Frequency-dependent alterations of global signal topography in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated not only with disorders in multiple brain networks but also with frequency-specific brain activities. The abnormality of spatiotemporal networks in patients with MDD remains largely unclear. METHODS: We investigated the alterations of the global spatiotemporal network in MDD patients using a large-sample multicenter resting-state functional magnetic resonance imaging dataset. The spatiotemporal characteristics were measured by the variability of global signal (GS) and its correlation with local signals (GSCORR) at multiple frequency bands. The association between these indicators and clinical scores was further assessed. RESULTS: The GS fluctuations were reduced in patients with MDD across the full frequency range (0-0.1852 Hz). The GSCORR was also reduced in the MDD group, especially in the relatively higher frequency range (0.0728-0.1852 Hz). Interestingly, these indicators showed positive correlations with depressive scores in the MDD group and relative negative correlations in the control group. CONCLUSION: The GS and its spatiotemporal effects on local signals were weakened in patients with MDD, which may impair inter-regional synchronization and related functions. Patients with severe depression may use the compensatory mechanism to make up for the functional impairments.

Spatiotemporal dedifferentiation of the global brain signal topography along the adult lifespan.

Age-related variations in many regions and/or networks of the human brain have been uncovered using resting-state functional magnetic resonance imaging. However, these findings did not account for the dynamical effect the brain's global activity (global signal [GS]) causes on local characteristics, which is measured by GS topography. To address this gap, we tested GS topography including its correlation with age using a large-scale cross-sectional adult lifespan dataset (n = 492). Both GS topography and its variation with age showed frequency-specific patterns, reflecting the spatiotemporal characteristics of the dynamic change of GS topography with age. A general trend toward dedifferentiation of GS topography with age was observed in both spatial (i.e., less differences of GS between different regions) and temporal (i.e., less differences of GS between different frequencies) dimensions. Further, methodological control analyses suggested that although most age-related dedifferentiation effects remained across different preprocessing strategies, some were triggered by neuro-vascular coupling and physiological noises. Together, these results provide the first evidence for age-related effects on global brain activity and its topographic-dynamic representation in terms of spatiotemporal dedifferentiation.

Frequency-dependent effective connections between local signals and the global brain signal during resting-state.

The psychological and physiological meanings of resting-state global brain signal (GS) and GS topography have been well confirmed. However, the causal relationship between GS and local signals was largely unknown. Based on the Human Connectome Project dataset, we investigated the effective GS topography using the Granger causality (GC) method. In consistent with GS topography, both effective GS topographies from GS to local signals and from local signals to GS showed greater GC values in sensory and motor regions in most frequency bands, suggesting that the unimodal superiority is an intrinsic architecture of GS topography. However, the significant frequency effect for GC values from GS to local signals was primarily located in unimodal regions and dominated at slow 4 frequency band whereas that from local signals to GS was mainly located in transmodal regions and dominated at slow 6 frequency band, consisting with the opinion that the more integrated the function, the lower the frequency. These findings provided valuable insight for the frequency-dependent effective GS topography, improving the understanding of the underlying mechanism of GS topography. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-022-09831-0.

The thalamus is the causal hub of intervention in patients with major depressive disorder: Evidence from the Granger causality analysis.

Major depressive disorder (MDD) is the leading mental disorder and afflicts more than 350 million people worldwide. The underlying neural mechanisms of MDD remain unclear, hindering the accurate treatment. Recent brain imaging studies have observed functional abnormalities in multiple brain regions in patients with MDD, identifying core brain regions is the key to locating potential therapeutic targets for MDD. The Granger causality analysis (GCA) measures directional effects between brain regions and, therefore, can track causal hubs as potential intervention targets for MDD. We reviewed literature employing GCA to investigate abnormal brain connections in patients with MDD. The total degree of effective connections in the thalamus (THA) is more than twice that in traditional targets such as the superior frontal gyrus and anterior cingulate cortex. Altered causal connections in patients with MDD mainly included enhanced bottom-up connections from the thalamus to various cortical and subcortical regions and reduced top-down connections from these regions to the THA, indicating excessive uplink sensory information and insufficient downlink suppression information for negative emotions. We suggest that the thalamus is the most crucial causal hub for MDD, which may serve as the downstream target for non-invasive brain stimulation and medication approaches in MDD treatment.

