State rumination predicts inhibitory control failures and dysregulation of default, salience, and cognitive control networks in youth at risk of depressive relapse: Findings from the RuMeChange trial.

Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets. Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART. Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsalmedial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination. Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC. Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target.

Neural correlates of stress-reactive rumination in depression - The role of childhood trauma and social anxiety.

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

Anxiety symptoms without depression are associated with cognitive control network (CNN) dysfunction: An fNIRS study.

Anxiety is a common psychological disorder associated with other mental disorders, with depression being the most common comorbidity. Few studies have examined the neural mechanisms underlying anxiety after controlling for depression. This study aimed to explore whether there are differences in cortical activation in anxiety patients with different severities whose depression are normal. In the current study, depression levels were normal for 366 subjects-139 healthy subjects, 117 with mild anxiety, and 110 with major anxiety. Using the Hospital Anxiety and Depression Scale (HADS) and a verbal fluency task (VFT) to test subjects' anxiety and depression and cognitive function, respectively. A 53-channel guided near-infrared spectroscopic imaging technology (fNIRS) detected the concentration of oxyhemoglobin (oxy-Hb). Correlation analysis between anxiety severity and oxy-Hb concentration in the brain cortex was performed, as well as ANOVA analysis of oxy-Hb concentration among the three anxiety severity groups. The results showed that anxiety severity was significantly and negatively correlated with oxy-Hb concentrations in the left frontal eye field (lFEF) and in the right dorsolateral prefrontal area (rDLPFC). The oxy-Hb concentration in the lFEF and the rDLPFC were significantly lower in the major anxiety disorder group than that in the control group. This suggests that decreased cortical activity of the lFEF and rDLPFC may be neural markers of anxiety symptoms after controlling for depression. Anxiety symptoms without depression may be result from the dysfunction of the cognitive control network (CCN) which includes the lFEF and rDLPFC.

Relationship between brain structural network integrity and emotional symptoms in youth with perinatally-acquired HIV.

Perinatally acquired HIV infection (PHIV) currently affects approximately 1.7 million children worldwide. Youth with PHIV (YPHIV) are at increased risk for emotional and behavioral symptoms, yet few studies have examined relationships between these symptoms and brain structure. Previous neuroimaging studies in YPHIV report alterations within the salience network (SN), cognitive control network (CCN), and default mode network (DMN). These areas have been associated with social and emotional processing, emotion regulation, and executive function. We examined structural brain network integrity from MRI using morphometric similarity networks and graph theoretical measures of segregation (transitivity), resilience (assortativity), and integration (global efficiency). We examined brain network integrity of 40 YPHIV compared to 214 youths without HIV exposure or infection. Amongst YPHIV, we related structural brain network metrics to the Emotional Symptoms Index of the Behavioral Assessment System for Children, 2nd edition. We also examined the relationship of inflammatory biomarkers in YPHIV to brain network integrity. YPHIV had significantly lower global efficiency in the SN, DMN, and the whole brain network compared to controls. YPHIV also demonstrated lower assortativity or resilience (i.e., network robustness) compared to controls in the DMN and whole brain network. Further, higher emotional symptom score was associated with higher global efficiency in the SN and lower global efficiency in the DMN, signaling more emotional challenges. A significant association was also found between several inflammatory and cardiac markers with structural network integrity. These findings suggest an impact of HIV on developing brain networks, and potential dysfunction of the SN and DMN in relation to network efficiency.

The functional connectome of 3,4-methyldioxymethamphetamine-related declarative memory impairments.

The chronic intake of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data-driven multi-voxel pattern analysis (MVPA) approach on participants' resting-state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well-matched controls with moderate-to-strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed-based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed-based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA-related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing.

Reduced connectivity of the cognitive control neural network at rest in young adults who had their first drink of alcohol prior to age 18.

