Disruption in structural-functional network repertoire and time resolved subcortical-frontoparietal connectivity in disorders of consciousness

Understanding recovery of consciousness and elucidating its underlying mechanism is believed to be crucial in the field of basic neuroscience and medicine. Ideas such as the global neuronal workspace and the mesocircuit theory hypothesize that failure of recovery in conscious states coincide with loss of connectivity between subcortical and frontoparietal areas, a loss of the repertoire of functional networks states and metastable brain activation. We adopted a time-resolved functional connectivity framework to explore these ideas and assessed the repertoire of functional network states as a potential marker of consciousness and its potential ability to tell apart patients in the unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS). In addition, prediction of these functional network states by underlying hidden spatial patterns in the anatomical network, i.e. so-called eigenmodes, were supplemented as potential markers. By analysing time-resolved functional connectivity from fMRI data, we demonstrated a reduction of metastability and functional network repertoire in UWS compared to MCS patients. This was expressed in terms of diminished dwell times and loss of nonstationarity in the default mode network and fronto-parietal subcortical network in UWS compared to MCS patients. We further demonstrated that these findings co-occurred with a loss of dynamic interplay between structural eigenmodes and emerging time-resolved functional connectivity in UWS. These results are, amongst others, in support of the global neuronal workspace theory and the mesocircuit hypothesis, underpinning the role of time-resolved thalamo-cortical connections and metastability in the recovery of consciousness.

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Pain Perception in Disorder of Consciousness: A Scoping Review on Current Knowledge, Clinical Applications, and Future Perspective

Brain Sciences ◽

10.3390/brainsci11050665 ◽

2021 ◽

Vol 11 (5) ◽

pp. 665

Author(s):

Rocco Salvatore Calabrò ◽

Loris Pignolo ◽

Claudia Müller-Eising ◽

Antonino Naro

Keyword(s):

Functional Connectivity ◽

Scoping Review ◽

Pain Perception ◽

Current Knowledge ◽

Conscious Experience ◽

Minimally Conscious State ◽

Conscious State ◽

Future Perspective ◽

Disorder Of Consciousness ◽

Minimally Conscious

Pain perception in individuals with prolonged disorders of consciousness (PDOC) is still a matter of debate. Advanced neuroimaging studies suggest some cortical activations even in patients with unresponsive wakefulness syndrome (UWS) compared to those with a minimally conscious state (MCS). Therefore, pain perception has to be considered even in individuals with UWS. However, advanced neuroimaging assessment can be challenging to conduct, and its findings are sometimes difficult to be interpreted. Conversely, multichannel electroencephalography (EEG) and laser-evoked potentials (LEPs) can be carried out quickly and are more adaptable to the clinical needs. In this scoping review, we dealt with the neurophysiological basis underpinning pain in PDOC, pointing out how pain perception assessment in these individuals might help in reducing the misdiagnosis rate. The available literature data suggest that patients with UWS show a more severe functional connectivity breakdown among the pain-related brain areas compared to individuals in MCS, pointing out that pain perception increases with the level of consciousness. However, there are noteworthy exceptions, because some UWS patients show pain-related cortical activations that partially overlap those observed in MCS individuals. This suggests that some patients with UWS may have residual brain functional connectivity supporting the somatosensory, affective, and cognitive aspects of pain processing (i.e., a conscious experience of the unpleasantness of pain), rather than only being able to show autonomic responses to potentially harmful stimuli. Therefore, the significance of the neurophysiological approach to pain perception in PDOC seems to be clear, and despite some methodological caveats (including intensity of stimulation, multimodal paradigms, and active vs. passive stimulation protocols), remain to be solved. To summarize, an accurate clinical and neurophysiological assessment should always be performed for a better understanding of pain perception neurophysiological underpinnings, a more precise differential diagnosis at the level of individual cases as well as group comparisons, and patient-tailored management.

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Functional Brain Network Topology Discriminates between Patients with Minimally Conscious State and Unresponsive Wakefulness Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm8030306 ◽

2019 ◽

Vol 8 (3) ◽

pp. 306 ◽

Cited By ~ 12

Author(s):

Alberto Cacciola ◽

Antonino Naro ◽

Demetrio Milardi ◽

Alessia Bramanti ◽

Leonardo Malatacca ◽

...

