Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model

BackgroundRegional homogeneity (ReHo), a measurement from resting-state functional magnetic imaging (rs-fMRI) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. SIV infected model for detecting the neurological changes with progression was studied.MethodsIn the study, six rhesus macaques infected by simian immunodeficiency virus (SIV) were scanned by resting-state fMRI at the following time points: before SIV inoculation (baseline), 12 weeks and 24 weeks post inoculation (12 wpi, 24 wpi). Meanwhile, the immunological parameters including serum percentage of CD4 + T cell, CD4/CD8 ratio and absolute CD4 + T cell number were measured and analyzed.ResultsIn comparison of baseline, significant decreased ReHo was found in the left superior frontal gyrus, left superior temporal gyrus, left hippocampus, right precuneus, left angular gyrus, and bilateral occipital gyrus; in contrast increased ReHo in putamen at 12 wpi. Moreover, at the time of 24 wpi, decreased ReHo was observed in the right postcentral gyrus, left precentral gyrus, posterior cingulated gyrus and thalamus, while ReHo was increased in the left putamen, hippocampus, left anterior cingulated cortex and precentral cortex. The correlation analysis revealed that ReHo in the superior frontal gyrus showed negative association with CD4/CD8 ratio and positive with absolute CD4 + T cell number. The correlation analysis showed that percentage of CD4 + was correlated with the ReHo values in right middle frontal gyrus, bilateral thalamus and amygdala positively; negative relationship with left putamen, left superior frontal gyrus, left superior and middle temporal gyrus.ConclusionThe study first indicates that hippocampus, putamen, frontal and occipital lobe were impaired by using rs-fMRI and correlated with immunological parameters. Thus, ReHo value can be utilized as a noninvasive biomarker of spontaneous brain activity changes caused by the progression of neurological impairments.     

以功能性核磁共振造影初探10Hz调制激光针灸刺激所引发人类大脑皮质的活化现象(英文)

使用10 Hz调制的低功率激光针灸刺激探究大脑皮质反应.以功能性核磁共振造影技术探讨当激光针灸刺激左脚涌泉穴(K1)时,大脑可能产生的反应机制.研究发现调制激光针灸所引发显著的大脑活化反应,包括右额叶中央前回、右额叶上回、左额叶中央前回、左顶叶中央后回、左侧下部顶叶、左小脑舌前叶、左海马旁回和左小脑山顶等区域.安慰剂组实验并没有发现在脑部有任何活化反应,大多数反应区域所涉及功能与记忆、注意力及自我意识等有关联.结果显示出调制激光针灸的大脑血液动力学反应,并隐含此反应机制不只是依据传入感觉信息处理,而且还有着随外部刺激的变化而有所改变的血液动力学性质.     

Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI

Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging and frequently represents the prodromal phase of Alzheimer's disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group-independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed an increased DMN activity in middle cingulate cortex, medial prefrontal cortex and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus and right angular gyrus. Although MTL volume difference between the two groups was not statistically significant, a decreased activity in left MTL was observed for the aMCI group. Positive correlations between the DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture that correlate with memory function, even before significant MTL atrophy is detectable by structural MRI.     

脑功能激活光诱发机理小世界网络分析研究

研究光诱发和静息两种状态下的脑功能网络的信息传输枢纽、网络聚合能力和信息传输的最小路径的差异性。采用小世界网络理论对脑功能网络进行建模,通过对脑功能网络连接度、簇系数和最小路径进行分析,得出光诱发状态下的信息传输重要枢纽为岛叶、后扣带回功能区;丘脑、海马两处功能网络有较大聚合能力。光诱发过程从额上回经颞中回传输到枕中回。静息状态下的信息传输重要枢纽为楔叶、舌回;中央旁小叶、颞上回脑功能网络有较大聚合能力。静息状态下的左半区最佳信息传输路径为左额上回、左颞中回、右楔叶最后到左枕中回;右脑半区的为右额上回、右前扣带回、左枕下回最后到右枕中回。光诱发状态与静息状态的最佳传输路径有明显的区别。     

结合局部一致性和低频振幅探究躯体症状障碍患者大脑自发性活动的改变

躯体症状障碍（somatic symptom disorder,SSD）是一种常见的医学疾病,致病原因涉及生物学、心理学及社会因素.目前关于SSD的神经机制知之甚少.本研究通过静息态功能磁共振成像（functional magnetic resonance imaging,fMRI）,结合低频振幅（amplitudes of low-frequency fluctuation,ALFF）和局部一致性（regional homogeneity,ReHo）分析探究45位SSD患者和43位健康对照自发性脑活动特征的区别.结果发现：与对照组相比,SSD患者右侧扣带回中部的ReHo值显著升高,而右侧楔前叶、左侧颞下回延伸到左侧颞中回和左侧海马旁回、右侧脑桥的ReHo值显著降低.同时,SSD患者扣带回中部延伸至左侧额中回、右侧脑岛延伸至右侧额下回、左侧额中回延伸至左侧前扣带回的ALFF值均显著升高.这些脑区的脑功能与自我加工、情绪处理、身体知觉等有关,与SSD发病机制有重要联系.     

Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance

Functional brain imaging studies have identified a set of brain areas typically activated during cognitive tasks (task-positive brain areas) and another set of brain areas typically deactivated during cognitive tasks (task-negative brain areas). Negative correlations, or anticorrelations, between task-positive and task-negative brain areas have been reported at rest. Furthermore, the strength of these anticorrelations appears to be related to cognitive function. However, studies examining anticorrelations have typically employed global regression or similar analysis steps that force anticorrelated relationships to exist between brain areas. Therefore the validity of these findings has been questioned. Here we examine anticorrelations between a task-negative region in the medial frontal gyrus/anterior cingulate cortex and dorsolateral prefrontal cortex, a classic task-positive area, using an analysis that does not include global regression. Instead, we control for whole-brain correlations in the group-level analysis. Using this approach, we demonstrate that the strength of the functional connection between the medial frontal cortex and the dorsolateral prefrontal cortex is related to cognitive function and that this relationship is not an artifact of global regression.     

Left inferior frontal gyrus is critical for response inhibition

Background  

Lesion studies in human and non-human primates have linked several different regions of prefrontal cortex (PFC) with the ability to inhibit inappropriate motor responses. However, recent functional neuroimaging studies have specifically implicated right inferior PFC in response inhibition. Right frontal dominance for inhibitory motor control has become a commonly accepted view, although support for this position has not been consistent. Particularly conspicuous is the lack of data on the importance of the homologous region in the left hemisphere. To investigate whether the left inferior frontal gyrus (IFG) is critical for response inhibition, we used neuropsychological methodology with carefully characterized brain lesions in neurological patients.     

c-MycERTAM transgene silencing in a genetically modified human neural stem cell line implanted into MCAo rodent brain

Background

To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients.

Results

Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas.

Conclusion

The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.     

Diffusion-weighted imaging features of brain in obesity

PURPOSE: Obesity is characterized by an altered distribution of body fluid. However, distribution of fluid (extracellular/intracellular) in brain tissues has not been studied in obese subjects yet. The purpose of this study was to detect possible brain diffusion changes especially in satiety and hunger related centers in obese subjects by diffusion weighted imaging (DWI). METHODS: Conventional MRI and DWI of the brain was obtained from 81 obese patients (obese=68, morbid obese=13) and 29 age-matched, nonobese. The apparent diffusion coefficient (ADC) values were calculated in hypothalamus; amygdala; hippocampal gyrus; thalamus; insula; cingulate gyrus; orbitofrontal, dorsomedial and dorsolateral frontal, middle temporal and occipital cortex; cerebellum; midbrain and corpus striatum. RESULTS: The ADC values of hypothalamus, hippocampal gyrus, amygdala, insula, cerebellum and midbrain were significantly increased in patients (n:81) when compared to nonobese subjects. The ADC values of thalamus, hippocampal gyrus, amygdala, orbitofrontal, occipital, dorsolateral and middle temporal cortex, insula and midbrain were significantly increased in morbid obese when compared to nonobese subjects. The ADC values of orbitofrontal and occipital cortex were significantly higher in morbid obese than the values in the obese. The body mass index positively correlated with ADC values of amygdala, insula, orbitofrontal and middle temporal cortex. CONCLUSION: We observed increased ADC values of distinct locations related to satiety and hunger that suggest altered fluid distribution and/or vasogenic edema in obese subjects. Awareness of this abnormalities in brain tissue composition/function in obesity may contribute to better understanding of the underlying mechanisms.     

Fractional amplitude of low-frequency fluctuation changes in monkeys with spinal cord injury: A resting-state fMRI study

Purpose

Although functional magnetic resonance imaging (fMRI) has revealed that spinal cord injury (SCI) causes anomalous changes in task-induced brain activation, its effect during the resting state remains unclear. The aim of this study is to explore the changes of the brain resting-state function in non-human primates with unilateral SCI.

Materials and methods

Eleven adult female rhesus monkeys were subjected to resting-state fMRI: five with unilateral thoracic SCI and six healthy monkeys, to obtain the fractional amplitude of low-frequency fluctuations (fALFF) of the blood oxygenation level-dependent (BOLD) contrast signal to determine the influence of SCI on the cerebral resting-state function.

Results

The SCI-induced fALFF vary significantly in several encephalic regions, including the left cerebellum, the left thalamus, the right lateral geniculate nucleus, the right superior parietal lobule, and the posterior cingulate gyrus.

