Going beyond Inferior Prefrontal Involvement in Semantic Control: Evidence for the Additional Contribution of Dorsal Angular Gyrus and Posterior Middle Temporal Cortex

Assigning meaning to words, sounds, and objects requires stored conceptual knowledge plus executive mechanisms that shape semantic retrieval according to the task or context. Despite the essential role of control in semantic cognition, its neural basis remains unclear. Neuroimaging and patient research has emphasized the importance of left inferior frontal gyrus (IFG)—however, impaired semantic control can also follow left temporoparietal lesions, suggesting that this function may be underpinned by a large-scale cortical network. We used repetitive transcranial magnetic stimulation in healthy volunteers to disrupt processing within 2 potential sites in this network—IFG and posterior middle temporal cortex. Stimulation of both sites selectively disrupted executively demanding semantic judgments: semantic decisions based on strong automatic associations were unaffected. Performance was also unchanged in nonsemantic tasks—irrespective of their executive demands—and following stimulation of a control site. These results reveal that an extended network of prefrontal and posterior temporal regions underpins semantic control.

Semantic control allows us to focus semantic activation on currently relevant aspects of knowledge, even in the face of competition or when the required information is weakly encoded. Diverse cortical regions, including left prefrontal and posterior temporal cortex, are implicated in semantic control, however; the relative contribution of these regions is unclear. For the first time, we compared semantic aphasia (SA) patients with damage restricted to temporoparietal cortex (TPC; N=8) to patients with infarcts encompassing prefrontal cortex (PF+; N=22), to determine if prefrontal lesions are necessary for semantic control deficits. These SA groups were also compared with semantic dementia (SD; N=10), characterised by degraded semantic representations. We asked whether TPC cases with semantic impairment show controlled retrieval deficits equivalent to PF+cases or conceptual degradation similar to patients with SD. Independent of lesion location, the SA subgroups showed similarities, whereas SD patients showed a qualitatively distinct semantic impairment. Relative to SD, both TPC and PF+SA subgroups: (1) showed few correlations in performance across tasks with differing control demands, but a strong relationship between tasks of similar difficulty; (2) exhibited attenuated effects of lexical frequency and concept familiarity, (3) showed evidence of poor semantic regulation in their verbal output - performance on picture naming was substantially improved when provided with a phonological cue, and (4) showed effects of control demands, such as retrieval difficulty, which were equivalent in severity across TPC and PF+groups. These findings show that semantic impairment in SA is underpinned by damage to a distributed semantic control network, instantiated across anterior and posterior cortical areas.

The left prefrontal cortex supports inhibitory processing during semantic memory retrieval

