Periodic Reporting for period 1 - AGEING PLASTICITY (Prefrontal plasticity underpinning resilience against cognitive ageing.)
Reporting period: 2020-03-26 to 2022-03-25
As global life expectancy increases, so do pathological age-related conditions impacting cognition. The worldwide prevalence of Alzheimer’s Disease is expected to rise from 46 to 131.5 million affected people in the next 30 years, which will drastically compromise quality of life for many individuals and place a considerable economic burden on society. As acknowledged by the EU Commission, there is an imperative to ‘improve our understanding of the causes and mechanisms underlying…healthy ageing and disease’. Older adults differ vastly in the extent to which their cognitive functions, such as memory, attention, and decision making remain healthy. Highlighting sources of interindividual variability in this resilience to cognitive ageing, particularly in the face of neuropathology such as Alzheimer’s Disease, will enhance the development of targeted neurorehabilitation interventions to prevent and redress cognitive decline.
The objectives of this project were to examine how resilience to age-related cognitive decline is supported by neuroanatomy (brain structure) and neurophysiology (brain function), and altered through a lifetime of cognitive and social enrichment. We provide increasing evidence that the right hemisphere fronto-parietal networks may be a critical correlate of cognitive resilience in ageing, and put forward a novel framework for investigating oscillatory markers which may vary according to cognitive health using mEEG. Through the use of these state-of-the-art cognitive neuroscience approaches to we aim to highlight optimal ways of altering brain health to benefit cognition, such that we can inform public health advise and translate basic research into concrete societal benefit.
The objectives of this project were to examine how resilience to age-related cognitive decline is supported by neuroanatomy (brain structure) and neurophysiology (brain function), and altered through a lifetime of cognitive and social enrichment. We provide increasing evidence that the right hemisphere fronto-parietal networks may be a critical correlate of cognitive resilience in ageing, and put forward a novel framework for investigating oscillatory markers which may vary according to cognitive health using mEEG. Through the use of these state-of-the-art cognitive neuroscience approaches to we aim to highlight optimal ways of altering brain health to benefit cognition, such that we can inform public health advise and translate basic research into concrete societal benefit.
Using MRI, I have recently observed, in collaboration with a colleague here at Oxford and our collaborator in Birmingham, that older individuals with greater resilience to cognitive decline exhibit less structural loss in the right fronto-parietal regions of the brain (Shalev, Brosnan, & Chechlacz, 2020 Cerebral Cortex Communications), and show altered (better) white matter structural properties (Brosnan et al., 2022, Brain Communications). Critical, older adults exposed to more cognitively and socially enriched environments showed better markers of brain, and subsequently cognitive health. We are excited by this work as it highlights a specific structural target for neurorehabilitation interventions to prevent and redress age-related cognitive deficits.
In addition I have been using neurophysiology (electroencephalography (EEG) and magnetoencephalography (MEG)) to understand the precise neurophysiological mechanisms underpinning variability in neurocognitive health in older adults. These results were well received at a recent conference (MEG UK) and we are currently preparing these for publication.
Emerging EEG work from an international collaboration between us here at Oxford (grant holder Méadhbh Brosnan and mentor Anna C. (Kia) Nobre), researchers at Monash University in Australia (PI Mark Bellgrove), and Trinity College in Dublin (Redmond O’Connell), highlights the particular relevance of a distinct neurophysiological signature (the centro-parietal positivity marker of sensory evidence accumulation) for indexing neurocognitive health in the ageing brain (Brosnan et al., under invited revision at Journal of Neuroscience, https://www.biorxiv.org/content/10.1101/2021.10.28.466233v1.full.pdf).
We are currently exploring whether a common oscillatory marker varies according to cognitive resilience using MEG data acquired using a ‘retro-cue’ working memory task. More specifically with this approach, we are investigating whether the speed at which an older adult can orientate their attention to items held in working memory (i) accounts for variability in longitudinal decline and (ii) difers according to oscillatory signatures in prefrontal cortex.
Finally, patients recovering from COVID-19 are experiencing persistent and often debilitating levels of fatigue, sustained attention and arousal difficulties (the latter which is often self-reported ‘brain fog’). My previous research, conducted as part of Marie Curie training network (the INDIREA project), focused on understanding the neurobiological basis of these symptoms in stroke survivors and designing novel intervention approaches to alleviate these deficits. Here at Oxford, in collaboration with the ‘C-MORE’ multi-organ study of COVID, I am applying this experience to investigate the neural basis of these symptoms in COVID survivors. We (Kia Nobre, Tom Marshall and I) have designed a novel MEG task to better understand the impact of covid on the brain, over and above the damage observed in other organs (most notably the lungs and heart). We have recently published some work developing the methods on this task to measure attention difficulties in patients who have experience stroke (Brosnan et al., 2022, Journal of the International Neuropsychological Society). In addition, to ensure widespread translational utility of this task, we have developed an online version of the task which is sensitive to deficits in attention across the lifespan. We are currently in conversation with industry parterns about the possibility of incorporating this into a commercially available product for better understanding cognitive health.
