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Such neurofunctional evidence aligns with the disconnection between IC and frontotemporal regions in the SL patient. click here It has been suggested that the information carried by these external stream must first be integrated with stimulus saliency (Seeley et al., 2007; Singer et al., 2009) and hedonic value (Yin and Knowlton, 2006). Thus, disrupted connections in SL might compromise integrative contextual processing of external-internal signals via a fronto-insulo-temporal network including the IC as a critical hub. Damage to this network in the SL patient may underlie ongoing contextual embedding deficits (Mesulam and Mufson, 1982b; Amoruso et al., 2011; Ib��?ez and Manes, 2012; Ibanez et al., 2014) leading to impairments in external domains which were spared in the IL patient (see also Couto et al., 2013c). This conjecture might be tested in future studies (Limongi et al., 2014). Internal stream of interoceptive afferents The GSK1120212 research buy IL patient exhibited cardiac interoceptive deficits with preserved processing of external signals. Cardiac interoception is a basic modality of visceral perception that relies on an internal drive. It has proven to influence both homeostasis (Oppenheimer et al., 1991, 1992) and affective-cognitive domains (Singer et al., 2009; Garfinkel et al., 2013). Additionally, a wealth of neuroimaging and electrophysiological evidence shows the engagement of the right anterior IC in heartbeat awareness (Craig, 2002; Critchley et al., 2004; Pollatos et al., 2007b; Dunn et al., 2010) and the correlation of this activity with physical and cardio-dynamic variables (Pollatos et al., 2007a). These data point to a critical role of the right IC in sensing cardiac signatures, in line with the cardiac interoceptive impairment evinced by the IL patient. Additionally, the SL patient showed no interoceptive impairment, suggesting that right insula and not their frontotemporal connections running through the external capsule have lazabemide a specific role in this domain. This is supported by the fact that she outperformed frontal patients, which is to be expected, given that frontal damage affects larger amounts of cortex and white matter than subcortical lesions, and leads to executive deficits (Miller and Cummings, 2007) (see Supplementary Table 1 for comparison between frontal damage and healthy controls, IFS compared with SL: t