Intracranial neural representation of phenomenal and access consciousness in the human brain.

After more than 30 years of extensive investigation, impressive progress has been made in identifying the neural correlates of consciousness (NCC). However, the functional role of spatiotemporally distinct consciousness-related neural activity in conscious perception is debated. An influential framework proposed that consciousness-related neural activities could be dissociated into two distinct processes: phenomenal and access consciousness. However, though hotly debated, its authenticity has not been examined in a single paradigm with more informative intracranial recordings. In the present study, we employed a visual awareness task and recorded the local field potential (LFP) of patients with electrodes implanted in cortical and subcortical regions. Overall, we found that the latency of visual awareness-related activity exhibited a bimodal distribution, and the recording sites with short and long latencies were largely separated in location, except in the lateral prefrontal cortex (lPFC). The mixture of short and long latencies in the lPFC indicates that it plays a critical role in linking phenomenal and access consciousness. However, the division between the two is not as simple as the central sulcus, as proposed previously. Moreover, in 4 patients with electrodes implanted in the bilateral prefrontal cortex, early awareness-related activity was confined to the contralateral side, while late awareness-related activity appeared on both sides. Finally, Granger causality analysis showed that awareness-related information flowed from the early sites to the late sites. These results provide the first LFP evidence of neural correlates of phenomenal and access consciousness, which sheds light on the spatiotemporal dynamics of NCC in the human brain.

The Performance of Saccade Tasks Correlates with Cognitive Test Scores in Elderly Population: Evidence for the Usefulness of Oculomotor Tests in Cognitive Assessment.

BACKGROUND: Among the elderly, dementia is a common and disabling disorder with primary manifestations of cognitive impairments. Diagnosis and intervention in its early stages is the key to effective treatment. Nowadays, the test of cognitive function relies mainly on neuropsychological tests, such as the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). However, they have noticeable shortcomings, e.g., the biases of subjective judgments from physicians and the cost of the labor of these well-trained physicians. Thus, advanced and objective methods are urgently needed to evaluate cognitive functions. METHODS: We developed a cognitive assessment system through measuring the saccadic eye movements in three tasks. The cognitive functions were evaluated by both our system and the neuropsychological tests in 310 subjects, and the evaluating results were directly compared. RESULTS: In general, most saccadic parameters correlate well with the MMSE and MoCA scores. Moreover, some subjects with high MMSE and MoCA scores have high error rates in performing these three saccadic tasks due to various errors. The primary error types vary among tasks, indicating that different tasks assess certain specific brain functions preferentially. Thus, to improve the accuracy of evaluation through saccadic tasks, we built a weighted model to combine the saccadic parameters of the three saccadic tasks, and our model showed a good diagnosis performance in detecting patients with cognitive impairment. CONCLUSION: The comprehensive analysis of saccadic parameters in multiple tasks could be a reliable, objective, and sensitive method to evaluate cognitive function and thus to help diagnose cognitive impairments.

The role of fixation disengagement and oculomotor preparation in gap saccade task is gap-duration dependent.

The influence of internal brain state on behavioral performance is well illustrated by the gap saccade task, in which saccades might be initiated with short latency (express saccade) or with long latency (regular saccade) even though the external visual condition is identical. Accumulated evidence has demonstrated that the internal brain state is different before the initiation of an express saccade than a regular saccade. However, the reported origin of the fluctuation of internal brain state is disputed among previous studies, e.g., the fixation disengagement theory versus the oculomotor preparation theory. The present study examined these two theories by analyzing the rate and direction of fixational saccades, i.e., small amplitude saccades during fixation, because they could be modulated by the internal brain state. Since fixation disengagement is not spatially tuned, it might affect the rate but not the direction of fixational saccades. In contrast, oculomotor preparation can contain spatial information for the upcoming saccade and thus affect fixational saccade direction. We found that the different spatiotemporal characteristics of fixational saccades among tasks with different gap durations reveal diverse driving force to change the internal brain state. Under short gap duration (100 ms), fixation disengagement plays a primary role in switching internal brain states. Conversely, oculomotor preparation plays a primary role under medium (200 ms) and long (400 ms) gap durations. These results suggest that both fixation disengagement and oculomotor preparation can change the internal brain state, but their relative contributions are gap-duration dependent.NEW & NOTEWORTHY While performing the gap saccade task, the role of fixation disengagement and oculomotor preparation in modulating the internal brain state is gap-duration dependent. Fixation disengagement plays a primary role when gap duration is shorter (100 ms), whereas oculomotor preparation plays a primary role when gap duration is longer (200 ms and 400 ms).

