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).