Inhibitory control following perinatal brain injury

Evidence from developmental, lesion, and neuroimaging studies indicates that the prefrontal cortex plays a major role in executive abilities, including inhibitory control. Proficient executive performance, however, relies not only on the integrity of the prefrontal cortex but also on its interactions with other brain regions. In the current study, the authors focused on the effect that early damage to the white matter tracts interconnecting prefrontal and other brain regions has on inhibitory control. Data were collected from 13 children with bilateral spastic cerebral palsy and from a control group of 20 children with no history of neurologic compromise. Converging evidence from 3 separate paradigms is presented that strongly suggests these children experience impairments in inhibitory control. Findings are discussed within the context of current cognitive and neuroanatomical models of inhibition.     

抑郁症的客观判别:基于光学脑成像的静息态功能性连接检测和分析

近年来,基于功能性近红外光谱的静息态功能性连接逐渐用于精神疾病的研究。然而,由功能性近红外光谱得到的静息态功能性连接是否可以用于抑郁症的客观判别仍然是一个未知数。采用42通道的功能性近红外光谱技术,测量28个抑郁症患者和30个健康对照组的8 min前额皮层的自发血液动力活动。在独立成分分析和0.008～0.09 Hz的带通滤波器滤除不相关的成分后,计算前额皮层3个区域(额下回、额中回和额上回)左右半球连接性。然后,选择其中两个有显著性差异的参数作为样本的两个特征维度,并采用线性判别分析和支持向量机对随机抽取的75%样本进行训练,并对剩余的25%样本进行预测。最终均获得73%~74%的预测正确率和83%~87%的辨别率。这个结果支持由功能性近红外光谱技术得到的大脑静息态功能性连接在客观辨别抑郁症患者的可行性和有效性。     

The ontogenetic development of serotonin (5-HT1) receptors in various cortical regions of the rat brain

Summary The distribution of serotonin (5-HT₁) receptors in various cortical regions of the rat brain has been examined during ontogenesis by quantitative autoradiography.An increase in binding site density between the first postnatal day and adult age was observed and could be approximated by a sigmoid shaped (logistic) growth curve. A marked heterochrony in the increase of binding site density is found in the 13 analyzed cortical regions. Binding sites develop earlier in neocortex than in allocortical areas. Fifty pereent of the binding site density of adult age is reached in the motor cortex at the 9th postnatal day, followed by the primary somatosensory cortex one day later, by the medial prefrontal cortex on the 12th day, by the fascia dentata on the 14th day and by the CA1-region on the 20th day. A detailed analysis of the frontal, medial prefrontal and hippocampal regions also shows a heterochrony within these regions. Adult values of binding site densities are also reached at different ages in the various cortical regions. The highest receptor densities were observed in the dorsal subiculum, the lowest in the primary somatosensory cortex.     

Decreased brain coordinated activity in autism spectrum disorders during executive tasks: Reduced long-range synchronization in the fronto-parietal networks

Current theories of brain function propose that the coordinated integration of transient activity patterns in distinct brain regions is the essence of brain information processing. The behavioural manifestations of individuals with autism spectrum disorders (ASD) suggest that their brains have a different style of information processing. Specifically, a current trend is to invoke functional disconnection in the brains of individuals with ASD as a possible explanation for some atypicalities in the behaviour of these individuals. Our observations indicate that the coordinated activity in brains of children with autism is lower than that found in control participants. Disruption of long-range phase synchronization among frontal, parietal and occipital areas was found, derived from magnetoencephalographic (MEG) recordings, in high-functioning children with ASD during the performance of executive function tasks and was associated with impaired execution, while enhanced long-range brain synchronization was observed in control children. Specifically, a more significant prefrontal synchronization was found in control participants during task performance. In addition, a robust enhancement in synchrony was observed in the parietal cortex of children with ASD relative to controls, which may be related to parietal lobe abnormalities detected in these individuals. These results, using synchronization analysis of brain electrical signals, provide support for the contention that brains of individuals with autism may not be as functionally connected as that of the controls, and may suggest some therapeutic interventions to improve information processing in specific brain areas, particularly prefrontal cortices.     

Altered functional brain networks in Prader–Willi syndrome

Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating‐related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting‐state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low‐frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting‐state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre‐/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating. Copyright © 2013 John Wiley & Sons, Ltd.     

