Complex Regional Pain Syndrome Is Associated With Structural Abnormalities in Pain-Related Regions of the Human Brain

Complex regional pain syndrome (CRPS) is a chronic condition that involves significant hyperalgesia of the affected limb, typically accompanied by localized autonomic abnormalities and frequently by motor dysfunction. Although central brain systems are thought to play a role in the development and maintenance of CRPS, these systems have not been well characterized. In this study, we used structural magnetic resonance imaging to characterize differences in gray matter volume between patients with right upper extremity CRPS and matched controls. Analyses were carried out using a whole brain voxel-based morphometry approach. The CRPS group showed decreased gray matter volume in several pain-affect regions, including the dorsal insula, left orbitofrontal cortex, and several aspects of the cingulate cortex. Greater gray matter volume in CRPS patients was seen in the bilateral dorsal putamen and right hypothalamus. Correlation analyses with self-reported pain were then performed on the CRPS group. Pain duration was associated with decreased gray matter in the left dorsolateral prefrontal cortex. Pain intensity was positively correlated with volume in the left posterior hippocampus and left amygdala, and negatively correlated with the bilateral dorsolateral prefrontal cortex. Our findings demonstrate that CRPS is associated with abnormal brain system morphology, particularly pain-related sensory, affect, motor, and autonomic systems.PerspectiveThis paper presents structural changes in the brains of patients with CRPS, helping us differentiate CRPS from other chronic pain syndromes and furthering our understanding of this challenging disease.     

Cortical thickness correlates of pain and temperature sensitivity

It is well established that there is individual variability in pain and temperature sensitivity. Functional brain imaging studies have found that interindividual heat pain variability correlates with brain activity in sensory and pain modulation areas. Thus, it is possible that these individual differences are associated with variability in gray matter thickness of cortical regions involved in thermoreception and pain. To test this, we investigated the relationship between thermal thresholds and cortical thickness in 80 healthy subjects. Subjects underwent a psychophysical session to determine their cool detection (CD), warm detection (WD), cold pain (CP), and heat pain (HP) threshold. A high-resolution structural magnetic resonance imaging scan was acquired for each subject. We correlated each threshold measure to cortical thickness of regions associated with thermoreception and pain. The mean (± SD) thresholds were 30.7 °C (± 0.8) for CD, 33.8 °C (± 0.7) for WD, 11.7 °C (± 9.7) for CP, and 45.3 °C (± 2.8) for HP. The brain gray matter analysis revealed a strong correlation between greater thermal and pain sensitivity and cortical thickening of the primary somatosensory cortex. Additionally, greater sensitivity to cool stimuli correlated with cortical thickening in the paracentral lobule, and greater WD correlated with cortical thinning in the anterior midcingulate cortex. We also found that greater HP sensitivity correlated with thickening in the posterior midcingulate cortex and the orbitofrontal cortex. These cortical gray matter correlates of thermal and pain sensitivity provide a neural basis for individual differences in thermal sensitivity.     

Neuroanatomy of adult strabismus: a voxel-based morphometric analysis of magnetic resonance structural scans

Cerebral deficit has been implicated in the genesis of strabismus and in the mechanisms adopted to compensate for the visual disorder. Voxel-based morphometry (VBM) was applied to magnetic resonance images of strabismic adults to detect any abnormal brain anatomy, which could not be easily identified by simple inspection. The gray matter volume in strabismic adults was smaller than that in normal subjects at the areas consistent with the occipital eye field (OEF) and parietal eye field (PEF). However, greater gray matter volume was found in strabismic adults relative to normal controls at the areas consistent with the frontal eye field (FEF), the supplementary eye field (SEF), the prefrontal cortex (PFC), and subcortical regions such as the thalamus and the basal ganglia. These opposite gray matter changes in the visual and the oculomotor processing areas are compatible with a hypothesis of plasticity in the oculomotor regions to compensate for the cortical deficits in the visual processing areas.     

