Cross-sectional associations between 24-hour time-use composition, grey matter volume and cognitive function in healthy older adults.

BACKGROUND: Increasing physical activity (PA) is an effective strategy to slow reductions in cortical volume and maintain cognitive function in older adulthood. However, PA does not exist in isolation, but coexists with sleep and sedentary behaviour to make up the 24-hour day. We investigated how the balance of all three behaviours (24-hour time-use composition) is associated with grey matter volume in healthy older adults, and whether grey matter volume influences the relationship between 24-hour time-use composition and cognitive function. METHODS: This cross-sectional study included 378 older adults (65.6 ± 3.0 years old, 123 male) from the ACTIVate study across two Australian sites (Adelaide and Newcastle). Time-use composition was captured using 7-day accelerometry, and T1-weighted magnetic resonance imaging was used to measure grey matter volume both globally and across regions of interest (ROI: frontal lobe, temporal lobe, hippocampi, and lateral ventricles). Pairwise correlations were used to explore univariate associations between time-use variables, grey matter volumes and cognitive outcomes. Compositional data analysis linear regression models were used to quantify associations between ROI volumes and time-use composition, and explore potential associations between the interaction between ROI volumes and time-use composition with cognitive outcomes. RESULTS: After adjusting for covariates (age, sex, education), there were no significant associations between time-use composition and any volumetric outcomes. There were significant interactions between time-use composition and frontal lobe volume for long-term memory (p = 0.018) and executive function (p = 0.018), and between time-use composition and total grey matter volume for executive function (p = 0.028). Spending more time in moderate-vigorous PA was associated with better long-term memory scores, but only for those with smaller frontal lobe volume (below the sample mean). Conversely, spending more time in sleep and less time in sedentary behaviour was associated with better executive function in those with smaller total grey matter volume. CONCLUSIONS: Although 24-hour time use was not associated with total or regional grey matter independently, total grey matter and frontal lobe grey matter volume moderated the relationship between time-use composition and several cognitive outcomes. Future studies should investigate these relationships longitudinally to assess whether changes in time-use composition correspond to changes in grey matter volume and cognition.

Characterising activity and diet compositions for dementia prevention: protocol for the ACTIVate prospective longitudinal cohort study.

INTRODUCTION: Approximately 40% of late-life dementia may be prevented by addressing modifiable risk factors, including physical activity and diet. Yet, it is currently unknown how multiple lifestyle factors interact to influence cognition. The ACTIVate Study aims to (1) explore associations between 24-hour time-use and diet compositions with changes in cognition and brain function; and (2) identify duration of time-use behaviours and the dietary compositions to optimise cognition and brain function. METHODS AND ANALYSIS: This 3-year prospective longitudinal cohort study will recruit 448 adults aged 60-70 years across Adelaide and Newcastle, Australia. Time-use data will be collected through wrist-worn activity monitors and the Multimedia Activity Recall for Children and Adults. Dietary intake will be assessed using the Australian Eating Survey food frequency questionnaire. The primary outcome will be cognitive function, assessed using the Addenbrooke's Cognitive Examination-III. Secondary outcomes include structural and functional brain measures using MRI, cerebral arterial pulse measured with diffuse optical tomography, neuroplasticity using simultaneous transcranial magnetic stimulation and electroencephalography, and electrophysiological markers of cognitive control using event-related potential and time frequency analyses. Compositional data analysis, testing for interactions between time point and compositions, will assess longitudinal associations between dependent (cognition, brain function) and independent (time-use and diet compositions) variables. CONCLUSIONS: The ACTIVate Study will be the first to examine associations between time-use and diet compositions, cognition and brain function. Our findings will inform new avenues for multidomain interventions that may more effectively account for the co-dependence between activity and diet behaviours for dementia prevention. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the University of South Australia's Human Research Ethics committee (202639). Findings will be disseminated through peer-reviewed manuscripts, conference presentations, targeted media releases and community engagement events. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry (ACTRN12619001659190).

Out-of-sync: disrupted neural activity in emotional circuitry during film viewing in melancholic depression.