Neuronal Correlates of Many-To-One Sensorimotor Mapping in Lateral Intraparietal Cortex.

Efficiently mapping sensory stimuli onto motor programs is crucial for rapidly choosing appropriate behavioral responses. While neuronal mechanisms underlying simple, one-to-one sensorimotor mapping have been extensively studied, how the brain achieves complex, many-to-one sensorimotor mapping remains unclear. Here, we recorded single neuron activity from the lateral intraparietal (LIP) cortex of monkeys trained to map multiple spatial positions of visual cue onto two opposite saccades. We found that LIP neurons' activity was consistent with directly mapping multiple cue positions to the associated saccadic direction (SDir) regardless of whether the visual cue appeared in or outside neurons' receptive fields. Unlike the explicit encoding of the visual categories, such cue-target mapping (CTM)-related activity covaried with the associated SDirs. Furthermore, the CTM was preferentially mediated by visual neurons identified by memory-guided saccade. These results indicate that LIP plays a crucial role in the early stage of many-to-one sensorimotor transformation.

Agricultural land-use change exacerbates the dissemination of antibiotic resistance genes via surface runoffs in Lake Tai Basin, China.

Agricultural runoff is an important antibiotic resistance genes (ARGs) dissemination pathway from farmlands to water environment, however few studies have focused on the influence of agricultural land-use change on the pattern of ARGs in runoff and assess the health risk to public. Lake Tai Basin which experiences agricultural land-use change was selected to elucidate this concern. Our findings revealed that the pattern of ARGs was more diverse and the gene abundance was higher in orchard runoffs by comparison with conventional cropland runoffs. Co-occurrence network analysis between mobile genetic elements and ARGs demonstrated that after agricultural land-use change, ARG dissemination via runoffs became more threatened. In addition, this study illustrated the correlations between the antibiotic resistome and microbiome in runoffs, finding that non-dominant microbial taxa were the limiting factor which determined the pattern of ARGs in surface runoffs. In summary, the pattern and dissemination risk of ARGs in the surface runoff after agricultural land-use change in Lake Tai Basin were clarified via this study.

Neuronal Representation of the Saccadic Timing Signals in Macaque Lateral Intraparietal Area.

Primates frequently make saccades direct fovea on interesting objects to receive acute visual information. However, saccade displaces the images on retina and disrupts the visual constancy. One possible mechanism to retain visual constancy is by integrating the presaccadic and postsaccadic visual information right at the time of saccade, which makes the timing of saccade crucial. So far, the saccadic timing signals have been found only in the subcortical regions, for example, the cerebellum and superior colliculus, but not in the neocortex. Here we report 2 types of saccadic timing signals in macaque lateral intraparietal area (LIP). First, many presaccadic response neurons started to decline activity either right around the start (saccade-on-decay) or the end (saccade-off-decay) of saccades. Notably, the time difference between saccade-off-decay and saccade-on-decay was highly correlated with the mean duration of saccades but not with the individual ones, and both saccade-off-decay and saccade-on-decay were better aligned with saccade end than saccade start-reflecting prediction. Second, the peak activity plateau of a group of postsaccadic response neurons was highly correlated with the actual duration of saccade-reflecting reality. While the predicted timing signals might facilitate the integration of visual information across saccades in LIP, the actual duration signals might calibrate the prediction errors.

Two subdivisions of macaque LIP process visual-oculomotor information differently.

