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"Hampshire, A."
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Profiles of objective and subjective cognitive function in Post-COVID Syndrome, COVID-19 recovered, and COVID-19 naïve individuals
2024
Post-COVID Syndrome has emerged as a significant public health concern worldwide with increasing evidence to suggest that individuals who have had an acute COVID-19 infection report lingering memory and attention difficulties, even in individuals who have fully recovered and no longer experiencing symptoms of COVID-19. The present study sought to investigate the profile of objective and subjective cognitive difficulties in people who have Post-COVID Syndrome, people who have fully recovered from an acute COVID infection and people who have never had COVID-19. We further sought to explore the extent to which self-reported fatigue and stress are related to subjective and objective cognitive difficulties. 162 participants including 50 people living with Post-COVID Syndrome, 59 people who have had COVID-19 but have fully recovered and 53 people who have never experienced symptoms of COVID-19 and had never tested positive for COVID-19 were recruited from Academic Prolific to complete a series of online questionnaires and neurocognitive tasks. Subjective cognitive function was measured using the Cognitive Failures Questionnaire and objective cognitive function was measured using the Cognitron cognitive test battery. We found that objective and subjective measures of cognitive function were not significantly related, suggesting that self-reports of “brain fog” are not reflecting objectively measured cognitive dysfunction. A MANOVA revealed that subjective cognitive deficits were driven by heightened perceived stress and fatigue and not significantly related to COVID-19 status. Objective cognitive function, however, was significantly related to perceived stress and COVID status whereby we observed significant objective cognitive deficits in people who have been exposed to an acute COVID-19 infection regardless of whether they had Post-COVID Syndrome or had fully recovered, as compared to people who had never had COVID-19. This suggests that an acute infection can have long term effects on cognitive function, even without persistent COVID-19 symptoms. Encouragingly, objective cognitive function was significantly associated with time since initial infection showing that cognitive deficits improved over time for people who had recovered from COVID-19. However, we did not observe the same improvement in individuals with Post-COVID Syndrome and observed that cognitive dysfunction was significantly related to the number of neurological symptoms presently experienced. These results add to the accumulating literature that COVID-19 is associated with significant cognitive difficulties following a COVID-19 infection, which appear to improve over time for those who have recovered from COVID-19 yet persist in people living with Post-COVID Syndrome.
Journal Article
Adaptive working memory strategy training in early Alzheimer's disease: Randomised controlled trial
by
Hampshire, A.
,
Howard, R. J.
,
Huntley, J. D.
in
Aged
,
Alzheimer Disease - physiopathology
,
Alzheimer Disease - rehabilitation
2017
Interventions that improve cognitive function in Alzheimer's disease are urgently required.
To assess whether a novel cognitive training paradigm based on 'chunking' improves working memory and general cognitive function, and is associated with reorganisation of functional activity in prefrontal and parietal cortices (trial registration: ISRCTN43007027).
Thirty patients with mild Alzheimer's disease were randomly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks. Pre- and post-intervention functional magnetic resonance imaging (fMRI) scans were also conducted.
Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function. Further, fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls.
Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer's disease.
Journal Article
Just a phase? Causal probing reveals spurious phasic dependence of sustained attention
by
Rhodes, E.
,
Hampshire, A.
,
Grossman, N.
in
Attention
,
Attention - physiology
,
Brain - physiology
2024
•We causally probed the role of spontaneous EEG rhythms in visual attention via phase-locking.•Theta phase predicted behaviour offline, but cues presented in real-time with these oscillations had no effect on behaviour.•Spurious theta rhythmic sampling is an artefact of the evoked potential and acausal analysis.•ecHT accurately computes the phase in real-time and mitigates erroneous phase-behaviour correlations.
For over a decade, electrophysiological studies have reported correlations between attention / perception and the phase of spontaneous brain oscillations. To date, these findings have been interpreted as evidence that the brain uses neural oscillations to sample and predict upcoming stimuli. Yet, evidence from simulations have shown that analysis artefacts could also lead to spurious pre-stimulus oscillations that appear to predict future brain responses. To address this discrepancy, we conducted an experiment in which visual stimuli were presented in time to specific phases of spontaneous alpha and theta oscillations. This allowed us to causally probe the role of ongoing neural activity in visual processing independent of the stimulus-evoked dynamics. Our findings did not support a causal link between spontaneous alpha / theta rhythms and behaviour. However, spurious correlations between theta phase and behaviour emerged offline using gold-standard time-frequency analyses. These findings are a reminder that care should be taken when inferring causal relationships between neural activity and behaviour using acausal analysis methods.
