Neuroscience and biobehavioral reviews
September 1, 2017
Georg Northoff, Zirui Huang
235 citations
The brain's intrinsic time and space are fundamental for consciousness. The Temporo-spatial Theory of Consciousness (TTC) proposes four distinct neuronal mechanisms that correspond to different dimensions of consciousness: (1) temporo-spatial nestedness of spontaneous activity accounts for the level or state of consciousness, serving as a neural predisposition; (2) temporo-spatial alignment of pre-stimulus activity accounts for the content or form of consciousness, acting as a neural prerequisite; (3) temporo-spatial expansion of early stimulus-induced activity accounts for phenomenal consciousness, as neural correlates; and (4) temporo-spatial globalization of late stimulus-induced activity accounts for cognitive features, as neural consequences.
Neuropsychologia
January 21, 2016
Zirui Huang, Natsuho Obara, Henry Davis et al.
144 citations
The temporal structure of spontaneous brain activity in the medial prefrontal cortex is linked to private self-consciousness. In 47 healthy subjects, the power-law exponent—a measure of long-range temporal correlations in resting-state fMRI signals—was correlated with scores on the private self-consciousness subscale of the Revised Self-Consciousness Scale. No such correlation appeared for public or social self-consciousness, nor for other resting-state measures like functional connectivity. This is the first evidence that the scale-free dynamics of cortical midline structures specifically relate to the private dimension of self-consciousness, suggesting a neural basis for the overlap between resting-state activity and self-related processing.
Annals of Neurology
August 20, 2015
Pengmin Qin, Xuehai Wu, Zirui Huang et al.
144 citations
Functional connectivity within two brain networks plays distinct roles in disorders of consciousness. Connectivity in the salience network, particularly between the supragenual anterior cingulate cortex and left anterior insula, was reduced in patients with unresponsive wakefulness syndrome compared to those in a minimally conscious state or fully conscious brain-lesioned patients. This connectivity correlated with behavioral signs of consciousness. In contrast, connectivity in the default-mode network, specifically between the posterior cingulate cortex and left lateral parietal cortex, was weaker in patients with unresponsive wakefulness syndrome who did not recover compared to those who later emerged from this state, suggesting this network predicts recovery of consciousness.
Human Brain Mapping
October 4, 2018
Annemarie Wolff, Daniel A. di Giovanni, Javier Gómez‐Pilar et al.
135 citations
Private self-consciousness—the tendency to focus on one's inner thoughts and feelings—is linked to specific temporal patterns in the brain's resting state activity. In an EEG study, higher scores on the Private dimension of the Self-Consciousness Scale correlated with three measures of resting state activity: a steeper power-law exponent (PLE), a longer auto-correlation window (ACW), and a stronger modulation index (MI). These temporal features reflect how self-related information is temporally nested, continuous, and integrated in spontaneous brain activity. Source localization further linked Private self-consciousness to activity in cortical midline structures, including the perigenual anterior cingulate cortex and posterior cingulate cortex. A machine learning algorithm could accurately classify individuals as having high or low Private self-consciousness based on these spatiotemporal measures.
Cell Reports
May 1, 2021
Zirui Huang, Vijay Tarnal, Phillip E. Vlisides et al.
119 citations
Conscious access to sensory information is likely gated at an intermediate site between primary sensory and transmodal association cortices, with the anterior insular cortex (AIC) playing a key role. Functional neuroimaging using a volitional mental imagery task in healthy volunteers, with propofol titrated to loss of behavioral responsiveness, showed that AIC dysfunction is associated with impaired transitions between default-mode and dorsal attention networks. Candidate subcortical regions such as the thalamus and basal forebrain did not show this association. In awake participants, pre-stimulus AIC activity near perceptual threshold predicted conscious access. These findings support the hypothesis that AIC regulates brain network transitions that gate conscious access.
Human Brain Mapping
July 1, 2013
Zirui Huang, Rui Dai, Xuehai Wu et al.
104 citations
Patients with disorders of consciousness (DOC) show reduced brain activity in midline regions (anterior and posterior cingulate cortex) during self-referential thinking tasks compared to healthy individuals. The degree of signal reduction in the perigenual anterior cingulate cortex predicts their level of consciousness. These same midline regions also display abnormal resting-state functional connectivity and low-frequency fluctuations. The findings link self-referential processing, resting-state brain activity, and consciousness, suggesting that neural abnormalities in these areas contribute to DOC.
Human Brain Mapping
January 28, 2018
Jianfeng Zhang, Zirui Huang, Yali Chen et al.
70 citations
During anesthetic-induced unconsciousness, two temporal features of brain activity—long-range temporal correlations (measured by power-law exponent) and temporal variability (measured by standard deviation)—both decrease globally across the brain compared to wakefulness. The spatial relationship between these two features becomes altered, or 'decoupled,' primarily due to changes in the spatial pattern of long-range temporal correlations rather than temporal variability. This suggests that the topographical organization of long-range temporal correlations is crucial for maintaining optimal neural dynamics during normal consciousness, supporting the temporo-spatial theory of consciousness.