Keyword(s):

Functional Connectivity ◽

Network Topology ◽

Minimally Conscious State ◽

Conscious State ◽

Clustering Coefficient ◽

Unresponsive Wakefulness Syndrome ◽

Topological Network ◽

Functional Brain Network ◽

Minimally Conscious ◽

Nodal Level

Consciousness arises from the functional interaction of multiple brain structures and their ability to integrate different complex patterns of internal communication. Although several studies demonstrated that the fronto-parietal and functional default mode networks play a key role in conscious processes, it is still not clear which topological network measures (that quantifies different features of whole-brain functional network organization) are altered in patients with disorders of consciousness. Herein, we investigate the functional connectivity of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) patients from a topological network perspective, by using resting-state EEG recording. Network-based statistical analysis reveals a subnetwork of decreased functional connectivity in UWS compared to in the MCS patients, mainly involving the interhemispheric fronto-parietal connectivity patterns. Network topological analysis reveals increased values of local-community-paradigm correlation, as well as higher clustering coefficient and local efficiency in UWS patients compared to in MCS patients. At the nodal level, the UWS patients showed altered functional topology in several limbic and temporo-parieto-occipital regions. Taken together, our results highlight (i) the involvement of the interhemispheric fronto-parietal functional connectivity in the pathophysiology of consciousness disorders and (ii) an aberrant connectome organization both at the network topology level and at the nodal level in UWS patients compared to in the MCS patients.

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Prolonged Disorders of Consciousness

Journal of the Korean Neurological Association ◽

10.17340/jkna.2020.1.2 ◽

2020 ◽

Vol 38 (1) ◽

pp. 9-15

Author(s):

Daeyoung Kim

Keyword(s):

Vegetative State ◽

Minimally Conscious State ◽

Conscious State ◽

Disorders Of Consciousness ◽

Assessment Tools ◽

Impaired Consciousness ◽

Transitional State ◽

Impaired Awareness ◽

Minimally Conscious ◽

Recovery Of Consciousness

Prolonged disorders of consciousness comprise a spectrum of impaired consciousness where arousal is preserved with impaired awareness, which last more than 4 weeks. Vegetative state is a prototype of the prolonged disorders of consciousness. A patient in the vegetative state has no signs of awareness. The minimally conscious state is characterized by inconsistent but reproducible signs of awareness and is regarded as a transitional state of recovery of consciousness. Differentiating patients in minimally conscious state from those in vegetative state is still challenging. Utilizing standardized neurobehavioral assessment tools could improve diagnostic accuracy. Recent advances in neuroimaging and electrophysiologic tools may aid the diagnosis and prognostication. Treatment for recovery of consciousness is still limited. More research on the diagnosis and treatment of prolonged disorders of consciousness is needed not only for improved care of patients with prolonged disorders of consciousness but also a greater understanding of human consciousness.

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Functional cortico-subcortical reorganization after complete hemispheric disconnection for intractable epilepsy

10.1101/707539 ◽

2019 ◽

Author(s):

Thomas Blauwblomme ◽

Athena Demertzi ◽

Jean-Marc Tacchela ◽

Ludovic Fillon ◽

Marie Bourgeois ◽

...

Keyword(s):

Functional Connectivity ◽

Right Hemisphere ◽

Intractable Epilepsy ◽

Minimally Conscious State ◽

Conscious State ◽

Subcortical Structures ◽

Drug Resistant Epilepsy ◽

Classification Probability ◽

The Right ◽

Minimally Conscious

AbstractHemispherotomy is a treatment for drug-resistant epilepsy with the whole hemisphere involved in seizure onset. As recovery mechanisms are still debated, we characterize functional reorganization with multimodal MRI in two children operated on the right hemisphere (RH). We found that interhemispheric functional connectivity was abolished in both patients. The healthy left hemispheres (LH) displayed focal hyperperfusion in motor and limbic areas, and preserved network-level organization. The disconnected RHs were hypoperfused despite sustained network-level organization. Functional connectivity was increased in the left thalamo-cortical loop and between the cerebelli. The classification probability of the RH corresponding to a minimally conscious state was smaller than for the LH. We conclude that after hemispherotomy, neurological rehabilitation is sustained by cortical disinhibition and reinforcement of connectivity driven by subcortical structures in the remaining hemisphere. Our results highlight the effect of vascularization on functional connectivity and raise inquiries about the conscious state of the isolated hemisphere.

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Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness

Brain Sciences ◽

10.3390/brainsci11030356 ◽

2021 ◽

Vol 11 (3) ◽

pp. 356

Author(s):

Anna Sontheimer ◽

Bénédicte Pontier ◽

Béatrice Claise ◽

Carine Chassain ◽

Jérôme Coste ◽

...

Keyword(s):

Functional Connectivity ◽

Minimally Conscious State ◽

Brain Structures ◽

Conscious State ◽

Disorders Of Consciousness ◽

Subcortical Structures ◽

Cortical Networks ◽

Chronic Disorders ◽

Minimally Conscious ◽

Chronic Disorders Of Consciousness

Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.

