Aging alters the multichemical networking profile of the human brain: an in vivo (1)H-MRS study of young versus middle-aged subjects

In our most recent study of normal aging, we found decreased concentration of multiple chemicals in the brain of middle-aged subjects, as compared with younger subjects using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). We hypothesized that these age-dependent differences in brain chemistry changes might be a reflection of the multichemical-networking-profile (MCNP) changes during aging. Using (1)H-MRS and correlation analysis, we examined the patterns of regional chemical levels and MCNP within and across multiple brain regions for all nine chemicals of (1)H-MR spectra. The brain chemistry changes and MCNP patterns were compared between 21 young (19--31-year-old) and 31 middle-aged (40--52-year-old) normal volunteers. Middle-aged subjects demonstrated a significant decrease of chemical levels in the prefrontal cortex and sensorimotor cortex (SMC), as compared with the young age group. Of these, neurotransmitters GABA and glutamate in the dorsolateral prefrontal cortex (DLPFC) were altered the most. We also found a significant increase of overall chemical correlation strength in MCNP within and across all studied brain regions with increased age. These changes were caused by alterations in the pattern of negative chemical connectivity across brain regions, which become weaker (less negative) in middle-aged subjects. The interregional chemical connectivity for the cingulate cortex, SMC and the thalamus was changed the most with increased age. Increased levels of chemical correlation strength across brain regions in aging were found for most chemicals studied (including neurotransmitters GABA and glutamate), and not for N-acetyl aspartate. These age-related differences in the connectivity of neurotransmitters were not region dependent. The results suggest that aging is associated with changes of the regional brain chemistry and the brain MCNP. The latter process may reflect an adaptive or compensatory response (possibly related to the elongation of dendrites with aging) to reduced levels of regional brain chemicals. The (1)H-MRS approach proposed here can be used as a valuable tool in the study of the brain chemistry, MCNP and their relationships in normal and abnormal aging.     

Recruitment of unique neural systems to support visual memory in normal aging.

The performance of many cognitive tasks changes in normal aging [1] [2] [3]. Recent behavioral work has identified some tasks that seem to be performed in an age-invariant manner [4]. To understand the brain mechanisms responsible for this, we combined psychophysical measurements of visual short-term memory with positron emission tomography (PET) in young and old individuals. Participants judged the differences between two visual stimuli, and the memory load was manipulated by interposing a delay between the two stimuli. Both age groups performed the task equally well, but the neural systems supporting performance differed between young and old individuals. Although there was some overlap in the brain regions supporting performance (for example, occipital, temporal and inferior prefrontal cortices, and caudate), the functional interconnections between these common regions were much weaker in old participants. This suggests that the regions were not operating effectively as a network in old individuals. Old participants recruited unique areas, however, including medial temporal and dorsolateral prefrontal cortices. These unique areas were strongly interactive and their activity was related to performance only in old participants. Therefore, these areas may have acted to compensate for reduced interactions between the other brain areas.     

重度OSAS患者前额叶皮质及岛叶1H-MR波谱研究

目的:利用氢质子MRS(1H-MRS)探讨重度阻塞性呼吸睡眠暂停综合症(Severe obstructive sleep apnea syndrome,S-OSAS)患者前额叶皮质及岛叶脑代谢产物特征。方法:选择18例S-OSAS患者(S-OSAS组)和15名健康志愿者(HC组)行左侧前额叶皮质及岛叶1H-MRS检查,测量两组左侧前额叶皮质区及岛叶N-乙酰天冬氨酸/肌酸(NAA/Cr)、胆碱/肌酸(Cho/Cr)值。对患S-OSAS累计时间与前额叶皮质及岛叶NAA/Cr作直线相关分析。结果:与正常对照组相比,S-OSAS患者左侧前额叶皮质、岛叶NAA/Cr比值降低,分别为1.43±0.47、1.34±0.06,对照组分别为1.51±0.65、1.45±0.07;S-OSAS组患者左侧前额叶皮质、岛叶Cho/Cr分别为0.90±0.08、1.19±0.13,对照组分别为0.87±0.07、1.09±0.02,两组差异有统计学意义。前额叶皮质及岛叶代谢物NAA/Cr与患S-OSAS累计时间成负相关性(r值分别为-0.965、-0.955,P<0.01)。结论:1H-MRS显示S-OSAS患者前额叶皮质及岛叶病理生理变化,从该区代谢物的改变反应出S-OSAS患者执行及情感功能的异常,其NAA/Cr改变程度与患S-OSAS累计时间相关。     

