Relationship between the anterior forebrain mesocircuit and the default mode network in the structural bases of disorders of consciousness

Abstract

The specific neural bases of disorders of consciousness (DOC) are still not well understood. Some studies have suggested that functional and structural impairments in the default mode network may play a role in explaining these disorders. In contrast, others have proposed that dysfunctions in the anterior forebrain mesocircuit involving striatum, globus pallidus, and thalamus may be the main underlying mechanism. Here, we provide the first report of structural integrity of fiber tracts connecting the nodes of the mesocircuit and the default mode network in 8 patients with DOC. We found evidence of significant damage to subcortico-cortical and cortico-cortical fibers, which were more severe in vegetative state patients and correlated with clinical severity as determined by Coma Recovery Scale-Revised (CRS-R) scores. In contrast, fiber tracts interconnecting subcortical nodes were not significantly impaired. Lastly, we found significant damage in all fiber tracts connecting the precuneus with cortical and subcortical areas. Our results suggest a strong relationship between the default mode network - and most importantly the precuneus - and the anterior forebrain mesocircuit in the neural basis of the DOC.

Keywords: Anterior forebrain mesocircuit; Basal ganglia; DTI; Default mode network; Disorders of consciousness; Hypoxic–ischemic brain injury; Minimally conscious state; Precuneus; Thalamus; Tractography; Traumatic brain injury; Vegetative state; White matter.

Fig. 1

Group probability maps of reconstructed tracts in healthy controls. Maps are thresholded at presence in at least 25% of healthy subjects. Regions of interest used for the tractography reconstruction are shown in blue. Images displayed in Montreal Neurological Institute standard stereotaxic space, and coordinates are provided for each slice.

Fig. 2

Fractional anisotropy of composite fiber tracts in DOC patients and healthy controls. Middle line is median, lower box bound first quartile, upper box bound third quartile, whiskers 95% C.I., open circles outliers from C.I. Group main effect *p < 0.05, **p < 0.01. Sub: subcortical, Cor: cortical.

Fig. 3

Spearman correlations of CRS-R scores and composite fiber tract FA values for DOC patients. Sub-Cor: subcortico-cortical composite fiber tract, Cor-Cor: cortico-cortical composite fiber tract.

Fig. 4

Individual tract analysis comparing FA values between DOC patients and healthy controls. Blue solid lines represent fiber tracts with no significant differences. Red dashed lines represent fiber tracts with significantly lower FA in DOC patients relative to healthy controls. Green dashed lines represent fiber tracts with significantly higher FA in DOC patients relative to controls. Weight of line represents level of significance of difference between DOC patients and healthy controls. P value calculated by univariate analysis of covariance with whole brain white matter FA as covariate. DOC: disorders of consciousness, HC: healthy control, FMC: frontal medial cortex, DLPFC: dorsolateral prefrontal cortex, Stri: striatum, GP: globus pallidus, Tha: thalamus, TPJ: temporoparietal junction, PCu: precuneus, L: left hemisphere, R: right hemisphere. PCu–FMC tract is considered midline.