Publications by authors named "Heidi Johansen-Berg"

175 Publications

Self-Reported and Objective Sleep Measures in Stroke Survivors With Incomplete Motor Recovery at the Chronic Stage.

Neurorehabil Neural Repair 2021 Jul 1:15459683211029889. Epub 2021 Jul 1.

Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, 6396University of Oxford, Oxford, UK.

. Stroke survivors commonly complain of difficulty sleeping. Poor sleep is associated with reduced quality of life and more understanding of long-term consequences of stroke on sleep is needed. The primary aims were to (1) compare sleep measures between chronic stroke survivors and healthy controls and (2) test for a relationship between motor impairment, time since stroke and sleep. Secondary aims were to explore mood and inactivity as potential correlates of sleep and test the correlation between self-reported and objective sleep measures. Cross-sectional sleep measures were obtained for 69 chronic stroke survivors (mean 65 months post-stroke, 63 years old, 24 female) and 63 healthy controls (mean 61 years old, 27 female). Self-reported sleep was assessed with the sleep condition indicator (SCI) and sleep diary ratings, objective sleep with 7-nights actigraphy and mood with the Hospital Anxiety and Depression Scale. Upper extremity motor impairment was assessed with the Fugl-Meyer assessment. Stroke survivors had significantly poorer SCI score ( < .001) and higher wake after sleep onset ( = .005) than controls. Neither motor impairment, nor time since stroke, explained significant variance in sleep measures for the stroke group. For all participants together, greater depression was associated with poorer SCI score ( = .197, < .001) and higher age with more fragmented sleep ( = .108, < .001). There were weak correlations between nightly sleep ratings and actigraphy sleep measures ( = .15-.24). Sleep disturbance is present long-term after stroke. Depressive symptoms may present a modifiable factor which should be investigated alongside techniques to improve sleep in this population.
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http://dx.doi.org/10.1177/15459683211029889DOI Listing
July 2021

Dual-task walking and automaticity after Stroke: Insights from a secondary analysis and imaging sub-study of a randomised controlled trial.

Clin Rehabil 2021 May 30:2692155211017360. Epub 2021 May 30.

Centre for Movement, Occupational and Rehabilitation Sciences, Oxford Brookes University, Oxford, UK.

Objective: To test the extent to which initial walking speed influences dual-task performance after walking intervention, hypothesising that slow walking speed affects automatic gait control, limiting executive resource availability.

Design: A secondary analysis of a trial of dual-task (DT) and single-task (ST) walking interventions comparing those with (walking speed ⩾0.8 m s,  = 21) and (walking speed <0.79 m s,  = 24) capacity at baseline.

Setting: Community.

Subjects: Adults six-months post stroke with walking impairment.

Interventions: Twenty sessions of 30 minutes treadmill walking over 10 weeks with (DT) or without (ST) cognitive distraction. and groups were formed regardless of intervention received.

Main Measures: A two-minute walk with (DT) and without (ST) a cognitive distraction assessed walking. NIRS measured prefrontal cortex activation during treadmill walking with (DT) and without (ST) Stroop and planning tasks and an MRI sub-study used ankle-dorsiflexion to simulate walking.

Results: ST walking improved in both groups (∆baseline:  8.9 ± 13.4 m,  = 5.3±8.9 m, Group × time =  < 0.151) but only the walkers improved DT walking (∆baseline:  10.4 ± 13.9 m,  = 1.3 ± 7.7 m, Group × time =  < 0.025). NIRS indicated increased ispilesional prefrontal cortex activation during DT walking following intervention ( = 0.021). MRI revealed greater DT cost activation for walkers, and increased resting state connectivity of contralesional M1 with cortical areas associated with conscious gait control at baseline. After the intervention, resting state connectivity between ipsilesional M1 and bilateral superior parietal lobe, involved in integrating sensory and motor signals, increased in the walkers compared with walkers.

Conclusion: In individual who walk slowly it may be difficult to improve dual-task walking ability. ISRCTN50586966.
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http://dx.doi.org/10.1177/02692155211017360DOI Listing
May 2021

Exploring activity levels in physical education lessons in the UK: a cross-sectional examination of activity types and fitness levels.

BMJ Open Sport Exerc Med 2021 9;7(1):e000924. Epub 2021 Mar 9.

Centre for Movement, Occupational and Rehabilitation Sciences (MOReS), Oxford Brookes University, Oxford, Oxfordshire, UK.

Objectives: To establish pupil fitness levels, and the relationship to global norms and physical education (PE) enjoyment. To measure and describe physical activity (PA) levels during secondary school PE lessons, in the context of recommended levels, and how levels vary with activity and lesson type.

Methods: A cross-sectional design; 10 697 pupils aged 12.5 (SD 0.30) years; pupils who completed a multistage fitness test and wore accelerometers to measure PA during PE lessons. Multilevel models estimated fitness and PE activity levels, accounting for school and class-level clustering.

Results: Cardiorespiratory fitness was higher in boys than girls (ß=-0.48; 95% CI -0.56 to -0.39, p<0.001), within absolute terms 51% of boys and 54% of girls above the 50th percentile of global norms. On average, pupils spent 23.8% of PE lessons in moderate-to-vigorous PA (MVPA), and 7.1% in vigorous PA (VPA). Fitness-focused lessons recorded most VPA in co-educational (ß=1.09; 95% CI 0.43 to 1.74) and boys-only lessons (ß=0.32; 95% CI -0.21 to 0.85). In girls-only lessons, track athletics recorded most VPA (ß=0.13; 95% CI -0.50 to 0.75) and net/wall/racket games (ß=0.97; 95% CI 0.12 to 1.82) the most MVPA. For all lesson types, field athletics was least active (ß=-0.85; 95% CI -1.33 to -0.36). There was a relationship of enjoyment of PE to fitness (ß=1.03; 95% CI 0.83 to 1.23), and this relationship did not vary with sex (ß=-0.14 to 0.23; 95% CI -0.16 to 0.60).

