The organization and neural basis of long-term memory and knowledge

The research group (Figure 1 below) is led by four MRC senior scientists:

Kim Graham, Rik Henson, John Hodges, Karalyn Patterson

with strong links to the MRC clinical programme of John Hodges at Addenbrooke's Hospital (Cambridge University Department of Neurology). Our research is also supported by an Alzheimer's Research Trust (ART) grant awarded to Kim Graham and John Hodges, and an Interdisciplinary Behavioural Science Centre grant from the US National Institute of Health (NIH) awarded to Karalyn Patterson. Members of the group are also supported by the Wellcome Trust, Glaxo-Smith-Kline (GSK) and Parkinson Disease Society (PDS).

The group consists of people at the CBU...

Postdoctoral scientists: Anna Adlam (MRC), Stephan Bandelow (ART), Andy Lee (ART), Vicki Scahill (ART), Anna Woollams (NIH)

Ph.D. students: Samrah Ahmed (ART), Morgan Barense (MRC), Fiona Clague (ART), Elias Mouchlianitis (MRC), Karen Taylor (MRC)

Research assistants/Administrative support: Sharon Davies (MRC), Joanna Drake (MRC), Tina Emery (ART), Hilary Green (MRC), Gini Hearn, Michael Hornberger (MRC), Elisa Pye (NIH), Margaret Tillson (MRC).

...together with people attached to the University Department of Neurology:

Neurologists and clinical training fellows: Thomas Bak (PDS), Rhys Davies (Wellcome), Andrew Graham (Wellcome), Christopher Kipps (MRC), Jonathan Knibb (MRC), Peter Nestor (GSK)

Research assistants/Administrative support: Robert Arnold (MRC), Kate Dawson (MRC), Eneida Mioshi (GSK), Joanna Mitchell (MRC), Alison Yorke (HEFCE)

Previous members include...

Postdoctoral scientists: Helen Bird, Sasha Bozeat, Naida Graham, Marion Kellenbach, Matt Lambon-Ralph , Tim Rogers, Eamon Strain

Neurologists and clinical training fellows: Peter Garrard, Clare Galton, John Greene, Richard Perry, Sian Thompson

PhD students: Linda Clare, Karen Croot, Toby Cumming, Raymond Knott, Anna Kropelnicki, Jon Simons

Figure 1

Research Programmes

Kim Graham: MRC Senior Scientist CBU Page

My main research interest is the cognitive and neural organisation of human long-term memory. Research techniques include neuropsychological testing of patients with progressive and nonprogressive memory impairments, and the use of structural and functional neuroimaging in patients and healthy subjects. Current projects include: (a) understanding the role of medial and lateral temporal lobe structures in memory consolidation; (b) investigating how semantic knowledge interacts with other cognitive domains, particularly new learning and language; (c) determining the role of non-hippocampal medial cortices in long-term memory, and investigating the interactions between memory and visual processing; (d) elucidating how frontal and temporal regions interact to support memory retrieval; (e) investigating possible strategies for the acquisition of previously lost semantic knowledge; (f) determining the dissociability, both cognitively and neurally, of different types of long-term memory (e.g., autobiographical, semantic and episodic memory).

Rik Henson: MRC Senior Scientist CBU Page

My research programme combines multimodal approaches towards understanding explicit and implicit memory, specifically recollection, familiarity and priming. Modalities include functional magnetic resonance imaging (fMRI) and electro- and magneto-encephalography (E/MEG). The research concentrates on healthy volunteers and the domain of visual word and visual object processing, particularly faces. It also entails further development of formal methods to integrate fMRI and E/MEG, and more detailed computational models that relate these data to neurophysiological data from single-cell recording. Projects include: i) fMRI and EEG studies of recognition memory, in particular further attempts to dissociate the neural correlates of familiarity and recollection (together with Kim Graham, Michael Hornberger, and Karen Taylor), ii) Detailed investigations of visual object priming, including masked priming, split visual-field priming and various object transformations (together with Elias Mouchlianitis), iii) Computational neural network models of priming that relate haemodynamic, electrophysiological, neurophysiological and behavioural data, iv) Methodological developments for analysing and integrating fMRI, EEG and MEG data.

