A holistic approach to preventing type 2 diabetes in Asian women with a history of gestational diabetes mellitus: a feasibility study and pilot randomized controlled trial.

Background: Gestational Diabetes Mellitus (GDM) exposes women to future risk of Type 2 Diabetes. Previous studies focused on diet and physical activity, less emphasis was given to tackle intertwined risk factors such as sleep and stress. Knowledge remains scarce in multi-ethnic Asian communities. This study explored the: (1) feasibility of a holistic digital intervention on improving diet, physical activity (PA), sleep and stress of Asian women with a history of GDM, and (2) preliminary efficacy of the holistic intervention on women's physical and mental well-being via a pilot randomized controlled trial. Methods: Female volunteers with a history of GDM but without pre-existing diabetes were recruited from multi-ethnic Singaporean community. Each eligible woman was given a self-monitoring opportunity using Oura Ring that provided daily feedback on step counts, PA, sleep and bedtime heart rate. Intervention group additionally received personalized recommendations aimed to reinforce healthy behaviors holistically (diet, PA, sleep and stress). Dietary intake was evaluated by a research dietitian, while step counts, PA, sleep and bedtime heart rate were evaluated by health coaches based on Oura Ring data. Perceived physical and mental health and well-being were self-reported. Clinical outcomes included glycemic status determined by HbA1c and OGTT tests, body mass index, blood pressures and lipid profile. Results: Of 196 women from the community, 72 women completed diabetes screening, 61 women were eligible and 56 women completed the study. The 56 completers had mean age of 35.8 ± 3.7 years, predominantly Chinese, majority had their first GDM diagnosed at least 2 years ago and had two GDM-affected pregnancies. After intervention period, more women in the Intervention group achieved at least 8,000 steps/day and had at least 6 hours of sleep per night. Noticeable reduction of added sugar in their food and beverages were observed after the dietary intervention. Changes in body weight and mental well-being were observed but group differences were not statistically significant. Conclusions: The holistic approach appeared feasible for personalizing lifestyle recommendations to promote physical and mental well-being among women with a history of GDM. Larger studies with sufficient assessment timepoints and follow-up duration are warranted to improve the evaluation of intervention effects on clinical outcomes. Clinical trial registration number: https://clinicaltrials.gov/show/NCT05512871, NCT05512871.

Reopening after lockdown: the influence of working-from-home and digital device use on sleep, physical activity, and wellbeing following COVID-19 lockdown and reopening.

STUDY OBJECTIVES: COVID-19 lockdowns drastically affected sleep, physical activity, and wellbeing. We studied how these behaviors evolved during reopening the possible contributions of continued working from home and smartphone usage. METHODS: Participants (N = 198) were studied through the lockdown and subsequent reopening period, using a wearable sleep/activity tracker, smartphone-delivered ecological momentary assessment (EMA), and passive smartphone usage tracking. Work/study location was obtained through daily EMA ascertainment. RESULTS: Upon reopening, earlier, shorter sleep and increased physical activity were observed, alongside increased self-rated stress and poorer evening mood ratings. These reopening changes were affected by post-lockdown work arrangements and patterns of smartphone usage. Individuals who returned to work or school in-person tended toward larger shifts to earlier sleep and wake timings. Returning to in-person work/school also correlated with more physical activity. Contrary to expectation, there was no decrease in objectively measured smartphone usage after reopening. A cluster analysis showed that persons with relatively heavier smartphone use prior to bedtime had later sleep timings and lower physical activity. CONCLUSIONS: These observations indicate that the reopening after lockdown was accompanied by earlier sleep timing, increased physical activity, and altered mental wellbeing. Moreover, these changes were affected by work/study arrangements and smartphone usage patterns.

Trait-like nocturnal sleep behavior identified by combining wearable, phone-use, and self-report data.

Using polysomnography over multiple weeks to characterize an individual's habitual sleep behavior while accurate, is difficult to upscale. As an alternative, we integrated sleep measurements from a consumer sleep-tracker, smartphone-based ecological momentary assessment, and user-phone interactions in 198 participants for 2 months. User retention averaged >80% for all three modalities. Agreement in bed and wake time estimates across modalities was high (rho = 0.81-0.92) and were adrift of one another for an average of 4 min, providing redundant sleep measurement. On the ~23% of nights where discrepancies between modalities exceeded 1 h, k-means clustering revealed three patterns, each consistently expressed within a given individual. The three corresponding groups that emerged differed systematically in age, sleep timing, time in bed, and peri-sleep phone usage. Hence, contrary to being problematic, discrepant data across measurement modalities facilitated the identification of stable interindividual differences in sleep behavior, underscoring its utility to characterizing population sleep and peri-sleep behavior.

Respiratory, cardiac, EEG, BOLD signals and functional connectivity over multiple microsleep episodes.