Morphometric gray matter differences of the medial frontal cortex influence the Social Simon Effect

Interacting with others plays a fundamental role in human life. Although several brain regions have recently been associated with complex cognitive control processes, surprisingly little is known about the structural correlates underlying cognitive control processes involved in social interactions. In the present study we used gray matter voxel-based morphometry (VBM) to investigate structural brain correlates of individual performance differences in a social Simon task. Here, two people share a Simon task, which requires each participant to respond to only one of two possible stimuli, rendering the paradigm a go-nogo task, so that a Simon effect - known as the Social Simon Effect (SSE) - is observable across both participants. Using a whole brain approach, we found that inter-individual differences in the SSE are negatively correlated with gray matter (GM) volume of the medial frontal cortex (MFC). The present data indicate that individuals with larger MFC GM volume were those with better conflict resolution in a social Simon task and vice versa. This brain-behavior relationship between cognitive control processes and individual GM volume differences might help to improve our understanding of social interactions in joint task performance.     

Verbal episodic memory impairment in Alzheimer's disease: a combined structural and functional MRI study

Anatomical and functional MRI images were acquired in a group of healthy elderly subjects (n = 11) and a group of patients diagnosed with probable Alzheimer's disease, from mild to moderate severity (n = 8). During functional sessions, verbal episodic Encoding and Recognition tasks were presented to subjects. Both groups were compared in terms of gray matter volume and cerebral activation. Furthermore, in the AD group, correlations between hippocampal gray matter volume and whole-brain activations were examined. When compared to healthy controls, AD patients presented significant gray matter atrophy as well as reduced activations during Encoding and Recognition in the medial temporal lobes and inferior parietal/superior temporal associative areas. In the same regions, the fMRI activity elicited by the Recognition task was positively correlated with hippocampal gray matter volume. Moreover, an increase of left prefrontal activity during Encoding and Recognition was observed in AD patients relative to controls and was correlated with memory performance. This additional activity elicited by episodic memory processes was not found to correlate with the degree of medial temporal atrophy in our group of patients. Our study shows that function in brain regions critical to episodic memory is altered in AD. During episodic Recognition, these functional changes may closely correlate with the progressive structural changes observed in the hippocampal region.     

膝骨性关节炎患者脑结构和功能变化的多模态MRI

目的  联合基于体素的形态学测量（VBM）技术和静息态功能磁共振成像（rs-fMRI）技术探究膝骨性关节炎（KOA）患者静息状态下脑灰质体积、脑神经元活动强度及基于种子点的功能连接强度改变,综合分析KOA相关异常脑网络。方法  前瞻性收集30例KOA患者（KOA组）及30例健康人（HC组）的3D高分辨率T1WI像和rs-fMRI图像,采用VBM、低频振幅、功能连接3种方法分析两组间脑灰质结构和功能数据差异。结果  与HC组相比,KOA组双侧梭状回、右侧颞中回低频振幅值增高,右侧楔前叶、右侧内侧前额叶皮质、左侧额中回低频振幅值减低（体素水平P<0.005,团块水平P<0.05）;右侧楔前叶、右侧顶下小叶、右侧初级视觉皮层、左侧颞中回、左侧中央后回灰质体积减小（体素水平P<0.002,团块水平P<0.05）;以右侧楔前叶为种子点,与右侧颞中回的功能连接增强,与左侧前扣带回、左侧背外侧前额叶皮质的功能连接降低（体素水平P<0.005,团块水平P<0.05）。结论  KOA患者感知皮层系统及联合皮层系统阵营均存在血氧水平依赖信号及灰质微结构的改变且有重叠,主要涉及视觉网络、感觉运动网络、默认状态网络、执行控制网络内及默认状态网络、执行控制网络、突显网络的部分脑区间,这可能提示KOA患者不仅处于慢性疼痛的病理状态,还伴有信息整合、注意力控制、情绪反应、情感解读等功能活动的异常。     

