Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

Functional connectivity of the attention networks is altered and relates to neuropsychological outcomes in children with prenatal alcohol exposure

Cognitive and functional brain alterations can occur in children with prenatal alcohol exposure (PAE). We examined the functional connectivity (FC) among regions within and between attention networks, and whether inter- and intranetwork FC moderated cognition in children with PAE (n = 37; age 12.8 ± 2.8 years) and nonexposed controls (n = 40; age 13.2 ± 2.8 years). Participants completed standardized attention and executive functioning tasks and resting state functional MRI. Inter- and intra-network FC and graph-theoretical metrics were calculated among attention network regions. Relative to controls, PAE was associated with reduced FC between the left temporoparietal junction and left ventral frontal cortex and anterior insula/frontal operculum (aI/fO), and between the left intraparietal sulcus and bilateral aI/fO. PAE was associated with increased FC between the right precuneus and intraparietal lobes, the right anterior prefrontal cortex and left ventral frontal cortex and aI/fO, and the left thalamus and dorsal frontal cortex. Graph-theoretical metrics did not differ by group. FC predicted cognitive performance, negatively in the children with PAE and positively in controls. Increased intra-network together with reduced internetwork FC suggests inefficient network specialization and impaired long-range FC among attention network regions after PAE. Results further suggest that those alterations may underlie attention and executive dysfunction in children with PAE.     

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity

Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications.     

Age and sex differences in frontal lobe cerebral oxygenation in older adults—Normative values using novel,scalable technology: Findings from the Irish Longitudinal Study on Ageing (TILDA)

AimsNear-infrared spectroscopy (NIRS) is a non-invasive, easy to apply, optical technology for measuring cerebral blood oxygenation, but there is lack of comprehensive population data to aid interpretation and clinical use. Given the importance of cerebral perfusion in the context of evolving guideline recommendations for more aggressive lowering of blood pressure (BP) in hypertension, even in the oldest old, understanding of normative NIRS values is timely. We estimated normative values of cerebral oxygenation measured by NIRS in a large community-dwelling population sample of adults aged > = 50 years (n = 3110). We hypothesized that measurements would be attenuated by cardiovascular risk factors.MethodsData from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA) was utilized. Frontal lobe cerebral oxygenation was continuously measured via a Portalite, while participants rested in the supine position. Beat-to-beat BP was measured simultaneously. Normative data was modelled using generalized additive models for location, scale, and shape (GAMLSS). Multivariate linear regressions were used to examine associations with cardiovascular risk factors.ResultsAll three measures of NIRS (TSI, O2Hb and HHb) declined with increasing age. O2Hb and HHb were significantly lower in males than females. Increased smoking, excess alcohol intake, a higher waist-hip ratio, diabetes, angina, congestive heart failure, transient ischemic attack and total cardiovascular disease burden were all associated with decreased cerebral oxygenation.ConclusionWe present for the first time, normative resting-state NIRS reference data from a large population, which contributes to clinical interpretation of NIRS and advances the use of NIRS as a standard clinical tool.     

Spatiotemporal dynamics of EEG microstates in four- to eight-year-old children: Age- and sex-related effects

The ultrafast spatiotemporal dynamics of large-scale neural networks can be examined using resting-state electroencephalography (EEG) microstates, representing transient periods of synchronized neural activity that evolve dynamically over time. In adults, four canonical microstates have been shown to explain most topographic variance in resting-state EEG. Their temporal structures are age-, sex- and state-dependent, and are susceptible to pathological brain states. However, no studies have assessed the spatial and temporal properties of EEG microstates exclusively during early childhood, a critical period of rapid brain development. Here we sought to investigate EEG microstates recorded with high-density EEG in a large sample of 103, 4–8-year-old children. Using data-driven k-means cluster analysis, we show that the four canonical microstates reported in adult populations already exist in early childhood. Using multiple linear regressions, we demonstrate that the temporal dynamics of two microstates are associated with age and sex. Source localization suggests that attention- and cognitive control-related networks govern the topographies of the age- and sex-dependent microstates. These novel findings provide unique insights into functional brain development in children captured with EEG microstates.     

