Assessing mismatch negativity (MMN) and P3b within-individual sensitivity - A comparison between the local-global paradigm and two specialized oddball sequences.

Mismatch negativity (MMN) and P3b are well known for their clinical utility. There exists no gold standard, however, for acquiring them as EEG markers of consciousness in clinical settings. This may explain why the within-individual sensitivity of MMN/P3b paradigms is often quite poor and why seemingly identical EEG markers can behave differently across Disorders of consciousness (DoC) studies. Here, we compare two traditional paradigms for MMN or P3b assessment with the recently more popular local-global paradigm that promises to assess MMN and P3b orthogonally within one oddball sequence. All three paradigms were administered to healthy participants (N = 15) with concurrent EEG. A clear MMN and local effect were found for 15/15 participants. The P3b and global effect were found for 14/15 and 13/15 participants, respectively. There were no systematic differences between the global effect and P3b. Indeed, P3b amplitude was highly correlated across paradigms. The local effect differed clearly from the MMN, however. It occurred earlier than MMN and was followed by a much more prominent P3a. The peak latencies and amplitudes were also not correlated across paradigms. Caution should therefore be exercised when comparing the local effect and MMN across studies. We conclude that the within-individual MMN sensitivity is adequate for both the local-global and a dedicated MMN paradigm. The within-individual sensitivity of P3b was lower than expected for both the local-global and a dedicated P3b paradigm, which may explain the often-low sensitivity of P3b paradigms in patients with DoC.

No validity without a theory-a critical look at subjective measures of consciousness.

Michel (The mismeasure of consciousness: a problem of coordination for the perceptual awareness scale. Philos Sci 2019;86:1239-49) claims that the Perceptual Awareness Scale (PAS) faces the problem of coordination (also known as validity). We argue that his claim holds only under certain theoretical assumptions which need to be made explicit as these are likely not in line with the PAS proponents' standpoint. We also call for terminological clarity, an example being the usage of 'levels' of consciousness. Precise terminology combined with an explicit reference to the chosen theoretical perspective is necessary conditions for making progress in consciousness research and the development of consciousness theories.

Coupling the State and Contents of Consciousness.

One fundamental feature of consciousness is that the contents of consciousness depend on the state of consciousness. Here, we propose an answer to why this is so: both the state and the contents of consciousness depend on the activity of cortical layer 5 pyramidal (L5p) neurons. These neurons affect both cortical and thalamic processing, hence coupling the cortico-cortical and thalamo-cortical loops with each other. Functionally this coupling corresponds to the coupling between the state and the contents of consciousness. Together the cortico-cortical and thalamo-cortical loops form a thalamo-cortical broadcasting system, where the L5p cells are the central elements. This perspective makes one quite specific prediction: cortical processing that does not include L5p neurons will be unconscious. More generally, the present perspective suggests that L5p neurons have a central role in the mechanisms underlying consciousness.

Individual differences in the effects of priors on perception: A multi-paradigm approach.

The present study investigated individual differences in how much subjects rely on prior information, such as expectations or knowledge, when faced with perceptual ambiguity. The behavioural performance of forty-four participants was measured on four different visual paradigms (Mooney face recognition, illusory contours, blur detection and representational momentum) in which priors have been shown to affect perception. In addition, questionnaires were used to measure autistic and schizotypal traits in the non-clinical population. We hypothesized that someone who in the face of ambiguous or noisy perceptual input relies heavily on priors, would exhibit this tendency across a variety of tasks. This general pattern would then be reflected in high pairwise correlations between the behavioural measures and an emerging common factor. On the contrary, our results imply that there is no single factor that explains the individual differences present in the aforementioned tasks, as further evidenced by the overall lack of robust correlations between the separate paradigms. Instead, a two-factor structure reflecting differences in the hierarchy of perceptual processing was the best fit for explaining the individual variance in these tasks. This lends support to the notion that mechanisms underlying the effects of priors likely originate from several independent sources and that it is important to consider the role of specific tasks and stimuli more carefully when reporting effects of priors on perception.

Juxtaposing the real-time unfolding of subjective experience and ERP neuromarker dynamics.

Electroencephalographic (EEG) potentials have remained a valuable source of data and theories concerning neural correlates of consciousness (NCC). The EEG based methods are far from being exhausted and are continually valuable in the quest for the markers of NCC. To set the background for the research presented in this issue, we review the published work on EEG-based markers of NCC. The article is organized according to the principle of the time-course aspect of brain potentials with regard to the stimuli for which subject's awareness is experimentally measured and/or manipulated. We treat brain potentials as the principal dependent measure as well as independent variable. More specifically, we also draw attention to the fact that in the overwhelming share of studies relative negativization of the ERPs tends to mark NCC.

