Changes In Resting-state Functional Connectivity Research Articles

Investigating resting-state functional connectivity changes within procedural memory network across neuropsychiatric disorders using fMRI

BackgroundCognitive networks impairments are common in neuropsychiatric disorders like Attention Deficit Hyperactivity Disorder (ADHD), bipolar disorder (BD), and schizophrenia (SZ). While previous research has focused on specific brain regions, the role of the procedural memory as a type of long-term memory to examine cognitive networks impairments in these disorders remains unclear. This study investigates alterations in resting-state functional connectivity (rs-FC) within the procedural memory network to explore brain function associated with cognitive networks in patients with these disorders.MethodsThis study analyzed resting-state functional magnetic resonance imaging (rs-fMRI) data from 40 individuals with ADHD, 49 with BD, 50 with SZ, and 50 healthy controls (HCs). A procedural memory network was defined based on the selection of 34 regions of interest (ROIs) associated with the network in the Harvard-Oxford Cortical Structural Atlas (default atlas). Multivariate region of interest to region of interest connectivity (mRRC) was used to analyze the rs-FC between the defined network regions. Significant differences in rs-FC between patients and HCs were identified (P < 0.001).ResultsADHD patients showed increased Cereb45 l - Cereb3 r rs-FC (p = 0.000067) and decreased Cereb1 l - Cereb6 l rs-FC (p = 0.00092). BD patients exhibited increased rs-FC between multiple regions, including Claustrum r - Caudate r (p = 0.00058), subthalamic nucleus r - Pallidum l (p = 0.00060), substantia nigra l - Cereb2 l (p = 0.00082), Cereb10 r - SMA r (p = 0.00086), and Cereb9 r - SMA l (p = 0.00093) as well as decreased rs-FC in subthalamic nucleus r - Cereb6 l (p = 0.00013) and Cereb9 r - Cereb9 l (p = 0.00033). SZ patients indicated increased Caudate r– putamen l rs-FC (p = 0.00057) and decreased rs-FC in subthalamic nucleus r – Cereb6 l (p = 0.000063), and Cereb1 r – subthalamic nucleus r (p = 0.00063).ConclusionsThis study found significant alterations in rs-FC within the procedural memory network in patients with ADHD, BD, and SZ compared to HCs. These findings suggest that disrupted rs-FC within this network may related to cognitive networks impairments observed in these disorders.Clinical trial numberNot applicable.

Exploring memory-related network via dorsal hippocampus suppression.

Memory is a complex brain process that requires coordinated activities in a large-scale brain network. However, the relationship between coordinated brain network activities and memory-related behavior is not well understood. In this study, we investigated this issue by suppressing the activity in the dorsal hippocampus (dHP) using chemogenetics and measuring the corresponding changes in brain-wide resting-state functional connectivity (RSFC) and memory behavior in awake rats. We identified an extended brain network contributing to the performance in a spatial memory related task. Our results were cross-validated using two different chemogenetic actuators, clozapine (CLZ) and clozapine-N-oxide (CNO). This study provides a brain network interpretation of memory performance, indicating that memory is associated with coordinated brain-wide neural activities.

Trajectories of human brain functional connectome maturation across the birth transition.

Understanding the sequence and timing of brain functional network development at the beginning of human life is critically important from both normative and clinical perspectives. Yet, we presently lack rigorous examination of the longitudinal emergence of human brain functional networks over the birth transition. Leveraging a large, longitudinal perinatal functional magnetic resonance imaging (fMRI) data set, this study models developmental trajectories of brain functional networks spanning 25 to 55 weeks of post-conceptual gestational age (GA). The final sample includes 126 fetal scans (GA = 31.36 ± 3.83 weeks) and 58 infant scans (GA = 48.17 ± 3.73 weeks) from 140 unique subjects. In this study, we document the developmental changes of resting-state functional connectivity (RSFC) over the birth transition, evident at both network and graph levels. We observe that growth patterns are regionally specific, with some areas showing minimal RSFC changes, while others exhibit a dramatic increase at birth. Examples with birth-triggered dramatic change include RSFC within the subcortical network, within the superior frontal network, within the occipital-cerebellum joint network, as well as the cross-hemisphere RSFC between the bilateral sensorimotor networks and between the bilateral temporal network. Our graph analysis further emphasized the subcortical network as the only region of the brain exhibiting a significant increase in local efficiency around birth, while a concomitant gradual increase was found in global efficiency in sensorimotor and parietal-frontal regions throughout the fetal to neonatal period. This work unveils fundamental aspects of early brain development and lays the foundation for future work on the influence of environmental factors on this process.

