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The current discussion on the neural correlates of the contents of consciousness (NCCc) focuses mainly on the post-stimulus period of task-related activity. This neglects the substantial impact of the spontaneous or ongoing activity of the brain as manifest in pre-stimulus activity. Does the interaction of pre- and post-stimulus activity shape the contents of consciousness? Addressing this gap in our knowledge, we review and converge two recent lines of findings, that is, pre-stimulus alpha power and pre- and post-stimulus alpha trial-to-trial variability (TTV). The data show that pre-stimulus alpha power modulates post-stimulus activity including specifically the subjective features of conscious contents like confidence and vividness. At the same time, alpha pre-stimulus variability shapes post-stimulus TTV reduction including the associated contents of consciousness. We propose that non-additive rather than merely additive interaction of the internal pre-stimulus activity with the external stimulus in the alpha band is key for contents to become conscious. This is mediated by mechanisms on different levels including neurophysiological, neurocomputational, neurodynamic, neuropsychological and neurophenomenal levels. Overall, considering the interplay of pre-stimulus intrinsic and post-stimulus extrinsic activity across wider timescales, not just evoked responses in the post-stimulus period, is critical for identifying neural correlates of consciousness. This is well in line with both processing and especially the Temporo-spatial theory of consciousness (TTC)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Consciousness science is marred by disparate constructs and methodologies, making it challenging to systematically compare theories. This foundational crisis casts doubts on the scientific character of the field itself. Addressing it, we propose a framework for systematically comparing consciousness theories by introducing a novel inter-theory classification interface, the Measure Centrality Index (MCI). Recognizing its gradient distribution, the MCI assesses the degree of importance a specific empirical measure has for a given consciousness theory. We apply the MCI to probe how the empirical measures of the Global Neuronal Workspace Theory (GNW), Integrated Information Theory (IIT), and Temporospatial Theory of Consciousness (TTC) would fare within the context of the other two. We demonstrate that direct comparison of IIT, GNW, and TTC is meaningful and valid for some measures like Lempel-Ziv Complexity (LZC), Autocorrelation Window (ACW), and possibly Mutual Information (MI). In contrast, it is problematic for others like the anatomical and physiological neural correlates of consciousness (NCC) due to their MCI-based differential weightings within the structure of the theories. In sum, we introduce and provide proof-of-principle of a novel systematic method for direct inter-theory empirical comparisons, thereby addressing isolated evolution of theories and confirmatory bias issues in the state-of-the-art neuroscience of consciousness., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Scale-free physiological processes are ubiquitous in the human organism. Resting-state functional MRI studies observed the loss of scale-free dynamics under anesthesia. In contrast, the modulation of scale-free dynamics during task-related activity remains an open question. We investigate scale-free dynamics in the cerebral cortex's unimodal periphery and transmodal core topography in rest and task states during three conscious levels (awake, sedation, and anesthesia) complemented by computational modelling (Stuart-Landau model). The empirical findings demonstrate that the loss of the brain's intrinsic scale-free dynamics in the core-periphery topography during anesthesia, where pink noise transforms into white noise, disrupts the brain's neuronal alignment with the task's temporal structure. The computational model shows that the stimuli's scale-free dynamics, namely pink noise distinguishes from brown and white noise, also modulate task-related activity. Together, we provide evidence for two mechanisms of consciousness, temporo-spatial nestedness and alignment, suggested by the Temporo-Spatial Theory of Consciousness (TTC)., (© 2023. The Author(s).)

Consciousness and its neural mechanisms remain a mystery. Current neuroscientific theories focus predominantly on the external input/stimulus and the associated stimulus-related activity during conscious contents. Despite all progress, we encounter two gaps: (i) a gap between spontaneous and stimulus-related activity; (ii) a gap between neuronal and phenomenal features. A novel, different, and unique approach, Temporo-spatial Theory of Consciousness (TTC) aims to bridge both gaps. The TTC focuses on the brain's spontaneous activity and how its spatial topography and temporal dynamic shape stimulus-related activity and resurface in the corresponding spatial and temporal features of consciousness, i.e., 'common currency'. The TTC introduces four temporo-spatial mechanisms: expansion, globalization, alignment, and nestedness. These are associated with distinct dimensions of consciousness including phenomenal content, access, form/structure, and level/state, respectively. Following up on the first introduction of the TTC in 2017, we review updates, further develop these temporo-spatial mechanisms, and postulate specific neurophenomenal hypotheses. We conclude that the TTC offers a viable approach for (i) linking spontaneous and stimulus-related activity in conscious states; (ii) determining specific neuronal and neurophenomenal mechanisms for the distinct dimensions of consciousness; (iii) an integrative and unifying framework of different neuroscientific theories of consciousness; and (iv) offers novel empirically grounded conceptual assumptions about the biological and ontological nature of consciousness and its relation to the brain., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The neural mechanism that enables the recovery of consciousness in patients with unresponsive wakefulness syndrome (UWS) remains unclear. The aim of the current study is to characterize the cortical hub regions related to the recovery of consciousness. In the current fMRI study, voxel-wise degree centrality analysis was adopted to identify the cortical hubs related to the recovery of consciousness, for which a total of 27 UWS patients were recruited, including 13 patients who emerged from UWS (UWS-E), and 14 patients who remained in UWS (UWS-R) at least three months after the experiment performance. Furthermore, other recoverable unconscious states were adopted as validation groups, including three independent N3 sleep datasets (n = 12, 9, 9 respectively) and three independent anesthesia datasets (n = 27, 14, 6 respectively). Spatial similarity of the hub characteristic with the validation groups between the UWS-E and UWS-R was compared using the dice coefficient. Finally, with the cortical regions persistently shown as hubs across UWS-E and validation states, functional connectivity analysis was further performed to explore the connectivity patterns underlying the recovery of consciousness. The results identified four cortical hubs in the UWS-E, which showed significantly higher degree centrality for UWS-E than UWS-R, including the anterior precuneus, left inferior parietal lobule, left inferior frontal gyrus, and left middle frontal gyrus, of which the degree centrality value also positively correlated with the patients' Glasgow Outcome Scale (GOS) score that assessed global brain functioning outcome after a brain injury. Furthermore, the anterior precuneus was found with significantly higher similarity of hub characteristics as well as functional connectivity patterns between UWS-E and the validation groups. The results suggest that the recovery of consciousness may be relevant to the integrity of cortical hubs in the recoverable unconscious states, especially the anterior precuneus. The identified cortical hub regions could serve as potential treatment targets for patients with UWS., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Consciousness is a mental characteristic of the human mind, whose exact neural features remain unclear. We aimed to identify the critical nodes within the brain's global functional network that support consciousness. To that end, we collected a large fMRI resting state dataset with subjects in at least one of the following three consciousness states: preserved (including the healthy awake state, and patients with a brain injury history (BI) that is fully conscious), reduced (including the N1-sleep state, and minimally conscious state), and lost (including the N3-sleep state, anesthesia, and unresponsive wakefulness state). We also included a unique dataset of subjects in rapid eye movement sleep state (REM-sleep) to test for the presence of consciousness with minimum movements and sensory input. To identify critical nodes, i.e., hubs, within the brain's global functional network, we used a graph-theoretical measure of degree centrality conjoined with ROI-based functional connectivity. Using these methods, we identified various higher-order sensory and motor regions including the supplementary motor area, bilateral supramarginal gyrus (part of inferior parietal lobule), supragenual/dorsal anterior cingulate cortex, and left middle temporal gyrus, that could be important hubs whose degree centrality was significantly reduced when consciousness was reduced or absent. Additionally, we identified a sensorimotor circuit, in which the functional connectivity among these regions was significantly correlated with levels of consciousness across the different groups, and remained present in the REM-sleep group. Taken together, we demonstrated that regions forming a higher-order sensorimotor integration circuit are involved in supporting consciousness within the brain's global functional network. That offers novel and more mechanism-guided treatment targets for disorders of consciousness., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Various theories for the neural basis of consciousness have been proposed, suggesting a diversity of neural signs and mechanisms. We ask to what extent this diversity is real, or whether many theories share the same basic ideas with a potential for convergence towards a more unified theory of the neural basis of consciousness. For that purpose, we review and compare the various neural signs, measures, and mechanisms proposed in the different theories. We demonstrate that different theories focus on neural signs and measures of distinct aspects of neural activity including stimulus-related, prestimulus, and resting state activity as well as on distinct features of consciousness. Therefore, the various mechanisms proposed in the different theories may, in part, complement each other. Together, we provide insight into the shared basis and convergences (and, in part, discrepancies) of the different theories of consciousness. We conclude that the different theories concern distinct aspects of both neural activity and consciousness which, as we suppose, may be integrated and nested within the brain's overall temporo-spatial dynamics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