In addition I have been using neurophysiology (electroencephalography (EEG) and magnetoencephalography (MEG)) to understand the precise neurophysiological mechanisms underpinning variability in neurocognitive health in older adults. These results were well received at a recent conference (MEG UK) and we are currently preparing these for publication.
Emerging EEG work from an international collaboration between us here at Oxford (grant holder Méadhbh Brosnan and mentor Anna C. (Kia) Nobre), researchers at Monash University in Australia (PI Mark Bellgrove), and Trinity College in Dublin (Redmond O’Connell), highlights the particular relevance of a distinct neurophysiological signature (the centro-parietal positivity marker of sensory evidence accumulation) for indexing neurocognitive health in the ageing brain (Brosnan et al., under invited revision at Journal of Neuroscience, https://www.biorxiv.org/content/10.1101/2021.10.28.466233v1.full.pdf).
We are currently exploring whether a common oscillatory marker varies according to cognitive resilience using MEG data acquired using a ‘retro-cue’ working memory task. More specifically with this approach, we are investigating whether the speed at which an older adult can orientate their attention to items held in working memory (i) accounts for variability in longitudinal decline and (ii) difers according to oscillatory signatures in prefrontal cortex.
Finally, patients recovering from COVID-19 are experiencing persistent and often debilitating levels of fatigue, sustained attention and arousal difficulties (the latter which is often self-reported ‘brain fog’). My previous research, conducted as part of Marie Curie training network (the INDIREA project), focused on understanding the neurobiological basis of these symptoms in stroke survivors and designing novel intervention approaches to alleviate these deficits. Here at Oxford, in collaboration with the ‘C-MORE’ multi-organ study of COVID, I am applying this experience to investigate the neural basis of these symptoms in COVID survivors. We (Kia Nobre, Tom Marshall and I) have designed a novel MEG task to better understand the impact of covid on the brain, over and above the damage observed in other organs (most notably the lungs and heart). We have recently published some work developing the methods on this task to measure attention difficulties in patients who have experience stroke (Brosnan et al., 2022, Journal of the International Neuropsychological Society). In addition, to ensure widespread translational utility of this task, we have developed an online version of the task which is sensitive to deficits in attention across the lifespan. We are currently in conversation with industry parterns about the possibility of incorporating this into a commercially available product for better understanding cognitive health.
Using an integrative, multi-modal approach combining MRI, EEG, and neuropsychological assessments we aim to provide a uniquely comprehensive and clinically useful understanding of how the both brain structure and function contribute to distinct signatures of healthy cognitive ageing. Additionally using these approaches we will assess the feasability of using the CPP as an objective neural phenotype to measure treatment success and vulnerability to future cognitive decline in older adults. An overarching aim of this work is to assess the potential for translating our brain-based assessments of neurocognitive health into widely accessible clinical assessments of brain health (similar to how blood pressure and heart rate measure are now widely available assessments of cardiovascular health).
The COVID study described above has been an ambitious, multidisciplinary endeavour, involving cross-talk between a wide range of specialist areas. It is an exciting, beyond the state of the art project to be a part of. Emerging results suggest that in many patients, covid is having a lasting negative impact on neurological function. Through better understanding the impact of covid on the brain, we aim to design superior interventions to alleviate the persistent and often debilitating symptoms of fatigue, arousal, and breathlessness, thereby having tangible societal implications for public health. With our novel collaborations, we additionally have sparked some interesting questions about the role of cognitive and emotional factors on physical symptoms leading to novel inter-disciplinary perspectives on the mind-body relationship.
The COVID study described above has been an ambitious, multidisciplinary endeavour, involving cross-talk between a wide range of specialist areas. It is an exciting, beyond the state of the art project to be a part of. Emerging results suggest that in many patients, covid is having a lasting negative impact on neurological function. Through better understanding the impact of covid on the brain, we aim to design superior interventions to alleviate the persistent and often debilitating symptoms of fatigue, arousal, and breathlessness, thereby having tangible societal implications for public health. With our novel collaborations, we additionally have sparked some interesting questions about the role of cognitive and emotional factors on physical symptoms leading to novel inter-disciplinary perspectives on the mind-body relationship.