Authors:

Henriques, R.N., HENSON, R. Cam-CAN & CORREIA, M.M.

Reference:

Year of publication:

In Press

CBU number:

8947

Abstract:

Diffusion Magnetic Resonance Imaging (dMRI) is sensitive to white matter microstructural changes across the human lifespan. Several models have been proposed to provide more sensitive and specific metrics than those provided by the conventional Diffusion Tensor Imaging (DTI) analysis. However, previous results using different metrics have led to contradictory conclusions regarding the effect of age on fibre demyelination and axonal loss in adults. Moreover, it remains unclear whether these metrics provide distinct information about the effects of age, e.g., on different white-matter tracts. To address this, we analysed dMRI data from 651 adults approximately uniformly aged from 18 to 88 years in the Cam-CAN cohort, using six dMRI metrics: Fractional Anisotropy (FA) from standard DTI; Mean Signal Diffusion (MSD) and Mean Signal Kurtosis (MSK) from Diffusional Kurtosis Imaging (DKI) applied to directional averaged diffusion-weighted signals; and Neurite Density Index (NDI), Orientation Dispersion Index (ODI) and isotropic Free water volume fraction (Fiso) estimated from Neurite Orientation Dispersion and Density Imaging (NODDI). Averaging across white-matter regions-of-interest (ROIs), second-order polynomial fits revealed that MSD, MSK and Fiso showed the strongest effects of age, with significant quadratic components suggesting more rapid and sometimes inverted effects in old age. Analysing the data in different age subgroups revealed that some apparent discrepancies in previous studies may be explained by the use of cohorts with different age ranges. Factor analysis of the six metrics across all ROIs revealed three independent factors that can be associated to 1) tissue microscopic properties (e.g. differences in fibre density/myelin), 2) free-water contamination, and 3) tissue configuration complexity (e.g. crossing, dispersing, fanning fibres). While FA captures a combination of different factors, other dMRI metrics are strongly aligned to specific factors (NDI and MSK with Factor 1, Fiso with Factor 2, and ODI with Factor 3). To assess whether directional diffusion and kurtosis quantities provide additional information about the effects of age, further factor analyses were also performed, which showed that additional information about the effects of age may be present in radial and axial kurtosis estimates (but not standard axial and radial diffusivity). In summary, our study offers an explanation for previous discrepancies reported in dMRI ageing studies and provides further insights on the interpretation of different dMRI metrics in the context of white matter microstructural properties.

Data available, click to request

Authors:

Watanabe, K., Kadoshina,, M, Kusunoki, M, Buckley, M.J., DUNCAN, J.

Reference:

Year of publication:

In Press

CBU number:

8946

Abstract:

While classic views proposed that working memory (WM) is mediated by sustained firing, recent evidence suggests a contribution of activity-silent states. Within WM, human neuroimaging studies suggest a switch between attentional foreground and background, with only the foregrounded item represented in active neural firing. To address this process at the cellular level, we recorded prefrontal (PFC) and posterior parietal (PPC) neurons in a complex problem-solving task, with monkeys searching for one or two target locations in a first cycle of trials, and retaining them for memory-guided revisits on subsequent cycles. When target locations were discovered, neither frontal nor parietal neurons showed sustained goal-location codes continuing into subsequent trials and cycles. Instead there were sequences of timely goal silencing and reactivation, and following reactivation, sustained states until behavioral response. With two target locations, goal representations in both regions showed evidence of transitions between foreground and background, but the PFC representation was more complete, extending beyond the current trial to include both past and future selections. In the absence of unbroken sustained codes, different neuronal states interact to support maintenance and retrieval of WM representations across successive trials.

Data available, click to request

Authors:

VON SETH, J., Nicholls, V., Tyler, L., Clarke, A.