NeuroImage
May 1, 2021
Pengmin Qin, Xuehai Wu, Changwei Wu et al.
51 citations
Consciousness depends on a network of brain regions that integrate sensory and motor information. Analyzing fMRI data from people in preserved (awake, fully conscious brain-injury survivors), reduced (N1-sleep, minimally conscious), and lost (N3-sleep, anesthesia, unresponsive wakefulness) states, plus a unique rapid-eye-movement (REM) sleep group, researchers identified key hubs whose degree centrality—a measure of network importance—dropped significantly when consciousness was reduced or absent. These hubs included the supplementary motor area, bilateral supramarginal gyrus, supragenual/dorsal anterior cingulate cortex, and left middle temporal gyrus. A higher-order sensorimotor circuit connecting these regions showed functional connectivity that correlated with consciousness levels across groups and remained active in REM sleep, suggesting this circuit supports consciousness and offers new targets for treating disorders of consciousness.
NeuroImage
June 1, 2023
Rui Dai, Tony E Larkin, Zirui Huang et al.
49 citations
Three different psychedelics—nitrous oxide, ketamine, and lysergic acid diethylamide—produce a common pattern of brain network changes despite having distinct molecular mechanisms and delivery methods. Each drug reduced connectivity within brain networks and enhanced connectivity between networks. Specifically, all three increased connections between the right temporoparietal junction and bilateral intraparietal sulcus, and between the precuneus and left intraparietal sulcus. These regions lie within the posterior cortical "hot zone," an area thought to mediate the qualitative aspects of experience. The findings identify a biologically plausible candidate for the subjective effects of both classical and non-classical psychedelics.
Communications Biology
May 9, 2023
Philipp Klar, Yasir Çatal, Robert Langner et al.
35 citations
Scale-free physiological processes are common in the human body. Resting-state fMRI studies found that anesthesia eliminates scale-free dynamics. This study examines scale-free dynamics in the cerebral cortex's unimodal periphery and transmodal core during rest and tasks at three conscious levels (awake, sedation, anesthesia), complemented by computational modeling. The results show that anesthesia transforms pink noise into white noise, disrupting the brain's alignment with a task's temporal structure. The model indicates that stimuli with pink noise, unlike brown or white noise, modulate task-related activity. The findings support two mechanisms of consciousness—temporo-spatial nestedness and alignment—proposed by the Temporo-Spatial Theory of Consciousness.
Nature Communications
September 9, 2024
Zirui Huang, George A. Mashour, Anthony G. Hudetz
23 citations
Anesthesia-induced unconsciousness involves a shift in the functional geometry of thalamocortical circuits, moving from a normal unimodal-transmodal pattern to a transmodal-deficient one. This alteration is linked to spatial variations in matrix cell composition within the thalamus, suggesting that disrupted connectivity of matrix cells plays a key role in the loss of consciousness. The study used functional magnetic resonance imaging in healthy volunteers during conscious baseline, deep sedation, and recovery, applying a functional gradient mapping technique to delineate these changes. The findings bridge cellular and systems-level understanding of consciousness.
Commun Biol
December 19, 2023
Rui Dai, Zirui Huang, Tony E. Larkin et al.
7 citations
At concentrations that produce psychedelic effects, nitrous oxide reduces the functional differentiation—the distinctness of activity patterns—within frontoparietal and somatomotor cortical networks. This suggests that the gas alters brain network organization, potentially contributing to its consciousness-altering properties. The finding points to a neural mechanism underlying the non-ordinary state induced by nitrous oxide, involving reduced specialization of key brain regions.
bioRxiv : the preprint server for biology
October 23, 2024
Rui Dai, Hyunwoo Jang, Anthony G Hudetz et al.
1 citation
preprint
Consciousness appears to depend on global interactions across multiple brain regions rather than on localized neural activity. Using fMRI data across psychedelic, sleep, and deep sedation states, the study found a mirror-image pattern: psychedelic states increased global functional connectivity and decreased local neural synchrony, while non-REM sleep and deep sedation showed the opposite pattern. This pattern was observed in anterior-posterior and posterior-posterior brain regions but not within the anterior brain alone. Anterior transmodal regions were key for anterior-posterior connectivity, while posterior transmodal and unimodal regions were critical for posterior-posterior connectivity. The findings support global theories of consciousness and bridge the Global Neuronal Workspace hypothesis and Integrated Information Theory by showing shared neural mechanisms.
bioRxiv : the preprint server for biology
June 1, 2026
Panagiotis Fotiadis, Hyunwoo Jang, Rui Dai et al.
