Using connectome-based models of working memory to predict emotion regulation in older adults.

Older adulthood is characterized by enhanced emotional well-being potentially resulting from greater reliance on adaptive emotion regulation strategies. However, not all older adults demonstrate an increase in emotional well-being and instead rely on maladaptive emotion regulation strategies. An important moderator of age-related shifts in strategy preferences is working memory (WM) and its underlying neural circuitry. As such, individual differences in the neural integrity underlying WM may predict older adults' emotion regulation strategy preferences. Our study used whole-brain WM networks-derived from young adults using connectome-based predictive modeling-to predict WM performance and acceptance strategy use in healthy older adults. Older adults (N = 110) completed baseline assessments as part of a randomized controlled trial examining the impact of mind-body interventions on healthy aging. Our results revealed that the WM networks predicted WM accuracy but not acceptance use or difficulties in emotion regulation in older adults. Individual differences in WM performance, but not WM networks, moderated relationships between image intensity and acceptance use. These findings highlight that robust neural markers of WM generalize to an independent sample of healthy older adults but may not generalize beyond cognitive domains to predict emotion-based behaviors.

Protocol for a randomized controlled trial of mindfulness-based stress reduction to improve attentional control in older adults (HealthyAgers trial).

BACKGROUND: Mindfulness meditation is a form of mind-body intervention that has increasing scientific support for its ability to reduce age-related declines in cognitive functioning, improve affective health, and strengthen the neural circuitry supporting improved cognitive and affective health. However, the majority of existent studies have been pilot investigations with small sample sizes, limited follow-up data, and a lack of attention to expectancy effects. Here, we present the study design of a Phase I/II, efficacy trial-HealthyAgers trial-that examines the benefits of a manualized mindfulness-based stress reduction program in improving attentional control and reducing mind-wandering in older adults. METHODS: One hundred fifty older adults (ages 65-85 years) will be randomized into one of two groups: an eight-week mindfulness program or an eight-week, placebo-controlled, lifestyle education program. Behavioral and neuroimaging assessments are conducted before and after the training. Participants are then invited to booster sessions once every three months for a period of 12 months with post-intervention follow-up assessments conducted at 6-months and 12-months. The primary outcomes for the study are behavioral measures of attentional control and mind-wandering. Additional, secondary outcomes include network strength in an a priori defined neuromarker of attentional control, fluid and everyday cognition, emotion regulation strategy use, and markers of inflammation. DISCUSSION: This study will establish the efficacy of a group-based, low-cost mind-body intervention for the inter-related facets of attentional control and mind-wandering in older adults. Strengths of this study include a well-designed, placebo-controlled comparison group, use of web/mobile application to track study adherence, and longitudinal follow-up. TRIAL REGISTRATION: Clinicaltrials.gov (# NCT03626532 ). Registered August 4, 2018.

Inter-relationships between changes in stress, mindfulness, and dynamic functional connectivity in response to a social stressor.

We conducted a study to understand how dynamic functional brain connectivity contributes to the moderating effect of trait mindfulness on the stress response. 40 male participants provided subjective reports of stress, cortisol assays, and functional MRI before and after undergoing a social stressor. Self-reported trait mindfulness was also collected. Experiencing stress led to significant decreases in the prevalence of a connectivity state previously associated with mindfulness, but no changes in two connectivity states with prior links to arousal. Connectivity did not return to baseline 30 min after stress. Higher trait mindfulness was associated with attenuated affective and neuroendocrine stress response, and smaller decreases in the mindfulness-related connectivity state. In contrast, we found no association between affective response and functional connectivity. Taken together, these data allow us to construct a preliminary brain-behaviour model of how mindfulness dampens stress reactivity and demonstrate the utility of time-varying functional connectivity in understanding psychological state changes.

Predicting response time variability from task and resting-state functional connectivity in the aging brain.