Reference:

Year of publication:

2023

CBU number:

8944

Abstract:

Visual object recognition has been traditionally conceptualised as a predominantly feedforward process through the ventral visual pathway. While feedforward artificial neural networks (ANNs) can achieve human-level classification on some image-labelling tasks, it's unclear whether computational models of vision alone can accurately capture the evolving spatiotemporal neural dynamics. Here, we probe these dynamics using a combination of representational similarity and connectivity analyses of fMRI and MEG data recorded during the recognition of familiar, unambiguous objects. Modelling the visual and semantic properties of our stimuli using an artificial neural network as well as a semantic feature model, we find that unique aspects of the neural architecture and connectivity dynamics relate to visual and semantic object properties. Critically, we show that recurrent processing between the anterior and posterior ventral temporal cortex relates to higher-level visual properties prior to semantic object properties, in addition to semantic-related feedback from the frontal lobe to the ventral temporal lobe between 250 and 500 ms after stimulus onset. These results demonstrate the distinct contributions made by semantic object properties in explaining neural activity and connectivity, highlighting it as a core part of object recognition not fully accounted for by current biologically inspired neural networks. Data availability statement The data used in this research was obtained from different experiments with different availabilities. The MEG data collected as part of the Cambridge Centre for Ageing and Neuroscience was part of stage III and is available upon requested (see https://camcan-archive.mrc-cbu.cam.ac.uk/dataaccess/). The remaining MEG data is found here https://osf.io/2uqf4/105, and fMRI data here https://osf.io/e2s59/106. The source data to produce the figures is hosted at the same OSF site.

URL:

Data for this project is available at: https://osf.io/e2s59/106

Authors:

RAYKOV, P., KNIGHTS, E., HENSON, R., CAM-CAN.

Reference:

Year of publication:

In Press

CBU number:

8943

Abstract:

Healthy aging is typically accompanied by cognitive decline. Previous work has shown that engaging in multiple, non-work activities during midlife can have a protective effect on cognition several decades later, rendering it less dependent on brain structural health; the definition of “cognitive reserve”. Other work has shown that increasing age is associated with reduced segregation of large-scale brain functional networks. Here we tested the hypothesis that functional segregation (SyS) mediates this effect of middle-aged lifestyle on late-life cognition. We used fMRI data from three tasks in the CamCAN dataset, together with cognitive data on fluid intelligence, episodic memory, and retrospective lifestyle data from the Lifetime of Experiences Questionnaire (LEQ). In all three tasks, we showed that SyS related to fluid intelligence even after adjusting for the (nonlinear) age effects. However, we found no evidence that SyS in late-life mediated the relationship between non-specific (non-occupation) midlife activities and either measure of cognition in late-life. Thus, the brain correlates of cognitive reserve arising from mid-life activities remain to be discovered. OSF: https://osf.io/bq3a7/

Data for this project is available at: https://osf.io/bq3a7/

Authors:

Wagner, A.P., Galante, J., Dufour, G., Barton, G., Stochl, J., VAINRE, M. and Jones, P.

Reference:

Year of publication:

2023

CBU number:

8942

Abstract:

Objective Increasing numbers of young people attending university has raised concerns about the capacity of student mental health services to support them. We conducted a randomised controlled trial (RCT) to explore whether provision of an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students-MSS), compared with university mental health support as usual (SAU), reduced psychological distress during the examination period. Here, we conduct an economic evaluation of MSS+SAU compared with SAU. Design and setting Economic evaluation conducted alongside a pragmatic, parallel, single-blinded RCT comparing provision of MSS+SAU to SAU. Participants 616 university students randomised. Primary and secondary outcome measures The primary economic evaluation assessed the cost per quality-adjusted life year (QALY) gained from the perspective of the university counselling service. Costs relate to staff time required to deliver counselling service offerings. QALYs were derived from the Clinical Outcomes in Routine Evaluation Dimension 6 Dimension (CORE-6D) preference based tool, which uses responses to six items of the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM; primary clinical outcome measure). Primary follow-up duration was 5 and 7 months for the two recruitment cohorts. Results It was estimated to cost £1584 (2022 prices) to deliver an MSS course to 30 students, £52.82 per student. Both costs (adjusted mean difference: £48, 95% CI £40-£56) and QALYs (adjusted mean difference: 0.014, 95% CI 0.008 to 0.021) were significantly higher in the MSS arm compared with SAU. The incremental cost-effectiveness ratio (ICER) was £3355, with a very high (99.99%) probability of being cost-effective at a willingness-to-pay threshold of £20 000 per QALY. Conclusions MSS leads to significantly improved outcomes at a moderate additional cost. The ICER of £3355 per QALY suggests that MSS is cost-effective when compared with the UK's National Institute for Health and Care Excellence thresholds of £20 000 per QALY. Trial registration number Australian and New Zealand Clinical Trials Registry, ACTRN12615001160527.

