Tests for consciousness in humans and beyond.

Which systems/organisms are conscious? New tests for consciousness ('C-tests') are urgently needed. There is persisting uncertainty about when consciousness arises in human development, when it is lost due to neurological disorders and brain injury, and how it is distributed in nonhuman species. This need is amplified by recent and rapid developments in artificial intelligence (AI), neural organoids, and xenobot technology. Although a number of C-tests have been proposed in recent years, most are of limited use, and currently we have no C-tests for many of the populations for which they are most critical. Here, we identify challenges facing any attempt to develop C-tests, propose a multidimensional classification of such tests, and identify strategies that might be used to validate them.

The neuronal basis of human creativity.

Human creativity is a powerful cognitive ability underlying all uniquely human cultural and scientific advancement. However, the neuronal basis of this creative ability is unknown. Here, I propose that slow, spontaneous fluctuations in neuronal activity, also known as "resting state" fluctuations, constitute a universal mechanism underlying all facets of human creativity. Support for this hypothesis is derived from experiments that directly link spontaneous fluctuations and verbal creativity. Recent experimental and modeling advances in our understanding of the spontaneous fluctuations offer an explanation for the diversity and innovative nature of creativity, which is derived from a unique integration of random, neuronal noise on the one hand with individually specified, deterministic information acquired through learning, expertise training, and hereditary traits. This integration between stochasticity and order leads to a process that offers, on the one hand, original, unexpected outcomes but, on the other hand, endows these outcomes with knowledge-based meaning and significance.

Perceptual stability reflected in neuronal pattern similarities in human visual cortex.

The magnitude of neuronal activation is commonly considered a critical factor for conscious perception of visual content. However, this dogma contrasts with the phenomenon of rapid adaptation, in which the magnitude of neuronal activation drops dramatically in a rapid manner while the visual stimulus and the conscious experience it elicits remain stable. Here, we report that the profiles of multi-site activation patterns and their relational geometry-i.e., the similarity distances between activation patterns, as revealed using intracranial electroencephalographic (iEEG) recordings-are sustained during extended visual stimulation despite the major magnitude decrease. These results are compatible with the hypothesis that conscious perceptual content is associated with the neuronal pattern profiles and their similarity distances, rather than the overall activation magnitude, in human visual cortex.

Retrospective behavioral sampling (RBS): A method to effectively track the cognitive fluctuations driven by naturalistic stimulation.

Everyday experiences are dynamic, driving fluctuations across simultaneous cognitive processes. A key challenge in the study of naturalistic cognition is to disentangle the complexity of these dynamic processes, without altering the natural experience itself. Retrospective behavioral sampling (RBS) is a novel approach to model the cognitive fluctuations corresponding to the time-course of naturalistic stimulation, across a variety of cognitive dimensions. We tested the effectiveness and reliability of RBS in a web-based experiment, in which 53 participants viewed short movies and listened to a story, followed by retrospective reporting. Participants recalled their experience of 55 discrete events from the stimuli, rating their quality of memory, magnitude of surprise, intensity of negative and positive emotions, perceived importance, reflectivity state, and mental time travel. In addition, a subset of the original cohort re-rated their memory of events in a follow-up questionnaire. Results show highly replicable fluctuation patterns across distinct cognitive dimensions, thereby revealing a stimulus-driven experience that is substantially shared among individuals. Remarkably, memory ratings more than a week after stimulation resulted in an almost identical time-course of memorability as measured immediately following stimulation. In addition, idiosyncratic response patterns were preserved across different stimuli, indicating that RBS characterizes individual differences that are stimulus invariant. The current findings highlight the potential of RBS as a powerful tool for measuring dynamic processes of naturalistic cognition. We discuss the promising approach of matching RBS fluctuations with dynamic processes measured via other testing modalities, such as neuroimaging, to study the neural manifestations of naturalistic cognitive processing.

A consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations.

Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.

Local neuronal relational structures underlying the contents of human conscious experience.

While most theories of consciousness posit some kind of dependence on global network activities, I consider here an alternative, localist perspective-in which localized cortical regions each underlie the emergence of a unique category of conscious experience. Under this perspective, the large-scale activation often found in the cortex is a consequence of the complexity of typical conscious experiences rather than an obligatory condition for the emergence of conscious awareness-which can flexibly shift, depending on the richness of its contents, from local to more global activation patterns. This perspective fits a massive body of human imaging, recordings, lesions and stimulation data but opens a fundamental problem: how can the information, defining each content, be derived locally in each cortical region. Here, I will discuss a solution echoing pioneering structuralist ideas in which the content of a conscious experience is defined by its relationship to all other contents within an experiential category. In neuronal terms, this relationship structure between contents is embodied by the local geometry of similarity distances between cortical activation patterns generated during each conscious experience, likely mediated via networks of local neuronal connections. Thus, in order for any conscious experience to appear in an individual's mind, two central conditions must be met. First, a specific configural pattern ("bar-code") of neuronal activity must appear within a local relational geometry, i.e. a cortical area. Second, the individual neurons underlying the activated pattern must be bound into a unified functional ensemble through a burst of recurrent neuronal firing: local "ignitions".

