Multimodal study of default‐mode network integrity in disorders of consciousness

Abstract

Objective: Understanding residual brain function in disorders of consciousness poses extraordinary challenges, and imaging examinations are needed to complement clinical assessment. The default-mode network (DMN) is known to be dysfunctional, although correlation with level of consciousness remains controversial. We investigated DMN activity with resting-state functional magnetic resonance imaging (rs-fMRI), alongside its structural and metabolic integrity, aiming to elucidate the corresponding associations with clinical assessment. Methods: We enrolled 119 consecutive patients: 72 in a vegetative state/unresponsive wakefulness state (VS/UWS), 36 in a minimally conscious state (MCS), and 11 with severe disability. All underwent structural MRI and rs-fMRI, and a subset also underwent 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Data were analyzed with manual and automatic approaches, in relation to diagnosis and clinical score. Results: Excluding the quartile with largest head movement, DMN activity was decreased in VS/UWS compared to MCS, and correlated with clinical score. Independent-component and seed-based analyses provided similar results, although the latter and their combination were most informative. Structural MRI and FDG-PET were less sensitive to head movement and had better diagnostic accuracy than rs-fMRI only when all cases were included. rs-fMRI indicated relatively preserved DMN activity in a small subset of VS/UWS patients, 2 of whom evolved to MCS. The integrity of the left hemisphere appears to be predictive of a better clinical status. Interpretation: rs-fMRI of the DMN is sensitive to clinical severity. The effect is consistent across data analysis approaches, but heavily dependent on head movement. rs-fMRI could be informative in detecting residual DMN activity for those patients who remain relatively still during scanning and whose diagnosis is uncertain.

Olfactory discrimination in disorders of consciousness: A new sniff protocol

“…Finally, the fMRI study of these patients is quite difficult due to their head movement. However, the percentage of excluded patients in this pilot research was in line with previous studies, as reported in a relatively recent work which showed that 62 patients out of 119 presented large head movements during the resting state fMRI(Rosazza et al, 2016).Moreover, the four patients excluded showed movement related mainly to the noise of the MRI rather than to olfactory stimuli.An interesting issue for possible future research could be the correlation between the ODP results and the quantitative analysis of the nasal airflow (e.g., the airflow resistance or the volume of air exhaled through the nostrils). After the development of a normative values table, this analysis could have an important impact in clinical practice because it could orient clinicians to analyze problems related to the respiratory system that, otherwise, remain without a diagnosis in these patients.…”

“…Importantly, ammonia was chosen in relation to its higher commerce availability more than other substances (e.g., CO 2 ) and also for the confidence of the clinicians with its use (ammonia was used for several years during the clinical assessment with the Coma Near Coma scale (Rosazza et al, 2016), an assessment tool that was commonly used for the evaluation of persons with DOC before the CRS-R development). Ammonia threshold was determined considering previous studies (Geisler & Murphy, 2000;Petrova, Diamond, Schuster, & Dalton, 2008).…”

Degrees of functional connectome abnormality in disorders of consciousness

“…The MCS and UWS groups did not show significant differences in this analysis. Although in previous studies these groups were reported to be different in certain features of functional connectivity in specific resting state networks (Demertzi et al, ; Rosazza et al, ), the effects and the relative importance of the networks are sensitive to the type of analysis applied. The present comparison suggests that a simple measure of connectivity equal to the mean correlation of ROIs in a network can capture the differences between healthy subjects and DOC patients, but not between MCS and UWS.…”

“…The observed effects in the Visual and Somatomotor networks are in line with the fact that in the recently developed ConnICA method (Amico et al, ), the so‐called VIS‐SM (visual and sensory motor) connectome component was one of the two traits (along with the fronto‐parietal‐DMN) that showed significant associations with clinical measures of awareness. The default network has probably been the most frequently reported system having abnormalities in DOC patients (Rosazza et al, ; Soddu et al, ; Vanhaudenhuyse et al, ). However, in accordance with recent reports (Demertzi et al, ), the above findings suggest that disorders of consciousness are associated with a massive disruption of most of the brain's functional networks, with only a moderate, and possibly subject‐dependent, specificity to particular systems.…”

“…Much of the research on functional connectivity in DOC has focused on the disruption of specific resting‐state networks, especially the default mode network (DMN) (Heine et al, ; Rosazza et al, ; Vanhaudenhuyse et al, ). Within the DMN, the posterior cingulate cortex/precuneus (PCC/PCU) regions were identified as particularly important.…”