Peripheral inflammation is associated with impaired sadness recognition in euthymic bipolar patients.

BACKGROUND: Inflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). METHODS: We recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. RESULTS: Regarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for. CONCLUSIONS: We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation.

Comparing fine motor performance among young children with autism spectrum disorder, intellectual disability, attention-deficit/hyperactivity disorder, and specific developmental disorder of motor function.

Objective: The acquisition of fine motor skills is considered to be a crucial developmental milestone throughout early childhood. This study aimed to investigate the fine motor performance of young children with different disability diagnoses. Methods: We enrolled a sample of 1,897 young children under the age of 6 years who were at risk of developmental delays and were identified by a transdisciplinary team. A series of standardized developmental assessments included the Bayley Scales of Infant Development-Third Edition, Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition, Peabody Developmental Motor Scale-Second Edition, and Movement Assessment Battery for Children-Second Edition were used. Retrospective chart reviews were conducted on all children to identify specific developmental disorders. The number of autism spectrum disorder (ASD), intellectual disability (ID), attention-deficit/hyperactivity disorder (ADHD), comorbidity, motor dysfunction, and unspecified developmental delays (DD) were 363 (19.1%), 223 (11.8%), 234 (12.3%), 285 (15.0%), 128 (6.7%), and 590 (31.1%), respectively. Results: Young children with ID, comorbidity, and motor dysfunction demonstrated significant difficulty in performing manual dexterity and visual motor integration tasks and scored significantly lower in these areas than children with ASD, ADHD, and unspecified DD. In addition, fine motor performance was associated with cognitive ability in children with different disability diagnoses, indicating that young children showed better fine motor performance when they demonstrated better cognitive ability. Conclusion: Our findings support that differences in fine motor performance differ by disability type. Close links between fine motor performance and cognitive ability in children under the age of 6 years were seen in all disability types.

Social cognitive deficit is associated with visuomotor coordination impairment and dopamine transporter availability in euthymic bipolar disorder.

BACKGROUND: Extensive evidence has suggested functional connections between co-occurring visuomotor and social cognitive deficits in neuropsychiatric disorders; however, such association has not been studied in bipolar disorder (BD). We aimed to investigate the relationship between visuomotor coordination and social cognition in the euthymic stage of BD (euBD). Given the shared neurobiological underpinnings involving the dopaminergic system and corticostriatal circuitry, we hypothesized a positive correlation between social cognition and visuomotor coordination in euBD patients. METHODS: 40 euBD patients and 59 healthy control (HC) participants underwent evaluation of social (Diagnostic Analysis of Nonverbal Accuracy 2-Taiwan version (DANVA-2-TW)), non-social cognitive function and visuomotor coordination. A subgroup of participants completed single-photon emission computed tomography for striatal dopamine transporter (DAT) availability assessment. RESULTS: EuBD patients showed impaired nonverbal emotion recognition (ps ≤ 0.033) and poorer visuomotor coordination (ps < 0.003) compared to HC, with a positive correlation between these two abilities (r = 0.55, p < 0.01). However, after considering potential confounding factors, instead of visuomotor coordination, striatal DAT availability was a unique predictor of emotion recognition accuracy in euBD (beta = 0.33, p = 0.001). CONCLUSION: Our study result supported a functional association between social cognition and visuomotor coordination in euBD, with striatal dopaminergic dysfunction emerged as a crucial contributing factor in their interrelation.

Interoceptive awareness: MBSR training alters information processing of salience network.

