Robust inference of causality in high-dimensional dynamical processes from the Information Imbalance of distance ranks.

We introduce an approach which allows detecting causal relationships between variables for which the time evolution is available. Causality is assessed by a variational scheme based on the Information Imbalance of distance ranks, a statistical test capable of inferring the relative information content of different distance measures. We test whether the predictability of a putative driven system Y can be improved by incorporating information from a potential driver system X, without explicitly modeling the underlying dynamics and without the need to compute probability densities of the dynamic variables. This framework makes causality detection possible even between high-dimensional systems where only few of the variables are known or measured. Benchmark tests on coupled chaotic dynamical systems demonstrate that our approach outperforms other model-free causality detection methods, successfully handling both unidirectional and bidirectional couplings. We also show that the method can be used to robustly detect causality in human electroencephalography data.

Perceptual History Biases Are Predicted by Early Visual-Evoked Activity.

What we see in the present is affected by what we saw in the recent past. Serial dependence, a bias making a current stimulus appear more similar to a previous one, has been indeed shown to be ubiquitous in vision. At the neural level, serial dependence is accompanied by a signature of stimulus history (i.e., past stimulus information) emerging from early visual-evoked activity. However, whether this neural signature effectively reflects the behavioral bias is unclear. Here we address this question by assessing the neural (electrophysiological) and behavioral signature of stimulus history in human subjects (both male and female), in the context of numerosity, duration, and size perception. First, our results show that while the behavioral effect is task-dependent, its neural signature also reflects task-irrelevant dimensions of a past stimulus, suggesting a partial dissociation between the mechanisms mediating the encoding of stimulus history and the behavioral bias itself. Second, we show that performing a task is not a necessary condition to observe the neural signature of stimulus history, but that in the presence of an active task such a signature is significantly amplified. Finally, and more importantly, we show that the pattern of brain activity in a relatively early latency window (starting at ∼35-65 ms after stimulus onset) significantly predicts the behavioral effect. Overall, our results thus demonstrate that the encoding of past stimulus information in neural signals does indeed reflect serial dependence, and that serial dependence occurs at a relatively early level of visual processing.SIGNIFICANCE STATEMENT What we perceive is determined not only by the information reaching our sensory organs, but also by the context in which the information is embedded. What we saw in the recent past (perceptual history) can indeed modulate the perception of a current stimulus in an attractive way, a bias that is ubiquitous in vision. Here we show that this bias can be predicted by the pattern of brain activity reflecting the encoding of past stimulus information, very early after the onset of a stimulus. This in turn suggests that the integration of past and present sensory information mediating the attractive bias occurs early in the visual processing stream, and likely involves early visual cortices.

The more numerous the longer: how the integration between numerosity and time leads to a common neural response.

If you are stuck in a traffic jam, the more numerous the queuing cars are, the longer you expect to wait. Time and numerosity are stimulus dimensions often associated in the same percept and whose interaction can lead to misjudgements. At brain level it is unclear to which extent time and numerosity recruit same/different neural populations and how their perceptual integration leads to changes in these populations' responses. Here we used high-spatial-resolution functional magnetic resonance imaging with neural model-based analyses to investigate how the topographic representations of numerosity and time change when these dimensions are varied together on the same visual stimulus in a congruent (the more numerous the items, the longer the display time) or incongruent manner. Compared to baseline conditions, where only one dimension was changed at a time, the variation of both stimulus dimensions led to changes in neural population responses that became more sensitive either to the two features or to one of them. Magnitude integration led also to degradation of topographies and shifts in response preferences. These changes were more pronounced in the comparison between parietal and frontal maps. Our results while pointing to partially distinct representations of time and numerosity show a common neural response to magnitude integration.

Subjective time is predicted by local and early visual processing.

Time is as pervasive as it is elusive to study, and how the brain keeps track of millisecond time is still unclear. Here we addressed the mechanisms underlying duration perception by looking for a neural signature of subjective time distortion induced by motion adaptation. We recorded electroencephalographic signals in human participants while they were asked to discriminate the duration of visual stimuli after different types of translational motion adaptation. Our results show that perceived duration can be predicted by the amplitude of the N200 event-related potential evoked by the adapted stimulus. Moreover, we show that the distortion of subjective time can be predicted by the activity in the Beta band frequency spectrum, at the offset of the adaptor and during the presentation of the subsequent adapted stimulus. Both effects were observed from posterior electrodes contralateral to the adapted stimulus. Overall, our findings suggest that local and low-level perceptual processes are involved in generating a subjective sense of time.