John Hodges: Professor of Behavioural Neurology CBU Page

At Addenbrooke's Hospital, I run the Memory Disorders Clinic (jointly with Dr. German Berrios, Dr Jeremy Brown and Dr Aidan Jones) and the multidisciplinary Early Onset Dementia Clinic. My main research interests can be divided into theoretical and clinical. The theoretical work based at the CBU focuses on the organisation and neural basis of long-term memory, especially semantic and autobiographical memory. The clinical work relates to the early diagnosis and differentiation of the dementias (Alzheimer's disease, semantic dementia, frontal dementia, PSP and Huntington's disease etc).

Karalyn Patterson: Senior Scientist at MRC-CBU CBU Page

My main interest is in the nature of semantic, phonological and orthographic representations of concepts and words, and how these interact in various common tasks such as object naming, word comprehension, word reading, short-term memory, etc. The principal source of evidence for this research comes from patterns of performance in patients with disorders of language and/or semantic memory. This neuropsychological approach is supplemented by experiments on normal language/memory processes (both behavioural, cognitive studies and functional imaging) and also by analysis of normal and "lesioned" networks that simulate some aspects of these abilities. A further focus, especially with respect to reading and its disorders, is cross-linguistic comparisons between English and Japanese, to help us understand which aspects of the reading process are universal and which are determined by the way that different writing systems encode meaning and phonology.

I am interested in understanding how we form, store and retrieve long-term episodic (event) and semantic (fact) memories. I am particularly interested in understanding how brain injury affects long-term declarative memory, and what this can tell us about the normal function and development of the human brain. I am currently working as a post-doctoral research associate, under the supervision of Professor John Hodges and Dr Karalyn Patterson, investigating the organisation and neural basis of semantic memory. Two main questions of interest are: a) how does semantic memory support both generalisations amongst and differentiation between related concepts?; and b) how is new conceptual information acquired? These questions will be addressed using neuropsychological measures (both standardised and experimental) and neuroimaging techniques (MRI and ERP paradigms).

My PhD will focus on the early diagnosis of early Alzheimer's Disease with a focus on a patient group referred to as having Mild Cognitive Impairment (MCI). MCI patients have a documented accelerated progression to Alzheimer's Disease. I hope to look into differential sensitivity to specific cognitive domains using novel tests.

During my PhD I used neural network models and behavioural tests to investigate language acquisition and the breakdown of language skills in neurodegenerative disorders. At the CBU I work on the role of the medial temporal lobes in human memory. My main interest relates to the neural organisation of memory and language skills, especially semantics, which involves the ability to abstract and generalise from specific examples. To investigate these processes, I aim to combine artificial neural network models and empirical data, for example by comparing the performance of lesioned networks to that of patients with neurodegenerative disorders. This approach provides a chance to test specific theoretical assumptions, which are implemented in the neural network models, against empirical data.

My PhD focuses on understanding the functions of different medial temporal lobe structures and developing a theoretical model for how damage to medial temporal lobe (MTL) regions in humans results in different profiles of memory impairment. Currently there is a discrepancy between the animal and human literature with respect to the role of the perirhinal cortex in object perception. My research attempts to resolve this discrepancy by directly adapting visual perception tasks from the animal literature for use in humans with MTL damage. Additionally, I plan to investigate the role of the perirhinal cortex in recognition memory and object perception through neuroimaging techniques.

The focus of my PhD is the early diagnosis of Alzheimer’s disease (AD) and its differentiation from other types of dementia using cognitive tasks. A key aspect of this project is investigating the sensitivity of specific task domains (including person knowledge, cross modal associate learning and spatial memory) to individuals with mild cognitive impairment (MCI) - a group at heightened risk of developing AD.

