Supplemental Material for The Rise and Fall of Semantic Cognition: Knowledge Accumulation in Later Life Is Offset by Declines in Semantic Control

Semantic cognition (use of acquired world knowledge to guide behavior) is critical in everyday life. Semantic cognition is often assumed to be preserved in later life, compensating for functional declines in other cognitive domains. However, aging research rarely considers age-related effects on nonverbal knowledge or on semantic control processes that regulate how knowledge is activated and used. We addressed this by conducting the most detailed assessment of semantic cognition across the adult lifespan to date, involving 537 adults aged between 20 and 91. Verbal semantic knowledge increased linearly across adulthood while nonverbal knowledge reached a plateau at age 50. In contrast, controlled semantic processing showed age-related decline, particularly in the ability to inhibit task-irrelevant semantic knowledge. These results indicate that semantic cognition is not uniformly preserved in old age: Though older people know more than young people, they are less able to use their knowledge flexibly in novel situations. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Built upon a wealth of neuroimaging, neurostimulation, and neuropsychology data, a recent proposal set forth a framework termed controlled semantic cognition (CSC) to account for how the brain underpins the ability to flexibly use semantic knowledge (Lambon Ralph et al., 2017; Nature Reviews Neuroscience). In CSC, the ‘semantic control’ system, underpinned predominantly by the prefrontal cortex, dynamically monitors and modulates the ‘semantic representation’ system that consists of a ‘hub’ (anterior temporal lobe, ATL) and multiple ‘spokes’ (modality-specific areas). CSC predicts that unfamiliar and exacting semantic tasks should intensify communication between the ‘control’ and ‘representation’ systems, relative to familiar and less taxing tasks. In the present study, we used functional magnetic resonance imaging (fMRI) to test this hypothesis. Participants paired unrelated concepts by canonical colours (a less accustomed task – e.g., pairing ketchup with fire-extinguishers due to both being red) or paired well-related concepts by semantic relationship (a typical task – e.g., ketchup is related to mustard). We found the ‘control’ system was more engaged by atypical than typical pairing. While both tasks activated the ATL ‘hub’, colour pairing additionally involved occipitotemporal ‘spoke’ regions abutting areas of hue perception. Furthermore, we uncovered a gradient along the ventral temporal cortex, transitioning from the caudal ‘spoke’ zones preferring canonical colour processing to the rostral ‘hub’ zones preferring semantic relationship. Functional connectivity also differed between the tasks: Compared with semantic pairing, colour pairing relied more upon the inferior frontal gyrus, a key node of the control system, driving enhanced connectivity with occipitotemporal ‘spoke’. Together, our findings characterise the interaction within the neural architecture of semantic cognition – the control system dynamically heightens its connectivity with relevant components of the representation system, in response to different semantic contents and difficulty levels.

The neural basis of semantic cognition: Converging evidence from neuropsychology, neuroimaging and TMS

We investigated semantic cognition in the logopenic variant of primary progressive aphasia, including (i) the status of verbal and non-verbal semantic performance; and (ii) whether the semantic deficit reflects impaired semantic control. Our a priori hypothesis that individuals with logopenic variant of primary progressive aphasia would exhibit semantic control impairments was motivated by the anatomical overlap between the temporoparietal atrophy typically associated with logopenic variant of primary progressive aphasia and lesions associated with post-stroke semantic aphasia and Wernicke's aphasia, which cause heteromodal semantic control impairments. We addressed the presence, type (semantic representation and semantic control; verbal and non-verbal), and progression of semantic deficits in logopenic variant of primary progressive aphasia. Since most people with logopenic variant of primary progressive aphasia have Alzheimer's disease pathology and are part of a broader multi-dimensional phenotype space encompassing Alzheimer's disease sub-types, we compared semantic performance in logopenic variant of primary progressive aphasia and typical amnestic Alzheimer's disease. Given the differences in lesion and atrophy patterns in semantic aphasia and Wernicke's aphasia versus semantic-dementia/semantic-variant primary progressive aphasia patients, our second aim was to examine atrophy patterns in people with logopenic variant of primary progressive aphasia and typical Alzheimer's disease compared to age-matched controls. Twenty-seven patients participated in the study. People were grouped into those meeting consensus criteria for logopenic variant of primary progressive aphasia (N = 10) and others who may have previously satisfied definitions of logopenic variant of primary progressive aphasia but had progressed with multi-domain cognitive impairments (herein referred to as 'logopenic variant of primary progressive aphasia+'; N = 8). People with typical amnestic Alzheimer's disease (N = 9) were relatively preserved across verbal and non-verbal semantic assessments. Logopenic variant of primary progressive aphasia patients were impaired on both verbal and non-verbal semantic tasks and their impairments showed the hallmark characteristics of a semantic control deficit. Logopenic variant of primary progressive aphasia and logopenic variant of primary progressive aphasia + patients showed effects of varying semantic control demands, positive cueing effects, and correlated performance between semantic and executive tasks. Whole-brain voxel-based morphometry, comparing each of the patient groups to age-matched controls, revealed significantly reduced grey and white matter in the bilateral hippocampi and lateral temporal regions in typical Alzheimer's disease patients. The logopenic variant of primary progressive aphasia group exhibited an asymmetric pattern of reduced grey and white matter intensity in the language-dominant left hemisphere, including a significant portion of the lateral and medial temporal lobe. Logopenic variant of primary progressive aphasia + patients demonstrated reduced grey and white matter in the left temporal lobe extending sub-cortically, anteriorly and posteriorly, as well as right temporal involvement. Our findings could aid diagnostic sub-typing of primary progressive aphasia by adopting semantic control features and offer improved clinical characterization of logopenic variant of primary progressive aphasia in the trajectory of semantic decline.

