Charlotte Martial

Function-structure connectivity in patients with severe brain injury as measured by MRI-DWI and FDG-PET.

A vast body of literature exists showing functional and structural dysfunction within the brains of patients with disorders of consciousness. However, the function (fluorodeoxyglucose FDG‐PET metabolism)–structure (MRI‐diffusion‐weighted images; DWI) relationship and how it is affected in severely brain injured patients remains ill‐defined. FDG‐PET and MRI‐DWI in 25 severely brain injured patients (19 Disorders of Consciousness of which 7 unresponsive wakefulness syndrome, 12 minimally conscious; 6 emergence from minimally conscious state) and 25 healthy control subjects were acquired here. Default mode network (DMN) function–structure connectivity was assessed by fractional anisotropy (FA) and metabolic standardized uptake value (SUV). As expected, a profound decline in regional metabolism and white matter integrity was found in patients as compared with healthy subjects. Furthermore, a function–structure relationship was present in brain‐damaged patients between functional metabolism of inferior‐parietal, precuneus, and frontal regions and structural integrity of the frontal‐inferiorparietal, precuneus‐inferiorparietal, thalamo‐inferioparietal, and thalamofrontal tracts. When focusing on patients, a stronger relationship between structural integrity of thalamo‐inferiorparietal tracts and thalamic metabolism in patients who have emerged from the minimally conscious state as compared with patients with disorders of consciousness was found. The latter finding was in line with the mesocircuit hypothesis for the emergence of consciousness. The findings showed a positive function–structure relationship within most regions of the DMN. Hum Brain Mapp 37:3707–3720, 2016.

Functional Connectivity Substrates for tDCS Response in Minimally Conscious State Patients

Transcranial direct current stimulation (tDCS) is a non-invasive technique recently employed in disorders of consciousness, and determining a transitory recovery of signs of consciousness in almost half of minimally conscious state (MCS) patients. Although the rising evidences about its possible role in the treatment of many neurological and psychiatric conditions exist, no evidences exist about brain functional connectivity substrates underlying tDCS response. We retrospectively evaluated resting state functional Magnetic Resonance Imaging (fMRI) of 16 sub-acute and chronic MCS patients (6 tDCS responders) who successively received a single left dorsolateral prefrontal cortex (DLPFC) tDCS in a double-blind randomized cross-over trial. A seed-based approach for regions of left extrinsic control network (ECN) and default-mode network (DMN) was performed. tDCS responders showed an increased left intra-network connectivity for regions co-activated with left DLPFC, and significantly with left inferior frontal gyrus. Non-responders (NR) MCS patients showed an increased connectivity between left DLPFC and midline cortical structures, including anterior cingulate cortex and precuneus. Our findings suggest that a prior high connectivity with regions belonging to ECN can facilitate transitory recovery of consciousness in a subgroup of MCS patients that underwent tDCS treatment. Therefore, resting state-fMRI could be very valuable in detecting the neuronal conditions necessary for tDCS to improve behavior in MCS.

Exploration of Functional Connectivity During Preferred Music Stimulation in Patients with Disorders of Consciousness

Preferred music is a highly emotional and salient stimulus, which has previously been shown to increase the probability of auditory cognitive event-related responses in patients with disorders of consciousness (DOC). To further investigate whether and how music modifies the functional connectivity of the brain in DOC, five patients were assessed with both a classical functional connectivity scan (control condition), and a scan while they were exposed to their preferred music (music condition). Seed-based functional connectivity (left or right primary auditory cortex), and mean network connectivity of three networks linked to conscious sound perception were assessed. The auditory network showed stronger functional connectivity with the left precentral gyrus and the left dorsolateral prefrontal cortex during music as compared to the control condition. Furthermore, functional connectivity of the external network was enhanced during the music condition in the temporo-parietal junction. Although caution should be taken due to small sample size, these results suggest that preferred music exposure might have effects on patients auditory network (implied in rhythm and music perception) and on cerebral regions linked to autobiographical memory.

Prevalence of coma-recovery scale-revised signs of consciousness in patients in minimally conscious state

ABSTRACT Different behavioural signs of consciousness can distinguish patients with an unresponsive wakefulness syndrome from patients in minimally conscious state (MCS). The Coma Recovery Scale-Revised (CRS-R) is the most sensitive scale to differentiate the different altered states of consciousness and eleven items detect the MCS. The aim of this study is to document the prevalence of these items. We analysed behavioural assessments of 282 patients diagnosed in MCS based on the CRS-R. Results showed that some items are particularly frequent among patients in MCS, namely fixation, visual pursuit, and reproducible movement to command, which were observed in more than 50% of patients. These responses were also the most probably observed items when the patients only showed one sign of consciousness. On the other hand, some items were rarely or never observed alone, e.g., object localisation (reaching), object manipulation, intelligible verbalisation, and object recognition. The results also showed that limiting the CRS-R assessment to the five most frequently observed items (i.e., fixation, visual pursuit, reproducible movement to command, automatic motor response and localisation to noxious stimulation) detected 99% of the patients in MCS. If clinicians have only limited time to assess patients with disorders of consciousness, we suggest to evaluate at least these five items of the CRS-R.

