Compulsive drug-taking is associated with habenula-frontal cortex connectivity.

As a critical node connecting the forebrain with the midbrain, the lateral habenula (LHb) processes negative feedback in response to aversive events and plays an essential role in value-based decision-making. Compulsive drug use, a hallmark of substance use disorder, is attributed to maladaptive decision-making regarding aversive drug-use-related events and has been associated with dysregulation of various frontal-midbrain circuits. To understand the contributions of frontal-habenula-midbrain circuits in the development of drug dependence, we employed a rat model of methamphetamine self-administration (SA) in the presence of concomitant footshock, which has been proposed to model compulsive drug-taking in humans. In this longitudinal study, functional MRI data were collected at pretraining baseline, after 20 d of long-access SA phase, and after 5 d of concomitant footshock coupled with SA (punishment phase). Individual differences in response to punishment were quantified by a "compulsivity index (CI)," defined as drug infusions at the end of punishment phase, normalized by those at the end of SA phase. Functional connectivity of LHb with the frontal cortices and substantia nigra (SN) after the punishment phase was positively correlated with the CI in rats that maintained drug SA despite receiving increasing-intensity footshock. In contrast, functional connectivity of the same circuits was negatively correlated with CI in rats that significantly reduced SA. These findings suggest that individual differences in compulsive drug-taking are reflected by alterations within frontal-LHb-SN circuits after experiencing the negative consequences from SA, suggesting these circuits may serve as unique biomarkers and potential therapeutic targets for individualized treatment of addiction.

Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence.

We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.

[Diversified Innovation Strategies for an Early Limb Rehabilitation Program in Patients With Stroke].

BACKGROUND & PROBLEMS: Early rehabilitation after stroke is important for the recovery of bodily functions in stroke patients. However, the percentage of completion of early limb rehabilitation among stroke patients is only 16%. PURPOSE: Raise the early rehabilitation intervention rate to 88% for patients with stroke within 24 hours of hospitalization. RESOLUTION: We developed an education course on post-stroke rehabilitation and a related e-Learning course as well as organized an 'alliance for recovery' team. In addition, we established a standard for post-stroke relay rehabilitation and designed rehabilitation relay cards, Xbox rehabilitation games, and nine squares challenge for brain stroke care. RESULTS: The accuracy of the knowledge of nursing staff related to physical rehabilitation improved from 72.4% to 100%; the accuracy of their perceptions regarding early limb rehabilitation increased from 16% to 100%; and patient satisfaction increased from 68% to 98%. CONCLUSIONS: We deployed diverse and innovative strategies to assist limb rehabilitation in patients with stroke. Patients and caregivers should be encouraged to participate in early rehabilitation and related programs and should apply the skills and rehabilitation activities learned to daily life.

Local awakening: regional reorganizations of brain oscillations after sleep.

Brain functions express rhythmic fluctuations accompanied by sleep and wakefulness each day, but how sleep regulates brain rhythms remains unclear. Following the dose-dependent local sleep concept, two succeeding questions emerge: (1) is the sleep regulation a network-specific process; and (2) is the awakening state dependent on the previous sleep stages? To answer the questions, we conducted simultaneous EEG and fMRI recordings over 22 healthy male participants, along pre-sleep, nocturnal sleep and awakening. Using paired comparisons between awakening and pre-sleep conditions, three scenarios of the regional specificity were demonstrated on awakening: (1) the default-mode and hippocampal networks maintained similar connectivity and spectral power; (2) the sensorimotor network presented reduced connectivity and spectral power; and (3) the thalamus demonstrated substantially enhanced connectivity to the neo-cortex with decreased spectral power. With regard to the stage effect, the deep sleep group had significant changes in both functional connectivity and spectral power on awakening, whereas the indices of light sleep group remained relatively quiescent after sleep. The phenomena implied that slow-wave sleep could be key to rebooting the BOLD fluctuations after sleep. In conclusion, the regional specificity and the stage effect were verified in support of the local awakening concept, indicating that sleep regulation leads to the reorganization of brain networks upon awakening.

Role of dorsal striatum circuits in relapse to opioid seeking after voluntary abstinence.

