3.1. A pattern of structural dysconnectivity suggestive of
AM and mesocircuit disruption
In light of converging TMS-EEG and fMRI evidence of consciousness in the
face of a severe impairment of motor initiation and execution, the
lesional pattern was re-analyzed on a finer grain to support a diagnosis
within the AM spectrum. To this aim, we performed a second-level sMRI
analysis utilizing the Network Modification Tool (NeMo) (Kuceyeskiet al. , 2013). Based on a large reference set of tractography
data, NeMo associates changes in WM integrity to expected changes in GM
connectivity. This allows the characterization of the effects of lesions
on cortical-subcortical connectivity and thus the assessment of the
structural underpinnings of AM. NeMo does not require tractography and
the most disconnected GM regions, were visualized through an
easy-to-use, flexible toolbox (SPIDER-NET, Software Package Ideal for
Deriving Enhanced Representations of Brain NETworks) for connectogram
generation (Coluzzi et al. , 2022). Such representation
highlighted a significant disconnection between frontal regions and
subcortical ventral basal ganglia, dorsal striatum and thalamus as well
as between bilateral frontal areas (Figure 6). Interestingly, this
pattern of dysconnectivity involving both frontal and anterior basal
forebrain not only was consistent with an AM diagnosis but also matched
the model of deafferentation proposed with the mesocircuit hypothesis
(Schiff, 2010; Fridman et al. , 2014; Edlow et al. , 2021).