Glucose-stimulated calcium dynamics in beta cells from C57BL/6J, C57BL/6N, and NMRI mice: A systematic comparison of activation, activity, and deactivation properties in tissue slices

Although mice are a very instrumental model in islet beta cell research, possible phenotypic differences between strains and substrains are largely neglected in the scientific community. In this study, we show important phenotypic differences in beta cell responses to glucose between NMRI, C57BL/6J, and C57BL/6N mice, i.e., the three most commonly used strains. High-resolution multicellular confocal imaging of beta cells in acute pancreas tissue slices was used to measure and quantitatively compare the calcium dynamics in response to a wide range of glucose concentrations. Strain- and substrain-specific features were found in all three phases of beta cell responses to glucose: a shift in the dose-response curve characterizing the delay to activation and deactivation in response to stimulus onset and termination, respectively, and distinct concentration-encoding principles during the plateau phase in terms of frequency, duration, and active time changes with increasing glucose concentrations. Our results underline the significance of carefully choosing and reporting the strain to enable comparison and increase reproducibility, emphasize the importance of analyzing a number of different beta cell physiological parameters characterizing the response to glucose, and provide a valuable standard for future studies on beta cell calcium dynamics in health and disease.

Increased insula activity precedes the formation of subjective Gestalt

The constructive nature of human perception sometimes leads us to perceiving rather complex impressions from simple sensory input. Bistable stimuli give us a rare opportunity to study the neural mechanisms behind this process. Such stimuli can be visually interpreted as simple or as more complex on the basis of the same sensory input. Previous studies demonstrated increased activity in the superior parietal cortex when participants perceived an illusory Gestalt impression compared to a simpler interpretation of individual elements. Here we tested whether activity related to the illusory Gestalt can be detected not only during, but also prior to it, by examining the slow fluctuations of resting-state-fMRI activity before the stimulus onset. We presented 31 participants with a bistable motion stimulus, which can be perceived either as four moving dot pairs (local) or two moving illusory squares (global). This allowed us to isolate the specific neural mechanisms that accompany the experience of an illusion under matched sensory input. fMRI was used to measure brain activity in a sparse event-related design. We observed stronger IPS and putamen responses to the stimulus when participants perceived the global interpretation compared to local, confirming the previously reported role of these areas in perceptual grouping. Most importantly, we also observed that the global stimulus interpretation was preceded by an increased activity of the bilateral dorsal insula, which is known to process saliency and gate information for conscious access. Our data suggest an important role of the dorsal insula in shaping an internally generated illusory Gestalt percept.

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.

Attention Limitations in the Detection and Identification of Alarms in Close Temporal Proximity

Objective The aim of this study was to establish the effects of simultaneous and asynchronous masking on the detection and identification of visual and auditory alarms in close temporal proximity. Background In complex and highly coupled systems, malfunctions can trigger numerous alarms within a short period of time. During such alarm floods, operators may fail to detect and identify alarms due to asynchronous and simultaneous masking. To date, the effects of masking on detection and identification have been studied almost exclusively for two alarms during single-task performance. This research examines 1) how masking affects alarm detection and identification in multitask environments and 2) whether those effects increase as a function of the number of alarms. Method Two experiments were conducted using a simulation of a drone-based package delivery service. Participants were required to ensure package delivery and respond to visual and auditory alarms associated with eight drones. The alarms were presented at various stimulus onset asynchronies (SOAs). The dependent measures included alarm detection rate, identification accuracy, and response time. Results Masking was observed intramodally and cross-modally for visual and auditory alarms. The SOAs at which asynchronous masking occurred were longer than reported in basic research on masking. The effects of asynchronous and, even more so, simultaneous masking became stronger as the number of alarms increased. Conclusion Masking can lead to breakdowns in the detection and identification of alarms in close temporal proximity in complex data-rich domains. Application The findings from this research provide guidance for the design of alarm systems.

Visual search training benefits from the integrative effect of enhanced covert attention and optimized overt eye movements

Visual search in a complex environment requires efficient discrimination between target and distractors. Training serves as an effective approach to improve visual search performance when the target does not automatically pop out from the distractors. In the present study, we trained subjects on a conjunction visual search task and examined the training effects in behavior and eye movement from Experiments 1 to 4. The results showed that training improved behavioral performance and reduced the number of saccades and overall scanning time. Training also increased the search initiation time before the first saccade and the proportion of trials in which the subjects correctly identified the target without any saccade, but these effects were modulated by stimulus' parameters. In Experiment 5, we replicated these training effects when eye movements and EEG signals were recorded simultaneously. The results revealed significant N2pc components after the stimulus onset (i.e., stimulus-locked) and before the first saccade (i.e., saccade-locked) when the search target was the trained one. These N2pc components can be considered as the neural signatures for the training-induced boost of covert attention to the trained target. The enhanced covert attention led to a beneficial tradeoff between search initiation time and the number of saccades as a small amount of increase in search initiation time could result in a larger reduction in scanning time. These findings suggest that the enhanced covert attention to target and optimized overt eye movements are coordinated together to facilitate visual search training.

