Dynamics of a Mutual Inhibition Circuit between Pyramidal Neurons Compared to Human Perceptual Competition.

Neural competition plays an essential role in active selection processes of noisy and ambiguous input signals, and it is assumed to underlie emergent properties of brain functioning, such as perceptual organization and decision-making. Despite ample theoretical research on neural competition, experimental tools to allow neurophysiological investigation of competing neurons have not been available. We developed a "hybrid" system where real-life neurons and a computer-simulated neural circuit interacted. It enabled us to construct a mutual inhibition circuit between two real-life pyramidal neurons. We then asked what dynamics this minimal unit of neural competition exhibits and compared them with the known behavioral-level dynamics of neural competition. We found that the pair of neurons shows bistability when activated simultaneously by current injections. The addition of modeled synaptic noise and changes in the activation strength showed that the dynamics of the circuit are strikingly similar to the known properties of bistable visual perception: The distribution of dominance durations showed a right-skewed shape, and the changes of the activation strengths caused changes in dominance, dominance durations, and reversal rates as stated in the well-known empirical laws of bistable perception known as Levelt's propositions.SIGNIFICANCE STATEMENT Visual perception emerges as the result of neural systems actively organizing visual signals that involves selection processes of competing neurons. While the neural competition, realized by a "mutual inhibition" circuit has been examined in many theoretical studies, its properties have not been investigated in real neurons. We have developed a "hybrid" system where two real-life pyramidal neurons in a mouse brain slice interact through a computer-simulated mutual inhibition circuit. We found that simultaneous activation of the neurons leads to bistable activity. We investigated the effect of noise and the effect of changes in the activation strength on the dynamics. We observed that the pair of neurons exhibit dynamics strikingly similar to the known properties of bistable visual perception.

Children's perception of visual and auditory ambiguity and its link to executive functions and creativity.

The phenomenon of perceptual bistability provides insights into aspects of perceptual processing not normally accessible to everyday experience. However, most experiments have been conducted in adults, and it is not clear to what extent key aspects of perceptual switching change through development. The current research examined the ability of 6-, 8-, and 10-year-old children (N = 66) to switch between competing percepts of ambiguous visual and auditory stimuli and links between switching rate, executive functions, and creativity. The numbers of switches participants reported in two visual tasks (ambiguous figure and ambiguous structure from motion) and two auditory tasks (verbal transformation and auditory streaming) were measured in three 60-s blocks. In addition, inhibitory control was measured with a Stroop task, set shifting was measured with a verbal fluency task, and creativity was measured with a divergent thinking task. The numbers of perceptual switches increased in all four tasks from 6 to 10 years of age but differed across tasks in that they were higher in the verbal transformation and ambigous structure-from-motion tasks than in the ambigous figure and auditory streaming tasks for all age groups. Although perceptual switching rates differed across tasks, there were predictive relationships between switching rates in some tasks. However, little evidence for the influence of central processes on perceptual switching was found. Overall, the results support the notion that perceptual switching is largely modality and task specific and that this property is already evident when perceptual switching emerges.

A randomized cross-over study on the blood pressure lowering effect of the combined passive head-up and -down movement with Device-Guided slow breathing.

Purpose: Baroreflex emerges as a therapeutic target of hypertension. We investigated blood pressure (BP) lowering effect of the combined passive head-up and -down movement with device-guided slow breathing in untreated mild hypertension or high-normal BP. Methods: In a randomized, cross-over trial, untreated subjects with an ambulatory systolic/diastolic BP of 125-140/80-90 mmHg and a clinic BP of 130-150/80-90 mmHg were randomized to intervention treatment with head movement and slow breathing or sham control, and then crossed over. Both treatments consisted of 1-week preparation, 2-week treatment, and 1-week recovery. During the 2-week treatment, subjects were treated for a session of 20 min/day. BP, pulse rate and respiration were measured before and after each treatment session. Ambulatory BP monitoring was performed at baseline and the end of the 2-week treatments' period, and home BP monitoring in the morning and evening for the whole 8-week follow-up period. Results: 14 subjects completed the study. The intervention treatment, compared to control, reduced respiration rate by -2.1 breaths/min (95% CI -2.9 to -1.2, p = .0001), but not clinic BP and pulse rate (p ≥ .67). The intervention treatment, compared to control, significantly reduced nighttime systolic/diastolic blood pressure by -5.63/-3.82 mm Hg (p ≤ .01) but not 24-h or daytime ambulatory blood pressure (p ≥ .69). Home BP decreased with the intervention treatment, but the between-treatment difference was not statistically significant (p ≥ .27). Conclusions: The combined head movement with slow breathing did not influence 24-h BP, but reduced nighttime BP in untreated mild hypertension or high-normal BP.

