A role for the default mode network in the bases of disorders of consciousness

Abstract

Objective: Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity. Nevertheless, the integrity of the structural architecture supporting this network and its relation with the exhibited functional disconnections are very poorly understood. We investigated the structural connectivity and white matter integrity of the DMN in patients with disorders of consciousness of varying clinical severity. Methods: Fifty-two patients-19 in a vegetative state (VS), 27 in a minimally conscious state (MCS), and 6 emerging from a minimally conscious state (EMCS)-and 23 healthy volunteers participated in the study. Structural connectivity was assessed by means of probabilistic tractography, and the integrity of the resulting fibers was characterized by their mean fractional anisotropy values. Results: Patients showed significant impairments in all of the pathways connecting cortical regions within this network, as well as the pathway connecting the posterior cingulate cortex/precuneus with the thalamus, relative to the healthy volunteers. Moreover, the structural integrity of this pathway, as well as that of those connecting the posterior areas of the network, was correlated with the patients' behavioral signs for awareness, being higher in EMCS patients than those in the upper and lower ranges of the MCS patients, and lowest in VS patients. Interpretation: These results provide a possible neural substrate for the functional disconnection previously described in these patients, and reinforce the importance of the DMN in the genesis of awareness and the neural bases of its disorders. ANN NEUROL 2012;72:335-343 P atients with disorders of consciousness (DOC) show metabolic impairments and functional disconnections within corticocortical and thalamic-cortical areas of the default mode network (DMN) [1][2][3][4] to an extent that appears to correspond to clinical severity. 5 Thus, poorer functional connectivity is observed in vegetative state (VS) patients (who show no behavioral signs of awareness) 6 than in minimally conscious state (MCS) patients (who show intermittent behavioral signs of awareness). 7It is generally assumed that functional connectivity within intrinsic networks reflects structural connectivity. A plausible hypothesis, then, is that the reduced functional connectivity observed in the DMN of DOC patients reflects structural disconnections within this network, providing anatomical support for the description of these patients as suffering from ''disconnection syndromes.'' 8 However, the relationship between structure and function in the DMN is not straightforward. 9 It has View this article online at wileyonlinelibrary.com.

Signature of consciousness in the dynamics of resting-state brain activity

“…Although these findings show that part of the resting state brain activity, at least, indexes ongoing mental content, this conclusion appears to be in conflict with other studies showing that long-range resting-state functional connectivity persists even after loss of consciousness (LOC) due to general anesthesia (10,11) or in vegetative state (VS) patients (12,13). Although a small proportion of VS patients show a high degree of residual cognitive activity (14,15), this is unlikely to be the case during general anesthesia, suggesting that complex functional connectivity patterns can also arise purely as the result of a semirandom circulation of spontaneous neural activity along fixed anatomical routes.…”

Stratification of unresponsive patients by an independently validated index of brain complexity

“…Several factors, in addition to the extent of structural lesions, may affect the ability of the residual brain to engage in complex interactions. One possibility to be investigated is whether the integrity of some specific structures, such as the precuneus,20, 37 the thalamus,5, 38 and the claustrum,39, 40 or a critical level of overall anatomical connectivity41 may be key in sustaining such interactions. Another non–mutually exclusive possibility is that the complexity of residual thalamocortical networks may be reduced by functional imbalances leading to an excessive degree of neuronal bistability 42.…”

Structural brain injury in patients with disorders of consciousness: A voxel-based morphometry study

“…Injury to the thalamus and brainstem and extensive cerebral injury are among the most frequent observations in DOC in post-mortem [19][20][21][22][23][24][25][26] and MRI studies [25][26][27][28][29][30]. Equally little is known about brain atrophy secondary to the injury causing DOC [31,32].…”