β-Amyloid affects frontal and posterior brain networks in normal aging

Although deposition of β-amyloid (Aβ), a pathological hallmark of Alzheimer's disease (AD), has also been reported in cognitively intact older people, its influence on brain structure and cognition during normal aging remains controversial. Using PET imaging with the radiotracer Pittsburgh compound B (PIB), structural MRI, and cognitive measures, we examined the relationships between Aβ deposition, gray matter volume, and cognition in older people without AD. Fifty-two healthy older participants underwent PIB-PET and structural MRI scanning and detailed neuropsychological tests. Results from the whole-brain voxel-based morphometry (VBM) analysis revealed that gray matter volume in the left inferior frontal cortex was negatively associated with amyloid deposition across all participants whereas reduced gray matter volume was shown in the posterior cingulate among older people with high amyloid deposition. When gray matter density measures extracted from these two regions were related to other brain regions by applying a structural covariance analysis, distinctive frontal and posterior brain networks were seen. Gray matter volume in these networks in relation to cognition, however, differed such that reduced frontal network gray matter volume was associated with poorer working memory performance while no relationship was found for the posterior network. The present findings highlight structural and cognitive changes in association with the level of Aβ deposition in cognitively intact normal elderly and suggest a differential role of Aβ-dependent gray matter loss in the frontal and posterior networks in cognition during normal aging.     

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.     

Development of attentional networks: an fMRI study with children and adults

Data on the development of the attentional systems remain scarce. We used structural and event-related functional magnetic resonance imaging to investigate differences in the neural mechanisms associated with alerting, reorienting, and executive control of attention between children (ages 8 to 12 years) and adults, while controlling for effects of performance and brain morphology. Behaviorally, children exhibited a numerically smaller alerting effect and significantly larger invalidity (reorienting) and interference (executive control of attention) effects. Neurally, children showed significantly reduced brain activation in a priori defined regions-of-interest in right-sided frontal-midbrain regions during alerting, in the right-sided temporo-parietal junction during reorienting of attention, and in the dorsolateral prefrontal cortex during executive control of attention. In addition, children activated significantly more brain regions outside the a priori defined regions-of-interest, such as the superior frontal gyrus during reorienting and the superior temporal gyrus during executive control of attention. Functional group differences overlapped with structural group differences in gray matter volume in particular within the frontopolar areas. The data suggest that there is a transition from functional yet immature systems supporting attentional functions in children to the more definitive adult networks and that the differences observed may reflect both developmental changes in cognitive strategies and morphology.     

Distinct mechanisms of altered brain activation in patients with multiple sclerosis

Cerebral reorganization may limit the effects of central nervous system tissue damage on cognition in patients with multiple sclerosis (MS). This study investigated fMRI activation patterns in patients with relapsing-remitting MS and healthy control subjects during performance of a delayed recognition task. As intended, fMRI task performance was similar in the MS and the control group, whereas neuropsychological testing revealed reduced performance in the patient group on the Paced Serial Addition Test, a reference task for the assessment of cognitive function in MS. Patients overall showed more activation in left posterior parietal cortex than healthy control subjects. Global gray matter atrophy in the patient group was associated with low PASAT scores. In a multiple regression analysis including white matter lesion load and gray matter atrophy as covariates, PASAT performance correlated with activation in left posterior parietal cortex and right anterior midfrontal gyrus, indicating a reallocation of neuronal resources to help preserve function. Global gray matter atrophy correlated with activation in bilateral prefrontal cortex, dorsal ACC and left posterior parietal cortex and, furthermore, was associated with a low degree of deactivation in rostral ACC, suggesting neural inefficiency and consistent with a reduced capacity to modulate between frontoparietal task-associated activation and 'default network' activity. The current study provides evidence that altered brain activation in MS patients has two distinct components, one related to compensatory processes and one to neural inefficiency associated with tissue damage.     