Mindfulness refers to a mental state of awareness of internal experience without judgment. Studies have suggested that each mindfulness practice may involve a unique mental state, but the underlying neurophysiological mechanisms remain unknown. Here we examined how distinct mindfulness practices after mindfulness-based intervention alter brain functionality. Specifically, we investigated the functional alterations of the salience network (SN) using functional magnetic resonance imaging (fMRI) among the two interoceptive mindfulness practices-breathing and body scan-associated with interoceptive awareness in fixed attention and shifted attention, respectively. Long-distance functional connectivity (FC) and regional homogeneity (ReHo) approaches were applied to measure distant and local neural information processing across various mental states. We hypothesized that mindful breathing and body scan would yield a unique information processing pattern in terms of long-range and local functional connectivity (FC). A total of 18 meditation-naïve participants were enrolled in an 8-week mindfulness-based stress reduction (MBSR) program alongside a waitlist control group (n = 14), with both groups undergoing multiple fMRI sessions during breathing, body scan and resting state for comparison. We demonstrated that two mindfulness practices affect both the long-distance FC SN and the local ReHo, only apparent after the MBSR program. Three functional distinctions between the mindfulness practices and the resting state are noted: (1) distant SN connectivity to occipital regions increased during the breathing practice (fixed attention), whereas the SN increased connection with the frontal/central gyri during the body scan (shifting attention); (2) local ReHo increased only in the parietal lobe during the body scan (shifting attention); (3) distant and local connections turned into a positive correlation only during the mindfulness practices after the MBSR training, indicating a global enhancement of the SN information processing during mindfulness practices. Though with limited sample size, the functional specificity of mindfulness practices offers a potential research direction on neuroimaging of mindfulness, awaiting further studies for verification.

Disrupted white matter network of brain structural connectomes in bipolar disorder patients revealed by q-ball imaging.

BACKGROUND: Structural and functional brain changes have been found to be associated with altered emotion and cognition in patients with bipolar disorder (BD). Widespread microstructural white matter abnormalities have been observed using traditional structural imaging in BD. q-Ball imaging (QBI) and graph theoretical analysis (GTA) improve the specificity and sensitivity and high accuracy of fiber tracking. We applied QBI and GTA to investigate and compare the structural connectivity alterations and network alterations in patients with and without BD. METHODS: Sixty-two patients with BD and 62 healthy controls (HCs) completed a MR scan. We evaluated the group differences in generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values by voxel-based statistical analysis with QBI. We also evaluated the group differences in topological parameters of GTA and subnetwork interconnections in network-based statistical analysis (NBS). RESULTS: The QBI indices in the BD group were significantly lower than those in the HC group in the corpus callosum, cingulate gyrus, and caudate. The GTA indices indicated that the BD group demonstrated less global integration and higher local segregation than the HC group, but they retained small-world properties. NBS evaluation showed that the majority of the more connected subnetworks in BD occurred in thalamo-temporal/parietal connectivity. CONCLUSION: Our findings supported white matter integrity with network alterations in BD.

Enhanced electroencephalography effective connectivity in frontal low-gamma band correlates of emotional regulation after mindfulness training.

Practicing mindfulness, focusing attention on the internal and external experiences occurring in the present moment with open and nonjudgement stance, can lead to the development of emotional regulation skills. Yet, the effective connectivity of brain regions during mindfulness has been largely unexplored. Studies have shown that mindfulness practice promotes functional connectivity in practitioners, potentially due to improved emotional regulation abilities and increased connectivity in the lateral prefrontal areas. To examine the changes in effective connectivity due to mindfulness training, we analyzed electroencephalogram (EEG) signals taken before and after mindfulness training, focusing on training-related effective connectivity changes in the frontal area. The mindfulness training group participated in an 8-week mindfulness-based stress reduction (MBSR) program. The control group did not take part. Regardless of the specific mindfulness practice used, low-gamma band effective connectivity increased globally after the mindfulness training. High-beta band effective connectivity increased globally only during Breathing. Moreover, relatively higher outgoing effective connectivity strength was seen during Resting and Breathing and Body-scan. By analyzing the changes in outgoing and incoming connectivity edges, both F7 and F8 exhibited strong parietal connectivity during Resting and Breathing. Multiple regression analysis revealed that the changes in effective connectivity of the right lateral prefrontal area predicted mindfulness and emotional regulation abilities. These results partially support the theory that the lateral prefrontal areas have top-down modulatory control, as these areas have high outflow effective connectivity, implying that mindfulness training cultivates better emotional regulation.

