System Integrated Information.

Integrated information theory (IIT) starts from consciousness itself and identifies a set of properties (axioms) that are true of every conceivable experience. The axioms are translated into a set of postulates about the substrate of consciousness (called a complex), which are then used to formulate a mathematical framework for assessing both the quality and quantity of experience. The explanatory identity proposed by IIT is that an experience is identical to the cause-effect structure unfolded from a maximally irreducible substrate (a Φ-structure). In this work we introduce a definition for the integrated information of a system (φs) that is based on the existence, intrinsicality, information, and integration postulates of IIT. We explore how notions of determinism, degeneracy, and fault lines in the connectivity impact system-integrated information. We then demonstrate how the proposed measure identifies complexes as systems, the φs of which is greater than the φs of any overlapping candidate systems.

Mechanism Integrated Information.

The Integrated Information Theory (IIT) of consciousness starts from essential phenomenological properties, which are then translated into postulates that any physical system must satisfy in order to specify the physical substrate of consciousness. We recently introduced an information measure (Barbosa et al., 2020) that captures three postulates of IIT-existence, intrinsicality and information-and is unique. Here we show that the new measure also satisfies the remaining postulates of IIT-integration and exclusion-and create the framework that identifies maximally irreducible mechanisms. These mechanisms can then form maximally irreducible systems, which in turn will specify the physical substrate of conscious experience.

Prior expectations modulate unconscious evidence accumulation.

Unconscious processes have been shown to affect both perception and behaviour. However, the flexibility of such processes remains unknown. Here we investigate whether unconscious decisional processes can adapt to the utility of sensory information. To this end, we had participants gradually accumulate information from noisy motion stimuli, until a decision was reached. We titrated conscious awareness of these stimuli by simultaneously presenting a dynamic dichoptic mask. Crucially, we manipulated the likelihood that the suppressed portion of each presentation would contain useful information. Our results show that the statistics of the environment can be used to modulate unconscious evidence accumulation, resulting in faster choices. Furthermore, computational modelling revealed that this modulation is due to a change in the quality of unconscious evidence accumulation, rather than a conscious change in strategy. Together, these results indicate that unconscious decisional mechanisms are capable of optimising performance by flexibly adapting to the statistical environment.

Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange.

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson's disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value-akin to reward prediction errors-whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia's main output structures reflect distinct social context and value signals.

Multiomic foundations of human prefrontal cortex tissue function.

The prefrontal cortex (PFC) is a region of the brain that in humans is involved in the production of higher-order functions such as cognition, emotion, perception, and behavior. Neurotransmission in the PFC produces higher-order functions by integrating information from other areas of the brain. At the foundation of neurotransmission, and by extension at the foundation of higher-order brain functions, are an untold number of coordinated molecular processes involving the DNA sequence variants in the genome, RNA transcripts in the transcriptome, and proteins in the proteome. These "multiomic" foundations are poorly understood in humans, perhaps in part because most modern studies that characterize the molecular state of the human PFC use tissue obtained when neurotransmission and higher-order brain functions have ceased (i.e., the postmortem state). Here, analyses are presented on data generated for the Living Brain Project (LBP) to investigate whether PFC tissue from individuals with intact higher-order brain function has characteristic multiomic foundations. Two complementary strategies were employed towards this end. The first strategy was to identify in PFC samples obtained from living study participants a signature of RNA transcript expression associated with neurotransmission measured intracranially at the time of PFC sampling, in some cases while participants performed a task engaging higher-order brain functions. The second strategy was to perform multiomic comparisons between PFC samples obtained from individuals with intact higher-order brain function at the time of sampling (i.e., living study participants) and PFC samples obtained in the postmortem state. RNA transcript expression within multiple PFC cell types was associated with fluctuations of dopaminergic, serotonergic, and/or noradrenergic neurotransmission in the substantia nigra measured while participants played a computer game that engaged higher-order brain functions. A subset of these associations - termed the "transcriptional program associated with neurotransmission" (TPAWN) - were reproduced in analyses of brain RNA transcript expression and intracranial neurotransmission data obtained from a second LBP cohort and from a cohort in an independent study. RNA transcripts involved in TPAWN were found to be (1) enriched for RNA transcripts associated with measures of neurotransmission in rodent and cell models, (2) enriched for RNA transcripts encoded by evolutionarily constrained genes, (3) depleted of RNA transcripts regulated by common DNA sequence variants, and (4) enriched for RNA transcripts implicated in higher-order brain functions by human population genetic studies. In PFC excitatory neurons of living study participants, higher expression of the genes in TPAWN tracked with higher expression of RNA transcripts that in rodent PFC samples are markers of a class of excitatory neurons that connect the PFC to deep brain structures. TPAWN was further reproduced by RNA transcript expression patterns differentiating living PFC samples from postmortem PFC samples, and significant differences between living and postmortem PFC samples were additionally observed with respect to (1) the expression of most primary RNA transcripts, mature RNA transcripts, and proteins, (2) the splicing of most primary RNA transcripts into mature RNA transcripts, (3) the patterns of co-expression between RNA transcripts and proteins, and (4) the effects of some DNA sequence variants on RNA transcript and protein expression. Taken together, this report highlights that studies of brain tissue obtained in a safe and ethical manner from large cohorts of living individuals can help advance understanding of the multiomic foundations of brain function.