Unraveling the Effects of Plasticity and Pain on Personality

Chronic pain resulting from physical stressors is often accompanied by psychological disorders such as depression. Although depressive disorders are associated with changes in brain anatomy, it remains unknown if changes in brain anatomy associated with increased state depression levels also occur in patients with chronic pain. When individuals are experiencing physical stressors such as ongoing pain, depressive personality traits may predispose them to develop depressive states. The aim of this study was to use brain morphometry to determine the interaction among chronic pain, state and trait depression, and regional brain structure. We investigated regional gray matter volume in 42 chronic pain patients and 35 controls using voxel-based morphometry of T1-weighted anatomical images. Significant relationships between regional gray matter volume and state or trait depressive values were determined. In chronic pain patients, state depression scores were significantly correlated to subtle changes in the thalamus and the cingulate, dorsolateral prefrontal, and hippocampal cortices. These same brain regions were also significantly correlated to trait depressive scores. Unexpectedly, gray matter volumes in these regions were not correlated to trait depressive scores in healthy controls. Because trait depressive values were not correlated to gray matter in controls, but were so in chronic pain patients, these data strongly suggest that subtle changes in brain anatomy can evoke changes in individuals' trait depression values. If these regional gray matter changes are severe enough, changes in an individual's personality trait may result.     

Inter-individual differences in empathy are reflected in human brain structure

Empathy is a multi-faceted concept consisting of our ability not only to share emotions but also to exert cognitive control and perspective taking in our interactions with others. Here we examined whether inter-individual variability in different components of empathy was related to differences in brain structure assessed using voxel-based morphometry. Following a magnetic resonance imaging (MRI) scan, participants completed the Interpersonal Reactivity Index (IRI). Multiple regression was then used to assess the relationship between individual differences in grey matter volume and individual differences in empathy traits. We found that individual differences in affective empathic abilities oriented towards another person were negatively correlated with grey matter volume in the precuneus, inferior frontal gyrus, and anterior cingulate. Differences in self-oriented affective empathy were negatively correlated with grey matter volume of the somatosensory cortex, but positively correlated with volume in the insula; cognitive perspective taking abilities were positively correlated with grey matter volume of the anterior cingulate; and the ability to empathise with fictional characters was positively related to grey matter changes in the right dorsolateral prefrontal cortex. These findings are discussed in relation to neurocognitive models of empathy.     

Ventromedial prefrontal volume predicts understanding of others and social network size

Cognitive abilities such as Theory of Mind (ToM), and more generally mentalizing competences, are central to human sociality. Neuroimaging has associated these abilities with specific brain regions including temporo-parietal junction, superior temporal sulcus, frontal pole, and ventromedial prefrontal cortex. Previous studies have shown both that mentalizing competence, indexed as the ability to correctly understand others' belief states, is associated with social network size and that social group size is correlated with frontal lobe volume across primate species (the social brain hypothesis). Given this, we predicted that both mentalizing competences and the number of social relationships a person can maintain simultaneously will be a function of gray matter volume in these regions associated with conventional Theory of Mind. We used voxel-based morphometry of Magnetic Resonance Images (MRIs) to test this hypothesis in humans. Specifically, we regressed individuals' mentalizing competences and social network sizes against gray matter volume. This revealed that gray matter volume in bilateral posterior frontal pole and left temporoparietal junction and superior temporal sucus varies parametrically with mentalizing competence. Furthermore, gray matter volume in the medial orbitofrontal cortex and the ventral portion of medial frontal gyrus, varied parametrically with both mentalizing competence and social network size, demonstrating a shared neural basis for these very different facets of sociality. These findings provide the first fine-grained anatomical support for the social brain hypothesis. As such, they have important implications for our understanding of the constraints limiting social cognition and social network size in humans, as well as for our understanding of how such abilities evolved across primates.     