The main part of my work involves maintaining up-to-date records in the form of databases for test results (both routine and experimental) for all of the patients involved in the group's research work at the CBU. I also keep records of scan dates, DoIs, pathology results, annual re-testing dates and any other relevant information relating to individual patients and hence another important part of my work is providing information, results, test materials, equipment etc for specific patients or groups of patients, to other members of the group and to external collaborators. I also carry out basic statistical analyses mostly using SPSS for specific projects, provide graphs and proof-read papers if required. I also organise the regular group business meetings and the quarterly Carer's Support Group meetings that we run for carers of patients with fronto-temporal dementia, including the production and distribution of a newsletter.

I am mainly responsible for neuropsychological testing of patients with Frontal and Semantic dementia, but also see patients with Alzheimer’s disease. I also assist with the collection of data for many specific projects involving Semantic dementia patients.

Working on the ART grant, I am mainly responsible for neuropsychological testing of patients either with Dementia with Lewy Bodies or with static lesions; I occasionally see patients with various forms of dementia too. I am responsible for some of the administrative and organisational duties of the ART group such as collating and centralising the data collected by group members.

I have recently joined the Memory group and will be working with Kim Graham’s team, looking at differentiation of function within the structures of the medial temporal lobe. I will be testing controls and patients, looking at changes in cognitive function with age. Later I will be using eye-tracking equipment to compare brain function between the lesioned and unlesioned hemispheres in patients with unilateral hippocampal damage.

I am currently working as an research assistant with Kim Graham and Rik Henson at the CBU while I am still doing my part-time PhD at UCL under the supervision of Leun Otten. I am particularly interested in combining different research methods in the field of recognition memory. My work here focuses mainly on two lines of research: a) ERP, fMRI & neuropsychological investigations of the role of familiarity and recollection in human recognition memory and b) neuropsychological investigations into semantic memory and the interaction of semantic knowledge with other memory domains.

I work with Dr Bak to investigate the neuropsychological and behavioural aspects of diseases such as PSP, Corticobasal degeneration, Lewy Body dementia, Multiple System Atrophy and Motor Neurone Disease. I organise the once or twice weekly Disorders of Movement and Cognition clinic at Addenbrooke's and use neuropsychological tests to assess the patients there. The results from these tests not only supplement Dr Bak’s medical examinations, but also form the basis of our research into these diseases. As part of our work with patients we are also participating in the NNIPPS study of the efficacy of a drug called Riluzole in the treatment of PSP and MSA. The report is expected by December 2005. Once I have collected the data from the patients, it is my job to get it into a computer, where it becomes part of a very large body of data that Professor Hodges and his team have collected over the years. We now have a new centralised database that allows us to share information more readily and efficiently within the group. This system also helps us to manage the running of our various Research Clinics. This new database has been developed from the one that my husband and I originally created and developed specifically for the DMC clinic data about 18 months ago and it is now rolled out, group wide, in its latest incarnation.I extract the relevant data for our research projects on various aspects of these diseases, such as their profiles of behavioural change, or their effect on language comprehension. I then apply data handling tools from Excel and SPSS to produce graphs and statistics for the publications that Dr Bak is involved in.

I am currently working in the group as a post-doctoral researcher. My work involves the use of functional neuroimaging techniques (fMRI and PET) and neuropsychological studies in brain damaged patients to explore the neural basis of human long-term memory. Particular areas of interest include: 1) The functions of different medial temporal lobe structures, e.g. the role of the perirhinal cortex in recognition memory and object perception; the importance of the hippocampus in spatial memory. 2) The functional relationship between frontal and temporal lobe regions in the encoding and retrieval of long-term memory. 3) The neural organisation of episodic and semantic memory and how different categories of knowledge may be organised in the human brain.

I am collaborating with Dr. Rik Henson in a project that aims to investigate hemispheric differences in view-dependent and independent priming. More specifically, by using the divided visual-field paradigm, we aim to identify whether same and different views of previously studied stimuli are processed differently in the right and left cerebral hemispheres. We intend to integrate behavioural, EEG and fMRI data and possibly relate findings to current theories (e.g. Marsolek, 2002) of dissociable neural systems in the processing of visual word-form and visual object recognition.

