Patients with Disorders of Consciousness: Are They Nonconscious, Unconscious, or Subconscious? Expanding the Discussion.

Unprecedented advancements in the diagnosis and treatment of patients with disorders of consciousness (DoC) have given rise to ethical questions about how to recognize and respect autonomy and a sense of agency of the personhood when those capacities are themselves disordered, as they typically are in patients with DoC. At the intersection of these questions rests the distinction between consciousness and unconsciousness. Indeed, evaluations of consciousness levels and capacity for recovery have a significant impact on decisions regarding whether to discontinue or prolong life-sustaining therapy for DoC patients. However, in the unconsciousness domain, there is the confusing array of terms that are regularly used interchangeably, making it quite challenging to comprehend what unconsciousness is and how it might be empirically grounded. In this opinion paper, we will provide a brief overview of the state of the field of unconsciousness and show how a rapidly evolving electroencephalogram (EEG) neuroimaging technique may offer empirical, theoretical, and practical tools to approach unconsciousness and to improve our ability to distinguish consciousness from unconsciousness and also nonconsciousness with greater precision, particularly in cases that are borderline (as is typical in patients with DoC). Furthermore, we will provide a clear description of three distant notions of (un)consciousness (unconsciousness, nonconsciousness, and subconsciousness) and discuss how they relate to the experiential selfhood which is essential for comprehending the moral significance of what makes life worth living.

Turning Back the Clock: A Retrospective Single-Blind Study on Brain Age Change in Response to Nutraceuticals Supplementation vs. Lifestyle Modifications.

BACKGROUND: There is a growing consensus that chronological age (CA) is not an accurate indicator of the aging process and that biological age (BA) instead is a better measure of an individual's risk of age-related outcomes and a more accurate predictor of mortality than actual CA. In this context, BA measures the "true" age, which is an integrated result of an individual's level of damage accumulation across all levels of biological organization, along with preserved resources. The BA is plastic and depends upon epigenetics. Brain state is an important factor contributing to health- and lifespan. METHODS AND OBJECTIVE: Quantitative electroencephalography (qEEG)-derived brain BA (BBA) is a suitable and promising measure of brain aging. In the present study, we aimed to show that BBA can be decelerated or even reversed in humans (N = 89) by using customized programs of nutraceutical compounds or lifestyle changes (mean duration = 13 months). RESULTS: We observed that BBA was younger than CA in both groups at the end of the intervention. Furthermore, the BBA of the participants in the nutraceuticals group was 2.83 years younger at the endpoint of the intervention compared with their BBA score at the beginning of the intervention, while the BBA of the participants in the lifestyle group was only 0.02 years younger at the end of the intervention. These results were accompanied by improvements in mental-physical health comorbidities in both groups. The pre-intervention BBA score and the sex of the participants were considered confounding factors and analyzed separately. CONCLUSIONS: Overall, the obtained results support the feasibility of the goal of this study and also provide the first robust evidence that halting and reversal of brain aging are possible in humans within a reasonable (practical) timeframe of approximately one year.

Contemplating on the Nature of Selfhood in DoC Patients: Neurophenomenological Perspective.

Medical well-regarded policy recommendations for patients with disorders of consciousness (DoC) are almost exclusively relied on behavioural examination and evaluation of higher-order cognition, and largely disregard the patients' self. This is so because practically establishing the presence of self-awareness or Selfhood is even more challenging than evaluating the presence of consciousness. At the same time, establishing the potential (actual physical possibility) of Selfhood in DoC patients is crucialy important from clinical, ethical, and moral standpoints because Selfhood is the most central and private evidence of being an independent and free agent that unites intention, embodiment, executive functions, attention, general intelligence, emotions and other components within the intra-subjective frame (first-person givenness). The importance of Selfhood is supported further by the observation that rebooting of self-awareness is the first step to recovery after brain damage. It seems that complex experiential Selfhood can be plausibly conceptualized within the Operational Architectonics (OA) of brain-mind functioning and reliably measured by quantitative electroencephalogram (qEEG) operational synchrony.

Self, Me and I in the repertoire of spontaneously occurring altered states of Selfhood: eight neurophenomenological case study reports.

This study investigates eight case reports of spontaneously emerging, brief episodes of vivid altered states of Selfhood (ASoSs) that occurred during mental exercise in six long-term meditators by using a neurophenomenological electroencephalography (EEG) approach. In agreement with the neurophenomenological methodology, first-person reports were used to identify such spontaneous ASoSs and to guide the neural analysis, which involved the estimation of three operational modules of the brain self-referential network (measured by EEG operational synchrony). The result of such analysis demonstrated that the documented ASoSs had unique neurophenomenological profiles, where several aspects or components of Selfhood (measured neurophysiologically and phenomenologically) are affected and expressed differently, but still in agreement with the neurophysiological three-dimensional construct model of the complex experiential Selfhood proposed in our earlier work (Fingelkurts et al. in Conscious Cogn 86:103031. 10.1016/j.concog.2020.103031, 2020).