An fMRI Investigation of Cortical Contributions to Spatial and Nonspatial Visual Working Memory

The experiments presented in this report were designed to test the hypothesis that visual working memory for spatial stimuli and for object stimuli recruits separate neuronal networks in prefrontal cortex. We acquired BOLD fMRI data from subjects while they compared each serially presented stimulus to the one that had appeared two or three stimuli previously. Three experiments failed to reject the null hypothesis that prefrontal cortical activity associated with spatial working memory performance cannot be dissociated from prefrontal cortical activity associated with nonspatial working memory performance. Polymodal regions of parietal cortex (inferior and superior parietal lobules), as well as cortex surrounding the superior frontal sulcus (and encompassing the frontal eye fields), also demonstrated equivalent levels of activation in the spatial and object conditions. Posterior cortical regions associated with the ventral visual processing stream (portions of lingual, fusiform, and inferior temporal gyri), however, demonstrated greater object than spatial working memory-related activity, particularly when stimuli varied only along spatial or featural dimensions. These experiments, representing fMRI studies of spatial and object working memory in which the testing procedure and the stimuli were identical in the two conditions, suggest that domain-specific visual working memory processing may be mediated by posterior regions associated with domain-specific sensory processing.     

Gray matter alterations in visual cortex of patients with loss of central vision due to hereditary retinal dystrophies

In patients with central visual field scotomata a large part of visual cortex is not adequately stimulated. Over time this lack of input could lead to a reduction of gray matter in the affected cortical areas. We used Voxel Based Morphometry to investigate structural brain changes in patients with central scotomata due to hereditary retinal dystrophies and compared their results to those of normal sighted subjects. Additionally we correlated clinical and demographic characteristics like duration of disease, scotoma size, visual acuity, fixation stability and reading speed to the amount of gray matter in whole brain analyses within the patient group. We found a decrease in gray matter around the lesion projection zone in visual cortex of patients in comparison to controls. Gray matter loss along the posterior and middle portions of the calcarine sulcus is also correlated with scotoma size, indicating that indeed the lack of functional input provokes the gray matter alterations. In whole brain regression analyses within the patient group we found an additional cluster in the right superior and middle frontal gyri, slightly anterior to the frontal eye fields, where gray matter correlated positively with fixation stability. This could be regarded as a consequence of oculomotor learning.     

注意缺陷多动障碍患儿脑结构和功能磁共振成像研究

目的使用三维高分辨结构磁共振和静息态功能磁共振成像技术研究注意缺陷多动障碍(attention deficit/hyperactivity disorder,ADHD)儿童的脑部改变,探讨其脑功能改变是否具有结构基础。材料与方法对10例ADHD患儿及10例正常对照组儿童进行全脑扫描,获取高分辨T1加权图像,得到每个被试的灰质及白质体积参数图;获取静息态功能图像,得到低频振幅(amplitude of low frequency fluctuation,ALFF)参数图。采用基于体素的分析方法比较两组被试参数图之间的差别。结果与正常对照组相比,ADHD患儿双侧额中回、中央前回、前扣带皮质、壳核,左侧眶额皮质、尾状核及右侧小脑的灰质体积减小;双侧前额叶白质、胼胝体前部和后部及左侧眶额白质体积减小。在前扣带回、前额叶、尾状核等区域,ADHD患儿存在显著的ALFF的升高,提示自发功能活动更加活跃。结论 ADHD儿童在脑部功能和结构两方面均有异常,且存在相互关联,揭示该疾病的病理机制。     

Correlation among body height, intelligence, and brain gray matter volume in healthy children

A significant positive correlation between height and intelligence has been demonstrated in children. Additionally, intelligence has been associated with the volume of gray matter in the brains of children. Based on these correlations, we analyzed the correlation among height, full-scale intelligence quotient (IQ) and gray matter volume applying voxel-based morphometry using data from the brain magnetic resonance images of 160 healthy children aged 5-18 years of age. As a result, body height was significantly positively correlated with brain gray matter volume. Additionally, the regional gray matter volume of several regions such as the bilateral prefrontal cortices, temporoparietal region, and cerebellum was significantly positively correlated with body height and that the gray matter volume of several of these regions was also significantly positively correlated with full-scale intelligence quotient (IQ) scores after adjusting for age, sex, and socioeconomic status. Our results demonstrate that gray and white matter volume may mediate the correlation between body height and intelligence in healthy children. Additionally, the correlations among gray and white matter volume, height, and intelligence may be at least partially explained by the effect of insulin-like growth factor-1 and growth hormones. Given the importance of the effect of environmental factors, especially nutrition, on height, IQ, and gray matter volume, the present results stress the importance of nutrition during childhood for the healthy maturation of body and brain.     