At the end of the 19th century Pierre Janet described dissociation as an altered state of consciousness manifested in disrupted integration of psychological functions. Clinically, such disruption comprises compartmentalization symptoms like amnesia, detachment symptoms like depersonalization/derealization, and structural dissociation of personality with changes in the sense of self. The exact neuronal mechanisms leading to these different symptoms remain unclear. We here suggest to put Janet's original account of dissociation as disrupted integration of psychological functions into a novel context, that is, a neuronal context as related to current brain imaging. This requires a combined theoretical and empirical approach on data supporting such neuronal reframing of Janet. For that, we here review (i) past and (ii) recent psychological and neuronal views on dissociation together with neuroscientific theories of integration, which (iii) are supported and complemented by preliminary fMRI data. We propose three neuronal mechanisms of dynamic integration operating at different levels of the brain's spontaneous activity - temporo-spatial binding on the regional level, temporo-spatial synchronization on the network level, and temporo-spatial globalization on the global level. These neuronal mechanisms, in turn, may be related to different symptomatic manifestation of dissociation operating at different levels, e.g., compartmentalization, detachment, and structural, which, as we suggest, can all be traced to disrupted integration of neuronal and psychological functions as originally envisioned by Janet., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We review neuroimaging research investigating self-referential processing (SRP), that is, how we respond to stimuli that reference ourselves, prefaced by a lexical-thematic analysis of words indicative of "self-feelings". We consider SRP as occurring verbally (V-SRP) and non-verbally (NV-SRP), both in the controlled, "top-down" form of introspective and interoceptive tasks, respectively, as well as in the "bottom-up" spontaneous or automatic form of "mind wandering" and "body wandering" that occurs during resting state. Our review leads us to outline a conceptual and methodological framework for future SRP research that we briefly apply toward understanding certain psychological and neurological disorders symptomatically associated with abnormal SRP. Our discussion is partly guided by William James' original writings on the consciousness of self., Competing Interests: Declaration of Competing Interest Lena Palaniyappan reports personal fees from Otsuka Canada, SPMM Course Limited, UK, Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Janssen Canada, Sunovion and Otsuka Canada outside the submitted work., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this study, we aimed to (1) identify white matter (WM) deficits underlying the consciousness level in patients with disorders of consciousness (DOCs) using diffusion tensor imaging (DTI), and (2) evaluate the relationship between DTI metrics and clinical measures of the consciousness level in DOC patients. With a cohort of 8 comatose, 8 unresponsive wakefulness syndrome/vegetative state, and 14 minimally conscious state patients and 25 patient controls, we performed group comparisons of the DTI metrics in 48 core WM regions of interest (ROIs), and examined the clinical relevance using correlation analysis. We identified multiple abnormal WM ROIs in DOC patients compared with normal controls, and the DTI metrics in these ROIs were significantly correlated with clinical measures of the consciousness level. Therefore, our findings suggested that multiple WM tracts are involved in the impaired consciousness levels in DOC patients and demonstrated the clinical relevance of DTI for DOC patients.