High relapse rate during abstinence is a defining characteristic of drug addiction. We previously found that opioid seeking progressively increases after voluntary abstinence induced by adverse consequences of oxycodone seeking (crossing an electric barrier). Functional MRI revealed that this effect is associated with changes in functional connectivity within medial orbitofrontal cortex (mOFC)- and dorsomedial striatum (DMS)-related circuits. Here, we used a pharmacological manipulation and fMRI to determine the causal role of mOFC and DMS in oxycodone seeking after electric barrier-induced abstinence. We trained rats to self-administer oxycodone (6 h/day, 14 days). Next, we induced voluntary abstinence by exposing them to an electric barrier for 2 weeks. We inactivated the mOFC and DMS with muscimol+baclofen (GABAa and GABAb receptor agonists) and then tested them for relapse to oxycodone seeking on abstinence days 1 or 15 without the electric barrier or oxycodone. Inactivation of DMS (p < 0.001) but not mOFC decreased oxycodone seeking before or after electric barrier-induced abstinence. Functional MRI data revealed that DMS inactivation decreased cerebral blood volume levels in DMS and several distant cortical and subcortical regions (corrected p < 0.05). Furthermore, functional connectivity of DMS with several frontal, sensorimotor, and auditory regions significantly increased after DMS inactivation (corrected p < 0.05). Finally, an exploratory analysis of an existing functional MRI dataset showed that DMS inactivation restored voluntary abstinence-induced longitudinal changes in DMS functional connectivity with these brain regions (p < 0.05). Results indicate a role of DMS and related brain circuits in oxycodone seeking after voluntary abstinence, suggesting potential targets for intervention.

Light extraction efficiency analysis of GaN-based light-emitting diodes with nanopatterned sapphire substrates.

In this paper, we propose a method to analyze the light extraction efficiency (LEE) enhancement of a nanopatterned sapphire substrates (NPSS) light-emitting diode (LED) by comparing wave optics software with ray optics software. Finite-difference time-domain (FDTD) simulations represent the wave optics software and Light Tools (LTs) simulations represent the ray optics software. First, we find the trends of and an optimal solution for the LEE enhancement when the 2D-FDTD simulations are used to save on simulation time and computational memory. The rigorous coupled-wave analysis method is utilized to explain the trend we get from the 2D-FDTD algorithm. The optimal solution is then applied in 3D-FDTD and LTs simulations. The results are similar and the difference in LEE enhancement between the two simulations does not exceed 8.5% in the small LED chip area. More than 10(4) times computational memory is saved during the LTs simulation in comparison to the 3D-FDTD simulation. Moreover, LEE enhancement from the side of the LED can be obtained in the LTs simulation. An actual-size NPSS LED is simulated using the LTs. The results show a more than 307% improvement in the total LEE enhancement of the NPSS LED with the optimal solution compared to the conventional LED.

Role of ventral subiculum neuronal ensembles in incubation of oxycodone craving after electric barrier-induced voluntary abstinence.

High relapse rate is a key feature of opioid addiction. In humans, abstinence is often voluntary due to negative consequences of opioid seeking. To mimic this human condition, we recently introduced a rat model of incubation of oxycodone craving after electric barrier-induced voluntary abstinence. Incubation of drug craving refers to time-dependent increases in drug seeking after cessation of drug self-administration. Here, we used the activity marker Fos, muscimol-baclofen (GABAa + GABAb receptor agonists) global inactivation, Daun02-selective inactivation of putative relapse-associated neuronal ensembles, and fluorescence-activated cell sorting of Fos-positive cells and quantitative polymerase chain reaction to demonstrate a key role of vSub neuronal ensembles in incubation of oxycodone craving after voluntary abstinence, but not homecage forced abstinence. We also used a longitudinal functional magnetic resonance imaging method and showed that functional connectivity changes in vSub-related circuits predict opioid relapse after abstinence induced by adverse consequences of opioid seeking.

Carbon fibre-supported hierarchical NiCo layered double hydroxide nanosheets as non-enzymatic glucose sensors for sport drinks and serum.

We report a systematic study of carbon fibre (CF)-supported NiCo layered double hydroxide nanosheets (LDHNs) with and without heat treatment at 200 and 400 °C (CF-NiCo LDHN200 and CF-NiCo oxide nanoparticles (NPs), respectively) as catalysts and sensors for glucose oxidation reactions (GORs). Tafel measurements for the GORs showed that the exchange current density of CF-NiCo LDHN was 1.91 × 10-3 mA·cm-2 at an early rest potential of -0.422 V. This was markedly higher than those of CF-NiCo LDHN200 (1.22 × 10-3 mA·cm-2 at - 0.352 V) and CF-NiCo oxide NP (1.18 × 10-3 mA·cm-2 at -0.327 V). The electron transfer number and Tafel slopes suggested that the glucose dehydrogenation step and one-electron release occurred first in the GORs. Amperometric measurements revealed high recoveries (101.92% and 98.92%) and low relative standard deviations (1.98% and 2.34%) for the determination of glucose using the CF-NiCo LDHN in sports drink samples and human serum.

