Dopamine firing plays a dual role in coding reward prediction errors and signaling motivation in a working memory task

Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. Here, we investigated midbrain DA activity in monkeys performing a discrimination task in which the animal had to use working memory (WM) to report which of two sequentially applied vibrotactile stimuli had the higher frequency. We found that perception was altered by an internal bias, likely generated by deterioration of the representation of the first frequency during the WM period. This bias greatly controlled the DA phasic response during the two stimulation periods, confirming that DA reward prediction errors reflected stimulus perception. In contrast, tonic dopamine activity during WM was not affected by the bias and did not encode the stored frequency. More interestingly, both delay-period activity and phasic responses before the second stimulus negatively correlated with reaction times of the animals after the trial start cue and thus represented motivated behavior on a trial-by-trial basis. During WM, this motivation signal underwent a ramp-like increase. At the same time, motivation positively correlated with accuracy, especially in difficult trials, probably by decreasing the effect of the bias. Overall, our results indicate that DA activity, in addition to encoding reward prediction errors, could at the same time be involved in motivation and WM. In particular, the ramping activity during the delay period suggests a possible DA role in stabilizing sustained cortical activity, hypothetically by increasing the gain communicated to prefrontal neurons in a motivation-dependent way.

The immediate effect of Sinapis nigra and Zingiber officinale as thermogenic substances during footbaths: A Randomized Controlled Cross-over Trial

Objective: Warm footbaths infused with Sinapis nigra (mustard, or MU) or Zingiber officinale (ginger, or GI) are used for various thermoregulatory conditions, but little is known about how they are perceived by individuals, both short- and long-term. We analyzed the immediate and long-term effects of MU and GI on warmth and stimulus perception in healthy adults. Methods: Seventeen individuals (mean age 22.1±2.4 years; 11 female) received three footbaths (mean temperature was 40 ± 0.2 ℃, administered between 1:30-6:30pm) in a randomized order with a cross-over design: 1. with warm water only (WA), 2. with warm water and MU and 3. with warm water and GI. Warmth and stimulus perception at the feet were assessed at the 1st, 5th, 10th, 15th, and 20th minute of the footbaths, in the late evening (EVE), and the following morning (MG). We further assessed well-being (at EVE and MG) and sleep quality (at MG). The primary outcome measure was the warmth perception at the feet at the 10th minute of the footbath. Results: At the 10th minute of the footbath, warmth perception at the feet was significantly higher with MU and GI compared to WA. The immediate thermogenic effects pointed to a quick increase in warmth and stimulus perception with MU, a slower increase with GI, and a gradual decrease with WA. Regarding the long-term effects, warmth and stimulus perception were still higher after GI compared to WA at EVE and MG. No differences were seen for general well-being and sleep quality. Conclusion: Thermogenic substances can significantly alter the dynamics of warmth and stimulus perception when added to footbaths. The different profiles in the application of GI and MU could be relevant for a more differentiated and specific use of both substances in different therapeutic indications.

A role of oligodendrocytes in information processing

Myelinating oligodendrocytes enable fast propagation of action potentials along the ensheathed axons. In addition, oligodendrocytes play diverse non-canonical roles including axonal metabolic support and activity-dependent myelination. An open question remains whether myelination also contributes to information processing in addition to speeding up conduction velocity. Here, we analyze the role of myelin in auditory information processing using paradigms that are also good predictors of speech understanding in humans. We compare mice with different degrees of dysmyelination using acute multiunit recordings in the auditory cortex, in combination with behavioral readouts. We find complex alterations of neuronal responses that reflect fatigue and temporal acuity deficits. We observe partially discriminable but similar deficits in well myelinated mice in which glial cells cannot fully support axons metabolically. We suggest a model in which myelination contributes to sustained stimulus perception in temporally complex paradigms, with a role of metabolically active oligodendrocytes in cortical information processing.

Sensory experience selectively reorganizes the late component of evoked responses

In response to sensory stimulation, the cortex exhibits an early transient response followed by a late and slower activation pattern. Recent studies suggest that the early component represents features of the stimulus while the late component is associated with stimulus perception. In this work we study how patterns of evoked activity are modified by experience at meso and microcircuit scales using voltage and extracellular glutamate transient recordings over widespread regions of mice dorsal neocortex or single-unit activity recordings with multi-shank silicon probes in rat cortex. We find that repeated tactile or auditory stimulation selectively modifies the spatiotemporal patterns of activity mainly of the late evoked response at the mesoscale and microcircuit levels. This modification results not only in an increase in amplitude of the late response, but also in an increased similarity between the spatiotemporal patterns of the early and late evoked activity across trials. These changes are only present in the sensory area corresponding to the modality that received the repeated stimulation and they persisted up to one hour. Thus, this selective long-lasting spatiotemporal modification of the cortical activity patterns provides new insights about how perception-related cortical activity changes with sensory experience at multiple scales.

To perceive or not to perceive? Individual differences in perception predict rule induction and response generalization

When novel stimuli trigger a previously learned response, this can be due to failure to perceive the novel stimulus as different from the trained stimulus (perception), or active extrapolation of learned properties from the trained stimulus (induction). To date, there has been little investigation of how individual differences in perceptual ability relate to differences in induction. In this paper, we perform cluster analysis in six datasets (four published datasets and two unpublished datasets, N = 992 total) to examine the relationship between individual differences in perception and induction, as well as the utility of perception in predicting generalization gradients. The datasets were obtained from predictive learning tasks where participants learned associations between different colored cues and the presence or absence of a hypothetical outcome. In these datasets, stimulus perception and response generalization (expectancy ratings) were assessed in separate phases. Using cluster analyses, we identified similar subgroups of good and bad perceivers in all six datasets, with distinct patterns of response generalization between these subgroups. Based on the differences in stimulus perception, we could predict where across the stimulus range generalized responses would differ between subgroups as well as the direction of the difference. Furthermore, participants classified as good perceivers were more likely to report a similarity generalization rule than a relational or linear rule, providing evidence that individual differences in perception predict differences in induction. These findings suggest that greater consideration should be given to inter-individual variability in perception and induction and their relationship in explaining response generalization.

Transcranial Magnetic Stimulation-induced motor cortex activity influences visual awareness judgments

The influence of non-visual information on visual awareness judgments has recently gained substantial interest. Using single-pulse Transcranial Magnetic Stimulation (TMS), we investigate the potential contribution of evidence from the motor system to judgment of visual awareness. We hypothesized that TMS-induced activity in the primary motor cortex (M1) would increase reported visual awareness as compared to the control condition. Additionally, we investigated whether TMS-induced motor-evoked potential could measure accumulated evidence for stimulus perception. Following stimulus presentation and TMS, participants first rated their visual awareness verbally using the Perceptual Awareness Scale, after which they responded manually to a Gabor orientation identification task. Delivering TMS to M1 resulted in higher average awareness ratings as compared to the control condition, in both correct and incorrect identification task response trials, when the hand with which participants responded was contralateral to the stimulated hemisphere (TMS-response-congruent trials). This effect was accompanied by longer Perceptual Awareness Scale response times, irrespective of the congruence between TMS and identification response. Moreover, longer identification response times were observed in TMS-response-congruent trials in the M1 condition as compared to the control condition. Additionally, the amplitudes of motor-evoked potentials were related to the awareness ratings when response congruence was taken into account. We argue that motor-evoked potential can serve as an indirect measure of evidence accumulated for stimulus perception and that longer Perceptual Awareness Scale response times and higher amplitudes of motor-evoked potentials in the M1 condition reflect integration of additional evidence with visual awareness judgment. In conclusion, we advocate that motor activity influences perceptual awareness judgments.