The cognitive control network (CCN) is an important network responsible for performing and modulating executive functions. In adolescents, alcohol use has been associated with weaker cognitive control, higher reward sensitivity, and later-in-life alcohol problems. Given that the CCN continues to develop into young adulthood, it is important to understand relations between early alcohol use, the CCN, and reward networks. Participants included individuals 18-23 years without alcohol use disorder. Based upon self-reported age of first alcoholic drink, participants were split into two groups: Early (onset) Drinkers (first drink < age 18, N = 52) and Late (onset) Drinkers (first drink > age 18, N = 44). All participants underwent an 8-minute resting-state fMRI scan. Seed regions of interest included the anterior dorsolateral prefrontal cortex (DLPFC), amygdala, and ventral striatum. Early Drinkers demonstrated significant reduced connectivity of CCN regions, including bilateral anterior DLPFC, compared to Late Drinkers. There were no significant differences between Early and Late Drinkers in connectivity between reward and CCN regions. These results suggest that individuals who begin drinking alcohol earlier in life may have alterations in the development of the CCN; however, longitudinal research is necessary to determine whether lower connectivity precedes or follows early alcohol use, and any other relevant factors.

Resource sharing in cognitive control: Behavioral evidence and neural substrates.

Cognitive control is a capacity-limited function responsible for the resolution of conflict among competing cognitive processes. However, whether cognitive control handles multiple concurrent requests through a single bottleneck or a resource sharing mechanism remains elusive. In this functional magnetic resonance imaging study, we examined the effect of dual flanker conflict processing on behavioral performance and on activation in regions of the cognitive control network (CCN). In each trial, participants completed two flanker conflict tasks (T1 and T2) sequentially, with the stimulus onset asynchrony (SOA) varied as short (100 ms) and long (1000 ms). We found a significant conflict effect (indexed by the difference between incongruent and congruent flanker conditions) in reaction time (RT) for both T1 and T2, together with a significant interaction between SOA and T1-conflict on RT for T2 with an additive effect. Importantly, there was a small but significant SOA effect on T1 with a prolonged RT under the short SOA compared to the long SOA. Increased activation in the CCN was associated with conflict processing and the main effect of SOA. The anterior cingulate cortex and anterior insular cortex showed a significant interaction effect between SOA and T1-conflict in activation parallel with the behavioral results. The behavioral and brain activation patterns support a central resource sharing model, in which the core resources for cognitive control are shared when multiple simultaneous conflicting processes are required.

Multivariate analysis differentiates intertemporal choices in both value and cognitive control network.

Choices between immediate smaller reward and long-term larger reward are referred to as intertemporal choice. Numerous functional magnetic resonance imaging (fMRI) studies have investigated the neural substrates of intertemporal choice via conventional univariate analytical approaches, revealing dissociable activations of decisions involving immediately available rewards and decisions involving delayed rewards in value network. With the help of multivariate analyses, which is more sensitive for evaluating information encoded in spatially distributed patterns, we showed that fMRI activity patterns represent viable signatures of intertemporal choice, as well as individual differences while controlling for age. Notably, in addition to value network, regions from cognitive control network play prominent roles in differentiating between different intertemporal choices as well as individuals with distinct discount rates. These findings provide clear evidence that substantiates the important role of value and cognitive control networks in the neural representation of one's intertemporal decisions.

Disrupted Dynamic Functional Network Connectivity Among Cognitive Control Networks in the Progression of Alzheimer's Disease.

Background: Alzheimer's disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from resting-state functional magnetic resonance imaging. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations. Methods: Group independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states, and then estimated a hidden Markov model and the occupancy rate for each subject. Then, we investigated the link between CCN dFC features and AD progression. Also, we investigated the link between sFC and AD progression and compared its results with dFC results. Results: Progression of AD symptoms was associated with increases in connectivity within the middle frontal gyrus. Also, the very mild AD (vmAD) showed less connectivity within the inferior parietal lobule (in both sFC and dFC) and between this region and the rest of CCN (in dFC analysis). Also, we found that within-middle frontal gyrus connectivity increases with AD progression in both sFC and dFC results. Finally, comparing with vmAD, we found that the normal brain spends significantly more time in a state with lower within-middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease. Conclusion: Our results suggest that AD progress not only alters the CCN connectivity strength but also changes the temporal properties in this brain network. This suggests the temporal and spatial pattern of CCN as a biomarker that differentiates different stages of AD.