重度OSAS患者前额叶皮质及岛叶1H—MR波谱研究

目的：利用氢质子MRS（IH-MRS）探讨重度阻塞性呼吸睡眠暂停综合症（Severeobstructivesleepapneasyndrome,S-OSAS）患者前额叶皮质及岛叶脑代谢产物特征。方法：选择18例S-OSAS患者（S-OSAS组）和15名健康志愿者（HC组）行左侧前额叶皮质及岛叶1H-MRS检查,测量两组左侧前额叶皮质区及岛叶N-乙酰天冬氨酸／肌酸（NAA／Cr）、胆碱／肌酸（Cho／Cr）值。对患S-OSAS累计时间与前额叶皮质及岛叶NAA／Cr作直线相关分析。结果：与正常对照组相比,S-OSAS患者左侧前额叶皮质、岛叶NAA／Cr比值降低,分别为1．43±0．47、1．34±0．06,对照组分别为1．51±0．65、1．45±0．07;S-OSAS组患者左侧前额叶皮质、岛叶Cho／Cr分别为0．90±0．08、1．195：0．13,对照组分别为0．87±0．07、1．09±0．02,两组差异有统计学意义。前额叶皮质及岛叶代谢物NAA／Cr与患S-OSAS累计时间成负相关性（r值分别为-0．965、-0．955,P〈0．01）。结论：1H-MRS显示S-OSAS患者前额叶皮质及岛叶病理生理变化,从该区代谢物的改变反应出S-OSAS患者执行及情感功能的异常,其NAA/Cr改变程度与患S-OSAS累计时间相关。     

Metabonomic alterations in hippocampus, temporal and prefrontal cortex with age in rats

The metabolic changes in hippocampus, temporal cortex and prefrontal cortex in SD rats along with aging were explored using a metabonomic approach, which based on high resolution “magic angle spinning” ¹H NMR spectroscopy. The metabolite profiles were analyzed by partial least squares-discriminant analysis, and the results showed that the metabolites of the above three brain regions in old rats were dramatically different from that in the adult and young rats. The old rats showed increased myo-inositol and lactate in all of the three brain regions, and decreased N-acetylaspartate in temporal and frontal cortex, Glutamate–GABA level became imbalance in temporal cortex of old rats. In addition, compared with the adult female rats, male rats had higher levels of N-acetylaspartate, taurine, and creatine in temporal or frontal cortex. The age-related metabolic changes may indicate the early functional alterations of neural cells in these brain regions, especially the temporal cortex. The gender-related metabolic changes suggest the significance of the hormonal regulation in brain metabolism. Our work highlights the potential of metabolic profiling to enhance our understanding of biological mechanisms of brain aging.     

Altered Resting-State Functional Connectivity of the Frontal-Striatal Reward System in Social Anxiety Disorder

We investigated differences in the intrinsic functional brain organization (functional connectivity) of the human reward system between healthy control participants and patients with social anxiety disorder. Functional connectivity was measured in the resting-state via functional magnetic resonance imaging (fMRI). 53 patients with social anxiety disorder and 33 healthy control participants underwent a 6-minute resting-state fMRI scan. Functional connectivity of the reward system was analyzed by calculating whole-brain temporal correlations with a bilateral nucleus accumbens seed and a ventromedial prefrontal cortex seed. Patients with social anxiety disorder, relative to the control group, had (1) decreased functional connectivity between the nucleus accumbens seed and other regions associated with reward, including ventromedial prefrontal cortex; (2) decreased functional connectivity between the ventromedial prefrontal cortex seed and lateral prefrontal regions, including the anterior and dorsolateral prefrontal cortices; and (3) increased functional connectivity between both the nucleus accumbens seed and the ventromedial prefrontal cortex seed with more posterior brain regions, including anterior cingulate cortex. Social anxiety disorder appears to be associated with widespread differences in the functional connectivity of the reward system, including markedly decreased functional connectivity between reward regions and between reward regions and lateral prefrontal cortices, and markedly increased functional connectivity between reward regions and posterior brain regions.     

