OBJECTIVE: The parabrachial nucleus (PBN) promotes wakefulness states under general anesthesia. Recent studies have shown that glutamatergic neurons within the PBN play a crucial role in facilitating emergence from anesthesia. Our previous study indicates that vesicular glutamate transporter 2 (vglut2) expression neurons of the PBN extend into the extended amygdala (EA). However, the modulation of PBNvglut2-EA in general anesthesia remains poorly understood. This study aims to investigate the role of PBNvglut2-EA in alterations of consciousness during sevoflurane anesthesia.
METHODS: We first validated vglut2-expressing neuron projections from the PBN to the EA using anterograde tracing. Then, we conducted immunofluorescence staining of c-Fos to investigate the role of the EA involved in the regulation of consciousness during sevoflurane anesthesia. After, we performed calcium fiber photometry recordings to determine the changes in PBNvglut2-EA activity. Lastly, we modulated PBNvglut2-EA activity under sevoflurane anesthesia using optogenetics, and electroencephalogram (EEG) was recorded during specific optogenetic modulation.
RESULTS: The expression of vglut2 in PBN neurons projected to the EA, and c-Fos expression in the EA was significantly reduced during sevoflurane anesthesia. Fiber photometry revealed that activity in the PBNvglut2-EA pathway was suppressed during anesthesia induction but restored upon awakening. Optogenetic activation of the PBNvglut2-EA delayed the induction of anesthesia. Meanwhile, EEG recordings showed significantly decreased δ oscillations and increased β and γ oscillations compared to the EYFP group. Furthermore, optogenetic activation of the PBNvglut2-EA resulted in an acceleration of awakening from anesthesia, accompanied by decreased δ oscillations on EEG recordings. Optogenetic inhibition of PBNvglut2-EA accelerated anesthesia induction. Surprisingly, we found a sex-specific regulation of PBNvglut2-EA in this study. The activity of PBNvglut2-EA was lower in males during the induction of anesthesia and decreased more rapidly during sevoflurane anesthesia compared to females. Photoactivation of the PBNvglut2-EA reduced the sensitivity of males to sevoflurane, showing more pronounced wakefulness behavior and EEG changes than females.
CONCLUSIONS: PBNvglut2-EA is involved in the promotion of wakefulness under sevoflurane anesthesia. Furthermore, PBNvglut2-EA shows sex differences in the changes of consciousness induced by sevoflurane anesthesia.

OBJECTIVE: Absence seizures impair psychosocial function, yet their detailed neuronal basis remains unknown. Recent work in a rat model suggests that cortical arousal state changes prior to seizures and that single neurons show diverse firing patterns during seizures. Our aim was to extend these investigations to a mouse model with studies of neuronal activity and arousal state to facilitate future fundamental investigations of absence epilepsy.
METHODS: We performed in vivo extracellular single unit recordings on awake head-fixed C3H/HeJ mice. Mice were implanted with tripolar electrodes for cortical electroencephalogram (EEG). Extracellular single unit recordings were obtained with glass micropipettes in the somatosensory barrel cortex, while animals ambulated freely on a running wheel. Signals were digitized and analyzed during seizures and baseline.
RESULTS: Neuronal activity was recorded from 36 cortical neurons in 19 mice while EEG showed characteristic 7-8 Hz spike-wave discharges. Different single neurons showed distinct firing patterns during seizures, but the overall mean population neuronal firing rate during seizures was no different from pre-seizure baseline. However, the rhythmicity of neuronal firing during seizures was significantly increased (p < 0.001). In addition, beginning 10s prior to seizure initiation, we observed a progressive decrease in cortical high frequency (>40 Hz) EEG and an increase in lower frequency (1-39 Hz) activity suggesting decreased arousal state.
CONCLUSIONS: We found that the awake head-fixed C3H/HeJ mouse model demonstrated rhythmic neuronal firing during seizures, and a decreased cortical arousal state prior to seizure onset. Unlike the rat model we did not observe an overall decrease in neuronal firing during seizures. Similarities and differences across species strengthen the ability to investigate fundamental key mechanisms. Future work in the mouse model will identify the molecular basis of neurons with different firing patterns, their role in seizure initiation and behavioral deficits, with ultimate translation to human absence epilepsy.