Conclusions: PE lessons were inactive compared with current guidelines. We propose that if we are to continue to develop a range of sporting skills in schools at the same time as increasing levels of fitness and PA, there is a need to introduce additional sessions of PE activity focused on increasing physical activity.

Trial Registration Number: NCT03286725.
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http://dx.doi.org/10.1136/bmjsem-2020-000924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944978PMC
March 2021

Multimodal Imaging Brain Markers in Early Adolescence Are Linked with a Physically Active Lifestyle.

J Neurosci 2021 02 12;41(5):1092-1104. Epub 2021 Jan 12.

Wellcome Centre for Integrative Neuroimaging, FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom.

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence. An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development.
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http://dx.doi.org/10.1523/JNEUROSCI.1260-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880281PMC
February 2021

Associations between fitness, physical activity and mental health in a community sample of young British adolescents: baseline data from the Fit to Study trial.

BMJ Open Sport Exerc Med 2020 2;6(1):e000819. Epub 2020 Oct 2.

Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Objectives: To examine relationships between fitness, physical activity and psychosocial problems among English secondary school pupils and to explore how components of physically active lifestyles are associated with mental health and well-being.

Methods: A total of 7385 participants aged 11-13 took a fitness test and completed self-reported measures of physical activity, attitudes to activity, psychosocial problems and self-esteem during the Fit to Study trial. Multilevel regression, which modelled school-level cluster effects, estimated relationships between activity, fitness and psychosocial problems; canonical correlation analysis (CCA) explored modes of covariation between active lifestyle and mental health variables. Models were adjusted for covariates of sex, free school meal status, age, and time and location of assessments.

Results: Higher fitness was linked with fewer internalising problems (β=-0.23; 95% CI -0.26 to -0.21; p<0.001). More activity was also related to fewer internalising symptoms (β=-0.24; 95% CI -0.27 to -0.20; p<0.001); the relationship between activity and internalising problems was significantly stronger for boys than for girls. Fitness and activity were also favourably related to externalising symptoms, with smaller effect sizes. One significant CCA mode, with a canonical correlation of 0.52 (p=0.001), was characterised high cross-loadings for positive attitudes to activity (0.46) and habitual activity (0.42) among lifestyle variables; and for physical and global self-esteem (0.47 and 0.42) among mental health variables.

Conclusion: Model-based and data-driven analysis methods indicate fitness as well as physical activity are linked to adolescent mental health. If effect direction is established, fitness monitoring could complement physical activity measurement when tracking public health.
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http://dx.doi.org/10.1136/bmjsem-2020-000819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547542PMC
October 2020

Effects of gender, activity type, class location and class composition on physical activity levels experienced during physical education classes in British secondary schools: a pilot cross-sectional study.

BMC Public Health 2020 Oct 21;20(1):1590. Epub 2020 Oct 21.

Centre for Movement, Occupational and Rehabilitation Sciences (MOReS), Oxford Brookes University, Headington Campus, Oxford, OX3 0BP, UK.

Background: Pupils in secondary schools do not meet the targets for physical activity levels during physical education (PE) sessions, and there is a lack of data on the vigorous physical activity domain (VPA) in PE known to be positively associated with cardio metabolic health While PE session intensity depends on a variety of factors, the large majority of studies investigating these factors have not taken into account the nested structure of this type of data set. Therefore, the aim of this study was to investigate the relationship between various factors (gender, activity type, class location and class composition) and various activity levels during PE classes in secondary schools, using a multi-level statistical approach.

Methods: Year eight (12-13 years old) adolescents (201 boys and 106 girls) from six schools were fitted with accelerometers during one PE session each, to determine the percentage (%) of the PE session time spent in sedentary (SPA), light (LPA), moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) intensity levels. Two- and three-level (pupils, n = 307; classes, n = 13, schools, n = 6) mixed-effect models were used to assess the relationship between accelerometer-measured physical activity levels (% of class time spent in various activity levels) and gender, activity type, class location and composition.

Results: Participants engaged in MVPA and VPA for 30.7 ± 1.2% and 11.5 ± 0.8% of PE classes, respectively. Overall, no significant association between gender or class composition and PA was shown. A significant relationship between activity type and PA was observed, with Artistic classes significantly less active than Fitness classes for VPA (5.4 ± 4.5 vs. 12.5 ± 7.1%, p = 0.043, d:1.19). We also found a significant association between class location and PA, with significantly less time spent in SPA (24.8 ± 4.8% vs. 30.0 ± 3.4%, p = 0.042, d:0.77) and significantly more time spent in VPA (12.4 ± 3.7% vs. 7.6 ± 2.0%, p = 0.022, d:1.93) and MVPA (32.3 ± 6.7% vs.24.8 ± 3.8%, p = 0.024, d:1.33) in outdoors vs. indoors classes.

Conclusions: The results suggest that class location and activity type could be associated with the intensity of PA in PE. It is essential to take into account the clustered nature of this type of data in similar studies if the sample size allows it.
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http://dx.doi.org/10.1186/s12889-020-09698-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580031PMC
October 2020

Fit to Study: Reflections on designing and implementing a large-scale randomized controlled trial in secondary schools.

Trends Neurosci Educ 2020 09 24;20:100134. Epub 2020 Jun 24.

Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU.

Background: The randomised controlled trial (RCT) design is increasingly common among studies seeking good-quality evidence to advance educational neuroscience, but conducting RCTs in schools is challenging. Fit to Study, one of six such trials funded by the Education Endowment Foundation and Wellcome Trust, tested an intervention to increase vigorous physical activity during PE lessons on maths attainment among pupils aged 12-13. This review of designing and conducting an RCT in 104 schools is intended as a resource on which researchers might draw for future studies.

