Recovery of consciousness after brain injury: a mesocircuit hypothesis

Abstract

Recovery of consciousness following severe brain injuries may occur over long time intervals. Importantly, evolving cognitive recovery can be strongly dissociated from motor recovery in some individuals, resulting in underestimation of cognitive capacities. Common mechanisms of cerebral dysfunction that arise at the neuronal population level may explain slow functional recoveries from severe brain injuries. This review proposes a "mesocircuit" model that predicts specific roles for different structural and dynamic changes that may occur gradually during recovery. Recent functional neuroimaging studies that operationally identify varying levels of awareness, memory and other higher brain functions in patients with no behavioral evidence of these cognitive capacities are discussed. Measuring evolving changes in underlying brain function and dynamics post-injury and post-treatment frames future investigative work.Recovery of conscious awareness and cognitive function following severe brain injuries can occur over surprisingly long time intervals of months, years and rarely decades [1][2][3][4][5]. Moreover, recovery of consciousness may significantly lag or be entirely dissociated from expressed motor behavior [6]. It is increasing recognized that very limited evidence of behavioral responsiveness at the bedside (or rarely, even a lack of any evidence) does not accurately predict underlying brain function. As a result, significant ambiguity can be present when encountering behavioral features consistent with clinical diagnoses ranging from vegetative state (no behavioral evidence of self or environmental awareness), minimally conscious state (at least some behavioral evidence of awareness), and up to and including patients in locked-in state (full consciousness with limited to no motor control). Importantly, bedside behavioral assessment cannot alone provide insight into likelihood of further recovery, avenues for specific intervention, or level of consciousness and cognitive capacity. The underlying mechanisms accounting for this wide variance in recovery patterns are unknown and provide a compelling scientific challenge for further understanding.This review considers aspects of current research aimed at understanding recovery of consciousness after brain injury. To best organize this advancing knowledge, a model at the neuronal population level is proposed that accounts for observed neuroimaging findings and response to treatments in the context of pathophysiological mechanisms associated with severe brain injury. This 'mesocircuit' model provides a parsimonious explanation of observations of recovery of consciousness after severe brain injuries and predicts several seemingly unrelated Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable...

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.…”

“…However, some patients may become unable to respond to stimuli despite still having conscious experiences 2, 3. This may happen because of motor or executive function impairments4, 5 and/or because of sensory disconnection from the environment 6. States of disconnected consciousness can occur in healthy subjects during dreaming7 and some forms of anesthesia,8 and may result from severe brain injury 9.…”

Synthetic consciousness: the distributed adaptive control perspective

“…B 371: 20150448 gate has been traced back to activity in core areas of the frontoparietal network using a fMRI analysis with healthy subjects (figure 4c), in particular, the middle and right superior frontal gyrus (Brodmann area 10, 11, yellow), right ACC (BA32, yellow) and left precuneus (BA7, orange) [180]. The latter area is part of the so-called default mode network [183], while the ACC is a central hub of executive control that is hypothesized to exert control over central thalamic nuclei [109], which in turn can switch selected cortical circuits on or off following the general TCD model described above [110,121]. Hence, this fMRI study reveals a circuit for selective prediction-based inhibitory filtering that the validation gate hypothesis proposes, which directly supports the idea that the fronto-parietal system can be considered the substrate of an autonomous consciousness memory system that can selectively couple and uncouple from sensory processing.…”

Can cranioplasty be effective in improving cognitive and motor function in patients with chronic disorders of consciousness? a case report

“…Therefore, many research topics are focused on developing of both biological and non-biological materials. Cranioplasty is performed mostly after traumatic brain injuries (10). Cancer surgery and the decompressive craniectomies are the leading causes of cranial defects.…”

“…Before performing a reconstructive cranioplasty, it is recommended to wait from 3 to 6 months in order to prevent the development of devitalized autograft or allograft infections (10). The "trephined" syndrome (or sinking skin flap, SSF) is due to a defect in the skull bone, and it is characterized by neurological symptoms such as seizures, severe headache, focal deficits and cognitive and behavioral changes.…”