Adolescent nicotine administration increases nicotinic acetylcholine receptor binding and functional connectivity in specific cortico-striatal-thalamic circuits.

Nicotine exposure is associated with regional changes in brain nicotinic acetylcholine receptors subtype expression patterns as a function of dose and age at the time of exposure. Moreover, nicotine dependence is associated with changes in brain circuit functional connectivity, but the relationship between such connectivity and concomitant regional distribution changes in nicotinic acetylcholine receptor subtypes following nicotine exposure is not understood. Although smoking typically begins in adolescence, developmental changes in brain circuits and nicotinic acetylcholine receptors following chronic nicotine exposure remain minimally investigated. Here, we combined in vitro nicotinic acetylcholine receptor autoradiography with resting state functional magnetic resonance imaging to measure changes in [3H]nicotine binding and α4ß2 subtype nicotinic acetylcholine receptor binding and circuit connectivity across the brain in adolescent (postnatal Day 33) and adult (postnatal Day 68) rats exposed to 6 weeks of nicotine administration (0, 1.2 and 4.8 mg/kg/day). Chronic nicotine exposure increased nicotinic acetylcholine receptor levels and induced discrete, developmental stage changes in regional nicotinic acetylcholine receptor subtype distribution. These effects were most pronounced in striatal, thalamic and cortical regions when nicotine was administered during adolescence but not in adults. Using these regional receptor changes as seeds, resting state functional magnetic resonance imaging identified dysregulations in cortico-striatal-thalamic-cortical circuits that were also dysregulated following adolescent nicotine exposure. Thus, nicotine-induced increases in cortical, striatal and thalamic nicotinic acetylcholine receptors during adolescence modifies processing and brain circuits within cortico-striatal-thalamic-cortical loops, which are known to be crucial for multisensory integration, action selection and motor output, and may alter the developmental trajectory of the adolescent brain. This unique multimodal study significantly advances our understanding of nicotine dependence and its effects on the adolescent brain.

Cross-Scale Dynamicity of Entropy and Connectivity in the Sleeping Brain.

Introduction: The concept of local sleep refers to the phenomenon of local brain activity that modifies neural networks during unresponsive global sleep. Such network rewiring may differ across spatial scales; however, the global and local alterations in brain systems remain elusive in human sleep. Materials and Methods: We examined cross-scale changes of brain networks in sleep. Functional magnetic resonance imaging data were acquired from 28 healthy participants during nocturnal sleep. We adopted both metrics of connectivity (functional connectivity [FC] and regional homogeneity [ReHo]) and complexity (multiscale entropy) to explore the global and local functionality of the neural assembly across nonrapid eye movement sleep stages. Results: Long-range FC decreased with sleep depth, whereas local ReHo peaked at the N2 stage and reached its lowest level at the N3 stage. Entropy exhibited a general decline at the local scale (Scale 1) as sleep deepened, whereas the coarse-scale entropy (Scale 3) was consistent across stages. Discussion: The negative correlation between Scale-1 entropy and ReHo reflects the enhanced signal regularity and synchronization in sleep, identifying the information exchange at the local scale. The N2 stage showed a distinctive pattern toward local information processing with scrambled long-distance information exchange, indicating a specific time window for network reorganization. Collectively, the multidimensional metrics indicated an imbalanced global-local relationship among brain functional networks across sleep-wake stages.

The Effects of Logotherapy on Distress, Depression, and Demoralization in Breast Cancer and Gynecological Cancer Patients: A Preliminary Study.

BACKGROUND: Globally, cancer is the second leading cause of death. Breast cancer and gynecological cancer can damage patients' body image and lead to psychological distress, depression, and demoralization syndrome. No studies have explored the effect of logotherapy in gynecological cancer patients' psychological distress, depression, and demoralization. OBJECTIVE: To evaluate the effects of logotherapy on distress, depression, and demoralization in breast cancer and gynecological cancer patients. METHODS: A quasi-experimental design was used in this study, involving 61 breast cancer and gynecological cancer patients: 31 in the experimental group and 30 in the control group. Participants in the experimental group received logotherapy 4 to 6 times during the 12 weeks of intervention. Outcomes were measured by the (1) Distress Thermometer, (2) Patient Health Questionnaire, and (3) Demoralization Scale Mandarin Version (DS-MV). RESULTS: Distress Thermometer did not differ between groups, but significant differences in favor of the intervention group were noted in the Patient Health Questionnaire (U = 674.500, P = .002); the DS-MV subcategories of loss of meaning (U = 706.500, P = .000), dysphoria (U = 673.000, P = .002), disheartenment (U = 670.000, P = .003), helplessness (U = 621.000, P = .022), and sense of failure (U = 629.500, P = .016); and the total score of the DS-MV (U = 728.500, P = .000). CONCLUSION: Logotherapy was effective in the reduction of breast cancer and gynecological cancer patients' depression and demoralization. IMPLICATIONS FOR PRACTICE: Clinical professionals could add logotherapy to the treatment for breast cancer and gynecological cancer patients to reduce their depression and demoralization.

