ORCID Profile
0000-0003-0735-4349
Current Organisation
University of Oxford
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Publisher: Oxford University Press (OUP)
Date: 18-03-2021
Abstract: Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.
Publisher: Elsevier BV
Date: 08-2015
Publisher: Elsevier BV
Date: 06-2015
Publisher: Society for Neuroscience
Date: 31-12-2013
DOI: 10.1523/JNEUROSCI.2899-13.2014
Abstract: Emerging evidence suggests that items held in working memory (WM) might not all be in the same representational state. One item might be privileged over others, making it more accessible and thereby recalled with greater precision. Here, using transcranial magnetic stimulation (TMS), we provide causal evidence in human participants that items in WM are differentially susceptible to disruptive TMS, depending on their state, determined either by task relevance or serial position. Across two experiments, we applied TMS to area MT+ during the WM retention of two motion directions. In Experiment 1, we used an “incidental cue” to bring one of the two targets into a privileged state. In Experiment 2, we presented the targets sequentially so that the last item was in a privileged state by virtue of recency. In both experiments, recall precision of motion direction was differentially affected by TMS, depending on the state of the memory target at the time of disruption. Privileged items were recalled with less precision, whereas nonprivileged items were recalled with higher precision. Thus, only the privileged item was susceptible to disruptive TMS over MT+. By contrast, precision of the nonprivileged item improved either directly because of facilitation by TMS or indirectly through reduced interference from the privileged item. Our results provide a unique line of evidence, as revealed by TMS over a posterior sensory brain region, for at least two different states of item representation in WM.
Publisher: Frontiers Media SA
Date: 06-11-2014
Publisher: Oxford University Press (OUP)
Date: 24-07-2016
DOI: 10.1093/BRAIN/AWW188
Publisher: Oxford University Press (OUP)
Date: 19-12-2020
DOI: 10.1093/BRAINCOMMS/FCAA219
Abstract: Female sex, age and carriage of the apolipoprotein E e4 allele are the greatest risk factors for sporadic Alzheimer’s disease. The hippoc us has a selective vulnerability to atrophy in ageing that may be accelerated in Alzheimer’s disease, including in those with increased genetic risk of the disease, years before onset. Within the hippoc al complex, subfields represent cytoarchitectonic and connectivity based isions. Variation in global hippoc al and subfield volume associated with sex, age and apolipoprotein E e4 status has the potential to provide a sensitive biomarker of future vulnerability to Alzheimer’s disease. Here, we examined non-linear age, sex and apolipoprotein E effects, and their interactions, on hippoc al and subfield volumes across several decades spanning mid-life to old age in 36 653 healthy ageing in iduals. FMRIB Software Library derived estimates of total hippoc al volume and Freesurfer derived estimates hippoc al subfield volume were estimated. A model-free, sliding-window approach was implemented that does not assume a linear relationship between age and subfield volume. The annualized percentage of subfield volume change was calculated to investigate associations with age, sex and apolipoprotein E e4 homozygosity. Hippoc al volume showed a marked reduction in apolipoprotein E e4/e4 female carriers after age 65. Volume was lower in homozygous e4 in iduals in specific subfields including the presubiculum, subiculum head, cornu ammonis 1 body, cornu ammonis 3 head and cornu ammonis 4. Nearby brain structures in medial temporal and subcortical regions did not show the same age, sex and apolipoprotein E interactions, suggesting selective vulnerability of the hippoc us and its subfields. The findings demonstrate that in healthy ageing, two factors—female sex and apolipoprotein E e4 status—confer selective vulnerability of specific hippoc al subfields to volume loss.
Publisher: Springer Science and Business Media LLC
Date: 07-09-2020
DOI: 10.1038/S41467-020-18201-5
Abstract: Healthy cognitive ageing is a societal and public health priority. Cerebrovascular risk factors increase the likelihood of dementia in older people but their impact on cognitive ageing in younger, healthy brains is less clear. The UK Biobank provides cognition and brain imaging measures in the largest population cohort studied to date. Here we show that cognitive abilities of healthy in iduals (N = 22,059) in this s le are detrimentally affected by cerebrovascular risk factors. Structural equation modelling revealed that cerebrovascular risk is associated with reduced cerebral grey matter and white matter integrity within a fronto-parietal brain network underlying executive function. Notably, higher systolic blood pressure was associated with worse executive cognitive function in mid-life (44–69 years), but not in late-life ( years). During mid-life this association did not occur in the systolic range of 110–140 mmHg. These findings suggest cerebrovascular risk factors impact on brain structure and cognitive function in healthy people.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for sanjay manohar.