Alterations in functional connectivity in the salience network shared by depressive symptoms and smartphone overuse

Globally, the age when children start using smartphones has decreased. Concurrently, the increased use of smartphones among children in developmental stages has caused serious effects, such as depression. While neuroimaging studies have predicted a significant overlap between the neurobiological changes caused by depression and smartphone overuse, few have simultaneously examined them. Therefore, we examined resting-state functional connectivity (FC) changes due to smartphone overuse and depressive symptoms in 69 children. We observed that FC in the salience network and regions involved in visual (e.g., the lateral occipital cortex) and motivational processing (e.g., the putamen) increased with smartphone overuse and depressive symptoms. Additionally, FC partially mediated the relationship between depressive symptoms and smartphone overuse, suggesting that changes in FC may be involved in the link between depressive symptoms and smartphone overuse. Our findings indicate that increased depressive symptoms could be associated with alterations in the salience network FC, which may influence visual attention or reward processing of salient stimuli, potentially contributing to smartphone overuse.

Associations among environmental unpredictability, changes in resting-state functional connectivity, and adolescent psychopathology in the ABCD study

Abstract Background Unpredictability is a core but understudied dimension of adversities and has been receiving increasing attention recently. The effects of unpredictability on psychopathology and the underlying neural mechanisms, however, remain unclear. It is also unknown how unpredictability interacts with other dimensions of adversities in predicting brain development and psychopathology of youth. Methods We applied cluster robust standard errors to examine how unpredictability was associated with the developmental changes in resting-state functional connectivity (rsFC) of large-scale brain networks implicated in psychopathology, as well as the moderating role of deprivation, using data from the Adolescent Brain Cognitive Development (ABCD) study, which included four measurements from baseline (mean ± s.d. age, 119.13 ± 7.51 months; 2815 females) to 3-year follow-up (N = 5885). Results After controlling for threat, unpredictability was associated with a smaller increase in rsFC within default mode network (DMN) and a smaller decrease in rsFC between cingulo-opercular network (CON) and DMN. Neighborhood educational deprivation moderated the associations between unpredictability and changes in rsFC within DMN and fronto-parietal network (FPN), as well as between CON and DMN. A smaller decrease in rsFC between CON and DMN mediated the association between unpredictability and externalizing problems. Neighborhood educational deprivation moderated the indirect pathway from unpredictability to externalizing problems via a smaller decrease in CON-DMN rsFC. Conclusions Our findings shed light on the neural mechanisms underlying the associations between unpredictability and adolescents' psychopathology and the moderating role of deprivation, highlighting the significance of providing stable environment and abundant educational opportunities to facilitate optimal development.

Changes in Resting-State Functional Connectivity and Cognitive-Affective Symptoms in Patients With Post-Concussion Syndrome Treated With N-Acetyl Cysteine.

Concussion accounts for more than 80% of people experiencing traumatic brain injury. Acute concussion is associated with characteristic cognitive and functional deficits that may persist for weeks to months. A subgroup of these patients (from 10% to 50%) have persistent symptoms referred to as chronic post-concussion syndrome (PCS). There are limited treatment options for these patients and the pathophysiology is poorly understood, though oxidative stress is thought to be a contributing factor. The purpose of this study was to evaluate whether an antioxidant, N-acetylcysteine (NAC), might be beneficial in patients with PCS. Outpatient medicine center. Fifty patients with chronic PCS for at least 3 months post injury. The patients with PCS were enrolled in this randomized unblinded clinical trial to receive the antioxidant NAC as a combination of daily oral and weekly intravenous infusions, or assigned to a waitlist control group where they would continue to receive standard of care. Resting-state functional connectivity (FC) magnetic resonance imaging (rsFC-MRI) was performed pre and post either NAC or the waitlist period along with cognitive, emotional, and sensory symptom assessments. The results demonstrated significant (P <.05) improvements in symptoms as determined by the Rivermead Post-Concussion Symptoms Questionnaire, Spielberger State-Trait Anxiety Inventory, and Profile of Mood Scale in the PCS group receiving NAC as compared to patients receiving ongoing standard care. Importantly, there were significant (P<.01) changes in FC in the NAC group, particularly in networks such as the default mode network, salience network, and executive control network. These changes in FC also correlated with improvements in symptoms. In patients with chronic PCS, NAC treatment was associated with significant changes in resting state FC and improvement in a variety of symptoms, particularly cognitive and affective symptoms.