Time and space are the basic building blocks of nature. As a unique existent in nature, our brain exists in time and takes up space. The brain's activity itself also constitutes and spreads in its own (intrinsic) time and space that is crucial for consciousness. Consciousness is a complex phenomenon including different dimensions: level/state, content/form, phenomenal aspects, and cognitive features. We propose a Temporo-spatial Theory of Consciousness (TTC) focusing primarily on the temporal and spatial features of the brain activity. We postulate four different neuronal mechanisms accounting for the different dimensions of consciousness: (i) "temporo-spatial nestedness" of the spontaneous activity accounts for the level/state of consciousness as neural predisposition of consciousness (NPC); (ii) "temporo-spatial alignment" of the pre-stimulus activity accounts for the content/form of consciousness as neural prerequisite of consciousness (preNCC); (iii) "temporo-spatial expansion" of early stimulus-induced activity accounts for phenomenal consciousness as neural correlates of consciousness (NCC); (iv) "temporo-spatial globalization" of late stimulus-induced activity accounts for the cognitive features of consciousness as neural consequence of consciousness (NCCcon)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Consciousness research has much focused on faster frequencies like alpha or gamma while neglecting the slower ones in the infraslow (0.001-0.1Hz) and slow (0.1-1Hz) frequency range. These slower frequency ranges have a "bad reputation" though; their increase in power can observed during the loss of consciousness as in sleep, anesthesia, and vegetative state. However, at the same time, slower frequencies have been conceived instrumental for consciousness. The present paper aims to resolve this paradox which I describe as "paradox of slow frequencies". I first show various data that suggest a central role of slower frequencies in integrating faster ones, i.e., "temporo-spatial integration and nestedness". Such "temporo-spatial integration and nestedness" is disrupted during the loss of consciousness as in anesthesia and sleep leading to "temporo-spatial fragmentation and isolation" between slow and fast frequencies. Slow frequencies are supposedly mediated by neural activity in upper cortical layers in higher-order associative regions as distinguished from lower cortical layers that are related to faster frequencies. Taken together, slower and faster frequencies take on different roles for the level/state of consciousness. Faster frequencies by themselves are sufficient and thus a neural correlate of consciousness (NCC) while slower frequencies are a necessary non-sufficient condition of possible consciousness, e.g., a neural predisposition of the level/state of consciousness (NPC). This resolves the "paradox of slow frequencies" in that it assigns different roles to slower and faster frequencies in consciousness, i.e., NCC and NPC. Taken as NCC and NPC, fast and slow frequencies including their relation as in "temporo-spatial integration and nestedness" can be considered a first "building bloc" of a future "temporo-spatial theory of consciousness" (TTC) (Northoff, 2013; Northoff, 2014b; Northoff & Huang, 2017)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Previous studies have demonstrated that altered states of consciousness are related to changes in resting state activity in the default-mode network (DMN). Anatomically, the DMN can be divided into anterior and posterior regions. The anterior DMN includes the perigenual anterior cingulate cortex and other medial prefrontal cortical regions, whereas the posterior DMN includes regions such as the posterior cingulate cortex (PCC) and the temporal parietal junction (TPJ). Although differential roles have been attributed to the anterior and posterior DMN regions, their exact contributions to consciousness levels remain unclear. To investigate the specific role of the posterior DMN in consciousness levels, we investigated 20 healthy controls (7 females, mean age = 33.6 years old) and 20 traumatic brain injury (TBI) patients (5 females, mean age = 43 years old) whose brain lesions were mainly restricted to the bilateral frontal cortex but retained a well-preserved posterior DMN (e.g., the PCC and the TPJ) and who exhibited varying levels of consciousness. We investigated the intra- and cross-functional connectivity strengths (FCSs) between the right/left PCC and the right/left TPJ and their correlation with consciousness levels. Significant reductions in both the intra- and cross-hemispheric FCSs were observed in patients compared with controls. A significant correlation with consciousness levels was observed only for the cross-hemispheric PCC-TPJ FCS but not for the intra-hemispheric PCC-TPJ FCS. Taken together, our results show that the cross-hemispheric posterior DMN is related to consciousness levels in a specific group of patients without posterior structural lesions. We therefore propose that the PCC may be central in maintaining consciousness through its cross-hemispheric FC with the TPJ.

