The neural underpinnings of attention network components in healthy ageing: a structural MRI study 31 Speaker: Hanna Lu (PhD Candidate of Medical Sciences, CUHK) Supervisor: Prof. Sandra S.M. Chan Co-supervisor: Prof. Linda C.W. Lam 36

Introduction There are only two things certain in life: death and taxes. But,I'd like to add a third certainty: ageing Hong Kong: Aspects of ageing: -- Biological -- Psychological Social Emotion Cognition Personality 2013 - 13% (1 in 8, is an elderly) “aged society” 2023 - 19% (1 in 5, is an elderly) 2033 - 27% (1 in 4, is an elderly) “super-aged society” Healthy ageing

A “GATE” to understand Healthy ageing Healthy ageing: age-related changes of cognition MCI / MND MND: an updated diagnosis in DSM-5*: an evolution of “MCI” Dementia Complex attention: sustained attention, divided attention, selective attention, processing speed. Fig 1. MND as a concept (revised graph based on Petersen, R. C., et al., 2004) Attention network theory * MCI=Mild Cognitive Impairment; MND= Mild Neurocognitive Disorders DSM-5: Fifth Edition of the Diagnosis and Statistical Manual of Mental Disorders

Attention Network + + + + + * + + * or * *  Cue types: No cue, Center cue, Double Cue, Spatial cue (Up and Down) + * or * * M. I. Posner (1990), three components of attention network: * Alerting Orienting Executive control Alerting Orienting What Where + cue How + * Target ≤ 1700 ms + 100 ms Tailor-made test: attention network test (ANT) + * Platform: E-Prime 2.0. Good reliability and validity Index: Accuracy and Reaction time (RT) + * 100 ms *  Flanker type: Congruent Incongruent Neutral + Executive Control Functional neuroimaging studies: evidence of anatomical basis

+ * Alerting Center Cue: 200msec No Cue PFC Posterior parietal area Frontal areas Alerting Thalamus Center Cue: 200msec No Cue + * PFC Picture revised on: Carter R, Frith C D. Mapping the mind[M]. University of California Press, 1998.

+ * Orienting Spatial Cue: Random, last 200msec PFC Superior parietal area Frontal eye fields (FEF) Orienting Temporal Parietal Junction (TPJ) Spatial Cue: Random, last 200msec + * PFC

+ Executive Control Incongruent: 500msec Click or ≥2 sec PFC Cingulate cortex Prefrontal cortex Executive Control Basal ganglia Incongruent: 500msec Click or ≥2 sec + PFC

Research question & Hypothesis Does the “Attention network-brain” correlates demonstrate the similar pattern as functional MRI did? Objective: To investigate the gray matter volume (GMV) correlates with ANT indices in healthy older adults. Hypothesis: The “Attention network-GMV” correlates would demonstrate the specific neural underpinnings as fMRI did.

Materials & Methods Design: cross-sectional study Global Design: cross-sectional study Participants: 30 healthy Chinese older adults Attention Short-term memory Executive function Neuropsychological battery Attention network test (ANT) Structural MRI (T1 images)

Morphological analysis: gray matter volume (GMV) T1 images processing: BrainSuite 14a (following UCLA processing pipeline) Regional GMV: calculated based on 70 ROIs Pearson’s correlation: Between ANT indices and regional GMV. Covariates: age, gender, education and total intracranial volume (TIV) L R

Alerting and GMV L_Superior parietal gyrus r=-0.385, p=0.027 R_Superior temporal gyrus r=-0.383, p=0.028 L_Supra marginal gyrus r=-0.436, p=0.011 L_Inferior temporal gyrus r=-0.373, p=0.032 - r

Orienting and GMV L_middle occipital gyrus R_Superior temporal gyrus r=0.375, p=0.031 R_Superior temporal gyrus r=0.375, p=0.031 R_Inferior temporal gyrus r=0.486, p=0.004 r

L_Orbital Inferior frontal gyrus Executive control and GMV L_Superior temporal gyrus r=-0.368, p=0.032 R_Superior temporal gyrus r=-0.402, p=0.018 L_Cingulate gyrus r=-0.496, p=0.003 L_Fusiform gyrus (BA37) r=-0.584, p<0.001 L_Orbital Inferior frontal gyrus (BA11 and BA47) r=-0.433, p=0.010 r -

Conclusion Specific patterns of “Attention network-Brain” correlates. Generally, the patterns are similar with fMRI Overlapped regions in healthy older adults such as MTL, needed further exploration. Alerting related regions Alerting related GMV Orienting related regions Orienting related GMV Executive control related regions Executive control related GMV

Limitation & Future prospective Major limitations: (1) Cross-sectional study design (2) A relative small sample size Future directions: (1) Explore the interaction between age and cognitive status (2) Combined functional MRI (task-free fMRI)

Acknowledgement & Reference This study is supported by Lui Che Woo Institute of Innovation Medicine grant at CUHK We thank all the participants and colleagues from CUHK  Reference： Lam, L. C. W., et al., International Psychogeriatrics,2008, 20(1), 135–48. Sachdev, et al. (2014). Classifying neurocognitive disorders: the DSM-5 approach. Nature Reviews Neurology. Petersen, R. C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of internal medicine, 256(3), 183-194 Thank you for your ATTENTION!