Refixation behavior in naturalistic viewing: Methods, mechanisms, and neural correlates.

When freely viewing a scene, the eyes often return to previously visited locations. By tracking eye movements and coregistering eye movements and EEG, such refixations are shown to have multiple roles: repairing insufficient encoding from precursor fixations, supporting ongoing viewing by resampling relevant locations prioritized by precursor fixations, and aiding the construction of memory representations. All these functions of refixation behavior are understood to be underpinned by three oculomotor and cognitive systems and their associated brain structures. First, immediate saccade planning prior to refixations involves attentional selection of candidate locations to revisit. This process is likely supported by the dorsal attentional network. Second, visual working memory, involved in maintaining task-related information, is likely supported by the visual cortex. Third, higher-order relevance of scene locations, which depends on general knowledge and understanding of scene meaning, is likely supported by the hippocampal memory system. Working together, these structures bring about viewing behavior that balances exploring previously unvisited areas of a scene with exploiting visited areas through refixations.

Functional and spatial rewiring principles jointly regulate context-sensitive computation.

Adaptive rewiring provides a basic principle of self-organizing connectivity in evolving neural network topology. By selectively adding connections to regions with intense signal flow and deleting underutilized connections, adaptive rewiring generates optimized brain-like, i.e. modular, small-world, and rich club connectivity structures. Besides topology, neural self-organization also follows spatial optimization principles, such as minimizing the neural wiring distance and topographic alignment of neural pathways. We simulated the interplay of these spatial principles and adaptive rewiring in evolving neural networks with weighted and directed connections. The neural traffic flow within the network is represented by the equivalent of diffusion dynamics for directed edges: consensus and advection. We observe a constructive synergy between adaptive and spatial rewiring, which contributes to network connectedness. In particular, wiring distance minimization facilitates adaptive rewiring in creating convergent-divergent units. These units support the flow of neural information and enable context-sensitive information processing in the sensory cortex and elsewhere. Convergent-divergent units consist of convergent hub nodes, which collect inputs from pools of nodes and project these signals via a densely interconnected set of intermediate nodes onto divergent hub nodes, which broadcast their output back to the network. Convergent-divergent units vary in the degree to which their intermediate nodes are isolated from the rest of the network. This degree, and hence the context-sensitivity of the network's processing style, is parametrically determined in the evolving network model by the relative prominence of spatial versus adaptive rewiring.

Planning to revisit: Neural activity in refixation precursors.

Eye tracking studies suggest that refixations-fixations to locations previously visited-serve to recover information lost or missed during earlier exploration of a visual scene. These studies have largely ignored the role of precursor fixations-previous fixations on locations the eyes return to later. We consider the possibility that preparations to return later are already made during precursor fixations. This process would mark precursor fixations as a special category of fixations, that is, distinct in neural activity from other fixation categories such as refixations and fixations to locations visited only once. To capture the neural signals associated with fixation categories, we analyzed electroencephalograms (EEGs) and eye movements recorded simultaneously in a free-viewing contour search task. We developed a methodological pipeline involving regression-based deconvolution modeling, allowing our analyses to account for overlapping EEG responses owing to the saccade sequence and other oculomotor covariates. We found that precursor fixations were preceded by the largest saccades among the fixation categories. Independent of the effect of saccade length, EEG amplitude was enhanced in precursor fixations compared with the other fixation categories 200 to 400 ms after fixation onsets, most noticeably over the occipital areas. We concluded that precursor fixations play a pivotal role in visual perception, marking the continuous occurrence of transitions between exploratory and exploitative modes of eye movement in natural viewing behavior.

A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression.