Method: We consider intervention design and delivery; recruitment, retention, trial management, data collection and analysis including ethical considerations and working with evaluators.

Results: Teacher training, intervention delivery and data collection during large-scale RCTs require a flexible approach appropriate to educational settings, which in turn entails planning and resources.

Conclusion: Simple interventions, with few outcome measures and minimal missing data, are preferable to more complex designs.
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http://dx.doi.org/10.1016/j.tine.2020.100134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488648PMC
September 2020

A critical evaluation of systematic reviews assessing the effect of chronic physical activity on academic achievement, cognition and the brain in children and adolescents: a systematic review.

Int J Behav Nutr Phys Act 2020 06 22;17(1):79. Epub 2020 Jun 22.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, OX3 7JX, UK.

Background: International and national committees have started to evaluate the evidence for the effects of physical activity on neurocognitive health in childhood and adolescence to inform policy. Despite an increasing body of evidence, such reports have shown mixed conclusions. We aimed to critically evaluate and synthesise the evidence for the effects of chronic physical activity on academic achievement, cognitive performance and the brain in children and adolescents in order to guide future research and inform policy.

Methods: MedLine, Embase, PsycINFO, Cochrane Library, Web of Science, and ERIC electronic databases were searched from inception to February 6th, 2019. Articles were considered eligible for inclusion if they were systematic reviews with or without meta-analysis, published in peer-reviewed (English) journals. Reviews had to be on school-aged children and/or adolescents that reported on the effects of chronic physical activity or exercise interventions, with cognitive markers, academic achievement or brain markers as outcomes. Reviews were selected independently by two authors and data were extracted using a pre-designed data extraction template. The quality of reviews was assessed using AMSTAR-2 criteria.

Results: Of 908 retrieved, non-duplicated articles, 19 systematic reviews met inclusion criteria. One high-quality review reported inconsistent evidence for physical activity-related effects on cognitive- and academic performance in obese or overweight children and adolescents. Eighteen (critically) low-quality reviews presented mixed favourable and null effects, with meta-analyses showing small effect sizes (0.1-0.3) and high heterogeneity. Low-quality reviews suggested physical activity-related brain changes, but lacked an interpretation of these findings. Systematic reviews varied widely in their evidence synthesis, rarely took intervention characteristics (e.g. dose), intervention fidelity or study quality into account and suspected publication bias. Reviews consistently reported that there is a lack of high-quality studies, of studies that include brain imaging outcomes, and of studies that include adolescents or are conducted in South American and African countries.

Conclusions: Inconsistent evidence exists for chronic physical activity-related effects on cognitive-, academic-, and brain outcomes. The field needs to refocus its efforts towards improving study quality, transparency of reporting and dissemination, and is urged to differentiate between intervention characteristics for its findings to have a meaningful impact on policy.
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http://dx.doi.org/10.1186/s12966-020-00959-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310146PMC
June 2020

Sleep Disruption After Brain Injury Is Associated With Worse Motor Outcomes and Slower Functional Recovery.

Neurorehabil Neural Repair 2020 07 7;34(7):661-671. Epub 2020 Jun 7.

University of Oxford, Oxford, UK.

. Sleep is important for consolidation of motor learning, but brain injury may affect sleep continuity and therefore rehabilitation outcomes. . This study aims to assess the relationship between sleep quality and motor recovery in brain injury patients receiving inpatient rehabilitation. . Fifty-nine patients with brain injury were recruited from 2 specialist inpatient rehabilitation units. Sleep quality was assessed (up to 3 times) objectively using actigraphy (7 nights) and subjectively using the Sleep Condition Indicator. Motor outcome assessments included Action Research Arm test (upper limb function), Fugl-Meyer Assessment (motor impairment), and the Rivermead Mobility Index. The Functional Independence Measure (FIM) was assessed at admission and discharge by the clinical team. Fifty-five age- and gender-matched healthy controls completed one assessment. . Inpatients demonstrated lower self-reported sleep quality ( < .001) and more fragmented sleep ( < .001) than controls. For inpatients, sleep fragmentation explained significant additional variance in motor outcomes, over and above that explained by admission FIM score ( < .017), such that more disrupted sleep was associated with poorer motor outcomes. Using stepwise linear regression, sleep fragmentation was the only variable found to explain variance in rate of change in FIM ( = 0.12, = .027), whereby more disrupted sleep was associated with slower recovery. . Inpatients with brain injury demonstrate impaired sleep quality, and this is associated with poorer motor outcomes and slower functional recovery. Further investigation is needed to determine how sleep quality can be improved and whether this affects outcome.
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http://dx.doi.org/10.1177/1545968320929669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327954PMC
July 2020

The effects of an aerobic training intervention on cognition, grey matter volumes and white matter microstructure.

Physiol Behav 2020 09 29;223:112923. Epub 2020 May 29.

FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK, OX3 9DU. Electronic address:

While there is strong evidence from observational studies that physical activity is associated with reduced risk of cognitive decline and dementia, the extent to which aerobic training interventions impact on cognitive health and brain structure remains subject to debate. In a pilot study of 46 healthy older adults (66.6 years ± 5.2 years, 63% female), we compared the effects of a twelve-week aerobic training programme to a waitlist control condition on cardiorespiratory fitness, cognition and magnetic resonance imaging (MRI) outcomes. Cardiorespiratory fitness was assessed by VO max testing. Cognitive assessments spanned executive function, memory and processing speed. Structural MRI analysis included examination of hippocampal volume, and voxel-wise assessment of grey matter volumes using voxel-based morphometry. Diffusion tensor imaging analysis of fractional anisotropy, axial diffusivity and radial diffusivity was performed using tract-based spatial statistics. While the intervention successfully increased cardiorespiratory fitness, there was no evidence that the aerobic training programme led to changes in cognitive functioning or measures of brain structure in older adults. Interventions that are longer lasting, multi-factorial, or targeted at specific high-risk populations, may yield more encouraging results.
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http://dx.doi.org/10.1016/j.physbeh.2020.112923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378567PMC
September 2020

Perceptions of active and inactive prototypes are associated with objective measures of physical activity in adolescents.