Sparse representation of brain aging: extracting covariance patterns from structural MRI

An enhanced understanding of how normal aging alters brain structure is urgently needed for the early diagnosis and treatment of age-related mental diseases. Structural magnetic resonance imaging (MRI) is a reliable technique used to detect age-related changes in the human brain. Currently, multivariate pattern analysis (MVPA) enables the exploration of subtle and distributed changes of data obtained from structural MRI images. In this study, a new MVPA approach based on sparse representation has been employed to investigate the anatomical covariance patterns of normal aging. Two groups of participants (group 1:290 participants; group 2:56 participants) were evaluated in this study. These two groups were scanned with two 1.5 T MRI machines. In the first group, we obtained the discriminative patterns using a t-test filter and sparse representation step. We were able to distinguish the young from old cohort with a very high accuracy using only a few voxels of the discriminative patterns (group 1:98.4%; group 2:96.4%). The experimental results showed that the selected voxels may be categorized into two components according to the two steps in the proposed method. The first component focuses on the precentral and postcentral gyri, and the caudate nucleus, which play an important role in sensorimotor tasks. The strongest volume reduction with age was observed in these clusters. The second component is mainly distributed over the cerebellum, thalamus, and right inferior frontal gyrus. These regions are not only critical nodes of the sensorimotor circuitry but also the cognitive circuitry although their volume shows a relative resilience against aging. Considering the voxels selection procedure, we suggest that the aging of the sensorimotor and cognitive brain regions identified in this study has a covarying relationship with each other.     

Developmental Changes in Task‐Induced Brain Deactivation in Humans Revealed by a Motor Task

Performing tasks activates relevant brain regions in adults while deactivating task‐irrelevant regions. Here, using a well‐controlled motor task, we explored how deactivation is shaped during typical human development and whether deactivation is related to task performance. Healthy right‐handed children (8–11 years), adolescents (12–15 years), and young adults (20–24 years; 20 per group) underwent functional magnetic resonance imaging with their eyes closed while performing a repetitive button‐press task with their right index finger in synchronization with a 1‐Hz sound. Deactivation in the ipsilateral sensorimotor cortex (SM1), bilateral visual and auditory (cross‐modal) areas, and bilateral default mode network (DMN) progressed with development. Specifically, ipsilateral SM1 and lateral occipital deactivation progressed prominently between childhood and adolescence, while medial occipital (including primary visual) and DMN deactivation progressed from adolescence to adulthood. In adults, greater cross‐modal deactivation in the bilateral primary visual cortices was associated with higher button‐press timing accuracy relative to the sound. The region‐specific deactivation progression in a developmental period may underlie the gradual promotion of sensorimotor function segregation required in the task. Task‐induced deactivation might have physiological significance regarding suppressed activity in task‐irrelevant regions. Furthermore, cross‐modal deactivation develops to benefit some aspects of task performance in adults.     

Quantitative 3.0T MR Spectroscopy Reveals Decreased Creatine Concentration in the Dorsolateral Prefrontal Cortex of Patients with Social Anxiety Disorder

Background

The brain biochemical changes of social anxiety have not been clarified although there have been a limited number of MR spectroscopic studies which utilized metabolite/creatine ratios. Present study aimed to explore the alteration of absolute metabolite concentration in social anxiety disorder using quantitative MR spectroscopy.

Materials and Methods

With a 3.0T MR scanner, single voxel MR spectroscopy (stimulated echo acquisition mode, TR/TE/TM = 2000/20/16 ms) was performed in the left dorsolateral prefrontal cortex and related regions of nine medication-free patients with social anxiety disorder and nine controls. Absolute metabolite concentration was calculated using tissue water as the internal reference and corrected for the partial volume of cerebrospinal fluid.

Results

In the left dorsolateral prefrontal cortex, the N-acetyl aspartate/creatine ratio of patients was significantly higher than that of controls, and this was due to the decrease of creatine concentration instead of the increase of N-acetyl aspartate concentration. Furthermore, the creatine concentration of the left dorsolateral prefrontal cortex was negatively correlated with the scores of Liebowitz social anxiety scale.

Conclusions

The alteration of creatine level in the left dorsolateral prefrontal cortex suggests abnormal energy metabolism and correlates with symptom severity in social anxiety disorder. And metabolite concentration is preferable to metabolite/creatine ratio for the investigation of individual, absolute metabolite changes in this region of social anxiety disorder.     

