Abstract
Recent research indicates prolonged disorders of consciousness (PDOC) result from structural and functional impairments to key cortical and subcortical networks, including the default mode network (DMN) and the anterior forebrain mesocircuit (AFM). However, the specific mechanisms which underpin such impairments remain unknown. It is known that disruptions in the striatal-pallidal pathway can result in the over inhibition of the thalamus and lack of excitation to the cortex that characterizes PDOC. Here, we used spectral dynamic causal modelling and parametric empirical Bayes on rs-fMRI data to assess whether DMN changes in PDOC are caused by disruptions in the AFM. PDOC patients displayed overall reduced coupling within the AFM, and specifically, decreased self-inhibition of the striatum, paired with reduced coupling from striatum to thalamus. This led to loss of inhibition from AFM to DMN, mostly driven by posterior areas including the precuneus and inferior parietal cortex. In turn, the DMN showed disruptions in self-inhibition of the precuneus and medial prefrontal cortex. Our results provide support for the anterior mesocircuit model at the subcortical level but highlight an inhibitory role for the AFM over the DMN, which is disrupted in PDOC.
Highlights
Recent years have seen an increasing interest in characterizing the neural bases underlying the lack of awareness in prolonged disorders of consciousness (PDOC)with neuroimaging techniques [1]
In terms of group differences, within the default mode network (DMN) we observe disruptions only in selfconnections of medial areas, with PDOC patients having decreased self-inhibition of the posterior cingulate cortex/precuneus (PCC) and increased self-inhibition of the medial prefrontal cortex (MPFC) compared to healthy controls
PDOC patients showed decreased coupling from both striata to the ipsilateral thalamus, which would result in an increased inhibitory tone
Summary
Recent years have seen an increasing interest in characterizing the neural bases underlying the (full or partial) lack of awareness in prolonged disorders of consciousness (PDOC)with neuroimaging techniques [1]. Recent years have seen an increasing interest in characterizing the neural bases underlying the (full or partial) lack of awareness in prolonged disorders of consciousness (PDOC). Much of the work to date has focused on structural and (resting-state) functional connectivity [3]. This has identified disconnections in long-range fronto-parietal networks, and the default mode network (DMN) [4,5,6,7,8,9,10,11,12,13], as a key contributor to the lack of awareness in PDOC. The DMN has a key role in the generation of self-referential processes and awareness [4,19], suggesting its deficits could explain the lack of self-awareness in PDOC
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