Psychol Health Med 2020 12 20;25(10):1216-1227. Epub 2020 Mar 20.

Department of Psychology, Social Work and Public Health, Oxford Brookes University , Oxford, UK.

The benefits of physical activity are known, but the proportion of adolescents meeting daily activity guidelines remains low. The Theory of Planned Behaviour (TPB), which assumes reasoned intentions explain actions, is a useful framework for predicting activity, but it leaves variance unexplained. The Prototype Willingness Model (PWM) which builds on the TPB, proposes a reasoned action pathway and a second social reactive pathway in which perceptions of social images, or prototypes, explain actions via behavioural willingness. We explored whether variables in the PWM's social reactive pathway explained variance in an objective measure of daily activity, over and above the reasoned action path. Participants aged 12-13 (n = 205) were invited to complete measures of constructs in the PWM and to wear an accelerometer for the next seven days. Overall, 126 students (65 males) participated. Reasoned intentions, attitudes and subjective norms explained 12.8% of variance in activity. Prototype perceptions and willingness explained an additional 13.1% of variance. Participants' perceived similarity to active prototypes, and unfavourable perceptions of inactive prototypes, significantly predicted activity. There were no significant differences between sexes on psychological variables. These findings highlight the importance of targeting prototype perceptions to encourage physical activity in this age group.
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http://dx.doi.org/10.1080/13548506.2020.1738018DOI Listing
December 2020

White matter structure and myelin-related gene expression alterations with experience in adult rats.

Prog Neurobiol 2020 04 27;187:101770. Epub 2020 Jan 27.

Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX3 9DU, UK.

White matter (WM) plasticity during adulthood is a recently described phenomenon by which experience can shape brain structure. It has been observed in humans using diffusion tensor imaging (DTI) and myelination has been suggested as a possible mechanism. Here, we set out to identify molecular and cellular changes associated with WM plasticity measured by DTI. We combined DTI, immunohistochemistry and mRNA expression analysis and examined the effects of somatosensory experience in adult rats. First, we observed experience-induced DTI differences in WM and in grey matter structure. C-Fos mRNA expression, a marker of cortical activity, in the barrel cortex correlated with the MRI WM metrics, indicating that molecular correlates of cortical activity relate to macroscale measures of WM structure. Analysis of myelin-related genes revealed higher myelin basic protein (MBP) mRNA expression. Higher MBP protein expression was also found via immunohistochemistry in WM. Finally, unbiased RNA sequencing analysis identified 134 differentially expressed genes encoding proteins involved in functions related to cell proliferation and differentiation, regulation of myelination and neuronal activity modulation. In conclusion, macroscale measures of WM plasticity are supported by both molecular and cellular evidence and confirm that myelination is one of the underlying mechanisms.
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http://dx.doi.org/10.1016/j.pneurobio.2020.101770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086231PMC
April 2020

Alcohol consumption is associated with reduced creatine levels in the hippocampus of older adults.

Psychiatry Res Neuroimaging 2020 01 16;295:111019. Epub 2019 Nov 16.

Department of Psychiatry, University of Oxford, Oxford, UK; Global Brain Health Institute, Department of Neurology, University of California San Francisco, San Francisco, California, USA.

Besides its well established susceptibility to ageing, the hippocampus has also been shown to be affected by alcohol consumption. Proton spectroscopy (H-MRS) of the hippocampus, particularly at high-field 7T MRI, may further our understanding of these associations. Here, we aimed to examine how hippocampal metabolites varied with age and alcohol consumption. Hippocampal metabolite spectra were acquired in 37 older adults using 7T H-MRS, from which we determined the absolute concentration of N-acetylaspartate (NAA), creatine, choline, myo-inositol, glutamate and glutamine. Thirty participants (mean age = 70.4 ± 4.7 years) also had self-reported data on weekly alcohol consumption. Total choline inversely correlated with age, although this did not survive multiple comparisons correction. Crucially, adults with a higher weekly alcohol consumption had significantly lower levels of creatine, suggesting a deficit in their hippocampal metabolism. These findings add to an increasing body of evidence linking alcohol to hippocampal function.
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http://dx.doi.org/10.1016/j.pscychresns.2019.111019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961205PMC
January 2020

Are People Ready for Personalized Brain Health? Perspectives of Research Participants in the Lifebrain Consortium.

Gerontologist 2020 08;60(6):1050-1059

Center for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Norway.

Background And Objectives: A healthy brain is central to physical and mental well-being. In this multi-site, qualitative study, we investigated views and attitudes of adult participants in brain research studies on the brain and personalized brain health as well as interest in maintaining a healthy brain.

Design And Methods: We conducted individual interviews with 44 adult participants in brain research cohorts of the Lifebrain consortium in Spain, Norway, Germany, and the United Kingdom. The interviews were audio recorded, transcribed, and coded using a cross-country codebook. The interview data were analyzed using qualitative content analysis.

Results: Most participants did not focus on their own brain health and expressed uncertainty regarding how to maintain it. Those actively focusing on brain health often picked one specific strategy like diet or memory training. The participants were interested in taking brain health tests to learn about their individual risk of developing brain diseases, and were willing to take measures to maintain their brain health if personalized follow-up was provided and the measures had proven impact. The participants were interested in more information on brain health. No differences in responses were identified between age groups, sex, or countries.

