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

2021 ◽  
Vol 11 (3) ◽  
pp. 356
Author(s):  
Anna Sontheimer ◽  
Bénédicte Pontier ◽  
Béatrice Claise ◽  
Carine Chassain ◽  
Jérôme Coste ◽  
...  

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.

2021 ◽  
Vol 70 (5) ◽  
pp. 23-36
Author(s):  
Ekaterina A. Kondratyeva ◽  
Alina O. Ivanova ◽  
Maria I. Yarmolinskaya ◽  
Elena G. Potyomkina ◽  
Natalya V. Dryagina ◽  
...  

BACKGROUND: Consciousness is the state of being awake and aware of oneself and the environment. The disorders of consciousness result from pathologies that impair awareness. The development of effective comprehensive personalized interventions contributing to the recovery of consciousness in patients with chronic disorders of consciousness is one of the most pressing and challenging tasks in modern rehabilitation. AIM: The aim of this study was to understand structural problems of the pituitary gland, blood levels of gonadotropins and melatonin as well as brain damage markers in the blood and cerebrospinal fluid in patients with chronic disorders of consciousness and to analyze the levels of the above markers among different groups of patients depending on the level of impaired consciousness. MATERIALS AND METHODS: We examined 61 chronic disorders of consciousness patients and identified three groups depending on the level of consciousness including 24 patients with unresponsive wakefulness syndrome, 24 patients with a minus minimally conscious state, and 13 patients with minimally conscious state plus. We performed magnetic resonance imaging of chiasmatic-sellar region and determined blood serum levels of follicle-stimulating and luteinizing hormones and melatonin, as well as urinary level of 6-sulfatoxymelatonin and the content of brain derived neurotrophic factor (BDNF), apoptosis antigen (APO-1), FasL, glutamate, and S100 protein in the blood serum and cerebrospinal fluid. RESULTS: The patients were examined in the age ranging from 15 to 61 years old. Patient groups were homogeneous by the level of consciousness in terms of age and duration of chronic disorders of consciousness by the time of examination. The patients did not differ in the pituitary volume regardless of the level of consciousness. No significant differences were found between the groups with different levels of consciousness when studying the levels of melatonin in the blood serum and its metabolite in the urine. A peak in melatonin secretion was detected at 3 a.m. in 54.5 % of the patients, which can be considered as a favorable prognostic marker for further recovery of consciousness. Hypogonadotropic ovarian failure was found in 34 % of the patients, with normogonadotropic ovarian failure in the remaining patients. Serum APO-1 and BDNF levels were significantly higher in patients with minimally conscious state relative to those with unresponsive wakefulness syndrome. Significantly lower levels of glutamate in the cerebrospinal fluid were detected in women with unresponsive wakefulness syndrome compared to patients with minimally conscious state. CONCLUSIONS: Further in-depth examination and accumulation of data on patients with chronic disorders of consciousness may provide an opportunity to identify highly informative markers for predicting outcomes and to develop new effective approaches to rehabilitation of consciousness in this category of patients.


2021 ◽  
Author(s):  
Benyan Luo ◽  
Jie Yu ◽  
Qisheng Cheng ◽  
Fangping He ◽  
Fanxia Meng ◽  
...  

Abstract Intestinal microbiotas regulate brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding intestinal microbiome of patients in chronic disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the difference of intestinal microbiome and short-chain fatty acids (SCFAs) among the patients in vegetative state (VS), minimally conscious state (MCS) and emerged from minimally conscious state (EMCS), as well as the influence of antibiotics on these patients, 16S rRNA sequencing and targeted lipidomics were performed on their fecal samples and EEG signals analysis were used to evaluate their brain function. Our results showed that intestinal microbiome among the three groups differed greatly and some microbial community with its production of SCFAs were reduced in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs along with attenuated brain functional connectivity were observed in MCS patients treated with antibiotics compared to those received no antibiotic treatment, but not in the other pairwise comparisons. Finally, three genera level of microbiota, Faecailbacterium, Enterococcus and Methanobrevibacter, were considered as potential biomarkers to distinguish patients in MCS from VS with high accuracy both in the discovery cohorts and validation cohorts. Together, our findings improved the understanding of patients with chronic DoC from intestinal microbiome and provided a new reference for therapeutic targets exploration.


2019 ◽  
Author(s):  
Thomas Blauwblomme ◽  
Athena Demertzi ◽  
Jean-Marc Tacchela ◽  
Ludovic Fillon ◽  
Marie Bourgeois ◽  
...  

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.


2019 ◽  
Vol 9 (5) ◽  
pp. 123
Author(s):  
Elena I. Kremneva ◽  
Liudmila A. Legostaeva ◽  
Sofya N. Morozova ◽  
Dmitry V. Sergeev ◽  
Dmitry O. Sinitsyn ◽  
...  