UNASSIGNED: Attaining movement proficiency under various constraints is well-researched; of particular interest here is how conscious processing and self-consciousness influence learning and performance. Current research relevant to these variables e.g., reinvestment, tends to utilize quantitative methods and thus overlooks a potentially rich source of understanding. Therefore, the purpose of this study was to apply a qualitative approach to explore the cognitive processes and self-consciousness within a less practiced population of adults participating in a non-competitive leisure activity.
UNASSIGNED: To achieve this, eleven semi-structured interviews were conducted with adult women learning or relearning to ride a bicycle.
UNASSIGNED: Using thematic analysis, two distinct themes were evident and corroborated those illustrated in scales such as the movement-specific reinvestment scale. These themes included Conscious Processing, Recalling Experiences and Movement Analysis, in addition to Style of Movement, and Self-Consciousness. Anxiety also emerged as an additional and relevant theme to learning a new complex movement skill.
UNASSIGNED: The findings indicated that participating women attuned to their movements to the extent that there was a conscious attempt to control their movements, but less so regarding movements being altered by self-awareness. Whilst further research is required, qualitative methods provide a promising basis for exploring the cognitive process involved with the conscious process involved in learning.

Scale-free statistics of coordinated neuronal activity, suggesting a universal operating mechanism across spatio-temporal scales, have been proposed as a necessary condition of healthy resting-state brain activity. Recent studies have focused on anesthetic agents to induce distinct neural states in which consciousness is altered to understand the importance of critical dynamics. However, variation in experimental techniques, species, and anesthetics, have made comparisons across studies difficult. Here we conduct a survey of several common anesthetics (isoflurane, pentobarbital, ketamine) at multiple dosages, using calcium wide-field optical imaging of the mouse cortex. We show that while low-dose anesthesia largely preserves scale-free statistics, surgical plane anesthesia induces multiple dynamical modes, most of which do not maintain critical avalanche dynamics. Our findings indicate multiple pathways away from default critical dynamics associated with quiet wakefulness, not only reflecting differences between these common anesthetics but also showing significant variations in individual responses. This is suggestive of a non-trivial relationship between criticality and the underlying state of the subject.

OBJECTIVE: For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries.
METHODS: We reviewed salient medical literature regarding covert consciousness.
METHODS: We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness.
METHODS: We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries.
CONCLUSIONS: Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited.

BACKGROUND: Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs.
METHODS: The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms.
RESULTS: Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children.
CONCLUSIONS: The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges.

In conscious states, the electrodynamics of the cortex are reported to work near a critical point or phase transition of chaotic dynamics, known as the edge-of-chaos, representing a boundary between stability and chaos. Transitions away from this boundary disrupt cortical information processing and induce a loss of consciousness. The entropy of the electroencephalogram (EEG) is known to decrease as the level of anesthesia deepens. However, whether the chaotic dynamics of electroencephalographic activity shift from this boundary to the side of stability or the side of chaotic enhancement during anesthesia-induced loss of consciousness remains poorly understood. We investigated the chaotic properties of EEGs at two different depths of clinical anesthesia using the maximum Lyapunov exponent, which is mathematically regarded as a formal measure of chaotic nature, using the Rosenstein algorithm. In 14 adult patients, 12 s of electroencephalographic signals were selected during two depths of clinical anesthesia (sevoflurane concentration 2% as relatively deep anesthesia, sevoflurane concentration 0.6% as relatively shallow anesthesia). Lyapunov exponents, correlation dimensions and approximate entropy were calculated from these electroencephalographic signals. As a result, maximum Lyapunov exponent was generally positive during sevoflurane anesthesia, and both maximum Lyapunov exponents and correlation dimensions were significantly greater during deep anesthesia than during shallow anesthesia despite reductions in approximate entropy. The chaotic nature of the EEG might be increased at clinically deeper inhalational anesthesia, despite the decrease in randomness as reflected in the decreased entropy, suggesting a shift to the side of chaotic enhancement under anesthesia.