Tracking dynamic interactions between structural and functional connectivity: a TMS/EEG-dMRI study

Transcranial magnetic stimulation (TMS) in combination with neuroimaging techniques allows to measure the effects of a direct perturbation of the brain. When coupled with high-density electroencephalography (TMS/hd-EEG), TMS pulses revealed electrophysiological signatures of different cortical modules in health and disease. However, the neural underpinnings of these signatures remain unclear. Here, by applying multimodal analyses of cortical response to TMS recordings and diffusion magnetic resonance imaging (dMRI) tractography, we investigated the relationship between functional and structural features of different cortical modules in a cohort of awake healthy volunteers. For each subject, we computed directed functional connectivity interactions between cortical areas from the source-reconstructed TMS/hd-EEG recordings and correlated them with the correspondent structural connectivity matrix extracted from dMRI tractography, in three different frequency bands (α, β, γ) and two sites of stimulation (left precuneus and left premotor). Each stimulated area appeared to mainly respond to TMS by being functionally elicited in specific frequency bands, that is, β for precuneus and γ for premotor. We also observed a temporary decrease in the whole-brain correlation between directed functional connectivity and structural connectivity after TMS in all frequency bands. Notably, when focusing on the stimulated areas only, we found that the structure-function correlation significantly increases over time in the premotor area controlateral to TMS. Our study points out the importance of taking into account the major role played by different cortical oscillations when investigating the mechanisms for integration and segregation of information in the human brain.

Regional brain volumetry and brain function in severely brain-injured patients: Regional Brain Volumetry and Function in DOC

The relationship between residual brain tissue in patients with disorders of consciousness (DOC) and the clinical condition is unclear. This observational study aimed to quantify gray (GM) and white matter (WM) atrophy in states of (altered) consciousness.

Objective assessment of visual pursuit in patients with disorders of consciousness: an exploratory study

Visual pursuit is a key marker of residual consciousness in patients with disorders of consciousness (DOC). Currently, its assessment relies on subjective clinical decisions. In this study, we explore the variability of such clinical assessments, and present an easy-to-use device composed of cameras and video processing algorithms that could help the clinician to improve the detection of visual pursuit in a clinical context. Visual pursuit was assessed by an experienced research neuropsychologist on 31 patients with DOC and on 23 healthy subjects, while the device was used to simultaneously record videos of both one eye and the mirror. These videos were then scored by three researchers: the experienced research neuropsychologist who did the clinical assessment, another experienced research neuropsychologist, and a neurologist. For each video, a consensus was decided between the three persons, and used as the gold standard of the presence or absence of visual pursuit. Almost 10% of the patients were misclassified at the bedside according to their consensus. An automatic classifier analyzed eye and mirror trajectories, and was able to identify patients and healthy subjects with visual pursuit, in total agreement with the consensus on video. In conclusion, our device can be used easily in patients with DOC while respecting the current guidelines of visual pursuit assessment. Our results suggest that our material and our classification method can identify patients with visual pursuit, as well as the three researchers based on video recordings can.

False memory susceptibility in coma survivors with and without a near-death experience

It has been postulated that memories of near-death experiences (NDEs) could be (at least in part) reconstructions based on experiencers’ (NDErs) previous knowledge and could be built as a result of the individual’s attempt to interpret the confusing experience. From the point of view of the experiencer, NDE memories are perceived as being unrivalled memories due to its associated rich phenomenology. However, the scientific literature devoted to the cognitive functioning of NDErs in general, and their memory performance in particular, is rather limited. This study examined NDErs’ susceptibility to false memories using the Deese–Roediger–McDermott (DRM) paradigm. We included 20 NDErs who reported having had their experience in the context of a life-threatening event (Greyson NDE scale total score ≥7/32) and 20 volunteers (matched for age, gender, education level, and time since brain insult) who reported a life-threatening event but without a NDE. Both groups were presented with DRM lists for a recall task during which they were asked to assign “Remember/Know/Guess” judgements to any recalled response. In addition, they were later asked to complete a post-recall test designed to obtain estimates of activation and monitoring of critical lures. Results demonstrated that NDErs and volunteers were equally likely to produce false memories, but that NDErs recalled them more frequently associated with compelling illusory recollection. Of particular interest, analyses of activation and monitoring estimates suggest that NDErs and volunteers groups were equally likely to think of critical lures, but source monitoring was less successful in NDErs compared to volunteers.

Clinical sub-categorization of minimally conscious state according to resting functional connectivity

Patients in minimally conscious state (MCS) have been subcategorized in MCS plus and MCS minus, based on command‐following, intelligible verbalization or intentional communication. We here aimed to better characterize the functional neuroanatomy of MCS based on this clinical subcategorization by means of resting state functional magnetic resonance imaging (fMRI). Resting state fMRI was acquired in 292 MCS patients and a seed‐based analysis was conducted on a convenience sample of 10 MCS plus patients, 9 MCS minus patients and 35 healthy subjects. We investigated the left and right frontoparietal networks (FPN), auditory network, default mode network (DMN), thalamocortical connectivity and DMN between‐network anticorrelations. We also employed an analysis based on regions of interest (ROI) to examine interhemispheric connectivity and investigated intergroup differences in gray/white matter volume by means of voxel‐based morphometry. We found a higher connectivity in MCS plus as compared to MCS minus in the left FPN, specifically between the left dorso‐lateral prefrontal cortex and left temporo‐occipital fusiform cortex. No differences between patient groups were observed in the auditory network, right FPN, DMN, thalamocortical and interhemispheric connectivity, between‐network anticorrelations and gray/white matter volume. Our preliminary group‐level results suggest that the clinical subcategorization of MCS may involve functional connectivity differences in a language‐related executive control network. MCS plus and minus patients are seemingly not differentiated by networks associated to auditory processing, perception of surroundings and internal awareness/self‐mentation, nor by interhemispheric integration and structural brain damage.

Multifaceted brain networks reconfiguration in disorders of consciousness uncovered by co-activation patterns

Given that recent research has shown that functional connectivity is not a static phenomenon, we aim to investigate the dynamic properties of the default mode networks (DMN) connectivity in patients with disorders of consciousness.