Aging is associated with declines in a host of cognitive functions, including attentional control, inhibitory control, episodic memory, processing speed, and executive functioning. Theoretical models attribute the age-related decline in cognitive functioning to deficits in goal maintenance and attentional inhibition. Despite these well-documented declines in executive control resources, older adults endorse fewer episodes of mind-wandering when assessed using task-embedded thought probes. Furthermore, previous work on the neural basis of mind-wandering has mostly focused on young adults with studies predominantly focusing on the activity and connectivity of a select few canonical networks. However, whole-brain functional networks associated with mind-wandering in aging have not yet been characterized. In this study, using response time variability-the trial-to-trial fluctuations in behavioral responses-as an indirect marker of mind-wandering or an "out-of-the-zone" attentional state representing suboptimal behavioral performance, we show that brain-based predictive models of response time variability can be derived from whole-brain task functional connectivity. In contrast, models derived from resting-state functional connectivity alone did not predict individual response time variability. Finally, we show that despite successful within-sample prediction of response time variability, our models did not generalize to predict response time variability in independent cohorts of older adults with resting-state connectivity. Overall, our findings provide evidence for the utility of task-based functional connectivity in predicting individual response time variability in aging. Future research is needed to derive more robust and generalizable models.

Pace yourself: Neural activation and connectivity changes over time vary by task type and pacing.

Performance deterioration over time, or time-on-task (TOT) effects, can be observed across a variety of tasks, but little attention has been paid to how TOT-related brain activity may differ based on task pacing and cognitive demands. Here, we employ a set of three closely related tasks to investigate the effect of these variables on fMRI activation and connectivity. When participants dictated the pace of their own responses, activation and network connectivity within the dorsal attention network (DAN) increased over short time scales (~2-3 min), a phenomenon that was not observed when participants had no control over their pace of work. Reaction time slowing was also the most pronounced in this self-paced task. In contrast, TOT-related changes in default-mode network (DMN) activity and connectivity, DAN-DMN anti-correlations, and pupil diameter did not differ based on pacing or task instructions. Over a longer (~10 min) time scale, task-positive activation and connectivity decreased in all paradigms, in agreement with older findings. These results highlight dynamic patterns of resource allocation that have not previously been observed in fMRI experiments, and speak to the idea that the brain may strategically allocate resources depending on the task at hand and the time scale of work.

Vigilance declines following sleep deprivation are associated with two previously identified dynamic connectivity states.

Robustly linking dynamic functional connectivity (DFC) states to behaviour is important for establishing the utility of the method as a functional measurement. We previously used a sliding window approach to identify two dynamic connectivity states (DCS) related to vigilance. A new sample of 32 healthy participants underwent two sets of task-free functional magnetic resonance imaging (fMRI) scans, once in a well-rested state and once after a single night of total sleep deprivation. Using a temporal difference method, DFC and clustering analysis on the task-free fMRI data revealed five centroids that were highly correlated with those found in previous work. In particular, two of these states were associated with high and low arousal respectively. Individual differences in vulnerability to sleep deprivation were measured by assessing state-related changes in Psychomotor Vigilance Test (PVT) performance. Changes in the duration spent in each of the arousal states from the well-rested to the sleep-deprived condition correlated with declines in PVT performance. The reproducibility of DFC measures and their association with vigilance highlight their utility in serving as a neuroimaging method with behavioural relevance. (178 words).

Dynamic functional connectivity markers of objective trait mindfulness.

While mindfulness is commonly viewed as a skill to be cultivated through practice, untrained individuals can also vary widely in dispositional mindfulness. Prior research has identified static neural connectivity correlates of this trait. Here, we use dynamic functional connectivity (DFC) analysis of resting-state fMRI to study time-varying connectivity patterns associated with naturally varying and objectively measured trait mindfulness. Participants were selected from the top and bottom tertiles of performers on a breath-counting task to form high trait mindfulness (HTM; N = 21) and low trait mindfulness (LTM; N = 18) groups. DFC analysis of resting state fMRI data revealed that the HTM group spent significantly more time in a brain state associated with task-readiness - a state characterized by high within-network connectivity and greater anti-correlations between task-positive networks and the default-mode network (DMN). The HTM group transitioned between brain states more frequently, but the dwell time in each episode of the task-ready state was equivalent between groups. These results persisted even after controlling for vigilance. Across individuals, certain connectivity metrics were weakly correlated with self-reported mindfulness as measured by the Five Facet Mindfulness Questionnaire, though these did not survive multiple comparisons correction. In the static connectivity maps, HTM individuals had greater within-network connectivity in the DMN and the salience network, and greater anti-correlations between the DMN and task-positive networks. In sum, DFC features robustly distinguish HTM and LTM individuals, and may be useful biological markers for the measurement of dispositional mindfulness.