Mindfulness Training Associated With Resting-State Electroencephalograms Dynamics in Novice Practitioners via Mindful Breathing and Body-Scan.

Objectives: Mindfulness-based stress reduction has been proven to improve mental health and quality of life. This study examined how mindfulness training and various types of mindfulness practices altered brain activity. Methods: Specifically, the spectral powers of scalp electroencephalography of the mindfulness-based stress reduction (MBSR) group (n=17) who underwent an 8-week MBSR training-including mindful breathing and body-scan-were evaluated and compared with those of the waitlist controls (n=14). Results: Empirical results indicated that the post-intervention effect of MBSR significantly elevated the resting-state beta powers and reduced resting-state delta powers in both practices; such changes were not observed in the waitlist control. Compared with mindful breathing, body-scanning resulted in an overall decline in electroencephalograms (EEG) spectral powers at both delta and low-gamma bands among trained participants. Conclusion: Together with our preliminary data of expert mediators, the aforementioned spectral changes were salient after intervention, but mitigated along with expertise. Additionally, after receiving training, the MBSR group's mindfulness and emotion regulation levels improved significantly, which were correlated with the EEG spectral changes in the theta, alpha, and low-beta bands. The results supported that MBSR might function as a unique internal processing tool that involves increased vigilant capability and induces alterations similar to other cognitive training.

l-Cystine is associated with the dysconnectivity of the default-mode network and salience network in attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Distributed dysconnectivity within both the default-mode network (DMN) and the salience network (SN) has been observed in ADHD. L-cystine may serve as a neuroprotective molecule and signaling pathway, as well as a biomarker of ADHD. The purpose of this study was to explore whether differential brain network connectivity is associated with peripheral L-cystine levels in ADHD patients. We recruited a total of 31 drug-naïve patients with ADHD (mean age: 10.4 years) and 29 healthy controls (mean age: 10.3 years) that underwent resting state functional magnetic resonance imaging scans. Functional connectomes were generated for each subject, and we examined the cross-sectional group difference in functional connectivity (FC) within and between DMN and SN. L-cystine plasma levels were determined using high-performance chemical isotope labeling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Compared to the control group, the ADHD group showed decreased FC of dorsal DMN (p = 0.031), as well as decreased FC of precuneus-post SN (p = 0.006) and ventral DMN-post SN (p = 0.001). The plasma L-cystine levels of the ADHD group were significantly higher than in the control group (p = 0.002). Furthermore, L-cystine levels were negatively correlated with FC of precuneus-post SN (r = -0.404, p = 0.045) and ventral DMN-post SN (r = -0.540, p = 0.007). The findings suggest that decreased synergies of DMN and SN may serve as neurobiomarkers for ADHD, while L-cystine may be involved in the pathophysiology of network dysconnectivity. Future studies on the molecular mechanism of the cystine-glutamate system in brain network connectivity are warranted.

Gray matter volume and microRNA levels in patients with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder often characterized by gray matter (GM) volume reductions. MicroRNAs, which participate in regulating gene expression, potentially influence neurodevelopment. This study aimed to explore whether differential GM volume is associated with differential miRNA levels in ADHD patients. We recruited a total of 30 drug-naïve patients with ADHD (mean age 10.6 years) and 25 healthy controls (mean age 10.6 years) that underwent a single session of 3.0-T whole brain structural MRI scanning. RNA samples from the participants' white blood cells were collected to identify the ΔCt values of three miRNAs (miR-30e-5p, miR-126-5p, and miR-140-3p) using the real-time quantitative reverse transcription polymerase chain reaction. In comparison to the control group, ADHD patients demonstrated a significantly lower GM volume in the cingulate gyrus, left middle temporal gyrus, right middle occipital gyrus, left fusiform gyrus, and significantly higher ΔCt values of miR-30e-5p, miR-126-5p, and miR-140-3p. In the ADHD group, the GM volume of cingulate gyrus and left fusiform gyrus was negatively correlated with the ΔCt values of miR-30e-5p, miR-140-3p. The GM volume of left fusiform gyrus was negatively correlated to ADHD behavioral symptoms. Using structural equation modeling (SEM), we observed that the effect of miR-140-3p on hyperactivity/impulsivity symptoms was mediated by left fusiform gyrus. Our findings support that GM volume reduction and miRNA increases may be biomarkers for ADHD in children and adolescents. Expression levels of miRNAs may affect the development of brain structures and further participate in the pathophysiology of ADHD.