Changes in resting-state functional connectivity of large-scale brain networks in bulimia nervosa: evidence from causal analysis.

Bulimia nervosa (BN) has been observationally linked to the functional connectivity (FC) of large-scale brain networks, but the biological mechanisms remain unclear. This study used two-sample Mendelian randomization (MR) with genetic variations as instrumental variables (IVs) to explore potential causal relationships between FC and BN. Summary data from genome-wide association studies (GWAS) involving 2,564 individuals were analyzed to identify genetically predicted BN. Functional magnetic resonance imaging parameters and materials were sourced from the UK Biobank. The variables underwent independent component analysis processing by the database to generate the final GWAS dataset. Various methods, including MR Pleiotropy RESidual Sum and Outlier, MR Egger, and weighted median, were employed to detect heterogeneity and pleiotropy, with inverse variance weighting serving as the principal estimation method (P < 0.05). The FC imaging-derived phenotypes revealed that BN exerted a causal influence on the FC between large-scale networks, including the visual network, default mode network (DMN), frontoparietal network, somatosensory network (SSN), and ventral attention network. Additionally, BN had a causal impact on the within-network FC of both the DMN and SSN. The study provides evidence that BN leads to further changes in FC patterns within and between large-scale brain networks.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

Abnormal resting-state functional connectivity of the right anterior cingulate cortex in chronic ketamine users and its correlation with cognitive impairments

BackgroundChronic ketamine use leads to cognitive impairments, however, the neural mechanisms underpinning these impairments are still unclear. AimsMany studies showed Anterior cingulate cortex (ACC)is strongly involved in cognition and drug addiction, as supported by our previous studies. The objective of this study was to assess the variations in resting-state functional connectivity (FC) changes in the right anterior cingulate cortex (ACC) of chronic ketamine users (CKUs) and their relationship with cognitive performance. MethodsThe study enrolled 28 chronic ketamine users (CKUs) and 30 healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) data were gathered from both groups. Cognitive functions were evaluated using the MATRICS Consensus Cognitive Battery (MCCB). ResultsCKUs demonstrated significantly poorer cognitive performance than HCs in various cognitive domains, including Visual Learning, Speed of Processing, Working Memory, and the composite score of MCCB. Group-level comparisons revealed that CKUs exhibited enhanced functional connectivity between the right ACC and the right postcentral gyrus (PCG) compared to HCs. There was a positive relationship between the connectivity of right ACC-PCG and reasoning and problem-solving score, but there was no significant association with the characteristics of ketamine use. ConclusionCKUs showed enhanced connectivity between the right ACC and the right PCG. This enhanced functional connectivity may indicate functional compensation for cognitive deficits in CKUs, especially for reasoning and problem-solving impairments in CKUs.

Associations Between Changes in Psychological Resilience and Resting-State Functional Connectivity Throughout Pediatric Concussion Recovery.

Purpose: This study investigated the association between psychological resilience and resting-state network functional connectivity of three major brain networks in pediatric concussion. Methods: This was a substudy of a randomized controlled trial, recruiting children with concussion and orthopedic injury. Participants completed the Connor-Davidson Resilience 10 Scale and underwent magnetic resonance imaging at 72 h and 4-weeks postinjury. We explored associations between resilience and connectivity with the default mode network (DMN), central executive network (CEN), and salience network (SN) at both timepoints and also any change that occurred over time. We also explored associations between resilience and connectivity within each network. Results: A total of 67 children with a concussion (median age = 12.87 [IQR: 11.79-14.36]; 46% female) and 30 with orthopedic injury (median age = 12.27 [IQR: 11.19-13.94]; 40% female) were included. Seed-to-voxel analyses detected a positive correlation between 72-h resilience and CEN connectivity in the concussion group. Group moderated associations between resilience and SN connectivity at 72 h, as well as resilience and DMN connectivity over time. Regions-of-interest analyses identified group as a moderator of longitudinal resilience and within-DMN connectivity. Conclusions: These results suggest that neural recovery from concussion could be reliant on resilience. Resilience was related to functional connectivity with three of the main networks in the brain that are often impacted by concussion. Improving resilience might be investigated as a modifiable variable in children as both a protective and restorative in the context of concussion. Clinical Trial Registration Identifier: NCT05105802. PedCARE+MRI team (see Supplementary Appendix S1).