Think Hard or Think Smart: Network Reconfigurations After Divergent Thinking Associate With Creativity Performance.

Evidence suggests divergent thinking is the cognitive basis of creative thoughts. Neuroimaging literature using resting-state functional connectivity (RSFC) has revealed network reorganizations during divergent thinking. Recent studies have revealed the changes of network organizations when performing creativity tasks, but such brain reconfigurations may be prolonged after task and be modulated by the trait of creativity. To investigate the dynamic reconfiguration, 40 young participants were recruited to perform consecutive Alternative Uses Tasks (AUTs) for divergent thinking and two resting-state scans (before and after AUT) were used for mapping the brain reorganizations after AUT. We split participants into high- and low-creative groups based on creative achievement questionnaire (CAQ) and targeted on reconfigurations of the two brain networks: (1) default-mode network (DMN) and (2) the network seeded at the left inferior frontal gyrus (IFG) because the between-group difference of AUT-induced brain activation located at the left IFG. The changes of post-AUT RSFCs (DMN and IFGN) indicated the prolonged effect of divergent thinking. More specifically, the alterations of RSFCIFG-AG and RSFCIFG-IPL (AG: angular gyrus, IPG: inferior parietal lobule) in the high-creative group had positive relationship with their AUT performances (originality and fluency), but not found in the low-creative group. Furthermore, the RSFC changes of DMN did not present significant relationships with AUT performances. The findings not only confirmed the possibility of brain dynamic reconfiguration following divergent thinking, but also suggested the distinct IFGN reconfiguration between individuals with different creativity levels.

Converging Structural and Functional Evidence for a Rat Salience Network.

BACKGROUND: The salience network (SN) is dysregulated in many neuropsychiatric disorders, including substance use disorder. Though the SN was initially described in humans, identification of a rodent SN would provide the ability to mechanistically interrogate this network in preclinical models of neuropsychiatric disorders. METHODS: We used modularity analysis on resting-state functional magnetic resonance imaging data of rats (n = 32) to parcellate rat insula into functional subdivisions and to identify a potential rat SN based on functional connectivity patterns from the insular subdivisions. We then used mouse tract tracing data from the Allen Brain Atlas to confirm the network's underlying structural connectivity. We next compared functional connectivity profiles of the SN across rats, marmosets (n = 10), and humans (n = 30). Finally, we assessed the rat SN's response to conditioned cues in rats (n = 21) with a history of heroin self-administration. RESULTS: We identified a putative rat SN, which consists of primarily the ventral anterior insula and anterior cingulate cortex, based on functional connectivity patterns from the ventral anterior insular division. Functional connectivity architecture of the rat SN is supported by the mouse neuronal tracer data. Moreover, the anatomical profile of the identified rat SN is similar to that of nonhuman primates and humans. Finally, we demonstrated that the rat SN responds to conditioned cues and increases functional connectivity to the default mode network during conditioned heroin withdrawal. CONCLUSIONS: The neurobiological identification of a rat SN, together with a demonstration of its functional relevance, provides a novel platform with which to interrogate its functional significance in normative and neuropsychiatric disease models.

The neurophysiological basis of the discrepancy between objective and subjective sleep during the sleep onset period: an EEG-fMRI study.

