Transient Attention Gates Access Consciousness: Coupling N2pc and P3 Latencies Using Dynamic Time Warping.

The N2pc and P3 event-related potentials (ERPs), used to index selective attention and access to working memory and conscious awareness, respectively, have been important tools in cognitive sciences. Although it is likely that these two components and the underlying cognitive processes are temporally and functionally linked, such links have not yet been convincingly demonstrated. Adopting a novel methodological approach based on dynamic time warping (DTW), we provide evidence that the N2pc and P3 ERP components are temporally linked. We analyzed data from an experiment where 23 participants (16 women) monitored bilateral rapid serial streams of letters and digits in order to report a target digit indicated by a shape cue, separately for trials with correct responses and trials where a temporally proximal distractor was reported instead (distractor intrusion). DTW analyses revealed that N2pc and P3 latencies were correlated in time, both when the target or a distractor was reported. Notably, this link was weaker on distractor intrusion trials. This N2pc-P3 association is discussed with respect to the relationship between attention and access consciousness. Our results demonstrate that our novel method provides a valuable approach for assessing temporal links between two cognitive processes and their underlying modulating factors. This method allows to establish links and their modulator for any two time-series across all domains of the field (general-purpose MATLAB functions and a Python module are provided alongside this paper).

Recovery after stroke: the severely impaired are a distinct group.

INTRODUCTION: Stroke causes different levels of impairment and the degree of recovery varies greatly between patients. The majority of recovery studies are biased towards patients with mild-to-moderate impairments, challenging a unified recovery process framework. Our aim was to develop a statistical framework to analyse recovery patterns in patients with severe and non-severe initial impairment and concurrently investigate whether they recovered differently. METHODS: We designed a Bayesian hierarchical model to estimate 3-6 months upper limb Fugl-Meyer (FM) scores after stroke. When focusing on the explanation of recovery patterns, we addressed confounds affecting previous recovery studies and considered patients with FM-initial scores <45 only. We systematically explored different FM-breakpoints between severe/non-severe patients (FM-initial=5-30). In model comparisons, we evaluated whether impairment-level-specific recovery patterns indeed existed. Finally, we estimated the out-of-sample prediction performance for patients across the entire initial impairment range. RESULTS: Recovery data was assembled from eight patient cohorts (n=489). Data were best modelled by incorporating two subgroups (breakpoint: FM-initial=10). Both subgroups recovered a comparable constant amount, but with different proportional components: severely affected patients recovered more the smaller their impairment, while non-severely affected patients recovered more the larger their initial impairment. Prediction of 3-6 months outcomes could be done with an R2=63.5% (95% CI=51.4% to 75.5%). CONCLUSIONS: Our work highlights the benefit of simultaneously modelling recovery of severely-to-non-severely impaired patients and demonstrates both shared and distinct recovery patterns. Our findings provide evidence that the severe/non-severe subdivision in recovery modelling is not an artefact of previous confounds. The presented out-of-sample prediction performance may serve as benchmark to evaluate promising biomarkers of stroke recovery.

Branching Time Active Inference with Bayesian Filtering.

Branching time active inference is a framework proposing to look at planning as a form of Bayesian model expansion. Its root can be found in active inference, a neuroscientific framework widely used for brain modeling, as well as in Monte Carlo tree search, a method broadly applied in the reinforcement learning literature. Up to now, the inference of the latent variables was carried out by taking advantage of the flexibility offered by variational message passing, an iterative process that can be understood as sending messages along the edges of a factor graph. In this letter, we harness the efficiency of an alternative method for inference, Bayesian filtering, which does not require the iteration of the update equations until convergence of the variational free energy. Instead, this scheme alternates between two phases: integration of evidence and prediction of future states. Both phases can be performed efficiently, and this provides a forty times speedup over the state of the art.

Damage to Broca's area does not contribute to long-term speech production outcome after stroke.

Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus.

Inflated Estimates of Proportional Recovery From Stroke: The Dangers of Mathematical Coupling and Compression to Ceiling.

