Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis.

ObjectiveTo investigate monoaminergic network abnormalities in patients with multiple sclerosis (MS) according to their fatigue and depressive status through a positron emission tomography (PET)-based constrained independent component analysis (ICA) on...

Fatigue is commonly observed in pediatric multiple sclerosis (pedMS) patients, but its underlying mechanisms remain largely unexplored. We evaluated whether resting-state (RS) functional connectivity (FC) abnormalities in monoaminergic networks contributed to explain fatigue in pedMS. Fifty-five pedMS and twenty-three matched healthy controls (HC) underwent clinical and RS functional MRI assessment. Patients with Fatigue Severity Scale (FSS) score ≥ 4 were classified as fatigued (F). Patterns of dopamine-, noradrenaline- and serotonin-related RS FC were derived by constrained independent component analysis, using PET atlases for dopamine, noradrenaline, and serotonin transporters obtained in HCs' brain. Compared to non-fatigued (NF)-pedMS patients and HC, F-pedMS patients (15/55, 27.3%) showed decreased dopamine-related RS FC in the right postcentral gyrus. They also showed decreased dopamine-related RS FC in the left insula vs. HC and increased dopamine-related RS FC in the left middle temporal gyrus and cerebellum (lobule VI) vs. NF patients. In the noradrenaline-related network, F-pedMS patients showed decreased RS FC in the left superior parietal lobule and increased RS FC in the right thalamus vs. HC and NF-pedMS. Compared to HC, F-pedMS patients also showed decreased RS FC in the right calcarine cortex and increased RS FC in the right middle frontal gyrus. In the serotonin-related network, F-pedMS patients showed decreased RS FC in the right angular gyrus and increased RS FC in the right postcentral gyrus vs. NF-pedMS patients. In pedMS, fatigue is associated with specific monoaminergic network abnormalities, providing pathological markers for this bothersome symptom and putative targets for its treatment.

Decreased functional connectivity in patients with major depressive disorder and a history of childhood traumatization through experiences of abuse

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

Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity.

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.

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.

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.

Psychosis is linked to aberrant salience or to viewing neutral stimuli as self-relevant, suggesting a possible impairment in self-relevance processing. Psychosis is also associated with increased dopamine in the dorsal striatum, especially the anterior caudate (Kegeles et al., 2010). Critically, the anterior caudate is especially connected to (a) the cortical default mode network (DMN), centrally involved in self-relevance processing, and (b) to a lesser extent, the cortical frontoparietal network (FPN; Choi, Yeo, & Buckner, 2012). However, no previous study has directly examined striatal-cortical DMN connectivity in psychosis risk. In Study 1, we examined resting-state functional connectivity in psychosis risk (n = 18) and control (n = 19) groups between (a) striatal DMN and FPN subregions and (b) cortical DMN and FPN. The psychosis risk group exhibited decreased connectivity between the striatal subregions and the cortical DMN. In contrast, the psychosis risk group exhibited intact connectivity between the striatal subregions and the cortical FPN. Additionally, recent distress was also associated with decreased striatal-cortical DMN connectivity. In Study 2, to determine whether the decreased striatal-cortical DMN connectivity was specific to psychosis risk or was related to recent distress more generally, we examined the relationship between connectivity and distress in individuals diagnosed with nonpsychotic emotional distress disorders (N = 25). In contrast to Study 1, here we found that distress was associated with evidence of increased striatal-cortical DMN connectivity. Overall, the present results suggest that decreased striatal-cortical DMN connectivity is associated with psychosis risk and could contribute to aberrant salience.

Developmental sex differences in resting state functional connectivity of amygdala sub-regions

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.

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.

This study investigates the relationship between gestational age (GA) and resting-state functional connectivity (rsFC) in a cohort of very preterm children at school age, and how these neural patterns relate to cognitive and theory of mind (ToM) performance. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 52 children (GA < 32 weeks, birth weight <1500 g) and independent component analysis was applied to extract the resting-state networks. Results showed that GA was positively associated with rsFC of the precuneus and the paracentral region within the left posterior cerebellar network (lpCER), while negatively associated with rsFC of the insula and putamen within the anterior default mode network (DMN), and with rsFC of the postcentral gyrus within the right frontoparietal network (rFPN). Cognitive and neuropsychological assessments revealed that increased connectivity involving the lpCER correlated with better verbal comprehension, visuospatial ability, fluid reasoning, working memory, and ToM performance. Conversely, increased aDMN connectivity was associated with lower working memory and decreased rFPN connectivity was found associated with lower intelligence quotient. These results underscore the influence of GA on intrinsic brain networks supporting cognitive and socio-cognitive functions, and highlight potential neural markers that could inform targeted intervention strategies for preterm children.

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.