Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - BRAIN2MIND_NEUROCOMP (Developing and delivering neurocomputational models to bridge between brain and mind.)

Teaser

What is the problem/issue being addressed?The promise of cognitive neuroscience is truly exciting – to link mind and brain in order to reveal the neural basis of higher cognitive functions. This is crucial, scientifically, if we are to understand the nature of mental...

Summary

What is the problem/issue being addressed?
The promise of cognitive neuroscience is truly exciting – to link mind and brain in order to reveal the neural basis of higher cognitive functions. This is crucial, scientifically, if we are to understand the nature of mental processes and how they arise from neural machinery but also, clinically, if we are to establish the basis of neurological patients’ impairments, their clinical management and treatment. Cognitive-clinical neuroscience depends on three ingredients: (a) investigating complex mental behaviours and the underlying cognitive processes; (b) mapping neural systems and their function; and (c) methods and tools that can bridge the gap between brain and mental behaviour. Experimental psychology and behavioural neurology has delivered the first component. In vivo neuroimaging and other allied technologies allow us to probe and map neural systems, their connectivity and neurobiological responses. The principal aim of this ERC Advanced grant is to secure, for the first time, the crucial third ingredient – the methods and tools for bridging systematically between cognitive science and systems neuroscience.

The grant is based on two main activities: (i) convergence of methods – instead of employing each neuroscience and cognitive method independently, they will be planned and executed simultaneously to force a convergence of results; and (ii) development of a new type of neurocomputational model - to provide a novel formalism for bridging between brain and cognition. Computational models are used in cognitive science to mimic normal and impaired behaviour. Such models also have an as-yet untapped potential to connect neuroanatomy and cognition: latent in every model is a kind of brain-mind duality – each model is based on a computational architecture which generates behaviour. We will retain the ability to simulate detailed cognitive behaviour but simultaneously make the models’ architecture reflect systems-level neuroanatomy and function.

Why is it important for society?
The strategic target of this ERC Advanced grant is to initiate a new drive towards the ultimate goal of cognitive neuroscience: to specify how neural machinery synthesises cognitive function and dysfunction after brain damage, at a computational-mechanistic level. The multi-disciplinary work will be focussed on the neural basis of language and its disorders (aphasia and acquired dyslexia). The results will be relevant to both basic and clinical disciplines (including psychology, linguistics, cognitive neuroscience, neuropsychology, speech pathology, behavioural neurology, etc.). The purpose of this grant is to develop and use state-of-the-art techniques in order to derive neuroanatomically-constrained, computationally-implemented models of normal and disordered language processing. The next generation of neurobiological and behavioural interventions for aphasia and acquired dyslexia requires a paradigm shift in our understanding of how the cognitive processes underlying language arise from the neurobiology of the brain. The topic focus of language is socially and strategically important given that language impairments are a common, disabling feature in many types of dementia (including Alzheimer’s disease and the progressive aphasias) and following stroke (1/3 patients acutely and 1/5 in the chronic phase) – diseases which are becoming ever more common in Europe’s ageing societies. The 2012 European Brain Council study on the costs of brain disorders estimated that, as at 2010, 6.3m people in the EU suffer from dementia and 8.2m people from stroke (with estimated, conservative total health costs of €105b and €64b, respectively). All future projections indicate a worrying escalation in the rate and costs of these two diseases.

What are the overall objectives
This ERC Advanced grant contains three work packages, which run in parallel. All three workpackages (WP) run for the entire durat

Work performed

Excellent progress has already been made in all three WPs. In many cases we have not only conducted the research but we have also submitted and published papers as well. This progress is summarised in the sections below. The PI has been working on all three WPs from the beginning of the award. Postdocs (Halai, Jackson, Chang, Zhao) have worked on specific aspects of each Workpackage. In excess of the award agreement (for two non-ERC funded PhDs to be aligned with the award), five PhD students have been aligned with my ERC project (Busby; Alyahya; Zhao; Ingram; Stefaniak). Their work has significant boosted the output of the grant already (see below).

1.1 Objectives:
The objectives specified for each Workpackage are listed below with a current status evaluation flag. Further details on the progress are provided in Section 1.2. Note that all three WPs last for the full five years.

Work Package 1 – Neurocomputational modelling (over five years):
a) Exploration of alternative architectures [status = underway and on track; major paper being finalised for submission]
b) The relationship between structural and functional connectivity [status = underway and on track]
c) An integrated model of spoken and written language processing [status = underway; currently collecting and analysing key data from WP2 and WP3; various papers on empirical data published and in preparation]
d) Recovery of function [status = underway and on track, first paper being prepared for submission]
e) A bilateral model of language and recovery [status = underway and on track, first paper being finalised for submission]


