Brain network connectivity and coma prognosis

Management of coma patients could soon undergo a major change, following study findings that the major consciousness deficit is related to breakdown in long-range neuronal communication supported by the precuneus (preCu) and posterior cingulate cortex (PCC).

Coma outcome appears to depend on a specific connectivity pattern in these networks, such that sparing of functional connectivity between the PCC and the medial prefrontal cortex (mPFC) is predictive, according to Stein Silva, MD, PhD, of Purpan University Teaching Hospital in Toulouse, France, and colleagues.

 

"The reorganization of PCC-centered, spontaneously synchronized, large-scale networks seems to be implicated in the loss of external and internal self-centered awareness observed during coma, largely independent of its etiology," the investigators reported online in Neurology. "The level of functional connectivity between PCC and mPFC appears to be related to patient neurologic outcome."

This finding supports previous work suggesting that connectivity measures may be used as an efficient diagnostic classifier for vegetative state and minimally conscious state. It could also pave the way for longitudinal studies, said Silva and colleagues.

To date, most of the studies that have analyzed the functional contribution of the PMC in patients with acquired disorders of consciousness have explored this large region as an indivisible structure, noted the investigators. There is a growing body of research, however, suggesting a structural and functional heterogeneity within this region, they pointed out.

Tract-tracing studies conducted in nonhuman primates as well as diffusion-tensor tractography in humans "have clearly identified structural connections between the ventral PCC and the medial temporal lobes, as well as connections from more dorsal PCC to the mPFC along the cingulum bundle," they added...

Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, regardless of the etiology of coma. "We observed at the same level, in both traumatic and anoxic patients, a significant disturbance in coactivation of distant regions from PCC, in particular with the midline forebrain areas," said Silva and colleagues.

The functional connectivity strength between PCC and the mPFC was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury, the investigators reported. On the other hand, no difference was found between the resting-state networks obtained from patients of traumatic versus anoxic origin at the defined statistical threshold (P<0.05, FDR-corrected)...

"We think that the prognostic value of the neuroimaging biomarkers obtained by this approach could significantly improve clinical decision-making processes following brain injury," he said. "Amazingly, this major impairment of connectivity seems to be affected in comatose patients independent of etiology (trauma or anoxia) and highlights the pivotal role of these neural networks in consciousness-related processes."

A network-based analysis of brain function in comatose patients could make it possible to develop new therapeutic tools aimed at assessing and modulating brain plasticity and facilitating neurological recovery, Silva said. "This would represent an enormous clinical shift from a current medical state-of-care, focused mainly on avoiding 'brain secondary insults' to a more personalized treatment, centered on brain functional 'network restoration,'" he told MedPage Today.

http://www.medpagetoday.com/Neurology/GeneralNeurology/54670