Thalamocortical excitability modulation guides human perception under uncertainty.

Knowledge about the relevance of environmental features can guide stimulus processing. However, it remains unclear how processing is adjusted when feature relevance is uncertain. We hypothesized that (a) heightened uncertainty would shift cortical networks from a rhythmic, selective processing-oriented state toward an asynchronous ("excited") state that boosts sensitivity to all stimulus features, and that (b) the thalamus provides a subcortical nexus for such uncertainty-related shifts. Here, we had young adults attend to varying numbers of task-relevant features during EEG and fMRI acquisition to test these hypotheses. Behavioral modeling and electrophysiological signatures revealed that greater uncertainty lowered the rate of evidence accumulation for individual stimulus features, shifted the cortex from a rhythmic to an asynchronous/excited regime, and heightened neuromodulatory arousal. Crucially, this unified constellation of within-person effects was dominantly reflected in the uncertainty-driven upregulation of thalamic activity. We argue that neuromodulatory processes involving the thalamus play a central role in how the brain modulates neural excitability in the face of momentary uncertainty.

Boosts in brain signal variability track liberal shifts in decision bias.

Adopting particular decision biases allows organisms to tailor their choices to environmental demands. For example, a liberal response strategy pays off when target detection is crucial, whereas a conservative strategy is optimal for avoiding false alarms. Using conventional time-frequency analysis of human electroencephalographic (EEG) activity, we previously showed that bias setting entails adjustment of evidence accumulation in sensory regions (Kloosterman et al., 2019), but the presumed prefrontal signature of a conservative-to-liberal bias shift has remained elusive. Here, we show that a liberal bias shift is reflected in a more unconstrained neural regime (boosted entropy) in frontal regions that is suited to the detection of unpredictable events. Overall EEG variation, spectral power and event-related potentials could not explain this relationship, highlighting that moment-to-moment neural variability uniquely tracks bias shifts. Neural variability modulation through prefrontal cortex appears instrumental for permitting an organism to adapt its biases to environmental demands.

Standard multiscale entropy reflects neural dynamics at mismatched temporal scales: What's signal irregularity got to do with it?

Multiscale Entropy (MSE) is used to characterize the temporal irregularity of neural time series patterns. Due to its' presumed sensitivity to non-linear signal characteristics, MSE is typically considered a complementary measure of brain dynamics to signal variance and spectral power. However, the divergence between these measures is often unclear in application. Furthermore, it is commonly assumed (yet sparingly verified) that entropy estimated at specific time scales reflects signal irregularity at those precise time scales of brain function. We argue that such assumptions are not tenable. Using simulated and empirical electroencephalogram (EEG) data from 47 younger and 52 older adults, we indicate strong and previously underappreciated associations between MSE and spectral power, and highlight how these links preclude traditional interpretations of MSE time scales. Specifically, we show that the typical definition of temporal patterns via "similarity bounds" biases coarse MSE scales-that are thought to reflect slow dynamics-by high-frequency dynamics. Moreover, we demonstrate that entropy at fine time scales-presumed to indicate fast dynamics-is highly sensitive to broadband spectral power, a measure dominated by low-frequency contributions. Jointly, these issues produce counterintuitive reflections of frequency-specific content on MSE time scales. We emphasize the resulting inferential problems in a conceptual replication of cross-sectional age differences at rest, in which scale-specific entropy age effects could be explained by spectral power differences at mismatched temporal scales. Furthermore, we demonstrate how such problems may be alleviated, resulting in the indication of scale-specific age differences in rhythmic irregularity. By controlling for narrowband contributions, we indicate that spontaneous alpha rhythms during eyes open rest transiently reduce broadband signal irregularity. Finally, we recommend best practices that may better permit a valid estimation and interpretation of neural signal irregularity at time scales of interest.

Single-trial characterization of neural rhythms: Potential and challenges.

The average power of rhythmic neural responses as captured by MEG/EEG/LFP recordings is a prevalent index of human brain function. Increasing evidence questions the utility of trial-/group averaged power estimates however, as seemingly sustained activity patterns may be brought about by time-varying transient signals in each single trial. Hence, it is crucial to accurately describe the duration and power of rhythmic and arrhythmic neural responses on the single trial-level. However, it is less clear how well this can be achieved in empirical MEG/EEG/LFP recordings. Here, we extend an existing rhythm detection algorithm (extended Better OSCillation detection: "eBOSC"; cf. Whitten et al., 2011) to systematically investigate boundary conditions for estimating neural rhythms at the single-trial level. Using simulations as well as resting and task-based EEG recordings from a micro-longitudinal assessment, we show that alpha rhythms can be successfully captured in single trials with high specificity, but that the quality of single-trial estimates varies greatly between subjects. Despite those signal-to-noise-based limitations, we highlight the utility and potential of rhythm detection with multiple proof-of-concept examples, and discuss implications for single-trial analyses of neural rhythms in electrophysiological recordings. Using an applied example of working memory retention, rhythm detection indicated load-related increases in the duration of frontal theta and posterior alpha rhythms, in addition to a frequency decrease of frontal theta rhythms that was observed exclusively through amplification of rhythmic amplitudes.

Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events.

The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.