Positive Effects of Mindfulness-Based Training on Energy Maintenance and the EEG Correlates of Sustained Attention in a Cohort of Nurses.

Mindfulness based training (MBT) is becoming increasingly popular as a means to improve general wellbeing through developing enhanced control over metacognitive processes. In this preliminary study, we tested a cohort of 36 nurses (mean age = 30.3, SD = 8.52; 2 male) who participated in an 8-week MBT intervention to examine the improvements in sustained attention and its energetic costs that may result from MBT. Changes in sustained attention were measured using the psychomotor vigilance task (PVT) and electroencephalography (EEG) was collected both during PVT performance, and during a brief period of meditation. As there was substantial variability in training attendance, this variable was used a covariate in all analyses. Following the MBT program, we observed changes in alpha power across all scalp regions during meditation that were correlated with attendance. Similarly, PVT performance worsened over the 8-week period, but that this decline was mitigated by good attendance on the MBT program. The subjective energy depletion due to PVT performance (measured using self-report on Likert-type scales) was also less in regular attendees. Finally, changes in known EEG markers of attention during PVT performance (P300 and alpha-band event-related desynchronization) paralleled these behavioral shifts. Taken together, our data suggest that sustained attention and its associated costs may be negatively affected over time in the nursing profession, but that regular attendance of MBT may help to attenuate these effects. However, as this study contained no control condition, we cannot rule out that other factors (e.g., motivation, placebo effects) may also account for our findings.

Modulating rest-break length induces differential recruitment of automatic and controlled attentional processes upon task reengagement.

Rest breaks are commonly administered as a countermeasure to reduce on-the-job fatigue, both physical and mental. However, this practice makes the assumption that recovery from fatigue, as measured by the reversal of performance declines, is the sole effect of taking a break on behavior. Here, through administering rest breaks of differing lengths in between blocks of a mentally demanding symbol decoding task, we show that this assumption may not be strictly true. First, we replicate previous work by showing that taking a longer break leads to two correlated effects: greater immediate rebound in performance, and greater subsequent time-on-task decline. Using fMRI, we reveal that time-on-task in this paradigm is associated with increasing recruitment of fronto-parietal areas associated with top-down control, and decreasing deactivation in the default-mode network. Finally, by analyzing individual differences, we reveal a potential neural basis for our behavioral observation: greater recovery following long breaks is associated with greater activity in the putamen, an area associated with the automatic generation of motor responses, followed by greater activity in left middle frontal gyrus by the end of those task periods. Taken together, this suggests a shift in the implicit engagement of automatic and controlled attentional processing following longer breaks. This shift may be undesirable or detrimental in real-world situations where maintaining a stable level of attention over time is necessary.

Early Practice Focus: Evidence-Based Practice in Facial Plastic Surgery.

The practice of evidence-based medicine combines physician experience, knowledge of current literature, and patient preferences. Different grading systems are used to evaluate current levels of evidence and recommendations. A variety of common instruments are used to measure outcomes in facial plastic surgery. These instruments are used for expert data collection, including assessment of pathology and response to treatment, or for patient-reported outcome measures, including quality of life, disability, and daily function. Integration of data collection requires storage and protection of health information. We provide an outline to what is involved in understanding evidence-based medicine and incorporating it into daily practice.

Histopathologic margin distance in survival in resection of cutaneous melanoma of the head and neck.

