The flexible and interactive neural, computational and neurobiological mechanisms underpinning semantic cognition and its disorders.
Lead Research Organisation:
University of Cambridge
Department Name: MRC Cognition and Brain Sciences Unit
Abstract
Semantic memory refers to the rich database of knowledge we have about the meanings of words, objects, people and all the stimuli present in our environment. We activate this information when we comprehend a word or recognise an object. We use the same knowledge for speech or non-verbal activities such as object use. The aim of communication, itself, is for meaning to be conveyed between people. It is evident, therefore, that semantic knowledge is crucial for many everyday activities both at work and at home. When this type of knowledge disintegrates or becomes inaccessible after brain damage, patients become significantly disabled in many aspects of their lives. Imagine, for example, being able to comprehend only a small proportion of the words in everyday conversation, a letter or newspaper; being stuck with significant word-finding problems; or being unable to understand everyday symbols or road signs.
Sadly, these kinds of problems are a common feature of many types of brain disease. Semantic impairment is a characteristic of certain types of dementia, brain infections and after stroke or neurosurgery. In our last research programme, we developed the necessary methods and clinical links to undertake unique, detailed comparisons of different patient groups (semantic dementia, semantic aphasia, herpes simplex virus encephalitis, Alzheimer's disease, resection for temporal lobe epilepsy, and Wernicke's aphasia) and linked these patient studies directly with parallel explorations of the healthy semantic system. In particular, we discovered that there are two subsystems - one for coding the database of semantic information and a separate brain network for manipulating and shaping this information depending on the task requirements or context.
The core aims of our continuing research programme, therefore, are (a) to investigate the nature and function of different key areas within each semantic brain network; (b) examine the flexible interaction between the networks when the system comes under pressure and the associated compensatory processes that are triggered by brain damage; and (c) we will begin to explore both the brain structures and brain chemicals that are involved in semantic function. These steps will be used to improve: detection of semantic deficits; differential diagnosis; clinical management; and evidence-based interventions.
Our ultimate aim is to build up a complete picture and model of the network of brain regions that support semantic processing. We have pioneered a new type of mathematical model which mirrors brain regions and their connections, and after training, generates human semantic behaviours. When these models are damaged they can mimic the types of impairment found in different patient groups. We will use the new findings from the studies of patients and healthy participants to generate a model of semantic processing that includes the networks for both semantic knowledge and semantic manipulation. We will use this model to reproduce each patient group's pattern of performance. We will then be able to use this model not only to understand the nature of semantic problems across all these different patient groups but also to use the model to gain new insights about minimising these problems and for generating new interventions that could be used by speech therapists with these patient groups.
Sadly, these kinds of problems are a common feature of many types of brain disease. Semantic impairment is a characteristic of certain types of dementia, brain infections and after stroke or neurosurgery. In our last research programme, we developed the necessary methods and clinical links to undertake unique, detailed comparisons of different patient groups (semantic dementia, semantic aphasia, herpes simplex virus encephalitis, Alzheimer's disease, resection for temporal lobe epilepsy, and Wernicke's aphasia) and linked these patient studies directly with parallel explorations of the healthy semantic system. In particular, we discovered that there are two subsystems - one for coding the database of semantic information and a separate brain network for manipulating and shaping this information depending on the task requirements or context.
The core aims of our continuing research programme, therefore, are (a) to investigate the nature and function of different key areas within each semantic brain network; (b) examine the flexible interaction between the networks when the system comes under pressure and the associated compensatory processes that are triggered by brain damage; and (c) we will begin to explore both the brain structures and brain chemicals that are involved in semantic function. These steps will be used to improve: detection of semantic deficits; differential diagnosis; clinical management; and evidence-based interventions.
Our ultimate aim is to build up a complete picture and model of the network of brain regions that support semantic processing. We have pioneered a new type of mathematical model which mirrors brain regions and their connections, and after training, generates human semantic behaviours. When these models are damaged they can mimic the types of impairment found in different patient groups. We will use the new findings from the studies of patients and healthy participants to generate a model of semantic processing that includes the networks for both semantic knowledge and semantic manipulation. We will use this model to reproduce each patient group's pattern of performance. We will then be able to use this model not only to understand the nature of semantic problems across all these different patient groups but also to use the model to gain new insights about minimising these problems and for generating new interventions that could be used by speech therapists with these patient groups.
Technical Summary
Semantic cognition allows us to retrieve the meanings of words, objects, people, etc., and to use this rich store of knowledge flexibly to produce time- and context-appropriate behaviour. Given the central role of semantic cognition in communication (the core goal of which is to pass meaning from one person to another) and everyday life (e.g., object use), it is not surprising that patients with semantic impairments suffer from considerable disability in both their professional and everyday lives. Semantic impairments are a common deficit across many different diseases of the neocortex. These include patients with neurodegenerative disease (e.g., frontotemporal dementia, Alzheimer's disease) or following an acute episode (e.g., cerebral vascular accident, herpes simplex encephalitis, head injury, neurosurgery). It is paramount, therefore, to understand the neural basis of normal and impaired semantic cognition, and then to use this knowledge to improve treatment and clinical management.
