Increased lucid dream frequency in long-term meditators but not following MBSR training.

Strong conceptual and theoretical connections have been made between meditation practice, mindfulness and lucid dreaming. However, only a handful of empirical studies have evaluated the relationship between lucid dreaming and meditation, and conclusions remain tempered by methodological limitations. Here we evaluate the relationship between meditation, mindfulness and lucid dream frequency using several complementary methods. First, using a cross-sectional design, we evaluate differences in lucid dream frequency between long-term meditators and meditation naïve individuals. Second, we evaluate the relationship between lucid dream frequency and specific facets of trait mindfulness in both meditators and non-meditators. Third, using a blinded randomized-controlled design, we evaluate the impact of an 8-week mindfulness course on lucid dreaming frequency. Our results show that lucid dreaming is more frequent in long-term meditators compared to meditation naïve individuals. Additionally, lucid dream frequency in meditation-naïve individuals was associated with a capacity to verbalize experience, while lucid dream frequency in long-term meditators was associated with observational and decentering facets of trait mindfulness. However, an 8-week mindfulness course did not increase the frequency of lucid dreams. Together these results support a continuity between increased awareness of waking and sleeping states, provide a novel form of evidence linking meditation training to meta-awareness, and support an association between meditation practice and lucid dreaming, but leave open the specific nature of this connection.

Functional split brain in a driving/listening paradigm.

We often engage in two concurrent but unrelated activities, such as driving on a quiet road while listening to the radio. When we do so, does our brain split into functionally distinct entities? To address this question, we imaged brain activity with fMRI in experienced drivers engaged in a driving simulator while listening either to global positioning system instructions (integrated task) or to a radio show (split task). We found that, compared with the integrated task, the split task was characterized by reduced multivariate functional connectivity between the driving and listening networks. Furthermore, the integrated information content of the two networks, predicting their joint dynamics above and beyond their independent dynamics, was high in the integrated task and zero in the split task. Finally, individual subjects' ability to switch between high and low information integration predicted their driving performance across integrated and split tasks. This study raises the possibility that under certain conditions of daily life, a single brain may support two independent functional streams, a "functional split brain" similar to what is observed in patients with an anatomical split.

Reversal of cortical information flow during visual imagery as compared to visual perception.

The role of bottom-up and top-down connections during visual perception and the formation of mental images was examined by analyzing high-density EEG recordings of brain activity using two state-of-the-art methods for assessing the directionality of cortical signal flow: state-space Granger causality and dynamic causal modeling. We quantified the directionality of signal flow in an occipito-parieto-frontal cortical network during perception of movie clips versus mental replay of the movies and free visual imagery. Both Granger causality and dynamic causal modeling analyses revealed an increased top-down signal flow in parieto-occipital cortices during mental imagery as compared to visual perception. These results are the first direct demonstration of a reversal of the predominant direction of cortical signal flow during mental imagery as compared to perception.

Consciousness in humans and non-human animals: recent advances and future directions.

This joint article reflects the authors' personal views regarding noteworthy advances in the neuroscience of consciousness in the last 10 years, and suggests what we feel may be promising future directions. It is based on a small conference at the Samoset Resort in Rockport, Maine, USA, in July of 2012, organized by the Mind Science Foundation of San Antonio, Texas. Here, we summarize recent advances in our understanding of subjectivity in humans and other animals, including empirical, applied, technical, and conceptual insights. These include the evidence for the importance of fronto-parietal connectivity and of "top-down" processes, both of which enable information to travel across distant cortical areas effectively, as well as numerous dissociations between consciousness and cognitive functions, such as attention, in humans. In addition, we describe the development of mental imagery paradigms, which made it possible to identify covert awareness in non-responsive subjects. Non-human animal consciousness research has also witnessed substantial advances on the specific role of cortical areas and higher order thalamus for consciousness, thanks to important technological enhancements. In addition, much progress has been made in the understanding of non-vertebrate cognition relevant to possible conscious states. Finally, major advances have been made in theories of consciousness, and also in their comparison with the available evidence. Along with reviewing these findings, each author suggests future avenues for research in their field of investigation.

Changes in effective connectivity by propofol sedation.