Although the cerebral cortex is thought to be composed of functionally distinct areas, the actual parcellation of area and assignment of function are still highly controversial. An example is the much-studied lateral intraparietal cortex (LIP). Despite the general agreement that LIP plays an important role in visual-oculomotor transformation, it remains unclear whether the area is primary sensory- or motor-related (the attention-intention debate). Although LIP has been considered as a functionally unitary area, its dorsal (LIPd) and ventral (LIPv) parts differ in local morphology and long-distance connectivity. In particular, LIPv has much stronger connections with two oculomotor centers, the frontal eye field and the deep layers of the superior colliculus, than does LIPd. Such anatomical distinctions imply that compared with LIPd, LIPv might be more involved in oculomotor processing. We tested this hypothesis physiologically with a memory saccade task and a gap saccade task. We found that LIP neurons with persistent memory activities in memory saccade are primarily provoked either by visual stimulation (vision-related) or by both visual and saccadic events (vision-saccade-related) in gap saccade. The distribution changes from predominantly vision-related to predominantly vision-saccade-related as the recording depth increases along the dorsal-ventral dimension. Consistently, the simultaneously recorded local field potential also changes from visual evoked to saccade evoked. Finally, local injection of muscimol (GABA agonist) in LIPv, but not in LIPd, dramatically decreases the proportion of express saccades. With these results, we conclude that LIPd and LIPv are more involved in visual and visual-saccadic processing, respectively.

A spatially nonselective baseline signal in parietal cortex reflects the probability of a monkey's success on the current trial.

We recorded the activity of neurons in the lateral intraparietal area of two monkeys while they performed two similar visual search tasks, one difficult, one easy. Each task began with a period of fixation followed by an array consisting of a single capital T and a number of lowercase t's. The monkey had to find the capital T and report its orientation, upright or inverted, with a hand movement. In the easy task the monkey could explore the array with saccades. In the difficult task the monkey had to continue fixating and find the capital T in the visual periphery. The baseline activity measured during the fixation period, at a time in which the monkey could not know if the impending task would be difficult or easy or where the target would appear, predicted the monkey's probability of success or failure on the task. The baseline activity correlated inversely with the monkey's recent history of success and directly with the intensity of the response to the search array on the current trial. The baseline activity was unrelated to the monkey's spatial locus of attention as determined by the location of the cue in a cued visual reaction time task. We suggest that rather than merely reflecting the noise in the system, the baseline signal reflects the cortical manifestation of modulatory state, motivational, or arousal pathways, which determine the efficiency of cortical sensorimotor processing and the quality of the monkey's performance.

Asymmetric representations of upper and lower visual fields in egocentric and allocentric references.

Two spatial reference systems, i.e., the observer-centered (egocentric) and object-centered (allocentric) references, are most commonly used to locate the position of the external objects in space. Although we sense the world as a unified entity, visual processing is asymmetric between upper and lower visual fields (VFs). For example, the goal-directed reaching responses are more efficient in the lower VF. Such asymmetry suggests that the visual space might be composed of different realms regarding perception and action. Since the peripersonal realm includes the space that one can reach, mostly in the lower VF, it is highly likely that the peripersonal realm might mainly be represented in the egocentric reference for visuomotor operation. In contrast, the extrapersonal realm takes place away from the observer and is mostly observed in the upper VF, which is presumably represented in the allocentric reference for orientation in topographically defined space. This theory, however, has not been thoroughly tested experimentally. In the present study, we assessed the contributions of the egocentric and allocentric reference systems on visual discrimination in the upper and lower VFs through measuring the manual reaction times (RTs) of human subjects. We found that: (a) the influence of a target's egocentric location on visual discrimination was stronger in the lower VF; and (b) the influence of a target's allocentric location on visual discrimination was stronger in the upper VF. These results support the hypothesis that the upper and lower VFs are primarily represented in the allocentric and egocentric references, respectively.

Stochastic Oscillation in Self-Organized Critical States of Small Systems: Sensitive Resting State in Neural Systems.