Antidepressants combined with psychodrama improve the coping style and cognitive control network in patients with childhood trauma-associated major depressive disorder.

BACKGROUND: The use of antidepressant therapy alone has a limited efficacy in patients with childhood trauma-associated major depressive disorder (MDD). However, the effectiveness of antidepressant treatment combined with psychodrama in these patients is unclear. AIM: To evaluate the effectiveness of antidepressant treatment combined with psychodrama. METHODS: Patients with childhood trauma-associated MDD treated with antidepressants were randomly assigned to either the psychodrama intervention (observation group) or the general health education intervention (control group) and received combination treatment for 6 mo. The observation group received general health education given by the investigator together with the "semi-structured group intervention model" of Yi Shu psychodrama. A total of 46 patients were recruited, including 29 cases in the observation group and 17 cases in the control group. Symptoms of depression and anxiety as well as coping style and resting-state functional magnetic resonance imaging were assessed before and after the intervention. RESULTS: Symptoms of depression and anxiety, measured by the Hamilton Depression Scale, Beck Depression Inventory, and Beck Anxiety Inventory, were reduced after the intervention in both groups of patients. The coping style of the observation group improved significantly in contrast to the control group, which did not. In addition, an interaction between treatment and time in the right superior parietal gyrus node was found. Furthermore, functional connectivity between the right superior parietal gyrus and left inferior frontal gyrus in the observation group increased after the intervention, while in the control group the connectivity decreased. CONCLUSION: This study supports the use of combined treatment with antidepressants and psychodrama to improve the coping style of patients with childhood trauma-associated MDD. Functional connectivity between the superior parietal gyrus and inferior frontal gyrus was increased after this combined treatment. We speculate that psychodrama enhances the internal connectivity of the cognitive control network and corrects the negative attention bias of patients with childhood trauma-associated MDD. Elucidating the neurobiological features of patients with childhood trauma-associated MDD is important for the development of methods that can assist in early diagnosis and intervention.

Distinct population and single-neuron selectivity for executive and episodic processing in human dorsal posterior cingulate.

Posterior cingulate cortex (PCC) is an enigmatic region implicated in psychiatric and neurological disease, yet its role in cognition remains unclear. Human studies link PCC to episodic memory and default mode network (DMN), while findings from the non-human primate emphasize executive processes more associated with the cognitive control network (CCN) in humans. We hypothesized this difference reflects an important functional division between dorsal (executive) and ventral (episodic) PCC. To test this, we utilized human intracranial recordings of population and single unit activity targeting dorsal PCC during an alternated executive/episodic processing task. Dorsal PCC population responses were significantly enhanced for executive, compared to episodic, task conditions, consistent with the CCN. Single unit recordings, however, revealed four distinct functional types with unique executive (CCN) or episodic (DMN) response profiles. Our findings provide critical electrophysiological data from human PCC, bridging incongruent views within and across species, furthering our understanding of PCC function.

Altered functional connectivity in first-episode and recurrent depression: A resting-state functional magnetic resonance imaging study.

Background: Functional magnetic resonance imaging (fMRI) studies examining differences in the activity of brain networks between the first depressive episode (FDE) and recurrent depressive episode (RDE) are limited. The current study observed and compared the altered functional connectivity (FC) characteristics in the default mode network (DMN), cognitive control network (CCN), and affective network (AN) between the RDE and FDE. In addition, we further investigated the correlation between abnormal FC and clinical symptoms. Methods: We recruited 32 patients with the RDE, 31 patients with the FDE, and 30 healthy controls (HCs). All subjects underwent resting-state fMRI. The seed-based FC method was used to analyze the abnormal brain networks in the DMN, CCN, and AN among the three groups and further explore the correlation between abnormal FC and clinical symptoms. Results: One-way analysis of variance showed significant differences the FC in the DMN, CCN, and AN among the three groups in the frontal, parietal, temporal, and precuneus lobes and cerebellum. Compared with the RDE group, the FDE group generally showed reduced FC in the DMN, CCN, and AN. Compared with the HC group, the FDE group showed reduced FC in the DMN, CCN, and AN, while the RDE group showed reduced FC only in the DMN and AN. Moreover, the FC in the left posterior cingulate cortices and the right inferior temporal gyrus in the RDE group were positively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17), and the FC in the left dorsolateral prefrontal cortices and the right precuneus in the FDE group were negatively correlated with the HAMD-17. Conclusions: The RDE and FDE groups showed multiple abnormal brain networks. However, the alterations of abnormal FC were more extensive and intensive in the FDE group.