Effect of scanner acoustic background noise on strict resting-state fMRI

Functional MRI (fMRI) resting-state experiments are aimed at identifying brain networks that support basal brain function. Although most investigators consider a ‘resting-state’ fMRI experiment with no specific external stimulation, subjects are unavoidably under heavy acoustic noise produced by the equipment. In the present study, we evaluated the influence of auditory input on the resting-state networks (RSNs). Twenty-two healthy subjects were scanned using two similar echo-planar imaging sequences in the same 3T MRI scanner: a default pulse sequence and a reduced “silent” pulse sequence. Experimental sessions consisted of two consecutive 7-min runs with noise conditions (default or silent) counterbalanced across subjects. A self-organizing group independent component analysis was applied to fMRI data in order to recognize the RSNs. The insula, left middle frontal gyrus and right precentral and left inferior parietal lobules showed significant differences in the voxel-wise comparison between RSNs depending on noise condition. In the presence of low-level noise, these areas Granger-cause oscillations in RSNs with cognitive implications (dorsal attention and entorhinal), while during high noise acquisition, these connectivities are reduced or inverted. Applying low noise MR acquisitions in research may allow the detection of subtle differences of the RSNs, with implications in experimental planning for resting-state studies, data analysis, and ergonomic factors.     

Resting-state beta and gamma activity in Internet addiction

Internet addiction is the inability to control one's use of the Internet and is related to impulsivity. Although a few studies have examined neurophysiological activity as individuals with Internet addiction engage in cognitive processing, no information on spontaneous EEG activity in the eyes-closed resting-state is available. We investigated resting-state EEG activities in beta and gamma bands and examined their relationships with impulsivity among individuals with Internet addiction and healthy controls. Twenty-one drug-naïve patients with Internet addiction (age: 23.33 ± 3.50 years) and 20 age-, sex-, and IQ-matched healthy controls (age: 22.40 ± 2.33 years) were enrolled in this study. Severity of Internet addiction was identified by the total score on Young's Internet Addiction Test. Impulsivity was measured with the Barratt Impulsiveness Scale-11 and a stop-signal task. Resting-state EEG during eyes closed was recorded, and the absolute/relative power of beta and gamma bands was analyzed. The Internet addiction group showed high impulsivity and impaired inhibitory control. The generalized estimating equation showed that the Internet-addiction group showed lower absolute power on the beta band than did the control group (estimate = − 3.370, p < 0.01). On the other hand, the Internet-addiction group showed higher absolute power on the gamma band than did the control group (estimate = 0.434, p < 0.01). These EEG activities were significantly associated with the severity of Internet addiction as well as with the extent of impulsivity. The present study suggests that resting-state fast-wave brain activity is related to the impulsivity characterizing Internet addiction. These differences may be neurobiological markers for the pathophysiology of Internet addiction.     

Miswiring the brain: Human prenatal Δ9-tetrahydrocannabinol use associated with altered fetal hippocampal brain network connectivity

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.     

基于局部一致性的重度抑郁症患者脑静息态功能磁共振成像研究

目的 采用脑静息态功能磁共振成像(rs-fMRI)局部一致性(ReHo)方法探讨重度抑郁症(MDD)患者脑区自发性活动特征,评价其与抑郁严重程度的相关性.方法 对24例MDD患者和26例相匹配的康对照组(HC)进行rs-fMRI扫描,分析两组ReHo值,将差异显著的脑区内平均ReHo值与HAMD-17评分进行相关性分析.结果 MDD患者较HC组左侧直回、左侧海马、右侧楔前叶、右侧顶上回、左侧顶下缘角回、右侧楔叶ReHo值显著升高;右背外侧前额叶、右侧后扣带回、左侧枕下回、双侧颞下回、右侧颞上回ReHo值降低(P<0.05,Alphasim矫正).Pearson相关分析显示两组差异脑区左侧海马ReHo值与HAMD-17评分呈正相关(r=0.593,P=0.002),右侧后扣带回ReHo值与HAMD-17评分呈负相关(r=-0.431,P=0.035).结论 MDD患者静息态下脑功能损害主要集中于边缘系统及默认网络等多个脑区,且左侧海马与右侧后扣带回局部脑区自发活动的时间同步性与抑郁严重程度存在相关性.ReHo分析可作为抑郁症严重程度评价的潜在生物学标记.