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.

Linking individual differences in semantic cognition to white matter microstructure

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.

Recent insights show that increased motivation can benefit executive control, but this effect has not been explored in relation to semantic cognition. Patients with deficits of controlled semantic retrieval in the context of semantic aphasia (SA) after stroke may benefit from this approach since ‘semantic control’ is considered an executive process. Deficits in this domain are partially distinct from the domain‐general deficits of cognitive control. We assessed the effect of both extrinsic and intrinsic motivation in healthy controls and SA patients. Experiment 1 manipulated extrinsic reward using high or low levels of points for correct responses during a semantic association task. Experiment 2 manipulated the intrinsic value of items using self‐reference, allocating pictures of items to the participant (‘self’) or researcher (‘other’) in a shopping game before participants retrieved their semantic associations. These experiments revealed that patients, but not controls, showed better performance when given an extrinsic reward, consistent with the view that increased external motivation may help ameliorate patients’ semantic control deficits. However, while self‐reference was associated with better episodic memory, there was no effect on semantic retrieval. We conclude that semantic control deficits can be reduced when extrinsic rewards are anticipated; this enhanced motivational state is expected to support proactive control, for example, through the maintenance of task representations. It may be possible to harness this modulatory impact of reward to combat the control demands of semantic tasks in SA patients.

Past work has demonstrated a link between semantic memory and verbal creativity. Yet, few studies have considered this relationship through the lens of the controlled semantic cognition account, which anticipates that multimodal concepts in long-term memory interact with semantic control processes to generate goal and context-appropriate patterns of retrieval. In particular, while the creativity literature has distinguished divergent and convergent aspects of creativity, little is known about their relationship with separable aspects of semantic control, or the semantic intrinsic functional architecture of the brain. We investigated whether tasks with greater reliance on controlled semantic retrieval (assessed through weak association) versus semantic selection (assessed through semantic feature matching) were differentially linked to divergent creativity (assessed with the unusual uses task; UUT) and convergent creativity (assessed with the remote associates task; RAT). Better performance on the RAT was linked to semantic selection, while stronger performance on UUT was linked to more efficient retrieval of weak associations. We also examined individual differences in the intrinsic functional architecture of the semantic system using resting-state fMRI. Greater coupling between the anterior temporal lobe (multimodal semantic store) and left inferior frontal gyrus (LIFG) (in the semantic control network) was linked to stronger convergent creativity. This pathway also correlated with semantic feature matching performance, but not the retrieval of weak associations. In contrast, better divergent creativity was linked to greater coupling between LIFG and language-related auditory-motor regions, and decoupling from the default mode and frontoparietal networks. These connections correlated with the retrieval of weak associations. Interestingly, whiledecouplingof LIFG with default mode and frontoparietal networks correlated with the retrieval of weak associations,couplingof LIFG with these networks correlated with semantic feature matching. These behavioural and neurocognitive dissociations show that semantic control and creativity are highly related yet multifaceted constructs that depend on the underlying intrinsic architecture of key sites related to semantic cognition.