URL:

Data available, click to request

Authors:

KUSEC, A., MURPHY, F.C., PEERS, P.V., Bennett, R., CARMONA, E., Korbacz, A., Lawrence, C., Cameron, E., Bateman, A., WATSON, P., Allanson, J., duToit, P., MANLY, T.

Reference:

Year of publication:

2023

CBU number:

8941

Abstract:

Background Acquired brain injury (ABI) is linked to increased depression risk. Existing therapies for depression in ABI (e.g., cognitive behavioural therapy) have mixed efficacy. Behavioural activation (BA), an intervention that encourages engaging in positively reinforcing activities, shows promise. The primary aims were to assess feasibility, acceptability, and potential efficacy of two 8-week BA groups. Methods Adults (≥ 18 years) recruited from local ABI services, charities, and self-referral via social media were randomised to condition. The Activity Planning group (AP; "traditional" BA) trained participants to plan reinforcing activities over 8 weeks. The Activity Engagement group (AE; "experiential" BA) encouraged engagement in positive activities within session only. Both BA groups were compared to an 8-week Waitlist group (WL). The primary outcomes, feasibility and acceptability, were assessed via recruitment, retention, attendance, and qualitative feedback on groups. The secondary outcome, potential efficacy, was assessed via blinded assessments of self-reported activity levels, depression, and anxiety (at pre- and post-intervention and 1 month follow-up) and were compared across trial arms. Data were collected in-person and remotely due to COVID-19. Results N = 60 participants were randomised to AP (randomised n = 22; total n = 29), AE (randomised n = 22; total n = 28), or re-randomised following WL (total n = 16). Whether in-person or remote, AP and AE were rated as similarly enjoyable and helpful. In exploring efficacy, 58.33% of AP members had clinically meaningful activity level improvements, relative to 50% AE and 38.5% WL. Both AP and AE groups had depression reductions relative to WL, but only AP participants demonstrated anxiety reductions relative to AE and WL. AP participants noted benefits of learning strategies to increase activities and learning from other group members. AE participants valued social discussion and choice in selecting in-session activities. Conclusions Both in-person and remote group BA were feasible and acceptable in ABI. Though both traditional and experiential BA may be effective, these may have different mechanisms. OSF: https://osf.io/e5btr

URL:

Data for this project is available at: https://osf.io/e5btr

Authors:

KUSEC, A., Methley, A., MURPHY, F.C., PEERS, P.V., CARMONA, E., MANLY, T.

Reference:

Year of publication:

2023

CBU number:

8940

Abstract:

Background Acquired brain injuries (ABI) from stroke, head injury, or resected brain tumours are associated with poor emotional wellbeing and heightened risk of mood disorder. Common sequalae of ABI, such as poor attention and memory, can create barriers to the efficacy of cognitively demanding mood interventions, such as Cognitive Behavioural Therapy (CBT). Behavioural Activation (BA), where individuals plan and engage in reinforcing activities, is a promising alternative due to lower cognitive demands. However, BA was initially developed in clinical populations without ABI where the primary barriers to activity engagement were low mood and anxious avoidance. Additionally, BA can incorporate a range of techniques (e.g., mood monitoring, activity scheduling, targeting avoidance, contingency management) and psychoeducational topics (e.g., mindfulness, managing uncertainty; social/communication skills). Exploring barriers and facilitators to adopting specific BA components in ABI is an important aim. Methods Semi-structured interviews were conducted with purposively selected ABI survivors (N = 16) with both low and high depressive symptoms, and family members (N = 7). Questions focused on routine and enjoyable activities, and feedback on 10 different BA techniques and associated psychoeducational topics. Transcripts were analysed using an interpretive description framework. Analysis was informed by field notes, reflexivity diaries, and peer debriefing. Results The final constructed framework, Creating Sustainable Engagement, comprises a two-tier hierarchy. Higher-level themes concerned core perspectives of BA, regardless of BA component discussed. This included identifying optimal time windows for different BA components (Right Tool at the Right Time), that BA components should, at least initially, not be burdensome or fatiguing (Perceived Effort), that emotional readiness to confront activity-mood relationships should be addressed (Emotional Impact), and that planned BA activities be consistent with individual values (Relation to Values). Lower-level themes concerned specific BA components: Of these, activity scheduling, procedures targeting avoidance, managing uncertainty and social/communication skills were generally well-received, while mood monitoring, contingency management, and mindfulness had mixed feedback. Conclusions BA is a widely scalable intervention that can be adapted for ABI. This study provides a novel framework on implementing a range of BA components in ABI and adds to the limited evidence on which components may be particularly suitable. OSF: http://osf.io/btwg3

