Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia

Abstract

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here, we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left-hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. In contrast, poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. Little insight was gained from functional disconnection symptom mapping. These results demonstrate that while left-lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

Ventral and dorsal aspects of the inferior frontal-occipital fasciculus support verbal semantic access and visually-guided behavioural control

“…In line with this functional anatomy, IFOF has long been associated with language and semantic cognition (Almairac et al, 2015;Binder et al, 2009;Han et al, 2013;Sierpowska et al, 2019). Stimulation of IFOF during neurosurgery elicits semantic errors in picture naming tasks (Duffau et al, 2008(Duffau et al, , 2005, while damage to IFOF is associated with semantic impairment (Han et al, 2013;Souter et al, 2022;Surbeck et al, 2020).…”

“…Since IFOF connects posterior temporal to prefrontal regions, it is likely to play a critical role in the controlled application of knowledge during semantic cognition (Duffau et al, 2013;Giampiccolo and Duffau, 2022;Nugiel et al, 2016). Patients with poor control of semantic cognition in the context of stroke aphasia have highly consistent damage to IFOF and ILF despite highly variable lesions affecting left inferior prefrontal or posterior temporal areas (Souter et al, 2022). Moreover, for phonological and semantic verbal uency tasks with high executive demands, IFOF integrity is correlated with performance (Almairac et al, 2015;Nugiel et al, 2016).…”

Longitudinal prediction of motor dysfunction after stroke: a disconnectome study

“…The disconnection analysis (Conrad et al, 2022;Hajhajate et al, 2022;Forkel et al 2022); Souter et al, 2022;Silvestri et al, 2022;Sperber et al, 2022) is different from the lesion network symptom mapping methods that estimate from a normative dataset the functional connectivity impaired by a lesion Bowren et al, 2022;Cototvio et al, 2022). Thus, prediction studies may benefit from the redirection of the focus in clinical research from lesion localisation analysis to the analysis of the disconnections where remote alterations of a focal damage to distant regions can also be considered as a contributor to a network of structures and functions.…”

Brain disconnections refine the relationship between brain structure and function

“…Second, are articles that indirectly measure disconnections in the brain by inferring disruptions based on imaging from large groups of healthy individuals with high-quality imaging or brain atlases (Thiebaut de Schotten et al 2015;Boes et al 2015). Articles in this category include: (Souter et al 2022;Conrad et al 2022;Sperber et al 2022;Hajhajate et al 2022;Tomaiuolo et al 2022;Dulyan et al 2022;Yeager et al 2022). As with any new field, there are many opportunities to refine and improve the methods of disconnectome mapping.…”

“…Further, when using indirect methods, there are many open questions, like the relative value of structural versus functional connectivity (Reber et al 2021;Salvalaggio et al 2020;Thiebaut de Schotten et al 2014), how these different modalities can be combined (Bowren et al 2022), and how much the specific normative datasets used influences the results. The third grouping of articles directly addresses these important methodological questions (Silvestri et al 2022;Cotovio et al 2022;Souter et al 2022;Sperber et al 2022).…”