Temporal and instantaneous connectivity of default mode network estimated using Gaussian Bayesian network frameworks

By probing its functional anatomy, the default mode network (DMN) can be considered consisting of two interacting hub and non-hub subsystems. The hub subsystem includes posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC) and bilateral inferior parietal cortex (IPC). The non-hub subsystem contains inferior temporal cortex (ITC) and (para) hippocampus (HC). In this study, Gaussian Bayesian Network (BN) and Gaussian Dynamic Bayesian Network (DBN) were applied separately to detect the instantaneous and temporal connection relationship within each and between the two DMN subsystems. It was found that the directional instantaneous interactions between the two subsystems were primarily “from non-hub to hub”. The temporal interactions between hub and non-hub regions, on the other hand, are less presented between the two subsystems. The hub subsystem demonstrated both strong instantaneous and temporal interactions among the hub regions, while the non-hub regions were only strongly inter-connected instantaneously but temporally isolated with each other. In addition, one of the hub regions, PCC, appears to be a confluent node and important in the functional integration within the network.     

Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain

Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1 null mouse embryos by generating a conditional mutation in the NF1 gene using Cre/loxP technology. Introduction of a Synapsin I promoter driven Cre transgenic mouse strain into the conditional NF1 background has ablated NF1 function in most differentiated neuronal populations. These mice have abnormal development of the cerebral cortex, which suggests that NF1 has an indispensable role in this aspect of CNS development. Furthermore, although they are tumor free, these mice display extensive astrogliosis in the absence of conspicuous neurodegeneration or microgliosis. These results indicate that NF1-deficient neurons are capable of inducing reactive astrogliosis via a non-cell autonomous mechanism.     

Dopamine modulates default mode network deactivation in elderly individuals during the Tower of London task

Task-induced deactivation is frequently reported in the ventro-medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), regions considered to belong to the default mode network. To investigate the effect of dopamine on task-induced deactivation, we used positron emission tomography to measure cerebral blood flow during performance of the Tower of London task before and after administration of the dopamine receptor agonist apomorphine in six healthy volunteers (49–66 years old) and six Parkinson disease patients (52–69 years old). Although task-induced deactivation was observed in the vmPFC and PCC in both groups and in both conditions, an inverse correlation between activation and problem complexity was observed in the vmPFC only in the apomorphine condition.     

Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning

During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyrus activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning.     

Rapid treatment-induced brain changes in pediatric CRPS

To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation.     

Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks

Mitochondrial Ca²⁺ uptake influences both brain energy metabolism and neural signaling. Given that brain mitochondrial organelles are distributed in relation to vascular density, which varies considerably across brain regions, we hypothesized different physiological impacts of mitochondrial Ca²⁺ uptake across brain regions. We tested the hypothesis by monitoring brain “intrinsic activity” derived from the resting state functional MRI (fMRI) blood oxygen level dependent (BOLD) fluctuations in different functional networks spanning the somatosensory cortex, caudate putamen, hippocampus and thalamus, in normal and perturbed mitochondrial Ca²⁺ uptake states. In anesthetized rats at 11.7 T, mitochondrial Ca²⁺ uptake was inhibited or enhanced respectively by treatments with Ru360 or kaempferol. Surprisingly, mitochondrial Ca²⁺ uptake inhibition by Ru360 and enhancement by kaempferol led to similar dose‐dependent decreases in brain‐wide intrinsic activities in both the frequency domain (spectral amplitude) and temporal domain (resting state functional connectivity; RSFC). The fact that there were similar dose‐dependent decreases in the frequency and temporal domains of the resting state fMRI‐BOLD fluctuations during mitochondrial Ca²⁺ uptake inhibition or enhancement indicated that mitochondrial Ca²⁺ uptake and its homeostasis may strongly influence the brain's functional organization at rest. Interestingly, the resting state fMRI‐derived intrinsic activities in the caudate putamen and thalamic regions saturated much faster with increasing dosage of either drug treatment than the drug‐induced trends observed in cortical and hippocampal regions. Regional differences in how the spectral amplitude and RSFC changed with treatment indicate distinct mitochondrion‐mediated spontaneous neuronal activity coupling within the various RSFC networks determined by resting state fMRI. Copyright © 2015 John Wiley & Sons, Ltd.     

Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P<0.001), caudate putamen (122%, P=0.002) and nucleus accumbens (170%, P<0.001) compared with controls; while lower but still significant increases of [(3)H]pirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.     

Parkinson's disease involves autophagy and abnormal distribution of cathepsin L

Intrinsic brain activity in a resting state incorporates components of the task negative network called default mode network (DMN) and task-positive networks called attentional networks. In the present study, the reciprocal neuronal networks in the elder group were compared with the young group to investigate the differences of the intrinsic brain activity using a method of temporal correlation analysis based on seed regions of posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC). We found significant decreased positive correlations and negative correlations with the seeds of PCC and vmPFC in the old group. The decreased coactivations in the DMN network components and their negative networks in the old group may reflect age-related alterations in various brain functions such as attention, motor control and inhibition modulation in cognitive processing. These alterations in the resting state anti-correlative networks could provide neuronal substrates for the aging brain.     

Development of the declarative memory system in the human brain

Brain regions that are involved in memory formation, particularly medial temporal lobe (MTL) structures and lateral prefrontal cortex (PFC), have been identified in adults, but not in children. We investigated the development of brain regions involved in memory formation in 49 children and adults (ages 8-24), who studied scenes during functional magnetic resonance imaging. Recognition memory for vividly recollected scenes improved with age. There was greater activation for subsequently remembered scenes than there was for forgotten scenes in MTL and PFC regions. These activations increased with age in specific PFC, but not in MTL, regions. PFC, but not MTL, activations correlated with developmental gains in memory for details of experiences. Voxel-based morphometry indicated that gray matter volume in PFC, but not in MTL, regions reduced with age. These results suggest that PFC regions that are important for the formation of detailed memories for experiences have a prolonged maturational trajectory.     

Abnormal Functional Connectivity Density in Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that occurs in individuals who have experienced life-threatening mental traumas. Previous neuroimaging studies have indicated that the pathology of PTSD may be associated with the abnormal functional integration among brain regions. In the current study, we used functional connectivity density (FCD) mapping, a novel voxel-wise data-driven approach based on graph theory, to explore aberrant FC through the resting-state functional magnetic resonance imaging of the PTSD. We calculated both short- and long-range FCD in PTSD patients and healthy controls (HCs). Compared with HCs, PTSD patients showed significantly increased long-range FCD in the left dorsolateral prefrontal cortex (DLPFC), but no abnormal short-range FCD was found in PTSD. Furthermore, seed-based FC analysis of the left DLPFC showed increased connectivity in the left superior parietal lobe and visual cortex of PTSD patients. The results suggested that PTSD patients experienced a disruption of intrinsic long-range functional connections in the fronto-parietal network and visual cortex, which are associated with attention control and visual information processing.     

Long-range synchronization and local desynchronization of alpha oscillations during visual short-term memory retention in children

Local alpha-band synchronization has been associated with both cortical idling and active inhibition. Recent evidence, however, suggests that long-range alpha synchronization increases functional coupling between cortical regions. We demonstrate increased long-range alpha and beta band phase synchronization during short-term memory retention in children 6–10 years of age. Furthermore, whereas alpha-band synchronization between posterior cortex and other regions is increased during retention, local alpha-band synchronization over posterior cortex is reduced. This constitutes a functional dissociation for alpha synchronization across local and long-range cortical scales. We interpret long-range synchronization as reflecting functional integration within a network of frontal and visual cortical regions. Local desynchronization of alpha rhythms over posterior cortex, conversely, likely arises because of increased engagement of visual cortex during retention.     

Changes in resting connectivity during recovery from severe traumatic brain injury

In the present study we investigate neural network changes after moderate and severe traumatic brain injury (TBI) through the use of resting state functional connectivity (RSFC) methods. Using blood oxygen level dependent functional MRI, we examined RSFC at 3 and 6 months following resolution of posttraumatic amnesia. The goal of this study was to examine how regional off-task connectivity changes during a critical period of recovery from significant neurological disruption. This was achieved by examining regional changes in the intrinsic, or “resting”, BOLD fMRI signal in separate networks: 1) regions linked to goal-directed (or external-state) networks and 2) default mode (or internal-state) networks. Findings here demonstrate significantly increased resting connectivity internal-state networks in the TBI sample during the first 6 months following recovery. The most consistent finding was increased connectivity in both internal and external state networks to the insula and medial temporal regions during recovery. These findings were dissociable from repeat measurements in a matched healthy control sample.     