Selfhood triumvirate: From phenomenology to brain activity and back again.

Recently, a three-dimensional construct model for complex experiential Selfhood has been proposed (Fingelkurts, Fingelkurts, & Kallio-Tamminen, 2016b,c). According to this model, three specific subnets (or modules) of the brain self-referential network (SRN) are responsible for the manifestation of three aspects/features of the subjective sense of Selfhood. Follow up multiple studies established a tight relation between alterations in the functional integrity of the triad of SRN modules and related to them three aspects/features of the sense of self; however, the causality of this relation is yet to be shown. In this article we approached the question of causality by exploring functional integrity within the three SRN modules that are thought to underlie the three phenomenal components of Selfhood while these components were manipulated mentally by experienced meditators in a controlled and independent manner. Participants were requested, in a block-randomised manner, to mentally induce states representing either increased (up-regulation) or decreased (down-regulation) sense of (a) witnessing agency ("Self"), or (b) body representational-emotional agency ("Me"), or (c) reflective/narrative agency ("I"), while their brain activity was recorded by an electroencephalogram (EEG). This EEG-data was complemented by first-person phenomenological reports and standardised questionnaires which focused on subjective contents of three aspects of Selfhood. The results of the study strengthen the case for a direct causative relationship between three phenomenological aspects of Selfhood and related to them three modules of the brain SRN. Furthermore, the putative integrative model of the dynamic interrelations among three modules of the SRN has been proposed.

Eye movement desensitization and reprocessing for post-traumatic stress disorder from the perspective of three-dimensional model of the experiential selfhood.

Eye Movement Desensitization and Reprocessing (EMDR) therapy is included in many international trauma treatment guidelines and is also shortlisted as an evidence-based practice for the treatment of psychological trauma and Post-Traumatic Stress Disorder (PTSD). However, its neurobiological mechanisms have not yet been fully understood. In this brief article we propose a hypothesis that a recently introduced neurophysiologically based three-dimensional construct model for experiential selfhood may help to fill this gap by providing the necessary neurobiological rationale of EMDR. In support of this proposal we briefly overview the neurophysiology of eye movements and the triad selfhood components, as well as EMDR therapy neuroimaging studies.

Brain-mind operational architectonics: At the boundary between quantum physics and Eastern metaphysics.

The Operational Architectonics (OA) of brain-mind functioning is a theory that unifies brain and mind through nested and dynamic hierarchy of electromagnetic brain fields. Recently, it has been enriched by concepts from physics like time, space, entropy, and self-organized criticality. This review paper advances OA theory further by delving into the foundations of quantum physics and Eastern metaphysics in relation to mind function. We aim to show that the brain-mind OA is the boundary between and integration point of quantum physics and Eastern metaphysics, and that it may inspire building a richer and more inclusive paradigm of the brain-mind relation, where quantum physics and Eastern metaphysics are inherently intertwined.

Brain space and time in mental disorders: Paradigm shift in biological psychiatry.

Contemporary psychiatry faces serious challenges because it has failed to incorporate accumulated knowledge from basic neuroscience, neurophilosophy, and brain-mind relation studies. As a consequence, it has limited explanatory power, and effective treatment options are hard to come by. A new conceptual framework for understanding mental health based on underlying neurobiological spatial-temporal mechanisms of mental disorders (already gained by the experimental studies) is beginning to emerge.

Alterations in the Three Components of Selfhood in Persons with Post-Traumatic Stress Disorder Symptoms: A Pilot qEEG Neuroimaging Study.

BACKGROUND AND OBJECTIVE: Understanding how trauma impacts the self-structure of individuals suffering from the Post-Traumatic Stress Disorder (PTSD) symptoms is a complex matter and despite several attempts to explain the relationship between trauma and the "Self", this issue still lacks clarity. Therefore, adopting a new theoretical perspective may help understand PTSD deeper and to shed light on the underlying psychophysiological mechanisms. METHODS: In this study, we employed the "three-dimensional construct model of the experiential selfhood" where three major components of selfhood (phenomenal first-person agency, embodiment, and reflection/narration) are related to three Operational Modules (OMs) of the self-referential brain network. These modules can be reliably estimated through operational synchrony analysis of the Electroencephalogram (EEG). Six individuals with PTSD symptoms and twenty-nine sex-, age- and demographic- (race, education, marital status) matched healthy controls underwent resting state EEG signal acquisition with the following estimation of the synchrony strength within every OM. RESULTS: Our results indicate that subjects with PTSD symptoms had significantly stronger EEG operational synchrony within anterior and right posterior OMs as well as significantly weaker EEG operational synchrony within left posterior OM compared to healthy controls. Moreover, increased the functional integrity of the anterior OM was positively associated with hyperactivity symptoms, reduced synchrony of the left posterior OM was associated with greater avoidance, and increased right posterior OM integrity was positively correlated with intrusion and mood symptoms. CONCLUSION: The results are interpreted in light of the triad model of selfhood and its theoretical and clinical implications (including a new treatment approach) are discussed.