The proportional recovery rule states that most survivors recover a fixed proportion (≈70%) of lost function after stroke. A strong (negative) correlation between the initial score and subsequent change (outcome minus initial; ie, recovery) is interpreted as empirical support for the proportional recovery rule. However, this rule has recently been critiqued, with a central observation being that the correlation of initial scores with change over time is confounded in the situations in which it is typically assessed. This critique has prompted reassessments of patients' behavioral trajectory following stroke in 2 prominent papers. The first of these, by van der Vliet et al presented an impressive modeling of upper limb deficits following stroke, which avoided the confounded correlation of initial scores with change. The second by Kundert et al reassessed the value of the proportional recovery rule, as classically formulated as the correlation between initial scores and change. They argued that while effective prediction of recovery trajectories of individual patients is not supported by the available evidence, group-level inferences about the existence of proportional recovery are reliable. In this article, we respond to the van der Vliet and Kundert papers by distilling the essence of the argument for why the classic assessment of proportional recovery is confounded. In this respect, we reemphasize the role of mathematical coupling and compression to ceiling in the confounded nature of the correlation of initial scores with change. We further argue that this confound will be present for both individual-level and group-level inference. We then focus on the difficulties that can arise from ceiling effects, even when initial scores are not being correlated with change/recovery. We conclude by emphasizing the need for new techniques to analyze recovery after stroke that are not confounded in the ways highlighted here.

How hot is the hot zone? Computational modelling clarifies the role of parietal and frontoparietal connectivity during anaesthetic-induced loss of consciousness.

In recent years, specific cortical networks have been proposed to be crucial for sustaining consciousness, including the posterior hot zone and frontoparietal resting state networks (RSN). Here, we computationally evaluate the relative contributions of three RSNs - the default mode network (DMN), the salience network (SAL), and the central executive network (CEN) - to consciousness and its loss during propofol anaesthesia. Specifically, we use dynamic causal modelling (DCM) of 10 min of high-density EEG recordings (N = 10, 4 males) obtained during behavioural responsiveness, unconsciousness and post-anaesthetic recovery to characterise differences in effective connectivity within frontal areas, the posterior 'hot zone', frontoparietal connections, and between-RSN connections. We estimate - for the first time - a large DCM model (LAR) of resting EEG, combining the three RSNs into a rich club of interconnectivity. Consistent with the hot zone theory, our findings demonstrate reductions in inter-RSN connectivity in the parietal cortex. Within the DMN itself, the strongest reductions are in feed-forward frontoparietal and parietal connections at the precuneus node. Within the SAL and CEN, loss of consciousness generates small increases in bidirectional connectivity. Using novel DCM leave-one-out cross-validation, we show that the most consistent out-of-sample predictions of the state of consciousness come from a key set of frontoparietal connections. This finding also generalises to unseen data collected during post-anaesthetic recovery. Our findings provide new, computational evidence for the importance of the posterior hot zone in explaining the loss of consciousness, highlighting also the distinct role of frontoparietal connectivity in underpinning conscious responsiveness, and consequently, suggest a dissociation between the mechanisms most prominently associated with explaining the contrast between conscious awareness and unconsciousness, and those maintaining consciousness.

Breakthrough percepts of online identity: Detecting recognition of email addresses on the fringe of awareness.

A key issue facing cybercrime investigations is connecting online identities to real-world identities. This paper shows that by combining the Fringe-P3 method with a concealed information test, we can detect a participant's familiarity with their own email address, thus connecting their real-world identity to their online one. Participants were shown Rapid Serial Visual Presentation (RSVP) streams of email addresses, some including their own email address (probe) or a target email address. Familiarity with the probe was accurately detected with significant results at the group level and for 7 of 11 participants at the individual level. These promising results demonstrate that the method can be successfully used to detect online identities. Factors that may affect how well an email address probe stands out in the RSVP streams are also discussed.

The missing N1 or jittered P2: Electrophysiological correlates of pattern glare in the time and frequency domain.