Background: Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD. Methods: The Phase 1 part (n = 8) of the trial investigated two single dose levels of GH001 (12 mg, 18 mg) with a primary endpoint of safety, and the Phase 2 part (n = 8) investigated an individualized dosing regimen (IDR) with up to three increasing doses of GH001 (6 mg, 12 mg, and 18 mg) within a single day, with a primary endpoint of efficacy, as assessed by the proportion of patients in remission (MADRS ≤ 10) on day 7. Results: Administration of GH001 via inhalation was well tolerated. The proportion of patients in remission (MADRS ≤ 10) at day 7 was 2/4 (50%) and 1/4 (25%) in the 12 mg and 18 mg groups of Phase 1, respectively, and 7/8 (87.5%) in the IDR group of Phase 2, meeting its primary endpoint (p < 0.0001). All remissions were observed from day 1, with 6/10 remissions observed from 2 h. The mean MADRS change from baseline to day 7 was -21.0 (-65%) and - 12.5 (-40%) for the 12 and 18 mg groups, respectively, and - 24.4 (-76%) for the IDR. Conclusion: Administration of GH001 to a cohort of 16 patients with TRD was well tolerated and provided potent and ultra-rapid antidepressant effects. Individualized dosing with up to three doses of GH001 on a single day was superior to single dose administration.Clinical Trial registration: Clinicaltrials.gov Identifier NCT04698603.

A Bayesian classifier for fractal characterization of short behavioral series.

Serial tasks in behavioral research often lead to correlated responses, invalidating the application of generalized linear models and leaving the analysis of serial correlations as the only viable option. We present a Bayesian analysis method suitable for classifying even relatively short behavioral series according to their correlation structure. Our classifier consists of three phases. Phase 1 distinguishes between mono- and possible multifractal series by modeling the distribution of the increments of the series. To the series labeled as monofractal in Phase 1, classification proceeds in Phase 2 with a Bayesian version of the evenly spaced averaged detrended fluctuation analysis (Bayesian esaDFA). Finally, Phase 3 refines the estimates from the Bayesian esaDFA. We tested our classifier with very short series (viz., 256 points), both simulated and empirical ones. For the simulated series, our classifier revealed to be maximally efficient in distinguishing between mono- and multifractality and highly efficient in assigning the monofractal class. For the empirical series, our classifier identified monofractal classes specific to experimental designs, tasks, and conditions. Monofractal classes are particularly relevant for skilled, repetitive behavior. Short behavioral series are crucial for avoiding potential confounders such as mind wandering or fatigue. Our classifier thus contributes to broadening the scope of time series analysis for behavioral series and to understanding the impact of fundamental behavioral constructs (e.g., learning, coordination, and attention) on serial performance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Perceptual bias contextualized in visually ambiguous stimuli.

The visual appearance of an object is a function of stimulus properties as well as perceptual biases imposed by the observer. The context-specific trade-off between both can be measured accurately in a perceptual judgment task, involving grouping by proximity in ambiguous dot lattices. Such grouping depends lawfully on a stimulus parameter of the dot lattices known as their aspect ratio (AR), whose effect is modulated by a perceptual bias representing the preference for a cardinal orientation. In two experiments, we investigated how preceding context can lead to bias modulation, either in a top-down fashion via visual working memory (VWM) or bottom-up via sensory priming. In Experiment 1, we embedded the perceptual judgment task in a change detection paradigm and studied how the factors of VWM load (complexity of the memory array) and content (congruency in orientation to the ensuing dot lattice) affect the prominence of perceptual bias. A robust vertical orientation bias was observed, which was increased by VWM load and modulated by congruent VWM content. In Experiment 2, dot lattices were preceded by oriented primes. Here, primes regardless of orientation elicited a vertical orientation bias in dot lattices compared to a neutral baseline. Taken together, the two experiments demonstrate that top-down context (VWM load and content) effectively controls orientation bias modulation, while bottom-up context (i.e., priming) merely acts as an undifferentiated trigger to perceptual bias. These findings characterize the temporal context sensitivity of Gestalt perception, shed light on the processes responsible for different perceptual outcomes of ambiguous stimuli, and identify some of the mechanisms controlling perceptual bias.

Problem type and externalization in problem-solving.