Visual masking with frontally applied pre-stimulus TMS and its subject-specific neural correlates.

The visibility of a visual target stimulus depends on the local state of the early visual cortex shortly before the stimulus itself is presented. This view is supported by the observation that occipitally applied pre-stimulus TMS can disrupt subsequent information processing leading to visual masking effects. According to another line of accumulating evidence, however, global pre-stimulus connectivity patterns could be as crucial as local cortical states. In line with the latter view we show that pre-stimulus masking occurs even if TMS is directed to the frontal cortex. Importantly, the individual extent of this effect is strongly correlated with the subject-specific peak latency of a late positive TMS-evoked potential. Our results thus suggest a third type of masking occurring neither through direct interaction with visual areas nor by a modal visual masking input. Our results also shed light on the inter-individual differences in TMS research in general.

General Markers of Conscious Visual Perception and Their Timing.

Previous studies have observed different onset times for the neural markers of conscious perception. This variability could be attributed to procedural differences between studies. Here we show that the onset times for the markers of conscious visual perception can strongly vary even within a single study. A heterogeneous stimulus set was presented at threshold contrast. Trials with and without conscious perception were contrasted on 100 balanced subsets of the data. Importantly, the 100 subsets with heterogeneous stimuli did not differ in stimulus content, but only with regard to specific trials used. This approach enabled us to study general markers of conscious visual perception independent of stimulus content, characterize their onset and its variability within one study. N200 and P300 were the two reliable markers of conscious visual perception common to all perceived stimuli and absent for all non-perceived stimuli. The estimated mean onset latency for both markers was shortly after 200 ms. However, the onset latency of these markers was associated with considerable variability depending on which subsets of the data were considered. We show that it is first and foremost the amplitude fluctuation in the condition without conscious perception that explains the observed variability in onset latencies of the markers of conscious visual perception.

Early effects of previous experience on conscious perception.

Constructive theories of brain function such as predictive coding posit that prior knowledge affects our experience of the world quickly and directly. However, it is yet unknown how swiftly prior knowledge impacts the neural processes giving rise to conscious experience. Here we used an experimental paradigm where prior knowledge augmented perception and measured the timing of this effect with magnetoencephalography (MEG). By correlating the perceptual benefits of prior knowledge with the MEG activity, we found that prior knowledge took effect in the time-window 80-95 ms after stimulus onset, thus reflecting an early influence on conscious perception. The sources of this effect were localized to occipital and posterior parietal regions. These results are in line with the predictive coding framework.

Occipital long-interval paired pulse TMS leads to slow wave components in NREM sleep.

Neural correlates of conscious vs unconscious states can be studied by contrasting EEG markers of brain activity between those two states. Here, a task-free experimental setup was used to study the state dependent effects of occipital transcranial magnetic stimulation (TMS). EEG responses to single and paired pulse TMS with an inter-stimulus-interval (ISI) of 100 ms were investigated under Non-REM (NREM) sleep and wakefulness. In the paired pulse TMS condition adopting this long ISI, a robust positive deflection starting around 200 ms after the second pulse was found. This component was not obtained under wakefulness or when a single TMS pulse was applied in sleep. These findings are discussed in the context of NREM sleep slow waves. The present results indicate that the long interval paired-pulse paradigm could be used to manipulate plasticity processes in the visual cortex. The present setup might also become useful for evaluating states of consciousness.

The effect of task-irrelevant visual backgrounds on human transcranial magnetic stimulation-evoked electroencephalography responses and cortical alpha activity.

Brain responses evoked by transcranial magnetic stimulation (TMS) in task-free experimental contexts are known to depend on psychophysiological states such as sleep, vegetative state and caffeine-induced arousal. Much less is known about how TMS-evoked responses depend on task-irrelevant steady perceptual input. Here, we examined ongoing alpha activity and the mean amplitude of EEG potentials in response to occipitally applied TMS as a function of task-irrelevant visual backgrounds. Responses to TMS were robustly modulated by photographs of natural scenes and man-made environments. These effects began as early as during the N100 and continued for several hundred milliseconds after the stimulation. There was also a more general effect of background along with other stimuli, such as blank backgrounds, sinusoidal gratings and moving dot-patterns. This effect was observable from ongoing alpha activity as well. Based on these results we conclude that different types of steady perceptual input modulate visual cortex reactivity and/or connectivity and it is possible to measure these modulations by combining TMS with electroencephalography.