Subjective perception of sleep is not necessarily consistent with electroencephalography (EEG) indications of sleep. The mismatch between subjective reports and objective measures is often referred to as "sleep state misperception." Previous studies evince that this mismatch is found in both patients with insomnia and in normal sleepers, but the neurophysiological mechanism remains unclear. The aim of the study is to explore the neurophysiological basis of this mechanism, from the perspective of both EEG power and functional magnetic resonance imaging (fMRI) fluctuations. Thirty-six healthy young adults participated in the study. Simultaneous EEG and fMRI recordings were conducted while the participants were trying to fall asleep in an MRI scanner at approximately 9:00 pm. They were awakened after achieving stable N1 or N2 sleep, or after 90 min without falling into stable sleep. Next they were asked to recall their conscious experiences from the moment immediately prior to awakening. Sixty-one instances of scheduled awakenings were collected: 21 of these after having achieved stable stage N2 sleep; 12, during stage N1 sleep; and, 20 during the waking state. Relative to those awakenings without subjective-objective discrepancy (n = 27), these awakenings with discrepancy (n = 14) were associated with lower θ power, as well as higher α, ß, and γ power. Moreover, we found that participants who exhibited the discrepancy, compared with those who did not, evinced a higher amplitude of low-frequency fluctuation levels in the prefrontal cortex. These results lend support to the conjecture that the subjective-objective discrepancy is associated with central nervous system hyperarousal.

Risk of ADHD After Multiple Exposures to General Anesthesia: A Nationwide Retrospective Cohort Study.

OBJECTIVE: To study the association between general anesthesia exposure before age 3 years and having a later ADHD diagnosis. METHOD: In a birth cohort, data were collected from a nationwide population database for children born between 1997 and 1999 who were exposed to general anesthesia before their third birthday. Age- and gender-matched enrollees without general anesthesia exposure were taken as the comparison. Groups were compared to identify the incidence of ADHD after age 4 and anesthesia-related predictive factors. RESULTS: Among the 1,146 exposed children, 74 ADHD cases were identified, and 158 ADHD cases were identified in 3,438 matched controls. After adjusting for comorbid conditions and possible confounding factors, if exposure on more than one occasion or ≥3 hr, an increased likelihood of having a later ADHD diagnosis was found (HR, 1.71 and 2.43, respectively). CONCLUSION: Children with multiple or ≥3 hr general anesthesia exposures before age 3 years have an increased likelihood of a later ADHD diagnosis.

Chronic obstructive pulmonary disease and anxiety disorders: a nationwide population-based study in Taiwan.

OBJECTIVE: Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and anxiety disorder outcomes. We sought to investigate the association in a large national sample. METHODS: Cases were identified from Taiwan's National Health Insurance Research Database who were aged 15 years and above, with a new primary diagnosis of COPD (International Classification of Diseases, Ninth Revision codes: 491, 492, 494 and 496) between 2000 and 2007. The 29,951 cases identified were compared to 29,951 controls matched on sex, age, urban/rural residence and socioeconomic status based on insurance premium. Both groups were followed until the end of 2008 for instances of anxiety disorders. Competing risk-adjusted Cox regression analyses were applied, adjusting for matching variables, Charlson comorbidity index, hospital admission days and daily dose of prednisone. RESULTS: Of the 59,902 subjects, 3951 were found to have anxiety disorders during a mean (SD) follow-up period of 5.5 (2.5) years. COPD, female, urban residence, lower dose of prednisone use, depressive disorders and higher outpatient visits were independent predictors of incident anxiety disorder. CONCLUSIONS: COPD was associated with increased risk of an anxiety disorder diagnosis, independent of a number of potential confounding factors.

Risk of bipolar disorder in patients with COPD: a population-based cohort study.

BAKCGROUND: Few studies have investigated the relationship between chronic obstructive pulmonary disease (COPD) and bipolar outcomes in the world. We sought to investigate the association between COPD and risk of bipolar disorder in a large national sample. METHODS: The insured aged 15 years or more with a new primary diagnosis of COPD (ICD-9: 491, 492, 494 and 496) between 2000 and 2007 were identified from Taiwan's National Health Insurance Research Database. We included individuals with an inpatient diagnosis of COPD and/or at least 1 year of two diagnoses of COPD in outpatient services. These 35,558 cases were compared to 35,558 sex-, age-, residence- and insurance premium-matched controls. We followed both groups until the end of 2008 for incidence of bipolar disorder, defined as ICD-9 codes 296.0-296.16, 296.4-296.81 and 296.89. Competing risk-adjusted Cox regression analyses were applied with adjusting for sex, age, residence, insurance premium, prednisone use, Charlson comorbidity index, diabetes, hypertension, hyperlipidemia, cardiovascular diseases, hospital admission days, outpatients' visits and mortality. RESULTS: Of the total 71,116 subjects, 202 were newly diagnosed with bipolar disorder during the study period. The mean follow-up time was 6.0 (SD=2.2) years. COPD, younger age, lower economic status, lower dose of prednisone use, higher hospital admission days and higher outpatient visits were independent predictors of bipolar disorder. CONCLUSIONS: COPD was associated with increased risk of bipolar disorder independent of a number of potential confounding factors in this study.