The long-term aim of our continuing research programme, therefore, is to understand the flexible and interactive nature of semantic cognition, at the behavioural, neural, computational and neurobiological levels. Using our innovative combinations of cognitive and clinical neuroscience investigations, we will tackle this target through three interlinked research themes: (a) Exploring the nature and components of the network for semantic cognition; (b) Investigating the flexible interaction and compensatory processes within the semantic network; and (c) to beging to extend the neurocognitive account of semantic cognition to neurobiological mechanisms. These three themes will be integrated through implementation of the first neurocomputational model of semantic representation and control, in which the model architecture will assimilate neuroanatomical and neurobiological information and the model will be required to generate normal semantic function and dysfunctions after damage.
The long-term aim of our continuing research programme, therefore, is to understand the flexible and interactive nature of semantic cognition, at the behavioural, neural, computational and neurobiological levels. Using our innovative combinations of cognitive and clinical neuroscience investigations, we will tackle this target through three interlinked research themes: (a) Exploring the nature and components of the network for semantic cognition; (b) Investigating the flexible interaction and compensatory processes within the semantic network; and (c) to beging to extend the neurocognitive account of semantic cognition to neurobiological mechanisms. These three themes will be integrated through implementation of the first neurocomputational model of semantic representation and control, in which the model architecture will assimilate neuroanatomical and neurobiological information and the model will be required to generate normal semantic function and dysfunctions after damage.
Planned Impact
Our specific plans for academic, clinical and other types of impact are summarised in the 'Case for Support' and 'Pathways to Impact'. A brief summary is provided here.
The most important beneficiaries of our research are the patients and carers, who are the core groups in our research programme. Improved diagnosis, assessment, clinical management and interventions will follow from a clearer understanding of the cognitive and neural processes that underpin semantic processing. If our methods can be extended and replicated to other aspects of higher cognitive function and its disorders (see 'academic beneficiaries' section) then our multidisciplinary, multi-method approach might also benefit other patient groups in the longer-term.
This patient-related benefit can be delivered directly (a significant proportion of our broader research group is dedicated to the translation of basic sciences through to new speech and language interventions) and indirectly through the patients' clinicians (who can also be considered to be beneficiaries of the research). Lambon Ralph also undertakes monthly specialist NHS clinics for speech therapy and a memory clinic. When we identify a new clinical impact possibility we act to develop it. For example, we recently found evidence that both speed and accuracy of retrieval may be critical for generalisation of naming therapy in stroke aphasia. We developed this new therapy approach and collected feasibility data through a targeted PhD, have secured an MRC-funded Confidence-in-Concept award and will later apply for NIHR RfPB support.
To increase the breadth of our impact, we disseminate the new assessment materials freely and openly, and work with local groups to generate appropriate translations. Our battery of semantic assessments and imaging protocols remain under high demand from clinicians and clinical researchers. Our tests are now used in clinics around the world (e.g., UK, USA, Italy, Spain, India, Japan Argentina and Australia). In addition, we regularly present and discuss our clinical findings and methods with (a) local patient and carer groups, boosting our PPI opportunities; (b) with local, national and international clinical interest groups; and (c) at international clinical conferences. For example, Lambon Ralph was a keynote speaker at international aphasiology and neurology conferences in the USA, Japan and Germany this year, following presentations in Holland, France, Italy and Japan last year.
Our research is intended to improve diagnosis, understanding of patients' disorders as well as preserved function, clinical management and interventions. This will be achieved through our 'communication plan' (see previous section) - not only in terms of disseminating information to clinician and patient groups but also in a more interactive fashion through workshops and seminars. These types of event, combined with our own clinical activities, provide a crucial opportunity to discuss and shape the clinical applicability of our research. Two of our recent research papers were based on questions and suggestions made by patients and carers in our PPI groups.
Our imaging related activities and methods development may also have wider impact both clinically and commercially. We work regularly with a local SME (Bioxydyn Ltd) who support trials and large-scale studies that utilise shared clinical protocols across large multi-centre studies. We are currently developing this relationship through an MRC PhD Case award.
The most important beneficiaries of our research are the patients and carers, who are the core groups in our research programme. Improved diagnosis, assessment, clinical management and interventions will follow from a clearer understanding of the cognitive and neural processes that underpin semantic processing. If our methods can be extended and replicated to other aspects of higher cognitive function and its disorders (see 'academic beneficiaries' section) then our multidisciplinary, multi-method approach might also benefit other patient groups in the longer-term.