I am assisting Dr. Karalyn Patterson and Dr. Anna Woollams on a research grant investigating semantic memory and its structure. This project is in collaboration with the Speech and Language group and utilises their EEG lab. I will be testing both healthy volunteers and patients with semantic dementia. EEG recordings will be taken while participants respond to words and pictures of objects. Amongst other things we will be looking to see when the recognition of items occurs in these two participant groups and if there are any differences. My main responsibilities include helping with stimuli selection, testing participants and analysing data.

Vicky Scahill: Post Doctoral Researcher (ART) CBU Page

I am working as a post-doctoral researcher in the group, where my daily work has two main threads. I help with the neuropsychological testing of patients with damage to the temporal lobes resulting from e.g. stroke, encephalitis or tumour removal, and also visit patients with semantic dementia, Dementia with Lewy Bodies and Alzheimer’s disease. My own research is focussed mainly on investigating the role of temporal lobe structures in configural, spatial and perceptual learning, and I have particular interest in the role of the perirhinal cortex in the recognition of complex visual objects, and of the hippocampus in spatial memory.

During my PhD I will be investigating various aspects of human long-term memory with the use of behavioural, neuropsychological and neuroimaging techniques. I am particularly interested in understanding the differential contributions of medial temporal lobe structures to recollection and familiarity, processes thought to contribute to recognition memory; memory for different stimulus types, for example, spatial vs. non spatial, visual vs. auditory.

I am the Secretary for the group, my role includes: Dealing with telephone enquiries from patients, families and those involved with care, liaising with the Brain Bank as necessary. Preparing and processing general correspondence from audio-taped dictation. Assisting in the preparation of Ethics submissions for members of the DMS Group. Assisting in the preparation of research grant proposals for members of the DMS Group. Assisting with preparation of research papers and chapters for publication and final submission. Maintaining and updating databases for published papers and papers in progress for the DMS Group. Processing reprint requests.Liaise with organisations and groups in which Prof. Hodges is involved eg: ART, WFN, PSP etc.

My main research interest concerns our ability to use language to refer to the many objects and concepts that exist in the world. Semantic information is involved in even simple tasks such as reading aloud, and it is for this reason that patients with semantic dementia show a deficit in word naming. In my doctoral research, I found that individuals differ substantially in their degree of reliance on semantic information during reading aloud. It is therefore possible that the severity of the word naming deficit seen in semantic dementia is affected by pre-morbid individual differences. In collaboration with Karalyn Patterson and Matthew Lambon Ralph (University of Manchester), I am using statistical meta-analyses to identify cases in which the observed word naming deficit differs substantially from that expected according to performance on semantic tasks. The influence of pre-morbid individual differences upon reading aloud in semantic dementia will be then be investigated in studies employing novel neuropsychological measures.

Based at University Department of Neurology

I am a grant-funded research assistant focusing on neuropsychological testing of patients with mild cognitive impairment and appropriate control subjects in connection with projects investigating suspected and actual dementia of Alzheimer's type. I am also involved from time to time in carrying out similar testing on other subjects, especially those with other dementias. I also occasionally undertake the testing of control and other subjects in connection with other specific projects including the validation and calibration of new tests.

The neuropsychological and behavioural aspects of subcortical diseases in comparison with dementia of frontal type. My main area of interest is the interaction between cortical and subcortical structures underlying human cognition, emotion and behaviour. The diseases I focus on are PSP (Progressive Supranuclear Palsy or Steele-Richardson-Olszewski syndrome) and corticobasal degeneration but I also work with patients with Huntington's and Wilson's disease, Lewy Body Dementia and Multiple System Atrophy. I am also very interested in the cognitive aspects of Motor Neurone Disease. Most patients are followed up by me in a specialist clinic for Disorders of Movement and Cognition. In addition to general neuropsychological assessment I am particularly interested in possible dissociations between noun/verb and action/object processing.