Chronotopic maps in human supplementary motor area.

Time is a fundamental dimension of everyday experiences. We can unmistakably sense its passage and adjust our behavior accordingly. Despite its ubiquity, the neuronal mechanisms underlying the capacity to perceive time remains unclear. Here, in two experiments using ultrahigh-field 7-Tesla (7T) functional magnetic resonance imaging (fMRI), we show that in the medial premotor cortex (supplementary motor area [SMA]) of the human brain, neural units tuned to different durations are orderly mapped in contiguous portions of the cortical surface so as to form chronomaps. The response of each portion in a chronomap is enhanced by neighboring durations and suppressed by nonpreferred durations represented in distant portions of the map. These findings suggest duration-sensitive tuning as a possible neural mechanism underlying the recognition of time and demonstrate, for the first time, that the representation of an abstract feature such as time can be instantiated by a topographical arrangement of duration-sensitive neural populations.

The nature of magnitude integration: Contextual interference versus active magnitude binding.

Magnitude dimensions such as duration and numerosity have been shown to systematically interact, biasing each other in a congruent fashion: the more numerous a set of items is, the longer it is perceived to last in time. This integration between dimensions plays an important role in defining how we perceive magnitude. So far, however, the nature of magnitude integration remains unclear. Is magnitude integration a contextual interference, occurring whenever different types of information are concurrently available in the visual field, or does it involve an active "binding" of the different dimensions of the same object? To address these possibilities, we measured the integration bias induced by numerosity on perceived duration, in two cases: with duration and numerosity conveyed by distinct stimuli, or by the same stimulus. We show that a congruent integration effect can be observed only when the two magnitudes belong to the same stimulus. Instead, when the two magnitudes are conveyed by distinct stimuli, we observed an opposite effect. These findings demonstrate for the first time that a congruent integration occurs only between the dimensions of the same stimulus, suggesting the involvement of an active mechanism integrating the different dimensions of the same object in a unified percept.

The specious interaction of time and numerosity perception.

Magnitude information is essential to create a representation of the external environment and successfully interact with it. Duration and numerosity, for example, can shape our predictions and bias each other (i.e. the greater the number of people queuing, the longer we expect to wait). While these biases suggest the existence of a generalized magnitude system, asymmetric effects (i.e. numerosity affecting duration but not vice versa) challenged this idea. Here, we propose that such asymmetric integration depends on the stimuli used and the neural processing dynamics they entail. Across multiple behavioural experiments employing different stimulus presentation displays (static versus dynamic) and experimental manipulations known to bias numerosity and duration perceptions (i.e. connectedness and multisensory integration), we show that the integration between numerosity and time can be symmetrical if the stimuli entail a similar neural time-course and numerosity unfolds over time. Overall, these findings support the idea of a generalized magnitude system, but also highlight the role of early sensory processing in magnitude representation and integration.

Serial dependence in time and numerosity perception is dimension-specific.

The perception of a visual event (e.g., a flock of birds) at the present moment can be biased by a previous perceptual experience (e.g., the perception of an earlier flock). Serial dependence is a perceptual bias whereby a current stimulus appears more similar to a previous one than it actually is. Whereas serial dependence emerges within several visual stimulus dimensions, whether it could simultaneously operate across different dimensions of the same stimulus (e.g., the numerosity and the duration of a visual pattern) remains unclear. Here we address this question by assessing the presence of serial dependence across duration and numerosity, two stimulus dimensions that are often associated and can bias each other. Participants performed either a duration or a numerosity discrimination task, in which they compared a constant reference with a variable test stimulus, varying along the task-relevant dimension (either duration or numerosity). Serial dependence was induced by a task-irrelevant inducer, that is, a stimulus presented before the reference and always varying in both duration and numerosity. The results show systematic serial dependencies only within the task-relevant stimulus dimension, that is, stimulus numerosity affects numerosity perception only, and duration affects duration perception only. Additionally, at least in the numerosity condition, the task-irrelevant dimension of the inducer (duration) had an opposite, repulsive effect. These findings thus show that attractive serial dependence operates in a highly specific fashion and does not transfer across different stimulus dimensions. Instead, the repulsive influence, possibly reflecting perceptual adaptation, can transfer from one dimension to another.