Falling asleep is common in fMRI studies. By using long eyelid closures to detect microsleep onset, we showed that the onset and termination of short sleep episodes invokes a systematic sequence of BOLD signal changes that are large, widespread, and consistent across different microsleep durations. The signal changes are intimately intertwined with shifts in respiration and heart rate, indicating that autonomic contributions are integral to the brain physiology evaluated using fMRI and cannot be simply treated as nuisance signals. Additionally, resting state functional connectivity (RSFC) was altered in accord with the frequency of falling asleep and in a manner that global signal regression does not eliminate. Our findings point to the need to develop a consensus among neuroscientists using fMRI on how to deal with microsleep intrusions. SIGNIFICANCE STATEMENT: Sleep, breathing and cardiac action are influenced by common brainstem nuclei. We show that falling asleep and awakening are associated with a sequence of BOLD signal changes that are large, widespread and consistent across varied durations of sleep onset and awakening. These signal changes follow closely those associated with deceleration and acceleration of respiration and heart rate, calling into question the separation of the latter signals as 'noise' when the frequency of falling asleep, which is commonplace in RSFC studies, correlates with the extent of RSFC perturbation. Autonomic and central nervous system contributions to BOLD signal have to be jointly considered when interpreting fMRI and RSFC studies.

Demystifying "free will": the role of contextual information and evidence accumulation for predictive brain activity.

Novel multivariate pattern classification analyses have enabled the prediction of decision outcomes from brain activity prior to decision-makers' reported awareness. These findings are often discussed in relation to the philosophical concept of "free will". We argue that these studies demonstrate the role of unconscious processes in simple free choices, but they do not inform the philosophical debate. Moreover, these findings are difficult to relate to cognitive decision-making models, due to misleading assumptions about random choices. We review evidence suggesting that sequential-sampling models, which assume accumulation of evidence towards a decision threshold, can also be applied to free decisions. If external evidence is eliminated by the task instructions, decision-makers might use alternative, subtle contextual information as evidence, such as their choice history, that is not consciously monitored and usually concealed by the experimental design. We conclude that the investigation of neural activity patterns associated with free decisions should aim to investigate how decisions are jointly a function of internal and external contexts, rather than to resolve the philosophical "free will" debate.

Unconscious cues bias first saccades in a free-saccade task.

Visual-spatial attention can be biased towards salient visual information without visual awareness. It is unclear, however, whether such bias can further influence free-choices such as saccades in a free viewing task. In our experiment, we presented visual cues below awareness threshold immediately before people made free saccades. Our results showed that masked cues could influence the direction and latency of the first free saccade, suggesting that salient visual information can unconsciously influence free actions.

Pre-existing brain states predict risky choices.

Rational decision-making models assume that people resolve an economic problem based on its properties and the underlying utility. Here we challenge this view by examining whether pre-stimulus endogenous neuronal fluctuations can bias economic decisions. We recorded subjects' pre-stimulus neural activation patterns with fMRI before presentation and choice between pairs of certain outcomes and risky gambles. Our results indicate that activities in the left nucleus accumbens and medial frontal gyrus can bias subsequent risky decision making, showing that neuronal activities in regions associated with uncertainty and reward processing are involved in biasing subsequent choice selection. This finding challenges theories which propose that choices merely reveal stable underlying distributions of hedonic utility. Endogenous brain states of this sort might originate from a systematic cause or a stochastic type of neural noise, which can be construed as contextual factors that shape people's decision making.

Preoccupied minds feel less control: sense of agency is modulated by cognitive load.

People have little difficulty distinguishing effects they cause and those they do not. An important question is what underlies this sense of agency. A prevailing idea is that the sense of agency arises from a comparison between a predictive representation of the effect (of a given action) and the actual effect that occurs, with a clear match between the two producing a strong sense of agency. Although there is general agreement on this comparison process, one important theoretical issue that has yet to be fully determined is whether these computations are consciously performed. Here, we studied this issue by requiring participants to perform a simple judgment of agency task under conditions of different concurrent working memory load. Working memory operations are known to tax conscious cognitive resources. We found that agency judgments were moderated by working memory load, with lower agency ratings being observed in the high load condition, suggesting that the sense of agency is dependent on the availability of conscious cognitive resources. An examination of the time-course of this load effect suggests that it is the construction of the mental representation of the predicted effect which is particularly dependent on said resources.

Predicting free choices for abstract intentions.