Excessive sensitivity to certain visual stimuli (cortical hyperexcitability) is associated with a number of neurological disorders including migraine, epilepsy, multiple sclerosis, autism and possibly dyslexia. Others show disruptive sensitivity to visual stimuli with no other obvious pathology or symptom profile (visual stress) which can extend to discomfort and nausea. We used event-related potentials (ERPs) to explore the neural correlates of visual stress and headache proneness. We analysed ERPs in response to thick (0.37 cycles per degree [c/deg]), medium (3 c/deg) and thin (12 c/deg) gratings, using mass univariate analysis, considering three factors in the general population: headache proneness, visual stress and discomfort. We found relationships between ERP features and the headache and discomfort factors. Stimulus main effects were driven by the medium stimulus regardless of participant characteristics. Participants with high discomfort ratings had larger P1 components for the initial presentation of medium stimuli, suggesting initial cortical hyperexcitability that is later suppressed. The participants with high headache ratings showed atypical N1-P2 components for medium stripes relative to the other stimuli. This effect was present only after repeated stimulus presentation. These effects were also explored in the frequency domain, suggesting variations in intertrial theta band phase coherence. Our results suggest that discomfort and headache in response to striped stimuli are related to different neural processes; however, more exploration is needed to determine whether the results translate to a clinical migraine population.

Realizing Active Inference in Variational Message Passing: The Outcome-Blind Certainty Seeker.

Active inference is a state-of-the-art framework in neuroscience that offers a unified theory of brain function. It is also proposed as a framework for planning in AI. Unfortunately, the complex mathematics required to create new models can impede application of active inference in neuroscience and AI research. This letter addresses this problem by providing a complete mathematical treatment of the active inference framework in discrete time and state spaces and the derivation of the update equations for any new model. We leverage the theoretical connection between active inference and variational message passing as described by John Winn and Christopher M. Bishop in 2005. Since variational message passing is a well-defined methodology for deriving Bayesian belief update equations, this letter opens the door to advanced generative models for active inference. We show that using a fully factorized variational distribution simplifies the expected free energy, which furnishes priors over policies so that agents seek unambiguous states. Finally, we consider future extensions that support deep tree searches for sequential policy optimization based on structure learning and belief propagation.

Breaking the circularity in circular analyses: Simulations and formal treatment of the flattened average approach.

There has been considerable debate and concern as to whether there is a replication crisis in the scientific literature. A likely cause of poor replication is the multiple comparisons problem. An important way in which this problem can manifest in the M/EEG context is through post hoc tailoring of analysis windows (a.k.a. regions-of-interest, ROIs) to landmarks in the collected data. Post hoc tailoring of ROIs is used because it allows researchers to adapt to inter-experiment variability and discover novel differences that fall outside of windows defined by prior precedent, thereby reducing Type II errors. However, this approach can dramatically inflate Type I error rates. One way to avoid this problem is to tailor windows according to a contrast that is orthogonal (strictly parametrically orthogonal) to the contrast being tested. A key approach of this kind is to identify windows on a fully flattened average. On the basis of simulations, this approach has been argued to be safe for post hoc tailoring of analysis windows under many conditions. Here, we present further simulations and mathematical proofs to show exactly why the Fully Flattened Average approach is unbiased, providing a formal grounding to the approach, clarifying the limits of its applicability and resolving published misconceptions about the method. We also provide a statistical power analysis, which shows that, in specific contexts, the fully flattened average approach provides higher statistical power than Fieldtrip cluster inference. This suggests that the Fully Flattened Average approach will enable researchers to identify more effects from their data without incurring an inflation of the false positive rate.

Bringing proportional recovery into proportion: Bayesian modelling of post-stroke motor impairment.