Event Abstract Back to Event Imaging of semantic association judgements reveals areas of functional disruption and compensation remote from lesion in chronic Wernicke's aphasia Holly Robson1*, Timothy D. Griffiths2 and Anna M. Woollams3 1 University of Reading, United Kingdom 2 Newcastle University, United Kingdom 3 University of Manchester, United Kingdom The essence of comprehension is the transfer of sensory into semantic information. A wealth of neuroimaging studies in the typical population has revealed the complexity of this process in which the recruited neural network differs depending on the cognitive requirements of the task, e.g., the stimulus modality or nature of the semantic judgement. The result has been the identification of an extensive array of bilateral frontal, temporal, parietal, occipital and medial structures which have been implicated in the comprehension process (Binder & Desai, 2011). Accordingly, stroke damage to numerous different branches of the vascular network can lead to comprehension deficits, but at the same time the very extent of this network may open up multiple routes for compensation/reorganisation. This study investigated patterns of neural network recruitment during verbal and non-verbal comprehension in Wernicke’s aphasia (WA), a condition which entails disruption to phonological input processing and activation of semantic knowledge due to damage to the left superior and middle temporal lobe and inferior parietal lobe. Method. Nine participants with chronic WA and ten age matched neurotypical controls participated in an fMRI study using 3T gradient-echo imaging. The block-design paradigm consisted of a semantic association task in written word and picture modalities, presented in blocks of animals and tools. These were contrasted against control association tasks involving false fonts (word modality control) and patterns (picture modality control). GLM analyses were performed and results interpreted at a threshold of p<0.005 for clusters>15 voxels. Results. Neurotypical participants showed greater activity in semantic association tasks than control tasks in the bilateral posterior ventral visual stream (occipital lobe and posterior fusiform gyrus), bilateral posterior middle temporal gyrus (pMTG) and left inferior frontal gyrus (IFG). For the same contrast the WA participants displayed overlapping activation in the right pMTG and left posterior fusiform gyrus and with additional clusters in the left precuneus and posterior cingulate and bilateral medial frontal gyrus (Figure 1A). When the semantic>control contrast was statistically compared between groups, the control participants showed significantly greater activity in the left superior anterior temporal lobe (ATL), left superior temporal gyrus, and right posterior insula. No area was more active in the WA participants (Figure 1B). Conclusions. The semantic association task activated a network typical of visually-based semantic tasks. Within this network, the left IFG is associated with a range of semantic cognition activities including semantic integration (Huang et al., 2012) and retrieval (Thompson-Schill, D’Esposito, Aguirre, & Farah, 1997). This region was not active in WA, despite lesions not impacting the area. However, the pMTG, which is also associated with semantic analysis (Noonan, Jefferies, Visser, & Lambon Ralph, 2013) and affected in WA, is frequently coactive with the IFG (Yarkoni, Poldrack, Nichols, Van Essen, & Wager, 2011) and disruption to one component may impact activity across the network. Damage to this network may impede access to higher order semantic regions, in particular the ATL. Participants with WA appear to supplement right hemisphere temporal activity by activating a medial frontal-posterior cingulate/precuneus network, associated with general declarative memory retrieval (Burianova, McIntosh, & Grady, 2010). Figure 1 Acknowledgements This work was funded by The Stroke Association (SRTF 2012/02). References Binder, J. R., & Desai, R. H. (2011). The neurobiology of semantic memory. Trends in Cognitive Sciences, 15(11), 527–536. Burianova, H., McIntosh, A. R., & Grady, C. L. (2010). A common functional brain network for autobiographical, episodic, and semantic memory retrieval. Neuroimage, 49(1), 865–874. Huang, J., Zhu, Z., Zhang, J. X., Wu, M., Chen, H.-C., & Wang, S. (2012). The role of left inferior frontal gyrus in explicit and implicit semantic processing. Brain Research, 1440, 56–64. Noonan, K. A., Jefferies, E., Visser, M., & Lambon Ralph, M. A. (2013). Going beyond inferior prefrontal involvement in semantic control: evidence for the additional contribution of dorsal angular gyrus and posterior middle temporal cortex. Journal of Cognitive Neuroscience, 25(11), 1824–1850. Thompson-Schill, S. L., D’Esposito, M., Aguirre, G. K., & Farah, M. J. (1997). Role of left inferior prefrontal cortex in retrieval of semantic knowledge: a reevaluation. Proceedings of the National Academy of Sciences, 94(26), 14792–14797. Yarkoni, T., Poldrack, R. A., Nichols, T. E., Van Essen, D. C., & Wager, T. D. (2011). NeuroSynth: a new platform for large-scale automated synthesis of human functional neuroimaging data. Frontiers in Neuroinformatics, 58. Keywords: Semantic Representation, semantic cognition, Language comprehension, fMRI — functional magnetic resonance imaging, Wernicke's aphasia Conference: Academy of Aphasia 57th Annual Meeting, Macau, Macao, SAR China, 27 Oct - 29 Oct, 2019. Presentation Type: Poster presentation Topic: Not eligible for student award Citation: Robson H, Griffiths TD and Woollams AM (2019). Imaging of semantic association judgements reveals areas of functional disruption and compensation remote from lesion in chronic Wernicke's aphasia. Front. Hum. Neurosci. Conference Abstract: Academy of Aphasia 57th Annual Meeting. doi: 10.3389/conf.fnhum.2019.01.00042 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 06 May 2019; Published Online: 09 Oct 2019. * Correspondence: Dr. Holly Robson, University of Reading, Reading, United Kingdom, h.v.robson@reading.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Holly Robson Timothy D Griffiths Anna M Woollams Google Holly Robson Timothy D Griffiths Anna M Woollams Google Scholar Holly Robson Timothy D Griffiths Anna M Woollams PubMed Holly Robson Timothy D Griffiths Anna M Woollams Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

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

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.

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Semantic judgments involve both representations of meaning plus executive mechanisms that guide knowledge retrieval in a task-appropriate way. These 2 components of semantic cognition—representation and control—are commonly linked to left temporal and prefrontal cortex, respectively. This simple proposal, however, remains contentious because in most functional neuroimaging studies to date, the number of concepts being activated and the involvement of executive processes during retrieval are confounded. Using functional magnetic resonance imaging, we examined a task in which semantic representation and control demands were dissociable. Words with multiple meanings like “bank” served as targets in a double-prime paradigm, in which multiple meaning activation and maximal executive demands loaded onto different priming conditions. Anterior inferior temporal gyrus (ITG) was sensitive to the number of meanings that were retrieved, suggesting a role for this region in semantic representation, while posterior middle temporal gyrus (pMTG) and inferior frontal cortex showed greater activation in conditions that maximized executive demands. These results support a functional dissociation between left ITG and pMTG, consistent with a revised neural organization in which left prefrontal and posterior temporal areas work together to underpin aspects of semantic control.