Discussion And Implications: Concise, practical, personalized, and evidence-based information about the brain may promote brain health. Based on our findings, we have launched an ongoing global brain health survey to acquire more extensive, quantitative, and representative data on public perception of personalized brain health.
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http://dx.doi.org/10.1093/geront/gnz155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427479PMC
August 2020

Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis.

Hum Brain Mapp 2019 10 29;40(15):4417-4431. Epub 2019 Jul 29.

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease-related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders.
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http://dx.doi.org/10.1002/hbm.24711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6772025PMC
October 2019

Structural Variability in the Human Brain Reflects Fine-Grained Functional Architecture at the Population Level.

J Neurosci 2019 07 31;39(31):6136-6149. Epub 2019 May 31.

FMRIB, Wellcome Centre for Integrative Neuroimaging,

Human brain structure topography is thought to be related in part to functional specialization. However, the extent of such relationships is unclear. Here, using a data-driven, multimodal approach for studying brain structure across the lifespan ( = 484, = 260 females), we demonstrate that numerous structural networks, covering the entire brain, follow a functionally meaningful architecture. These gray matter networks (GMNs) emerge from the covariation of gray matter volume and cortical area at the population level. We further reveal fine-grained anatomical signatures of functional connectivity. For example, within the cerebellum, a structural separation emerges between lobules that are functionally connected to distinct, mainly sensorimotor, cognitive and limbic regions of the cerebral cortex and subcortex. Structural modes of variation also replicate the fine-grained functional architecture seen in eight well defined visual areas in both task and resting-state fMRI. Furthermore, our study shows a structural distinction corresponding to the established segregation between anterior and posterior default-mode networks (DMNs). These fine-grained GMNs further cluster together to form functionally meaningful larger-scale organization. In particular, we identify a structural architecture bringing together the functional posterior DMN and its anticorrelated counterpart. In summary, our results demonstrate that the relationship between structural and functional connectivity is fine-grained, widespread across the entire brain, and driven by covariation in cortical area, i.e. likely differences in shape, depth, or number of foldings. These results suggest that neurotrophic events occur during development to dictate that the size and folding pattern of distant, functionally connected brain regions should vary together across subjects. Questions about the relationship between structure and function in the human brain have engaged neuroscientists for centuries in a debate that continues to this day. Here, by investigating intersubject variation in brain structure across a large number of individuals, we reveal modes of structural variation that map onto fine-grained functional organization across the entire brain, and specifically in the cerebellum, visual areas, and default-mode network. This functionally meaningful structural architecture emerges from the covariation of gray matter volume and cortical folding. These results suggest that the neurotrophic events at play during development, and possibly evolution, which dictate that the size and folding pattern of distant brain regions should vary together across subjects, might also play a role in functional cortical specialization.
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http://dx.doi.org/10.1523/JNEUROSCI.2912-18.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668209PMC
July 2019

Magnetic Resonance Techniques for Imaging White Matter.

Methods Mol Biol 2019 ;1936:397-407

NDCN Department, Wellcome Centre for Integrative Neuroimaging, FMRIB Centre, University of Oxford, Oxford, UK.

The white matter is a complex network of brain fibers connecting different information processing regions in the brain. In recent years, the investigation of white matter in humans and in animal models has greatly benefitted from the introduction of in vivo noninvasive magnetic resonance imaging (MRI) techniques. MRI allows for multiple in vivo time-point whole-brain acquisition in the same subject, thus it can be used longitudinally to monitor white matter brain change, intervention effects, as well as disease progression. However, MRI has low spatial resolution compared to gold standard cellular techniques and MRI measures are sensitive to a number of tissue properties resulting in a lack of specificity.The following chapter describes in simple technical terms to non-imaging experts some common MRI techniques that can be used to investigate white matter structure noninvasively, covering some of the advantages and pitfalls of each technique.
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http://dx.doi.org/10.1007/978-1-4939-9072-6_22DOI Listing
July 2019

Transcranial direct current stimulation for promoting motor function in cerebral palsy: a review.

J Neuroeng Rehabil 2018 12 20;15(1):121. Epub 2018 Dec 20.

Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.

Transcranial direct current stimulation (tDCS) has the potential to improve motor function in a range of neurological conditions, including Cerebral Palsy (CP). Although there have been many studies assessing tDCS in adult stroke, the literature regarding the efficacy of tDCS in CP is more limited. This review therefore focuses on the neurophysiological and clinical findings in children and adolescents with CP. Initial studies applying anodal tDCS to promote lower limb function are promising, with improvements in gait, mobility and balance reported. However, the results of upper limb studies are mixed and more research is needed. Studies investigating neurophysiological changes or predictors of response are also lacking. Large-scale longitudinal studies are needed for the lower limb to ascertain whether the initial pilot results translate into clinically meaningful improvements. Future studies of the upper limb should focus on determining the optimal stimulation parameters and consider tailoring stimulation to the individual based on the (re)organisation of their motor system.
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http://dx.doi.org/10.1186/s12984-018-0476-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302403PMC
December 2018

Neural basis of induced phantom limb pain relief.

Ann Neurol 2019 01 7;85(1):59-73. Epub 2019 Jan 7.

Wellcome Centre for Integrative Neuroimaging, FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.

Objective: Phantom limb pain (PLP) is notoriously difficult to treat, partly due to an incomplete understanding of PLP-related disease mechanisms. Noninvasive brain stimulation (NIBS) is used to modulate plasticity in various neuropathological diseases, including chronic pain. Although NIBS can alleviate neuropathic pain (including PLP), both disease and treatment mechanisms remain tenuous. Insight into the mechanisms underlying both PLP and NIBS-induced PLP relief is needed for future implementation of such treatment and generalization to related conditions.