Fronto-parietal hypo-activation during working memory independent of structural abnormalities: conjoint fMRI and sMRI analyses in adolescent offspring of schizophrenia patients

Adolescent offspring of schizophrenia patients (HR-S) are an important group in whom to study impaired brain function and structure, particularly of the frontal cortices. Studies of working memory have suggested behavioral deficits and fMRI-measured hypoactivity in fronto-parietal regions in these subjects. Independent structural MRI (sMRI) studies have suggested exaggerated frontal gray matter decline. Therefore the emergent view is that fronto-parietal deficits in function and structure characterize HR-S. However, it is unknown if fronto-parietal sub-regions in which fMRI-measured hypo-activity might be observed are precisely those regions of the cortex in which gray matter deficits are also observed. To investigate this question we conducted conjoint analyses of fronto-parietal function and structure in HR-S (n=19) and controls (n=24) with no family history of psychoses using fMRI data during a continuous working memory task (2 back), and sMRI collected in the same session. HR-S demonstrated significantly reduced BOLD activation in left dorso-lateral prefrontal cortex (BA 9/46) and bilateral parietal cortex (BA 7/40). Sub-regions of interest were created from the significant fronto-parietal functional clusters. Analyses of gray matter volume from volume-modulated gray matter segments in these clusters did not reveal significant gray matter differences between groups. The results suggest that functional impairments in adolescent HR-S can be independent of impairments in structure, suggesting that the relationship between impaired function and structure is complex. Further studies will be needed to more closely assess whether impairments in function and structure provide independent or interacting pathways of vulnerability in this population.     

应用基于体素的形态测量学分析工作记忆老化的脑灰质萎缩基础

目的利用基于体素的形态测量学(VBM)方法探讨老年人工作记忆能力衰退与脑灰质萎缩间的关系。方法在30名老年人(老年组)和38名青壮年人(对照组)中分别进行keep-track任务和2-back任务两种工作记忆任务检测。对所有受试者进行高分辨力MR扫描,并使用统计参数图(SPM)8软件进行VBM分析,比较老年组与对照组的脑灰质体积差异,并在老年组内利用多元回归分析寻找与工作记忆任务能力下降相关的责任萎缩脑区。结果与对照组相比,老年组工作记忆能力显著衰退,且出现广泛的脑灰质萎缩。老年组中,与keep-track任务能力相关的萎缩脑区主要位于双侧前额叶中下部、运动前区、顶叶后下部和小脑;与2-back任务相关的萎缩脑区主要位于左侧的前额叶下部、运动前区和颞叶。左腹侧运动前区(BA6)皮层的灰质体积与两个任务的行为学数据均存在显著相关性。结论老年人工作记忆能力下降与工作记忆神经网络的灰质萎缩有关。     

Segregated neural representation of distinct emotion dimensions in the prefrontal cortex-an fMRI study

Emotions are frequently characterized by distinct dimensions such as valence, intensity, and recognition. However, the exact neural representation of these dimensions in different prefrontal cortical regions remains unclear. One of the problems in revealing prefrontal cortical representation is that the very same regions are also involved in cognitive functions associated with emotion processing. We therefore conducted an fMRI study involving the viewing of emotional pictures (using the International Affective Picture System; IAPS) and controlled for associated cognitive processing like judgment and preceding attention. Functional activation was correlated with subjective post-scanning ratings of valence, intensity, and recognition. Valence significantly correlated with the functional response in ventromedial prefrontal cortex (VMPFC) and dorsolateral prefrontal cortex (DLPFC), intensity with activation in ventrolateral prefrontal cortex (VLPFC) and dorsomedial prefrontal cortex (DMPFC), and recognition with the functional response in perigenual anterior cingulate cortex (PACC). In conclusion, our results indicate segregated neural representation of the different emotion dimensions in different prefrontal cortical regions.