Hannah E. Thompson

Exploring the role of the posterior middle temporal gyrus in semantic cognition : Integration of anterior temporal lobe with executive processes

Making sense of the world around us depends upon selectively retrieving information relevant to our current goal or context. However, it is unclear whether selective semantic retrieval relies exclusively on general control mechanisms recruited in demanding non-semantic tasks, or instead on systems specialised for the control of meaning. One hypothesis is that the left posterior middle temporal gyrus (pMTG) is important in the controlled retrieval of semantic (not non-semantic) information; however this view remains controversial since a parallel literature links this site to event and relational semantics. In a functional neuroimaging study, we demonstrated that an area of pMTG implicated in semantic control by a recent meta-analysis was activated in a conjunction of (i) semantic association over size judgements and (ii) action over colour feature matching. Under these circumstances the same region showed functional coupling with the inferior frontal gyrus — another crucial site for semantic control. Structural and functional connectivity analyses demonstrated that this site is at the nexus of networks recruited in automatic semantic processing (the default mode network) and executively demanding tasks (the multiple-demand network). Moreover, in both task and task-free contexts, pMTG exhibited functional properties that were more similar to ventral parts of inferior frontal cortex, implicated in controlled semantic retrieval, than more dorsal inferior frontal sulcus, implicated in domain-general control. Finally, the pMTG region was functionally correlated at rest with other regions implicated in control-demanding semantic tasks, including inferior frontal gyrus and intraparietal sulcus. We suggest that pMTG may play a crucial role within a large-scale network that allows the integration of automatic retrieval in the default mode network with executively-demanding goal-oriented cognition, and that this could support our ability to understand actions and non-dominant semantic associations, allowing semantic retrieval to be ‘shaped’ to suit a task or context.

Automatic and Controlled Semantic Retrieval: TMS Reveals Distinct Contributions of Posterior Middle Temporal Gyrus and Angular Gyrus

Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the “default mode network” and “frontoparietal control system,” respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label “Alsatian” not “animal”). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval. SIGNIFICANCE STATEMENT We demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to assess different aspects of semantics (item identity and thematic matching), we tested two alternative theoretical accounts. Neither site showed the pattern expected for a “thematic hub” (i.e., a site storing associations between concepts) since stimulation disrupted both tasks. Instead, the data indicated that pMTG contributes to the controlled retrieval of conceptual knowledge, while AG is critical for the efficient automatic retrieval of specific semantic information.

Varieties of semantic ‘access’ deficit in Wernicke’s aphasia and semantic aphasia

Comprehension deficits are common in both Wernicke’s aphasia and semantic aphasia. Thompson et al. compare these groups of patients on a task in which related items are repeatedly presented, increasing semantic competition across repetitions. Both groups show semantic impairment, but only individuals with prefrontal damage show harmful effects of repetition.

The role of the right hemisphere in semantic control: A case-series comparison of right and left hemisphere stroke.

Semantic control processes guide conceptual retrieval so that we are able to focus on non-dominant associations and features when these are required for the task or context, yet the neural basis of semantic control is not fully understood. Neuroimaging studies have emphasised the role of left inferior frontal gyrus (IFG) in controlled retrieval, while neuropsychological investigations of semantic control deficits have almost exclusively focussed on patients with left-sided damage (e.g., patients with semantic aphasia, SA). Nevertheless, activation in fMRI during demanding semantic tasks typically extends to right IFG. To investigate the role of the right hemisphere (RH) in semantic control, we compared nine RH stroke patients with 21 left-hemisphere SA patients, 11 mild SA cases and 12 healthy, aged-matched controls on semantic and executive tasks, plus experimental tasks that manipulated semantic control in paradigms particularly sensitive to RH damage. RH patients had executive deficits to parallel SA patients but they performed well on standard semantic tests. Nevertheless, multimodal semantic control deficits were found in experimental tasks involving facial emotions and the ‘summation’ of meaning across multiple items. On these tasks, RH patients showed effects similar to those in SA cases – multimodal deficits that were sensitive to distractor strength and cues and miscues, plus increasingly poor performance in cyclical matching tasks which repeatedly probed the same set of concepts. Thus, despite striking differences in single-item comprehension, evidence presented here suggests semantic control is bilateral, and disruption of this component of semantic cognition can be seen following damage to either hemisphere.