Mindfulness-Enhanced Computerized Cognitive Training for Depression: An Integrative Review and Proposed Model Targeting the Cognitive Control and Default-Mode Networks.

Depression is often associated with co-occurring neurocognitive deficits in executive function (EF), processing speed (PS) and emotion regulation (ER), which impact treatment response. Cognitive training targeting these capacities results in improved cognitive function and mood, demonstrating the relationship between cognition and affect, and shedding light on novel targets for cognitive-focused interventions. Computerized cognitive training (CCT) is one such new intervention, with evidence suggesting it may be effective as an adjunct treatment for depression. Parallel research suggests that mindfulness training improves depression via enhanced ER and augmentation of self-referential processes. CCT and mindfulness training both act on anti-correlated neural networks involved in EF and ER that are often dysregulated in depression-the cognitive control network (CCN) and default-mode network (DMN). After practicing CCT or mindfulness, downregulation of DMN activity and upregulation of CCN activity have been observed, associated with improvements in depression and cognition. As CCT is posited to improve depression via enhanced cognitive function and mindfulness via enhanced ER ability, the combination of both forms of training into mindfulness-enhanced CCT (MCCT) may act to improve depression more rapidly. MCCT is a biologically plausible adjunct intervention and theoretical model with the potential to further elucidate and target the causal mechanisms implicated in depressive symptomatology. As the combination of CCT and mindfulness has not yet been fully explored, this is an intriguing new frontier. The aims of this integrative review article are four-fold: (1) to briefly review the current evidence supporting the efficacy of CCT and mindfulness in improving depression; (2) to discuss the interrelated neural networks involved in depression, CCT and mindfulness; (3) to present a theoretical model demonstrating how MCCT may act to target these neural mechanisms; (4) to propose and discuss future directions for MCCT research for depression.

Statistical Nonparametric fMRI Maps in the Analysis of Response Inhibition in Abstinent Individuals with History of Alcohol Use Disorder.

Inhibitory impairments may persist after abstinence in individuals with alcohol use disorder (AUD). Using traditional statistical parametric mapping (SPM) fMRI analysis, which requires data to satisfy parametric assumptions often difficult to satisfy in biophysical system as brain, studies have reported equivocal findings on brain areas responsible for response inhibition, and activation abnormalities during inhibition found in AUD persist after abstinence. Research is warranted using newer analysis approaches. fMRI scans were acquired during a Go/NoGo task from 30 abstinent male AUD and 30 healthy control participants with the objectives being (1) to characterize neuronal substrates associated with response inhibition using a rigorous nonparametric permutation-based fMRI analysis and (2) to determine whether these regions were differentially activated between abstinent AUD and control participants. A blood oxygen level dependent contrast analysis showed significant activation in several right cortical regions and deactivation in some left cortical regions during successful inhibition. The largest source of variance in activation level was due to group differences. The findings provide evidence of cortical substrates employed during response inhibition. The largest variance was explained by lower activation in inhibition as well as ventral attentional cortical networks in abstinent individuals with AUD, which were not found to be associated with length of abstinence, age, or impulsiveness.

Effect of Acupuncture on the Cognitive Control Network of Patients with Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial.