Methods: We used a within-participants, double-blind, and sham-controlled design to alleviate PLP via task-concurrent NIBS over the primary sensorimotor missing hand cortex (S1/M1). To specifically influence missing hand signal processing, amputees performed phantom hand movements during anodal transcranial direct current stimulation. Brain activity was monitored using neuroimaging during and after NIBS. PLP ratings were obtained throughout the week after stimulation.

Results: A single session of intervention NIBS significantly relieved PLP, with effects lasting at least 1 week. PLP relief associated with reduced activity in the S1/M1 missing hand cortex after stimulation. Critically, PLP relief and reduced S1/M1 activity correlated with preceding activity changes during stimulation in the mid- and posterior insula and secondary somatosensory cortex (S2).

Interpretation: The observed correlation between PLP relief and decreased S1/M1 activity confirms our previous findings linking PLP with increased S1/M1 activity. Our results further highlight the driving role of the mid- and posterior insula, as well as S2, in modulating PLP. Lastly, our novel PLP intervention using task-concurrent NIBS opens new avenues for developing treatment for PLP and related pain conditions. ANN NEUROL 2019;85:59-73.
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http://dx.doi.org/10.1002/ana.25371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492189PMC
January 2019

Modulating Regional Motor Cortical Excitability with Noninvasive Brain Stimulation Results in Neurochemical Changes in Bilateral Motor Cortices.

J Neurosci 2018 08 20;38(33):7327-7336. Epub 2018 Jul 20.

Nuffield Department of Clinical Neurosciences, Functional Magnetic Resonance Imaging of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, OX3 9DU, United Kingdom, and

Learning a novel motor skill is dependent both on regional changes within the primary motor cortex (M1) contralateral to the active hand and also on modulation between and within anatomically distant but functionally connected brain regions. Interregional changes are particularly important in functional recovery after stroke, when critical plastic changes underpinning behavioral improvements are observed in both ipsilesional and contralesional M1s. It is increasingly understood that reduction in GABA in the contralateral M1 is necessary to allow learning of a motor task. However, the physiological mechanisms underpinning plasticity within other brain regions, most importantly the ipsilateral M1, are not well understood. Here, we used concurrent two-voxel magnetic resonance spectroscopy to simultaneously quantify changes in neurochemicals within left and right M1s in healthy humans of both sexes in response to transcranial direct current stimulation (tDCS) applied to left M1. We demonstrated a decrease in GABA in both the stimulated (left) and nonstimulated (right) M1 after anodal tDCS, whereas a decrease in GABA was only observed in nonstimulated M1 after cathodal stimulation. This GABA decrease in the nonstimulated M1 during cathodal tDCS was negatively correlated with microstructure of M1:M1 callosal fibers, as quantified by diffusion MRI, suggesting that structural features of these fibers may mediate GABA decrease in the unstimulated region. We found no significant changes in glutamate. Together, these findings shed light on the interactions between the two major network nodes underpinning motor plasticity, offering a potential framework from which to optimize future interventions to improve motor function after stroke. Learning of new motor skills depends on modulation both within and between brain regions. Here, we use a novel two-voxel magnetic resonance spectroscopy approach to quantify GABA and glutamate changes concurrently within the left and right primary motor cortex (M1) during three commonly used transcranial direct current stimulation montages: anodal, cathodal, and bilateral. We also examined how the neurochemical changes in the unstimulated hemisphere were related to white matter microstructure between the two M1s. Our results provide insights into the neurochemical changes underlying motor plasticity and may therefore assist in the development of further adjunct therapies.
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http://dx.doi.org/10.1523/JNEUROSCI.2853-17.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096041PMC
August 2018

Reaffirming the link between chronic phantom limb pain and maintained missing hand representation.

Cortex 2018 09 31;106:174-184. Epub 2018 May 31.

Wellcome Centre for Integrative Neuroimaging, MRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Institute of Cognitive Neuroscience, University College London, London, United Kingdom. Electronic address:

Phantom limb pain (PLP) is commonly considered to be a result of maladaptive brain plasticity. This model proposes that PLP is mainly caused by reorganisation in the primary somatosensory cortex, presumably characterised by functional degradation of the missing hand representation and remapping of other body part representations. In the current study, we replicate our previous results by showing that chronic PLP correlates with maintained representation of the missing hand in the primary sensorimotor missing hand cortex. We asked unilateral upper-limb amputees to move their phantom hand, lips or other body parts and measured the associated neural responses using functional magnetic resonance imaging (fMRI). We confirm that amputees suffering from worse chronic PLP have stronger activity in the primary sensorimotor missing hand cortex while performing phantom hand movements. We find no evidence of lip representation remapping into the missing hand territory, as assessed by measuring activity in the primary sensorimotor missing hand cortex during lip movements. We further show that the correlation between chronic PLP and maintained representation of the missing hand cannot be explained by the experience of chronic non-painful phantom sensations or compensatory usage of the residual arm or an artificial arm (prosthesis). Together, our results reaffirm a likely relationship between persistent peripheral inputs pertaining to the missing hand representation and chronic PLP. Our findings emphasise a need to further study the role of peripheral inputs from the residual nerves to better understand the mechanisms underlying chronic PLP.
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http://dx.doi.org/10.1016/j.cortex.2018.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143485PMC
September 2018

Cognition and mobility show a global association in middle- and late-adulthood: Analyses from the Canadian Longitudinal Study on Aging.

Gait Posture 2018 07 19;64:238-243. Epub 2018 Jun 19.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Human Brain Activity, Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Global Brain Health Institute, Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA. Electronic address:

Background: Given our aging population, there's great interest in identifying modifiable risk factors for cognitive decline. Studies have highlighted the relationship between aspects of mobility and cognitive processes. However, cognition and mobility are both multifaceted concepts and their interrelationships remain to be well defined.