Work Package 2 – understanding how language functions arise from the underlying neural machinery (over five years):
a) Further development and explorations of pseudo-neurosurgery to anatomical connectivity maps [status = underway and on track; first major paper published]
b) Relationship between functional and structural connectivity [status = underway and on track; first paper published]
c) Additional mapping of the language pathways [status = started and on track]
d) Division of labour across the dorsal and ventral pathways [not due to be started yet]
e) Using rTMS to shift functional connectivity [not due to be started yet]

Work Package 3 – how damage and recovery in neural systems give rise to acquired language impairments (aphasia) after brain damage (over five years):
a) PCA-based VLSM analysis [status = underway and on track; several papers published]
b) Error analysis [status = underway and on track; paper published]
c) Acquired dyslexias [status = underway and on track; paper published]
d) Connectivity analyses [status = underway and on track; paper published]
e) Establishing plasticity-related changes in functional connectivity [status = underway and on track; paper published]


1.2 Explanation of the work carried per WP
1.2.1 Work Package 1– Neurocomputational modelling (over five years):
Both Lambon Ralph (PI) and Jackson (1st postdoc) have been working on this WP. Building computational models is highly demanding, yet we have made excellent progress. Jackson has completed a critical initial phase of training in computational modelling skills and has already built various models to tackle some key theoretical questions. These relate to the first two objectives in WP1:
a) Exploration of alternative architectures [status = underway and on track; major paper being finalised for submission]
b) The relationship between structural and functional connectivity [status = underway and on track]
Our original neurocognitive models of semantics and language did not consider alternative computational architectures and how these interact with the nature of the representations to be learned and the interaction with cognitive-executive control mechanisms. We have, therefore, completed three sets of simulations to explore (i) the impact of the depth on a model of semantics (how many hidden layers); (ii) the interaction with different de

Final results

As well as tackling all stated targets in the ERC funded project, we have also taken the chance to go beyond these when exciting opportunities have arisen. These split into two sets – further basic cognitive neuroscience and clinical translation.

Further basic cognitive neuroscience:
(A) As well as contemporary tractography based studies, we have also explored the historical accounts of human white matter neuroanatomy from post mortem studies. This includes the seminal work of the Dejerines who produced the first formal investigations at the end of the nineteenth century. This work was published in French and we provided the first English translation with an accompanying opinion article:

“Reconnecting with Joseph and Augusta Dejerine: 100 years on”
Bajada et al., Brain 140; doi - 10.1093/brain/awx225
Abstract: Joseph Dejerine passed away on 28 February 1917 in the midst of a world at war. One hundred years later we celebrate the legacy of this pioneer in neuroscience. In 1895, Joseph Jules Dejerine published the first volume of their seminal work, Anatomie des centres nerveux; volume 2 was published in 1901. In a major section of this tome (vol. 1 pp. 749 – 780), Joseph Dejerine and his wife and long-term collaborator, Augusta Dejerine-Klumpke, produced a treatise on the white matter pathways of the brain, composed of anatomical descriptions of meticulous detail and beautiful illustration (drawn by H. Gillet) that reflected a combination of the most advanced methodologies of the day and a review of leading neuroscientific research. We have selected and focussed this specific output (which is provided for the first time as an English translation in the Supplementary Materials) from the many that the Dejerines published because its ideas and findings continue to be of relevance to modern neuroscience researchers today; especially those with an interest in connectional anatomy.

(B) As a part of exploring the semantic function of the anterior temporal lobe, we have explored the region’s response to various social and non-social concepts. We utilised these data in the explorations of patients with temporal lobe epilepsy (see WP 3) but also to examine how these types of concept map into the anterior temporal region. The paper has been published:

“Concrete versus abstract forms of social concept: an fMRI comparison of knowledge about people versus social terms.”
Rice et al., Philosophical Transactions of the Royal Society B: Biological Sciences 373; doi - 10.1098/rstb.2017.0136
Abstract: The anterior temporal lobes (ATLs) play a key role in conceptual knowledge representation. The hub-and-spoke theory suggests that the contribution of the ATLs to semantic representation is (a) transmodal, i.e., integrating information from multiple sensorimotor and verbal modalities, and (b) pan-categorical, representing concepts from all categories. Another literature, however, suggests that this region’s responses are modality- and category-selective; prominent examples include category selectivity for socially-relevant concepts and face recognition. The predictions of each approach have never been directly compared. We used data from three studies to compare category-selective responses within the ATLs. Study 1 compared ATL responses to famous people vs. another conceptual category (landmarks) from visual vs. auditory inputs. Study 2 compared ATL responses to famous people from pictorial and written word inputs. Study 3 compared ATL responses to a different kind of socially-relevant stimuli, namely abstract non-person related words, in order to ascertain whether ATL subregions are engaged for social concepts more generally or only for person-related knowledge. Across all three studies a dominant bilateral ventral ATL cluster responded to all categories in all modalities. Anterior to this “pan-category” transmodal region, a second cluster responded more weakly overall yet selectively for people, but did so equally for spo

Website & more info

More info: https://www.mrc-cbu.cam.ac.uk/people/matt.lambon-ralph/.