While a rich body of research in controlled experiments has established changes in the neural circuitry of emotion in major depressive disorders, little is known as to how such alterations might translate into complex, naturalistic settings--namely involving dynamic multimodal stimuli with rich contexts, such as those provided by films. Neuroimaging paradigms employing dynamic natural stimuli alleviate the anxiety often associated with complex tasks and eschew the need for laboratory-style abstractions, hence providing an ecologically valid means of elucidating neural underpinnings of neuropsychiatric disorders. To probe the neurobiological signature of refined depression subtypes, we acquired functional neuroimaging data in patients with the melancholic subtype of major depressive disorder during free viewing of emotionally salient films. We found a marked disengagement of ventromedial prefrontal cortex during natural viewing of a film with negative emotional valence in patients with melancholia. This effect significantly correlated with depression severity. Such changes occurred on the background of diminished consistency of neural activity in visual and auditory sensory networks, as well as higher-order networks involved in emotion and attention, including bilateral intraparietal sulcus and right anterior insula. These findings may reflect a failure to re-allocate resources and diminished reactivity to external emotional stimuli in melancholia.

Disrupted effective connectivity of cortical systems supporting attention and interoception in melancholia.

IMPORTANCE: Patients with melancholia report a distinct and intrusive dysphoric state during internally generated thought. Melancholia has long been considered to have a strong biological component, but evidence for its specific neurobiological origins is limited. The distinct neurocognitive, psychomotor, and mood disturbances observed in melancholia do, however, suggest aberrant coordination of frontal-subcortical circuitry, which may best be captured through analysis of complex brain networks. OBJECTIVE: To investigate the effective connectivity between spontaneous (resting-state) brain networks in melancholia, focusing on networks underlying attention and interoception. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional, observational, resting-state functional magnetic resonance imaging study of 16 participants with melancholia, 16 with nonmelancholic depression, and 16 individuals serving as controls at a hospital-based research institute between August 30, 2010, and June 27, 2012. We identified 5 canonical resting-state networks (default mode, executive control, left and right frontoparietal attention, and bilateral anterior insula) and inferred spontaneous interactions among these networks using dynamic causal modeling. MAIN OUTCOMES AND MEASURES: Graph theoretic measures of brain connectivity, namely, in-degree and out-degree of each network and edge connectivity, between regions composed our principal between-group contrasts. RESULTS: Melancholia was characterized by a pervasive disconnection involving anterior insula and attentional networks compared with participants in the control (Mann-Whitney, 189.00; z = 2.38; P = .02) and nonmelancholic depressive (Mann-Whitney, 203.00; z = 2.93; P = .004) groups. Decreased effective connectivity between the right frontoparietal and insula networks was present in participants with melancholic depression compared with those with nonmelancholic depression (χ2 = 8.13; P = .004). Reduced effective connectivity between the insula and executive networks was found in individuals with melancholia compared with healthy controls (χ2 = 8.96; P = .003). CONCLUSIONS AND RELEVANCE: We observed reduced effective connectivity in resting-state functional magnetic resonance imaging between key networks involved in attention and interoception in melancholia. We propose that these abnormalities underlie the impoverished variety and affective quality of internally generated thought in this disorder.

BrainModes: a principled approach to modeling and measuring large-scale neuronal activity.

Complex systems, such as the brain, exhibit multiple levels of organization due to processes which support the separation of scales across time and/or space. That is, cooperative phenomena--or "modes" of activity--occurring at one scale give rise to coherent spatiotemporal structures at a coarser scale. In turn, structures at the coarser scale constrain--and hence influence--emerging activity at a finer scale. BrainModes is an annual scientific summit which seeks to bring together experimental, computational and theoretical neuroscientists engaged at different levels of organization, with the goal of advancing a principled approach to understanding brain function based on the concept of cooperative phenomena in complex systems. Phenomena of particular interest include synchronization, stochastic influences, and spatiotemporal processes in both healthy and pathological states such as seizures. This Special Issue reports the 2008 BrainModes Workshop, held in Amsterdam (December 2008) which focused on the application of this framework to the analysis of brain oscillations and synchronization phenomena across time scales.