Expectation violations produce error signals in mouse V1

Repeated exposure to visual sequences changes the form of evoked activity in the primary visual cortex (V1). Predictive coding theory provides a potential explanation for this, namely that plasticity shapes cortical circuits to encode spatiotemporal predictions and that subsequent responses are modulated by the degree to which actual inputs match these expectations. Here we use a recently developed statistical modeling technique called Model-Based Targeted Dimensionality Reduction (MbTDR) to study visually-evoked dynamics in mouse V1 in context of a previously described experimental paradigm called "sequence learning". We report that evoked spiking activity changed significantly with training, in a manner generally consistent with the predictive coding framework. Neural responses to expected stimuli were suppressed in a late window (100-150ms) after stimulus onset following training, while responses to novel stimuli were not. Omitting predictable stimuli led to increased firing at the expected time of stimulus onset, but only in trained mice. Substituting a novel stimulus for a familiar one led to changes in firing that persisted for at least 300ms. In addition, we show that spiking data can be used to accurately decode time within the sequence. Our findings are consistent with the idea that plasticity in early visual circuits is involved in coding spatiotemporal information.

Emotional salience modulates the forward flow of memory

Conditional response probability (CRP) analyses applied to free recall data indicate that recall occurs for contiguous items with forward-directionality, thought to reflect the shared encoding context of nearby items. We hypothesized that a context disruption, produced by presenting infrequent oddballs, would modulate CRP curves, increasing the forward-flow of recall due to strong binding of items presented after these oddballs to the new encoding context. Seventy young, healthy male and female participants encoded word lists containing either emotional or perceptual oddballs at varying stimulus onset asynchronies (SOA) followed by free recall. Serial recall transitions from emotional, but not perceptual, oddballs were enhanced in the forward direction except at the shortest SOA (1s). The present results provide empirical evidence of CRP modulation selectively by emotional salience and suggest that recall patterns after presenting emotional and perceptual oddballs are mediated by different mechanisms.

The interplay between unexpected events and behavior in the development of explicit knowledge in implicit sequence learning

Some studies in implicit learning investigate the mechanisms by which implicitly acquired knowledge (e.g., learning a sequence of responses) becomes consciously aware. It has been suggested that unexpected changes in the own behavior can trigger search processes, of which the outcome then becomes aware. A consistent empirical finding is that participants who develop explicit knowledge show a sudden decrease in reaction times, when responding to sequential events. This so called RT-drop might indicate the point of time when explicit knowledge occurs. We investigated whether an RT-drop is a precursor for the development of explicit knowledge or the consequence of explicit knowledge. To answer this question, we manipulated in a serial reaction time task the timing of long and short stimulus-onset asynchronies (SOA). For some participants, the different SOAs were presented in blocks of either long or short SOAs, while for others, the SOAs changed randomly. We expected the participants who were given a blocked presentation to express an RT-drop because of the predictable timing. In contrast, randomly changing SOAs should hamper the expression of an RT-drop. We found that more participants in the blocked-SOA condition than in the random-SOA condition showed an RT-drop. Furthermore, the amount of explicit knowledge did not differ between the two conditions. The findings suggest that the RT-drop does not seem to be a presupposition to develop explicit knowledge. Rather, it seems that the RT-drop indicates a behavioral strategy shift as a consequence of explicit knowledge.

Top-down contribution to motor network reorganization during action preparation

It is unclear whether the Bereitschaftspotential (BP) recorded in humans during action preparation mirrors motor areas activation escalation, or if its early and late phases reflect the engagement of different functional networks. Here, we aimed at recording the TMS evoked-potentials (TEP) stimulating the supplementary motor area (SMA) to assess whether and how cortical excitability and functional connectivity of this region change as the BP increases. We hypothesize that, at later stages, the SMA functional network should become more connected to regions relevant for the implementation of the final motor plan. We performed TMS-EEG recordings on fourteen healthy subjects during the performance of a visuomotor Go/No-go task, eliciting and recording cortical activity and functional connectivity at -700 ms and -300 ms before the onset of visual stimuli over the SMA. When approaching stimulus onset, and thus BP peak, the SMA increased its functional connectivity with movement-related structures in the gamma and alpha bands, indicating a regional top-down preparation to implement the motor act. Beta-band connectivity, instead, was maintained constant for the whole BP time-course, being potentially related to sustained attention required by the experimental task. These findings reveal that the BP is not a mere result of increased activation of the SMA, but the functional networks in which this region is involved qualitatively changes over time, becoming more related to the execution of the motor act.

Fearful temperament in middle childhood predicts adolescent attention bias and anxiety symptoms: The moderating role of frontal EEG asymmetry

The current study provided first analyses of the moderating effect of baseline-to-task frontal EEG asymmetry on the associations between 9-year fearful temperament and adolescent attention bias to threat as well as anxiety symptoms. Participants include a community sample of 122 children (60 boys, 62 girls; Mage = 14.66 years; Range = 11.82–18.13 years). Baseline-to-task frontal EEG asymmetry at age 9 moderated the relation between fearful temperament at age 9 and adolescent anxiety symptoms. Specifically, fearful temperament predicted adolescent anxiety symptoms when children showed greater right activation from baseline to an executive function task, but not greater left activation. Baseline-to-task frontal EEG asymmetry moderated the association between fearful temperament and sustained (i.e., stimulus onset asynchrony is 1250 ms) but not automatic attention bias (i.e., stimulus onset asynchrony is 500 ms). Children with greater left frontal activation from baseline to task more efficiently direct attention away from threat. Adolescent automatic attention bias to threat was related to concurrent anxiety symptoms. These findings illustrate the importance of considering frontal EEG asymmetry to shape how fearful children process threat and to influence their behavioral problems.