A review of attentional bias modification trainings for depression.

Negative attentional bias is a basic character of depression. The attentional bias modification training (ABMT), being a highly promising and easy-to-use depression intervention technique, has attracted much attention to alleviate depressive symptoms in recent years. However, the effectiveness of ABMT programs was mixed across studies, since it remained unclear the underlying mechanisms of ABMT on alleviating depressive symptoms. We systematically analyzed the main ABMT paradigms to clarify possible mechanisms of effective training and reasons of ineffective training. Valid ABMT programs might alleviate depressive symptoms through regulating self-related rumination or two subcomponents of attentional bias: facilitated attention and impaired attentional disengagement. The reasons for the invalidity of ABMT mainly included the suboptimal design of training procedures, mixed effects of participants' personal characteristics, and the unclear relationship between attentional bias and depression. The ABMT is promising for alleviating depressive symptoms, but training procedures are required to be improved to obtain stable training effects.

Brain mechanisms of mental processing: from evoked and spontaneous brain activities to enactive brain activity.

Within the context of the computer metaphor, evoked brain activity acts as a primary carrier for the brain mechanisms of mental processing. However, many studies have found that evoked brain activity is not the major part of brain activity. Instead, spontaneous brain activity exhibits greater intensity and coevolves with evoked brain activity through continuous interaction. Spontaneous and evoked brain activities are similar but not identical. They are not separate parts, but always dynamically interact with each other. Therefore, the enactive cognition theory further states that the brain is characterized by unified and active patterns of activity. The brain adjusts its activity pattern by minimizing the error between expectation and stimulation, adapting to the ever-changing environment. Therefore, the dynamic regulation of brain activity in response to task situations is the core brain mechanism of mental processing. Beyond the evoked brain activity and spontaneous brain activity, the enactive brain activity provides a novel framework to completely describe brain activities during mental processing. It is necessary for upcoming researchers to introduce innovative indicators and paradigms for investigating enactive brain activity during mental processing.

The temporal dedifferentiation of global brain signal fluctuations during human brain ageing.

The variation of brain functions as healthy ageing has been discussed widely using resting-state brain imaging. Previous conclusions may be misinterpreted without considering the effects of global signal (GS) on local brain activities. Up to now, the variation of GS with ageing has not been estimated. To fill this gap, we defined the GS as the mean signal of all voxels in the gray matter and systematically investigated correlations between age and indices of GS fluctuations. What's more, these tests were replicated with data after hemodynamic response function (HRF) de-convolution and data without noise regression as well as head motion data to verify effects of non-neural information on age. The results indicated that GS fluctuations varied as ageing in three ways. First, GS fluctuations were reduced with age. Second, the GS power transferred from lower frequencies to higher frequencies with age. Third, the GS power was more evenly distributed across frequencies in ageing brain. These trends were partly influenced by HRF and physiological noise, indicating that the age effects of GS fluctuations are associated with a variety of physiological activities. These results may indicate the temporal dedifferentiation hypothesis of brain ageing from the global perspective.

[The physiological and psychological mechanisms of infra-slow oscillation].

Infra-slow oscillation (ISO) is a kind of brain rhythm between 0.01 and 0.5 Hz. ISO is widely distributed in multiple brain regions. As an important psychophysiological activity, the ISO interacts with high-frequency neural rhythm via cross-frequency coupling, but has different activity patterns from high-frequency neural activity. Physiologically, the ISO may be generated by the dynamic activity of thalamus, glia, and ions. Psychologically, the frequency, amplitude, and phase of ISO could all regulate cognitive activities, but in different ways. Investigations on the ISO expands the neural rhythm research to lower frequency range, further promoting the construction of rhythmic theory of brain function.

Surgical outcomes of cesarean scar pregnancy: an 8-year experience at a single institution.

