ALT Multi-panel figure comparing brain-state dynamics in Alzheimer’s disease (red) and healthy controls (blue). Box plots show controls spend more time in State 1, the global coherence state, with higher probability, longer dwell time and greater synchrony, while people with Alzheimer’s make more visits to states and more transitions overall. Transition-likelihood matrices and scatter plots show that more time in State 1 goes with higher synchrony, and that greater locus coeruleus integrity is associated with fewer transitions between states.

ALT Four-panel figure showing that pupil size, a proxy for arousal, tracks cortical synchrony. An example timecourse shows pupil size (green) rising and falling with synchrony (black) and being higher during the brain’s global coherence state. Across participants, higher pupil size is associated with higher synchrony in both the Alzheimer’s and control groups, and pupil size is greater during the global coherence state and during stable, non-transitioning periods.

ALT Schematic comparing a healthy brain and an Alzheimer’s brain. In health, the brain’s “attractor landscape” has deep wells, so dominant states such as State 1 are stable and synchrony swings widely over time. In Alzheimer’s, reduced arousal flattens the landscape, the dominant state becomes shallower, and synchrony is lower and less stable, with more frequent transitions out of State 1. Colour indicates arousal level, from low (blue) to high (red).

ALT The locus coeruleus (blue) in the pons sends noradrenaline projections widely across the cortex; the substantia nigra and VTA (red) send dopamine projections to deep brain regions. Lower panels show brainstem cross-sections: midbrain (SN, VTA) and pons (LC).