We compared problem-solving in four sets of classical insight and analytic problems in the verbal and spatial domains, and examined the impact of externalization (verbalization or sketching). In a within-participants factorial design, we presented 24 classical insight and analytic problems, half verbal and half spatial. Participants solved these problems either while thinking aloud, while sketching, or in a baseline condition where neither was allowed. Higher solving accuracy was found in the analytic problems than in the insight ones as well as in the verbal problems than in the spatial ones. The verbal problems were also found to be solved faster than were spatial ones; in particular, verbal-insight problems were solved faster than spatial-insight and verbal-analytic ones. Therefore, spatial-insight problems stand out as particularly hard among the ones typically found in the literature. Surprisingly, no effects of externalization were found on problem-solving speed or accuracy. We discuss the implications of our results for the theses that insight problems involve special processes.

The No-Report Paradigm: A Revolution in Consciousness Research?

In the cognitive neuroscience of consciousness, participants have commonly been instructed to report their conscious content. This, it was claimed, risks confounding the neural correlates of consciousness (NCC) with their preconditions, i.e., allocation of attention, and consequences, i.e., metacognitive reflection. Recently, the field has therefore been shifting towards no-report paradigms. No-report paradigms draw their validity from a direct comparison with no-report conditions. We analyze several examples of such comparisons and identify alternative interpretations of their results and/or methodological issues in all cases. These go beyond the previous criticism that just removing the report is insufficient, because it does not prevent metacognitive reflection. The conscious mind is fickle. Without having much to do, it will turn inward and switch, or timeshare, between the stimuli on display and daydreaming or mind-wandering. Thus, rather than the NCC, no-report paradigms might be addressing the neural correlates of conscious disengagement. This observation reaffirms the conclusion that no-report paradigms are no less problematic than report paradigms.

Adaptive rewiring in nonuniform coupled oscillators.

Structural plasticity of the brain can be represented in a highly simplified form as adaptive rewiring, the relay of connections according to the spontaneous dynamic synchronization in network activity. Adaptive rewiring, over time, leads from initial random networks to brain-like complex networks, that is, networks with modular small-world structures and a rich-club effect. Adaptive rewiring has only been studied, however, in networks of identical oscillators with uniform or random coupling strengths. To implement information-processing functions (e.g., stimulus selection or memory storage), it is necessary to consider symmetry-breaking perturbations of oscillator amplitudes and coupling strengths. We studied whether nonuniformities in amplitude or connection strength could operate in tandem with adaptive rewiring. Throughout network evolution, either amplitude or connection strength of a subset of oscillators was kept different from the rest. In these extreme conditions, subsets might become isolated from the rest of the network or otherwise interfere with the development of network complexity. However, whereas these subsets form distinctive structural and functional communities, they generally maintain connectivity with the rest of the network and allow the development of network complexity. Pathological development was observed only in a small proportion of the models. These results suggest that adaptive rewiring can robustly operate alongside information processing in biological and artificial neural networks.

A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers.

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-MeO-DMT formulation (GH001) administered via inhalation as single doses of 2 (N = 4), 6 (N = 6), 12 (N = 4) and 18 mg (N = 4), and in an individualized dose escalation regimen (N = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (N = 22). The psychedelic experience was assessed with a novel Peak Experience Scale (PES), the Mystical Experience Questionnaire (MEQ), the Ego Dissolution Inventory (EDI), the Challenging Experience Questionnaire (CEQ), and the 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Further aims were to assess the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. Higher doses of 5-MeO-DMT produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the CEQ. Prominent effects were observed following single doses of 6, 12, and 18 mg on PES and MEQ ratings, while maximal effects on PES, MEQ, EDI, and 5D-ASC ratings were observed following individualized dose escalation of 5-MeO-DMT. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. Individualized dose escalation of 5-MeO-DMT may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response.

Effects of Temporal Expectations on the Perception of Motion Gestalts.

