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.

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.

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.

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.

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.

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.

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.

Body odors (even when masked) make you more emotional: behavioral and neural insights.

Morality evolved within specific social contexts that are argued to shape moral choices. In turn, moral choices are hypothesized to be affected by body odors as they powerfully convey socially-relevant information. We thus investigated the neural underpinnings of the possible body odors effect on the participants' decisions. In an fMRI study we presented to healthy individuals 64 moral dilemmas divided in incongruent (real) and congruent (fake) moral dilemmas, using different types of harm (intentional: instrumental dilemmas, or inadvertent: accidental dilemmas). Participants were required to choose deontological or utilitarian actions under the exposure to a neutral fragrance (masker) or body odors concealed by the same masker (masked body odor). Smelling the masked body odor while processing incongruent (not congruent) dilemmas activates the supramarginal gyrus, consistent with an increase in prosocial attitude. When processing accidental (not instrumental) dilemmas, smelling the masked body odor activates the angular gyrus, an area associated with the processing of people's presence, supporting the hypothesis that body odors enhance the saliency of the social context in moral scenarios. These results suggest that masked body odors can influence moral choices by increasing the emotional experience during the decision process, and further explain how sensory unconscious biases affect human behavior.

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.

Representations of time in human frontoparietal cortex.

Precise time estimation is crucial in perception, action and social interaction. Previous neuroimaging studies in humans indicate that perceptual timing tasks involve multiple brain regions; however, whether the representation of time is localized or distributed in the brain remains elusive. Using ultra-high-field functional magnetic resonance imaging combined with multivariate pattern analyses, we show that duration information is decoded in multiple brain areas, including the bilateral parietal cortex, right inferior frontal gyrus and, albeit less clearly, the medial frontal cortex. Individual differences in the duration judgment accuracy were positively correlated with the decoding accuracy of duration in the right parietal cortex, suggesting that individuals with a better timing performance represent duration information in a more distinctive manner. Our study demonstrates that although time representation is widely distributed across frontoparietal regions, neural populations in the right parietal cortex play a crucial role in time estimation.

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.

Contributions of pitch and bandwidth to sound-induced enhancement of visual cortex excitability in humans.

Multisensory interactions have been documented within low-level, even primary, cortices and at early post-stimulus latencies. These effects are in turn linked to behavioral and perceptual modulations. In humans, visual cortex excitability, as measured by transcranial magnetic stimulation (TMS) induced phosphenes, can be reliably enhanced by the co-presentation of sounds. This enhancement occurs at pre-perceptual stages and is selective for different types of complex sounds. However, the source(s) of auditory inputs effectuating these excitability changes in primary visual cortex remain disputed. The present study sought to determine if direct connections between low-level auditory cortices and primary visual cortex are mediating these kinds of effects by varying the pitch and bandwidth of the sounds co-presented with single-pulse TMS over the occipital pole. Our results from 10 healthy young adults indicate that both the central frequency and bandwidth of a sound independently affect the excitability of visual cortex during processing stages as early as 30 msec post-sound onset. Such findings are consistent with direct connections mediating early-latency, low-level multisensory interactions within visual cortices.

Adaptive tuning of perceptual timing to whole body motion.

In a previous work we have shown that sinusoidal whole-body rotations producing continuous vestibular stimulation, affected the timing of motor responses as assessed with a paced finger tapping (PFT) task (Binetti et al. (2010). Neuropsychologia, 48(6), 1842-1852). Here, in two new psychophysical experiments, one purely perceptual and one with both sensory and motor components, we explored the relationship between body motion/vestibular stimulation and perceived timing of acoustic events. In experiment 1, participants were required to discriminate sequences of acoustic tones endowed with different degrees of acceleration or deceleration. In this experiment we found that a tone sequence presented during acceleratory whole-body rotations required a progressive increase in rate in order to be considered temporally regular, consistent with the idea of an increase in "clock" frequency and of an overestimation of time. In experiment 2 participants produced self-paced taps, which entailed an acoustic feedback. We found that tapping frequency in this task was affected by periodic motion by means of anticipatory and congruent (in-phase) fluctuations irrespective of the self-generated sensory feedback. On the other hand, synchronizing taps to an external rhythm determined a completely opposite modulation (delayed/counter-phase). Overall this study shows that body displacements "remap" our metric of time, affecting not only motor output but also sensory input.

Learning about time: plastic changes and interindividual brain differences.

Learning the timing of rapidly changing sensory events is crucial to construct a reliable representation of the environment and to efficiently control behavior. The neurophysiological mechanisms underlying the learning of time are unknown. We used functional and structural magnetic resonance imaging to investigate neurophysiological changes and individual brain differences underlying the learning of time in the millisecond range. We found that the representation of a trained visual temporal interval was associated with functional and structural changes in a sensory-motor network including occipital, parietal, and insular cortices, plus the cerebellum. We show that both types of neurophysiological changes correlated with changes of performance accuracy and that activity and gray-matter volume of sensorimotor cortices predicted individual learning abilities. These findings represent neurophysiological evidence of functional and structural plasticity associated with the learning of time in humans and highlight the role of sensory-motor circuits in the perceptual representation of time in the millisecond range.