Accurate predictions of motor impairment after stroke are of cardinal importance for the patient, clinician, and healthcare system. More than 10 years ago, the proportional recovery rule was introduced by promising that high-fidelity predictions of recovery following stroke were based only on the initially lost motor function, at least for a specific fraction of patients. However, emerging evidence suggests that this recovery rule is subject to various confounds and may apply less universally than previously assumed. Here, we systematically revisited stroke outcome predictions by applying strategies to avoid confounds and fitting hierarchical Bayesian models. We jointly analysed 385 post-stroke trajectories from six separate studies-one of the largest overall datasets of upper limb motor recovery. We addressed confounding ceiling effects by introducing a subset approach and ensured correct model estimation through synthetic data simulations. Subsequently, we used model comparisons to assess the underlying nature of recovery within our empirical recovery data. The first model comparison, relying on the conventional fraction of patients called 'fitters', pointed to a combination of proportional to lost function and constant recovery. 'Proportional to lost' here describes the original notion of proportionality, indicating greater recovery in case of a more severe initial impairment. This combination explained only 32% of the variance in recovery, which is in stark contrast to previous reports of >80%. When instead analysing the complete spectrum of subjects, 'fitters' and 'non-fitters', a combination of proportional to spared function and constant recovery was favoured, implying a more significant improvement in case of more preserved function. Explained variance was at 53%. Therefore, our quantitative findings suggest that motor recovery post-stroke may exhibit some characteristics of proportionality. However, the variance explained was substantially reduced compared to what has previously been reported. This finding motivates future research moving beyond solely behaviour scores to explain stroke recovery and establish robust and discriminating single-subject predictions.

Sedation Modulates Frontotemporal Predictive Coding Circuits and the Double Surprise Acceleration Effect.

Two important theories in cognitive neuroscience are predictive coding (PC) and the global workspace (GW) theory. A key research task is to understand how these two theories relate to one another, and particularly, how the brain transitions from a predictive early state to the eventual engagement of a brain-scale state (the GW). To address this question, we present a source-localization of EEG responses evoked by the local-global task-an experimental paradigm that engages a predictive hierarchy, which encompasses the GW. The results of our source reconstruction suggest three phases of processing. The first phase involves the sensory (here auditory) regions of the superior temporal lobe and predicts sensory regularities over a short timeframe (as per the local effect). The third phase is brain-scale, involving inferior frontal, as well as inferior and superior parietal regions, consistent with a global neuronal workspace (GNW; as per the global effect). Crucially, our analysis suggests that there is an intermediate (second) phase, involving modulatory interactions between inferior frontal and superior temporal regions. Furthermore, sedation with propofol reduces modulatory interactions in the second phase. This selective effect is consistent with a PC explanation of sedation, with propofol acting on descending predictions of the precision of prediction errors; thereby constraining access to the GNW.

Recovery after stroke: not so proportional after all?

The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. To the extent that this is true, recovery from stroke can be predicted accurately from baseline measures of acute post-stroke impairment alone. Reports that baseline scores explain more than 80%, and sometimes more than 90%, of the variance in the patients' recoveries, are rapidly accumulating. Here, we show that these headline effect sizes are likely inflated. The key effects in this literature are typically expressed as, or reducible to, correlation coefficients between baseline scores and recovery (outcome scores minus baseline scores). Using formal analyses and simulations, we show that these correlations will be extreme when outcomes are significantly less variable than baselines, which they often will be in practice regardless of the real relationship between outcomes and baselines. We show that these effect sizes are likely to be over-optimistic in every empirical study that we found that reported enough information for us to make the judgement, and argue that the same is likely to be true in other studies as well. The implication is that recovery after stroke may not be as proportional as recent studies suggest.

The Sync/deSync Model: How a Synchronized Hippocampus and a Desynchronized Neocortex Code Memories.