EEG Correlates of Preparatory Orienting, Contextual Updating, and Inhibition of Sensory Processing in Left Spatial Neglect.

Studies with event-related potentials have highlighted deficits in the early phases of orienting to left visual targets in right-brain-damaged patients with left spatial neglect (N+). However, brain responses associated with preparatory orienting of attention, with target novelty and with the detection of a match/mismatch between expected and actual targets (contextual updating), have not been explored in N+. Here in a study in healthy humans and brain-damaged patients of both sexes we demonstrate that frontal activity that reflects supramodal mechanisms of attentional orienting (Anterior Directing Attention Negativity, ADAN) is entirely spared in N+. In contrast, posterior responses that mark the early phases of cued orienting (Early Directing Attention Negativity, EDAN) and the setting up of sensory facilitation over the visual cortex (Late Directing Attention Positivity, LDAP) are suppressed in N+. This uncoupling is associated with damage of parietal-frontal white matter. N+ also exhibit exaggerated novelty reaction to targets in the right side of space and reduced novelty reaction for those in the left side (P3a) together with impaired contextual updating (P3b) in the left space. Finally, we highlight a drop in the amplitude and latency of the P1 that over the left hemisphere signals the early blocking of sensory processing in the right space when targets occur in the left one: this identifies a new electrophysiological marker of the rightward attentional bias in N+. The heterogeneous effects and spatial biases produced by localized brain damage on the different phases of attentional processing indicate relevant functional independence among their underlying neural mechanisms and improve the understanding of the spatial neglect syndrome.SIGNIFICANCE STATEMENT Our investigation answers important questions: are the different components of preparatory orienting (EDAN, ADAN, LDAP) functionally independent in the healthy brain? Is preparatory orienting of attention spared in left spatial neglect? Does the sparing of preparatory orienting have an impact on deficits in reflexive orienting and in the assignment of behavioral relevance to the left space? We show that supramodal preparatory orienting in frontal areas is entirely spared in neglect patients though this does not counterbalance deficits in preparatory parietal-occipital activity, reflexive orienting, and contextual updating. This points at relevant functional dissociations among different components of attention and suggests that improving voluntary attention in N+ might be behaviorally ineffective unless associated with stimulations boosting the response of posterior parietal-occipital areas.

How the visual brain encodes and keeps track of time.

Time is embedded in any sensory experience: the movements of a dance, the rhythm of a piece of music, the words of a speaker are all examples of temporally structured sensory events. In humans, if and how visual cortices perform temporal processing remains unclear. Here we show that both primary visual cortex (V1) and extrastriate area V5/MT are causally involved in encoding and keeping time in memory and that this involvement is independent from low-level visual processing. Most importantly we demonstrate that V1 and V5/MT come into play simultaneously and seem to be functionally linked during interval encoding, whereas they operate serially (V1 followed by V5/MT) and seem to be independent while maintaining temporal information in working memory. These data help to refine our knowledge of the functional properties of human visual cortex, highlighting the contribution and the temporal dynamics of V1 and V5/MT in the processing of the temporal aspects of visual information.

No inherent left and right side in human 'mental number line': evidence from right brain damage.

Spatial reasoning has a relevant role in mathematics and helps daily computational activities. It is widely assumed that in cultures with left-to-right reading, numbers are organized along the mental equivalent of a ruler, the mental number line, with small magnitudes located to the left of larger ones. Patients with right brain damage can disregard smaller numbers while mentally setting the midpoint of number intervals. This has been interpreted as a sign of spatial neglect for numbers on the left side of the mental number line and taken as a strong argument for the intrinsic left-to-right organization of the mental number line. Here, we put forward the understanding of this cognitive disability by discovering that patients with right brain damage disregard smaller numbers both when these are mapped on the left side of the mental number line and on the right side of an imagined clock face. This shows that the right hemisphere supports the representation of small numerical magnitudes independently from their mapping on the left or the right side of a spatial-mental layout. In addition, the study of the anatomical correlates through voxel-based lesion-symptom mapping and the mapping of lesion peaks on the diffusion tensor imaging-based reconstruction of white matter pathways showed that the rightward bias in the imagined clock-face was correlated with lesions of high-level middle temporal visual areas that code stimuli in object-centred spatial coordinates, i.e. stimuli that, like a clock face, have an inherent left and right side. In contrast, bias towards higher numbers on the mental number line was linked to white matter damage in the frontal component of the parietal-frontal number network. These anatomical findings show that the human brain does not represent the mental number line as an object with an inherent left and right side. We conclude that the bias towards higher numbers in the mental bisection of number intervals does not depend on left side spatial, imagery or object-centred neglect and that it rather depends on disruption of an abstract non-spatial representation of small numerical magnitudes.