Research Question: Here, we firstly aimed to replicate cross-sectional associations between objective measures of mobility and cognition. Second, we tested whether these associations remained after the consideration of multiple age-related confounders. Finally, to test the hypothesis that the association between mobility and cognition is stronger in older adults, we examined the moderating effect of age in the association between mobility and cognition.

Methods: In the Canadian Longitudinal Study on Aging, 28,808 community-dwelling adults (aged 45-87; 51% female) completed mobility (gait, balance and chair stands) and cognitive (memory, executive function and processing speed) assessments. General linear models were used to examine mobility-cognition relationships and the moderating effect of age.

Results: Cognitive measures were significantly associated with mobility measures (all p < 0.001). Further, age significantly moderated the mobility-cognition relationship, with the strength of the associations generally increasing with age.

Significance: All cognitive measures were related to indices of mobility, suggesting a global association. In our moderation analyses, the mobility-cognition relationship often increased with age. However, the small effect sizes observed suggest that mobility is, in isolation, not a strong correlate of cognitive performance in middle and late-adulthood.
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http://dx.doi.org/10.1016/j.gaitpost.2018.06.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6052573PMC
July 2018

Development of white matter microstructure in relation to verbal and visuospatial working memory-A longitudinal study.

PLoS One 2018 24;13(4):e0195540. Epub 2018 Apr 24.

Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.

Working memory capacity is pivotal for a broad specter of cognitive tasks and develops throughout childhood. This must in part rely on development of neural connections and white matter microstructure maturation, but there is scarce knowledge of specific relations between this and different aspects of working memory. Diffusion tensor imaging (DTI) enables us to study development of brain white matter microstructure. In a longitudinal DTI study of 148 healthy children between 4 and 11 years scanned twice with an on average 1.6 years interval, we characterized change in fractional anisotropy (FA), mean (MD), radial (RD) and axial diffusivity (AD) in 10 major white matter tracts hypothesized to be of importance for working memory. The results showed relationships between change in several tracts and change in visuospatial working memory. Specifically, improvement in visuospatial working memory capacity was significantly associated with decreased MD, RD and AD in inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in the right hemisphere, as well as forceps major (FMaj). No significant relationships were found between change in DTI metrics and change in verbal working memory capacity. These findings yield new knowledge about brain development and corresponding working memory improvements in childhood.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195540PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916522PMC
July 2018

A community-based physical activity intervention to prevent mobility-related disability for retired older people (REtirement in ACTion (REACT)): study protocol for a randomised controlled trial.

Trials 2018 Apr 17;19(1):228. Epub 2018 Apr 17.

Centre for Exercise, Nutrition and Health Sciences, School for Policy Studies, University of Bristol, Bristol, BS8 1TZ, UK.

Background: The REtirement in ACTion (REACT) study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial (RCT) with an internal pilot phase. It aims to test the effectiveness and cost-effectiveness of a community, group-based physical activity intervention for reducing, or reversing, the progression of functional limitations in older people who are at high risk of mobility-related disability.

Methods/design: A sample of 768 sedentary, community-dwelling, older people aged 65 years and over with functional limitations, but who are still ambulatory (scores between 4 and 9 out of 12 in the Short Physical Performance Battery test (SPPB)) will be randomised to receive either the REACT intervention, delivered over a period of 12 months by trained facilitators, or a minimal control intervention. The REACT study incorporates comprehensive process and economic evaluation and a nested sub-study which will test the hypothesis that the REACT intervention will slow the rate of brain atrophy and of decline in cognitive function assessed using magnetic resonance imaging (MRI). Outcome data will be collected at baseline, 6, 12 and 24 months for the main study, with MRI sub-study data collected at baseline, 6 and 12 months. The primary outcome analysis (SPPB score at 24 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals.

Discussion: REACT represents the first large-scale, pragmatic, community-based trial in the UK to target the non-disabled but high-risk segment of the older population with an intervention to reduce mobility-related disability. A programme that can successfully engage this population in sufficient activity to improve strength, aerobic capacity, coordination and balance would have a major impact on sustaining health and independence. REACT is also the first study of its kind to conduct a full economic and comprehensive process evaluation alongside the RCT. If effective and cost-effective, the REACT intervention has strong potential to be implemented widely in the UK and elsewhere.

Trial Registration: ISRCTN, ID: ISRCTN45627165 . Retrospectively registered on 13 June 2016. Trial sponsor: University of Bath. Protocol Version 1.5.
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http://dx.doi.org/10.1186/s13063-018-2603-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905123PMC
April 2018

Artificial limb representation in amputees.

Brain 2018 05;141(5):1422-1433

Institute of Cognitive Neuroscience, University College London, London, UK.

The human brain contains multiple hand-selective areas, in both the sensorimotor and visual systems. Could our brain repurpose neural resources, originally developed for supporting hand function, to represent and control artificial limbs? We studied individuals with congenital or acquired hand-loss (hereafter one-handers) using functional MRI. We show that the more one-handers use an artificial limb (prosthesis) in their everyday life, the stronger visual hand-selective areas in the lateral occipitotemporal cortex respond to prosthesis images. This was found even when one-handers were presented with images of active prostheses that share the functionality of the hand but not necessarily its visual features (e.g. a 'hook' prosthesis). Further, we show that daily prosthesis usage determines large-scale inter-network communication across hand-selective areas. This was demonstrated by increased resting state functional connectivity between visual and sensorimotor hand-selective areas, proportional to the intensiveness of everyday prosthesis usage. Further analysis revealed a 3-fold coupling between prosthesis activity, visuomotor connectivity and usage, suggesting a possible role for the motor system in shaping use-dependent representation in visual hand-selective areas, and/or vice versa. Moreover, able-bodied control participants who routinely observe prosthesis usage (albeit less intensively than the prosthesis users) showed significantly weaker associations between degree of prosthesis observation and visual cortex activity or connectivity. Together, our findings suggest that altered daily motor behaviour facilitates prosthesis-related visual processing and shapes communication across hand-selective areas. This neurophysiological substrate for prosthesis embodiment may inspire rehabilitation approaches to improve usage of existing substitutionary devices and aid implementation of future assistive and augmentative technologies.
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http://dx.doi.org/10.1093/brain/awy054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5917779PMC
May 2018

Structural Plasticity in Adulthood with Motor Learning and Stroke Rehabilitation.