Task-based and resting-state fMRI reveal compensatory network changes following damage to left inferior frontal gyrus

Damage to left inferior prefrontal cortex in stroke aphasia is associated with semantic deficits reflecting poor control over conceptual retrieval, as opposed to loss of knowledge. However, little is known about how functional recruitment within the semantic network changes in patients with executive-semantic deficits. The current study acquired functional magnetic resonance imaging (fMRI) data from 14 patients with semantic aphasia, who had difficulty with flexible semantic retrieval following left prefrontal damage, and 16 healthy age-matched controls, allowing us to examine activation and connectivity in the semantic network. We examined neural activity while participants listened to spoken sentences that varied in their levels of lexical ambiguity and during rest. We found group differences in two regions thought to be good candidates for functional compensation: ventral anterior temporal lobe (vATL), which is strongly implicated in comprehension, and posterior middle temporal gyrus (pMTG), which is hypothesized to work together with left inferior prefrontal cortex to support controlled aspects of semantic retrieval. The patients recruited both of these sites more than controls in response to meaningful sentences. Subsequent analysis identified that, in control participants, the recruitment of pMTG to ambiguous sentences was inversely related to functional coupling between pMTG and anterior superior temporal gyrus (aSTG) at rest, while the patients showed the opposite pattern. Moreover, stronger connectivity between pMTG and aSTG in patients was associated with better performance on a test of verbal semantic association, suggesting that this temporal lobe connection supports comprehension in the face of damage to left inferior prefrontal cortex. These results characterize network changes in patients with executive-semantic deficits and converge with studies of healthy participants in providing evidence for a distributed system underpinning semantic control that includes pMTG in addition to left inferior prefrontal cortex.

Semantic control deficits impair understanding of thematic relationships more than object identity

ABSTRACT Recent work has suggested a potential link between the neurocognitive mechanisms supporting the retrieval of events and thematic associations (i.e., knowledge about how concepts relate in a meaningful context) and semantic control processes that support the capacity to shape retrieval to suit the circumstances. Thematic associations and events are inherently flexible: the meaning of an item changes depending on the context (for example, lamp goes with reading, bicycle and police). Control processes might stabilise weak yet currently‐relevant interpretations during event understanding. In contrast, semantic retrieval for objects (to understand what items are, and the categories they belong to) is potentially constrained by sensory‐motor features (e.g., bright light) that change less across contexts. Semantic control and event understanding produce overlapping patterns of activation in healthy participants in left prefrontal and temporoparietal regions, but the potential causal link between these aspects of semantic cognition has not been examined. We predict that event understanding relies on semantic control, due to associations being necessarily context‐dependent and variable. We tested this hypothesis in two ways: (i) by examining thematic associations and object identity in patients with semantic aphasia, who have well‐documented deficits of semantic control following left frontoparietal stroke and (ii) using the same tasks in healthy controls under dual‐task conditions that depleted the capacity for cognitive control. The patients were impaired on both identity and thematic matching tasks, and they showed particular difficulty on non‐dominant thematic associations which required greater control over semantic retrieval. Healthy participants showed the same pattern under conditions of divided attention. These findings support the view that semantic control is necessary for organising and constraining the retrieval of thematic associations. HIGHLIGHTSThis manuscript compares performance on thematic and identity tasks.We predict that thematic tasks will require additional semantic‐executive mechanisms.Semantic Aphasia patients show particular deficits in the thematic task in relation to the identity task, particularly weak associations.Healthy subjects, in an executively demanding dual‐task, showed a similar pattern to the patients.These results support the Controlled Semantic Cognition framework, and provide evidence against the dual hub account.