Intracranial Recordings of Occipital Cortex Responses to Illusory Visual Events.

UNLABELLED: Ambiguous visual stimuli elicit different perceptual interpretations over time, creating the illusion that a constant stimulus is changing. We investigate whether such spontaneous changes in visual perception involve occipital brain regions specialized for processing visual information, despite the absence of concomitant changes in stimulation. Spontaneous perceptual changes observed while viewing a binocular rivalry stimulus or an ambiguous structure-from-motion stimulus were compared with stimulus-induced perceptual changes that occurred in response to an actual stimulus change. Intracranial recordings from human occipital cortex revealed that spontaneous and stimulus-induced perceptual changes were both associated with an early transient increase in high-frequency power that was more spatially confined than a later transient decrease in low-frequency power. We suggest that the observed high-frequency and low-frequency modulations relate to initiation and maintenance of a percept, respectively. Our results are compatible with the idea that spontaneous changes in perception originate from competitive interactions within visual neural networks. SIGNIFICANCE STATEMENT: Ambiguous visual stimuli elicit different perceptual interpretations over time, creating the illusion that a constant stimulus is changing. The literature on the neural correlates of conscious visual perception remains inconclusive regarding the extent to which such spontaneous changes in perception involve sensory brain regions. In an attempt to bridge the gap between existing animal and human studies, we recorded from intracranial electrodes placed on the human occipital lobe. We compared two different kinds of ambiguous stimuli, binocular rivalry and the phenomenon of ambiguous structure-from-motion, enabling generalization of our findings across different stimuli. Our results indicate that spontaneous and stimulus-induced changes in perception (i.e., "illusory" and "real" changes in the stimulus, respectively) may involve sensory regions to a similar extent.

"Smooth operator": Music modulates the perceived creaminess, sweetness, and bitterness of chocolate.

There has been a recent growth of interest in determining whether sound (specifically music and soundscapes) can enhance not only the basic taste attributes associated with food and beverage items (such as sweetness, bitterness, sourness, etc.), but also other important components of the tasting experience, such as, for instance, crunchiness, creaminess, and/or carbonation. In the present study, participants evaluated the perceived creaminess of chocolate. Two contrasting soundtracks were produced with such texture-correspondences in mind, and validated by means of a pre-test. The participants tasted the same chocolate twice (without knowing that the chocolates were identical), each time listening to one of the soundtracks. The 'creamy' soundtrack enhanced the perceived creaminess and sweetness of the chocolates, as compared to the ratings given while listening to the 'rough' soundtrack. Moreover, while the participants preferred the creamy soundtrack, this difference did not appear to affect their overall enjoyment of the chocolates. Interestingly, and in contrast with previous similar studies, these results demonstrate that in certain cases, sounds can have a perceptual effect on gustatory food attributes without necessarily altering the hedonic experience.

Visual suppression at the offset of binocular rivalry.

Various paradigms can make visual stimuli disappear from awareness, but they often involve stimuli that are either relatively weak, competing with other salient inputs, and/or presented for a prolonged period of time. Here we explore a phenomenon that involves controlled perceptual disappearance of a peripheral visual stimulus without these limitations. It occurs when one eye's stimulus is abruptly removed during a binocular rivalry situation. This manipulation renders the remaining stimulus, which is still being presented to the other eye, invisible for up to several seconds. Our results suggest that this perceptual disappearance depends on a visual offset-transient that promotes dominance of the eye in which it occurs regardless of whether the eye is dominant or suppressed at the moment of the transient event. Using computational modeling, we demonstrate that standard rivalry mechanisms of interocular inhibition can indeed be complemented by a hypothesized transient-driven gating mechanism to explain the phenomenon. In essence, such a system suggests that visual awareness is dominated by the eye that receives transients and "sticks with" this eye-based dominance for some time in the absence of further transient events. We refer to this phenomenon as the "disrupted rivalry effect" and suggest that it is a potentially powerful paradigm for the study of cortical suppression mechanisms and the neural correlates of visual awareness.

