Limbic hyperconnectivity in the vegetative state

Abstract

Objective: To investigate functional connectivity between the default mode network (DMN) and other networks in disorders of consciousness. Methods:We analyzed MRI data from 11 patients in a vegetative state and 7 patients in a minimally conscious state along with age-and sex-matched healthy control subjects. MRI data analysis included nonlinear spatial normalization to compensate for disease-related anatomical distortions. We studied brain connectivity data from resting-state MRI temporal series, combining noninferential (independent component analysis) and inferential (seed-based general linear model) methods.Results: In DMN hypoconnectivity conditions, a patient's DMN functional connectivity shifts and paradoxically increases in limbic structures, including the orbitofrontal cortex, insula, hypothalamus, and the ventral tegmental area. Conclusions:Concurrently with DMN hypoconnectivity, we report limbic hyperconnectivity in patients in vegetative and minimally conscious states. This hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops, which, in turn, could disrupt normal patterns of connectivity. Patients in a vegetative state (VS) (also called "unresponsive wakefulness syndrome" 1 ) exhibit apparent dissociation between wakefulness and awareness, the 2 cardinal elements of consciousness.2 Onset of a VS, in which awareness is negatively affected, typically follows a coma and can be chronic and may evolve into a minimally conscious state (MCS).3 The current literature assumes a "passive" model of unawareness in both the VS and MCS, which is associated with widespread cerebral connectivity loss.In severe brain injury and postcomatose states, the default mode network (DMN), a major frontoparietal connectivity network of the resting brain connecting anterior and posterior cingulate with parietal and hippocampal regions, shows a breakdown of connectivity depending on the level of consciousness.4 Similar findings were found in healthy controls during altered states of consciousness such as anesthesia and sleep. 5The DMN 6 has been proposed as a correlate of the baseline cognitive state of a subject, and its link to memory and executive functions in normal and pathologic conditions suggests profound implications for consciousness. 7To date, interplay between the DMN and other brain networks has not been well explored in disorders of consciousness. We hypothesized that neural connectivity measured by resting-state From the Department of Neuroradiology (C.D.P., A.P., P.V.),

Resting brain activity in disorders of consciousness

“…DMN resting functional connectivity and size (number of voxels inside the DMN) were significantly reduced in patients with DOC compared with HCs. 16,18,19,21,23,24,30,33,40 Two of these studies exclusively evaluated patients with anoxic brain injury; both demonstrated decreased connectivity within the DMN. 19,30 Studies demonstrated a relationship between the degree of impaired consciousness and DMN connectivity, with greater reductions in connectivity in VS compared with MCS.…”

Functional neuroanatomy of disorders of consciousness

“…3). The effect was greater in patients with VS/UWS than in patients with MCS [37]. This limbic hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops which may disrupt normal patterns of connectivity, including synchronized neural activity in DMN.…”

“…This limbic hyperconnectivity may reflect the persistent engagement of residual neural activity in self-reinforcing neural loops which may disrupt normal patterns of connectivity, including synchronized neural activity in DMN. A loss of connectivity is, therefore, not necessarily the global hallmark of impaired consciousness but only an aspect of a multifaceted dysfunction in the architecture of brain connectivity [37]. Correspondingly, patients with complex partial seizures due to temporal lobe epilepsy associated with mesial sclerosis show increased regional synchronization in areas outside the DMN, such as the ipsilateral parahippocampal gyrus, midbrain, insula, corpus callosum, bilateral sensorimotor cortex, and frontoparietal subcortical structures [38].…”

“…Correlation from random effect (p b 0.01) and clustered-corrected (p b 0.05) results based on general linear model maps with seed region of interest comparing patients with VS/ UWS to healthy controls. Adapted from [37]. during propofol anesthesia, while a decrease of corticocortical connectivity was still observed, especially in backward connections between the frontal and parietal cortices [65].…”

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

“…195 The future integration of 'high-tech' brain measurements with existing clinical and behavioural methods of assessment should pave the way for new and innovative applications, and further elucidation of pathophysiological mechanisms could provide new opportunities for restoration of function through interventional neuromodulation. 46,196 These emerging technologies also bring new ethical challenges, and have important implications for medicolegal decision-making. 197 The novel neuroimaging and electrophysiological technologies await large-scale, multicentre validation studies.…”