OBJECTIVE: The mechanism underlying the reversible unconsciousness induced by general anesthetics (GA) remains unclear. Recent studies revealed the critical roles of myelin and oligodendrocytes (OLs) in higher functions of the brain. However, it is unknown whether myelin actively participates in the regulation of GA. The aim of this study is to investigate the roles and possible mechanisms of myelin in the regulation of consciousness alterations induced by isoflurane anesthesia.
METHODS: First, demyelination models for the entire brain and specific neural nuclei were established to investigate the potential role of myelination in the regulation of GA, as well as its possible regional specificity. c-Fos staining was then performed on the demyelinated nuclei to verify the impact of myelin loss on neuronal activity. Finally, the activity of neurons during isoflurane anesthesia in demyelinated mice was recorded by optical fiber photometric calcium signal. The related behavioral indicators and EEG were recorded and analyzed.
RESULTS: A prolonged emergence time was observed from isoflurane anesthesia in demyelinated mice, which suggested the involvement of myelin in regulating GA. The demyelination in distinct nuclei by LPC further clarified the region-specific roles of isoflurane anesthesia regulation by myelin. The effect of demyelination on isoflurane anesthesia in the certain nucleus was consistent with that in neurons towards isoflurane anesthesia. Finally, we found that the mechanism of myelin in the modulation of isoflurane anesthesia is possibly through the regulation of neuronal activity.
CONCLUSIONS: In brief, myelin in the distinct neural nucleus plays an essential role in regulating the process of isoflurane anesthesia. The possible mechanism of myelin in the regulation of isoflurane anesthesia is neuronal activity modification by myelin integrity during GA. Our findings enhanced the comprehension of myelin function, and offered a fresh perspective for investigating the neural mechanisms of GA.

Many technology ethicists hold that the time has come to articulate neurorights: our normative claims vis-à-vis our brains and minds. One such claim is the right to mental integrity (\'MI\'). I begin by considering some paradigmatic threats to MI (§1) and how the dominant autonomy-based conception (\'ABC\') of MI attempts to make sense of them (§2). I next consider the objection that the ABC is overbroad in its understanding of what threatens MI and suggest a friendly revision to the ABC that addresses the objection (§3). I then consider a second objection: that the ABC cannot make sense of the MI of the non-autonomous This objection appears fatal even to the revised ABC (§4). On that basis, I develop an alternative conception on which MI is grounded in a plurality of simpler capacities, namely, those for affect, cognition, and volition Each of these more basic capacities grounds a set of fundamental interests, and they are for that reason worthy of protection even when they do not rise to the level of complexity necessary for autonomy (§5). This yields a fully general theory of MI that accounts for its manifestations in both the autonomous and the non-autonomous.

There is such a vast proliferation of scientific theories of consciousness that it is worrying some scholars. There are even competitions to test different theories, and the results are inconclusive. Consciousness research, far from converging toward a unifying framework, is becoming more discordant than ever, especially with respect to theoretical elements that do not have a clear neurobiological basis. Rather than dueling theories, an integration across theories is needed to facilitate a comprehensive view on consciousness and on how normal nervous system dynamics can develop into pathological states. In dealing with what is considered an extremely complex matter, we try to adopt a perspective from which the subject appears in relative simplicity. Grounded in experimental and theoretical observations, we advance an encompassing biophysical theory, MaxCon, which incorporates aspects of several of the main existing neuroscientific consciousness theories, finding convergence points in an attempt to simplify and to understand how cellular collective activity is organized to fulfill the dynamic requirements of the diverse theories our proposal comprises. Moreover, a computable index indicating consciousness level is presented. Derived from the level of description of the interactions among cell networks, our proposal highlights the association of consciousness with maximization of the number of configurations of neural network connections -constrained by neuroanatomy, biophysics and the environment- that is common to all consciousness theories.