Gamification in Physical Therapy: More Than Using Games.

The implementation of computer games in physical therapy is motivated by characteristics such as attractiveness, motivation, and engagement, but these do not guarantee the intended therapeutic effect of the interventions. Yet, these characteristics are important variables in physical therapy interventions because they involve reward-related dopaminergic systems in the brain that are known to facilitate learning through long-term potentiation of neural connections. In this perspective we propose a way to apply game design approaches to therapy development by "designing" therapy sessions in such a way as to trigger physical and cognitive behavioral patterns required for treatment and neurological recovery. We also advocate that improving game knowledge among therapists and improving communication between therapists and game designers may lead to a novel avenue in designing applied games with specific therapeutic input, thereby making gamification in therapy a realistic and promising future that may optimize clinical practice.

Multisensory Stimulation to Improve Low- and Higher-Level Sensory Deficits after Stroke: A Systematic Review.

The aim of this systematic review was to integrate and assess evidence for the effectiveness of multisensory stimulation (i.e., stimulating at least two of the following sensory systems: visual, auditory, and somatosensory) as a possible rehabilitation method after stroke. Evidence was considered with a focus on low-level, perceptual (visual, auditory and somatosensory deficits), as well as higher-level, cognitive, sensory deficits. We referred to the electronic databases Scopus and PubMed to search for articles that were published before May 2015. Studies were included which evaluated the effects of multisensory stimulation on patients with low- or higher-level sensory deficits caused by stroke. Twenty-one studies were included in this review and the quality of these studies was assessed (based on eight elements: randomization, inclusion of control patient group, blinding of participants, blinding of researchers, follow-up, group size, reporting effect sizes, and reporting time post-stroke). Twenty of the twenty-one included studies demonstrate beneficial effects on low- and/or higher-level sensory deficits after stroke. Notwithstanding these beneficial effects, the quality of the studies is insufficient for valid conclusion that multisensory stimulation can be successfully applied as an effective intervention. A valuable and necessary next step would be to set up well-designed randomized controlled trials to examine the effectiveness of multisensory stimulation as an intervention for low- and/or higher-level sensory deficits after stroke. Finally, we consider the potential mechanisms of multisensory stimulation for rehabilitation to guide this future research.

Octave effect in auditory attention.

After hearing a tone, the human auditory system becomes more sensitive to similar tones than to other tones. Current auditory models explain this phenomenon by a simple bandpass attention filter. Here, we demonstrate that auditory attention involves multiple pass-bands around octave-related frequencies above and below the cued tone. Intriguingly, this "octave effect" not only occurs for physically presented tones, but even persists for the missing fundamental in complex tones, and for imagined tones. Our results suggest neural interactions combining octave-related frequencies, likely located in nonprimary cortical regions. We speculate that this connectivity scheme evolved from exposure to natural vibrations containing octave-related spectral peaks, e.g., as produced by vocal cords.

Visible and invisible stimulus parts integrate into global object representations as revealed by combining monocular and binocular rivalry.

Our visual system faces the challenging task to construct integrated visual representations from the visual input projected on our retinae. Previous research has provided mixed evidence as to whether visual awareness of the stimulus parts is required for such integration to occur. Here, we address this issue by taking a novel approach in which we combine a monocular rivalry stimulus (i.e., a bistable rotating cylinder) with binocular rivalry. The results of Experiment 1 show that in a rivalry condition, where one half of the cylinder is perceptually suppressed, significantly more perceptual switches occur that are consistent with visual integration of the whole cylinder than occur in a control condition, where only half of the cylinder is presented at a time and the presentation of the two images is physically alternated. In Experiment 2, stimulation in the observer's dominant eye was kept dominant by presenting the half cylinder in this eye at higher contrast and by surrounding it with a flickering context. Results show that the strong convexity bias that was found in a control condition, where no stimulus was presented in the suppressed eye, almost completely disappears when the unseen half is presented in the suppressed eye, indicating that both halves visually integrate and, subsequently, compete for convexity. These findings provide evidence that unseen visual information is biased towards a representation that is congruent with the current visible representation and, hence, that principles of perceptual organization also apply to parts of the visual input that remain unseen by the observer.