Noradrenaline tracks emotional modulation of attention in human amygdala.

The noradrenaline (NA) system is one of the brain's major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain.1,2 The LC-NA system is believed to regulate arousal and attention3,4 and is a pharmacological target in multiple clinical conditions.5,6,7 Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing8,9 and receives dense LC-NA projections,10 while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images,11 which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity,12 supported a hypothesis that pupil-NA coupling changes with cognitive state,13,14 with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a low-arousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.

A measure for intrinsic information.

We introduce an information measure that reflects the intrinsic perspective of a receiver or sender of a single symbol, who has no access to the communication channel and its source or target. The measure satisfies three desired properties-causality, specificity, intrinsicality-and is shown to be unique. Causality means that symbols must be transmitted with probability greater than chance. Specificity means that information must be transmitted by an individual symbol. Intrinsicality means that a symbol must be taken as such and cannot be decomposed into signal and noise. It follows that the intrinsic information carried by a specific symbol increases if the repertoire of symbols increases without noise (expansion) and decreases if it does so without signal (dilution). An optimal balance between expansion and dilution is relevant for systems whose elements must assess their inputs and outputs from the intrinsic perspective, such as neurons in a network.

Establishing the objective sleep phenotype in hypersomnolence disorder with and without comorbid major depression.

STUDY OBJECTIVES: To clarify whether hypersomnolence disorder is associated with a specific sleep phenotype and altered neurophysiological function in persons with and without hypersomnolence disorder and major depressive disorder (MDD). METHODS: Eighty-three unmedicated persons with and without hypersomnolence disorder and/or MDD underwent ad libitum high-density EEG polysomnography. Clinical and sleep architecture variables were compared between groups. Topographic patterns of slow-wave activity (SWA) relative to healthy controls were compared, with correlations between topographic SWA and daytime sleepiness assessed. Reductions in SWA in hypersomnolence disorder were mapped to specific cortical areas using source localization. RESULTS: Regardless of the presence or absence of comorbid MDD, persons with hypersomnolence disorder had increased sleep duration relative to both controls and persons with MDD without hypersomnolence. Participants with hypersomnolence disorder also demonstrated reduced bilateral centroparietal low-frequency activity during nonrapid eye movement sleep relative to controls, a pattern not observed in persons with MDD but without hypersomnolence. SWA in these regions was negatively correlated with subjective measures of daytime sleepiness. Source localization demonstrated reductions in SWA in the supramarginal gyrus, somatosensory, and transverse temporal cortex in participants with hypersomnolence disorder. CONCLUSIONS: Hypersomnolence disorder is characterized by increased sleep duration with normal sleep continuity, regardless of the presence or absence of comorbid depression. Reduced local SWA may be a specific neurophysiological finding in hypersomnolence disorder. Further research is warranted to elucidate the mechanisms through which these cortical changes are related to clinical complaints of daytime sleepiness.

Prior Expectation Modulates Repetition Suppression without Perceptual Awareness.

Stimulus repetition induces attenuated brain responses. This phenomenon, termed repetition suppression (RS), is classically held to stem from bottom-up neuronal adaptation. However, recent studies suggest that RS is driven by top-down predictive mechanisms. It remains controversial whether these top-down mechanisms of RS rely on conscious strategies, or if they represent a more fundamental aspect of perception, coding for physical properties of the repeated feature. The presence of top-down effects in the absence of perceptual awareness would indicate that conscious strategies are not sufficient to explain top-down mechanisms of RS. We combined an unconscious priming paradigm with EEG recordings and tested whether RS can be modulated by the probability of encountering a repetition, even in the absence of awareness. Our results show that both behavioural priming and RS near occipital areas are modulated by repetition probability, regardless of prime awareness. This contradicts previous findings that have argued that RS modulation is a by-product of conscious strategies. In contrast, we found that the increase in theta-band power following unrepeated trials - an index of conflict detection - is modulated only by expectations during conscious primes, implicating the use of conscious strategies. Together, our results suggest that the influence of predictions on RS can be either automatic in sensory brain regions or dependent on conscious strategies.

