Dysfunctional resting state network connectivity predicts postoperative delirium after major surgery.

Emotional empathy is the ability to experience and/or share another person’s emotional states and responses. Although some research has examined the neural correlates of emotional empathy, there has been little research investigating whether this component of empathy is related to the functional connectivity of resting state networks in the brain. In the current study, 32 participants answered a trait emotional empathy questionnaire in a session previous to their functional magnetic resonance imaging scan. Results indicate that emotional empathy scores were correlated with different patterns of functional connectivity in the default mode network (DMN), salience network (SN), and left and right central executive networks. For example, within the DMN, emotional empathy scores positively correlated with connectivity in the premotor cortex. Within the SN, empathy scores were positively correlated with the fusiform gyrus and cuneus. These findings demonstrate that emotional empathy is associated with unique patterns of functional connectivity in four of the brain’s resting state networks.

目的 探讨精神分裂症患者脑静息态默认网络、中心执行网络及突显网络的网络内及网络间的功能连接特点.方法 对74例精神分裂症患者(患者组)和79名相匹配的健康者(对照组)进行静息态fMRI扫描.采取功能连接分析方法,以内侧前额叶皮质及右侧前岛叶为感兴趣区域分别提取默认网络、中心执行网络及突显网络,分析3个网络内及网络间静息态功能连接情况;并对有差异的功能连接与精神症状及病程等进行偏相关分析.结果 与对照组相比,患者组内侧前额叶皮质与双侧背外侧前额叶皮质(左侧-0.02±0.18与-0.12±0.12,t=4.25,P＜0.01;右侧-0.02±0.11与-0.10±0.10,t=5.40,P＜0.01)、双侧豆状壳核(左侧0.14±0.12与0.04±0.10,t=5.03,P＜0.01;右侧0.13±0.11与0.03±0.98,t=4.96,P＜0.01)的功能连接增强;右侧前岛叶与左侧额中回(-0.05±0.17与-0.07±0.17,t=4.60,P＜0.01)及楔前叶/后扣带回(0.01±0.13与-0.09±0.14,t=4.01,P＜0.01)的功能连接增强(均采用高斯随机场理论校正,体素水平P＜0.01,簇水平P＜0.05);默认网络与中心执行网络、突显网络间的负向功能连接减小甚至消失(Bonferroni校正P＜0.05).患者组PANSS阳性症状分与右侧前岛叶与楔前叶/后扣带回皮质间的功能连接呈正相关(r=0.232,P=0.025);患者组病程与右侧前岛叶与左侧额中回(r=0.288,P=0.007)、楔前叶/后扣带回(r=0.196,P=0.049)间的功能连接呈正相关.结论 精神分裂症患者存在静息态默认网络、中心执行网络及突显网络3个网络间的连接异常,可能与精神分裂症的病理机制有关.

Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation. Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network. At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward). Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

Stress exposures and dysregulated responses to stress are implicated in psychiatric disorders of mood, anxiety, and cognition. Perceived stress, an individual's appraisal of experienced stress and ability for coping, relates to dysregulated functioning in resting state brain networks. Alterations in GABAergic function may underlie perceived stress-related functional dysregulation in resting state networks but this has not yet been explored. Therefore, the current study examined the association of perceived stress, via the Perceived Stress Scale (PSS), with prefrontal GABA levels and corresponding resting state functional connectivity (RSFC) alterations. Twelve women and five men, ages 35–61, participated. MR spectroscopy was used to measure brain GABA levels in the anterior cingulate cortex (ACC), left dorsolateral prefrontal cortex (DLPFC), and ventromedial prefrontal cortex (VMPFC). Resting state functional scans acquired at 3 Tesla were used to measure RSFC within and between the default mode (DMN), salience (SN), and central executive networks (CEN), hippocampus and amygdala. We observed significant negative correlations between total PSS scores and left DLPFC GABA levels (r = −0.62, p = 0.023). However, PSS scores were not significantly correlated with RSFC measures (all p > 0.148). These preliminary results support a relationship between perceived stress and GABAergic functioning in DLPFC, a core node of the CEN, an intrinsic network thought to underlie goal-directed attentional processes. Our findings extend previous work suggesting that functioning in the CEN is related to perceived stress and may inform treatment strategies to improve outcomes in stress-related conditions.