Implicit perceptual memory modulates early visual processing of ambiguous images.

The way we perceive the present visual environment is influenced by past visual experiences. Here we investigated the neural basis of such experience dependency. We repeatedly presented human observers with an ambiguous visual stimulus (structure-from-motion) that can give rise to two distinct perceptual interpretations. Past visual experience is known to influence the perception of such stimuli. We recorded fast dynamics of neural activity shortly after stimulus onset using event-related electroencephalography. The number of previous occurrences of a certain percept modulated early posterior brain activity starting as early as 50 ms after stimulus onset. This modulation developed across hundreds of percept repetitions, reflecting several minutes of accumulating perceptual experience. Importantly, there was no such modulation when the mere number of previous stimulus presentations was considered regardless of how they were perceived. This indicates that the effect depended on previous perception rather than previous visual input. The short latency and posterior scalp location of the effect suggest that perceptual history modified bottom-up stimulus processing in early visual cortex. We propose that bottom-up neural responses to a given visual presentation are shaped, in part, by feedback modulation that occurred during previous presentations, thus allowing these responses to be biased in light of previous perceptual decisions.

Multisensory Stimulation and Priming (MuSSAP) in 4-10 Months Old Infants with a Unilateral Brain Lesion: A Pilot Randomised Clinical Trial.

Aim: To explore the effect of an Early Intensive-Upper Limb intervention (EI-UL) compared to EI-UL with integrated Multisensory Stimulation And Priming (MuSSAP) training on improving manual ability in infants with a unilateral brain lesion. Method: A pilot randomised clinical trial with pre- and postintervention and follow-up measurements (T0, T1, and T2) was conducted. Sixteen infants with a unilateral brain lesion (corrected age is 4-10 months) received home-based intervention with video coaching. Eight infants received EI-UL and eight infants received EI-UL with integrated MuSSAP training. Primary outcome was the Hand Assessment for Infants (HAI) score. Additionally, effects were explored on initiation of goal-directed movements in both groups and on attention in the EI-UL with integrated MuSSAP training group. Results: No significant group differences in HAI scores were found. Overall, HAI 'Affected hand score' increased between T0 and T1 (p = 0.001, Cohen's d = 1.04) and between T0 and T2 (p < 0.001, Cohen's d = 1.28); and the HAI 'Both Hands Measure' increased between T0 and T1 (p < 0.001, Cohen's d = 1.72) and between T0 and T2 (p < 0.001, Cohen's d = 1.81). At the start of the intervention, six infants (three in both groups) did not demonstrate initiation of goal-directed contralesional upper limb movements. During the intervention one infant receiving EI-UL and all three infants receiving EI-UL with integrated MuSSAP training started to initiate goal-directed movements. Conclusion: The results suggest manual ability of infants with unilateral brain lesion improved with both interventions. We hypothesize that the integrated MuSSAP training may facilitate attention and initiation of contralesional upper limb goal-directed movements. This trial is registered with NCT05533476).

The role of frontal and parietal brain areas in bistable perception.

When sensory input allows for multiple, competing perceptual interpretations, observers' perception can fluctuate over time, which is called bistable perception. Imaging studies in humans have revealed transient responses in a right-lateralized network in the frontal-parietal cortex (rFPC) around the time of perceptual transitions between interpretations, potentially reflecting the neural initiation of transitions. We investigated the role of this activity in male human observers, with specific interest in its relation to the temporal structure of transitions, which can be either instantaneous or prolonged by periods during which observers experience a mix of both perceptual interpretations. Using both bistable apparent motion and binocular rivalry, we show that transition-related rFPC activity is larger for transitions that last longer, suggesting that rFPC remains active as long as a transition lasts. We also replicate earlier findings that rFPC activity during binocular rivalry transitions exceeds activity during yoked transitions that are simulated using video replay. However, we show that this established finding holds only when perceptual transitions are replayed as instantaneous events. When replay, instead, depicts transitions with the actual durations reported during rivalry, yoked transitions and genuine rivalry transitions elicit equal activity. Together, our results are consistent with the view that at least a component of rFPC activation during bistable perception reflects a response to perceptual transitions, both real and yoked, rather than their cause. This component of activity could reflect the change in sensory experience and task demand that occurs during transitions, which fits well with the known role of these areas in attention and decision making.

