Stampacchia, S. | bioRxiv Science

bioRxiv2022

Fingerprinting of brain disease: Connectome identifiability in cognitive decline and neurodegeneration

In analogy to the friction ridges of a human finger, the functional connectivity patterns of the human brain can be used to identify a given individual from a population. In other words, functional connectivity patterns constitute a marker of human identity, or a brain fingerprint. Yet remarkably, very little is known about whether brain fingerprints are preserved in brain ageing and in the presence of cognitive decline due to Alzheimers disease (AD). Using fMRI data from two independent datasets of healthy and pathologically ageing subjects, here we show that individual functional connectivity profiles remain unique and highly heterogeneous across early and late stages of cognitive decline due to AD. Yet, the patterns of functional connectivity making subjects identifiable, change across health and disease, revealing a functional reconfiguration of the brain fingerprint. We observed a fingerprint change towards between-functional system connections when transitioning from healthy to dementia, and to lower-order cognitive functions in the earliest stages of the disease. These findings show that functional connectivity carries important individualised information to evaluate regional and network dysfunction in cognitive impairment and highlight the importance of switching the focus from group differences to individual variability when studying functional alterations in AD. The present data establish the foundation for clinical fingerprinting of brain diseases by showing that functional connectivity profiles maintain their uniqueness, yet go through functional reconfiguration, during cognitive decline. These results pave the way for a more personalised understanding of functional alterations during cognitive decline, moving towards brain fingerprinting in personalised medicine and treatment optimization during cognitive decline.

neuroscience↗

bioRxiv2021

Motivated semantic control: Exploring the effects of extrinsic reward and self-reference on semantic retrieval in semantic aphasia

Recent insights show increased motivation can benefit executive control, but this effect has not been explored in relation to semantic cognition. Patients with deficits of controlled semantic retrieval in the context of semantic aphasia (SA) after stroke may benefit from this approach since semantic control is considered an executive process. Deficits in this domain are partially distinct from domain-general deficits of cognitive control. We assessed the effect of both extrinsic and intrinsic motivation in healthy controls and semantic aphasia patients. Experiment 1 manipulated extrinsic reward using high or low levels of points for correct responses during a semantic association task. Experiment 2 manipulated the intrinsic value of items using self-reference; allocating pictures of items to the participant ( self) or researcher ( other) in a shopping game before people retrieved their semantic associations. These experiments revealed that patients, but not controls, showed better performance when given an extrinsic reward, consistent with the view that increased external motivation may help to ameliorate patients semantic control deficits. However, while self-reference was associated with better episodic memory, there was no effect on semantic retrieval. We conclude that semantic control deficits can be reduced when extrinsic rewards are anticipated; this enhanced motivational state is expected to support proactive control, for example, through the maintenance of task representations. It may be possible to harness this modulatory impact of reward to combat the control demands of semantic tasks in SA patients.

neuroscience↗