Backward renormalization-group inference of cortical dipole sources and neural connectivity efficacy.

Proper neural connectivity inference has become essential for understanding cognitive processes associated with human brain function. Its efficacy is often hampered by the curse of dimensionality. In the electroencephalogram case, which is a noninvasive electrophysiological monitoring technique to record electrical activity of the brain, a possible way around this is to replace multichannel electrode information with dipole reconstructed data. We use a method based on maximum entropy and the renormalization group to infer the position of the sources, whose success hinges on transmitting information from low- to high-resolution representations of the cortex. The performance of this method compares favorably to other available source inference algorithms, which are ranked here in terms of their performance with respect to directed connectivity inference by using artificially generated dynamic data. We examine some representative scenarios comprising different numbers of dynamically connected dipoles over distinct cortical surface positions and under different sensor noise impairment levels. The overall conclusion is that inverse problem solutions do not affect the correct inference of the direction of the flow of information as long as the equivalent dipole sources are correctly found.

Neural dynamics of prediction and surprise in infants.

Prior expectations shape neural responses in sensory regions of the brain, consistent with a Bayesian predictive coding account of perception. Yet, it remains unclear whether such a mechanism is already functional during early stages of development. To address this issue, we study how the infant brain responds to prediction violations using a cross-modal cueing paradigm. We record electroencephalographic responses to expected and unexpected visual events preceded by auditory cues in 12-month-old infants. We find an increased response for unexpected events. However, this effect of prediction error is only observed during late processing stages associated with conscious access mechanisms. In contrast, early perceptual components reveal an amplification of neural responses for predicted relative to surprising events, suggesting that selective attention enhances perceptual processing for expected events. Taken together, these results demonstrate that cross-modal statistical regularities are used to generate predictions that differentially influence early and late neural responses in infants.

Complex linguistic rules modulate early auditory brain responses.

During speech perception, listeners compensate for phonological rules of their language. For instance, English place assimilation causes green boat to be typically pronounced as greem boat; English listeners, however, perceptually compensate for this rule and retrieve the intended sound (n). Previous research using EEG has focused on rules with clear phonetic underpinnings, showing that perceptual compensation occurs at an early stage of speech perception. We tested whether this early mechanism also accounts for the compensation for more complex rules. We examined compensation for French voicing assimilation, a rule with abstract phonological restrictions on the contexts in which it applies. Our results reveal that perceptual compensation for this rule by French listeners modulates an early ERP component. This is evidence that early stages of speech sound categorization are sensitive to complex phonological rules of the native language.

Inducing task-relevant responses to speech in the sleeping brain.

Falling asleep leads to a loss of sensory awareness and to the inability to interact with the environment [1]. While this was traditionally thought as a consequence of the brain shutting down to external inputs, it is now acknowledged that incoming stimuli can still be processed, at least to some extent, during sleep [2]. For instance, sleeping participants can create novel sensory associations between tones and odors [3] or reactivate existing semantic associations, as evidenced by event-related potentials [4-7]. Yet, the extent to which the brain continues to process external stimuli remains largely unknown. In particular, it remains unclear whether sensory information can be processed in a flexible and task-dependent manner by the sleeping brain, all the way up to the preparation of relevant actions. Here, using semantic categorization and lexical decision tasks, we studied task-relevant responses triggered by spoken stimuli in the sleeping brain. Awake participants classified words as either animals or objects (experiment 1) or as either words or pseudowords (experiment 2) by pressing a button with their right or left hand, while transitioning toward sleep. The lateralized readiness potential (LRP), an electrophysiological index of response preparation, revealed that task-specific preparatory responses are preserved during sleep. These findings demonstrate that despite the absence of awareness and behavioral responsiveness, sleepers can still extract task-relevant information from external stimuli and covertly prepare for appropriate motor responses.

A neural marker of perceptual consciousness in infants.

Infants have a sophisticated behavioral and cognitive repertoire suggestive of a capacity for conscious reflection. Yet, demonstrating conscious access in infants remains challenging, mainly because they cannot report their thoughts. Here, to circumvent this problem, we studied whether an electrophysiological signature of consciousness found in adults, corresponding to a late nonlinear cortical response [~300 milliseconds (ms)] to brief pictures, already exists in infants. We recorded event-related potentials while 5-, 12-, and 15-month-old infants (N = 80) viewed masked faces at various levels of visibility. In all age groups, we found a late slow wave showing a nonlinear profile at the expected perceptual thresholds. However, this late component shifted from a weak and delayed response in 5-month-olds (starting around 900 ms) to a more sustained and faster response in older infants (around 750 ms). These results reveal that the brain mechanisms underlying the threshold for conscious perception are already present in infancy but undergo a slow acceleration during development.