The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction

Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., 2015, Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal ‘hub’ in combination with modality‐specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time‐ and task‐appropriate behaviour. Executive–semantic goal representations, largely supported by executive regions such as frontal and parietal cortex, are thought to allow the generation of non‐dominant aspects of knowledge when these are appropriate for the task or context. Semantic aphasia (SA) patients have executive–semantic deficits, and these are correlated with general executive impairment. If the CSC proposal is correct, patients with executive impairment should not only exhibit impaired semantic cognition, but should also show characteristics that align with those observed in SA. This possibility remains largely untested, as patients selected on the basis that they show executive impairment (i.e., with ‘dysexecutive syndrome’) have not been extensively tested on tasks tapping semantic control and have not been previously compared with SA cases. We explored conceptual processing in 12 patients showing symptoms consistent with dysexecutive syndrome (DYS) and 24 SA patients, using a range of multimodal semantic assessments which manipulated control demands. Patients with executive impairments, despite not being selected to show semantic impairments, nevertheless showed parallel patterns to SA cases. They showed strong effects of distractor strength, cues and miscues, and probe–target distance, plus minimal effects of word frequency on comprehension (unlike semantic dementia patients with degradation of conceptual knowledge). This supports a component process account of semantic cognition in which retrieval is shaped by control processes, and confirms that deficits in SA patients reflect difficulty controlling semantic retrieval.

When comprehension elicits incomprehension: Deterioration of semantic categorisation in the absence of stimulus repetition

Repetition improves retrieval from memory; however, under some circumstances, it can also impair performance. Separate literatures have investigated this phenomenon, including studies showing subjective loss of meaning following ‘semantic satiation’, slowed naming and categorisation when semantically related items are repeated and semantic ‘access deficits’ in aphasia. Such effects have been variously explained in terms of habituation of repeatedly accessed representations, increased interference from strongly activated competitors and long-term weight changes reflecting the suppression of non-targets on earlier trials (i.e., retrieval-induced forgetting). While studies of semantic satiation involve massed repetition of individual items, competition and weight changes at the conceptual level should elicit declining comprehension for non-repeated items: this pattern has been demonstrated for picture naming but effects in categorisation are less clear. We developed a paced serial semantic task (PSST), in which participants identified category members among distracters. Performance in healthy young adults deteriorated with ongoing retrieval for non-repeated words belonging to functional categories (e.g., picnic), taxonomic categories (e.g., animal) and feature-based categories (e.g., colour red – ‘tomato’, ‘post box’). This decline was greatest at fast presentation speeds (when there was less time to overcome competition/inhibition) and for strongly associated targets (which may have accrued more inhibition to facilitate earlier target categorisation). Deteriorating performance was also seen across words and pictures, consistent with a conceptual locus. We observed a release from deteriorating categorisation following a switch to a new category, demonstrating that this was not a general effect of time on task. Patients with semantic aphasia, who have deficient semantic control, maintained their performance throughout the categories, unlike younger adults: this finding is hard to reconcile with accounts of declining performance that propose a build-up of competition, since the patients should have had greater difficulty resolving such competition. These results instead suggest that declining performance on our goal-driven categorisation task was linked to the use of a controlled retrieval strategy by healthy young adults. Patients may not have inhibited related non-target knowledge to facilitate initial categorisation like younger volunteers, and consequently they were less vulnerable to declining comprehension in this paradigm. Together, these results demonstrate circumstances which produce declines in continuous categorisation in healthy adults.

Reduced neural 'effort' after naming treatment in anomia

One of the most revolutionary scientific concepts for patients with stroke is that of neuroplasticity. Reorganization of brain structure and function allows for measurable behavioural improvements, even years post-stroke (Hope et al., 2017). Yet understanding the process by which regions change functional responsibility, and which patterns of reorganization are most advantageous to stroke outcome, has proven challenging. These issues have been studied extensively with reference to aphasia. This research has produced conflicting results concerning the role of perilesional and contralesional regions in language recovery. For example, there is an ongoing debate concerning the extent to which perilesional and contralesional regions play a facilitatory role, and whether some contralesional regions may in fact impede performance (Geranmayeh et al., 2014). In this issue of Brain, Nardo and co-workers present an exciting advance on previous work by using functional imaging not only to consider therapeutic outcomes, but also to study the processes that support therapeutic improvements (Nardo et al., 2017).