Perceptual experience modulates cortical circuits involved in visual awareness.

Successful interactions with the environment entail interpreting ambiguous sensory information. To address this challenge it has been suggested that the brain optimizes performance through experience. Here we used functional magnetic resonance imaging (fMRI) to investigate whether perceptual experience modulates the cortical circuits involved in visual awareness. Using ambiguous visual stimuli (binocular rivalry or ambiguous structure-from-motion) we were able to disentangle the co-occurring influences of stimulus repetition and perceptual repetition. For both types of ambiguous stimuli we observed that the mere repetition of the stimulus evoked an entirely different pattern of activity modulations than the repetition of a particular perceptual interpretation of the stimulus. Regarding stimulus repetition, decreased fMRI responses were evident during binocular rivalry but weaker during 3-D motion rivalry. Perceptual repetition, on the other hand, entailed increased activity in stimulus-specific visual brain regions - for binocular rivalry in the early visual regions and for ambiguous structure-from-motion in both early as well as higher visual regions. This indicates that the repeated activation of a visual network mediating a particular percept facilitated its later reactivation. Perceptual repetition was also associated with a response change in the parietal cortex that was similar for the two types of ambiguous stimuli, possibly relating to the temporal integration of perceptual information. We suggest that perceptual repetition is associated with a facilitation of neural activity within and between percept-specific visual networks and parietal networks involved in the temporal integration of perceptual information, thereby enhancing the stability of previously experienced percepts.

On the functional relevance of frontal cortex for passive and voluntarily controlled bistable vision.

In bistable vision, one constant ambiguous stimulus leads to 2 alternating conscious percepts. This perceptual switching occurs spontaneously but can also be influenced through voluntary control. Neuroimaging studies have reported that frontal regions are activated during spontaneous perceptual switches, leading some researchers to suggest that frontal regions causally induce perceptual switches. But the opposite also seems possible: frontal activations may themselves be caused by spontaneous switches. Classically implicated in attentional processes, these same regions are also candidates for the origins of voluntary control over bistable vision. Here too, it remains unknown whether frontal cortex is actually functionally relevant. It is even possible that spontaneous perceptual switches and voluntarily induced switches are mediated by the same top-down mechanisms. To directly address these issues, we here induced "virtual lesions," with transcranial magnetic stimulation, in frontal, parietal, and 2 lower level visual cortices using an established ambiguous structure-from-motion stimulus. We found that dorsolateral prefrontal cortex was causally relevant for voluntary control over perceptual switches. In contrast, we failed to find any evidence for an active role of frontal cortex in passive bistable vision. Thus, it seems the same pathway used for willed top-down modulation of bistable vision is not used during passive bistable viewing.

Personalized tDCS for Focal Epilepsy-A Narrative Review: A Data-Driven Workflow Based on Imaging and EEG Data.

Conventional transcranial electric stimulation(tES) using standard anatomical positions for the electrodes and standard stimulation currents is frequently not sufficiently selective in targeting and reaching specific brain locations, leading to suboptimal application of electric fields. Recent advancements in in vivo electric field characterization may enable clinical researchers to derive better relationships between the electric field strength and the clinical results. Subject-specific electric field simulations could lead to improved electrode placement and more efficient treatments. Through this narrative review, we present a processing workflow to personalize tES for focal epilepsy, for which there is a clear cortical target to stimulate. The workflow utilizes clinical imaging and electroencephalography data and enables us to relate the simulated fields to clinical outcomes. We review and analyze the relevant literature for the processing steps in the workflow, which are the following: tissue segmentation, source localization, and stimulation optimization. In addition, we identify shortcomings and ongoing trends with regard to, for example, segmentation quality and tissue conductivity measurements. The presented processing steps result in personalized tES based on metrics like focality and field strength, which allow for correlation with clinical outcomes.

An immersive virtual reality game to train spatial attention orientation after stroke: A feasibility study.

