Single-neuron spiking variability in hippocampus dynamically tracks sensory content during memory formation in humans.

During memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world.

A spatiotemporal complexity architecture of human brain activity.

The human brain operates in large-scale functional networks. These networks are an expression of temporally correlated activity across brain regions, but how global network properties relate to the neural dynamics of individual regions remains incompletely understood. Here, we show that the brain's network architecture is tightly linked to critical episodes of neural regularity, visible as spontaneous "complexity drops" in functional magnetic resonance imaging signals. These episodes closely explain functional connectivity strength between regions, subserve the propagation of neural activity patterns, and reflect interindividual differences in age and behavior. Furthermore, complexity drops define neural activity states that dynamically shape the connectivity strength, topological configuration, and hierarchy of brain networks and comprehensively explain known structure-function relationships within the brain. These findings delineate a principled complexity architecture of neural activity-a human "complexome" that underpins the brain's functional network organization.

Moment-to-Moment Brain Signal Variability Reliably Predicts Psychiatric Treatment Outcome.

BACKGROUND: Biomarkers of psychiatric treatment response remain elusive. Functional magnetic resonance imaging (fMRI) has shown promise, but low reliability has limited the utility of typical fMRI measures (e.g., average brain signal) as harbingers of treatment success. Notably, although historically considered a source of noise, temporal brain signal variability continues to gain momentum as a sensitive and reliable indicator of individual differences in neural efficacy, yet has not been examined in relation to psychiatric treatment outcomes. METHODS: A total of 45 patients with social anxiety disorder were scanned twice (11 weeks apart) using simple task-based and resting-state fMRI to capture moment-to-moment neural variability. After fMRI test-retest, patients underwent a 9-week cognitive behavioral therapy. Multivariate modeling and reliability-based cross-validation were used to perform brain-based prediction of treatment outcomes. RESULTS: Task-based brain signal variability was the strongest contributor in a treatment outcome prediction model (total rACTUAL,PREDICTED = 0.77), outperforming self-reports, resting-state neural variability, and standard mean-based measures of neural activity. Notably, task-based brain signal variability showed excellent test-retest reliability (intraclass correlation coefficient = 0.80), even with a task length less than 3 minutes long. CONCLUSIONS: Rather than a source of undesirable noise, moment-to-moment fMRI signal variability may instead serve as a highly reliable and efficient prognostic indicator of clinical outcome.

Modality-specific tracking of attention and sensory statistics in the human electrophysiological spectral exponent.

A hallmark of electrophysiological brain activity is its 1/f-like spectrum - power decreases with increasing frequency. The steepness of this 'roll-off' is approximated by the spectral exponent, which in invasively recorded neural populations reflects the balance of excitatory to inhibitory neural activity (E:I balance). Here, we first establish that the spectral exponent of non-invasive electroencephalography (EEG) recordings is highly sensitive to general (i.e., anaesthesia-driven) changes in E:I balance. Building on the EEG spectral exponent as a viable marker of E:I, we then demonstrate its sensitivity to the focus of selective attention in an EEG experiment during which participants detected targets in simultaneous audio-visual noise. In addition to these endogenous changes in E:I balance, EEG spectral exponents over auditory and visual sensory cortices also tracked auditory and visual stimulus spectral exponents, respectively. Individuals' degree of this selective stimulus-brain coupling in spectral exponents predicted behavioural performance. Our results highlight the rich information contained in 1/f-like neural activity, providing a window into diverse neural processes previously thought to be inaccessible in non-invasive human recordings.

Behavior needs neural variability.

Human and non-human animal behavior is highly malleable and adapts successfully to internal and external demands. Such behavioral success stands in striking contrast to the apparent instability in neural activity (i.e., variability) from which it arises. Here, we summon the considerable evidence across scales, species, and imaging modalities that neural variability represents a key, undervalued dimension for understanding brain-behavior relationships at inter- and intra-individual levels. We believe that only by incorporating a specific focus on variability will the neural foundation of behavior be comprehensively understood.

Local cortical desynchronization and pupil-linked arousal differentially shape brain states for optimal sensory performance.