Although state anxiety has been characterized by hyper-responsive subcortical activity and its bottom-up connectivity with cortical regions, the role of cortical networks in state anxiety is not yet well understood. To this end, we decoded individual state anxiety by using a machine-learning approach based on resting-state functional connectivity (RSFC) with functional near-infrared spectroscopy (fNIRS). Our results showed that the RSFC among a set of cortical networks were highly predictive of state anxiety, rather than trait anxiety. Specifically, these networks included connectivity between cortical areas in the default mode network (DMN) and dorsal attention network (DAN), and connectivity within the DMN, which were negatively correlated with state anxiety; connectivity between cortical areas in the DMN and frontoparietal network (FPN), FPN and salience network (SN), FPN and DAN, DMN and SN, which were positively correlated with state anxiety. These findings suggest a predictive role of intrinsic cortical organization in the assessment of state anxiety. The work provides new insights into potential neural mechanisms of emotion states and implications for prognosis, diagnosis, and treatment of affective disorders.

Background:The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown.Method:We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales.Results:Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv.Conclusion:Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.

Children born extremely preterm (EP; < 28 weeks of gestation) or extremely low birth weight (ELBW; < 1000 g) are at increased risk of working memory deficits compared with their term-born peers and may benefit from working memory training. This study aimed to determine whether Cogmed Working Memory Training®, compared with a placebo training program, was associated with changes in resting-state functional connectivity (rsfc) and whether these changes correlated with working memory performance in EP/ELBW children. Twenty-one 7-year-old EP/ELBW children were enrolled in a double-blinded randomized controlled trial and had magnetic resonance imaging (MRI) assessments (Cogmed, n = 12; placebo (a non-adaptive version of Cogmed), n = 9). Prior to training (baseline) and 2 weeks post-training, all children received a cognitive assessment, inclusive of immediate memory and working memory measures and an MRI. The Cogmed Improvement Index was used as a measure of improvement in trained activities in the Cogmed group. Resting-state functional MRI was used to measure training-related changes in intra- and inter-network rsfc. The networks assessed include the default mode network, the left and right central executive networks, the bilateral executive network, the dorsal attention network, and the salience network. rsfc data were compared between treatment groups and investigated in relation to changes in working memory performance. There was little evidence of differences in intra- or inter-network rsfc strength changes from baseline to post-training between treatment groups. In the Cogmed group, working memory performance was associated with increased rsfc from baseline to post-training within the precuneus network, but not in the placebo group. In the Cogmed group, results that did not survive multiple comparison correction further showed that improvement in trained activities was associated with increased rsfc between the left central and bilateral executive networks, and with decreased rsfc within the right central executive network and between the right central executive and salience networks. Changes in rsfc may facilitate working memory performance following Cogmed training. Further studies are needed to investigate how changes in rsfc are associated with behavioral changes to better support working memory in vulnerable groups.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression

The present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS). PedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K-means clustering on cognitive scores. MRI metrics included brain T2-hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting-state (RS) functional connectivity (FC) were estimated. Three cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005). We identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.

A single bout of aerobic exercise can provide acute benefits to cognition and emotion in children. Yet, little is known about how acute exercise may impact children's underlying brain networks' resting-state functional connectivity (rsFC). Using a data-driven multivariate pattern analysis, we investigated the effects of a single dose of exercise on acute rsFC changes in 9-to-13-year-olds. On separate days in a crossover design, participants (N = 21) completed 20-mins of acute treadmill walking at 65-75% heart rate maximum (exercise condition) and seated reading (control condition), with pre- and post-fMRI scans. Multivariate pattern analysis was used to investigate rsFC change between conditions. Three clusters in the left lateral prefrontal cortex (lPFC) of the frontoparietal network (FPN) had significantly different rsFC after the exercise condition compared to the control condition. Post-hoc analyses revealed that from before to after acute exercise, activity of these FPN clusters became more correlated with bilateral lPFC and the left basal ganglia. Additionally, the left lPFC became more anti-correlated with the precuneus of the default mode network (DMN). An opposite pattern was observed from before to after seated reading. The findings suggest that a single dose of exercise increases connectivity within the FPN, FPN integration with subcortical regions involved in movement and cognition, and segregation of FPN and DMN. Such patterns, often associated with healthier cognitive and emotional control, may underlie the transient mental benefits observed following acute exercise in youth.

