The self and its resting state in consciousness: An investigation of the vegetative state

Abstract

Recent studies have demonstrated resting-state abnormalities in midline regions in vegetative state/unresponsive wakefulness syndrome and minimally conscious state patients. However, the functional implications of these resting-state abnormalities remain unclear. Recent findings in healthy subjects have revealed a close overlap between the neural substrate of self-referential processing and the resting-state activity in cortical midline regions. As such, we investigated task-related neural activity during active self-referential processing and various measures of resting-state activity in 11 patients with disorders of consciousness (DOC) and 12 healthy control subjects. Overall, the results revealed that DOC patients exhibited task-specific signal changes in anterior and posterior midline regions, including the perigenual anterior cingulate cortex (PACC) and posterior cingulate cortex (PCC). However, the degree of signal change was significantly lower in DOC patients compared with that in healthy subjects. Moreover, reduced signal differentiation in the PACC predicted the degree of consciousness in DOC patients. Importantly, the same midline regions (PACC and PCC) in DOC patients also exhibited severe abnormalities in the measures of resting-state activity, that is functional connectivity and the amplitude of low-frequency fluctuations. Taken together, our results provide the first evidence of neural abnormalities in both the self-referential processing and the resting state in midline regions in DOC patients. This novel finding has important implications for clinical utility and general understanding of the relationship between the self, the resting state, and consciousness.

Resting brain activity in disorders of consciousness

“…Finally, areas that correlated with CRS-R score (4 studies, 119 subjects and 36 foci) 26,29,31,40 included the left superior and middle frontal and cingulate gyri (table 2, figure 2B). Two studies using the ALFF methodology met our inclusion criteria 16,25 ; metaanalysis with and without ALFF studies yielded similar results (table 2). DISCUSSION The systematic review indicates widespread decreases in activity in bilateral cerebral cortices and thalamus when contrasting DOC patients with HCs.…”

“…55 Modifications in DMN structure and function have been reported in a range of neurologic and psychiatric disorders, 6 and converging evidence points to significant DMN alterations in patients with DOC including dimensional reductions and decreased intrinsic functional and anatomical connectivity. 16,18,19,23,25,30,34,40,56 In our systematic review and meta-analysis, the thalamus and PCC/precuneus complex appear to be most frequently affected in DOC, and activity or connectivity of the precuneus may correlate with the magnitude of impairment in consciousness. 29,33,40 The precuneus is the posterior region of the medial parietal cortex (Brodmann area 7) and represents one of the most highly connected and metabolically active regions of the brain 57,58 ; it is believed to be involved (with other nodes of the DMN) in self-referential tasks.…”

“…26,31,42 fMRI findings. Three studies using ALFF or ReHo showed that patients with DOC had decreased activity in the PCC, 16,21,25 precuneus, 21 thalamus, orbitofrontal cortex, and medial prefrontal cortex 16,25 structures that have been linked to the default mode network (DMN). A reciprocal increase in activity was noted in the supplementary motor area and the insula, sites linked to external awareness and task activation.…”

Disorders of consciousness after acquired brain injury: the state of the science

“…The minority of patients in VS who exhibited high-level activation often showed clinical signs of recovery at long-term follow-up. [80][81][82] Despite their potential value as prognostic markers, the diagnostic value and interpretation of activation fMRI studies in DOC in terms of the presence or absence of residual consciousness have remained controversial. Indeed, in the absence of a full understanding of the neural correlates of consciousness, deficient cortical activation to external stimuli does not necessarily prove the absence of consciousness.…”

Why Is the Distinction Between Neural Predispositions, Prerequisites, and Correlates of the Level of Consciousness Clinically Relevant?

“…1,7,[11][12][13] Because fMRI measures functional connectivity in the infraslow frequency range (0.001-0.1 Hz), 1 would assume these low frequencies to be central for the level of consciousness. 7 This is supported by a recent study by Huang et al, 16 who investigated not only functional connectivity but also variability, that is, temporal variance (SD) of resting state activity. He observed significantly reduced temporal variance in resting state activity in midline regions, such as perigenual anterior and PCC (as part of the DMN) in, especially, the infraslow frequency ranges (0.001-0.023 Hz; slow 5) in VS/UWS Hence, the degree of spontaneous change as index by temporal variance seems to be significantly reduced in VS/UWS.…”