Liz Mc Manus Biobank Brain MRI The Effects

Liz Mc. Manus Biobank Brain MRI: The Effects of Life Stress on the Ageing Brain

Brain MRI in the UK Biobank • Aim to scan 100, 000 from original cohort • 48, 765 individuals scanned • 39, 767 available data sets • Raw data & Imaging derived phenotypes (IDP)

Brain MRI: Acquisition Slide provided by Karla Miller

Brain MRI: Expected Neuropathology • 100, 000 people (45 -75 yo, if scanned in 2016) Slide provided by Karla Miller

Slide provided by Karla Miller

Brain MRI: Structural IDPs • Category 110: T 1 structural brain MRI • IDPs for volumes of cortical and sub cortical regions • Processed using: • FSL (volumes) • Freesurfer (volumes, cortical thickness, surface areas & complex measures)

Brain MRI: Diffusion IDPs • Category 107: Diffusion brain MRI • Measures the ability of water molecules to diffuse within their local tissue environment • IDPs for DTI and NODDI metrics Fractional Anisotropy (FA) Mean Diffusivity (MD) Intra-cellular Volume Fraction (ICVF) Isotropic Volume Fraction (ISOVF)

Brain MRI: Task Based Functional MRI (f. MRI) • Category 106: Task functional brain MRI • Shapes and face matching task • IDPs available for face, shapes and contrast: • 90 th Percentile BOLD effect • 90 th percentile z-statistic • Median BOLD effect • Median z-statistic shapes faces>shapes

Brain MRI: Resting State Functional MRI (rf. MRI) • Category 111: Resting functional brain MRI • Measures changes in blood oxygenation associated with intrinsic brain activity • Full and partial correlation matrix available

Downloading Data • Raw data • Bulk download • Need sufficient research data storage on the CSF • IDP data • Select categories required in application • Easy download into csv format • R/MATLAB to handle and run stats • Reasonably powerful computer • Not necessarily suitable to run analysis on CSF

Benefits of Brain MRI • Participant scan costs ~ £ 450 -500 • Much larger samples possible • Quantity of data allows for development of new data processing pipelines and analyses • Population study- so some disease and some healthy • Recruitment for diseases can be difficult • Match with other data types- cognitive/health/demographic etc

Benefits of Brain MRI IDPs • Robust and reliable processing pipelines developed by the biobank imaging team • Well quality controlled data[1] • Lots of time saved by already having reliably processed data • Less expertise required [1] Alfaro-Almagro, F. , Jenkinson, M. , Bangerter, N. K. , Andersson, J. L. , Griffanti, L. , Douaud, G. , . . . & Vidaurre, D. (2018). Image processing and Quality Control for the first 10, 000 brain imaging datasets from UK Biobank. Neuroimage, 166, 400 -424.

Issues with Biobank Brain MRI data • IDP’s only specific regions of interest • Scans done years after initial session/cognitive assessments • Some difficulties linking brain images to other data types • Currently no central storage/centrally stored copy of Biobank brain data • Particularly for raw images

The Effects of Life Stress on the Ageing Brain

Study Rational • Stress most commonly associated with the limbic system • High levels of stress can lead to regional volume reductions • May also cause microstructure damage • Potentially leads to cognitive impairments • Similar effects seen for stress related mental health disorders • i. e. PTSD and anxiety

Defining Stress • 157, 000 participants with relevant data • Calculated a child & Adult stress score for all participants with appropriate data Adult life stress questions Childhood stress questions Biobank Field ID When I was growing up I… Reverse coding 20487 Felt hated by a family member No 20488 Was physically abused by a family member No 20489 Felt loved Yes 20490 Was sexually molested No 20491 Had someone to take me to a doctor when needed Yes Rating scale Biobank Field ID Since I was sixteen I…. Reverse coding 20521 Have experienced belittlement by a partner or ex-partner No 20522 Have been in a confiding relationship Yes 20523 Have experienced physical violence from a partner or expartner No 20524 Have experienced sexual interference by a partner or expartner without consent No 20525 Have had money to pay rent/mortgage when needed Yes Biobank Answer Numeric coding Never true 0 Rarely true 1 Sometimes true 2 Often true 3 Very often true 4 Prefer not to answer Data removed

Defining Stress Groups • Low Stress = 0 Child • High Stress > mean + 2 SD Adult Low High Low 1 3 High 2 4

Results: Grey Matter Volume • Covarying for age and sex • No group differences for grey matter volume in: • Amygdala • Hippocampus • Thalamus • Significant effects of age and sex in hippocampus and thalamus • No effects in amygdala

Results: Microstructural Changes • Covarying for age and sex • No group difference in Hippocampus • Group differences in Thalamus seen for: • FA • ISOVF • ICVF (didn’t survive multiple comparisons correction) • Significant effects of age and sex

Sex Differences: Males • Whole male sample with relevant data (N = 11, 290) • Partial correlations to control for age • All significant correlations occurred in the thalamus • Adult stress FA in the left thalamus (r = -. 034, p =. 003) • Adult stress OD in the left thalamus (r =. 030, p =. 01) • Child stress FA in the right thalamus (r = -. 026, p =. 04)

Sex Differences: Females • N = 13, 285 • Thalamus only

Conclusions • At the group level: • Microstructural changes are seen in the thalamus • Even before macrostructural grey matter volume • Stress disproportionately impacts female brain • The thalamus in particular

Other Current Research • Early life adversity and family history of depression may affect the brain- Franziska Goer • Associations between social isolation/loneliness and changes in grey matter volumes in cases of depression- Zhenhong He • How different types of social support affect mental health outcomes and how this is related to the structure and functioning of the brain- Jessica Stepanous • Can socioeconomic factors affect the relationship between depression and anxiety and brain structure- Sasha Johns