OBJECTIVES/HYPOTHESIS: Treatment of cutaneous melanoma involves surgical excision with wide clinical margins. No guidelines regarding safe histopathologic margin distance exist. This study examines the impact of histopathologic margin, measured from closest cut edge of the specimen, on overall survival in resection of cutaneous melanoma of the head and neck. We hypothesize that close histopathologic margins (<2 mm) are associated with decreased survival. STUDY DESIGN: Retrospective chart review. METHODS: A total of 637 patients were treated for cutaneous melanoma of the head and neck between 2001 and 2011. Demographics, tumor characteristics, histopathologic margin distance (from a pathology database), and survival data from state health registries and health system clinical data repositories were used to create a dataset. Cox regression models and Kaplan-Meier curves were used to analyze data, adjusting for age, tumor location, ulceration, and depth of invasion (DOI). RESULTS: When analyzing for overall survival, Cox multivariate regression analysis showed age (hazard ratio [HR] = 1.0-1.1), DOI (HR = 1.2-1.5), ulceration (HR = 1.3-3.8), and subsite (ear, HR = 1.0-3.9) were significant predictors of survival. Histopathologic margin distance was not significant for predicting survival. Three percent of histopathologic margins were <1 mm. CONCLUSIONS: In a large dataset of head and neck cutaneous melanoma, known factors associated with overall survival (age, DOI, ulceration, subsite) proved significant, validating the dataset. Examining the effect of histopathologic margin distance on survival, while controlling for these factors, we failed to reject the null hypothesis. Margin distance as measured by histopathology does not affect survival. LEVEL OF EVIDENCE: 4.

Cervical spine injury: analysis and comparison of patients by mode of transportation.

BACKGROUND: Cervical spine injury (CSI) studies have identified different factors contributing to CSI, but none compares the incidence and pattern of injury of patients arriving at the Emergency Department (ED) by private vehicle (PV). OBJECTIVE: We compared the characteristics and injury patterns in CSI patients who were transported to the ED via Emergency Medical Services (EMS) versus PV. METHODS: We conducted a three-hospital retrospective review of patients with CSI from January 1, 2000 to December 31, 2007. We excluded transfers and follow-up visits. Using a standardized data collection form, we reviewed demographics, mode of transport, mechanism of injury, imaging results, injury type and level, and neurologic deficits. Means and proportions were compared using t-tests and chi-squared as appropriate. RESULTS: Of 1174 charts identified, 718 met all study criteria; 671 arrived by EMS and 47 by PV. There was no difference between groups in age or gender. Ground-level fall was more likely in PV patients (32%, 95% confidence interval [CI] 20-46% vs. 6%, 95% CI 4-9%), whereas motor vehicle collision was less likely (32%, 95% CI 20-46% vs. 67%, 95% CI 63-70%). PV patients more often sustained a stable injury (66%, 95% CI 52-78% vs. 40%, 95% CI 36-44%), and were more often triaged to a lower-acuity area (25%, 95% CI 15-40% vs. 4%, 95% CI 3-6%). The incidence of neurologic deficit was similar (32%, 95% CI 20-46% vs. 24%, 95% CI 21-28%), though more PV patients had spinal cord injury without radiographic abnormality (21%, 95% CI 12-35% vs. 5%, 95% CI 4-7%). CONCLUSION: A small proportion of patients with CSI present to the ED by PV. Although most had stable injuries, a surprising number had unstable injuries with neurologic deficits, and were triaged to lower-acuity areas in the ED.

Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons.

Sensory nerves detect an extensive array of somatosensory stimuli, including environmental temperatures. Despite activating only a small cohort of sensory neurons, cold temperatures generate a variety of distinct sensations that range from pleasantly cool to painfully aching, prickling, and burning. Psychophysical and functional data show that cold responses are mediated by both C- and A delta-fibers with separate peripheral receptive zones, each of which likely provides one or more of these distinct cold sensations. With this diversity in the neural basis for cold, it is remarkable that the majority of cold responses in vivo are dependent on the cold and menthol receptor transient receptor potential melastatin 8 (TRPM8). TRPM8-null mice are deficient in temperature discrimination, detection of noxious cold temperatures, injury-evoked hypersensitivity to cold, and nocifensive responses to cooling compounds. To determine how TRPM8 plays such a critical yet diverse role in cold signaling, we generated mice expressing a genetically encoded axonal tracer in TRPM8 neurons. Based on tracer expression, we show that TRPM8 neurons bear the neurochemical hallmarks of both C- and A delta-fibers, and presumptive nociceptors and non-nociceptors. More strikingly, TRPM8 axons diffusely innervate the skin and oral cavity, terminating in peripheral zones that contain nerve endings mediating distinct perceptions of innocuous cool, noxious cold, and first- and second-cold pain. These results further demonstrate that the peripheral neural circuitry of cold sensing is cellularly and anatomically complex, yet suggests that cold fibers, caused by the diverse neuronal context of TRPM8 expression, use a single molecular sensor to convey a wide range of cold sensations.