Recovery of consciousness has been associated with connectivity in the frontal cortex and parietal regions modulated by the thalamus. To examine this model and to relate alterations to deficits in cognitive functioning and conscious processing, we investigated topological network properties in patients with chronic disorders of consciousness recovered from coma. Resting state fMRI data of 34 patients with unresponsive wakefulness syndrome and 25 in minimally conscious state were compared to 28 healthy controls. We investigated global and local network characteristics. Additionally, behavioral measures were correlated with the local metrics of 28 regions within the fronto-parietal network and the thalamus. In chronic disorders of consciousness, modularity at the global level was reduced suggesting a disturbance in the optimal balance between segregation and integration. Moreover, network properties were altered in several regions which are associated with conscious processing (particularly, in medial parietal, and frontal regions, as well as in the thalamus). Between minimally conscious and unconscious patients the local efficiency of medial parietal regions differed. Alterations in the thalamus were particularly evident in non-conscious patients. Most of the regions affected in patients with impaired consciousness belong to the so-called 'rich club' of highly interconnected central nodes. Disturbances in their topological characteristics have severe impact on information integration and are reflected in deficits in cognitive functioning probably leading to a total breakdown of consciousness.

Diagnosis of patients with a disorder of consciousness is very challenging. Previous studies investigating resting state networks demonstrate that 2 main features of the so-called default mode network (DMN), metabolism and functional connectivity, are impaired in patients with a disorder of consciousness. However, task-induced deactivation – a third main feature of the DMN – has not been explored in a group of patients. Deactivation of the DMN is supposed to reflect interruptions of introspective processes. Seventeen patients with unresponsive wakefulness syndrome (UWS, former vegetative state), 8 patients in minimally conscious state (MCS), and 25 healthy controls were investigated with functional magnetic resonance imaging during a passive sentence listening task. Results show that deactivation in medial regions is reduced in MCS and absent in UWS patients compared to healthy controls. Moreover, behavioral scores assessing the level of consciousness correlate with deactivation in patients. On single-subject level, all control subjects but only 2 patients in MCS and 6 with UWS exposed deactivation. Interestingly, all patients who deactivated during speech processing (except for one) showed activation in left frontal regions which are associated with conscious processing. Our results indicate that deactivation of the DMN can be associated with the level of consciousness by selecting those who are able to interrupt ongoing introspective processes. In consequence, deactivation of the DMN may function as a marker of consciousness.

The intrinsic connectivity of the default mode network has been associated with the level of consciousness in patients with severe brain injury. Especially medial parietal regions are considered to be highly involved in impaired consciousness. To better understand what aspect of this intrinsic architecture is linked to consciousness, we applied spectral dynamic causal modeling to assess effective connectivity within the default mode network in patients with disorders of consciousness. We included 12 controls, 12 patients in minimally conscious state and 13 in vegetative state in this study. For each subject, we first defined the four key regions of the default mode network employing a subject-specific independent component analysis approach. The resulting regions were then included as nodes in a spectral dynamic causal modeling analysis in order to assess how the causal interactions across these regions as well as the characteristics of neuronal fluctuations change with the level of consciousness. The resulting pattern of interaction in controls identified the posterior cingulate cortex as the main driven hub with positive afferent but negative efferent connections. In patients, this pattern appears to be disrupted. Moreover, the vegetative state patients exhibit significantly reduced self-inhibition and increased oscillations in the posterior cingulate cortex compared to minimally conscious state and controls. Finally, the degree of self-inhibition and strength of oscillation in this region is correlated with the level of consciousness. These findings indicate that the equilibrium between excitatory connectivity towards posterior cingulate cortex and its feedback projections is a key aspect of the relationship between alterations in consciousness after severe brain injury and the intrinsic functional architecture of the default mode network. This impairment might be principally due to the disruption of the mechanisms underlying self-inhibition and neuronal oscillations in the posterior cingulate cortex.

The promotion of recovery in patients who have entered a disorder of consciousness (DOC; e.g., coma or vegetative states) following severe brain injury remains an enduring medical challenge despite an ever-growing scientific understanding of these conditions. Indeed, recent work has consistently implicated altered cortical modulation by deep brain structures (e.g., the thalamus and the basal ganglia) following brain damage in the arising of, and recovery from, DOCs. The (re)emergence of low-intensity focused ultrasound (LIFU) neuromodulation may provide a means to selectively modulate the activity of deep brain structures noninvasively for the study and treatment of DOCs. This technique is unique in its combination of relatively high spatial precision and noninvasive implementation. Given the consistent implication of the thalamus in DOCs and prior results inducing behavioral recovery through invasive thalamic stimulation, here we applied ultrasound to the central thalamus in 11 acute DOC patients, measured behavioral responsiveness before and after sonication, and applied functional MRI during sonication. With respect to behavioral responsiveness, we observed significant recovery in the week following thalamic LIFU compared with baseline. With respect to functional imaging, we found decreased BOLD signals in the frontal cortex and basal ganglia during LIFU compared with baseline. In addition, we also found a relationship between altered connectivity of the sonicated thalamus and the degree of recovery observed post-LIFU.

Menstrual cycle dependent changes have been reported for a variety of functions, including cognition, attention, emotion, inhibition and perception. For several of these functions an effect of hormonal contraceptives has also been discussed. Cognitive, attentional, emotional, inhibitory and perceptual functions have been linked to distinct intrinsic connectivity networks during the resting state. However, changes in resting state connectivity across the menstrual cycle phase and due to hormonal contraceptive use have only been investigated in two selected networks and without controlling for the type of hormonal contraceptives. In the present study, we demonstrate menstrual cycle and hormonal contraceptive-dependent changes in several intrinsic connectivity networks, including networks that have been related to emotion processing, olfaction, audition, vision, coordination and two lateralized fronto-parietal networks related to a variety of cognitive functions. These changes parallel behavioral changes in the functions associated with these networks. Changes in connectivity and changes in behavior occur during the same cycle phases. Furthermore, hormonal contraceptive dependent effects were observed in the same networks and same target sites as menstrual cycle related changes and were dependent on the androgenicity of the progestin component contained in the hormonal contraceptive.

An increasing amount of studies suggest that brain dynamics measured with resting-state functional magnetic resonance imaging (fMRI) are related to the state of consciousness. However, the challenge of investigating neuronal correlates of consciousness is the confounding interference between (recovery of) consciousness and behavioral responsiveness. To address this issue, and validate the interpretation of prior work linking brain dynamics and consciousness, we performed a longitudinal fMRI study in patients recovering from coma. Patients were assessed twice, 6 months apart, and assigned to one of two groups. One group included patients who were unconscious at the first assessment but regained consciousness and improved behavioral responsiveness by the second assessment. The other group included patients who were already conscious and improved only behavioral responsiveness. While the two groups were matched in terms of the average increase in behavioral responsiveness, only one group experienced a categorical change in their state of consciousness allowing us to partially dissociate consciousness and behavioral responsiveness. We find the variance in network metrics to be systematically different across states of consciousness, both within and across groups. Specifically, at the first assessment, conscious patients exhibited significantly greater variance in network metrics than unconscious patients, a difference that disappeared once all patients had recovered consciousness. Furthermore, we find a significant increase in dynamics for patients who regained consciousness over time, but not for patients who only improved responsiveness. These findings suggest that changes in brain dynamics are indeed linked to the state of consciousness and not just to a general level of behavioral responsiveness.