Self-organized critical states (SOCs) and stochastic oscillations (SOs) are simultaneously observed in neural systems, which appears to be theoretically contradictory since SOCs are characterized by scale-free avalanche sizes but oscillations indicate typical scales. Here, we show that SOs can emerge in SOCs of small size systems due to temporal correlation between large avalanches at the finite-size cutoff, resulting from the accumulation-release process in SOCs. In contrast, the critical branching process without accumulation-release dynamics cannot exhibit oscillations. The reconciliation of SOCs and SOs is demonstrated both in the sandpile model and robustly in biologically plausible neuronal networks. The oscillations can be suppressed if external inputs eliminate the prominent slow accumulation process, providing a potential explanation of the widely studied Berger effect or event-related desynchronization in neural response. The features of neural oscillations and suppression are confirmed during task processing in monkey eye-movement experiments. Our results suggest that finite-size, columnar neural circuits may play an important role in generating neural oscillations around the critical states, potentially enabling functional advantages of both SOCs and oscillations for sensitive response to transient stimuli.

Parietal cortical neuronal activity is selective for express saccades.

Saccadic eye movements are central to primate behavior and serve to move the eyes to visual objects of interest. Express saccades, unlike regular saccades, occur with very short reaction times, a behavior necessary for speeded reactions in goal-directed behavior. Previous studies have shown that introduction of a blank interval (gap) between the fixation point offset and the saccadic target onset leads to an increase in the number of express saccades and that the superior colliculus plays a crucial role in the generation of express saccades. A longstanding hypothesis asserted that express saccades are mediated largely by a subcortical circuit, circumventing extrastriate visual cortex. An alternative "posterior pathway" hypothesis proposed the involvement of posterior parietal cortex. In the present study, using a gap saccade task, we investigated the role of nonhuman primate's lateral intraparietal cortex (LIP) in generation of express saccades. We show that roughly half of recorded LIP neurons were modulated during the gap interval. Moreover, a group of neurons with persistent activity in a memory-guided saccade task enhanced their activity during express saccades relative to that during regular saccades. After reducing the target's certainty by increasing the potential target locations, neuronal activity remained in the similar level during express saccades but markedly reduced during regular saccades that correlated with the increase of saccadic reaction time in the regular saccade. Our results suggest that area LIP is directly involved in generating saccades in express mode.

Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque.

Even though retinal images of objects change their locations following each eye movement, we perceive a stable and continuous world. One possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal information. There have been several proposals on how this may be done, including eye-position modulation (gain fields) of retinotopic receptive fields (RFs) and craniotopic RFs. In the present study, we investigated coordinate systems used by RFs in the lateral intraparietal (LIP) cortex and frontal eye fields (FEF) and compared the two areas. We mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate representation. The same recording and analysis procedures were applied to the two brain areas. We found that, in both areas, RFs were distributed from retinotopic to craniotopic representations. There was no significant difference between the distributions in the LIP and FEF. Only a small fraction of neurons was fully craniotopic, whereas most neurons were between the retinotopic and craniotopic representations. The distributions were strongly biased toward the retinotopic side but with significant craniotopic shifts. These results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF, and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.

Perisaccadic and attentional remapping of receptive fields in lateral intraparietal area and frontal eye fields.

The nature and function of perisaccadic receptive field (RF) remapping have been controversial. We use a delayed saccade task to reduce previous confounds and examine the remapping time course in the lateral intraparietal area and frontal eye fields. In the delay period, the RF shift direction turns from the initial fixation to the saccade target. In the perisaccadic period, RFs first shift toward the target (convergent remapping), but around the time of saccade onset/offset, the shifts become predominantly toward the post-saccadic RF locations (forward remapping). Thus, unlike forward remapping that depends on the corollary discharge (CD) of the saccade command, convergent remapping appears to follow attention from the initial fixation to the target. We model the data with attention-modulated and CD-gated connections and show that both sets of connections emerge automatically in neural networks trained to update stimulus retinal locations across saccades. Our work thus unifies previous findings into a mechanism for transsaccadic visual stability.

The involvement of the human prefrontal cortex in the emergence of visual awareness.