PURPOSE: To summarize the outcomes of different surgical treatment modalities for cesarean scar pregnancy (CSP) at a single institution over 8 years. METHODS: A case series of patients diagnosed with CSP who were admitted to Nanjing Drum Tower Hospital from January 2011 to December 2018 was retrospectively studied. Medical records of all the patients were carefully reviewed. Data on patient demographics, pregnancy characteristics, treatment modalities, response to therapy, and subsequent pregnancy outcomes were collected and analyzed. RESULTS: A total of 117 patients undergoing surgical treatments for CSP were included. Thirty-three patients (28.21%) underwent ultrasound-guided curettage; while, 74 (63.25%) and 10 (8.55%) patients received laparoscopy-monitored curettage and laparoscopic CSP resection, respectively. Most of the patients (21/33) who underwent ultrasound-guided surgery had type I CSP; while, 54 out of 84 patients who opted for laparoscopic surgeries had type II CSP. Eleven women underwent a uterine artery embolization procedure before the operation. There was no difference in the use of an intrauterine balloon for hemostasis among the three groups. Only 8 patients needed additional systemic methotrexate treatment. Twenty-four out of 57 women (42.11%) succeeded in conceiving again and gave birth to 21 healthy babies. Only 1 woman (1/24, 4.17%) experienced recurrence of CSP. CONCLUSIONS: These data indicated the safety and efficiency of ultrasound-guided curettage, laparoscopy-monitored curettage, and laparoscopic CSP resection for the treatment of CSP.

Spatial variability of low frequency brain signal differentiates brain states.

Temporal variability of the neural signal has been demonstrated to be closely related to healthy brain function. Meanwhile, the evolving brain functions are supported by dynamic relationships among brain regions. We hypothesized that the spatial variability of brain signal might provide important information about brain function. Here we used the spatial sample entropy (SSE) to investigate the spatial variability of neuroimaging signal during a steady-state presented face detection task. Lower SSE was found during task state than during resting state, associating with more repetitive functional interactions between brain regions. The standard deviation (SD) of SSE during the task was negatively related to the SD of reaction time, suggesting that the spatial pattern of neural activity is reorganized according to particular cognitive function and supporting the previous theory that greater variability is associated with better task performance. These results were replicated with reordered data, implying the reliability of SSE in measuring the spatial organization of neural activity. Overall, the present study extends the research scope of brain signal variability from the temporal dimension to the spatial dimension, improving our understanding of the spatiotemporal characteristics of brain activities and the theory of brain signal variability.

Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities.

Reliable Attention Network Scores and Mutually Inhibited Inter-network Relationships Revealed by Mixed Design and Non-orthogonal Method.

The attention system can be divided into alerting, orienting, and executive control networks. The efficiency and independence of attention networks have been widely tested with the attention network test (ANT) and its revised versions. However, many studies have failed to find effects of attention network scores (ANSs) and inter-network relationships (INRs). Moreover, the low reliability of ANSs can not meet the demands of theoretical and empirical investigations. Two methodological factors (the inter-trial influence in the event-related design and the inter-network interference in orthogonal contrast) may be responsible for the unreliability of ANT. In this study, we combined the mixed design and non-orthogonal method to explore ANSs and directional INRs. With a small number of trials, we obtained reliable and independent ANSs (split-half reliability of alerting: 0.684; orienting: 0.588; and executive control: 0.616), suggesting an individual and specific attention system. Furthermore, mutual inhibition was observed when two networks were operated simultaneously, indicating a differentiated but integrated attention system. Overall, the reliable and individual specific ANSs and mutually inhibited INRs provide novel insight into the understanding of the developmental, physiological and pathological mechanisms of attention networks, and can benefit future experimental and clinical investigations of attention using ANT.

Tissues distribution of R-(-)- and S-(+)-m-nisoldipine after single enantiomer administration in rats.

Rapid, sensitive, and selective high-performance liquid chromatography methods were developed and validated for determination of m-nisoldipine enantiomers in rat tissues. All of the samples were prepared based on a simple and efficient liquid-liquid extraction method. After validating that no racemation occurred by ULTRON ES-OVM (Japan), m-nisoldipine enantiomers were determined, respectively, on a reverse-phase C(18) column (5 microm, 250 x 4.6 mm). This method was applied to study tissue distribution of m-nisoldipine enantiomers in rats after a single administration of m-nisoldipine enantiomers. By the two-sample t test, there were basically no significant differences between the two enantiomers in each tissue ( p > .05), which indicates that they may have the same potency in rats. In small intestine, lung, liver, and spleen, the concentrations of R-(-)- and S-(+)-m-nisoldipine were high at 30 and 150 min than that at 90 min, which showed that m-nisoldipine enantiomers may have the phenomenon of hepatoenteral circulation. A small quantity of the prototype of R-(-)- and S-(+)-m-nisoldipine in brain showed that they can cross the blood-brain barrier to arrive at the brain tissue. The high quantity of distribution in lung and brain implied that the lipophilicity of the drug was powerful.