Translation of monosynaptic circuits underlying amygdala fMRI neurofeedback training.

fMRI neurofeedback using autobiographical memory recall to upregulate the amygdala is associated with resting-state functional connectivity (rsFC) changes between the amygdala and the salience and default mode networks (SN and DMN, respectively). We hypothesize the existence of anatomical circuits underlying these rsFC changes. Using a cross-species brain parcellation, we identified in non-human primates locations homologous to the regions of interest (ROIs) from studies showing pre-to-post-neurofeedback changes in rsFC with the left amygdala. We injected bidirectional tracers in the basolateral, lateral, and central amygdala nuclei of adult macaques and used bright- and dark-field microscopy to identify cells and axon terminals in each ROI (SN: anterior cingulate, ventrolateral, and insular cortices; DMN: temporal pole, middle frontal gyrus, angular gyrus, precuneus, posterior cingulate cortex, parahippocampal gyrus, hippocampus, and thalamus). We also performed additional injections in specific ROIs to validate the results following amygdala injections and delineate potential disynaptic pathways. Finally, we used high-resolution diffusion MRI data from four post-mortem macaque brains and one in vivo human brain to translate our findings to the neuroimaging domain. Different amygdala nuclei had significant monosynaptic connections with all the SN and DMN ipsilateral ROIs. Amygdala connections with the DMN contralateral ROIs are disynaptic through the hippocampus and parahippocampal gyrus. Diffusion MRI in both species benefitted from using the ground-truth tracer data to validate its findings, as we identified false-negative ipsilateral and false-positive contralateral connectivity results. This study provides the foundation for future causal investigations of amygdala neurofeedback modulation of the SN and DMN through these anatomic connections.

From convergence insufficiency to functional reorganization: Alongitudinal randomized controlled trial of treatment-induced connectivity plasticity.

Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting-state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office-based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task-related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms. A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one-hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting-state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t-tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group-level analysis for correlations with clinical measures. Paired t-test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)-SEF-Right (R)-V1, L-SEF-CV, R-SEF-R-PEF, R-SEF-L-V1, R-SEF-R-V1, R-SEF-CV, R-PEF-CV, L-V1-CV, R-V1-CV, and L-V1-R-V1. Significant correlations were observed between the RSFC strength of the R-SEF-R-PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05). OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants.

Association of plasma metals with resting-state functional connectivity in ischemic stroke

BackgroundMetal exposure has long been considered a significant risk factor for ischemic stroke. However, existing data on the effects of metal exposure on brain function in ischemic stroke are limited. Therefore, this study aimed to explore the correlation between exposure to various metals and changes in resting-state functional connectivity (rs-FC) in ischemic stroke patients. MethodsThis study included 28 acute ischemic stroke patients with hemiplegia and 28 matched healthy controls (HCs). All participants underwent T1-weighted MRI and 3.0 T resting-state functional magnetic resonance imaging (fMRI). After MRI acquisition, the rs-FC between 137 cortical and subcortical regions was extracted and preprocessed. Plasma levels of 19 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). The Bayesian kernel machine regression (BKMR) model and the weighted quantile sum regression (WQS) model were used to assess the overall effect of metal mixture exposure. The severity of neurological deficits in each acute ischemic stroke patient was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Additionally, the associations between exposure to various metals and modifications in brain functional connectivity were determined using Pearson or Spearman correlation analysis. ResultsBilateral brain connectivity was significantly decreased compared to controls and was associated with neurological impairment in ischemic stroke. In patients with ischemic stroke, the plasma concentrations of Cr (p < 0.001), Cu (p = 0.004), As (p = 0.010), Cs (p = 0.046), Rb (p = 0.041), and Sb (p = 0.001) were significantly higher than those in the HCs, whereas the plasma Tl concentrations (p = 0.022) were significantly lower. The results of the BKMR and WQS models showed that combined exposure to metal mixtures was linked to a higher risk of ischemic stroke. Cr was positively correlated with the rs-FC between the left Rolandic_Oper and the left Supp_Motor_Area (r = 0.414, p = 0.029), while negatively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal (r = −0.398, p = 0.037). Cu was negatively correlated with the rs-FC between the left paracentral lobule and the left thalamus (r = −0.409, p = 0.031). Tl was positively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal cortex (r = 0.590, p = 0.001). A negative correlation was observed between Cs and rs-FC between the right Cingulate_Mid and left Occipital_Sup (r = −0.429, p = 0.024). Sb was negatively correlated with the rs-FC between the left Parietal_Inf and the right SupraMarginal (r = −0.384, p = 0.044), the right Parietal_Inf and the left SupraMarginal (r = −0.583, p = 0.001), and the left SupraMarginal and the right SupraMarginal (r = −0.377, p = 0.048). ConclusionPlasma levels of Cr, Cu, Tl, Cs, and Sb were associated with altered rs-FC in brain regions related to motor control, sensory integration, executive function, language processing, and emotional regulation in ischemic stroke patients with basal ganglia infarction.

