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. Poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. 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.

Motivated semantic control: Exploring the effects of extrinsic reward and self‐reference on semantic retrieval in semantic aphasia

“…Analysis was restricted to left hemisphere aspects of each network, such that it reflects a percentage of all voxels that could possibly be lesioned in an exclusively left‐hemisphere stroke sample. While right‐hemisphere aspects of these networks may be affected by disconnection (Souter, Wang, et al, 2021), this is beyond the scope of the current article. As seen in Figure 1e, patients showed the most damage to ‘Demands’ regions followed by ‘Semantic’ regions.…”

“…While there is evidence that semantic and domain‐general control are dissociable (Gonzalez Alam, Murphy, Smallwood, & Jefferies, 2018), samples of SA patients can show associations between performance on tests of these functions (Thompson et al, 2018). Semantic and executive control substrates are adjacent, such that damage to one system is frequently accompanied by damage to the other (Souter, Wang, et al, 2021; Wang et al, 2018). Accordingly, the current study revealed a positive correlation between semantic ability and performance on the Brixton Spatial Anticipation Test, a complex nonverbal executive test (Burgess & Shallice, 1997).…”

“…However, semantic control is dissociable from domain‐general control: the peak activations in fMRI studies that manipulate semantic control demands in healthy participants fall outside the multiple‐demand network (Gao et al, 2021; Noonan, Jefferies, Visser, & Lambon Ralph, 2013), and inhibitory stimulation of semantic control sites temporarily disrupts control‐demanding semantic tasks, but not demanding visual judgements (Whitney, Kirk, O’Sullivan, Lambon Ralph, & Jefferies, 2011). Moreover, while impaired semantic control is ubiquitous in SA, some but not all of these patients have general deficits of cognitive control: lesion‐symptom mapping shows that these semantic and non‐semantic control deficits are associated with different patterns of structural damage (Souter, Wang, et al, 2021). Given this distinction, there is a need to investigate the effects of motivation in tasks with high semantic control demands to establish if this domain can benefit from ‘gamification’ strategies to the same degree as other cognitive tasks.…”

How do valence and meaning interact? The contribution of semantic control

“…to allow for the integration of long-term abstract memory representations with goal states (Wang et al, 2020). This network, damaged in SA patients (Souter, Wang et al, 2021), may support the control of both meaning and emotion.…”

“…Individuals with SA have infarcts centred on these regions (Jefferies & Lambon Ralph, 2006). Furthermore, semantic deficits in SA are associated with structural disconnection between these left-hemisphere regions, while domain-general executive deficits are associated with more cross-hemisphere disconnection (Souter, Wang et al, 2021). Regions of the SCN are also implicated in tasks involving valenceincluding comparisons of lexical decision for valenced versus neutral words (Pauligk et al, 2019) and the resolution of conflict from valence incongruency (Gao et al, 2020).…”