URL:

Data for this project is available at: http://osf.io/btwg3

Authors:

MANLY, T., Farooqui, A.

Reference:

Year of publication:

In Press

CBU number:

8938

Abstract:

Why do we divide (‘chunk’) long tasks into a series of shorter subtasks? A popular view is that limits in working memory (WM) prevent us from simultaneously maintaining all task relevant information in mind. We therefore chunk the task into smaller units so that we only maintain information in WM that is relevant to the current unit. In contrast to this view, we show that long tasks that are not constrained by WM limits are nonetheless chunked into smaller units. Participants executed long sequences of standalone but demanding trials that were not linked to any WM representation and whose execution was not constrained by how much information could be simultaneously held in WM. Using signs well-known to reflect beginning of new task units, we show that such trial sequences were not executed as a single task unit but were spontaneously chunked and executed as series smaller units. We also found that sequences made of easier trials were executed as longer task units and vice-versa, further suggesting that the length of task executed as one unit may be constrained by cognitive limits other than WM. Cognitive limits are typically seen to constrain how many things can be done simultaneously e.g., how many events can be maintained in WM or attended at the same time. We show a new aspect of these limits that constrains the length of behaviour that can be executed sequentially as a single task- unit.

Data for this project is held by an external institution. Please contact the authors to request a copy.

Authors:

MAGNABOSCO, F. HAUK, O.

Reference:

Year of publication:

2023

CBU number:

8936

Abstract:

We used eye-tracking during natural reading to study how semantic control and representation mechanisms interact for the successful comprehension of sentences, by manipulating sentence context and single-word meaning. Specifically, we examined whether a word’s semantic characteristic (concreteness) affects first fixation and gaze durations (FFDs and GDs) and whether it interacts with the predictability of a word. We used a linear mixed effects model including several possible psycholinguistic covariates. We found a small but reliable main effect of concreteness and replicated predictability effect on FFDs, but we found no interaction between the two. The results parallel previous findings of additive effects of predictability (context) and frequency (lexical level) in fixation times. Our findings suggest that the semantics of a word and the context created by the preceding words additively influence early stages of word processing in natural sentence reading. Link to raw data: https://osf.io/wyp7a/ Link to analysis scripts: https://github.com/magna-fede/EOS/

URL:

Data available, click to request

Authors:

ACHTERBERG, J., AKARCA, D., Strouse, D.J., DUNCAN, J., ASTLE, D.E.

Reference:

Year of publication:

2023

CBU number:

8935

Abstract:

Brain networks exist within the confines of resource limitations. As a result, a brain network must overcome metabolic costs of growing and sustaining the network within its physical space, while simultaneously implementing its required information processing. To observe the effect of these processes, we introduce the spatially-embedded recurrent neural network (seRNN). seRNNs learn basic task-related inferences while existing within a 3D Euclidean space, where the communication of constituent neurons is constrained by a sparse connectome. We find that seRNNs converge on structural and functional features that are also commonly found in primate cerebral cortices. Specifically, they converge on solving inferences using modular small-world networks, in which functionally similar units spatially configure themselves to utilize an energetically efficient mixed-selective code. Because these features emerge in unison, seRNNs reveal how many common structural and functional brain motifs are strongly intertwined and can be attributed to basic biological optimization processes. seRNNs incorporate biophysical constraints within a fully artificial system and can serve as a bridge between structural and functional research communities to move neuroscientific understanding forward. Code available at: https://codeocean.com/capsule/2879348/tree/v2

URL:

Data available, click to request