Childhood maltreatment and transdiagnostic connectivity of the default-mode network: The importance of duration of exposure

Childhood maltreatment (CM) has been demonstrated to be associated with changes in resting-state functional connectivity of the default-mode network (DMN) across various mental disorders. Growing evidence regarding severity of CM is available but transdiagnostic research considering the role of both severity and duration of CM for DMN connectivity at rest is still scarce. We recruited a sample of participants with varying levels of CM suffering from three disorders in which a history of CM is frequently found, namely, post-traumatic stress disorder, major depressive disorder, or somatic symptom disorder, as well as healthy volunteers to examine DMN connectivity in a transdiagnostic sample. We expected to find changes in inter-network connectivity of the DMN related to higher self-reported levels of CM severity and duration. Resting-state functional magnetic resonance imaging scans of 128 participants were analyzed focusing on regions of interest (ROI-to-ROI approach) and whole-brain Seed-to-Voxel analyses with retrospectively assessed CM as predictor in a regression model. Changes in connectivity between nodes of the DMN and the visual network were identified to be associated with CM duration but not severity. CM duration showed associations with increased connectivity of the precuneus and visual regions, as well as sensory-motor regions. The observed changes in connectivity could be interpreted as an impairment of information transfer between the transmodal DMN and unimodal visual and sensory-motor regions with impairment increasing with duration of exposure to CM.

Neural correlates of approach–avoidance behavior in healthy subjects: Effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right dorsolateral prefrontal cortex

The dorsolateral prefrontal cortex (dlPFC) is implicated in top-down regulation of emotion, but the detailed network mechanisms require further elucidation. To investigate network-level functions of the dlPFC in emotion regulation, this study measured changes in task-based activation, resting-state and task-based functional connectivity (FC) patterns following suppression of dlPFC excitability by 1-Hz repetitive transcranial magnetic stimulation (rTMS). In a sham-controlled within-subject design, 1-Hz active or sham rTMS was applied to the right dlPFC of 19 healthy volunteers during two separate counterbalanced sessions. Following active and sham rTMS, functional magnetic resonance imaging (fMRI) was conducted in the resting state (rs-fMRI) and during approach–avoidance task responses to pictures with positive and negative emotional content (task-based fMRI). Activation and generalized psychophysiological interaction analyses were performed on task-based fMRI, and seed-based FC analysis was applied to rs-fMRI data. Task-based fMRI revealed greater and more lateralized activation in the right hemisphere during negative picture responses compared to positive picture responses. After active rTMS, greater activation was observed in the left middle prefrontal cortex compared to sham rTMS. Further, rTMS reduced response times and error rates in approach to positive pictures compared to negative pictures. Significant FC changes due to rTMS were observed predominantly in the frontoparietal network (FPN) and visual network (VN) during the task, and in the default mode network (DMN) and VN at rest. Suppression of right dlPFC activity by 1-Hz rTMS alters large-scale neural networks and modulates emotion, supporting potential applications for the treatment of mood disorders.