Global waves synchronize the brain's functional systems with fluctuating arousal.

We propose and empirically support a parsimonious account of intrinsic, brain-wide spatiotemporal organization arising from traveling waves linked to arousal. We hypothesize that these waves are the predominant physiological process reflected in spontaneous functional magnetic resonance imaging (fMRI) signal fluctuations. The correlation structure ("functional connectivity") of these fluctuations recapitulates the large-scale functional organization of the brain. However, a unifying physiological account of this structure has so far been lacking. Here, using fMRI in humans, we show that ongoing arousal fluctuations are associated with global waves of activity that slowly propagate in parallel throughout the neocortex, thalamus, striatum, and cerebellum. We show that these waves can parsimoniously account for many features of spontaneous fMRI signal fluctuations, including topographically organized functional connectivity. Last, we demonstrate similar, cortex-wide propagation of neural activity measured with electrocorticography in macaques. These findings suggest that traveling waves spatiotemporally pattern brain-wide excitability in relation to arousal.

Hippocampal ripples and their coordinated dialogue with the default mode network during recent and remote recollection.

Hippocampal ripples are prominent synchronization events generated by hippocampal neuronal assemblies. To date, ripples have been primarily associated with navigational memory in rodents and short-term episodic recollections in humans. Here, we uncover different profiles of ripple activity in the human hippocampus during the retrieval of recent and remote autobiographical events and semantic facts. We found that the ripple rate increased significantly before reported recall compared to control conditions. Patterns of ripple activity across multiple hippocampal sites demonstrated remarkable specificity for memory type. Intriguingly, these ripple patterns revealed a semantization dimension, in which patterns associated with autobiographical contents become similar to those of semantic memory as a function of memory age. Finally, widely distributed sites across the neocortex exhibited ripple-coupled activations during recollection, with the strongest activation found within the default mode network. Our results thus reveal a key role for hippocampal ripples in orchestrating hippocampal-cortical communication across large-scale networks involved in conscious recollection.

The surprising role of the default mode network in naturalistic perception.

The default mode network (DMN) is a group of high-order brain regions recently implicated in processing external naturalistic events, yet it remains unclear what cognitive function it serves. Here we identified the cognitive states predictive of DMN fMRI coactivation. Particularly, we developed a state-fluctuation pattern analysis, matching network coactivations across a short movie with retrospective behavioral sampling of movie events. Network coactivation was selectively correlated with the state of surprise across movie events, compared to all other cognitive states (e.g. emotion, vividness). The effect was exhibited in the DMN, but not dorsal attention or visual networks. Furthermore, surprise was found to mediate DMN coactivations with hippocampus and nucleus accumbens. These unexpected findings point to the DMN as a major hub in high-level prediction-error representations.

Face-Selective Units in Human Ventral Temporal Cortex Reactivate during Free Recall.

Research in functional neuroimaging has suggested that category-selective regions of visual cortex, including the ventral temporal cortex (VTC), can be reactivated endogenously through imagery and recall. Face representation in the monkey face-patch system has been well studied and is an attractive domain in which to explore these processes in humans. The VTCs of 8 human subjects (4 female) undergoing invasive monitoring for epilepsy surgery were implanted with microelectrodes. Most (26 of 33) category-selective units showed specificity for face stimuli. Different face exemplars evoked consistent and discriminable responses in the population of units sampled. During free recall, face-selective units preferentially reactivated in the absence of visual stimulation during a 2 s window preceding face recall events. Furthermore, we show that in at least 1 subject, the identity of the recalled face could be predicted by comparing activity preceding recall events to activity evoked by visual stimulation. We show that face-selective units in the human VTC are reactivated endogenously, and present initial evidence that consistent representations of individual face exemplars are specifically reactivated in this manner.SIGNIFICANCE STATEMENT The role of "top-down" endogenous reactivation of native representations in higher sensory areas is poorly understood in humans. We conducted the first detailed single-unit survey of ventral temporal cortex (VTC) in human subjects, showing that, similarly to nonhuman primates, humans encode different faces using different rate codes. Then, we demonstrated that, when subjects recalled and imagined a given face, VTC neurons reactivated with the same rate codes as when subjects initially viewed that face. This suggests that the VTC units not only carry durable representations of faces, but that those representations can be endogenously reactivated via "top-down" mechanisms.