Journal Article
Frictiotaxis underlies focal adhesion-independent durotaxis
2025
Cells move directionally along gradients of substrate stiffness — a process called durotaxis. In the situations studied so far, durotaxis relies on cell-substrate focal adhesions to sense stiffness and transmit forces that drive directed motion. However, whether and how durotaxis can take place in the absence of focal adhesions remains unclear. Here, we show that confined cells can perform durotaxis despite lacking focal adhesions. This durotactic migration depends on an asymmetric myosin distribution and actomyosin retrograde flow. We propose that the mechanism of this focal adhesion-independent durotaxis is that stiffer substrates offer higher friction. We put forward a physical model that predicts that non-adherent cells polarise and migrate towards regions of higher friction — a process that we call frictiotaxis. We demonstrate frictiotaxis in experiments by showing that cells migrate up a friction gradient even when stiffness is uniform. Our results broaden the potential of durotaxis to guide any cell that contacts a substrate, and they reveal a mode of directed migration based on friction. These findings have implications for cell migration during development, immune response and cancer progression, which usually takes place in confined environments that favour adhesion-independent amoeboid migration.
Cells typically migrate toward stiffer substrates via durotaxis, relying on focal adhesions. Here, the authors show that confined cells can migrate up friction gradients without focal adhesions, revealing a mode of directed migration called frictiotaxis.
Journal Article
When thoughts become action: An fMRI paradigm to study volitional brain activity in non-communicative brain injured patients
2007
The assessment of voluntary behavior in non-communicative brain injured patients is often challenging due to the existence of profound motor impairment. In the absence of a full understanding of the neural correlates of consciousness, even a normal activation in response to passive sensory stimulation cannot be considered as proof of the presence of awareness in these patients. In contrast, predicted activation in response to the instruction to perform a mental imagery task would provide evidence of voluntary task-dependent brain activity, and hence of consciousness, in non-communicative patients. However, no data yet exist to indicate which imagery instructions would yield reliable single subject activation. The aim of the present study was to establish such a paradigm in healthy volunteers. Two exploratory experiments evaluated the reproducibility of individual brain activation elicited by four distinct mental imagery tasks. The two most robust mental imagery tasks were found to be spatial navigation and motor imagery. In a third experiment, where these two tasks were directly compared, differentiation of each task from one another and from rest periods was assessed blindly using a priori criteria and was correct for every volunteer. The spatial navigation and motor imagery tasks described here permit the identification of volitional brain activation at the single subject level, without a motor response. Volunteer as well as patient data [Owen, A.M., Coleman, M.R., Boly, M., Davis, M.H., Laureys, S., Pickard J.D., 2006. Detecting awareness in the vegetative state. Science 313, 1402] strongly suggest that this paradigm may provide a method for assessing the presence of volitional brain activity, and thus of consciousness, in non-communicative brain-injured patients.
Journal Article
Selective tuning of the right inferior frontal gyrus during target detection
by
Thompson, Russell
,
Owen, Adrian M.
,
Hampshire, Adam
in
Adult
,
Analysis of Variance
,
Anatomical correlates of behavior
2009
In the human brain, a network of frontal and parietal regions is commonly recruited during tasks that demand the deliberate, focused control of thought and action. Previously, using a simple target detection task, we reported striking differences in the selectivity of the BOLD response in anatomically distinct subregions of this network. In particular, it was observed that the right inferior frontal gyrus (IFG) followed a tightly tuned function, selectively responding only to the current target object. Here, we examine this functional specialization further, using adapted versions of our original task. Our results demonstrate that the response of the right IFG to targets is a strong and replicable phenomenon. It occurs under increased attentional load, when targets and distractors are equally frequent, and when controlling for inhibitory processes. These findings support the hypothesis that the right IFG responds selectively to those items that are of the most relevance to the currently intended task schema.
Journal Article
The neural basis of effective memory therapy in a patient with limbic encephalitis
Background:An fMRI study is described in which a postencephalitic woman with amnesia used a wearable camera which takes photographs passively, without user intervention, to record and review recent autobiographical events. “SenseCam” generates hundreds of images which can subsequently be reviewed quickly or one by one.Results:Memory for a significant event was improved substantially when tested after 4.5 weeks, if the patient viewed SenseCam images of the event every 2 days for 3 weeks. In contrast, after only 3.5 weeks, her memory was at chance levels for a similarly significant event which was reviewed equally often, but using a written diary. During the fMRI scan, the patient viewed images of these two events, plus images of an unrehearsed event and images from a novel “control” event that she had never experienced. There was no difference in behavioural responses or in activation when the unrehearsed and novel conditions were compared. Relative to the written-rehearsed condition, successful recognition of the images in the SenseCam-rehearsed condition was associated with activation of frontal and posterior cortical regions associated with normal episodic memory.Conclusion:SenseCam images may provide powerful cues that trigger the recall and consolidation of stored but inaccessible memories.