Mechanisms of propofol-induced loss of consciousness remain poorly understood. Recent fMRI studies have shown decreases in functional connectivity during unconsciousness induced by this anesthetic agent. Functional connectivity does not provide information of directional changes in the dynamics observed during unconsciousness. The aim of the present study was to investigate, in healthy humans during an auditory task, the changes in effective connectivity resulting from propofol induced loss of consciousness. We used Dynamic Causal Modeling for fMRI (fMRI-DCM) to assess how causal connectivity is influenced by the anesthetic agent in the auditory system. Our results suggest that the dynamic observed in the auditory system during unconsciousness induced by propofol, can result in a mixture of two effects: a local inhibitory connectivity increase and a decrease in the effective connectivity in sensory cortices.

Thalamus, brainstem and salience network connectivity changes during propofol-induced sedation and unconsciousness.

In this functional magnetic resonance imaging study, we examined the effect of mild propofol sedation and propofol-induced unconsciousness on resting state brain connectivity, using graph analysis based on independent component analysis and a classical seed-based analysis. Contrary to previous propofol research, which mainly emphasized the importance of connectivity in the default mode network (DMN) and external control network (ECN), we focused on the salience network, thalamus, and brainstem. The importance of these brain regions in brain arousal and organization merits a more detailed examination of their connectivity response to propofol. We found that the salience network disintegrated during propofol-induced unconsciousness. The thalamus decreased connectivity with the DMN, ECN, and salience network, while increasing connectivity with sensorimotor and auditory/insular cortices. Brainstem regions disconnected from the DMN with unconsciousness, while the pontine tegmental area increased connectivity with the insulae during mild sedation. These findings illustrate that loss of consciousness is associated with a wide variety of decreases and increases of both cortical and subcortical connectivity. It furthermore stresses the necessity of also examining resting state connectivity in networks representing arousal, not only those associated with awareness.

Connectivity changes underlying spectral EEG changes during propofol-induced loss of consciousness.

The mechanisms underlying anesthesia-induced loss of consciousness remain a matter of debate. Recent electrophysiological reports suggest that while initial propofol infusion provokes an increase in fast rhythms (from beta to gamma range), slow activity (from delta to alpha range) rises selectively during loss of consciousness. Dynamic causal modeling was used to investigate the neural mechanisms mediating these changes in spectral power in humans. We analyzed source-reconstructed data from frontal and parietal cortices during normal wakefulness, propofol-induced mild sedation, and loss of consciousness. Bayesian model selection revealed that the best model for explaining spectral changes across the three states involved changes in corticothalamic interactions. Compared with wakefulness, mild sedation was accounted for by an increase in thalamic excitability, which did not further increase during loss of consciousness. In contrast, loss of consciousness per se was accompanied by a decrease in backward corticocortical connectivity from frontal to parietal cortices, while thalamocortical connectivity remained unchanged. These results emphasize the importance of recurrent corticocortical communication in the maintenance of consciousness and suggest a direct effect of propofol on cortical dynamics.

Willful modulation of brain activity in disorders of consciousness.

BACKGROUND: The differential diagnosis of disorders of consciousness is challenging. The rate of misdiagnosis is approximately 40%, and new methods are required to complement bedside testing, particularly if the patient's capacity to show behavioral signs of awareness is diminished. METHODS: At two major referral centers in Cambridge, United Kingdom, and Liege, Belgium, we performed a study involving 54 patients with disorders of consciousness. We used functional magnetic resonance imaging (MRI) to assess each patient's ability to generate willful, neuroanatomically specific, blood-oxygenation-level-dependent responses during two established mental-imagery tasks. A technique was then developed to determine whether such tasks could be used to communicate yes-or-no answers to simple questions. RESULTS: Of the 54 patients enrolled in the study, 5 were able to willfully modulate their brain activity. In three of these patients, additional bedside testing revealed some sign of awareness, but in the other two patients, no voluntary behavior could be detected by means of clinical assessment. One patient was able to use our technique to answer yes or no to questions during functional MRI; however, it remained impossible to establish any form of communication at the bedside. CONCLUSIONS: These results show that a small proportion of patients in a vegetative or minimally conscious state have brain activation reflecting some awareness and cognition. Careful clinical examination will result in reclassification of the state of consciousness in some of these patients. This technique may be useful in establishing basic communication with patients who appear to be unresponsive.

Reaching across the abyss: recent advances in functional magnetic resonance imaging and their potential relevance to disorders of consciousness.