William James postulated a "stream of consciousness" that presupposes temporal continuity. The neuronal mechanisms underlying the construction of such temporal continuity remain unclear, however, in my contribution, I propose a neuro-phenomenal hypothesis that is based on slow cortical potentials and their extension of the present moment as described in the phenomenal term of "width of present". More specifically, I focus on the way the brain's neural activity needs to be encoded in order to make possible the "stream of consciousness." This leads us again to the low-frequency fluctuations of the brain's neural activity and more specifically to slow cortical potentials (SCPs). Due to their long phase duration as low-frequency fluctuations, SCPs can integrate different stimuli and their associated neural activity from different regions in one converging region. Such integration may be central for consciousness to occur, as it was recently postulated by He and Raichle. They leave open, however, the question of the exact neuronal mechanisms, like the encoding strategy, that make possible the association of the otherwise purely neuronal SCP with consciousness and its phenomenal features. I hypothesize that SCPs allow for linking and connecting different discrete points in physical time by encoding their statistically based temporal differences rather than the single discrete time points by themselves. This presupposes difference-based coding rather than stimulus-based coding. The encoding of such statistically based temporal differences makes it possible to "go beyond" the merely physical features of the stimuli; that is, their single discrete time points and their conduction delays (as related to their neural processing in the brain). This, in turn, makes possible the constitution of "local temporal continuity" of neural activity in one particular region. The concept of "local temporal continuity" signifies the linkage and integration of different discrete time points into one neural activity in a particular region. How does such local temporal continuity predispose the experience of time in consciousness? For that, I turn to phenomenological philosopher Edmund Husserl and his description of what he calls "inner time consciousness" (Husserl and Brough, 1990). One hallmark of humans' "inner time consciousness" is that we experience events and objects in succession and duration in our consciousness; according to Husserl, this amounts to what he calls the "width of [the] present." The concept of the width of present describes the extension of the present beyond the single discrete time point, such as, for instance, when we perceive different tones as a melody. I now hypothesize the degree of the width of present to be directly dependent upon and thus predisposed by the degree of the temporal differences between two (or more) discrete time points as they are encoded into neural activity. I therefore conclude that the SCPs and their encoding of neural activity in terms of temporal differences must be regarded a neural predisposition of consciousness (NPC) as distinguished from a neural correlate of consciousness (NCC)., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Recent studies have demonstrated an overlap between the neural substrate of resting-state activity and self-related processing in the cortical midline structures (CMS). However, the neural and psychological mechanisms mediating this so-called "rest-self overlap" remain unclear. To investigate the neural mechanisms, we estimated the temporal structure of spontaneous/resting-state activity, e.g. its long-range temporal correlations or self-affinity across time as indexed by the power-law exponent (PLE). The PLE was obtained in resting-state activity in the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in 47 healthy subjects by functional magnetic resonance imaging (fMRI). We performed correlation analyses of the PLE and Revised Self-Consciousness Scale (SCSR) scores, which enabled us to access different dimensions of self-consciousness and specified rest-self overlap in a psychological regard. The PLE in the MPFC's resting-state activity correlated with private self-consciousness scores from the SCSR. Conversely, we found no correlation between the PLE and the other subscales of the SCSR (public, social) or between other resting-state measures, including functional connectivity, and the SCSR subscales. This is the first evidence for the association between the scale-free dynamics of resting-state activity in the CMS and the private dimension of self-consciousness. This finding implies the relationship of especially the private dimension of self with the temporal structure of resting-state activity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: We aimed to investigate the roles of different resting-state networks in predicting both the actual level of consciousness and its recovery in brain injury patients., Methods: We investigated resting-state functional connectivity within different networks in patients with varying levels of consciousness: unresponsive wakefulness syndrome (UWS; n = 56), minimally conscious state (MCS; n = 29), and patients with brain lesions but full consciousness (BL; n = 48). Considering the actual level of consciousness, we compared the strength of network connectivity among the patient groups. We then checked the presence of connections between specific regions in individual patients and calculated the frequency of this in the different patient groups. Considering the recovery of consciousness, we split the UWS group into 2 subgroups according to recovery: those who emerged from UWS (UWS-E) and those who remained in UWS (UWS-R). The above analyses were repeated on these 2 subgroups., Results: Functional connectivity strength in salience network (SN), especially connectivity between the supragenual anterior cingulate cortex (SACC) and left anterior insula (LAI), was reduced in the unconscious state (UWS) compared to the conscious state (MCS and BL). Moreover, at the individual level, SACC-LAI connectivity was more present in MCS than in UWS. Default-mode network (DMN) connectivity strength, especially between the posterior cingulate cortex (PCC) and left lateral parietal cortex (LLPC), was reduced in UWS-R compared with UWS-E. Furthermore, PCC-LLPC connectivity was more present in UWS-E than in UWS-R., Interpretation: Our findings show that SN (SACC-LAI) connectivity correlates with behavioral signs of consciousness, whereas DMN (PCC-LLPC) connectivity instead predicts recovery of consciousness., (© 2015 American Neurological Association.)

William James famously characterized consciousness by 'stream of consciousness' which describes the temporal continuity and flow of the contents of consciousness in our 'inner time consciousness'. More specifically he distinguished between "substantive parts", the contents of consciousness, and "transitive parts", the linkages between different contents. While much research has recently focused on the substantive parts, the neural mechanisms underlying the transitive parts and their characterization by the balance between 'sensible continuity' and 'continuous change' remain unclear. The aim of this paper is to develop so-called neuro-phenomenal hypothesis about specifically the transitive parts and their two phenomenal hallmark features, sensible continuity and continuous change in 'inner time consciousness'. Based on recent findings, I hypothesize that the cortical midline structures and their high degree of variability and strong low frequency fluctuations play an essential role in mediating the phenomenal balance between sensible continuity and continuous change., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Recent studies have demonstrated resting-state abnormalities in midline regions in vegetative state/unresponsive wakefulness syndrome and minimally conscious state patients. However, the functional implications of these resting-state abnormalities remain unclear. Recent findings in healthy subjects have revealed a close overlap between the neural substrate of self-referential processing and the resting-state activity in cortical midline regions. As such, we investigated task-related neural activity during active self-referential processing and various measures of resting-state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task-specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). However, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of consciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients also exhibited severe abnormalities in the measures of resting-state activity, that is functional connectivity and the amplitude of low-frequency fluctuations. Taken together, our results provide the first evidence of neural abnormalities in both the self-referential processing and the resting state in midline regions in DOC patients. This novel finding has important implications for clinical utility and general understanding of the relationship between the self, the resting state, and consciousness., (Copyright © 2013 Wiley Periodicals, Inc.)

Current neuroscience applies a bi-dimensional model to consciousness. Content and level of consciousness have been distinguished from each other in their underlying neuronal mechanisms. This though leaves open the role of the brain's intrinsic activity and its particular temporal and spatial structure in consciousness. I here review and investigate the spatial and temporal features of the brain's intrinsic activity in detail and postulate what I describe as spatiotemporal structure that implies a virtual (e.g., statistically based) spatiotemporal continuity. Such spatiotemporal continuity is supposed to structure and organize the neural processing of the incoming extrinsic stimuli and their potential association with consciousness. I therefore conclude that the current bi-dimensional view of consciousness focusing only on content and level may need to be complemented by a third dimension, the form, e.g., spatiotemporal structure, as provided by the intrinsic activity. In short, I here opt for tri-rather than bi-dimensional view of consciousness., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The early philosopher Immanuel Kant suggested that the mind’s intrinsic features are intimately linked to the extrinsic stimuli of the environment it processes. Currently, the field faces an analogous problem with regard to the brain. Kant’s ideas may provide novel insights into how the brain’s intrinsic features must be so that they can be linked to the neural processing of extrinsic stimuli to enable the latter’s association with consciousness and self.

Objectives: The aim of this study was to investigate the relationship between medial cortical activation and the presence of self and consciousness in healthy subjects and patients with vegetative state and minimally conscious state using functional magnetic resonance imaging (fMRI)., Experiment Design: We first conducted two fMRI experiments in healthy subjects to identify brain regions specifically associated with self-perception through the use of different auditory stimuli that had different grades of self-relatedness. We then applied these regions as functional localizers to examine the relationship between neural activity changes during self-relatedness and consciousness level in the patients with disorders of consciousness (DOC)., Principal Observations: We demonstrated recruitment of various anterior medial cortical regions including the anterior cingulate cortex (ACC) in healthy subjects during auditory perception of self-related stimuli. We further showed that patients with DOC showed signal changes in the ACC during auditory perception of self-related stimuli. Finally, it was shown that these signal changes correlate with the level of consciousness in the patients with DOC., Conclusion: The degree of consciousness in patients with DOC was correlated with neural activity in the ACC induced by self-related stimuli. Our results not only shed light on the pathophysiology of DOC, but may also suggest a useful neural, and thus diagnostic, marker of the dysfunction of consciousness in vegetative patients., (Copyright © 2010 Wiley-Liss, Inc.)