Unconscious neural activity has been repeatedly shown to precede and potentially even influence subsequent free decisions. However, to date, such findings have been mostly restricted to simple motor choices, and despite considerable debate, there is no evidence that the outcome of more complex free decisions can be predicted from prior brain signals. Here, we show that the outcome of a free decision to either add or subtract numbers can already be decoded from neural activity in medial prefrontal and parietal cortex 4 s before the participant reports they are consciously making their choice. These choice-predictive signals co-occurred with the so-called default mode brain activity pattern that was still dominant at the time when the choice-predictive signals occurred. Our results suggest that unconscious preparation of free choices is not restricted to motor preparation. Instead, decisions at multiple scales of abstraction evolve from the dynamics of preceding brain activity.

Preparatory patterns of neural activity predict visual category search speed.

Rapidly detecting target object categories when objects are embedded in naturalistic scenes is facilitated by preparatory baseline signal changes. However, it is unclear as to what information most strongly predicts perceptual speed in terms of the minimal exposure duration required for accurate detection. Using novel surface-based spatiotemporal pattern classification, we found that while category-specific biases resulting from merely providing a category name can be detected in multiple cortical areas, only biases in lateral occipital complex predicted perceptual speed. These biases likely carry visual semantic information regarding multiple object categories placed in familiar scene contexts. Discriminatory voxels during the preparatory period showed congruent category-selectivity during visual stimulation.

Functional imaging correlates of impaired distractor suppression following sleep deprivation.

Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived.

The neural encoding of guesses in the human brain.

Human perception depends heavily on the quality of sensory information. When objects are hard to see we often believe ourselves to be purely guessing. Here we investigated whether such guesses use brain networks involved in perceptual decision making or independent networks. We used a combination of fMRI and pattern classification to test how visibility affects the signals, which determine choices. We found that decisions regarding clearly visible objects are predicted by signals in sensory brain regions, whereas different regions in parietal cortex became predictive when subjects were shown invisible objects and believed themselves to be purely guessing. This parietal network was highly overlapping with regions, which have previously been shown to encode free decisions. Thus, the brain might use a dedicated network for determining choices when insufficient sensory information is available.

Sleep deprivation reduces default mode network connectivity and anti-correlation during rest and task performance.

Sleep deprivation (SD) can alter extrinsic, task-related fMRI signal involved in attention, memory and executive function. However, its effects on intrinsic low-frequency connectivity within the Default Mode Network (DMN) and its related anti-correlated network (ACN) have not been well characterized. We investigated the effect of SD on functional connectivity within the DMN, and on DMN-ACN anti-correlation, both during the resting state and during performance of a visual attention task (VAT). 26 healthy participants underwent fMRI twice: once after a normal night of sleep in rested wakefulness (RW) and once following approximately 24h of total SD. A seed-based approach was used to examine pairwise correlations of low-frequency fMRI signal across different nodes in each state. SD was associated with significant selective reductions in DMN functional connectivity and DMN-ACN anti-correlation. This was congruent across resting state and VAT analyses, suggesting that SD induces a robust alteration in the intrinsic connectivity within and between these networks.

Tracking the unconscious generation of free decisions using ultra-high field fMRI.

Recently, we demonstrated using functional magnetic resonance imaging (fMRI) that the outcome of free decisions can be decoded from brain activity several seconds before reaching conscious awareness. Activity patterns in anterior frontopolar cortex (BA 10) were temporally the first to carry intention-related information and thus a candidate region for the unconscious generation of free decisions. In the present study, the original paradigm was replicated and multivariate pattern classification was applied to functional images of frontopolar cortex, acquired using ultra-high field fMRI at 7 Tesla. Here, we show that predictive activity patterns recorded before a decision was made became increasingly stable with increasing temporal proximity to the time point of the conscious decision. Furthermore, detailed questionnaires exploring subjects' thoughts before and during the decision confirmed that decisions were made spontaneously and subjects were unaware of the evolution of their decision outcomes. These results give further evidence that FPC stands at the top of the prefrontal executive hierarchy in the unconscious generation of free decisions.

Reduced visual processing capacity in sleep deprived persons.

Multiple experiments have found sleep deprivation to lower task-related parietal and extrastriate visual activation, suggesting a reduction of visual processing capacity in this state. The perceptual load theory of attention (Lavie, 1995) predicts that our capacity to process unattended distractors will be reduced by increasing perceptual difficulty of task-relevant stimuli. Here, we evaluated the effects of sleep deprivation and perceptual load on visual processing capacity by measuring neural repetition-suppression to unattended scenes while healthy volunteers attended to faces embedded in face-scene pictures. Perceptual load did not affect repetition suppression after a normal night of sleep. Sleep deprivation reduced repetition suppression in the parahippocampal place area (PPA) in the high but not low perceptual load condition. Additionally, the extent to which task-related fusiform face area (FFA) activation was reduced after sleep deprivation correlated with behavioral performance and lowered repetition suppression in the PPA. The findings concerning correct responses indicate that a portion of stimulus related activation following a normal night of sleep contributes to potentially useful visual processing capacity that is attenuated following sleep deprivation. Finally, when unattended stimuli are not highly intrusive, sleep deprivation does not appear to increase distractibility.

Cortical surface-based searchlight decoding.

Local voxel patterns of fMRI signals contain specific information about cognitive processes ranging from basic sensory processing to high level decision making. These patterns can be detected using multivariate pattern classification, and localization of these patterns can be achieved with searchlight methods in which the information content of spherical sub-volumes of the fMRI signal is assessed. The only assumption made by this approach is that the patterns are spatially local. We present a cortical surface-based searchlight approach to pattern localization. Voxels are grouped according to distance along the cortical surface-the intrinsic metric of cortical anatomy-rather than Euclidean distance as in volumetric searchlights. Using a paradigm in which the category of visually presented objects is decoded, we compare the surface-based method to a standard volumetric searchlight technique. Group analyses of accuracy maps produced by both methods show similar distributions of informative regions. The surface-based method achieves a finer spatial specificity with comparable peak values of significance, while the volumetric method appears to be more sensitive to small informative regions and might also capture information not located directly within the gray matter. Furthermore, our findings show that a surface centered in the middle of the gray matter contains more information than to the white-gray boundary or the pial surface.

Role of medial cortical, hippocampal and striatal interactions during cognitive set-shifting.

To date, few studies have examined the functional connectivity of brain regions involved in complex executive function tasks, such as cognitive set-shifting. In this study, eighteen healthy volunteers performed a cognitive set-shifting task modified from the Wisconsin card sort test while undergoing functional magnetic resonance imaging. These modifications allowed better disambiguation between cognitive processes and revealed several novel findings: 1) peak activation in the caudate nuclei in the first instance of negative feedback signaling a shift in rule, 2) lowest caudate activation once the rule had been identified, 3) peak hippocampal activation once the identity of the rule had been established, and 4) decreased hippocampal activation during the generation of new rule candidates. This pattern of activation across cognitive set-shifting events suggests that the caudate nuclei play a role in response generation when the identity of the new rule is unknown. In contrast, the reciprocal pattern of hippocampal activation suggests that the hippocampi help consolidate knowledge about the correct stimulus-stimulus associations, associations that become inappropriate once the rule has changed. Functional connectivity analysis using Granger Causality Mapping revealed that caudate and hippocampal regions interacted indirectly via a circuit involving the medial orbitofrontal and posterior cingulate regions, which are known to bias attention towards stimuli based on expectations built up from task-related feedback. Taken together, the evidence suggests that these medial regions may mediate striato-hippocampal interactions and hence affect goal-directed attentional transitions from a response strategy based on stimulus-reward heuristics (caudate-dependent) to one based on stimulus-stimulus associations (hippocampus-dependent).

Unconscious determinants of free decisions in the human brain.

There has been a long controversy as to whether subjectively 'free' decisions are determined by brain activity ahead of time. We found that the outcome of a decision can be encoded in brain activity of prefrontal and parietal cortex up to 10 s before it enters awareness. This delay presumably reflects the operation of a network of high-level control areas that begin to prepare an upcoming decision long before it enters awareness.

Left insula activation: a marker for language attainment in bilinguals.

Several lines of evidence suggest the importance of phonological working memory (PWM) in language acquisition. We investigated the neural correlates of PWM in young adults who were under compelling social pressure to be bilingual. Equal bilinguals had high proficiency in English and Chinese as measured by a standardized examination, whereas unequal bilinguals were proficient in English but not Chinese. Both groups were matched on several measures of nonverbal intelligence and working memory. In-scanner behavioral results did not show between-group differences. Of the regions showing load-dependent increments in activation, the left insula showed greater activation in equal bilinguals. Unequal bilinguals showed greater task-related deactivation in the anterior medial frontal region and greater anterior cingulate activation. Although unequal bilinguals kept apace with equal bilinguals in the simple PWM task, the differential cortical activations suggest that more optimal engagement of PWM in the latter may correlate with better second-language attainment.

Stimulus repetition and hemodynamic response refractoriness in event-related fMRI.

We investigated the extent of hemodynamic recovery following the paired presentation of either identical or different faces at two different inter-stimulus intervals (ISI). Signal recovery was consistently better at an ISI of 6 sec compared to 3 sec. Significantly less signal recovery was associated with identical faces compared to different faces in bilateral mid-fusiform and right prefrontal regions but not in the calcarine and posterior fusiform regions. Repetition suppression effects contributed significantly to incomplete signal recovery in a region-specific manner. Simulations using empirically derived data suggest that experiments with shorter ISI (average 4.5-6.0 sec) are as sensitive as experiments with intermediate ISI (average 9 sec) in detecting response differences if experimental duration is equivalent. However, designs using intermediate ISI may be more appropriate if the expected difference in responses is small and if the number of suitable stimuli is limited.