Annu Rev Neurosci 2018 07 28;41:25-40. Epub 2018 Feb 28.

Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, United Kingdom; email: ,

The development of advanced noninvasive techniques to image the human brain has enabled the demonstration of structural plasticity during adulthood in response to motor learning. Understanding the basic mechanisms of structural plasticity in the context of motor learning is essential to improve motor rehabilitation in stroke patients. Here, we review and discuss the emerging evidence for motor-learning-related structural plasticity and the implications for stroke rehabilitation. In the clinical context, a few studies have started to assess the effects of rehabilitation on structural measures to understand recovery poststroke and additionally to predict intervention outcomes. Structural imaging will likely have a role in the future in providing measures that inform patient stratification for optimal outcomes.
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http://dx.doi.org/10.1146/annurev-neuro-080317-062015DOI Listing
July 2018

Functional Strength Training and Movement Performance Therapy for Upper Limb Recovery Early Poststroke-Efficacy, Neural Correlates, Predictive Markers, and Cost-Effectiveness: FAST-INdiCATE Trial.

Front Neurol 2017 25;8:733. Epub 2018 Jan 25.

Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.

Background: Variation in physiological deficits underlying upper limb paresis after stroke could influence how people recover and to which physical therapy they best respond.

Objectives: To determine whether functional strength training (FST) improves upper limb recovery more than movement performance therapy (MPT). To identify: (a) neural correlates of response and (b) whether pre-intervention neural characteristics predict response.

Design: Explanatory investigations within a randomised, controlled, observer-blind, and multicentre trial. Randomisation was computer-generated and concealed by an independent facility until baseline measures were completed. Primary time point was outcome, after the 6-week intervention phase. Follow-up was at 6 months after stroke.

Participants: With some voluntary muscle contraction in the paretic upper limb, not full dexterity, when recruited up to 60 days after an anterior cerebral circulation territory stroke.

Interventions: Conventional physical therapy (CPT) plus either MPT or FST for up to 90 min-a-day, 5 days-a-week for 6 weeks. FST was "hands-off" progressive resistive exercise cemented into functional task training. MPT was "hands-on" sensory/facilitation techniques for smooth and accurate movement.

Outcomes: The primary efficacy measure was the Action Research Arm Test (ARAT). Neural measures: fractional anisotropy (FA) corpus callosum midline; asymmetry of corticospinal tracts FA; and resting motor threshold (RMT) of motor-evoked potentials.

Analysis: Covariance models tested ARAT change from baseline. At outcome: correlation coefficients assessed relationship between change in ARAT and neural measures; an interaction term assessed whether baseline neural characteristics predicted response.

Results: 288 Participants had: mean age of 72.2 (SD 12.5) years and mean ARAT 25.5 (18.2). For 240 participants with ARAT at baseline and outcome the mean change was 9.70 (11.72) for FST + CPT and 7.90 (9.18) for MPT + CPT, which did not differ statistically ( = 0.298). Correlations between ARAT change scores and baseline neural values were between 0.199,  = 0.320 for MPT + CPT RMT ( = 27) and -0.147,  = 0.385 for asymmetry of corticospinal tracts FA ( = 37). Interaction effects between neural values and ARAT change between baseline and outcome were not statistically significant.

Conclusions: There was no significant difference in upper limb improvement between FST and MPT. Baseline neural measures did not correlate with upper limb recovery or predict therapy response.

Trial Registration: Current Controlled Trials: ISRCT 19090862, http://www.controlled-trials.com.
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http://dx.doi.org/10.3389/fneur.2017.00733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810279PMC
January 2018

White Matter Plasticity in the Adult Brain.

Neuron 2017 12;96(6):1239-1251

Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.

The study of brain plasticity has tended to focus on the synapse, where well-described activity-dependent mechanisms are known to play a key role in learning and memory. However, it is becoming increasingly clear that plasticity occurs beyond the synapse. This review focuses on the emerging concept of white matter plasticity. For example, there is growing evidence, both from animal studies and from human neuroimaging, that activity-dependent regulation of myelin may play a role in learning. This previously overlooked phenomenon may provide a complementary but powerful route through which experience shapes the brain.
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http://dx.doi.org/10.1016/j.neuron.2017.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766826PMC
December 2017

Advances in noninvasive myelin imaging.

Dev Neurobiol 2018 02 10;78(2):136-151. Epub 2017 Nov 10.

Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom.

Myelin is important for the normal development and healthy function of the nervous system. Recent developments in MRI acquisition and tissue modeling aim to provide a better characterization and more specific markers for myelin. This allows for specific monitoring of myelination longitudinally and noninvasively in the healthy brain as well as assessment of treatment and intervention efficacy. Here, we offer a nontechnical review of MRI techniques developed to specifically monitor myelin such as magnetization transfer (MT) and myelin water imaging (MWI). We further summarize recent studies that employ these methods to measure myelin in relation to development and aging, learning and experience, and neuropathology and psychiatric disorders. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 78: 136-151, 2018.
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http://dx.doi.org/10.1002/dneu.22552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813152PMC
February 2018
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