AIM The surgical treatment of gliomas poses significant challenges due to the involvement of complex neural networks critical for cognitive functions. This study reviews the application of connectome-based approaches to minimize cognitive impairments and delirium during glioma resection, focusing on networks related to cognitive functions: the Default Mode Network (DMN), Dorsal Attention Network (DAN), Salience Network (SN), and Central Executive Network (CEN). METHODS Ten patients underwent surgery utilizing cloud-based connectomics software (Quicktome®), which maps the brain’s structural and functional connectivity. Preoperative MRIs with structural and functional connectome were performed for preoperative planning and intraoperative navigation. Preoperative neuropsychological assessments were conducted for elective cases. Only one patient was able to undergo awake craniotomy due to various medical, neurological and psychological limitations. Intraoperatively, with connectome-navigation guidance, a connectomics-based approach was conducted to preserve the networks. A semiquantitative analysis was performed as described (https://pubmed.ncbi.nlm.nih.gov/36719613). Pre- and postoperative (inpatient and 2 week follow up) RASS and NuDESC delirium screenings were performed, with long-term cognitive evaluations and repeat connectomics imaging planned. RESULTS Three out of ten patients presented with rapid functional deterioration and needed urgent surgical decompression had postoperative delirium. Connectome analysis showed involvement of cognition-related networks in these patients. Two out of 3 patients showed improvement in delirium scores at a two-week follow-up after tumor resection. CONCLUSION This pilot study suggests that factors such as acute presentation, emergency surgery, and tumor location involving and disrupting the DMN, SN, DAN, and CEN networks may contribute to early postoperative delirium. The study may pave the way for the efficacy of connectomics in preserving cognitive functions post-operatively, particularly when awake craniotomy is not possible. This approach holds promise for improving surgical outcomes, survival, and the quality of life for patients with gliomas by mitigating the cognitive impacts of tumor resection and postoperative complications.

Treatment non-response and recurrence are the main sources of disease burden in major depressive disorder (MDD). However, little is known about its neurobiological mechanism concerning the brain network changes accompanying pharmacotherapy. The present study investigated the changes in the intrinsic brain networks during 6-month antidepressant treatment phase associated with the treatment response and recurrence in MDD. Resting-state functional magnetic resonance imaging was acquired from untreated patients with MDD and healthy controls at baseline. The patients' depressive symptoms were monitored by using the Hamilton Rating Scale for Depression (HAMD). After 6 months of antidepressant treatment, patients were re-scanned and followed up every 6 months over 2 years. Traditional statistical analysis as well as machine learning approaches were conducted to investigate the longitudinal changes in macro-scale resting-state functional network connectivity (rsFNC) strength and micro-scale resting-state functional connectivity (rsFC) associated with long-term treatment outcome in MDD. Repeated measures of the general linear model demonstrated a significant difference in the default mode network (DMN) rsFNC change before and after the 6-month antidepressant treatment between remitters and non-remitters. The difference in the rsFNC change over the 6-month antidepressant treatment between recurring and stable MDD was also specific to DMN. Machine learning analysis results revealed that only the DMN rsFC change successfully distinguished non-remitters from the remitters at 6 months and recurring from stable MDD during the 2-year follow-up. Our findings demonstrated that the intrinsic DMN connectivity could be a unique and important target for treatment and recurrence prevention in MDD.

Association between function and structure of the triple network and catechol-O-methyltransferase val158met polymorphism in the first episode schizophrenia

BackgroundSubcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. White matter hyperintensities (WMH) secondary to SIVCI often result in impaired executive function. Cognitive reserve is a property of the brain that allows for preserved cognitive performance given brain injury or disease. In an unpublished cross‐sectional study, we found the strength of intra‐network connectivity in fronto‐executive network (FEN), fronto‐parietal network (FPN) and default mode network (DMN) moderated the relationship between WMH and executive function in older adults with SIVCI. Thus, these networks may be involved in cognitive reserve. Exercise is hypothesized to contribute to cognitive reserve. We explored the effect of resistance training (RT) on functional connectivity (FC) in FEN, FPN, and DMN, as well as executive function, in older adults with SIVCI.MethodIn a 12‐month randomized controlled trial that randomized adults with SIVCI to either 2x/week of RT or 2x/week of balance and tone training (BAT; control). Resting‐state functional MRI was collected from a subset of 29 participants (RT = 14; BAT = 15) at baseline and trial completion. FC of FEN, FPN, and DMN was quantified using priori‐selected region‐of‐interest masks. Executive function was measured by Trail Making Test (TMT), Digit Symbol Substitution Test (DSST) and Stroop Test (ST). Analysis of covariance was conducted to compare differences in group means of intra‐network FC of FEN, FPN and DMN and executive function tests performance at trial completion, with baseline outcome scores as covariate. Pearson correlations were computed to determine whether changes in executive performance between baseline and trial completion were related to changes in FC in the RT group.ResultAt trial completion, there were no significant between‐group differences in intra‐network FC of FEN, FPN and DMN. RT significantly improved ST performance (estimated mean change[95%CI]: ‐11.322[‐22.366, ‐0.277], p = 0.045) compared with BAT; there were no significant between‐group differences in TMT and DSST. Within RT group, improved ST performance was significantly correlated with increased intra‐network FC of FEN (r = ‐0.697, p = 0.006).ConclusionRT‐induced improvement in ST performance was associated with increased intra‐network FC of FEN. More research is needed to determine whether exercise training has an effect on the neural correlates of cognitive reserve.

Network-specific effects of age and in-scanner subject motion: A resting-state fMRI study of 238 healthy adults