Anticipated, experienced, and remembered subjective effort and discomfort on sustained attention versus working memory tasks.

This study examined individuals' ability to accurately anticipate how cognitively effortful and uncomfortable a task will feel based on a short sample of the task. Participants completed a sustained attention or working memory task. Post-practice, participants rated the effort and discomfort that they anticipated their task would require and engender, respectively. Participants also rated their effort and discomfort during task-administration and the effort and discomfort they recalled feeling after task-administration. Sustained attention task participants anticipated significantly less effort than working memory task participants. Sustained attention task participants felt significantly more effort during the task and remembered feeling more effort than they had anticipated. Working memory task participants felt significantly less effort during the task than they had anticipated. Sustained attention task participants anticipated, experienced, and recalled feeling more discomfort than working memory task participants. Individuals' anticipation of effort required depends on the task and is different from the effort they actually feel during the task and later recall feeling.

Deficits in auditory sensory discrimination among children with attention-deficit/hyperactivity disorder.

Research into children with attention-deficit/hyperactivity disorder (ADHD) has focused on complex cognitive dysfunction, but less attention has been paid to sensory perception processes underlying the symptoms of ADHD. Based on signal detection theory, the present study compared the sensory discrimination ability and decision bias of children with and without ADHD. It also investigated the differences between ADHD with predominantly inattentive (ADHDi) and combined presentations (ADHDc). The sample of 75 children and adolescents with ADHD (24 ADHDi, 51 ADHDc) (16 females and 59 males) and 22 typical developing controls (TD) (8 females and 14 males) completed an auditory signal detection task. Participants were asked to detect signals against levels of transient background noise (35, 45, 55, and 65 dB). The results showed that with the increase of noise levels, both the ADHD and TD groups demonstrated decreased sensory discrimination. Although both groups successfully detected signal against noise levels from 35 to 55 dB, the ADHD group showed lower discrimination ability than that of the TD group. For decision bias, no group difference was found. Further comparisons regarding the predominant symptom presentation of ADHD sub-groups showed no differences. Current research has suggested that the deficit in ADHD people's signal detection performance can be attributed to sensory discrimination rather than decision bias. We suggest that background noise should be taken into account when using auditory stimuli to investigate cognitive functions in people with ADHD.

Mental effort and discomfort: Testing the peak-end effect during a cognitively demanding task.

We applied the peak-end paradigm that was first introduced in the pain literature to examine the experience of effort and discomfort during a cognitively demanding working memory task. A total of 401 participants were asked to rate their effort and discomfort during and after the administration of a working memory task, which systematically varied task difficulty within participants and task duration between participants. Over the course of the task, participants reported a decrease in reported effort and an increase in reported discomfort. Peak and end real-time ratings were significant predictors of retrospective ratings for effort and discomfort; average and initial ratings predicted a small amount of additional variance. The regression analyses with effort and discomfort were largely consistent, with some exceptions. End discomfort significantly predicted willingness to do the task again, but not end effort. These findings highlight the ways in which the experience of effort and discomfort are integrally related, yet importantly separate, during a cognitively demanding task.