The nature of the self has been one of the central problems in philosophy and most recently in neuroscience. Here, we suggest that animals and humans share a 'core self' represented in homologous underlying neural networks. We argue that the core self might be constituted by an integrative neuronal mechanism that enables self-related processing (SRP). Because mammalian organisms are capable of relating bodily states, intrinsic brain states (e.g. basic attentional, emotional and motivational systems) and environmental stimuli to various life-supporting goal-orientations, SRP appears to be a core ability preserved across numerous species. Recent data suggest that SRP is operating via a central integrative neural system made up of subcortical-cortical midline structures (SCMSs), that are homologous across mammalian species.

Time delays are a signature of many physical systems, including the brain, and considerably shape their dynamics; moreover, they play a key role in consciousness, as postulated by the temporo-spatial theory of consciousness (TTC). However, they are often not known a priori and need to be estimated from time series. In this study, we propose the use of permutation entropy (PE) to estimate time delays from neural time series as a more robust alternative to the widely used autocorrelation window (ACW). In the first part, we demonstrate the validity of this approach on synthetic neural data, and we show its resistance to regimes of nonstationarity in time series. Mirroring yet another example of comparable behavior between different nonlinear systems, permutation entropy–time delay estimation (PE-TD) is also able to measure intrinsic neural timescales (INTs) (temporal windows of neural activity at rest) from hd-EEG human data; additionally, this replication extends to the abnormal prolongation of INT values in disorders of consciousness (DoCs). Surprisingly, the correlation between ACW-0 and PE-TD decreases in a state-dependent manner when consciousness is lost, hinting at potential different regimes of nonstationarity and nonlinearity in conscious/unconscious states, consistent with many current theoretical frameworks on consciousness. In summary, we demonstrate the validity of PE-TD as a tool to extract relevant time scales from neural data; furthermore, given the divergence between ACW and PE-TD specific to DoC subjects, we hint at its potential use for the characterization of conscious states. [ABSTRACT FROM AUTHOR]

This article introduces a process-oriented approach for improving present moment conceptualization in psychotherapy that is in alignment with neuroscience: the Temporospatial movements of mind (TSMM) model. We elaborate on seven temporal movements that describe the moment-to-moment morphogenesis of emotional feelings and thoughts from inception to maturity. Temporal refers to the passage of time through which feelings and thoughts develop, and electromagnetic activity, that among other responsibilities, bind information across time. Spatial dynamics extend from an undifferentiated to three dimensional experiences of emotional and cognitive processes. Neurophysiologically, spatial refers to structures within the brain and their varying interactions with one another. This article culminates in the development of an atheoretical temporospatial grid that may help clinicians conceptualize where patients are in their cognitive and emotional development to further guide technique. [ABSTRACT FROM AUTHOR]

In this article we investigate levels of time in the Zhuangzi, through a conceptual framework rooted in Leibniz' philosophy of time. We begin by drawing three different levels of time in Leibniz: cognition-based, experience-based, and world-based. We then show that not only can parallel levels of time be identified in the Zhuangzi, but also a distinctively new, that is, fourth level of time can be distinguished, which pertains to bodily skill. We finally discuss the significance of this study in a contemporary context. [ABSTRACT FROM AUTHOR]

Variability quenching is a widespread neural phenomenon in which trial‐to‐trial variability (TTV) of neural activity is reduced by repeated presentations of a sensory stimulus. However, its neural mechanism and functional significance remain poorly understood. Recurrent network dynamics are suggested as a candidate mechanism of TTV, and they play a key role in consciousness. We thus asked whether the variability‐quenching phenomenon is related to the level of consciousness. We hypothesized that TTV reduction would be compromised during reduced level of consciousness by propofol anesthetics. We recorded functional magnetic resonance imaging signals of resting‐state and stimulus‐induced activities in three conditions: wakefulness, sedation, and unconsciousness (i.e., deep anesthesia). We measured the average (trial‐to‐trial mean, TTM) and variability (TTV) of auditory stimulus‐induced activity under the three conditions. We also examined another form of neural variability (temporal variability, TV), which quantifies the overall dynamic range of ongoing neural activity across time, during both the resting‐state and the task. We found that (a) TTM deceased gradually from wakefulness through sedation to anesthesia, (b) stimulus‐induced TTV reduction normally seen during wakefulness was abolished during both sedation and anesthesia, and (c) TV increased in the task state as compared to resting‐state during both wakefulness and sedation, but not anesthesia. Together, our results reveal distinct effects of propofol on the two forms of neural variability (TTV and TV). They imply that the anesthetic disrupts recurrent network dynamics, thus prevents the stabilization of cortical activity states. These findings shed new light on the temporal dynamics of neuronal variability and its alteration during anesthetic‐induced unconsciousness. [ABSTRACT FROM AUTHOR]

Decision making based on behavioral and neural observations of living systems has been extensively studied in brain science, psychology, neuroeconomics, and other disciplines. Decision-making mechanisms have also been experimentally implemented in physical processes, such as single photons and chaotic lasers. The findings of these experiments suggest that there is a certain common basis in describing decision making, regardless of its physical realizations. In this study, we propose a local reservoir model to account for choice-based learning (CBL). CBL describes decision consistency as a phenomenon where making a certain decision increases the possibility of making that same decision again later. This phenomenon has been intensively investigated in neuroscience, psychology, and other related fields. Our proposed model is inspired by the viewpoint that a decision is affected by its local environment, which is referred to as a local reservoir. If the size of the local reservoir is large enough, consecutive decision making will not be affected by previous decisions, thus showing lower degrees of decision consistency in CBL. In contrast, if the size of the local reservoir decreases, a biased distribution occurs within it, which leads to higher degrees of decision consistency in CBL. In this study, an analytical approach for characterizing local reservoirs is presented, as well as several numerical demonstrations. Furthermore, a physical architecture for CBL based on single photons is discussed, and the effects of local reservoirs are numerically demonstrated. Decision consistency in human decision-making tasks and in recruiting empirical data is evaluated based on the local reservoir. This foundation based on a local reservoir offers further insights into the understanding and design of decision making. [ABSTRACT FROM AUTHOR]

