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.

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.

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.

Publications

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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

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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

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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

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Jackson RL (2019) Exploring distinct default mode and semantic networks using a systematic ICA approach. in Cortex; a journal devoted to the study of the nervous system and behavior

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Rice GE (2018) Concrete versus abstract forms of social concept: an fMRI comparison of knowledge about people versus social terms. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences