Sex Differences in Magnetoencephalography-Identified Functional Connectivity in the Human Connectome Project Connectomics of Brain Aging and Dementia Cohort.

Introduction: The human brain shows modest traits of sexual dimorphism, with the female brain, on average, 10% smaller than the male brain. These differences do not imply a lowered cognitive performance, but suggest a more optimal brain organization in women. Here we evaluate the patterns of functional connectivity (FC) in women and men from the Connectomics of Brain Aging and Dementia sample. Methods: We used phase locking values to calculate FC from the magnetoencephalography time series in a sample of 138 old adults (87 females and 51 males). We compared the FC patterns between sexes, with the intention of detecting regions with different levels of connectivity. Results: We found a frontal cluster, involving anterior cingulate and the medial frontal lobe, where women showed higher FC values than men. Involved connections included the following: (1) medial parietal areas, such as posterior cingulate cortices and precunei; (2) right insula; and (3) medium cingulate and paracingulate cortices. Moreover, these differences persisted when considering only cognitively intact individuals, but not when considering only cognitively impaired individuals. Discussion: Increased anteroposterior FC has been identified as a biomarker for increased risk of developing cognitive impairment or dementia. In our study, cognitively intact women showed higher levels of FC than their male counterparts. This result suggests that neurodegenerative processes could be taking place in these women, but the changes are undetected by current diagnosis tools. FC, as measured here, might be valuable for early identification of this neurodegeneration.

Connectomics in Brain Aging and Dementia - The Background and Design of a Study of a Connectome Related to Human Disease.

The natural history of Alzheimer's Disease (AD) includes significant alterations in the human connectome, and this disconnection results in the dementia of AD. The organizing principle of our research project is the idea that the expression of cognitive dysfunction in the elderly is the result of two independent processes - the neuropathology associated with AD, and second the neuropathological changes of cerebrovascular disease. Synaptic loss, senile plaques, and neurofibrillary tangles are the functional and diagnostic hallmarks of AD, but it is the structural changes as a consequence of vascular disease that reduce brain reserve and compensation, resulting in an earlier expression of the clinical dementia syndrome. This work is being completed under the auspices of the Human Connectome Project (HCP). We have achieved an equal representation of Black individuals (vs. White individuals) and enrolled 60% Women. Each of the participants contributes demographic, behavioral and laboratory data. We acquire data relative to vascular risk, and the participants also undergo in vivo amyloid imaging, and magnetoencephalography (MEG). All of the data are publicly available under the HCP guidelines using the Connectome Coordinating Facility and the NIMH Data Archive. Locally, we use these data to address specific questions related to structure, function, AD, aging and vascular disease in multi-modality studies leveraging the differential advantages of magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), MEG, and in vivo beta amyloid imaging.

Cardiac-induced cerebral pulsatility, brain structure, and cognition in middle and older-aged adults.

Changes of cardiac-induced regional pulsatility can be associated with specific regions of brain volumetric changes, and these are related with cognitive alterations. Thus, mapping of cardiac pulsatility over the entire brain can be helpful to assess these relationships. A total of 108 subjects (age: 66.5 ± 8.4 years, 68 females, 52 healthy controls, 11 subjective cognitive decline, 17 impaired without complaints, 19 MCI and 9 AD) participated. The pulsatility map was obtained directly from resting-state functional MRI time-series data at 3T. Regional brain volumes were segmented from anatomical MRI. Multidomain neuropsychological battery was performed to test memory, language, attention and visuospatial construction. The Montreal Cognitive Assessment (MoCA) was also administered. The sparse partial least square (SPLS) method, which is desirable for better interpreting high-dimensional variables, was applied for the relationship between the entire brain voxels of pulsatility and 45 segmented brain volumes. A multiple holdout SPLS framework was used to optimize sparsity for assessing the pulsatility-volume relationship model and to test the reliability by fitting the models to 9 different splits of the data. We found statistically significant associations between subsets of pulsatility voxels and subsets of segmented brain volumes by rejecting the omnibus null hypothesis (any of 9 splits has p < 0.0056 (=0.05/9) with the Bonferroni correction). The pulsatility was positively associated with the lateral ventricle, choroid plexus, inferior lateral ventricle, and 3rd ventricle and negatively associated with hippocampus, ventral DC, and thalamus volumes for the first pulsatility-volume relationship. The pulsatility had an additional negative relationship with the amygdala and brain stem volumes for the second pulsatility-volume relationship. The spatial distribution of correlated pulsatility was observed in major feeding arteries to the brain regions, ventricles, and sagittal sinus. The indirect mediating pathways through the volumetric changes were statistically significant between the pulsatility and multiple cognitive measures (p < 0.01). Thus, the cerebral pulsatility, along with volumetric measurements, could be a potential marker for better understanding of pathophysiology and monitoring disease progression in age-related neurodegenerative disorders.

Tract Specific White Matter Lesion Load Affects White Matter Microstructure and Their Relationships With Functional Connectivity and Cognitive Decline.

White matter hyperintensities (WMHs) are associated with cognitive decline. Assessing the effect of WMH on WM microstructural changes and its relationships with structural and functional connectivity to multiple cognitive domains are helpful to better understand the pathophysiological processes of cognitive impairment. 65 participants (49 normal and 16 MCI subjects, age: 67.4 ± 8.3 years, 44 females) were studied at 3T. The WMHs and fifty fiber tracts were automatically segmented from the T1/T2-weighted images and diffusion-weighted images, respectively. Tract-profiles of WMH were compared with those of apparent fiber density (AFD). The relationship between AFD and tract connectivity (TC) was assessed. Functional connectivity (FC) between tract ends obtained from resting-state functional MRI was examined in relation to TC. Tract-specific relationships of WMH, TC and FC with a multi-domain neuropsychological test battery and Montreal Cognitive Assessment (MoCA) were also separately assessed by lasso linear regression. Indirect pathways of TC and FC between WMH and multiple cognitive measures were tested using the mediation analysis. Higher WMH loads in WM tracts were locally matched with the reduced AFD, which was related to decrease in TC. However, no direct relationship was found between TC and FC. Tract-specific changes on WMH, TC and FC for each cognitive performance may explain that macro- and microstructural and functional changes are associated differently with each cognitive domain in a fiber specific manner. In these identified tracts, the differences between normal and MCI for WMH and TC were increased, and the relationships of WMH, TC and FC with cognitive outcomes were more significant, compared to the results from all tracts. Indirect pathways of two-step (TC-FC) between WMH and all cognitive domains were significant (p < 0.0083 with Bonferroni correction), while the separated indirect pathways through TC and through FC were different depending on cognitive domain. Deterioration in specific cognitive domains may be affected by alterations in a set of different tracts that are differently associated with macrostructural, microstructural, and function changes. Thus, assessments of WMH and its associated changes on specific tracts help for better understanding of the interrelationships of multiple changes in cognitive impairment.

The Development and Evaluation of a Text Message Program to Prevent Perceived Insufficient Milk Among First-Time Mothers: Retrospective Analysis of a Randomized Controlled Trial.

BACKGROUND: Several recent trials have examined the feasibility and efficacy of automated SMS text messaging to provide remote breastfeeding support to mothers, but these texting systems vary in terms of design features and outcomes examined. OBJECTIVE: This study examined user engagement with and feedback on a theory-grounded SMS text messaging intervention intended to prevent perceived insufficient milk (PIM)-the single, leading modifiable cause of unintended breastfeeding reduction and cessation. METHODS: We recruited 250 nulliparous individuals intending to breastfeed between 13 and 25 weeks of pregnancy in southwestern Pennsylvania. Participants were randomly assigned with equal allocation to either an SMS intervention to prevent PIM and unintended breastfeeding reduction or cessation (MILK, a Mobile, semiautomated text message-based Intervention to prevent perceived Low or insufficient milK supply; n=126) or a control group receiving general perinatal SMS text messaging-based support via the national, free Text4Baby system (n=124). Participants in both groups received SMS text messages 3 to 7 times per week from 25 weeks of pregnancy to 8 weeks postpartum. The MILK intervention incorporated several automated interactivity and personalization features (eg, keyword texting for more detailed information on topics and branched response logic) as well as an option to receive one-on-one assistance from an on-call study lactation consultant. We examined participant interactions with the MILK system, including response rates to SMS text messaging queries. We also sought participant feedback on MILK content, delivery preferences, and overall satisfaction with the system via interviews and a remote survey at 8 weeks postpartum. RESULTS: Participants randomized to MILK (87/124, 70.2% white and 84/124, 67.7% college educated) reported that MILK texts increased their breastfeeding confidence and helped them persevere through breastfeeding problems. Of 124 participants, 9 (7.3%) elected to stop MILK messages, and 3 (2.4%) opted to reduce message frequency during the course of the study. There were 46 texts through the MILK system for individualized assistance from the study lactation consultant (25/46, 54% on weekends or after-hours). The most commonly texted keywords for more detailed information occurred during weeks 4 to 6 postpartum and addressed milk volume intake and breastfeeding and sleep patterns. MILK participants stated a preference for anticipatory guidance on potential breastfeeding issues and less content addressing the benefits of breastfeeding. Suggested improvements included extending messaging past 8 weeks, providing access to messaging for partners, and tailoring content based on participants' pre-existing breastfeeding knowledge and unique breastfeeding trajectory. CONCLUSIONS: Prenatal and postpartum evidence-based breastfeeding support delivered via semiautomated SMS text messaging is a feasible and an acceptable intervention for first-time mothers. To optimize engagement with digital breastfeeding interventions, enhanced customization features should be considered. TRIAL REGISTRATION: ClinicalTrials.gov NCT02724969; https://clinicaltrials.gov/ct2/show/NCT02724969.

Impact of shift duration on alertness among air-medical emergency care clinician shift workers.

BACKGROUND: Greater than half of Emergency Medical Services (EMS) shift workers report fatigue at work and most work long duration shifts. We sought to compare the alertness level of EMS shift workers by shift duration. METHODS: We used a multi-site, 14-day prospective observational cohort study design of EMS clinician shift workers at four air-medical EMS organizations. The primary outcome was behavioral alertness as measured by psychomotor vigilance tests (PVT) at the start and end of shifts. We stratified shifts by duration (< 24 h and 24 h), night versus day, and examined the impact of intra-shift napping on PVT performance. RESULTS: One hundred and twelve individuals participated. The distribution of shifts <24 h and 24 h with complete data were 54% and 46%, respectively. We detected no differences in PVT performance measures stratified by shift duration (P > 0.05). Performance for selected PVT measures (lapses and false starts) was worse on night shifts compared to day shifts (P < 0.05). Performance also worsened with decreasing time between waking from a nap and the end of shift PVT assessment. CONCLUSIONS: Deficits in performance in the air-medical setting may be greatest during night shifts and proximal to waking from an intra-shift nap. Future research should examine alertness and performance throughout air-medical shifts, as well as investigate the timing and duration of intra-shift naps on outcomes.

Real-Time Fatigue Mitigation with Air-Medical Personnel: The SleepTrackTXT2 Randomized Trial.

Objective: The aims of this study were: 1) to determine the short-term impact of the SleepTrackTXT2 intervention on air-medical clinician fatigue during work shifts and 2) determine the longer-term impact on sleep quality over 120 days. Methods: We used a multi-site randomized controlled trial study design with a targeted enrollment of 100 (ClinicalTrials.gov NCT02783027). The intervention was behavioral (non-pharmacological) and participation was scheduled for 120 days. Participation was voluntary. All consented participants answered baseline as well as follow-up surveys. All participants answered text message queries, which assessed self-rated fatigue, sleepiness, concentration, recovery, and hours of sleep. Intervention participants received additional text messages with recommendations for behaviors that can mitigate fatigue. Intervention participants received weekly text messages that promoted sleep. Our analysis was guided by the intent-to-treat principle. For the long-term outcome of interest (sleep quality at 120 days), we used a two-sample t-test on the change in sleep quality to determine the intervention effect. Results: Eighty-three individuals were randomized and 2,828 shifts documented (median shifts per participant =37, IQR 23-49). Seventy-one percent of individuals randomized (n = 59) participated up to the 120-day study period and 52% (n = 43) completed the follow-up survey. Of the 69,530 text messages distributed, participants responded to 61,571 (88.6%). Mean sleep quality at 120 days did not differ from baseline for intervention (p > 0.05) or control group participants (p > 0.05), and did not differ between groups (p > 0.05). There was no change from baseline to 120 days in the proportion with poor sleep quality in either group. Intra-shift fatigue increased (worsened) over the course of 12-hour shifts for participants in both study arms. Fatigue at the end of 12-hour shifts was higher among control group participants than participants in the intervention group (p < 0.05). Pre-shift hours of sleep were often less than 7 hours and did not differ between the groups over time. Conclusions: The SleepTrackTXT2 behavioral intervention showed a positive short-term impact on self-rated fatigue during 12-hour shifts, but did not impact longer duration shifts or have a longer-term impact on sleep quality among air-medical EMS clinicians.

Fatigue mitigation with SleepTrackTXT2 in air medical emergency care systems: study protocol for a randomized controlled trial.

BACKGROUND: Most air medical Emergency Medical Services (EMS) clinicians work extended duration shifts, and more than 50% report inadequate sleep, poor sleep quality, and/or poor recovery between shifts. The SleepTrackTXT pilot trial (ClinicalTrials.gov, NCT02063737) showed that use of mobile phone text messages could impact EMS clinician self-reported fatigue and sleepiness during long duration shifts. The purpose of the SleepTrackTXT2 trial is to leverage lessons learned from the first SleepTrackTXT study and test an enhanced intervention targeting air medical EMS clinicians. METHODS/DESIGN: We will conduct a multi-site randomized trial with a sample of adult EMS clinicians recruited from four air medical EMS systems located in the midwest, northeastern, and southern USA. Participants will be allocated to one of two possible arms for a 4-month (120-day) study period. The intervention arm will involve text-message assessments of sleepiness, fatigue, and difficulty concentrating at the beginning, every 4 hours during, and at the end of scheduled shifts. Participants reporting high levels of sleepiness, fatigue, or difficulty with concentration will receive one of nine randomly selected intervention messages to promote behavior change during shift work to improve alertness. Intervention participants will receive a text-message report on Friday of each week that shows their sleep debt over the previous 7 days followed by a text message to promote paying back sleep debt recovery when feasible. Participants in the control group receive text messages that only include assessments. Both arms will receive text-message assessments of perceived recovery since last shift, sleepiness, fatigue, or difficulty with concentration at noon (1200 hours) on days between scheduled shifts (off-duty days). We have two aims for this study: (1) to determine the short-term impact of the enhanced SleepTrackTXT2 intervention on air medical clinician fatigue reported in real time during and at the end of shift work, and (2) to determine the long-term impact of the SleepTrackTXT2 intervention on sleep quality and sleep health indicators including hours of sleep and recovery between shift work. DISCUSSION: The SleepTrackTXT2 trial may provide evidence of real-world effectiveness that would support widespread expansion of fatigue mitigation interventions in emergency care clinician shift workers. The trial may specifically support use of real-time assessments and interventions delivered via mobile technology such as text messaging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02783027 . Registered on 23 May 2016.

Real-time fatigue reduction in emergency care clinicians: The SleepTrackTXT randomized trial.

BACKGROUND: We assessed performance characteristics and impact of a mobile phone text-message intervention for reducing intra-shift fatigue among emergency clinician shift workers. METHODS: We used a randomized controlled trial of 100 participants. All participants received text-message assessments at the start, every 4 hr during, and at end of scheduled shifts over a 90-day period. Text-message queries measured self-rated sleepiness, fatigue, and difficulty with concentration. Additional text-messages were sent to intervention participants to promote alertness. A performance measure of interest was compliance with answering text-messages. RESULTS: Ninety-nine participants documented 2,621 shifts and responded to 36,073 of 40,947 text-messages (88% compliance rate). Intervention participants reported lower mean fatigue and sleepiness at 4 hr, 8 hr, and at the end of 12 hr shifts compared to controls (P < 0.05). Intervention participants reported better sleep quality at 90-days compared to baseline (P = 0.01). CONCLUSIONS: We showed feasibility and short-term efficacy of a text-message based assessment and intervention tool.