural oscillations in the alpha (8–12 Hz) and gamma (40–100 Hz) bands. Although a neural mechanism that allows relevant information to be selectively processed has its advantages, it may lead to lucrative or dangerous information going unnoticed. Neural systems are also in place for processing rewarding and punishing information. Here, we examine the interaction between selective attention (left vs. right) and stimulus's learned value associations (neutral, punished, or rewarded) and how they compete for control of posterior neural oscillations. We found that both attention and stimulus–value associations influenced neural oscillations. Whereas selective attention had comparable effects on alpha and gamma oscillations, value associations had dissociable effects on these neural markers of attention. Salient targets (associated with positive and negative outcomes) hijacked changes in alpha power—increasing hemispheric alpha lateralization when salient targets were attended, decreasing it when they were being ignored. In contrast, hemispheric gamma-band lateralization was specifically abolished by negative distractors. Source analysis indicated occipital generators of both attentional and value effects. Thus, posterior cortical oscillations support both the ability to selectively attend while at the same time retaining the ability to remain sensitive to valuable features in the environment. Moreover, the versatility of our attentional system to respond separately to salient from merely positively valued stimuli appears to be carried out by separate neural processes reflected in different frequency bands.