Diagnostic accuracy of different chronic disorders of consciousness (DOC) can be affected by the false negative errors in up to 40% cases. In the present study, we aimed to investigate the feasibility of a non-Gaussian diffusion approach in chronic DOC and to estimate a sensitivity of diffusion kurtosis imaging (DKI) metrics for the differentiation of vegetative state/unresponsive wakefulness syndrome (VS/UWS) and minimally conscious state (MCS) from a healthy brain state. We acquired diffusion MRI data from 18 patients in chronic DOC (11 VS/UWS, 7 MCS) and 14 healthy controls. A quantitative comparison of the diffusion metrics for grey (GM) and white (WM) matter between the controls and patient group showed a significant (p < 0.05) difference in supratentorial WM and GM for all evaluated diffusion metrics, as well as for brainstem, corpus callosum, and thalamus. An intra-subject VS/UWS and MCS group comparison showed only kurtosis metrics and fractional anisotropy differences using tract-based spatial statistics, owing mainly to macrostructural differences on most severely lesioned hemispheres. As a result, we demonstrated an ability of DKI metrics to localise and detect changes in both WM and GM and showed their capability in order to distinguish patients with a different level of consciousness.


Author(s):  
Antonino Naro ◽  
Maria Grazia Maggio ◽  
Antonino Leo ◽  
Rocco Salvatore Calabrò

The deterioration of specific topological network measures that quantify different features of whole-brain functional network organization can be considered a marker for awareness impairment. Such topological measures reflect the functional interactions of multiple brain structures, which support the integration of different sensorimotor information subtending awareness. However, conventional, single-layer, graph theoretical analysis (GTA)-based approaches cannot always reliably differentiate patients with Disorders of Consciousness (DoC). Using multiplex and multilayer network analyses of frequency-specific and area-specific networks, we investigated functional connectivity during resting-state EEG in 17 patients with Unresponsive Wakefulness Syndrome (UWS) and 15 with Minimally Conscious State (MCS). Multiplex and multilayer network metrics indicated the deterioration and heterogeneity of functional networks and, particularly, the frontal-parietal (FP), as the discriminant between patients with MCS and UWS. These data were not appreciable when considering each individual frequency-specific network. The distinctive properties of multiplex/multilayer network metrics and individual frequency-specific network metrics further suggest the value of integrating the networks as opposed to analyzing frequency-specific network metrics one at a time. The hub vulnerability of these regions was positively correlated with the behavioral responsiveness, thus strengthening the clinically-based differential diagnosis. Therefore, it may be beneficial to adopt both multiplex and multilayer network analyses when expanding the conventional GTA-based analyses in the differential diagnosis of patients with DoC. Multiplex analysis differentiated patients at a group level, whereas the multilayer analysis offered complementary information to differentiate patients with DoC individually. Although further studies are necessary to confirm our preliminary findings, these results contribute to the issue of DoC differential diagnosis and may help in guiding patient-tailored management.


2018 ◽  
Vol 8 (8) ◽  
pp. 144 ◽  
Author(s):  
Sofya Morozova ◽  
Elena Kremneva ◽  
Dmitry Sergeev ◽  
Dmitry Sinitsyn ◽  
Lyudmila Legostaeva ◽  
...  

Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS.


2020 ◽  
Vol 26 (6) ◽  
pp. 301-309
Author(s):  
Zahra Imani-Goghary ◽  
Mahnaz Ghaljeh

Background: Management of a patient with chronic disorders of consciousness is a long-term and stressful situation for family caregivers. Aims: The aim of this study was to describe the experiences of family caregivers of patients with chronic disorders of consciousness. Methods: Purposeful sampling was used, data were collected through semi-structured, in-depth interviews at participants' homes. Data were analysed using qualitative content analysis. Findings: Results indicated that family caregivers of patients with chronic disorders of consciousness face many difficulties in providing care to vegetative state (VS) and minimally conscious state (MCS) patients; they experience it as a challenging type of care, which influences their mental health. Conclusion: Family caregivers are faced with many challenges because of the high burden of care, round-the-clock concern, taking care of an alive but unresponsive patient without receiving enough support. They experience mental and inner turmoil because of social isolation and dealing with contradictory feelings in their daily life.


Author(s):  
Mihail Kanarskii ◽  
Julia Yu. Nekrasova ◽  
Irina Vorob'eva ◽  
Il'ya Borisov

Among the possible points of therapeutic action and predicting the outcome in patients in a vegetative state and minimally conscious state, the analysis of circadian rhythms, such as the sleep-wake cycle, melatonin secretion, temperature trends, heart rate, and blood pressure, attracts more and more attention. In this review, we analyzed studies on circadian rhythms in patients with chronic disorders of consciousness, assessed the possible limitations of standard methods, proposed a concept for the development of an assessment of the sleep-wake cycle, and assessed the role of exogenous factors that are likely to be involved in the disturbance of circadian rhythms in intensive care units. Based on the results of the study, we came to the conclusion that for the full realization of the rehabilitation potential, it is necessary to develop methods for assessing circadian rhythms based on a multicomponent approach, including 24-hour monitoring using actigraphy for more accurate identification of the rest -activity cycle, video monitoring of the orofascial area to increase the reliability of oculographic assessment and revealing hidden patterns, analysis of the temperature curve, the level of melatonin, TSH, cortisol, as well as exogenous factors. It is necessary to use the information obtained for therapeutic, prognostic, diagnostic and rehabilitation purposes


2021 ◽  
Vol 11 (5) ◽  
pp. 665
Author(s):  
Rocco Salvatore Calabrò ◽  
Loris Pignolo ◽  
Claudia Müller-Eising ◽  
Antonino Naro

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.


2019 ◽  
Vol 8 (3) ◽  
pp. 306 ◽  
Author(s):  
Alberto Cacciola ◽  
Antonino Naro ◽  
Demetrio Milardi ◽  
Alessia Bramanti ◽  
Leonardo Malatacca ◽  
...  

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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