Gestalt psychology has traditionally ignored the role of attention in perception, leading to the view that autonomous processes create perceptual configurations that are then attended. More recent research, however, has shown that spatial attention influences a form of Gestalt perception: the coherence of random-dot kinematograms (RDKs). Using ERPs, we investigated whether temporal expectations exert analogous attentional effects on the perception of coherence level in RDKs. Participants were presented fixed-length sequences of RDKs and reported the coherence level of a target RDK. The target was indicated immediately after its appearance by a postcue. Target expectancy increased as the sequence progressed until target presentation; afterward, remaining RDKs were perceived without target expectancy. Expectancy influenced the amplitudes of ERP components P1 and N2. Crucially, expectancy interacted with coherence level at N2, but not at P1. Specifically, P1 amplitudes decreased linearly as a function of RDK coherence irrespective of expectancy, whereas N2 exhibited a quadratic dependence on coherence: larger amplitudes for RDKs with intermediate coherence levels, and only when they were expected. These results suggest that expectancy at early processing stages is an unspecific, general readiness for perception. At later stages, expectancy becomes stimulus specific and nonlinearly related to Gestalt coherence.

Adaptive Rewiring in Weighted Networks Shows Specificity, Robustness, and Flexibility.

Brain network connections rewire adaptively in response to neural activity. Adaptive rewiring may be understood as a process which, at its every step, is aimed at optimizing the efficiency of signal diffusion. In evolving model networks, this amounts to creating shortcut connections in regions with high diffusion and pruning where diffusion is low. Adaptive rewiring leads over time to topologies akin to brain anatomy: small worlds with rich club and modular or centralized structures. We continue our investigation of adaptive rewiring by focusing on three desiderata: specificity of evolving model network architectures, robustness of dynamically maintained architectures, and flexibility of network evolution to stochastically deviate from specificity and robustness. Our adaptive rewiring model simulations show that specificity and robustness characterize alternative modes of network operation, controlled by a single parameter, the rewiring interval. Small control parameter shifts across a critical transition zone allow switching between the two modes. Adaptive rewiring exhibits greater flexibility for skewed, lognormal connection weight distributions than for normally distributed ones. The results qualify adaptive rewiring as a key principle of self-organized complexity in network architectures, in particular of those that characterize the variety of functional architectures in the brain.

Neural correlates of task-related refixation behavior.

Eye movement research has shown that attention shifts from the currently fixated location to the next before a saccade is executed. We investigated whether the cost of the attention shift depends on higher-order processing at the time of fixation, in particular on visual working memory load differences between fixations and refixations on task-relevant items. The attention shift is reflected in EEG activity in the saccade-related potential (SRP). In a free viewing task involving visual search and memorization of multiple targets amongst distractors, we compared the SRP in first fixations versus refixations on targets and distractors. The task-relevance of targets implies that more information will be loaded in memory (e.g. both identity and location) than for distractors (e.g. location only). First fixations will involve greater memory load than refixations, since first fixations involve loading of new items, while refixations involve rehearsal of previously visited items. The SRP in the interval preceding the saccade away from a target or distractor revealed that saccade preparation is affected by task-relevance and refixation behavior. For task-relevant items only, we found longer fixation duration and higher SRP amplitudes for first fixations than for refixations over the occipital region and the opposite effect over the frontal region. Our findings provide first neurophysiological evidence that working memory loading of task-relevant information at fixation affects saccade planning.

Adaptive rewiring evolves brain-like structure in weighted networks.

Activity-dependent plasticity refers to a range of mechanisms for adaptively reshaping neuronal connections. We model their common principle in terms of adaptive rewiring of network connectivity, while representing neural activity by diffusion on the network: Where diffusion is intensive, shortcut connections are established, while underused connections are pruned. In binary networks, this process is known to steer initially random networks robustly to high levels of structural complexity, reflecting the global characteristics of brain anatomy: modular or centralized small world topologies. We investigate whether this result extends to more realistic, weighted networks. Both normally- and lognormally-distributed weighted networks evolve either modular or centralized topologies. Which of these prevails depends on a single control parameter, representing global homeostatic or normalizing regulation mechanisms. Intermediate control parameter values exhibit the greatest levels of network complexity, incorporating both modular and centralized tendencies. The simulation results allow us to propose diffusion based adaptive rewiring as a parsimonious model for activity-dependent reshaping of brain connectivity structure.