Exploring the neural mechanisms of awareness is a fundamental task of cognitive neuroscience. There is an ongoing dispute regarding the role of the prefrontal cortex (PFC) in the emergence of awareness, which is partially raised by the confound between report- and awareness-related activity. To address this problem, we designed a visual awareness task that can minimize report-related motor confounding. Our results show that saccadic latency is significantly shorter in the aware trials than in the unaware trials. Local field potential (LFP) data from six patients consistently show early (200-300ms) awareness-related activity in the PFC, including event-related potential and high-gamma activity. Moreover, the awareness state can be reliably decoded by the neural activity in the PFC since the early stage, and the neural pattern is dynamically changed rather than being stable during the representation of awareness. Furthermore, the enhancement of dynamic functional connectivity, through the phase modulation at low frequency, between the PFC and other brain regions in the early stage of the awareness trials may explain the mechanism of conscious access. These results indicate that the PFC is critically involved in the emergence of awareness.

Impacts of education level on Montreal Cognitive Assessment and saccades in community residents from Western China.

OBJECTIVES: This cross-sectional study sought to evaluate the effectiveness of the Montreal Cognitive Assessment (MoCA) and saccade in discerning the cognitive function levels among community populations characterized by diverse educational backgrounds. METHODS: Data from 665 Western China individuals encompassed MoCA scores and saccade performance. The study examined how education level and age influenced these assessments and highlighted the contrasting abilities of these measures in detecting cognitive abnormalities. RESULTS: The saccade model revealed a consistent cognitive impairment prevalence (15.5%) compared to previous clinical data (9.7% to 23.3%), while MoCA exhibited variable rates (25.1% to 52.8%). Notably, saccades and MoCA significantly diverged in detecting cognitive dysfunction. Additionally, education level had a greater impact on MoCA (effect size: 0.272) compared to saccades (0.024) affecting all MoCA sub-items, with age exerting a smaller influence on MoCA (0.037) compared to saccades (0.056). CONCLUSION: Saccades are less susceptible to the influence of education level when compared to MoCA, making saccade a potentially more suitable cognitive screening tool for rural community populations. SIGNIFICANCE: This study represents a pioneering approach by employing saccade detection within community populations to distinguish cognitive function status.

Asymmetric Influence of Egocentric Representation onto Allocentric Perception.

Objects in the visual world can be represented in both egocentric and allocentric coordinates. Previous studies have found that allocentric representation can affect the accuracy of spatial judgment relative to an egocentric frame, but not vice versa. Here we asked whether egocentric representation influenced the processing speed of allocentric perception. We measured the manual reaction time of human subjects in a position discrimination task in which the behavioral response purely relied on the target's allocentric location, independent of its egocentric position. We used two conditions of stimulus location: the compatible condition-allocentric left and egocentric left or allocentric right and egocentric right; the incompatible condition-allocentric left and egocentric right or allocentric right and egocentric left. We found that egocentric representation markedly influenced allocentric perception in three ways. First, in a given egocentric location, allocentric perception was significantly faster in the compatible condition than in the incompatible condition. Second, as the target became more eccentric in the visual field, the speed of allocentric perception gradually slowed down in the incompatible condition but remained unchanged in the compatible condition. Third, egocentric-allocentric incompatibility slowed allocentric perception more in the left egocentric side than the right egocentric side. These results cannot be explained by interhemispheric visuomotor transformation and stimulus-response compatibility theory. Our findings indicate that each hemisphere preferentially processes and integrates the contralateral egocentric and allocentric spatial information, and the right hemisphere receives more ipsilateral egocentric inputs than left hemisphere does.

Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation.

Neuronal responses to prolonged stimulation attenuate over time. Here, we ask a fundamental question: is adaptation a simple process for the neural system during which sustained input is ignored, or is it actually part of a strategy for the neural system to adjust its encoding properties dynamically? After simultaneously recording the activities of a group of bullfrog's retinal ganglion cells (dimming detectors) in response to sustained dimming stimulation, we applied a combination of information analysis approaches to explore the time-dependent nature of information encoding during the adaptation. We found that at the early stage of the adaptation, the stimulus information was mainly encoded in firing rates, whereas at the late stage of the adaptation, it was more encoded in neural correlations. Such a transition in encoding properties is not a simple consequence of the attenuation of neuronal firing rates, but rather involves an active change in the neural correlation strengths, suggesting that it is a strategy adopted by the neural system for functional purposes. Our results reveal that in encoding a prolonged stimulation, the neural system may utilize concerted, but less active, firings of neurons to encode information.