Human and nonhuman primate brains: Are they allometrically scaled versions of the same design?

Allometric analyses of brain structure sizes across the primate order demonstrate that human, ape, and other anthropoid brains are not simply allometrically scaled versions of the same generalized design. Both human and ape brains exhibit specializations with respect to other anthropoid brains. Ape specializations include elaboration of the cerebellum (all apes) and frontal lobes (great apes only), and probably connectivity between them. Human brain specializations include an overall larger proportion of neocortex, with disproportionate enlargement of prefrontal and temporal association cortices; an apparent increase in cerebellar connections with cerebral cortical association areas involved in cognition; and a probable augmentation of intracortical connectivity in prefrontal cortex.     

Memory trace in prefrontal cortex: theory for the cognitive switch

The dorsolateral prefrontal cortex in human and non-human primates functions as the highest-order executor for the perception-action cycle. According to this view, when perceptual stimuli from the environment are novel or complex, the dorsolateral prefrontal cortex serves to set consciously a goal-directed scheme which broadly determines an action repertory to meet the particular demand from the environment. In this respect, the dorsolateral prefrontal cortex is a short-term activation device with the properties of a cognitive switch', because it couples a particular set of perceptual stimuli to a particular set of actions. Here, I suggest that, in order for the organism to react systematically to the environment, neural traces for the switch function must be stored in the brain. Thus, the highest-order, perception-action interface function of the dorsolateral prefrontal cortex per se depends on permanently stored neural traces in the dorsolateral prefrontal cortex and related structures. Such a memory system may be located functionally between two of the well-documented memory systems in the brain: the declarative memory system and the procedural memory system. Finally, based on available neurophysiological data, the possible mechanisms underlying the formation of cognitive switch traces are proposed.     

Differential effects of normal aging on sources of standard N1, target N1 and target P300 auditory event-related brain potentials revealed by low resolution electromagnetic tomography (LORETA)

The P300 event-related potential (ERP) is considered to be closely related to cognitive processes. In normal aging, P300 scalp latencies increase, parietal P300 scalp amplitudes decrease and the scalp potential field shifts to a relatively more frontal distribution. Based on ERPs recorded in 172 normal healthy subjects aged between 20 and 88 years in an auditory oddball paradigm, the effects of age on the electrical activity in the brain corresponding to N1 and P300 components were estimated by means of low resolution electromagnetic tomography (LORETA). This distributed approach directly computes a unique 3-dimensional electrical source distribution by assuming that neighbouring neurons are simultaneously and synchronously active. N1 LORETA generators, located predominantly in both auditory cortices and also symmetrically in prefrontal areas, increased with advancing age for standards but remained stable for targets. P300 LORETA generators, located symmetrically in the prefrontal cortex, in the parieto-occipital junction and in the inferior parietal cortex (supramarginal gyrus) and medially in the superior parietal cortex, were differentially affected by age. While age did not affect parieto-occipital sources, superior parietal and right prefrontal sources decreased pronouncedly. Thus, in normal aging, P300 current density decreased in regions were a fronto-parietal network for sustained attention was localized.     

Sex- and age-related characteristics of brain functioning during task switching (fMRI study)

This study is focused on changes in the brain function throughout the adulthood in healthy men and women performing task switching (TS) in the visual modality. One hundred and forty healthy subjects aged 20 to 65 years (69 men) participated in the experiments. In the fMRI study, the subjects performed a test that required switching attention between two objectives (classifying figures according to their form or number). Using the voxel-based morphometry (VBM), we calculated the volumes of gray and white matter in the whole brain and in selected areas. The results showed that a common feature of different age and sex groups performing the TS was bilateral activation of the dorsolateral prefrontal areas, the inferior parietal lobes and the inferior occipital gyrus. We also found a transition from local to diffuse activation occurring with age. In young men (20 to 30 years of age) compared to women, a greater increase in the BOLD signal was found in the prefrontal areas bilaterally, the right parietal lobe and insula, and, in addition, bilateral activation in the supplementary motor area which were not observed in women. Older men and women (51 to 65 years) had no significant differences. The study of the BOLD signal correlations with age in women at the age from 20 to 40 and men from 20 to 55 years showed no significant changes. With further increase of age in both groups we found a consequent increase in the number of brain areas which are activated. The VBM analysis showed a significant decrease in the volume of gray, but not white, matter with age. No significant correlations between age-related changes in the gray matter volume (both in the whole brain and in the specific areas) and BOLD signal in this age group were detected.     

Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity

Obesity is characterized by an imbalance in the brain circuits promoting reward seeking and those governing cognitive control. Here we show that the dorsal caudate nucleus and its connections with amygdala, insula and prefrontal cortex contribute to abnormal reward processing in obesity. We measured regional brain glucose uptake in morbidly obese (n = 19) and normal weighted (n = 16) subjects with 2-[18F]fluoro-2-deoxyglucose ([¹⁸F]FDG) positron emission tomography (PET) during euglycemic hyperinsulinemia and with functional magnetic resonance imaging (fMRI) while anticipatory food reward was induced by repeated presentations of appetizing and bland food pictures. First, we found that glucose uptake rate in the dorsal caudate nucleus was higher in obese than in normal-weight subjects. Second, obese subjects showed increased hemodynamic responses in the caudate nucleus while viewing appetizing versus bland foods in fMRI. The caudate also showed elevated task-related functional connectivity with amygdala and insula in the obese versus normal-weight subjects. Finally, obese subjects had smaller responses to appetizing versus bland foods in the dorsolateral and orbitofrontal cortices than did normal-weight subjects, and failure to activate the dorsolateral prefrontal cortex was correlated with high glucose metabolism in the dorsal caudate nucleus. These findings suggest that enhanced sensitivity to external food cues in obesity may involve abnormal stimulus-response learning and incentive motivation subserved by the dorsal caudate nucleus, which in turn may be due to abnormally high input from the amygdala and insula and dysfunctional inhibitory control by the frontal cortical regions. These functional changes in the responsiveness and interconnectivity of the reward circuit could be a critical mechanism to explain overeating in obesity.     

Cerebral Inefficient Activation in Schizophrenia Patients and Their Unaffected Parents during the N-Back Working Memory Task: A Family fMRI Study

Background

It has been suggested that working memory deficits is a core feature of symptomatology of schizophrenia, which can be detected in patients and their unaffected relatives. The impairment of working memory has been found related to the abnormal activity of human brain regions in many functional magnetic resonance imaging (fMRI) studies. This study investigated how brain region activation was altered in schizophrenia and how it was inherited independently from performance deficits.

Method

The authors used fMRI method during N-back task to assess working memory related cortical activation in four groups (N = 20 in each group, matching task performance, age, gender and education): schizophrenic patients, their unaffected biological parents, young healthy controls for the patients and older healthy controls for their parents.

Results

Compared to healthy controls, patients showed an exaggerated response in the right dorsolateral prefrontal cortex (brodmann area [BA] 46) and bilateral ventrolateral prefrontal cortex, and had reduced activation in bilateral dorsolateral prefrontal cortex (BA 9). In the conjunction analysis, the effect of genetic risk (parents versus older control) shared significantly overlapped activation with effect of disease (patients versus young control) in the right middle frontal gyrus (BA 46) and left inferior parietal gyrus (BA 40).

Conclusions

Physiological inefficiency of dorsal prefrontal cortex and compensation involvement of ventral prefrontal cortex in working memory function may one physiological characteristics of schizophrenia. And relatively inefficient activation in dorsolateral prefrontal cortex probably can be a promising intermediate phenotype for schizophrenia.     

Activation of the sensorimotor cortex using a device for mechanical stimulation of the plantar support zones

Numerous studies on the mechanisms of the motor control carried out in the interests of space medicine resulted in a concept on the leading role of the support afferent input in the regulation of the postural tonic system in mammals. The implementation of functional magnetic resonance imaging (fMRI) has permitted in vivo brain mapping during stimulation of the support afferent input. The goal of this study was to identify activated regions in the brain during mechanical stimulation of the plantar support zones in different modes using a special Korvit simulator. Twelve healthy volunteers (six women and six men) aged from 22 to 42 years were studied using fMRI, each of them was scanned once. The fMRI protocol for each subject consisted of two different blocked paradigms: (1) with the soles of a subject stimulated in an imitated standing mode and (2) with the soles stimulated in an imitation slow-walking mode. The patterns of activation in each mode were analyzed using the SPM5 statistical software package for each subject and for the group as a whole. All the paradigms showed significant activation (p _correct < 0. 05 at the cluster level) in the primary somatosensory, premotor, dorsolateral and prefrontal cortices, as well as in the insula. The involvement of the prefrontal cortex during simulation of standing and a broad involvement of the primary and secondary sensorimotor cortices during simulation of slow walking were found.     