Differences in Perceived Mental Effort Required and Discomfort during a Working Memory Task between Individuals At-risk And Not At-risk for ADHD.

Objective: The avoidance of mental effort is a symptom criterion for Attention-Deficit/Hyperactivity Disorder (ADHD), but the experience of mental effort has received relatively little attention in the empirical study of individuals at-risk for ADHD. We explored a novel method to assess the experience of effort and discomfort during a working memory task in a sample of young adults at-risk and not at-risk for ADHD. Method: A sample of 235 undergraduate students (Mean age = 21.02, 86 males) were included in this study. Based on an ADHD-screener (ASRS), 136 participants met criteria for the ADHD-risk group and 99 were in the non-ADHD risk group. Results: Individuals at-risk for ADHD reported higher mental effort and discomfort than individuals not at-risk for ADHD, even when performance on the working memory task was comparable or statistically controlled. Mental effort required and discomfort were more strongly correlated for at-risk compared to not at-risk participants. Individuals at-risk for ADHD displayed a stronger correlation between mental effort required and actual accuracy, but individuals not at-risk for ADHD displayed a stronger association between perceived accuracy and actual accuracy for the hardest experimental conditions. The most intense moment of effort required predicted retrospective discomfort ratings of the task in the ADHD-risk group, but not in the non-risk group. Conclusion: The subjective experience of in the moment mental effort is an important and viable construct that should be more carefully defined and measured. In particular, the experience of effort required (or how taxing a task is) differentiated between individuals at-risk and individuals not at-risk for ADHD in the present study. Whereas previous ADHD research has explored effort exerted, the present work demonstrated that investigating the experience of being mentally taxed might provide a productive line of investigation that could be used to advance our understanding of the cognitive and affective mechanisms underlying the regulation of effort in individuals at-risk of ADHD.

Electrophysiological evidence during episodic prospection implicates medial prefrontal and bilateral middle temporal gyrus.

fMRI studies have implicated the medial prefrontal cortex and medial temporal lobe, components of the default mode network (DMN), in episodic prospection. This study compared quantitative EEG localized to these DMN regions during prospection and during resting and while waiting for rewards. EEG was recorded in twenty-two adults while they were asked to (i) envision future monetary episodes; (ii) wait for rewards and (iii) rest. Activation sources were localized to core DMN regions. EEG power and phase coherence were compared across conditions. Prospection, compared to resting and waiting, was associated with reduced power in the medial prefrontal gyrus and increased power in the bilateral medial temporal gyrus across frequency bands as well as greater phase synchrony between these regions in the delta band. The current quantitative EEG analysis confirms prior fMRI research suggesting that medial prefrontal and medial temporal gyrus interactions are central to the capacity for episodic prospection.

The Malnutrition Universal Screening Tool (MUST) and a nutrition education program for high risk cancer patients: strategies to improve dietary intake in cancer patients.

Four hundred and forty-four high-risk oncology patients with malnutrition participated in this study aimed at assessing the effectiveness of nutrition education on improving an oncology patient's dietary intake. We used a nutritional risk screening to select oncology patients in need of nutritional care. Team Nutrition provides technical assistance for foodservice, nutrition education for patients and their caregivers, and support for healthy eating and physical activity to improve their diets and their lives. The average contribution of protein and total energy of each patient increased after imparting the nutritional education to them. Thus, nutritional education is an effective measure to bring about a favorable and significant change in oncology patients' nutrient intake.

Spontaneous activity in the waiting brain: a marker of impulsive choice in attention-deficit/hyperactivity disorder?