Effective connectivity in a duration selective cortico-cerebellar network.

How the human brain represents millisecond unit of time is far from clear. A recent neuroimaging study revealed the existence in the human premotor cortex of a topographic representation of time i.e., neuronal units selectively responsive to specific durations and topographically organized on the cortical surface. By using high resolution functional Magnetic Resonance Images here, we go beyond this previous work, showing duration preferences across a wide network of cortical and subcortical brain areas: from cerebellum to primary visual, parietal, premotor and prefrontal cortices. Most importantly, we identify the effective connectivity structure between these different brain areas and their duration selective neural units. The results highlight the role of the cerebellum as the network hub and that of medial premotor cortex as the final stage of duration recognition. Interestingly, when a specific duration is presented, only the communication strength between the units selective to that specific duration and to the neighboring durations is affected. These findings link for the first time, duration preferences within single brain region with connectivity dynamics between regions, suggesting a communication mode that is partially duration specific.

Encoding of temporal probabilities in the human brain.

Anticipating the timing of future events is a necessary precursor to preparing actions and allocating resources to sensory processing. This requires elapsed time to be represented in the brain and used to predict the temporal probability of upcoming events. While neuropsychological, imaging, magnetic stimulation studies, and single-unit recordings implicate the role of higher parietal and motor-related areas in temporal estimation, the role of earlier, purely sensory structures remains more controversial. Here we demonstrate that the temporal probability of expected visual events is encoded not by a single area but by a wide network that importantly includes neuronal populations at the very earliest cortical stages of visual processing. Moreover, we show that activity in those areas changes dynamically in a manner that closely accords with temporal expectations.

Physiological correlates of subjective time: evidence for the temporal accumulator hypothesis.

Clock-counter models, the most influential cognitive models of temporal computation, have been successful in explaining a large set of behavioral data. However, it remains unclear whether the component operations postulated in these models correspond to any specific biological mechanism. Using stimuli in different sensory modalities and manipulating physical properties known to bias the 'subjective' perception of time (speed for vision and pitch for audition), the present study aimed to highlight brain areas where activity correlates with the 'subjective' perception of time: a time accumulator according to clock-counter models. Using functional MRI we found that during the encoding of a temporal interval in the millisecond range (600 and 1000 ms), the hemodynamic response of a few brain regions correlated with the interval reproduction performance. For the visual modality, the activity of the putamen, the mid-insula and the mid-temporal cortex reflected the subjective interval duration, which was biased according to the different speeds of the visual stimuli. This effect was found only when subjects encoded the stimulus duration and was specific for the visual modality, where a significant overestimation of time with increasing speed was observed. These results demonstrate a definite relation between 'subjective time' and brain activity, supporting the hypothesis of a physiological correlate of time 'accumulation'.

Adaptive motion processing in bilateral vestibular failure.

BACKGROUND: Patients with bilateral vestibular failure (BVF) suffer from oscillopsia during head movements. This is secondary to the loss of the vestibulo-ocular reflex which is responsible for stabilising retinal images during head movements of high frequency or velocity. Previous studies documented decreased visual motion sensitivity in such patients at low velocities. The authors now examine motion coherence tasks, which have two advantages: (1) the task is associated with the functions of the middle temporal area; and (2) it affords testing at low and high motion velocities, as relevant for patients with oscillopsia due to BVF. METHODS: Nine BVF patients and nine healthy control subjects were examined with a random dot pattern with variable percentages of dots moving in the target direction. Participants were asked to indicate in which of two possible directions they perceived the coherent motion. Horizontal and vertical planes were tested at speeds from 0.156 to 40°/s. RESULTS: Motion coherence thresholds were lower at higher speeds in both groups (p<0.0001). BVF patients had raised motion coherence thresholds (p=0.002) across all velocities as compared with the control subject group. CONCLUSION: In a motion coherence paradigm, BVF patients show raised thresholds. This is the first demonstration of diminished visual motion processing at high velocities, supporting the view that the changes allow BVF patients to partly compensate for the oscillopsia. The findings are interpreted as an adaptive process likely to involve the middle temporal visual motion processing areas.