Semantic short-term memory (STM) patients have a reduced ability to retain semantic information over brief delays but perform well on other semantic tasks; this pattern suggests damage to a dedicated buffer for semantic information. Alternatively, these difficulties may arise from mild disruption to domain-general semantic processes that have their greatest impact on demanding STM tasks. In this study, mild semantic processing impairments were demonstrated in 2 semantic STM patients. They performed well on untimed semantic tasks but were deficient in accuracy and reaction times on speeded tasks. Demanding semantic production tasks were also affected. These patients were compared with a case series of individuals with semantic aphasia whose multimodal semantic difficulties stemmed from poor cognitive control. STM and semantic performance were more impaired in this group, but there were qualitative similarities to the semantic STM patients. The difference between the 2 patient types may be a matter of degree. In semantic aphasia, severe disruption to semantic control leads to global semantic impairments, whereas in semantic STM milder disruption might impact mainly on STM tests because of the high control demands of these tasks.

Semantic cognition--semantically driven verbal and nonverbal behavior--is composed of at least two interactive principal components: conceptual representations and executive control processes that regulate and shape activation within the semantic system. Previous studies indicate that semantic dementia follows from a progressive yet specific degradation of conceptual knowledge. In contrast, multimodal semantic impairment in aphasic patients (semantic aphasia [SA]) reflects damage to the control component of semantic cognition [Jefferies, E., & Lambon Ralph, M. A. Semantic impairment in stroke aphasia versus semantic dementia: A case-series comparison. Brain, 129, 2132-2147, 2006]. The purpose of the present study was to examine the nature of the semantic control deficits in SA in detail for the first time. Seven patients with SA were tested on four comprehension and naming tasks that directly manipulated the requirement for executive control in different ways. In line with many theories of cognitive control, the SA patients demonstrated three core features of impaired control: (i) they exhibited poor on-line manipulation and exploration of semantic knowledge; (ii) they exhibited poor inhibition of strongly associated distractors; and (iii) they exhibited reduced ability to focus on or augment less dominant aspects of semantic information, although the knowledge itself remained and could be successfully cued by external constraints provided by the examiner. Our findings are consistent with the notion that the anterior temporal lobes are crucial for conceptual knowledge whereas the left prefrontal and temporo-parietal cortices, damaged in patients with SA, play a critical role in regulating semantic activation in a task-appropriate fashion.

Refractory effects in stroke aphasia: A consequence of poor semantic control

To understand the meanings of words and objects, we need to have knowledge about these items themselves plus executive mechanisms that compute and manipulate semantic information in a task-appropriate way. The neural basis for semantic control remains controversial. Neuroimaging studies have focused on the role of the left inferior frontal gyrus (LIFG), whereas neuropsychological research suggests that damage to a widely distributed network elicits impairments of semantic control. There is also debate about the relationship between semantic and executive control more widely. We used TMS in healthy human volunteers to create "virtual lesions" in structures typically damaged in patients with semantic control deficits: LIFG, left posterior middle temporal gyrus (pMTG), and intraparietal sulcus (IPS). The influence of TMS on tasks varying in semantic and nonsemantic control demands was examined for each region within this hypothesized network to gain insights into (i) their functional specialization (i.e., involvement in semantic representation, controlled retrieval, or selection) and (ii) their domain dependence (i.e., semantic or cognitive control). The results revealed that LIFG and pMTG jointly support both the controlled retrieval and selection of semantic knowledge. IPS specifically participates in semantic selection and responds to manipulations of nonsemantic control demands. These observations are consistent with a large-scale semantic control network, as predicted by lesion data, that draws on semantic-specific (LIFG and pMTG) and domain-independent executive components (IPS).

Aphasic patients with multimodal semantic impairment following pFC or temporo-parietal (TP) cortex damage (semantic aphasia [SA]) have deficits characterized by poor control of semantic activation/retrieval, as opposed to loss of semantic knowledge per se. In line with this, SA patients show "refractory effects"; that is, declining accuracy in cyclical word-picture matching tasks when semantically related sets are presented rapidly and repeatedly. This is argued to follow a build-up of competition between targets and distractors. However, the link between poor semantic control and refractory effects is still controversial for two reasons. (1) Some theories propose that refractory effects are specific to verbal or auditory tasks, yet SA patients show poor control over semantic processing in both word and picture semantic tasks. (2) SA can result from lesions to either the left pFC or TP cortex, yet previous work suggests that refractory effects are specifically linked to the left inferior frontal cortex. For the first time, verbal, visual, and nonverbal auditory refractory effects were explored in nine SA patients who had pFC (pFC+) or TP cortex (TP-only) lesions. In all modalities, patient accuracy declined significantly over repetitions. This refractory effect at the group level was driven by pFC+ patients and was not shown by individuals with TP-only lesions. These findings support the theory that SA patients have reduced control over multimodal semantic retrieval and, additionally, suggest there may be functional specialization within the posterior versus pFC elements of the semantic control network.

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.