Syntax meets semantics during brain logical computations.

The discrepancy between syntax and semantics is a painstaking issue that hinders a better comprehension of the underlying neuronal processes in the human brain. In order to tackle the issue, we at first describe a striking correlation between Wittgenstein's Tractatus, that assesses the syntactic relationships between language and world, and Perlovsky's joint language-cognitive computational model, that assesses the semantic relationships between emotions and "knowledge instinct". Once established a correlation between a purely logical approach to the language and computable psychological activities, we aim to find the neural correlates of syntax and semantics in the human brain. Starting from topological arguments, we suggest that the semantic properties of a proposition are processed in higher brain's functional dimensions than the syntactic ones. In a fully reversible process, the syntactic elements embedded in Broca's area project into multiple scattered semantic cortical zones. The presence of higher functional dimensions gives rise to the increase in informational content that takes place in semantic expressions. Therefore, diverse features of human language and cognitive world can be assessed in terms of both the logic armor described by the Tractatus, and the neurocomputational techniques at hand. One of our motivations is to build a neuro-computational framework able to provide a feasible explanation for brain's semantic processing, in preparation for novel computers with nodes built into higher dimensions.

Longitudinal Dynamics of 3-Dimensional Components of Selfhood After Severe Traumatic Brain Injury: A qEEG Case Study.

In this report, we describe the case of a patient who sustained extremely severe traumatic brain damage with diffuse axonal injury in a traffic accident and whose recovery was monitored during 6 years. Specifically, we were interested in the recovery dynamics of 3-dimensional components of selfhood (a 3-dimensional construct model for the complex experiential selfhood has been recently proposed based on the empirical findings on the functional-topographical specialization of 3 operational modules of brain functional network responsible for the self-consciousness processing) derived from the electroencephalographic (EEG) signal. The analysis revealed progressive (though not monotonous) restoration of EEG functional connectivity of 3 modules of brain functional network responsible for the self-consciousness processing, which was also paralleled by the clinically significant functional recovery. We propose that restoration of normal integrity of the operational modules of the self-referential brain network may underlie the positive dynamics of 3 aspects of selfhood and provide a neurobiological mechanism for their recovery. The results are discussed in the context of recent experimental studies that support this inference. Studies of ongoing recovery after severe brain injury utilizing knowledge about each separate aspect of complex selfhood will likely help to develop more efficient and targeted rehabilitation programs for patients with brain trauma.

Topodynamics of metastable brains.

The brain displays both the anatomical features of a vast amount of interconnected topological mappings as well as the functional features of a nonlinear, metastable system at the edge of chaos, equipped with a phase space where mental random walks tend towards lower energetic basins. Nevertheless, with the exception of some advanced neuro-anatomic descriptions and present-day connectomic research, very few studies have been addressing the topological path of a brain embedded or embodied in its external and internal environment. Herein, by using new formal tools derived from algebraic topology, we provide an account of the metastable brain, based on the neuro-scientific model of Operational Architectonics of brain-mind functioning. We introduce a "topodynamic" description that shows how the relationships among the countless intertwined spatio-temporal levels of brain functioning can be assessed in terms of projections and mappings that take place on abstract structures, equipped with different dimensions, curvatures and energetic constraints. Such a topodynamical approach, apart from providing a biologically plausible model of brain function that can be operationalized, is also able to tackle the issue of a long-standing dichotomy: it throws indeed a bridge between the subjective, immediate datum of the naïve complex of sensations and mentations and the objective, quantitative, data extracted from experimental neuro-scientific procedures. Importantly, it opens the door to a series of new predictions and future directions of advancement for neuroscientific research.

Three-dimensional components of selfhood in treatment-naive patients with major depressive disorder: A resting-state qEEG imaging study.

Based on previous studies implicating increased functional connectivity within the self-referential brain network in major depressive disorder (MDD), and considering the functional roles of three distinct modules of such brain net (responsible for three-dimensional components of Selfhood) together with the documented abnormalities of self-related processing in MDD, we tested the hypothesis that patients with depression would exhibit increased connectivity within each module of the self-referential brain network and that the strength of these connections would correlate positively with depression severity. Applying the electroencephalogram (EEG) operational synchrony analysis to extract three modules of the self-referential brain network in 12 medication-free depressive outpatients and 10 control subjects we have found an increase in the strength of EEG synchrony within all three modules in depressive patients (though non-significant for the right module). Furthermore, multiple regression analysis that used 3 factors (values of synchrony strength for all three modules) as input indicated that combined increase in the strength of synchrony in all three modules was positively associated with severity of depression. Taken together the findings of this study suggest that depression is primarily associated with hypersynchrony in all three modules of the brain self-referential network (the anterior module been responsible for "witnessing observation and first-person perspective", the left posterior module been responsible for "reflective agency and narration" and the right posterior module been responsible for "bodily representational-emotional agency"), thus contributing to excessive self-focus, rumination, and body tension.