Instantaneous brain states have consequences for our sensation, perception, and behaviour. Fluctuations in arousal and neural desynchronization likely pose perceptually relevant states. However, their relationship and their relative impact on perception is unclear. We here show that, at the single-trial level in humans, local desynchronization in sensory cortex (expressed as time-series entropy) versus pupil-linked arousal differentially impact perceptual processing. While we recorded electroencephalography (EEG) and pupillometry data, stimuli of a demanding auditory discrimination task were presented into states of high or low desynchronization of auditory cortex via a real-time closed-loop setup. Desynchronization and arousal distinctly influenced stimulus-evoked activity and shaped behaviour displaying an inverted u-shaped relationship: States of intermediate desynchronization elicited minimal response bias and fastest responses, while states of intermediate arousal gave rise to highest response sensitivity. Our results speak to a model in which independent states of local desynchronization and global arousal jointly optimise sensory processing and performance.

Prestimulus neural alpha power predicts confidence in discriminating identical auditory stimuli.

When deciding upon a sensory stimulus, the power of prestimulus neural alpha oscillations (~10 Hz) has been shown to hold information on a perceiver's bias, or confidence, as opposed to perceptual sensitivity per se. Here, we test whether this link between prestimulus alpha power and decision confidence, previously established in vision and somatosensation, also holds in the auditory modality. Moreover, confidence usually depends on the physical evidence available in the stimulus as well as on decision accuracy. It is unclear in how far the link between prestimulus alpha power and confidence holds when physical stimulus evidence is entirely absent, and thus accuracy does not vary. We here analysed electroencephalography data from a paradigm where human listeners (N = 17) rated their confidence in the discrimination of the pitch of two tones that were, unbeknownst to the listeners, identical. Lower prestimulus alpha power as recorded at central channel sites was predictive of higher confidence ratings. Furthermore, this link was not mediated by auditory evoked activity. Our results support a direct link between prestimulus alpha power and decision confidence. This effect, first, shows up in the auditory modality similar to vision and somatosensation, and second, is present also in the complete absence of physical evidence in the stimulus and in the absence of varying accuracy. These findings speak to a model wherein low prestimulus alpha power increases neural baseline excitability, which is reflected in enhanced stimulus-evoked neural responses and higher confidence.

States and traits of neural irregularity in the age-varying human brain.

Sensory representations, and thus human percepts, of the physical world are susceptible to fluctuations in brain state or "neural irregularity". Furthermore, aging brains display altered levels of neural irregularity. We here show that a single, within-trial, information-theoretic measure (weighted permutation entropy) captures neural irregularity in the human electroencephalogram as a proxy for both, trait-like differences between individuals of varying age, and state-like fluctuations that bias perceptual decisions. First, the overall level of neural irregularity increased with participants' age, paralleled by a decrease in variability over time, likely indexing age-related changes at structural and functional levels of brain activity. Second, states of higher neural irregularity were associated with optimized sensory encoding and a subsequently increased probability of choosing the first of two physically identical stimuli to be higher in pitch. In sum, neural irregularity not only characterizes behaviourally relevant brain states, but also can identify trait-like changes that come with age.

Selective overweighting of larger magnitudes during noisy numerical comparison.

Humans are often required to compare average magnitudes in numerical data; for example, when comparing product prices on two rival consumer websites. However, the neural and computational mechanisms by which numbers are weighted, integrated and compared during categorical decisions are largely unknown1,2,3,4,5. Here, we show a systematic deviation from 'optimality' in both visual and auditory tasks requiring averaging of symbolic numbers. Participants comparing numbers drawn from two categories selectively overweighted larger numbers when making a decision, and larger numbers evoked disproportionately stronger decision-related neural signals over the parietal cortex. A representational similarity analysis6 showed that neural (dis)similarity in patterns of electroencephalogram activity reflected numerical distance, but that encoding of number in neural data was systematically distorted in a way predicted by the behavioural weighting profiles, with greater neural distance between adjacent larger numbers. Finally, using a simple computational model, we show that although it is suboptimal for a lossless observer, this selective overweighting policy paradoxically maximizes expected accuracy by making decisions more robust to noise arising during approximate numerical integration2. In other words, although selective overweighting discards decision information, it can be beneficial for limited-capacity agents engaging in rapid numerical averaging.