How do the blind 'see'? The role of spontaneous brain activity in self-generated perception.

Spontaneous activity of the human brain has been well documented, but little is known about the functional role of this ubiquitous neural phenomenon. It has previously been hypothesized that spontaneous brain activity underlies unprompted (internally generated) behaviour. We tested whether spontaneous brain activity might underlie internally-generated vision by studying the cortical visual system of five blind/visually-impaired individuals who experience vivid visual hallucinations (Charles Bonnet syndrome). Neural populations in the visual system of these individuals are deprived of external input, which may lead to their hyper-sensitization to spontaneous activity fluctuations. To test whether these spontaneous fluctuations can subserve visual hallucinations, the functional MRI brain activity of participants with Charles Bonnet syndrome obtained while they reported their hallucinations (spontaneous internally-generated vision) was compared to the: (i) brain activity evoked by veridical vision (externally-triggered vision) in sighted controls who were presented with a visual simulation of the hallucinatory streams; and (ii) brain activity of non-hallucinating blind controls during visual imagery (cued internally-generated vision). All conditions showed activity spanning large portions of the visual system. However, only the hallucination condition in the Charles Bonnet syndrome participants demonstrated unique temporal dynamics, characterized by a slow build-up of neural activity prior to the reported onset of hallucinations. This build-up was most pronounced in early visual cortex and then decayed along the visual hierarchy. These results suggest that, in the absence of external visual input, a build-up of spontaneous fluctuations in early visual cortex may activate the visual hierarchy, thereby triggering the experience of vision.

Resting-State Fluctuations Underlie Free and Creative Verbal Behaviors in the Human Brain.

Resting-state fluctuations are ubiquitous and widely studied phenomena of the human brain, yet we are largely in the dark regarding their function in human cognition. Here we examined the hypothesis that resting-state fluctuations underlie the generation of free and creative human behaviors. In our experiment, participants were asked to perform three voluntary verbal tasks: a verbal fluency task, a verbal creativity task, and a divergent thinking task, during functional magnetic resonance imaging scanning. Blood oxygenation level dependent (BOLD)-activity during these tasks was contrasted with a control- deterministic verbal task, in which the behavior was fully determined by external stimuli. Our results reveal that all voluntary verbal-generation responses displayed a gradual anticipatory buildup that preceded the deterministic control-related responses. Critically, the time-frequency dynamics of these anticipatory buildups were significantly correlated with resting-state fluctuations' dynamics. These correlations were not a general BOLD-related or verbal-response related result, as they were not found during the externally determined verbal control condition. Furthermore, they were located in brain regions known to be involved in language production, specifically the left inferior frontal gyrus. These results suggest a common function of resting-state fluctuations as the neural mechanism underlying the generation of free and creative behaviors in the human cortex.

Inter-participant consistency of language-processing networks during abstract thoughts.

Human brain imaging typically employs structured and controlled tasks to avoid variable and inconsistent activation patterns. Here we expand this assumption by showing that an extremely open-ended, high-level cognitive task of thinking about an abstract content, loosely defined as "abstract thinking" - leads to highly consistent activation maps. Specifically, we show that activation maps generated during such cognitive process were precisely located relative to borders of well-known networks such as internal speech, visual and motor imagery. The activation patterns allowed decoding the thought condition at >95%. Surprisingly, the activated networks remained the same regardless of changes in thought content. Finally, we found remarkably consistent activation maps across individuals engaged in abstract thinking. This activation bordered, but strictly avoided visual and motor networks. On the other hand, it overlapped with left lateralized language networks. Activation of the default mode network (DMN) during abstract thought was similar to DMN activation during rest. These observations were supported by a quantitative neuronal distance metric analysis. Our results reveal that despite its high level, and varied content nature - abstract thinking activates surprisingly precise and consistent networks in participants' brains.

The Noisy Brain: Power of Resting-State Fluctuations Predicts Individual Recognition Performance.

The unique profile of strong and weak cognitive traits characterizing each individual is of a fundamental significance, yet their neurophysiological underpinnings remain elusive. Here, we present intracranial electroencephalogram (iEEG) measurements in humans pointing to resting-state cortical "noise" as a possible neurophysiological trait that limits visual recognition capacity. We show that amplitudes of slow (<1 Hz) spontaneous fluctuations in high-frequency power measured during rest were predictive of the patients' performance in a visual recognition 1-back task (26 patients, total of 1,389 bipolar contacts pairs). Importantly, the effect was selective only to task-related cortical sites. The prediction was significant even across long (mean distance 4.6 ± 2.8 days) lags. These findings highlight the level of the individuals' internal "noise" as a trait that limits performance in externally oriented demanding tasks.

Convergent evolution of face spaces across human face-selective neuronal groups and deep convolutional networks.