Neural oscillations are important for memory formation in the brain. The desynchronization of alpha (10 Hz) oscillations in the neocortex has been shown to predict successful memory encoding and retrieval. However, when engaging in learning, it has been found that the hippocampus synchronizes in theta (4 Hz) oscillations, and that learning is dependent on the phase of theta. This inconsistency as to whether synchronization is "good" for memory formation leads to confusion over which oscillations we should expect to see and where during learning paradigm experiments. This paper seeks to respond to this inconsistency by presenting a neural network model of how a well functioning learning system could exhibit both of these phenomena, i.e., desynchronization of alpha and synchronization of theta during successful memory encoding.We present a spiking neural network (the Sync/deSync model) of the neocortical and hippocampal system. The simulated hippocampus learns through an adapted spike-time dependent plasticity rule, in which weight change is modulated by the phase of an extrinsically generated theta oscillation. Additionally, a global passive weight decay is incorporated, which is also modulated by theta phase. In this way, the Sync/deSync model exhibits theta phase-dependent long-term potentiation and long-term depression. We simulated a learning paradigm experiment and compared the oscillatory dynamics of our model with those observed in single-cell and scalp-EEG studies of the medial temporal lobe. Our Sync/deSync model suggests that both the desynchronization of neocortical alpha and the synchronization of hippocampal theta are necessary for successful memory encoding and retrieval.SIGNIFICANCE STATEMENT A fundamental question is the role of rhythmic activation of neurons, i.e., how and why their firing oscillates between high and low rates. A particularly important question is how oscillatory dynamics between the neocortex and hippocampus support memory formation. We present a spiking neural-network model of such memory formation, with the central ideas that (1) in neocortex, neurons need to break out of an alpha oscillation to represent a stimulus (i.e., alpha desynchronizes), whereas (2) in hippocampus, the firing of neurons at theta facilitates formation of memories (i.e., theta synchronizes). Accordingly, successful memory formation is marked by reduced neocortical alpha and increased hippocampal theta. This pattern has been observed experimentally and gives our model its name-the Sync/deSync model.

The Temporal Signature of Memories: Identification of a General Mechanism for Dynamic Memory Replay in Humans.

Reinstatement of dynamic memories requires the replay of neural patterns that unfold over time in a similar manner as during perception. However, little is known about the mechanisms that guide such a temporally structured replay in humans, because previous studies used either unsuitable methods or paradigms to address this question. Here, we overcome these limitations by developing a new analysis method to detect the replay of temporal patterns in a paradigm that requires participants to mentally replay short sound or video clips. We show that memory reinstatement is accompanied by a decrease of low-frequency (8 Hz) power, which carries a temporal phase signature of the replayed stimulus. These replay effects were evident in the visual as well as in the auditory domain and were localized to sensory-specific regions. These results suggest low-frequency phase to be a domain-general mechanism that orchestrates dynamic memory replay in humans.

Replay of Stimulus-specific Temporal Patterns during Associative Memory Formation.

Forming a memory often entails the association of recent experience with present events. This recent experience is usually an information-rich and dynamic representation of the world around us. We here show that associating a static cue with a previously shown dynamic stimulus yields a detectable, dynamic representation of this stimulus. We further implicate this representation in the decrease of low-frequency power (∼4-30 Hz) in the ongoing EEG, which is a well-known correlate of successful memory formation. The reappearance of content-specific patterns in desynchronizing brain oscillations was observed in two sensory domains, that is, in a visual condition and in an auditory condition. Together with previous results, these data suggest a mechanism that generalizes across domains and processes, in which the decrease in oscillatory power allows for the dynamic representation of information in ongoing brain oscillations.

Placing meta-stable states of consciousness within the predictive coding hierarchy: The deceleration of the accelerated prediction error.

While many studies have linked prediction errors and event related potentials at a single processing level, few consider how these responses interact across levels. In response, we present a factorial analysis of a multi-level oddball task - the local-global task - and we explore it when participants are sedated versus recovered. We found that the local and global levels in fact interact. This is of considerable current interest, since it has recently been argued that the MEEG response evoked by the global effect corresponds to a distinct processing mode that moves beyond predictive coding. This interaction suggests that the two processing modes are not distinct. Additionally, we observed that sedation modulates this interaction, suggesting that conscious awareness may not be completely restricted to a single (global) processing level.

Illusions of integration are subjectively impenetrable: Phenomenological experience of Lag 1 percepts during dual-target RSVP.

We investigated the relationship between different kinds of target reports in a rapid serial visual presentation task, and their associated perceptual experience. Participants reported the identity of two targets embedded in a stream of stimuli and their associated subjective visibility. In our task, target stimuli could be combined together to form more complex ones, thus allowing participants to report temporally integrated percepts. We found that integrated percepts were associated with high subjective visibility scores, whereas reports in which the order of targets was reversed led to a poorer perceptual experience. We also found a reciprocal relationship between the chance of the second target not being reported correctly and the perceptual experience associated with the first one. Principally, our results indicate that integrated percepts are experienced as a unique, clear perceptual event, whereas order reversals are experienced as confused, similar to cases in which an entirely wrong response was given.