一重和多重脑震荡大鼠前额叶髓鞘脂蛋白(PLP)的变化

目的:为探索一重(pure cerebral concussion,PCC)和多重脑震荡(multiple cerebral concussion,MCC)后大鼠前额叶中隔断面髓鞘脂蛋白(myelin protein lipoprotein,PLP)分布与表达变化规律。方法:采用自制单摆式机械打击装置复制PCC和MCC大鼠模型,伤后随机分为PCC中1、2、4、8、16和24 d组(n=6),MCC中1、2、4、8、16和24 d组(n=6),另设正常对照组(n=6)。用小鼠抗-PLP单克隆抗体免疫组织化学SP法染色,观察致伤后大鼠中隔断面区PLP表达的动态变化。结果:正常状态下,PLP主要表达于皮质分子层和颗粒层的白质纤维;中隔区核团包括前脑内侧束(Mfb)、斜角带垂直支(VDB)、外侧隔核中间部(LSI)和杏仁核(amygdaloid nucle-us,AN);胼胝体(cc)、纹状体(CPu)和前联合(an)。PCC后多数脑区PLP表达变化无差异;MCC后皮质前额叶分子层、斜角带垂直臂核和纹状体脑区的PLP表达明显下调(P<0.05)。结论:结果提示MCC可能存在损伤累积效应,加重了中隔断面区神经纤维的损伤。     

Chronic mild restraint stress rats decreased CMKLR1 expression in distinct brain region

Inflammation contributes to the pathophysiology of depression. Chemokine-like receptor-1 (CMKLR1) plays an important role both in the development of inflammation and in the mechanism of antidepressant effect of Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs), ecosapeatanolicacid (EPA). The present study was to investigate the modification of CMKLR1 in chronic restraint stress (CRS) rats. CMKLR1 was examined in different brain region from CRS rats by using western blot and quantitative real-time PCR. The CMKLR1 expression in the hippocampus, prefrontal cortex and cerebellum was determined on 3, 7, 10 and 21 days of repeated restraint stress and was compared to controls. The results showed that the protein and mRNA level of CMKLR1 in the prefrontal cortex and hippocampus were significantly increased on day 3 and then decreased on day 7, 10 and 21 in the CRS rats. The protein and mRNA level of CMKLR1 in cerebellum was similar to that of control group throughout the whole experiment. Changed expression of brain CMKLR1 is suggested to be involved in the mechanism of depression.     

Increased interhemispheric resting‐state functional connectivity in functional dyspepsia: a pilot study

Recent brain imaging studies have emphasized the role of regional brain activity abnormalities in the pathophysiology of functional dyspepsia (FD). However, whether the functional connectivity between brain regions is changed, especially between the cerebral hemispheres, in patients with FD remains unknown. Thus, the present study aimed to examine the interhemispheric resting‐state functional connectivity (RSFC) changes in patients with FD. Resting‐state functional MRI (fMRI) was performed in 26 patients with FD and in 20 matched healthy controls. An interhemispheric RSFC map was obtained by calculating the Pearson correlation (Fisher Z transformed) between each pair of homotopic voxel time series for each subject. The between‐group difference in interhemispheric RSFC was then examined at global and voxelwise levels separately. The global difference in interhemispheric RSFC between groups was tested using the independent two‐sample t‐test. Voxelwise comparisons were carried out using a permutation‐based nonparametric test, and multiple comparisons across space were corrected using the threshold‐free cluster enhancement (TFCE) method. The results showed that patients with FD had higher global interhemispheric RSFC than healthy controls (p < 0.01). Furthermore, voxelwise analysis revealed that patients with FD had increased interhemispheric RSFC in brain regions including the anterior cingulate cortex, insula and thalamus (p < 0.01, TFCE corrected). Our findings provide preliminary evidence of interhemispheric correlation abnormalities in patients with FD and contribute to a better understanding of the pathophysiology of the disease. Copyright © 2012 John Wiley & Sons, Ltd.