Abstract: Which temporal features that can characterize different brain states (i.e., consciousness or unconsciousness) is a fundamental question in the neuroscience of consciousness. Using resting‐state functional magnetic resonance imaging (rs‐fMRI), we investigated the spatial patterns of two temporal features: the long‐range temporal correlations (LRTCs), measured by power‐law exponent (PLE), and temporal variability, measured by standard deviation (SD) during wakefulness and anesthetic‐induced unconsciousness. We found that both PLE and SD showed global reductions across the whole brain during anesthetic state comparing to wakefulness. Importantly, the relationship between PLE and SD was altered in anesthetic state, in terms of a spatial “decoupling.” This decoupling was mainly driven by a spatial pattern alteration of the PLE, rather than the SD, in the anesthetic state. Our results suggest differential physiological grounds of PLE and SD and highlight the functional importance of the topographical organization of LRTCs in maintaining an optimal spatiotemporal configuration of the neural dynamics during normal level of consciousness. The central role of the spatial distribution of LRTCs, reflecting temporo‐spatial nestedness, may support the recently introduced temporo‐spatial theory of consciousness (TTC). [ABSTRACT FROM AUTHOR]

Who am I? What is the self and where does it come from? This may be one of the oldest problems in philosophy. Beyond traditional philosophy, only very recently approaches from neuroscience (in particular imaging studies) have tried to address these questions, too. So what are neural substrates of our self? An increasing body of evidence has demonstrated that a set of structures labeled as cortical midline structures are fundamental components to generate a conscious self. Moreover, recent theories on embodied cognition propose that this conscious self might be supplemented by additional structures, for example, in the somatosensory cortices, which enable our brain to create an "embodied mind". While the self based on cortical midline structures may be related to a conscious self, we here propose that the embodied facet of the self may be linked to something we call unconscious self. In this article we describe problems of this model of a conscious and unconscious self and discuss possible solutions from a theoretical point of view. [ABSTRACT FROM AUTHOR]

The literature about the care givers of patients with Disorders of Consciousness (DOCs) has highlighted the impact on both mental and physical dimensions of quality of life. This study aimed to: (1) describe emotional burden, quality of life, and coping styles in care givers of hospitalized patients with DOCs, compared to Italian normative data; (2) explore the relationships between these variables and their associations with socio-demographic features; and (3) describe their changes over time.Fifteen care givers of patients with DOCs, mostly middle-aged women, were assessed using the Family Strain Questionnaire, the SF-36 Health Survey, and the Coping Orientation to Problems Experienced – Nuova Versione Italiana. Eleven subjects were also assessed after 6 and 12 months. Data were analysed through descriptive statistics, correlations, and nonparametric tests of group differences.Compared to the Italian normative data, our sample showed a worse outcome in mental health, social functioning, global mental component, and emotional role functioning. Furthermore, subjects with high emotional burden had more thoughts of death compared to subjects with low emotional burden. Follow-up analyses revealed no variables changed over time.These results highlight the need for psychological interventions and support, since care givers represent an important part of an all-embracing support and care network for patients with DOCs. [ABSTRACT FROM AUTHOR]

The focus of the present article is on sketching a psychopathology of the body in schizophrenia and linking it to brain activity. This is done providing converging data from psychopathological evidence (phenomenal), phenomenological contructs (transphenomenal) and neuroscientific measures (pre-phenomenal). The phenomenal level is the detailed documentation of the patients' subjective anomalous experiences. These phenomena are explicit contents in the patients' field of consciousness. The trans-phenomenal level targets the implicit yet operative matrix that underlies these anomalous subjective experiences. Abnormal phenomena are viewed as expressions of a modification of trans-phenomenal matrix, that is, in terms of an abnormal synthesis or integration through time of intero-, proprio- and extero-ceptive stimuli. Finally, we link the abnormalities of the trans-phenomenal matrix to pre-phenomenal alterations of the brain resting state and of its spatio-temporal organization, as documented by neurobiological methods providing spatial and temporal resolution of intrinsic brain activity (with many features of the resting state remaining yet unclear though). Based on phenomenological research, the body in schizophrenia is typically experienced in an itemized way as an object external to one's self and unrelated to events in the external world. Based on neurobiological data, we tentatively hypothesize that such anomalies of the lived body are related to decreased integration between intero-, extero- and proprioceptive experiences by the brain's spontaneous activity and its temporal structure. Taken all together, this suggests that we view abnormalities of bodily experience in terms of their underlying abnormal spatiotemporal features which, as we suppose, can be traced back to the spatiotemporal features of the brain's spontaneous activity. [ABSTRACT FROM AUTHOR]

What is the self? This is a question that has long been discussed in (Western) philosophy where the self is traditionally conceived a higher-order function at the apex or pinnacle of all functions. This tradition has been transferred to recent neuroscience where the self is often considered to be a higher-order cognitive function reflected in memory and other high-level judgements. However, other lines of research demonstrate a close and intimate relationship between self-specificity and more basic functions like perceptions, emotions and reward. This paper focuses on the relationship between self-specificity and other basic functions relating to emotions, reward and perception. I propose the basis model that conceives self-specificity as a fundamental feature of the brain's spontaneous activity. This is supported by recent findings showing rest-self overlap in midline regions as well as findings demonstrating that the resting state can predict subsequent degrees of self-specificity. I conclude that such self-specificity in the brain's spontaneous activity may be central in linking the self to either internal or external stimuli. This may also provide the basis for coding the self as subject in relation to internal (i.e., self-consciousness) or external (i.e., phenomenal consciousness) mental events. [ABSTRACT FROM PUBLISHER]