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Structural and functional connectivity of the ascending arousal network for prediction of outcome in patients with acute disorders of consciousness

Scientific Reports ◽

10.1038/s41598-021-98506-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cesar O. Enciso-Olivera ◽

Edgar G. Ordóñez-Rubiano ◽

Rosángela Casanova-Libreros ◽

Diana Rivera ◽

Carol J. Zarate-Ardila ◽

...

Keyword(s):

Functional Connectivity ◽

Diffusion Tensor ◽

Cardiopulmonary Arrest ◽

Univariate Analysis ◽

Minimally Conscious State ◽

Predictive Biomarkers ◽

Conscious State ◽

Blood Oxygen Level Dependent ◽

Imaging Biomarkers ◽

Minimally Conscious

AbstractTo determine the role of early acquisition of blood oxygen level-dependent (BOLD) signals and diffusion tensor imaging (DTI) for analysis of the connectivity of the ascending arousal network (AAN) in predicting neurological outcomes after acute traumatic brain injury (TBI), cardiopulmonary arrest (CPA), or stroke. A prospective analysis of 50 comatose patients was performed during their ICU stay. Image processing was conducted to assess structural and functional connectivity of the AAN. Outcomes were evaluated after 3 and 6 months. Nineteen patients (38%) had stroke, 18 (36%) CPA, and 13 (26%) TBI. Twenty-three patients were comatose (44%), 11 were in a minimally conscious state (20%), and 16 had unresponsive wakefulness syndrome (32%). Univariate analysis demonstrated that measurements of diffusivity, functional connectivity, and numbers of fibers in the gray matter, white matter, whole brain, midbrain reticular formation, and pontis oralis nucleus may serve as predictive biomarkers of outcome depending on the diagnosis. Multivariate analysis demonstrated a correlation of the predicted value and the real outcome for each separate diagnosis and for all the etiologies together. Findings suggest that the above imaging biomarkers may have a predictive role for the outcome of comatose patients after acute TBI, CPA, or stroke.

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Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2016.00257 ◽

2016 ◽

Vol 10 ◽

Cited By ~ 19

Author(s):

Carlo Cavaliere ◽

Marco Aiello ◽

Carol Di Perri ◽

Enrico Amico ◽

Charlotte Martial ◽

...

Keyword(s):

Functional Connectivity ◽

Minimally Conscious State ◽

Conscious State ◽

Minimally Conscious

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Structural and Functional Connectivity of the Ascending Arousal Network for Prediction of Outcome in Patients with Acute Disorders of Consciousness

10.21203/rs.3.rs-244211/v1 ◽

2021 ◽

Author(s):

Cesar O. Enciso-Olivera ◽

Edgar G. Ordóñez-Rubiano ◽

Rosángela Casanova-Libreros ◽

Diana Rivera ◽

Carol J. Zarate-Ardila ◽

...

Keyword(s):

Functional Connectivity ◽

Diffusion Tensor ◽

Cardiopulmonary Arrest ◽

Univariate Analysis ◽

Minimally Conscious State ◽

Predictive Biomarkers ◽

Conscious State ◽

Blood Oxygen Level Dependent ◽

Imaging Biomarkers ◽

Minimally Conscious

Abstract Object: To determine the role of early acquisition of blood oxygen level-dependent (BOLD) signals and diffusion tensor imaging (DTI) for analysis of the connectivity of the ascending arousal network (AAN) in predicting neurological outcomes after acute traumatic brain injury (TBI), cardiopulmonary arrest (CPA), or stroke.Methods: A prospective analysis of 50 comatose patients was performed during their ICU stay. Image processing was conducted to assess structural and functional connectivity of the AAN. Outcomes were evaluated after 3 and 6 months.Results: Nineteen patients (38%) had stroke, 18 (36%) CPA, and 13 (26%) TBI. Twenty-three patients were comatose (44%), 11 were in a minimally conscious state (20%), and 16 had unresponsive wakefulness syndrome (32%). Univariate analysis demonstrated that measurements of diffusivity, functional connectivity, and numbers of fibers in the gray matter, white matter, whole brain, midbrain reticular formation, and pontis oralis nucleus may serve as predictive biomarkers of outcome depending on the diagnosis. Multivariate analysis demonstrated a correlation of the predicted value and the real outcome for each separate diagnosis and for all the etiologies together.Conclusion: Findings suggest that the above imaging biomarkers may have a predictive role for the outcome of comatose patients after acute TBI, CPA, or stroke.

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