Longitudinal Assessment of Clinical Signs of Recovery in Patients with Unresponsive Wakefulness Syndrome after Traumatic or Nontraumatic Brain Injury.

Although clinical examination is the gold standard for differential diagnosis between unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), clinical signs denoting the first occurrence of conscious behavior in patients with UWS have not been clarified. In this prospective single-center cohort study, 31 consecutive patients with UWS after traumatic brain injury (TBI) (17 patients) or non-TBI were assessed with the Coma Recovery Scale Revised (CRS-R) at admission to a rehabilitation department and after 1, 2, 3, 6, and 12 months. Of the 21 patients who recovered consciousness during the study, 90.5% recovered consciousness within the first 3 months. At the first diagnosis of emergence from UWS, 52.4% of patients showed signs of awareness in only one CRS-R subscale. In particular, 42.9% of patients showed conscious behaviors on the visual CRS-R subscale (23.8% showed visual fixation and 19.1% showed visual pursuit), and 9.5% showed conscious behaviors on the motor CRS-R subscale (half showed localization to a noxious stimulus and half showed object manipulation). Moreover, 23.8% of patients had conscious behaviors on two CRS subscales, always involving the visual and motor CRS-R subscales. The remaining patients showed conscious behaviors on more than two CRS-R subscales. In conclusion, visual fixation and visual pursuit are the commonest early clinical signs denoting MCS. When emerging from UWS, patients with TBI often showed more signs of consciousness and had higher CRS-R scores than patients with non-TBI.

Changes in Standard Electroencephalograms Parallel Consciousness Improvements in Patients With Unresponsive Wakefulness Syndrome.

OBJECTIVE: To identify changes in the standard electroencephalograms (EEGs) of patients with unresponsive wakefulness syndrome (UWS) who did or did not recover consciousness 6 months after admission to a rehabilitation department. DESIGN: Prospective cohort study. SETTING: Unit for severe acquired brain injuries. PARTICIPANTS: Consecutive patients with UWS (N=28). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: EEG amplitude (reduced or normal), dominant frequency (alpha, theta, or delta), and reactivity (absent or present) were scored at admission and 6 months later. The cumulative Amplitude-Frequency-Reactivity score was evaluated. Clinical assessments were made using the Coma Recovery Scale-Revised. RESULTS: Sixteen (57.1%) of the 28 patients with UWS recovered consciousness after 6 months, while 12 patients (42.9%) did not recover consciousness. EEG improvements occurred in 14 patients with consciousness recovery (87.5%) and 2 patients without consciousness recovery (16.7%) only. Improvements in EEG dominant frequency (from the theta to the alpha band or from the delta to the theta band), reappearance of EEG reactivity, and Amplitude-Frequency-Reactivity score increase (P<.01) differentiated patients with consciousness improvement from those without consciousness improvement. Six months after admission for rehabilitation, patients with EEG improvements showed higher Coma Recovery Scale-Revised scores than did those without EEG changes (P<.01). CONCLUSIONS: Most patients who emerge from UWS demonstrate improvement in basic EEG characteristics over time. EEG changes in patients with UWS may aid in the timely recognition of patients transitioning into a minimally conscious state.

The Chief Role of Frontal Operational Module of the Brain Default Mode Network in the Potential Recovery of Consciousness from the Vegetative State: A Preliminary Comparison of Three Case Reports.

It has been argued that complex subjective sense of self is linked to the brain default-mode network (DMN). Recent discovery of heterogeneity between distinct subnets (or operational modules - OMs) of the DMN leads to a reconceptualization of its role for the experiential sense of self. Considering the recent proposition that the frontal DMN OM is responsible for the first-person perspective and the sense of agency, while the posterior DMN OMs are linked to the continuity of 'I' experience (including autobiographical memories) through embodiment and localization within bodily space, we have tested in this study the hypothesis that heterogeneity in the operational synchrony strength within the frontal DMN OM among patients who are in a vegetative state (VS) could inform about a stable self-consciousness recovery later in the course of disease (up to six years post-injury). Using EEG operational synchrony analysis we have demonstrated that among the three OMs of the DMN only the frontal OM showed important heterogeneity in VS patients as a function of later stable clinical outcome. We also found that the frontal DMN OM was characterized by the process of active uncoupling (stronger in persistent VS) of operations performed by the involved neuronal assemblies.