From children to adults: motor performance across the life-span

The life-span approach to development provides a theoretical framework to examine the general principles of life-long development. This study aims to investigate motor performance across the life span. It also aims to investigate if the correlations between motor tasks increase with aging. A cross-sectional design was used to describe the effects of aging on motor performance across age groups representing individuals from childhood to young adult to old age. Five different motor tasks were used to study changes in motor performance within 338 participants (7-79 yrs). Results showed that motor performance increases from childhood (7-9) to young adulthood (19-25) and decreases from young adulthood (19-25) to old age (66-80). These results are mirroring results from cognitive research. Correlation increased with increasing age between two fine motor tasks and two gross motor tasks. We suggest that the findings might be explained, in part, by the structural changes that have been reported to occur in the developing and aging brain and that the theory of Neural Darwinism can be used as a framework to explain why these changes occur.     

Changes in brain activity after a diet-induced obesity

Compared to lean subjects, obese men have less activation in the dorsolateral prefrontal cortex, a brain area implicated in the inhibition of inappropriate behavior, satiety, and meal termination. Whether this deficit precedes weight gain or is an acquired feature of obesity remains unknown. An adult animal model of obesity may provide insight to this question since brain imaging can be performed in lean vs. obese conditions in a controlled study. Seven diet-induced obese adult minipigs were compared to nine lean adult minipigs housed in the same conditions. Brain activation after an overnight fasting was mapped in lean and obese subjects by single photon emission computed tomography. Cerebral blood flow, a marker of brain activity, was measured in isoflurane-anesthetized animals after the intravenous injection of 99mTc-HMPAO (750 MBq). Statistical analysis was performed using statistical parametric mapping (SPM) software and cerebral blood flow differences were determined using co-registered T1 magnetic resonance imaging (MRI) and histological atlases. Deactivations were observed in the dorsolateral and anterior prefrontal cortices in obese compared to lean subjects. They were also observed in several other structures, including the ventral tegmental area, the nucleus accumbens, and nucleus pontis. On the contrary, activations were found in four different regions, including the ventral posterior nucleus of the thalamus and middle temporal gyrus. Moreover, the anterior and dorsolateral prefrontal cortices as well as the insular cortex activity was negatively associated with the body weight. We suggested that the reduced activation of prefrontal cortex observed in obese humans is probably an acquired feature of obesity since it is also found in minipigs with a diet-induced obesity.     

带状疱疹后遗神经痛患者脑基础活动改变的功能核磁共振研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是临床上一种慢性顽固性神经病理性疼痛,然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨带状疱疹后遗神经痛患者的相关脑区活动,利用功能核磁共振成像低频振幅振荡(ALFF)技术观察带状疱疹后遗神经痛患者的基础脑区活动.8名带状疱疹后遗神经痛患者与8名性别、年龄相匹配的健康者行静息态功能磁共振(f MRI)成像扫描,用SPM8中的多重回归分析,在控制被试年龄、性别、教育年限的影响下,将每个体素的ALFF值同每个被试的病程、视觉模拟评分(visual analog scale,VAS)进行相关分析.与健康志愿者相比,PHN组与VAS评分相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA11/46/47)、右侧顶叶(BA40)、右侧舌回(BA17/18/19);与VAS评分相关的ALFF值降低的脑区有:右侧颞中回(BA21)、左侧舌回(BA17/18)、右侧小脑前叶、左侧后扣带回(BA30/19)和右侧中央前回(BA3/4/6);PHN组与病程相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA9/10/11/47)、左侧颞上回(BA38)、右侧顶叶和右侧舌回(BA17/18/19);与病程相关ALFF值降低的脑区有:左侧海马旁回(BA28)、右侧小脑前叶、左侧扣带回(BA24)、右侧颞上回(BA13)、左侧中央前回和右侧顶下小叶(BA39/40).研究结果提示,涉及疼痛的情绪、警觉行为、注意的脑区在带状疱疹后遗痛慢性疼痛的产生和维持中发挥重要作用.