Conclusion

Analysis of the resting-state fMRI provides evidence of abnormal spontaneous brain activations in primates with SCI, which may help us understand the pathophysiologic mechanisms underlying the changes in neural plasticity in the central nervous system after SCI.     

Enhancing the effect of repetitive I-wave paired-pulse TMS (iTMS) by adjusting for the individual I-wave periodicity

Background

The aberrant pyramidal tract (APT) refers to the collateral pathway of the pyramidal tract (PT) through the medial lemniscus in the midbrain and pons. Using diffusion tensor tractography (DTT), we investigated the characteristics of the APT in comparison with the PT in the normal human brain.

Results

In thirty-four (18.3%, right hemisphere: 20, left hemisphere: 14) of the 186 hemispheres, the APTs separated from the PT at the upper midbrain level, descended through the medial lemniscus from the midbrain to the pons, and then rejoined with the PT at the upper medulla. Nine (26.5%) of the 34 APTs were found to originate from the primary somatosensory cortex without a primary motor cortex origin. Values of fractional anisotropy (FA) and tract volume of the APT were lower than those of the PT (P < 0.05); however, no difference in mean diffusivity (MD) value was observed (P > 0.05).

Conclusion

We found that the APT has different characteristics, including less directionality, fewer neural fibers, and less origin from the primary motor cortex than the PT.     

The imaging appearance of Creutzfeldt-Jakob disease caused by the E200K mutation

The E200K mutation on chromosome 20 can cause familial Creutzfeldt-Jakob disease (CJD). Patients with this mutation are clinically similar to those with sporadic CJD, but their imaging features are not well documented. We report here the quantitative and qualitative evaluation of the magnetic resonance (MR) imaging characteristics of this unique group of patients using three-dimensional spoiled gradient recalled (SPGR) echo images, diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurements, MR spectroscopy and a fluid-attenuated inversion recovery (FLAIR) sequence. The SPGR and ADC data were analyzed with SPM99. ANCOVA and regression models were used for a region-of-interest (ROI) analysis of ADC and metabolic ratios. CJD patients had a decreased fraction of gray matter and an increased fraction of cerebrospinal fluid (P=.001) in the cortex and cerebellum and increased ADC values in the cortex (P<.001). Focal decreases of ADC were found in the putamen via ROI analysis (548+/-83 vs. 709+/-9 microm(2)/s, P=.02). N-acetyl aspartate (NAA) was generally reduced, with the NAA/Cho ratio lowest in the cingulate gyrus. Qualitative assessment revealed hyperintensities on FLAIR, DWI or both in the putamen (three out of four patients), caudate (three out of four patients) and thalamus. These results provide a framework for future study of patients with genetically defined familial CJD.     

Voxel- and atlas-based analysis of diffusion tensor imaging may reveal focal axonal injuries in mild traumatic brain injury -- comparison with diffuse axonal injury

Background

The diagnosis and management of mild traumatic brain injury (MTBI) continue to be subjects of debate, with varying opinions regarding the extent to which tissue-based impairments versus the impacts of other stressors cause ongoing disability. Detecting areas of the brain with abnormalities that can explain symptoms and behavior in patients with MTBI is important in order to confirm the diagnosis of MTBI.

Methods

In this study, we calculated diffusion maps from results of diffusion tensor imaging (DTI) performed in an apparently healthy control group. We then compared these maps with those of patients with MTBI (MTBI group) or diffuse axonal injury (DAI group). All diffusion maps were normalized to the International Consortium for Brain Mapping atlas for atlas-based analysis and were segmented and normalized by the Diffeomorphic Anatomical Registration Through Exponentiated Lie tool in SPM8 to reduce misregistration.

Results

All diffusion measures in the DAI group were lower than in the control group. There were significant differences in the body and splenium of the corpus callosum, fornix and right cerebral peduncle in the DAI group compared with the control group (P<.001). The MTBI group had higher axial diffusivity than the control group in the right corticospinal tract, left medial lemniscus, left inferior cerebellar peduncle, bilateral anterior limb of the internal capsule, right anterior corona radiata, bilateral cingulum (cingulate gyrus) and left superior frontooccipital fasciculus (P<.05).

Conclusions

Voxel- and atlas-based analysis of DTI might suggest that patients with MTBI have focal axonal injury and that the pathophysiology is significantly different from that of DAI. These findings will help in the diagnosis of patients with MTBI.     

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

Background

Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal.

Results

We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal, medial prefrontal areas and hypothalamic autonomic centers were also connected with the amygdala.

Conclusions

Descending pathways from orbitofrontal and medial prefrontal cortices, which are also linked with the amygdala, provide the means for speedy influence of the prefrontal cortex on the autonomic system, in processes underlying appreciation and expression of emotions.