Disorders of consciousness (DOC) raise profound scientific, clinical, ethical, and philosophical issues. Growing knowledge on fundamental principles of brain organization in healthy individuals offers new opportunities for a better understanding of residual brain function in DOCs. We here discuss new perspectives derived from a recently proposed scheme of brain organization underlying consciousness in healthy individuals. In this scheme, thalamo-cortical networks can be divided into two, often antagonistic, global systems: (i) a system of externally oriented, sensory-motor networks (the "extrinsic" system); and (ii) a system of inward-oriented networks (the "intrinsic" or default system). According to this framework, four distinct mental states would be possible that could be relevant for understanding DOCs. In normal healthy volunteers and locked-in syndrome patients, a state of high functionality of both the extrinsic and intrinsic or default systems is expected--associated with full awareness of environment and self. In this case, mental imagery tasks combined with fMRI can be used to detect covert awareness in patients that are unable to communicate. According to the framework, two complementary states of system imbalance are also possible, in which one system is in a hyperfunctional state, while the other is hypoactive. Extrinsic system hyperfunction is expected to lead to a state of total sensory-motor "absorption" or "lost self." In contrast, intrinsic or default system hyperfunction is expected to lead to a state of complete detachment from the external world. A state where both extrinsic and intrinsic systems are hypofunctional is predicted to lead to markedly impaired consciousness as seen in DOCs. Finally, we review the potential use of ultra-slow fluctuations in BOLD signal as a tool for assessing the functional integrity of extrinsic and intrinsic systems during "resting state" fMRI acquisitions. In particular, we discuss the potential provided by assessment of these slow spontaneous BOLD fluctuations as a novel tool in assessing the cognitive state and chances of recovery from brain pathologies underlying DOCs.

Neuroimaging activation studies in the vegetative state: predictors of recovery?

The vegetative state (VS) is a devastating clinical condition characterised by wakefulness without awareness. Functional neuroimaging permits to objectively measure brain responsiveness to external stimuli in VS. The literature on functional magnetic resonance imaging and positron emission tomography studies in these patients has been reviewed. Results from 15 studies were classified in: absent cortical activation or 'typical' activation of 'low level' primary sensory cortices and 'atypical' activation spreading to 'higher level' associative cortices. This descriptive review on 48 published cases suggests that 'atypical' activation patterns seem to herald recovery from VS with a 93% specificity and 69% sensitivity. Passive stimulation paradigms, however, do not permit to make strong claims about the absence or presence of consciousness. Recently proposed mental imagery paradigms permit to identify signs of consciousness in non-communicative brain damaged patients. The clinical application of these functional neuroimaging techniques awaits validation from ongoing multi-centric cohort studies in these challenging patients with chronic disorders of consciousness.

Perception of pain in the minimally conscious state with PET activation: an observational study.

BACKGROUND: Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. METHODS: We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. FINDINGS: In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. INTERPRETATION: Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.

Functional neuroanatomy of the hypnotic state.

The neural mechanisms underlying hypnosis and especially the modulation of pain perception by hypnosis remain obscure. Using PET we first described the distribution of regional cerebral blood flow during the hypnotic state. Hypnosis relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness". The hypnotic state was related to the activation of a widespread set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal and anterior cingulate cortices. This pattern of activation shares some similarities with mental imagery, from which it mainly differs by the relative deactivation of precuneus. Second, we looked at the anti-nociceptive effects of hypnosis. Compared to the resting state, hypnosis reduced pain perception by approximately 50%. The hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation were modulated by the activity in the midcingulate cortex (area 24a'). Finally, we assessed changes in cerebral functional connectivity related to hypnosis. Compared to normal alertness (i.e., rest and mental imagery), the hypnotic state, significantly enhanced the functional modulation between midcingulate cortex and a large neural network involved in sensory, affective, cognitive and behavioral aspects of nociception. These findings show that not only pharmacological but also psychological strategies for pain control can modulate the cerebral network involved in noxious perception.

Cerebral processing of auditory and noxious stimuli in severely brain injured patients: differences between VS and MCS.

We review cerebral processing of auditory and noxious stimuli in minimally conscious state (MCS) and vegetative state (VS) patients. In contrast with limited brain activation found in VS patients, MCS patients show activation similar to controls in response to auditory, emotional and noxious stimuli. Despite an apparent clinical similarity between MCS and VS patients, functional imaging data show striking differences in cortical segregation and integration between these two conditions. However, in the absence of a generally accepted neural correlate of consciousness as measured by functional neuroimaging, clinical assessment remains the gold standard for the evaluation and management of severely brain damaged patients.

Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state.

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception.

Brain function in the vegetative state.

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.