Purpose: Abnormal central nervous system function is the key central pathological factor leading to chronic pain in patients with knee osteoarthritis (KOA). Acupuncture can effectively relieve the pain of KOA patients. However, the central nervous mechanism of acupuncture treating KOA is not fully understood. This trial will use functional magnetic resonance imaging (fMRI) analysis techniques to investigate the potential central nervous mechanism of acupuncture treatment of KOA. Materials and Methods: A total of 108 patients will be randomized (in a 1:1:1 ratio) into three groups, this trial will include 4-week treatment, patients in groups A and B will receive 20 acupuncture and sham acupuncture sessions, respectively, patients in group C will not receive any intervention, and all patients will receive fMRI scans before and after the intervention. The Western Ontario and McMaster Universities Osteoarthritis Index score (WOMAC) will be the primary clinical outcome. Then, we will explore the functional changes of the cognitive control network (CCN) in the brains of KOA patients through whole brain functional connectivity (FC) analysis and seed-based functional connectivity (sFC) analysis. Pearson correlation coefficient will be used to analyze the relationship between the improved value of the clinical correlation scale and the change of fMRI data. Discussion: This trial will analyze the efficacy of verum acupuncture, sham acupuncture and the waiting-list for KOA and explore the activity of the CCN in three groups of patients by fMRI, so as to reveal the central nervous mechanisms of acupuncture in the treatment of KOA. Study Registration: This study is approved by the Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine (No: 2019HL-133-01) and registered in the Chinese Clinical Trial Registry, ChiCTR2000038554.

Methylphenidate remediates aberrant brain network dynamics in children with attention-deficit/hyperactivity disorder: A randomized controlled trial.

Methylphenidate is a widely used first-line treatment for attention deficit/hyperactivity disorder (ADHD), but the underlying circuit mechanisms are poorly understood. Here we investigate whether a single dose of osmotic release oral system methylphenidate can remediate attention deficits and aberrancies in functional circuit dynamics in cognitive control networks, which have been implicated in ADHD. In a randomized placebo-controlled double-blind crossover design, 27 children with ADHD were scanned twice with resting-state functional MRI and sustained attention was examined using a continuous performance task under methylphenidate and placebo conditions; 49 matched typically-developing (TD) children were scanned once for comparison. Dynamic time-varying cross-network interactions between the salience (SN), frontoparietal (FPN), and default mode (DMN) networks were examined in children with ADHD under both administration conditions and compared with TD children. Methylphenidate improved sustained attention on a continuous performance task in children with ADHD, when compared to the placebo condition. Children with ADHD under placebo showed aberrancies in dynamic time-varying cross-network interactions between the SN, FPN and DMN, which were remediated by methylphenidate. Multivariate classification analysis confirmed that methylphenidate remediates aberrant dynamic brain network interactions. Furthermore, dynamic time-varying network interactions under placebo conditions predicted individual differences in methylphenidate-induced improvements in sustained attention in children with ADHD. These findings suggest that a single dose of methylphenidate can remediate deficits in sustained attention and aberrant brain circuit dynamics in cognitive control circuits in children with ADHD. Findings identify a novel brain circuit mechanism underlying a first-line pharmacological treatment for ADHD, and may inform clinically useful biomarkers for evaluating treatment outcomes.

[Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia].

OBJECTIVE: To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI). METHODS: A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO15) and Shen (CO10) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain. RESULTS: After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01). CONCLUSION: taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.

To Regulate or Not to Regulate: Emotion Regulation in Participants With Low and High Impulsivity.

Successful emotion regulation plays a key role in psychological health and well-being. This study examines (1) whether cognitive control and corresponding neural connectivity are associated with emotion regulation and (2) to what extent external instructions can improve emotion regulation in individuals with low vs. high cognitive control capacity. For this, emotion regulation capabilities and the impact of emotion regulation on a subsequent emotional Stroop task was tested in participants with low (N = 25) vs. high impulsivity (N = 32). The classification according to impulsivity is based upon the stable correlation between high impulsivity and reduced cognitive control capacity. A negative emotion inducing movie scene was presented with the instruction to either suppress or allow all emotions that arose. This was followed by an emotional Stroop task. Electromyography (EMG) over the corrugator supercilii was used to assess the effects of emotion regulation. Neurophysiological mechanisms were measured using functional near-infrared spectroscopy over frontal brain areas. While EMG activation was low in the low-impulsive group independent of instruction, high-impulsive participants showed increased EMG activity when they were not explicitly instructed to suppress arising emotions. Given the same extent of functional connectivity within frontal lobe networks, the low-impulsive participants controlled their emotions better (less EMG activation) than the high-impulsive participants. In the Stroop task, the low-impulsive subjects performed significantly better. The emotion regulation condition had no significant effect on the results. We conclude that the cognitive control network is closely associated with emotion regulation capabilities. Individuals with high cognitive control show implicit capabilities for emotion regulation. Individuals with low cognitive control require external instructions (= explicit emotion regulation) to achieve similarly low expressions of emotionality. Implications for clinical applications aiming to improve emotion regulation are discussed.