BACKGROUND: Spontaneous very low frequency oscillations (VLFO), seen in the resting brain, are attenuated when individuals are working on attention demanding tasks or waiting for rewards (Hsu et al., 2013). Individuals with attention-deficit/hyperactivity disorder (ADHD) display excess VLFO when working on attention tasks. They also have difficulty waiting for rewards. Here we examined the waiting brain signature in ADHD and its association with impulsive choice. METHODS: DC-EEG from 21 children with ADHD and 21 controls (9-15 years) were collected under four conditions: (i) resting; (ii) choosing to wait; (iii) being "forced" to wait; and (iv) working on a reaction time task. A questionnaire measured two components of impulsive choice. RESULTS: Significant VLFO reductions were observed in controls within anterior brain regions in both working and waiting conditions. Individuals with ADHD showed VLFO attenuation while working but to a reduced level and none at all when waiting. A closer inspection revealed an increase of VLFO activity in temporal regions during waiting. Excess VLFO activity during waiting was associated with parents' ratings of temporal discounting and delay aversion. CONCLUSIONS: The results highlight the potential role for waiting-related spontaneous neural activity in the pathophysiology of impulsive decision-making of ADHD.

"Can waiting awaken the resting brain?" A comparison of waiting- and cognitive task-induced attenuation of very low frequency neural oscillations.

The default mode network (DMN) is characterised by coherent very low frequency (VLF) neural oscillations in the resting brain. The attenuation of this activity has been demonstrated following the transition from rest to performance of a broad range of cognitive goal-directed tasks. Whether the activity of resting state VLF oscillations is attenuated during non-cognitive goal-directed tasks such as waiting for rewarding outcomes is not known. This study examined the VLF EEG power from resting to performance of attention demanding task and two types of goal-directed waiting tasks. The association between the attenuation of VLF EEG power and Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms was examined. Direct current EEG (DC-EEG) data were collected from 32 healthy young adults (half high and half low ADHD symptom scorers) during (i) a rest state, (ii) while performing a cognitive demanding reaction time task (2CRT), and (iii) while undertaking each of two different goal-directed waiting conditions: "forced-to-wait (FW)" and "choose-to-wait (CW)" tasks. The spatial distribution of VLF EEG power across scalp was similar to that seen in previous resting VLF EEG studies. Significant rest-to-task attenuation of VLF EEG power occurred during the 2CRT and the CW task, but not during the FW task. The association between self-ratings of ADHD symptoms and waiting-induced attenuation was not significant. This study suggests VLF EEG power attenuation that occurs following rest-to-task transition is not simply determined by changes in cognitive load. The goal-directed nature of a task, its motivated nature and/or the involvement of effortful attention may also contribute. Future studies should explore the attenuation of resting state VLF oscillations during waiting and impulsive choice.

Estimation of premorbid general fluid intelligence using traditional Chinese reading performance in Taiwanese samples.

AIMS: The aims of the present study were to (i) investigate if traditional Chinese word reading ability can be used for estimating premorbid general intelligence; and (ii) to provide multiple regression equations for estimating premorbid performance on Raven's Standard Progressive Matrices (RSPM), using age, years of education and Chinese Graded Word Reading Test (CGWRT) scores as predictor variables. METHODS: Four hundred and twenty-six healthy volunteers (201 male, 225 female), aged 16-93 years (mean +/- SD, 41.92 +/- 18.19 years) undertook the tests individually under supervised conditions. Seventy percent of subjects were randomly allocated to the derivation group (n = 296), and the rest to the validation group (n = 130). RESULTS: RSPM score was positively correlated with CGWRT score and years of education. RSPM and CGWRT scores and years of education were also inversely correlated with age, but the declining trend for RSPM performance against age was steeper than that for CGWRT performance. Separate multiple regression equations were derived for estimating RSPM scores using different combinations of age, years of education, and CGWRT score for both groups. The multiple regression coefficient of each equation ranged from 0.71 to 0.80 with the standard error of estimate between 7 and 8 RSPM points. When fitting the data of one group to the equations derived from its counterpart group, the cross-validation multiple regression coefficients ranged from 0.71 to 0.79. There were no significant differences in the 'predicted-obtained' RSPM discrepancies between any equations. CONCLUSION: The regression equations derived in the present study may provide a basis for estimating premorbid RSPM performance.