Brain waves coordinate neural communication and shape conscious perception. Analyzing blood oxygen level-dependent activity from the Human Connectome Project and other datasets across sleep, propofol anesthesia, and psychedelic states (LSD, DMT, psilocybin, nitrous oxide, ketamine), four dominant wave propagation motifs were identified: a global synchronized wave, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave.
bioRxiv
November 26, 2025
Rui Dai, Rodrigo Cofré, Christopher Timmermann et al.
preprint
Classical psychedelics (DMT, LSD, psilocybin) and non-classical ones (nitrous oxide, ketamine) all disrupt local synchrony in small brain regions (<1 cm³) in humans, as measured by functional magnetic resonance imaging. This disruption occurred extensively in cortical regions and sparsely in subcortical regions. As local synchrony declined, large-scale functional connectivity increased. For classical psychedelics, the disruption was most strongly associated with 5-HT receptors; for nitrous oxide and ketamine, it was most strongly associated with NMDA receptors. Both neuronal and non-neuronal cell types were linked to these changes. The findings suggest diverse molecular events converge on a common outcome of disrupted local synchrony, which then mediates drug-specific global connectivity changes.
Nature communications
October 24, 2024
Hyunwoo Jang, George A Mashour, Anthony G Hudetz et al.
A metric called the integration-segregation difference (ISD), derived from fMRI data, captures two key brain network properties: efficiency (integration) and clustering (segregation). During anesthesia with propofol, brain networks shift profoundly toward segregation as consciousness is lost. A common sequence of disintegration and reintegration occurs in unimodal and transmodal networks during loss and return of responsiveness. Machine learning models using these measures accurately identify awake versus unresponsive states. Metastability is more closely linked to integration, while complexity is linked to segregation. Similar patterns appear in sleep. The ISD reliably indexes states of consciousness.
Brain sciences
August 30, 2024
Hyunwoo Jang, Rui Dai, George A Mashour et al.
A machine learning model that combines functional connectivity, graph-theoretic metrics, and cortical gradient features can classify brain states—including unconsciousness (NREM2 sleep, propofol sedation and anesthesia), psychedelic states (ketamine, LSD, nitrous oxide), and neuropsychiatric disorders (ADHD, bipolar disorder, schizophrenia)—with an average balanced accuracy of 79% (range 62–98%). The ensemble model outperformed individual feature-based models (70–76%). Transferability across datasets varied, and feature importance analysis indicated that different brain states rely on distinct neural mechanisms, suggesting that tailored approaches are needed for accurate classification. The findings highlight the value of integrating multiple feature types for robust brain-state classification, though further work is needed for broader generalizability.
Nature Communications
January 5, 2023
Zirui Huang, G. Mashour, A. Hudetz
Dimensions of consciousness such as wakefulness and awareness are encoded in multiple neurofunctional dimensions of the brain's cortical geometry. Disruptions of consciousness from pharmacological, neuropathological, or psychiatric causes degrade one or more major cortical gradients depending on the condition. Network-specific reconfigurations within this multidimensional gradient space are associated with behavioral unresponsiveness across various etiologies, and these spatial reconfigurations correlate with a temporal disruption of structured transitions of dynamic brain states. The work provides a unifying neurofunctional framework for multiple dimensions of human consciousness in both health and disease.
Frontiers in Systems Neuroscience
December 1, 2021
Minkyung Kim, Hyoungkyu Kim, Zirui Huang et al.
The brain's ability to switch between internal and external modes is crucial for generating models of self and world, and this switching may rely on a state near criticality—a balanced condition between order and disorder. Large synchronization fluctuations of brain networks near criticality create temporal windows that favor either integrating internal information or processing external stimuli. Using computational modeling, EEG, and fMRI analyses across altered states of consciousness, synchronized networks bias toward internal information while incoherent networks bias toward external information. These preferences are most prominent at criticality and in conscious states associated with 4–12 Hz bandwidth.
Science Advances
March 1, 2020
Zirui Huang, Jun Zhang, Jinsong Wu et al.
Consciousness depends on frequent access between two key brain networks: the default mode network and the dorsal attention network, which normally alternate their activity in an anticorrelated manner. A 'temporal circuit' of dynamic brain activity trajectories regulates transitions between these networks. Balanced reciprocal accessibility of brain states within this circuit characterizes consciousness, while isolation of the networks from the temporal circuit is associated with unresponsiveness from various causes. These findings advance understanding of how anticorrelated brain systems support consciousness.
Rui Dai, Hyunwoo Jang, Anthony G Hudetz et al.
Across altered states of consciousness, psychedelics and sedatives produce opposite patterns of brain network organization. Psychedelics increase large-scale integration and reduce segregation of brain network interactions, while sleep and propofol sedation show the opposite pattern. These opposing integration-segregation patterns were consistently observed across multiple measures of functional connectivity, network topology, and interaction complexity, and reliably differentiated conscious states in an unbiased, data-driven manner. The findings demonstrate that psychedelic and sedated states are characterized by systematic and opposing shifts in large-scale brain organization.