I study the anatomical basis of fronto-temporal dementia by means of in vivo structural imaging and neuropathological techniques, with particular focus on patients with the semantic dementia syndrome. Findings have included the establishment of perirhinal cortex in the anterior temporal lobe as a key site of damage in semantic dementia and, more recently, the discovery of strong parallels between the microscopic pathology of semantic dementia and that of motor neuron disease.

I run clinical trials for patients with mild to moderate Alzheimer's disease. All patients participating in the trial are seen as outpatients. At each visit, patients will have various safety (blood tests and ECG's) and efficacy measures (MMSE, Adas(Cog) CIBIC, PDS and GDS) performed.

I am a post-CCST neurologist, currently undertaking a three-year Wellcome research fellowship. I attend the Memory Clinic at Addenbrooke’s but am primarily based at the MRC-CBU. I am interested in the profiles of behavioural disturbance and cognitive dysfunction associated with injury to the orbitofrontal cortex, with particular reference to the disorder of frontal variant frontotemporal dementia (fvFTD). Patients with fvFTD are well known to display a range of behavioural disturbances that would be consistent with orbitofrontal dysfunction, and a number of structural imaging studies have demonstrated selective orbitofrontal atrophy in this condition. However, there is less agreement over the nature and extent of cognitive dysfunction in patients with fvFTD. My current work therefore involves the development and piloting of novel tasks designed to tap orbitofrontal function, with paradigms ranging from delayed matching to sample / non-matching to sample to associative memory for reward and memory for source, the results of which will be correlated with structural MRI measures of orbitofrontal atrophy.

My interest is in the neural basis of social cognition, and I am funded by the Wellcome Trust to study this in frontotemporal dementia using FDG-PET, MRI and neuropsychological testing. Particular areas of interest involve aspects of cognition such as the Theory of Mind, decision-making and emotional processing. I am also interested in longitudinal imaging methods in dementia, and their relationship to clinical assessment.

My interest is in progressive aphasic syndromes, and my work follows two parallel paths. One concerns the spectrum of deficits seen in people with progressive language problems, and how these compare to other degenerative cognitive syndromes. I am also investigating the relationship of these clinical syndromes to the post-mortem pathological features. The overall goal of my research is to contribute to establishing an objective nosology of these disorders and a rational basis for treatment.

I've been helping Prof. Hodges on the revision of the Addenbrooke's Cognitive Examination (ACE-R) by re-designing it. I’ve been testing the revised version, organising its data and also contacting group members who have been using it in various clinical and research settings. Therefore I've been working closely to Kate Dawson at the Memory Clinic and Drug Clinic at R3 - Addenbrooke's. I've been also involved in a new project, which is aiming to investigate functional performance of patients in everyday life. These patients are diagnosed as Mild Cognitive Impairment (MCI), Alzheimer's Disease and Fronto-Temporal Disease patients. We'll be assessing them with existing Instrumental Activities of Daily Living (IADLs) and Activities of Daily Living (ADLs) scales in order to investigate the spectrum of IADL and ADL impairment in those populations, and any correlation between IADL/ADL performance with executive function and apathy. We also intend to draw performance profiles in each diagnosis group and compare sensitivity and specificity of some existing ADL scales on these different patients' population.

I have recently joined the group, based at R3 at Addenbrooke’s, as data manger working closely with John and with Kate Dawson. My aim is to establish a comprehensive database containing all of the clinical and eventually radiological and neuropath data.

My interest is the neural substrate for higher mental processes and behaviour, particularly episodic memory. The study population are groups of individuals with degenerative disorders (specifically variants of Alzheimer's and frontotemporal dementia) in whom I am trying to correlate cognitive performance to regional brain metabolism using 18-flourodeoxyglucose PET scanning and magnetic resonance imaging.

I am the secretary to Prof John Hodges, and also perform work for Chris Kipps, Andrew Graham, Jonathan Knibb, Peter Nestor, Thomas Bak and Robert Arnold, together with Jo and Kate.

For comments/updates to this page, please email Rik Henson