The discovery that deep convolutional neural networks (DCNNs) achieve human performance in realistic tasks offers fresh opportunities for linking neuronal tuning properties to such tasks. Here we show that the face-space geometry, revealed through pair-wise activation similarities of face-selective neuronal groups recorded intracranially in 33 patients, significantly matches that of a DCNN having human-level face recognition capabilities. This convergent evolution of pattern similarities across biological and artificial networks highlights the significance of face-space geometry in face perception. Furthermore, the nature of the neuronal to DCNN match suggests a role of human face areas in pictorial aspects of face perception. First, the match was confined to intermediate DCNN layers. Second, presenting identity-preserving image manipulations to the DCNN abolished its correlation to neuronal responses. Finally, DCNN units matching human neuronal group tuning displayed view-point selective receptive fields. Our results demonstrate the importance of face-space geometry in the pictorial aspects of human face perception.

Hippocampal sharp-wave ripples linked to visual episodic recollection in humans.

Hippocampal sharp-wave ripples (SWRs) constitute one of the most synchronized activation events in the brain and play a critical role in offline memory consolidation. Yet their cognitive content and function during awake, conscious behavior remains unclear. We directly examined this question using intracranial recordings in human patients engaged in episodic free recall of previously viewed photographs. Our results reveal a content-selective increase in hippocampal ripple rate emerging 1 to 2 seconds prior to recall events. During recollection, high-order visual areas showed pronounced SWR-coupled reemergence of activation patterns associated with recalled content. Finally, the SWR rate during encoding predicted subsequent free-recall performance. These results point to a role for hippocampal SWRs in triggering spontaneous recollections and orchestrating the reinstatement of cortical representations during free episodic memory retrieval.

Where Does Time Go When You Blink?

Retinal input is frequently lost because of eye blinks, yet humans rarely notice these gaps in visual input. Although previous studies focused on the perceptual and neural correlates of diminished awareness to blinks, the impact of these correlates on the perceived time of concurrent events is unknown. Here, we investigated whether the subjective sense of time is altered by spontaneous blinks. We found that participants (N = 22) significantly underestimated the duration of a visual stimulus when a spontaneous blink occurred during stimulus presentation and that this underestimation was correlated with the blink duration of individual participants. Importantly, the effect was not present when durations of an auditory stimulus were judged (N = 23). The results point to a link between spontaneous blinks, previously demonstrated to induce activity suppression in the visual cortex, and a compression of subjective time. They suggest that ongoing encoding within modality-specific sensory cortices, independent of conscious awareness, informs the subjective sense of time.

Resting-State Activity in High-Order Visual Areas as a Window into Natural Human Brain Activations.

A major limitation of conventional human brain research has been its basis in highly artificial laboratory experiments. Due to technical constraints, little is known about the nature of cortical activations during ecological real life. We have previously proposed the "spontaneous trait reactivation (STR)" hypothesis arguing that resting-state patterns, which emerge spontaneously in the absence of external stimulus, reflect the statistics of habitual cortical activations during real life. Therefore, these patterns can serve as a window into daily life cortical activity. A straightforward prediction of this hypothesis is that spontaneous patterns should preferentially correlate to patterns generated by naturalistic stimuli compared with artificial ones. Here we targeted high-level category-selective visual areas and tested this prediction by comparing BOLD functional connectivity patterns formed during rest to patterns formed in response to naturalistic stimuli, as well as to more artificial category-selective, dynamic stimuli. Our results revealed a significant correlation between the resting-state patterns and functional connectivity patterns generated by naturalistic stimuli. Furthermore, the correlations to naturalistic stimuli were significantly higher than those found between resting-state patterns and those generated by artificial control stimuli. These findings provide evidence of a stringent link between spontaneous patterns and the activation patterns during natural vision.

Motion cues modulate responses to emotion in movies.

Film theorists and practitioners suggest that motion can be manipulated in movie scenes to elicit emotional responses in viewers. However, our understanding of the role of motion in emotion perception remains limited. On the one hand, movies continuously depict local motion- movements of objects and humans, which are crucial for generating emotional responses. Movie scenes also frequently portray global motion, mainly induced by large camera movements, global motion being yet another source of information used by the brain during natural vision. Here we used functional MRI to elucidate the contributions of local and global motion to emotion perception during movie viewing. Subjects observed long (1 min) movie segments depicting emotional or neutral content. Brain activity in areas that showed preferential responses to emotional content was strongly linked over time with frame-wide variations in global motion, and to a lesser extent with local motion information. Similarly, stronger responses to emotional content were recorded within regions of interest whose activity was attuned to global and local motion over time. Since global motion fields are experienced during self-motion, we suggest that camera movements may induce illusory self-motion cues in viewers that interact with the movie's narrative and with other emotional cues in generating affective responses.