Schizophrenia is a multifaceted disorder with various symptoms including auditory hallucinations, egodisturbances, passivity phenomena, and delusions. Recent neurobiological approaches have focused on, especially, the abnormal contents of consciousness, the “substantive parts” as James said, to associate them with the neural mechanisms related to sensory, motor, and cognitive functions, and the brain’s underlying stimulus-induced or task-evoked activity. This leaves open, however, the neural mechanisms that provide the temporal linkage or glue between the various contents, the transitive parts that makes possible the “stream of consciousness.” Interestingly, schizophrenic patients seem to suffer from abnormalities specifically in the “transitive parts” when they experience contents as temporally disconnected or fragmented which in phenomenological psychiatry has been described as “temporal fragmentation.” The aim of this article is to develop so-called neurophenomenal hypothesis about the direct relationship between phenomenal features of the “stream of consciousness,” the “transitive parts,” and the specific neuronal mechanisms in schizophrenia as based on healthy subjects. Rather than emphasizing stimulus-induced and task-evoked activity and sensory and lateral prefrontal cortical regions as in neurocognitive approaches with their focus on the “substantive parts,” the focus shifts here to the brain’s intrinsic activity, its resting state activity, which may account for the temporal linkage or glue between the contents of consciousness, the transitive parts. [ABSTRACT FROM PUBLISHER]

The self is central in our experience and has often been assumed to be necessary for any kind of consciousness in philosophy. Recent investigations in neuroscience demonstrate a particular set of regions such as the cortical midline regions to be associated with the processing of stimuli specifically related to the self as distinguished from those remaining unrelated to the self. Furthermore, findings show a close overlap between self-related activity and high levels of resting state activity in especially anterior midline regions. Interestingly, recent findings in psychiatric disorders such as depression and schizophrenia show resting state abnormalities in exactly these regions, that is in the cortical midline structures. Based on phenomenal and neural observations, I here suggest a neurophenomenal approach that directly links neuronal and phenomenal features (without sandwiching cognitive or sensorimotor functions) to psychopathological symptoms of self in depression and schizophrenia. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp 35:5368-5378, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Time is a key element of consciousness as it includes multiple timescales from shorter to longer ones. This is reflected in our experience of various short-term phenomenal contents at discrete points in time as part of an ongoing, more continuous, and long-term 'stream of consciousness'. Can Integrated Information Theory (IIT) account for this multitude of timescales of consciousness? According to the theory, the relevant spatiotemporal scale for consciousness is the one in which the system reaches the maximum cause-effect power; IIT currently predicts that experience occurs on the order of short timescales, namely, between 100 and 300 ms (theta and alpha frequency range). This can well account for the integration of single inputs into a particular phenomenal content. However, such short timescales leave open the temporal relation of specific phenomenal contents to others during the course of the ongoing time, that is, the stream of consciousness. For that purpose, we converge the IIT with the Temporo-spatial Theory of Consciousness (TTC), which, assuming a multitude of different timescales, can take into view the temporal integration of specific phenomenal contents with other phenomenal contents over time. On the neuronal side, this is detailed by considering those neuronal mechanisms driving the non-additive interaction of pre-stimulus activity with the input resulting in stimulus-related activity. Due to their non-additive interaction, the single input is not only integrated with others in the short-term timescales of 100–300 ms (alpha and theta frequencies) (as predicted by IIT) but, at the same time, also virtually expanded in its temporal (and spatial) features; this is related to the longer timescales (delta and slower frequencies) that are carried over from pre-stimulus to stimulus-related activity. Such a non-additive pre-stimulus-input interaction amounts to temporo-spatial expansion as a key mechanism of TTC for the constitution of phenomenal contents including their embedding or nesting within the ongoing temporal dynamic, i.e., the stream of consciousness. In conclusion, we propose converging the short-term integration of inputs postulated in IIT (100–300 ms as in the alpha and theta frequency range) with the longer timescales (in delta and slower frequencies) of temporo-spatial expansion in TTC. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we consider two major issues: conceptual–experimental approaches to the self, and the neuroanatomical substrate of the self. We distinguish content- and processed-based concepts of the self that entail different experimental strategies, and anatomically, we investigate the concept of midline structures in further detail and present a novel view on the anatomy of an integrated subcortical–cortical midline system. Presenting meta-analytic evidence, we show that the anterior paralimbic, e.g. midline, regions do indeed seem to be specific for self-specific stimuli. We conclude that future investigation of the self need to develop novel concepts that are more empirically plausible than those currently in use. Different concepts of self will require novel experimental designs that include, for example, the brain’s resting state activity as an independent variable. Modifications of both conceptual and anatomical dimensions will allow an empirically more plausible account of the relationship between brain and self. [Copyright &y& Elsevier]

Background: Based on animal data, NMDA receptor hypofunction has been suggested as a model for positive symptoms in schizophrenia. NMDA receptor hypofunction affects several corticolimbic brain regions, of which the posterior cingulate seems to be the most sensitive. However, empirical support for a crucial role of posterior cingulate NMDA hypofunction in the pathophysiology of positive symptoms is still missing in humans. We therefore conducted an fMRI study using the NMDA antagonist ketamine in healthy human subjects during episodic memory retrieval, which is supposed to activate the posterior cingulate. Methods: We investigated 16 healthy subjects which were assigned to either placebo (n = 7; saline) or ketamine (n = 9; 0.6 mg/kg/h) group in a double-blind study design. All subjects received their infusion while performing an episodic memory retrieval task in the scanner. Immediately after the fMRI session, psychopathological effects of ketamine were measured using the Altered States of Consciousness Questionnaire. Results: The placebo group showed BOLD signal increases in the posterior and anterior cingulate during retrieval. Signal increases were significantly lower in the ketamine group. Lower signal increases in the posterior cingulate correlated significantly with positive (i.e. psychosis-like) symptoms induced by ketamine. Conclusion: The present study for the first time demonstrates a relationship between NMDA receptors, posterior cingulate and positive (i.e. psychosis-like) symptoms in humans. Confirming findings from animal studies, it supports the hypothesis of a pathophysiological role of NMDA receptor hypofunction in the posterior cingulate in schizophrenia. [ABSTRACT FROM AUTHOR]