Effects of acute aerobic exercise on resting state functional connectivity of motor cortex in college students

This study intends to inspect the effects of acute aerobic exercise (AE) on resting state functional connectivity (RSFC) in motor cortex of college students and the moderating effect of fitness level. Methods: 20 high fitness level college students and 20 ordinary college students were recruited in public. Subjects completed 25 min of moderate- and high-intensity acute aerobic exercise respectively by a bicycle ergometer, and the motor cortex’s blood oxygen signals in resting state were monitored by functional Near Infrared Spectroscopy (fNIRS, the Shimadzu portable Light NIRS, Japan) in pre- and post-test. Results: At the moderate intensity level, the total mean value of RSFC pre- and post-test was significantly different in the high fitness level group (pre-test 0.62 ± 0.18, post-test 0.51 ± 0.17, t(19) = 2.61, p = 0.02, d = 0.58), but no significant change was found in the low fitness level group. At the high-intensity level, there was no significant difference in the difference of total RSFC between pre- and post-test in the high and low fitness group. According to and change trend of 190 “edges”: at the moderate-intensity level, the number of difference edges in the high fitness group (d = 0.58, 23) were significantly higher than those in the low fitness group (d = 0.32, 15), while at high-intensity level, there was a reverse trend between the high fitness group (d = 0.25, 18) and the low fitness group (d = 0.39, 23). Conclusions: moderate-intensity AE can cause significant changes of RSFC in the motor cortex of college students with high fitness, while high fitness has a moderating effect on the relationship between exercise intensity and RSFC. RSFC of people with high fitness is more likely to be affected by AE and show a wider range of changes.

Effects of bilateral tDCS over DLPFC on response inhibition, craving, and brain functional connectivity in Internet gaming disorder: Arandomized, double-blind, sham-controlled trial with fMRI.

Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

Reduced resting-state functional connectivity between insula and inferior frontal gyrus and superior temporal gyrus in hoarding disorder.

Hoarding disorder (HD) is characterized by cognitive control impairments and abnormal brain activity in the insula and anterior cingulate cortex (ACC) during disposal of personal items or certain executive function tasks. However, whether there are any changes in resting-state functional connectivity of the insula and ACC remains unclear. A total of 55 subjects, including 24 patients with HD and 31 healthy controls (HCs), participated in the study. We acquired resting-state functional magnetic resonance imaging data and examined group differences in functional connectivity from the insula and ACC in whole-brain voxels. In patients with HD, functional connectivity was significantly lower between the right insula and right inferior frontal gyrus (IFG) and left superior temporal gyrus (STG) compared to HCs. There was no correlation between these connectivities and HD symptoms. Although the clinical implication is uncertain, our results suggest that patients with HD have resting-state functional alterations between the insula and IFG and STG, corresponding with the results of previous fMRI studies. These findings provide new insight into the neurobiological basis of HD.

Acute Exercise Improves Large-Scale Brain Network Segregation in Healthy Older Adults.

Introduction: Age-related cognitive decline and mental health problems are accompanied by changes in resting-state functional connectivity (rsFC) indices, such as reduced brain network segregation. Meanwhile, exercise can improve cognition, mood, and neural network function in older adults. Studies on effects of exercise on rsFC outcomes in older adults have chiefly focused on changes after exercise training and suggest improved network segregation through enhanced within-network connectivity. However, effects of acute exercise on rsFC measures of neural network integrity in older adults, which presumably underlie changes observed after exercise training, have received less attention. In this study, we hypothesized that acute exercise in older adults would improve functional segregation of major cognition and affect-related brain networks. Methods: To test this, we analyzed rsFC data from 37 healthy and physically active older adults after they completed 30 min of moderate-to-vigorous intensity cycling and after they completed a seated rest control condition. Conditions were performed in a counterbalanced order across separate days in a within-subject crossover design. We considered large-scale brain networks associated with cognition and affect, including the frontoparietal network (FPN), salience network (SAL), default mode network (DMN), and affect-reward network (ARN). Results: We observed that after acute exercise, there was greater segregation between SAL and DMN, as well as greater segregation between SAL and ARN. Conclusion: These findings indicate that acute exercise in active older adults alters rsFC measures in key cognition and affect-related networks in a manner that opposes age-related dedifferentiation of neural networks that may be detrimental to cognition and mental health.