Dynamic Functional Connectivity Predicts Treatment Response to Electroconvulsive Therapy in Major Depressive Disorder.

Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder. Recently, there has been increasing attention to evaluate the effect of ECT on resting-state functional magnetic resonance imaging (rs-fMRI). This study aims to compare rs-fMRI of depressive disorder (DEP) patients with healthy participants, investigate whether pre-ECT dynamic functional network connectivity network (dFNC) estimated from patients rs-fMRI is associated with an eventual ECT outcome, and explore the effect of ECT on brain network states. Method: Resting-state functional magnetic resonance imaging (fMRI) data were collected from 119 patients with depression or depressive disorder (DEP) (76 females), and 61 healthy (HC) participants (34 females), with an age mean of 52.25 (N = 180) years old. The pre-ECT and post-ECT Hamilton Depression Rating Scale (HDRS) were 25.59 ± 6.14 and 11.48 ± 9.07, respectively. Twenty-four independent components from default mode (DMN) and cognitive control network (CCN) were extracted, using group-independent component analysis from pre-ECT and post-ECT rs-fMRI. Then, the sliding window approach was used to estimate the pre-and post-ECT dFNC of each subject. Next, k-means clustering was separately applied to pre-ECT dFNC and post-ECT dFNC to assess three distinct states from each participant. We calculated the amount of time each subject spends in each state, which is called "occupancy rate" or OCR. Next, we compared OCR values between HC and DEP participants. We also calculated the partial correlation between pre-ECT OCRs and HDRS change while controlling for age, gender, and site. Finally, we evaluated the effectiveness of ECT by comparing pre- and post-ECT OCR of DEP and HC participants. Results: The main findings include (1) depressive disorder (DEP) patients had significantly lower OCR values than the HC group in state 2, where connectivity between cognitive control network (CCN) and default mode network (DMN) was relatively higher than other states (corrected p = 0.015), (2) Pre-ECT OCR of state, with more negative connectivity between CCN and DMN components, is linked with the HDRS changes (R = 0.23 corrected p = 0.03). This means that those DEP patients who spent less time in this state showed more HDRS change, and (3) The post-ECT OCR analysis suggested that ECT increased the amount of time DEP patients spent in state 2 (corrected p = 0.03). Conclusion: Our finding suggests that dynamic functional network connectivity (dFNC) features, estimated from CCN and DMN, show promise as a predictive biomarker of the ECT outcome of DEP patients. Also, this study identifies a possible underlying mechanism associated with the ECT effect on DEP patients.

Abnormality of Resting-State Functional Connectivity in Major Depressive Disorder: A Study With Whole-Head Near-Infrared Spectroscopy.

Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that has advantages in clinical usage. Previous functional magnetic resonance imaging (fMRI) studies have found that the resting-state functional connectivity (RSFC) of the default mode network (DMN) is increased, while the RSFC of the cognitive control network (CCN) is reduced in patients with major depressive disorder (MDD) compared with healthy controls. This study tested whether the NIRS-based RSFC measurements can detect the abnormalities in RSFC that have been associated with MDD in previous fMRI studies. We measured 8 min of resting-state brain activity in 34 individuals with MDD and 78 age- and gender-matched healthy controls using a whole-head NIRS system. We applied a previously established partial correlation analysis for estimating RSFCs between the 17 cortical regions. We found that MDD patients had a lower RSFC between the left dorsolateral prefrontal cortex and the parietal lobe that comprise the CCN, and a higher RSFC between the right orbitofrontal cortex and ventrolateral prefrontal cortex, compared to those in healthy controls. The RSFC strength of the left CCN was negatively correlated with the severity of depressive symptoms and the dose of antipsychotic medication and positively correlated with the level of social functioning. The results of this study suggest that NIRS-based measurements of RSFCs have potential clinical applications.