The overlapping modular organization of human brain functional networks across the adult lifespan.

Previous studies have demonstrated that the brain functional modular organization, which is a fundamental feature of the human brain, would change along the adult lifespan. However, these studies assumed that each brain region belonged to a single functional module, although there has been convergent evidence supporting the existence of overlap among functional modules in the human brain. To reveal how age affects the overlapping functional modular organization, this study applied an overlapping module detection algorithm that requires no prior knowledge to the resting-state fMRI data of a healthy cohort (N = 570) aged from 18 to 88 years old. A series of measures were derived to delineate the characteristics of the overlapping modular structure and the set of overlapping nodes (brain regions participating in two or more modules) identified from each participant. Age-related regression analyses on these measures found linearly decreasing trends in the overlapping modularity and the modular similarity. The number of overlapping nodes was found increasing with age, but the increment was not even over the brain. In addition, across the adult lifespan and within each age group, the nodal overlapping probability consistently had positive correlations with both functional gradient and flexibility. Further, by correlation and mediation analyses, we showed that the influence of age on memory-related cognitive performance might be explained by the change in the overlapping functional modular organization. Together, our results revealed age-related decreased segregation from the brain functional overlapping modular organization perspective, which could provide new insight into the adult lifespan changes in brain function and the influence of such changes on cognitive performance.

Across the adult lifespan the ipsilateral sensorimotor cortex negative BOLD response exhibits decreases in magnitude and spatial extent suggesting declining inhibitory control.

Ipsilateral sensorimotor (iSM1) cortex negative BOLD responses (NBR) are observed to unilateral tasks and are thought to reflect a functionally relevant component of sensorimotor inhibition. Evidence suggests that sensorimotor inhibitory mechanisms degrade with age, along with aspects of motor ability and dexterity. However, understanding of age-related changes to NBR is restricted by limited comparisons between young vs old adults groups with relatively small samples sizes. Here we analysed a BOLD fMRI dataset (obtained from the CamCAN repository) of 581 healthy subjects, gender-balanced, sampled from the whole adult lifespan performing a motor response task to an audiovisual stimulus. We aimed to investigate how sensorimotor and default-mode NBR characteristics of magnitude, spatial extent and response shape alter at every decade of the aging process. We observed a linear decrease in iSM1 NBR magnitude across the whole lifespan, whereas the contralateral sensorimotor (cSM1) PBR magnitude was unchanged. An age-related decrease in the spatial extent of NBR and an increase in the ipsilateral positive BOLD response (PBR) was observed. This occurred alongside an increasing negative correlation between subject's iSM1 NBR and cSM1 PBR magnitude, reflecting a change in the balance between cortical excitation and inhibition. Conventional GLM analysis, using a canonical haemodynamic response (HR) function, showed disappearance of iSM1 NBR in subjects over 50 years of age. However, a deconvolution analysis showed that the shape of the iSM1 HR altered throughout the lifespan, with significantly delayed time-to-peak and decreased magnitude. The most significant decreases in iSM1 HR magnitude occurred in older age (>60 years) but the first changes in HR shape and timing occurred as early as 30 years, suggesting the possibility of separate mechanisms underlying these alterations. Reanalysis using data-driven HRs for each decade detected significant sensorimotor NBR into late older age, showing the importance of taking changes in HR morphology into account in fMRI aging studies. These results may reflect fMRI measures of the age-related decreases in transcollosal inhibition exerted upon ipsilateral sensorimotor cortex and alterations to the excitatory-inhibitory balance in the sensorimotor network.

Transient neural network dynamics in cognitive ageing.

It is important to maintain cognitive function in old age, yet the neural substrates that support successful cognitive ageing remain unclear. One factor that might be crucial, but has been overlooked due to limitations of previous data and methods, is the ability of brain networks to flexibly reorganize and coordinate over a millisecond time-scale. Magnetoencephalography (MEG) provides such temporal resolution, and can be combined with Hidden Markov Models (HMMs) to characterise transient neural states. We applied HMMs to resting-state MEG data from a large cohort (N=595) of population-based adults (aged 18-88), who also completed a range of cognitive tasks. Using multivariate analysis of neural and cognitive profiles, we found that decreased occurrence of "lower-order" brain networks, coupled with increased occurrence of "higher-order" networks, was associated with both increasing age and decreased fluid intelligence. These results favour theories of age-related reductions in neural efficiency over current theories of age-related functional compensation, and suggest that this shift might reflect a stable property of the ageing brain.

Age-related changes in word retrieval vary by self-reported anxiety but not depression symptoms.

Tip-of-the-tongue states (TOTs) are known to increase in frequency across adulthood, but there is wide variability in older adults' TOT rates, suggesting that individual difference factors contribute to TOT incidence. We investigated the role of affect by examining the relationship between self-reported anxiety and depression symptoms and the frequency of TOTs during a laboratory task. Participants were young, middle-aged and older adults in a population-based sample of adults aged 18-87. Increased anxiety was associated with fewer TOTs for the middle-aged group but more TOTs for the older adult group. There was no relationship between anxiety and TOTs for younger adults and no relationships between depression symptoms and TOT incidence for any age group. We discuss our results in terms of attentional control theory, which provides an explanation of how age may affect the relationship between anxiety and TOTs.