To navigate the world, we store knowledge about relationships between concepts and retrieve this information flexibly to suit our goals. The semantic control network, comprising left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG), is thought to orchestrate this flexible retrieval by modulating sensory inputs. However, interactions between semantic control and input regions are not sufficiently understood. Moreover, pMTG's well-formed structural connections to IFG and visual cortex suggest it as a candidate region to integrate control and input processes. We used magnetoencephalography to investigate oscillatory dynamics during semantic decisions to pairs of words, when participants (both sexes) did or did not know the type of semantic relation between them. IFG showed increases and decreases in oscillatory activity to prior task knowledge, while pMTG only showed positive task knowledge effects. Furthermore, IFG provided sustained feedback to pMTG when task goals were known, while in the absence of goals this feedback was delayed until receiving bottom-up input from the second word. This goal-dependent feedback coincided with an earlier onset of feedforward signalling from visual cortex to pMTG, indicating rapid retrieval of task-relevant features. This pattern supports a model of semantic cognition in which pMTG integrates top-down control from IFG with bottom-up input from visual cortex to activate task-relevant semantic representations. Our findings elucidate the separate roles of anterior and posterior components of the semantic control network and reveal the spectro-temporal cascade of interactions between semantic and visual regions that underlie our ability to flexibly adapt cognition to the current goals.Significance Statement Using magnetoencephalography, we characterize the spectro-temporal dynamics that underlie our ability to flexibly adapt semantic cognition to the current context and goals. We find that semantic goals increase oscillatory activity in IFG and pMTG, and ultimately facilitate visual processing. Effective connectivity analyses reveal more sustained feedback from IFG to pMTG, and more rapid feedforward signalling from visual cortex to pMTG, resulting in rapid retrieval when semantic goals are known. Crucially, our findings suggest differential roles for the two semantic control regions: while IFG controls goal-dependent retrieval, pMTG integrates top-down information from IFG with bottom-up visual input.

Semantic cognition, i.e. processing of meaning is based on semantic representations and their controlled retrieval. Semantic control has been shown to be implemented in a network that consists of left inferior frontal (IFG), and anterior and posterior middle temporal gyri (a/pMTG). We aimed to disrupt semantic control processes with continuous theta burst stimulation (cTBS) over left IFG and pMTG and to study whether behavioral effects are moderated by induced alterations in resting-state functional connectivity. To this end, we applied real cTBS over left IFG and left pMTG as well as sham stimulation on 20 healthy participants in a within-subject design. Stimulation was followed by resting-state functional magnetic resonance imaging and a semantic priming paradigm. Resting-state functional connectivity of regions of interest in left IFG, pMTG and aMTG revealed highly interconnected left-lateralized fronto-temporal networks representing the semantic system. We did not find any significant direct modulation of either task performance or resting-state functional connectivity by effective cTBS. However, after sham cTBS, functional connectivity between IFG and pMTG correlated with task performance under high semantic control demands in the semantic priming paradigm. These findings provide evidence for the functional relevance of interactions between IFG and pMTG for semantic control processes. This interaction was functionally less relevant after cTBS over aIFG which might be interpretable in terms of an indirect disruptive effect of cTBS.

Background The ability to efficiently select specific aspects of our semantic representations that are relevant for current goals or the context is supported by semantic control processes (controlled semantic cognition framework). This semantic control component is impaired in patients with semantic aphasia, who have multimodal semantic impairment following left hemisphere stroke and are highly sensitive to the control demands of semantic tasks. However, relatively little is known about how this control deficit interacts with aspects of semantic representation. Aims Here we tested whether the relevance of semantic features can influence the demands of control resources in the selection of information within the semantic store in patients with semantic aphasia. Methods & Procedure Participants performed a feature selection task, where they were asked to indicate which of three features was semantically related to a given concept. Outcomes & Results We found that patients with semantic aphasia had a greater impairment on low relevance features, suggesting that the selection of target features with low relevance requires greater semantic control than target features with high relevance. Conclusions Our results confirm the necessity of control processes for the selection of aspects of conceptual knowledge that are only weakly activated within semantic storage when these are task-relevant. The study therefore highlights that semantic cognition emerges from the interaction of control and representational systems.

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Semantic cognition refers to the storage and appropriate use of knowledge acquired over the lifespan and underpins our everyday verbal and non-verbal behaviours. Successful semantic cognition requires representation of knowledge and control processes which ensure that currently relevant aspects of knowledge are retrieved and selected. Although these abilities have been widely studied in healthy young populations and semantically impaired patients, it is unclear how they change as a function of healthy ageing, especially for non-verbal semantic processing. Here, we addressed this issue by comparing the performance profiles of young and older people on a semantic knowledge task and a semantic control task, across verbal (word) and non-verbal (picture) versions. The results revealed distinct patterns of change during adulthood for semantic knowledge and semantic control. Older people performed better in both verbal and non-verbal knowledge tasks than young people. However, although the older group showed preserved controlled retrieval for verbal semantics, they demonstrated a specific impairment for non-verbal semantic control. These findings indicate that the effects of ageing on semantic cognition are more complex than previously assumed, and that input modality plays an important role in the shifting cognitive architecture of semantics in later life.