Journal Article
Putting brain training to the test
by
Ballard, Clive G.
,
Owen, Adrian M.
,
Dajani, Said
in
631/378/2649
,
631/477
,
Attention - physiology
2010
A no trainer?
Although the public spends millions of pounds per year on various 'brain training' programs, the efficacy and performance of these training regimes remain unclear. In a collaboration with the BBC science series
Bang Goes The Theory
, Adrian Owen and colleagues conducted a six-week trial of various online training regimes. And although they observed improvements on the specific tasks used for training, the authors concluded that any improvements failed to transfer to other untrained cognitive tasks.
Millions of pounds per year are spent on various 'brain-training' programs; however, the efficacy and performance of these training regimes is still unclear. In collaboration with the BBC, a six-week online study of brain training was conducted. Although improvements were observed in the specific tasks used for training, in the authors' view there was no evidence that these improvements transferred to other untrained cognitive tasks.
‘Brain training’, or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry
1
, yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals
2
,
3
and preschool children
4
, and video-game players outperform non-players on some tests of visual attention
5
. However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.
Journal Article
Gamma knife stereotactic radiosurgery for unilateral acoustic neuromas
Objective:To evaluate the clinical results achievable using current techniques of gamma knife stereotactic radiosurgery to treat sporadic unilateral acoustic neuromas. Methods:A retrospective review of 234 consecutive patients treated for unilateral acoustic neuromas between 1996 and 1999, with a mean (SD) follow up of 35 (16) months. Tumour control was assessed with serial radiological imaging and by the need for surgical intervention. Hearing preservation was assessed using Gardner-Robertson grades. Details of complications including cranial neuropathies and non-specific vestibulo-cochlear symptoms are included. Results:A tumour control rate in excess of 92% was achieved, with only 3% of patients undergoing surgery after radiosurgery. Results were less good for larger tumours, but control rates of 75% were achieved for 35–45 mm diameter lesions. Of patients with discernible hearing, Gardner-Robertson grades were unchanged in 75%. Facial nerve function was adversely affected in 4.5%, but fewer than 1% of patients had persistent weakness. Trigeminal symptoms improved in 3%, but developed in 5% of patients, being persistent in less than 1.5%. Transient non-specific vestibulo-cochlear symptoms were reported by 13% of patients. Conclusions:Tumour control rates, while difficult to define, are comparable after radiosurgery with those experienced after surgery. The complications and morbidity after radiosurgery are far less frequent than those encountered after surgery. This, combined with its minimally invasive nature, may make radiosurgery increasingly the treatment of choice for small and medium sized acoustic neuromas.
Journal Article
Sports-related concussion not associated with long-term cognitive or behavioural deficits: the PROTECT-TBI study
2025
BackgroundThe cognitive effects of sports-related concussion (SRC) have been the subject of vigorous debate but there has been little research into long-term outcomes in non-athlete populations.MethodsThis cohort study of UK community-dwelling adults (aged 50–90 years) was conducted between November 2015 and November 2020, with up to 4 years annual follow-up (n=15 214). Lifetime history of concussions was collected at baseline using the Brain Injury Screening Questionnaire. The first analysis grouped participants by type of concussion (no concussion, only SRC, only non-SRC (nSRC), mixed concussions (both SRC and nSRC)) and the second grouped the participants by number (0, 1, 2 or 3+ SRC or nSRC). Mixed models were used to assess the effect of concussion on outcomes including four cognitive domains and one behavioural measure (Mild Behavioural Impairment-C).ResultsAnalysis of the included participants (24% male, mean age=64) at baseline found that the SRC group had significantly better working memory (B=0.113, 95% CI 0.038, 0.188) and verbal reasoning (B=0.199, 95% CI 0.092, 0.306) compared with those without concussion. Those who had suffered one SRC had significantly better verbal reasoning (B=0.111, 95% CI 0.031, 0.19) and attention (B=0.115, 95% CI 0.028, 0.203) compared with those with no SRC at baseline. Those with 3+ nSRCs had significantly worse processing speed (B=−0.082, 95% CI −0.144 to –0.019) and attention (B=−0.156, 95% CI −0.248 to –0.063). Those with 3+ nSRCs had a significantly worse trajectory of verbal reasoning with increasing age (B=−0.088, 95% CI −0.149 to –0.026).ConclusionsCompared with those reporting no previous concussions, those with SRC had no cognitive or behavioural deficits and seemed to perform better in some tasks. As indicated by previous studies, sports participation may confer long-term cognitive benefits.
Journal Article