Sensitivity enhancement of task-evoked fMRI using ensemble empirical mode decomposition.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is widely used to investigate dynamic brain functions in neurological and psychological issues; however, high noise level limits its applicability for intensive and sophisticated investigations in the field of neuroscience. NEW METHOD: To deal with both issue (low sensitivity and dynamic signal), we used ensemble empirical mode decomposition (EEMD), an adaptive data-driven analysis method for nonstationary and nonlinear features, to filter task-irrelevant noise from raw fMRI signals. Using both simulations and representative fMRI data, we optimized the analytic parameters and identified non-meaningful intrinsic mode functions (IMFs) to remove noise. RESULTS: We revealed the following advantages of EEMD in fMRI analysis: (1) EEMD achieved high detectability for task engagement; (2) the functional sensitivity was markedly enhanced by removing task-irrelevant artifacts based on EEMD. COMPARISON WITH EXISTING METHOD(S): Compared with other noise-removal methods (e.g., band-pass filtering and independent component analysis), the EEMD-based artifact-removal method exhibited better spatial specificity and superior Gaussianity of the resulting t-score distribution. CONCLUSIONS: We found that EEMD method was efficient to enhance the functional sensitivity of evoked fMRI. The same strategy would be applicable to resting-state fMRI signal in the general purpose.

Reduced neuro-integration from the dorsolateral prefrontal cortex to the whole brain and executive dysfunction in schizophrenia patients and their relatives.

Executive dysfunction is one of the core symptoms of schizophrenia. Functional neuro-imaging studies have suggested an association between deficits in activating the dorsolateral prefrontal cortex (DLPFC) and executive dysfunction, but neuro-integration from the DLPFC to the whole brain remains unclear. Studies investigating the neuro-integration from the DLPFC to the whole brain in unaffected but genetically liable family members are scant. In this study, we report DLPFC neuro-integrative deficits correlated with executive dysfunction and family history of schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Using seed regions in DLPFC, we examined resting-state functional connectivity in 25 patients with schizophrenia, 25 unaffected first-degree relatives (UR), and 25 healthy control (HC) persons. Schizophrenia patients and UR have impaired connectivity from DLPFC to its coordinated regions (ANOVA: F=7.316-10.974, p<0.001). These coordinated brain regions are distributed in the bilateral caudate, left middle/inferior frontal gyrus, left precentral gyrus, and right cerebellum. The individual functional connectivity strength between the left DLPFC and its coordinated regions was correlated with individual executive function performance among whole persons. (Pearson's r=0.244-0.366, p=0.035-0.008) Our findings support that distributed neuro-integrative DLPFC deficits reflect a genetic risk for schizophrenia and that these deficits are present, to a lesser degree, in unaffected first-degree relatives. Our findings also support that neuro-integration might correlate with a patient's executive function performance.

Variations in connectivity in the sensorimotor and default-mode networks during the first nocturnal sleep cycle.

The function of sleep in humans has been investigated using simultaneous electroencephalography (EEG) and functional magnetic resonance imaging recordings to provide accurate sleep scores with spatial precision. Recent studies have demonstrated that spontaneous brain oscillations and functional connectivity dissociate during nonrapid eye movement (NREM) sleep; this leads to spontaneous cognitive processes, such as memory consolidation and emotional modulation. However, variations in network connectivity across the sleep stages or between sleep/wake transitions require further elucidation. We observed changes in the connectivity of the sensorimotor and default-mode networks (DMN) mediated by midnight sleep among 18 healthy participants. The results indicated that (1) functional connectivity in both networks showed increasing dissociation as NREM sleep deepened, whereas hyperconnectivity occurred during rapid eye movement (REM) sleep; and (2) compared with connectivity before sleep, the DMN presented a comparable connectivity pattern immediately after awakening, whereas the connectivity of the sensorimotor network remained disrupted. These findings showed that connectivity patterns dissociate and reconnect coherently in both cortical networks during NREM and REM sleep, respectively. After the person awakened, the DMN connectivity was re-established before the sensorimotor reconnection. These dynamic sleep-related dissociations and reconnections between sleep/wake conditions might provide the key to understanding cognitive modulations in sleep. If so, connectivity changes might serve as an alternative indicator beyond the EEG signature to unveil the spontaneous processes that occur during sleep.