Immersive virtual reality (IVR) may boost neglect recovery, as it can provide an engaging experience in a 3D environment. We designed an IVR rehabilitation game for neglect patients using the Oculus Rift. Multisensory cues were presented in the neglected visual field in a patient-tailored way. We acquired pilot data in 15 neurologically healthy controls and 7 stroke patients. First, we compared cybersickness before and after VR exposure. Second, we assessed the user experience through a questionnaire. Third, we tested whether neglect symptoms corresponded between the VR game and a computerized cancelation task. Fourth, we evaluated the effect of the multisensory cueing on target discrimination. Last, we tested two algorithms to tailor the game to the characteristics of the neglected visual field. Cybersickness significantly reduced after VR exposure in six stroke patients and was low in healthy controls. Patients rated the user experience neutral to positive. In addition, neglect symptoms were consistent between a computerized cancelation and VR rehabilitation task. The multisensory cue positively affected target discrimination in the game and we successfully presented sensory stimulation to the neglected visual field in a patient-tailored way. Our results show that it is promising to use gamified patient-tailored immersive VR for neglect rehabilitation.

Human middle temporal cortex, perceptual bias, and perceptual memory for ambiguous three-dimensional motion.

When faced with inconclusive or conflicting visual input human observers experience one of multiple possible perceptions. One factor that determines perception of such an ambiguous stimulus is how the same stimulus was perceived on previous occasions, a phenomenon called perceptual memory. We examined perceptual memory of an ambiguous motion stimulus while applying transcranial magnetic stimulation (TMS) to the motion-sensitive areas of the middle temporal cortex (hMT+). TMS increased the predominance of whichever perceptual interpretation was most commonly reported by a given observer at baseline, with reduced perception of the less favored interpretation. This increased incidence of the preferred percept indicates impaired long-term buildup of perceptual memory traces that normally act against individual percept biases. We observed no effect on short-term memory traces acting from one presentation to the next. Our results indicate that hMT+ is important for the long-term buildup of perceptual memory for ambiguous motion stimuli.

Percept-switch nucleation in binocular rivalry reveals local adaptation characteristics of early visual processing.

When the two eyes view incompatible images that subtend the entire visual field, perception alternates between the two images unpredictably: at seemingly random times and locations, observers experience sudden changes in the awareness of the unchanging visual stimulation. Here we focus on the very first spontaneous breakout from the very first suppression phase after onset of the two eyes' competing whole-field stimuli. We call such spontaneous local breakout an "initial percept-switch nucleation." We employed homogeneous visual input to examine where, and how, spontaneous local initial percept-switch nucleations originate, demonstrating that their spatial distribution contains locally random inhomogeneities, which are eye- and observer-dependent. We were able to predict the occurrence probability of the percept nucleations by adaptation buildup of the neurons associated with the representation of one eye's image. Intriguingly, the neuronal processes related to both cross-inhibition and local eye dominance could not predict nucleation probability; this is because nucleation inhomogeneity appeared to be different from another previously reported local inhomogeneity known as "onset bias" signifying the local first dominance-choice inhomogeneity upon stimulus onset. Collectively, we reveal a governing role of local adaptation in the neurons associated with early visual processing of one eye's image, in the origination of new phases in awareness.

The Use of the Term Virtual Reality in Post-Stroke Rehabilitation: A Scoping Review and Commentary.

Virtual reality (VR) offers many opportunities for post-stroke rehabilitation. However, "VR" can refer to several types of computer-based rehabilitation systems. Since these systems may impact the feasibility and the efficacy of VR interventions, consistent terminology is important. In this study, we aimed to optimize the terminology for VR-based post-stroke rehabilitation by assessing whether and how review papers on this topic defined VR and what types of mixed reality systems were discussed. In addition, this review can inspire the use of consistent terminology for other researchers working with VR. We assessed the use of the term VR in review papers on post-stroke rehabilitation extracted from Scopus, Web of Science and PubMed. We also developed a taxonomy distinguishing 16 mixed reality systems based on three factors: immersive versus semi-immersive displays, the way in which real and virtual information is mixed, and the main input device. 64% of the included review papers (N = 121) explicitly defined VR and 33% of them described different subtypes of VR, with immersive and non-immersive VR as the most common distinction. The most frequently discussed input devices were motion-capture cameras and handheld devices, while regular 2D monitors were the most frequently mentioned output devices. Our analysis revealed that reviews on post-stroke VR rehabilitation did not or only broadly defined "VR" and did not focus on a specific system. Since the efficacy and feasibility of rehabilitation may depend on the specific system, we propose a new data-driven taxonomy to distinguish different systems, which is expected to facilitate communication amongst researchers and clinicians working with virtual reality.