This patient-related benefit can be delivered directly (a significant proportion of our broader research group is dedicated to the translation of basic sciences through to new speech and language interventions) and indirectly through the patients' clinicians (who can also be considered to be beneficiaries of the research). Lambon Ralph also undertakes monthly specialist NHS clinics for speech therapy and a memory clinic. When we identify a new clinical impact possibility we act to develop it. For example, we recently found evidence that both speed and accuracy of retrieval may be critical for generalisation of naming therapy in stroke aphasia. We developed this new therapy approach and collected feasibility data through a targeted PhD, have secured an MRC-funded Confidence-in-Concept award and will later apply for NIHR RfPB support.
To increase the breadth of our impact, we disseminate the new assessment materials freely and openly, and work with local groups to generate appropriate translations. Our battery of semantic assessments and imaging protocols remain under high demand from clinicians and clinical researchers. Our tests are now used in clinics around the world (e.g., UK, USA, Italy, Spain, India, Japan Argentina and Australia). In addition, we regularly present and discuss our clinical findings and methods with (a) local patient and carer groups, boosting our PPI opportunities; (b) with local, national and international clinical interest groups; and (c) at international clinical conferences. For example, Lambon Ralph was a keynote speaker at international aphasiology and neurology conferences in the USA, Japan and Germany this year, following presentations in Holland, France, Italy and Japan last year.
Our research is intended to improve diagnosis, understanding of patients' disorders as well as preserved function, clinical management and interventions. This will be achieved through our 'communication plan' (see previous section) - not only in terms of disseminating information to clinician and patient groups but also in a more interactive fashion through workshops and seminars. These types of event, combined with our own clinical activities, provide a crucial opportunity to discuss and shape the clinical applicability of our research. Two of our recent research papers were based on questions and suggestions made by patients and carers in our PPI groups.
Our imaging related activities and methods development may also have wider impact both clinically and commercially. We work regularly with a local SME (Bioxydyn Ltd) who support trials and large-scale studies that utilise shared clinical protocols across large multi-centre studies. We are currently developing this relationship through an MRC PhD Case award.
Publications
Alyahya RSW
(2020)
Mapping psycholinguistic features to the neuropsychological and lesion profiles in aphasia.
in Cortex; a journal devoted to the study of the nervous system and behavior
Alyahya RSW
(2020)
A unified model of post-stroke language deficits including discourse production and their neural correlates.
in Brain : a journal of neurology
Bajada CJ
(2020)
A tutorial and tool for exploring feature similarity gradients with MRI data.
in NeuroImage
Branzi FM
(2021)
The Left Angular Gyrus Is Causally Involved in Context-dependent Integration and Associative Encoding during Narrative Reading.
in Journal of cognitive neuroscience
Branzi FM
(2020)
Revealing the neural networks that extract conceptual gestalts from continuously evolving or changing semantic contexts.
in NeuroImage
Busby N
(2019)
Mapping whole brain connectivity changes: The potential impact of different surgical resection approaches for temporal lobe epilepsy.
in Cortex; a journal devoted to the study of the nervous system and behavior
Chiou R
(2023)
Bipartite functional fractionation within the neural system for social cognition supports the psychological continuity of self versus other.
in Cerebral cortex (New York, N.Y. : 1991)
Chiou R
(2018)
Controlled semantic cognition relies upon dynamic and flexible interactions between the executive 'semantic control' and hub-and-spoke 'semantic representation' systems.
in Cortex; a journal devoted to the study of the nervous system and behavior
Chiou R
(2020)
Bipartite Functional Fractionation within the Default Network Supports Disparate Forms of Internally Oriented Cognition.
in Cerebral cortex (New York, N.Y. : 1991)
Chiou R
(2023)
A middle ground where executive control meets semantics: the neural substrates of semantic control are topographically sandwiched between the multiple-demand and default-mode systems.
in Cerebral cortex (New York, N.Y. : 1991)
Ding J
(2020)
A unified neurocognitive model of semantics language social behaviour and face recognition in semantic dementia.
in Nature communications
Frisby S
(2022)
Decoding semantic representations in mind and brain
Gore KR
(2022)
Direct Neural Evidence for the Contrastive Roles of the Complementary Learning Systems in Adult Acquisition of Native Vocabulary.
in Cerebral cortex (New York, N.Y. : 1991)
Halai AD
(2022)
Efficient and effective assessment of deficits and their neural bases in stroke aphasia.
in Cortex; a journal devoted to the study of the nervous system and behavior
Hauk O
(2021)
Face-selective responses in combined EEG/MEG recordings with fast periodic visual stimulation (FPVS).