     

Hippocampal CA1/subiculum-prefrontal cortical pathways induce plastic changes of nociceptive responses in cingulate and prelimbic areas

Background  

Projections from hippocampal CA1-subiculum (CA1/SB) areas to the prefrontal cortex (PFC), which are involved in memory and learning processes, produce long term synaptic plasticity in PFC neurons. We examined modifying effects of these projections on nociceptive responses recorded in the prelimbic and cingulate areas of the PFC.     

Exploratory voxel-based analysis of diffusion indices and hemispheric asymmetry in normal aging

Age-related microstructural changes in brain white matter can be studied by utilizing indices derived from diffusion tensor imaging (DTI): apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The objective of this study is to examine alterations in FA and ADC by employing exploratory voxel-based analysis (VBA) and region(s) of interest (ROI)-based analysis. A highly nonlinear registration algorithm was used to align the ADC and FA image volumes of different subjects to perform accurate voxel-level statistics for two age groups, as well as for hemispheric asymmetry for both age groups. VBA shows significant age-related decline in FA with frontal predominance (frontal white matter, and genu and anterior body of the corpus callosum), superior portions of a splenium and highly oriented fibers of the posterior limb of the internal capsule and the anterior and posterior limbs of the external capsule. Hemispheric asymmetry of FA, as assessed by VBA, showed that for the young-age group, significant right-greater-than-left asymmetry exists in the genu, splenium and body of the corpus callosum and that left-greater-than-right asymmetry exists in the anterior limb of the external capsule and in the posterior limb of the internal capsule, thalamus, cerebral peduncle and temporal-parietal regions. VBA of the hemispheric asymmetry of the middle-age group revealed much less asymmetry. Regions showing age-related changes and hemispheric asymmetry from VBA were, for a majority of the findings, in conformance with ROI analysis and with the known pattern of development and age-related degradation of fiber tracks. The study shows the feasibility of the VBA of DTI indices for exploratory investigations of subtle differences in population cohorts, especially when findings are not localized and/or known a priori.     

Blockade of stress-induced increase of glutamate release in the rat prefrontal/frontal cortex by agomelatine involves synergy between melatonergic and 5-HT2C receptor-dependent pathways

Background

Agomelatine is a melatonergic receptor agonist and a 5HT_2C receptor antagonist that has shown antidepressant efficacy. In order to analyze separately the effect of the two receptorial components, rats were chronically treated with agomelatine, melatonin (endogenous melatonergic agonist), or S32006 (5-HT_2C antagonist), and then subjected to acute footshock-stress.

Results

Only chronic agomelatine, but not melatonin or S32006, completely prevented the stress-induced increase of glutamate release in the rat prefrontal/frontal cortex.

Conclusions

These results suggest a potential synergy between melatonergic and serotonergic pathways in the action of agomelatine.     

MRS study of the effects of minocycline on markers of neuronal and microglial integrity in ALS

Objective

Magnetic resonance spectroscopy (MRS) allows to monitor brain metabolites noninvasively in amyotrophic lateral sclerosis (ALS). The objective of this study was to use MRS to monitor the effect of minocycline treatment (200 mg/day) over a short period (6 weeks) on the brain metabolites in the precentral gyrus and brainstem in newly diagnosed ALS patients.

Methods

Ten ALS patients (not on riluzole treatment) were recruited and submitted to single-voxel proton MRS longitudinal examinations (1) before minocycline treatment, (2) 3 weeks and (3) 6 weeks after initiation of treatment.

Results

Results did not show the expected decrease of N-acetylaspartate/creatine (NAA/Cr) in the precentral gyrus, and an increased NAA/Cr ratio in the brainstem suggested neuronal recovery. The myo-inositol (mI)/Cr ratio was unchanged in the precentral gyrus, but increased in the brainstem, indicating a glial reaction.

Conclusions

MRS results suggest that minocycline treatment could be beneficial in the early stages of ALS.     

Quantification of the power changes in BOLD signals using Welch spectrum method during different single-hand motor imageries

Motor imagery is an experimental paradigm implemented in cognitive neuroscience and cognitive psychology. To investigate the asymmetry of the strength of cortical functional activity due to different single-hand motor imageries, functional magnetic resonance imaging (fMRI) data from right handed normal subjects were recorded and analyzed during both left-hand and right-hand motor imagery processes. Then the average power of blood oxygenation level-dependent (BOLD) signals in temporal domain was calculated using the developed tool that combines Welch power spectrum and the integral of power spectrum approach of BOLD signal changes during motor imagery. Power change analysis results indicated that cortical activity exhibited a stronger power in the precentral gyrus and medial frontal gyrus with left-hand motor imagery tasks compared with that from right-hand motor imagery tasks. These observations suggest that right handed normal subjects mobilize more cortical nerve cells for left-hand motor imagery. Our findings also suggest that the approach based on power differences of BOLD signals is a suitable quantitative analysis tool for quantification of asymmetry of brain activity intensity during motor imagery tasks.