Consciousness is a central issue in neuroscience, however, we still lack a formal framework that can address the nature of the relationship between consciousness and its physical substrates. In this review, we provide a novel mathematical framework of category theory (CT), in which we can define and study the sameness between different domains of phenomena such as consciousness and its neural substrates. CT was designed and developed to deal with the relationships between various domains of phenomena. We introduce three concepts of CT which include (i) category; (ii) inclusion functor and expansion functor; and, most importantly, (iii) natural transformation between the functors. Each of these mathematical concepts is related to specific features in the neural correlates of consciousness (NCC). In this novel framework, we will examine two of the major theories of consciousness, integrated information theory (IIT) of consciousness and temporospatial theory of consciousness (TTC). We conclude that CT, especially the application of the notion of natural transformation, highlights that we need to go beyond NCC and unravels questions that need to be addressed by any future neuroscientific theory of consciousness. [ABSTRACT FROM AUTHOR]

Merker argues that subcortical regions are sufficient for the constitution of consciousness as ‘immediate, unreflective experience’ as distinguished from self-consciousness. My point here is that Merker neglects the differentiation between pre-reflective self-awareness and reflective self-consciousness. Pre-reflective self-awareness allows us to immediately and unreflectively experience our self, which functionally may be mediated by what I call self-related processing in subcortical regions. [ABSTRACT FROM AUTHOR]

We are continuously bombarded by external inputs of various timescales from the environment. How does the brain process this multitude of timescales? Recent resting state studies show a hierarchy of intrinsic neural timescales (INT) with a shorter duration in unimodal regions (e.g., visual cortex and auditory cortex) and a longer duration in transmodal regions (e.g., default mode network). This unimodal–transmodal hierarchy is present across acquisition modalities [electroencephalogram (EEG)/magnetoencephalogram (MEG) and fMRI] and can be found in different species and during a variety of different task states. Together, this suggests that the hierarchy of INT is central to the temporal integration (combining successive stimuli) and segregation (separating successive stimuli) of external inputs from the environment, leading to temporal segmentation and prediction in perception and cognition. The brain exhibits a hierarchy of intrinsic neural timescales with transmodal regions showing longer timescales compared with unimodal regions. This hierarchy of intrinsic neural timescales is present in human and non-human primates as well as on cellular and regional-systemic levels. The hierarchy of intrinsic neural timescales is carried over from resting state to task states including task-unspecific and task-specific effects. Intrinsic neural timescales mediate behavior, cognition, and mental features like sense of self and consciousness, including their alterations in neurologic and psychiatric disorders. Intrinsic neural timescales shape input processing through temporal segmentation of the input. The generation of empirical priors, as in predictive coding, may be strongly shaped by the intrinsic neural timescales allowing for temporal self-evidencing as 'deep temporal model'. [ABSTRACT FROM AUTHOR]

Two aspects of the low frequency fluctuations of spontaneous brain activity have been proposed which reflect the complex and dynamic features of resting-state activity, namely temporal variability and signal synchronization. The relationship between them, especially its role in consciousness, nevertheless remains unclear. Our study examined the temporal variability and signal synchronization of spontaneous brain activity, as well as their relationship during loss of consciousness. We applied an intra-subject design of resting-state functional magnetic resonance imaging (rs-fMRI) in two conditions: during wakefulness, and under anesthesia with clinical unconsciousness. In addition, an independent group of patients with disorders of consciousness (DOC) was included in order to test the reliability of our findings. We observed a global reduction in the temporal variability, local and distant brain signal synchronization for subjects during anesthesia. Importantly, we found a link between temporal variability and both local and distant signal synchronizations during wakefulness: the higher the degree of temporal variability, the higher its intra-regional homogeneity and inter-regional functional connectivity. In contrast, this link was broken down under anesthesia, implying a decoupling between temporal variability and signal synchronization; this decoupling was reproduced in patients with DOC. Our results suggest that there exist some as yet unclear physiological mechanisms of consciousness which “couple” the two mathematically independent measures, temporal variability and signal synchronization of spontaneous brain activity. Our findings not only extend our current knowledge of the neural correlates of anesthetic-induced unconsciousness, but have implications for both computational neural modeling and clinical practice, such as in the diagnosis of loss of consciousness in patients with DOC. [ABSTRACT FROM AUTHOR]

Determining the level of consciousness in patients with disorders of consciousness (DOC) remains challenging. To address this challenge, resting-state fMRI (rs-fMRI) has been widely used for detecting the local, regional, and network activity differences between DOC patients and healthy controls. Although substantial progress has been made towards this endeavor, the identification of robust rs-fMRI-based biomarkers for level of consciousness is still lacking. Recent developments in machine learning show promise as a tool to augment the discrimination between different states of consciousness in clinical practice. Here, we investigated whether machine learning models trained to make a binary distinction between conscious wakefulness and anesthetic-induced unconsciousness would then be capable of reliably identifying pathologically induced unconsciousness. We did so by extracting rs-fMRI-based features associated with local activity, regional homogeneity, and interregional functional activity in 44 subjects during wakefulness, light sedation, and unresponsiveness (deep sedation and general anesthesia), and subsequently using those features to train three distinct candidate machine learning classifiers: support vector machine, Extra Trees , artificial neural network. First, we show that all three classifiers achieve reliable performance within-dataset (via nested cross-validation), with a mean area under the receiver operating characteristic curve (AUC) of 0.95, 0.92, and 0.94, respectively. Additionally, we observed comparable cross-dataset performance (making predictions on the DOC data) as the anesthesia-trained classifiers demonstrated a consistent ability to discriminate between unresponsive wakefulness syndrome (UWS/VS) patients and healthy controls with mean AUC's of 0.99, 0.94, 0.98, respectively. Lastly, we explored the potential of applying the aforementioned classifiers towards discriminating intermediate states of consciousness, specifically, subjects under light anesthetic sedation and patients diagnosed as having a minimally conscious state (MCS). Our findings demonstrate that machine learning classifiers trained on rs-fMRI features derived from participants under anesthesia have potential to aid the discrimination between degrees of pathological unconsciousness in clinical patients. • Anesthetic-induced unconsciousness informs pathological unconsciousness. • Rs-fMRI-based machine learning is applied to distinguish conscious from unconscious subjects. • Machine learning models achieve reliable performance in cross-dataset generalizations. • Hyperparameter optimization significantly improves model performance. • Network-level functional connectivity features are most informative for classification. [ABSTRACT FROM AUTHOR]