Restoration of thalamo‐cortical connectivity after brain injury: recovery of consciousness, complex behavior, or passage of time?

Abstract

In 2000, a landmark case report described the concurrent restoration of consciousness and thalamo-frontal connectivity after severe brain injury (Laureys et al., 2000). Being a single case however, this study could not disambiguate whether the result was specific to the restoration of consciousness per se as opposed to the return of complex cognitive function in general or simply the temporal evolution of post-injury pathophysiological events. To test whether the restoration of thalamo-cortical connectivity is specific to consciousness, 20 moderate-to-severe brain injury patients (from a recruited sample of 42) underwent resting-state functional magnetic resonance imaging within a week after injury and again six months later. As described in the single case report, we find thalamo-frontal connectivity to be increased at the chronic, compared with the acute, time-point. The increased connectivity was independent of whether patients had already recovered consciousness prior to the first assessment or whether they recovered consciousness in-between the two. Conversely, we did find an association between restoration of thalamofrontal connectivity and the return of complex cognitive function. While we did replicate the findings of Laureys et al. (2000), our data suggests that the restoration of thalamo-frontal connectivity is not as tightly linked to the reemergence of consciousness per se. However, the degree to which the return of connectivity is linked to the return of complex cognitive function, or to the evolution of other time-dependent post-injury mechanisms, remains to be understood. K E Y W O R D Sbrain injury, thalamus, coma, disorders of consciousness, large-scale network connectivity

Conventional Structural Magnetic Resonance Imaging in Differentiating Chronic Disorders of Consciousness

“…Monti et al demonstrated with fMRI that a small proportion of patients with DOC had brain activation while performing some mental-imagery tasks, suggesting some awareness and cognition [15]. Another study demonstrated an association between restoration of thalamo-frontal connectivity based on resting state fMRI data and the recovery of cognitive function [17]. Furthermore, functional connectivity analysis in another resting state fMRI study [18] showed that the default mode network, frontoparietal, salience, auditory, sensorimotor, and visual networks had a high discriminative capacity (>80%) for separating patients with MCS and UWS.…”

Imaging biomarkers of posttraumatic epileptogenesis

“…[23][24][25][26] Imaging biomarkers are appealing because they are based on noninvasive procedures that are routinely performed as part of a patient's workup protocol and are capable of detecting patterns across the whole brain that may indicate or precede epileptogenesis. [23][24][25][26] Imaging biomarkers are appealing because they are based on noninvasive procedures that are routinely performed as part of a patient's workup protocol and are capable of detecting patterns across the whole brain that may indicate or precede epileptogenesis.…”

“…Several studies have attempted to identify the progression of injury with longitudinal imaging acquisition, 25,26,53,[91][92][93] but the need for imaging at multiple time points in association with PTE remains unmet. To adequately assess the utility of imaging biomarkers and secure a mechanistic understanding of PTE, the progression of various imaging phenotypes across sequential imaging sessions must be understood.…”

“…Advancements in neuroimaging have greatly advanced PTE research by allowing researchers to identify global and subtle structural and functional alterations that follow injury and coincide with subsequent epilepsy diagnosis. [23][24][25][26] Imaging biomarkers are appealing because they are based on noninvasive procedures that are routinely performed as part of a patient's workup protocol and are capable of detecting patterns across the whole brain that may indicate or precede epileptogenesis. Brain imaging is especially important in TBI, where injuries are spatially heterogenous, 9 involve both cortical and subcortical structures, 9 and vary between patients with similar clinical severity of injury.…”

“…To adequately assess the utility of imaging biomarkers and secure a mechanistic understanding of PTE, the progression of various imaging phenotypes across sequential imaging sessions must be understood. Several studies have attempted to identify the progression of injury with longitudinal imaging acquisition, 25,26,53,[91][92][93] but the need for imaging at multiple time points in association with PTE remains unmet.…”