in NeuroImage
Hodgson VJ
(2021)
Multiple dimensions underlying the functional organization of the language network.
in NeuroImage
Hoffman P
(2018)
Concepts, control, and context: A connectionist account of normal and disordered semantic cognition.
in Psychological review
Hoffman P
(2018)
From percept to concept in the ventral temporal lobes: Graded hemispheric specialisation based on stimulus and task.
in Cortex; a journal devoted to the study of the nervous system and behavior
Humphreys G
(2021)
A Unifying Account of Angular Gyrus Contributions to Episodic and Semantic Cognition
in Trends in Neurosciences
Humphreys G
(2022)
The convergence and divergence of episodic and semantic functions across lateral parietal cortex
in Cerebral Cortex
Humphreys GF
(2020)
Overarching Principles and Dimensions of the Functional Organization in the Inferior Parietal Cortex.
in Cerebral cortex (New York, N.Y. : 1991)
Humphreys GF
(2023)
Dual-axes of functional organisation across lateral parietal cortex: the angular gyrus forms part of a multi-modal buffering system.
in Brain structure & function
Jackson R
(2019)
Exploring distinct default mode and semantic networks using a systematic ICA approach
in Cortex
Jackson RL
(2018)
An emergent functional parcellation of the temporal cortex.
in NeuroImage
Jackson RL
(2021)
Reverse-engineering the cortical architecture for controlled semantic cognition.
in Nature human behaviour
Jackson RL
(2020)
The Graded Change in Connectivity across the Ventromedial Prefrontal Cortex Reveals Distinct Subregions.
in Cerebral cortex (New York, N.Y. : 1991)
Jackson RL
(2021)
The neural correlates of semantic control revisited.
in NeuroImage
Jung J
(2023)
Distinct but cooperating brain networks supporting semantic cognition.
in Cerebral cortex (New York, N.Y. : 1991)
Jung J
(2018)
Establishing the cognitive signature of human brain networks derived from structural and functional connectivity.
in Brain structure & function
| Description | CUH |
| Organisation | Cambridge University Hospitals NHS Foundation Trust |
| Country | United Kingdom |
| Sector | Public |
| PI Contribution | Collaboration with the Stroke Team and SLT Team at Cambridge University Hospitals Collaboration with the Early Dementia Clinic |
| Collaborator Contribution | Collaboration on patient screening (clinical), translation of research findings to clinic, and identification of potentially suitable research participants. |
| Impact | Stroke medicine Speech and language therapy Cognitive Neurology |
| Start Year | 2020 |
| Description | "Drawing out degraded concepts in patients with impaired semantic cognition." Images2Symbols CogSci Symposium - Invited Talk (online). |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Interdisciplinary workshop hosted by the Cognitive Science Society exploring the use of drawing for assessment of children, adults and patients. |
| Year(s) Of Engagement Activity | 2022 |
| Description | "The neurocognitive bases of semantic cognition and its disorders." Keynote lecture - Danish Neuropsychology Society (Nyborg). |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Continued professional development for Danish Neuropsychological Society |
| Year(s) Of Engagement Activity | 2022 |
| Description | Cambridge Festival (online) science night event - live from 26 March - 5 April |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Online pre-recorded talks, games and demos. Normally in person for this annual event but moved online due to ongoing pandemic. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Dec 2019: "Re-mapping acquired disorders of reading into a multidimensional model of post-stroke aphasia." Invited speaker - UK Stroke Forum (Telford, UK) |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | CPD for stroke-related health care professionals |
| Year(s) Of Engagement Activity | 2019 |
| Description | Feb 2022: "Transdiagnostic approaches to cognitive disorders and their underlying brain pathology." Invited talk - Brain Conference 2022 (online). |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | CPD for neurologists and other health care workers, and postgrad students. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Invited keynote lecture - Swiss Association of Neuropsychologists: "Semantic disorders in neurodegenerative and other diseases." (online) |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Continued professional development |
| Year(s) Of Engagement Activity | 2022 |
| Description | Jan 2021: "The neural basis of semantic cognition and its disorders". Invited lecture - Kobe University Medical School (virtual). |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | CPD for neurologist and associated health care professionals |
| Year(s) Of Engagement Activity | 2021 |
| Description | June 2020: "The neural and computational bases of conceptual knowledge and its breakdown in neurological disorders." Keynote speaker - Interdisciplinary Approaches in the Language Sciences Conference 2020 (MPI Nijmegen - virtual). |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Postgraduate training |
| Year(s) Of Engagement Activity | 2020 |
| Description | Oct 2019: "Comparing post-stroke and primary progressive aphasia: A data-driven transdiagnostic approach" Invited speaker - World Congress of Neurology, Dubai. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | CPD for neurologists |
| Year(s) Of Engagement Activity | 2019 |