Modality-independent role of the primary auditory cortex in time estimation.

It has been argued that both modality-specific and supramodal mechanisms dedicated to time perception underlie the estimation of interval durations. While it is generally assumed that early sensory areas are dedicated to modality-specific time estimation, we hypothesized that early sensory areas such as the primary visual cortex or the auditory cortex might be involved in time perception independently of the sensory modality of the input. To test this possibility, we examined whether disruption of the primary visual cortex or the auditory cortex would disrupt time estimation of auditory stimuli and visual stimuli using transcranial magnetic stimulation (TMS). We found that disruption of the auditory cortex impaired not only time estimation of auditory stimuli but also impaired that of visual stimuli to the same degree. This finding suggests a supramodal role of the auditory cortex in time perception. On the other hand, TMS over the primary visual cortex impaired performance only in visual time discrimination. These asymmetric contributions of the auditory and visual cortices in time perception may be explained by a superiority of the auditory cortex in temporal processing. Here, we propose that time is primarily encoded in the auditory system and that visual inputs are automatically encoded into an auditory representation in time discrimination tasks.

Auditory temporal expectations modulate activity in visual cortex.

Temporal expectation is the ability to make predictions and to use temporal information to anticipate the occurrence of future events. This capacity is associated with highly efficient perceptual and motor behaviors. However, how cognitive systems use temporal information to optimize behavior and what brain structures are engaged during these processes remains largely unknown. Neurophysiological and recent neuroimaging data have suggested that temporal expectations modulate activity not only in parietal and motor-related frontal regions, but also in occipital visual cortex, when the expected stimulus is a simple visual object. Here we investigate crossmodal properties and category selectivity of temporal expectations examining activity in visual cortex during expectation of auditory stimuli (the sound of hand-clapping or of a hammer-hammering). We found that activity in occipital cortex changed over time, reflecting the subject's temporal expectations about the upcoming auditory event. This modulatory effect included extrastriate visual areas known to process body-parts and tools, despite these were never presented visually during the experiment. However activity in these areas was not specific for the expected sound category, but it was rather related to the overall probability of the auditory target to occur. We conclude that crossmodal associations can influence activity in sensory-specific visual areas in an anticipatory manner, consistent with temporal expectations affecting activity in a distributed system of motor-related and sensory-related brain regions.

Time Processing: Multiple Topographic Representations of Time across Human Cortex.

How is millisecond unit of time represented in the human brain? A new neuroimaging study at high spatial resolution has revealed the existence of a topographic representation of event duration and frequency in ten cortical locations along a functional hierarchy that goes from occipital to frontal regions of the brain.

Brainstem Correlates of a Cold Pressor Test Measured by Ultra-High Field fMRI.

INTRODUCTION: Modern imaging techniques such as blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) allow the non-invasive and indirect measurement of brain activity. Whether changes in signal intensity can be detected in small brainstem regions during a cold pressor test (CPT) has not been explored thoroughly. The aim of this study was to measure whole brain and brainstem BOLD signal intensity changes in response to a modified CPT. METHODS: BOLD fMRI was measured in healthy normotensive participants during a randomized crossover study (modified CPT vs. control test) using ultra-high field 7 Tesla MRI scanner. Data were analyzed using Statistical Parametric Mapping (SPM) in a whole-brain approach, and with a brainstem-specific analysis using the spatially unbiased infra-tentorial template (SUIT) toolbox. Blood pressure (BP) and hormonal responses (norepinephrine and epinephrine levels) were also measured. Paired t-test statistics were used to compare conditions. RESULTS: Eleven participants (six women, mean age 28 ± 8.9 years) were analyzed. Mean arterial BP increased from 83 ± 12 mm Hg to 87 ± 12 mm Hg (p = 0.0009) during the CPT. Whole-brain analysis revealed significant activations linked to the CPT in the right supplementary motor cortex, midcingulate (bilateral) and the right anterior insular cortex. The brainstem-specific analysis showed significant activations in the dorsal medulla. CONCLUSION: Changes in BOLD fMRI signal intensity in brainstem regions during a CPT can be detected, and show an increased response during a cold stress in healthy volunteers. Consequently, BOLD fMRI at 7T is a promising tool to explore and acquire new insights in the comprehension of neurogenic hypertension.