Factoring in the spatial effects of symbolic number representation.

Spatial constituents of adult symbolic number representation produce effects of size-value congruity, Spatial Numerical Association of Response Codes (SNARC), and numerical distance. According to behavioral experiments, these effects belong to distinct processing stages. Yet, these effects evoke overlapping responses in both early and late Event Related Potentials (ERPs). To probe whether these overlaps indicate sharing of resources, all relevant stimulus and response conditions were factorially combined in a numerical value comparison task. To secure ERP validity, same numbers were compared against variable reference values. This design resulted in previously unobserved interactions in behavior but inhibited late ERP effects. All effects arose early in the P1 component (around 100 ms) and most showed hemispheric specificity. Independency of congruity and SNARC effects was observed, whereas SNARC and numerical distance were closely intertwined. Differences in hemispheric specificity, rather than stage-wise separation, were key to independence.

Large-scale cortical travelling waves predict localized future cortical signals.

Predicting future brain signal is highly sought-after, yet difficult to achieve. To predict the future phase of cortical activity at localized ECoG and MEG recording sites, we exploit its predominant, large-scale, spatiotemporal dynamics. The dynamics are extracted from the brain signal through Fourier analysis and principal components analysis (PCA) only, and cast in a data model that predicts future signal at each site and frequency of interest. The dominant eigenvectors of the PCA that map the large-scale patterns of past cortical phase to future ones take the form of smoothly propagating waves over the entire measurement array. In ECoG data from 3 subjects and MEG data from 20 subjects collected during a self-initiated motor task, mean phase prediction errors were as low as 0.5 radians at local sites, surpassing state-of-the-art methods of within-time-series or event-related models. Prediction accuracy was highest in delta to beta bands, depending on the subject, was more accurate during episodes of high global power, but was not strongly dependent on the time-course of the task. Prediction results did not require past data from the to-be-predicted site. Rather, best accuracy depended on the availability in the model of long wavelength information. The utility of large-scale, low spatial frequency traveling waves in predicting future phase activity at local sites allows estimation of the error introduced by failing to account for irreducible trajectories in the activity dynamics.

Long-term dynamics of mind wandering: ultradian rhythms in thought generation.

Using the method of experience sampling, we studied the fluctuations in thought generation and cognitive control strength during the wakeful hours of the day, centered around episodes of mind wandering. Thought generation, measured in terms of the number of thoughts that concurrently occupy the mind at sampling time, goes through regular 4-6 h cycles, suggesting the mind operates with an alternation of focused and multitasking modes. Cognitive control strength rises and falls in relative coordination with thought generation, implying that both are occasionally misaligned. This happens, in particular, when cognitive control suddenly drops after having been keeping up with a cycle of thought generation. When this drop occurs while the thought generation cycle is still up, mind wandering appears. As cognitive control quickly resumes before returning to intermediate values, the thought generation cycle begins to fall again, and the mind wandering episode comes to an end. Implications regarding the role of long-term regulation in mind-wandering processes are discussed.

Refixation patterns reveal memory-encoding strategies in free viewing.

We investigated visual working memory encoding across saccadic eye movements, focusing our analysis on refixation behavior. Over 10-s periods, participants performed a visual search for three, four, or five targets and remembered their orientations for a subsequent change-detection task. In 50% of the trials, one of the targets had its orientation changed. From the visual search period, we scored three types of refixations and applied measures for quantifying eye-fixation recurrence patterns. Repeated fixations on the same regions as well as repeated fixation patterns increased with memory load. Correct change detection was associated with more refixations on targets and less on distractors, with increased frequency of recurrence, and with longer intervals between refixations. The results are in accordance with the view that patterns of eye movement are an integral part of visual working memory representation.