Pharmacokinetic study of three active flavonoid glycosides in rat after intravenous administration of Trollius ledebourii extract by liquid chromatography.

A selective and sensitive reversed-phase high-performance liquid chromatography method was developed and validated for the simultaneous determination of orientin-2''-O-beta-L-galactopyranosyl (OGA), orientin and vitexin in rat plasma. Blood samples were collected via the fossa orbitalis vein at time intervals after intravenous administration and the concentrations of the three ingredients in plasma were analyzed by HPLC after the plasma protein had been precipitated directly with methanol. OGA, orientin and vitexin were successfully separated using a C18 column with gradient elution composed of acetonitrile and 0.1% acetic acid and were detected at the detection wavelength of 348 nm. Calibration curves of OGA, orientin and vitexin were generated over the range 0.315-161, 0.326-167 and 0.215-110 microg/mL, respectively. The intra- and inter-day precisions (relative standard deviation) for the analysis of the three analytes were between 1.68 and 8.43% with accuracies (relative error) below 8.55%. The mean extraction recoveries were between 70.35 and 86.42%. The developed method was suitable for simultaneous determination of these three active flavonoid glycosides in rat plasma and was successfully applied to investigate the pharmacokinetics of glycosides from Trollius ledebourii in rats.

HPLC study of pharmacokinetics and tissue distribution of morroniside in rats.

Morroniside is an important constituent of traditional Chinese medicines Fructus Corni with several bioactivities. An HPLC method for determination of morroniside in rat plasma and tissues was developed and the pharmacokinetic and tissue distribution characteristics of morroniside after intravenous and oral administrations were investigated. The bio-samples were prepared based on a simple protein precipitation and the separation of morroniside was achieved on a C(18) column with a mobile phase consisted of acetonitrile-methanol-0.1% formic acid (10:10:80, v/v) at a flow rate of 1.0 ml/min. Chromatograms were monitored at 239 nm and the temperature of column was kept at 25 degrees C. Pharmacokinetic study found that morroniside was absorbed and eliminated rapidly in rat and manifested linear dynamics at 10-40 mg/kg range and absolute bioavailability of morroniside was lower. Tissue distribution showed the highest level was observed in small intestine, then in kidney and stomach, but no morroniside was detected in brain, which indicated that small intestine, kidney and stomach were major distribution tissues of morroniside in rats, and morroniside had difficulty in crossing the blood-brain barrier. It was also found there was no long-term accumulation of morroniside in rat tissues.

Determination of piceid in rat plasma and tissues by high-performance liquid chromatographic method with UV detection.

A rapid, sensitive and selective HPLC method was developed and validated for determination of piceid in rat plasma and tissues. The drug was isolated from plasma and tissues by a simple protein precipitation procedure. Chromatographic separation was performed on a C(18) column with acetonitrile-water (26:74, v/v) as mobile phase. The method was successfully applied to the pharmacokinetics and tissue distribution research after oral administration of a 50 mg/kg dose of piceid to healthy male Wistar rats. The pharmacokinetic parameters showed that piceid was quickly absorbed, distributed and eliminated within 4 h after oral administration. The tissue distribution results showed that, at 10 min, the concentrations of piceid in most tissues reached peak level except in heart and testis. The highest level of piceid was found in stomach, then in small intestine, spleen, lung, brain, testis, liver, kidney and heart. The amount of piceid in testis and heart reached the peak level at 30 min. At 120 min, the amount of piceid in all tissues decreased to a low percentage of the initial concentration. Piceid was absorbed throughout the gastrointestinal tract with considerable absorption taking place in the stomach and small intestine. There was no long-term accumulation of piceid in rat tissues.