Multiple step saccades are generated by internal real-time saccadic error correction.

Objectives: Multiple step saccades (MSSs) are an atypical form of saccade that consists of a series of small-amplitude saccades. It has been argued that the mechanism for generating MSS is due to the automatic saccadic plan. This argument was based on the observation that trials with MSS had shorter saccadic latency than trials without MSS in the reactive saccades. However, the validity of this argument has never been verified by other saccadic tasks. Alternatively, we and other researchers have speculated that the function of MSS is the same as that of the corrective saccade (CS), i.e., to correct saccadic errors. Thus, we propose that the function of the MSS is also to rectify saccadic errors and generated by forward internal models. The objective of the present study is to examine whether the automatic theory is universally applicable for the generation of MSSs in various saccadic tasks and to seek other possible mechanisms, such as error correction by forward internal models. Methods: Fifty young healthy subjects (YHSs) and fifty elderly healthy subjects (EHSs) were recruited in the present study. The task paradigms were prosaccade (PS), anti-saccade (AS) and memory-guided saccade (MGS) tasks. Results: Saccadic latency in trials with MSS was shorter than without MSS in the PS task but similar in the AS and MGS tasks. The intersaccadic intervals (ISI) were similar among the three tasks in both YHSs and EHSs. Conclusion: Our results indicate that the automatic theory is not a universal mechanism. Instead, the forward internal model for saccadic error correction might be an important mechanism.

Multilevel and multifaceted brain response features in spiking, ERP and ERD: experimental observation and simultaneous generation in a neuronal network model with excitation-inhibition balance.

Brain as a dynamic system responds to stimulations with specific patterns affected by its inherent ongoing dynamics. The patterns are manifested across different levels of organization-from spiking activity of neurons to collective oscillations in local field potential (LFP) and electroencephalogram (EEG). The multilevel and multifaceted response activities show patterns seemingly distinct and non-comparable from each other, but they should be coherently related because they are generated from the same underlying neural dynamic system. A coherent understanding of the interrelationships between different levels/aspects of activity features is important for understanding the complex brain functions. Here, based on analysis of data from human EEG, monkey LFP and neuronal spiking, we demonstrated that the brain response activities from different levels of neural system are highly coherent: the external stimulus simultaneously generated event-related potentials, event-related desynchronization, and variation in neuronal spiking activities that precisely match with each other in the temporal unfolding. Based on a biologically plausible but generic network of conductance-based integrate-and-fire excitatory and inhibitory neurons with dense connections, we showed that the multiple key features can be simultaneously produced at critical dynamical regimes supported by excitation-inhibition (E-I) balance. The elucidation of the inherent coherency of various neural response activities and demonstration of a simple dynamical neural circuit system having the ability to simultaneously produce multiple features suggest the plausibility of understanding high-level brain function and cognition from elementary and generic neuronal dynamics. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09889-w.

Perisaccadic and Attentional Remapping of Receptive Fields in Lateral Intraparietal Area and Frontal Eye Fields.

The nature and function of perisaccadic receptive-field (RF) remapping have been controversial. We used a delayed saccade task to reduce previous confounds and examined the remapping time course in areas LIP and FEF. In the delay period, the RF shift direction turned from the initial fixation to the saccade target. In the perisaccadic period, RFs first shifted toward the target (convergent remapping) but around the time of saccade onset/offset, the shifts became predominantly toward the post-saccadic RF locations (forward remapping). Thus, unlike forward remapping that depends on the corollary discharge (CD) of the saccade command, convergent remapping appeared to follow attention from the initial fixation to the target. We modelled the data with attention-modulated and CD-gated connections, and showed that both sets of connections emerged automatically in neural networks trained to update stimulus retinal locations across saccades. Our work thus unifies previous findings into a mechanism for transsaccadic visual stability.