High-resolution Structural Data Research Articles

NMR studies on lignocellulose deconstructions in the digestive system of the lower termite Coptotermes formosanus Shiraki

Termites represent one of the most efficient lignocellulose decomposers on earth. The mechanism by which termites overcome the recalcitrant lignin barrier to gain access to embedded polysaccharides for assimilation and energy remains largely unknown. In the present study, softwood, hardwood, and grass lignocellulose diets were fed to Coptotermes formosanus workers, and structural differences between the original lignocellulose diets and the resulting feces were examined by solution-state multidimensional nuclear magnetic resonance (NMR) techniques as well as by complementary wet-chemical methods. Overall, our data support the view that lignin polymers are partially decomposed during their passage through the termite gut digestive system, although polysaccharide decomposition clearly dominates the overall lignocellulose deconstruction process and the majority of lignin polymers remain intact in the digestive residues. High-resolution NMR structural data suggested preferential removal of syringyl aromatic units in hardwood lignins, but non-acylated guaiacyl units as well as tricin end-units in grass lignins. In addition, our data suggest that termites and/or their gut symbionts may favor degradation of C–C-bonded β–5 and resinol-type β–β lignin inter-monomeric units over degradation of ether-bonded β–O–4 units, which is in contrast to what has been observed in typical lignin biodegradation undertaken by wood-decaying fungi.

Role of Language-Related Functional Connectivity in Patients with Benign Childhood Epilepsy with Centrotemporal Spikes.

Background and PurposeBenign childhood epilepsy with centrotemporal spikes (BECTS) does not always have a benign cognitive outcome. We investigated the relationship between cognitive performance and altered functional connectivity (FC) in the resting-state brain networks of BECTS patients.MethodsWe studied 42 subjects, comprising 19 BECTS patients and 23 healthy controls. Cognitive performance was assessed using the Korean version of the Wechsler Intelligence Scale for Children-III, in addition to verbal and visuospatial memory tests and executive function tests. Resting-state functional magnetic resonance imaging was acquired in addition to high-resolution structural data. We selected Rolandic and language-related areas as regions of interest (ROIs) and analyzed the seed-based FC to voxels throughout the brain. We evaluated the correlations between the neuropsychological test scores and seed-based FC values using the same ROIs.ResultsThe verbal intelligence quotient (VIQ) and full-scale intelligence quotient (FSIQ) were lower in BECTS patients than in healthy controls (p<0.001). The prevalence of subjects with a higher performance IQ than VIQ was significantly higher in BECTS patients than in healthy controls (73.7% vs. 26.1%, respectively; p=0.002). Both the Rolandic and language-related ROIs exhibited more enhanced FC to voxels in the left inferior temporal gyrus in BECTS patients than in healthy controls. A particularly interestingly finding was that the enhanced FC was correlated with lower cognitive performance as measured by the VIQ and the FSIQ in both patients and control subjects.ConclusionsOur findings suggest that the FC alterations in resting-state brain networks related to the seizure onset zone and language processing areas could be related to adaptive plasticity for coping with cognitive dysfunction.

Redox-sensing iron-sulfur cluster regulators.

Iron-sulfur cluster proteins carry out a wide range of functions, including as regulators of gene transcription/translation in response to environmental stimuli. In all known cases, the cluster acts as the sensory module, where the inherent reactivity/fragility of iron-sulfur clusters towards small/redox active molecules is exploited to effect conformational changes that modulate binding to DNA regulatory sequences. This promotes an often substantial re-programming of the cellular proteome that enables the organism or cell to adapt to, or counteract, its changing circumstances. Recent Advances. Significant progress has been made recently in the structural and mechanistic characterization of iron-sulfur cluster regulators and, in particular, the O2 and NO sensor FNR, the NO sensor NsrR, and WhiB-like proteins of Actinobacteria. These are the main focus of this review. Striking examples of how the local environment controls the cluster sensitivity and reactivity are now emerging, but the basis for this is not yet fully understood for any regulatory family. Characterization of iron-sulfur cluster regulators has long been hampered by a lack of high resolution structural data. Though this still presents a major future challenge, recent advances now provide a firm foundation for detailed understanding of how a signal is transduced to effect gene regulation. This requires the identification of often unstable intermediate species, which are difficult to detect and may be hard to distinguish using traditional techniques. Novel approaches will be required to solve these problems.

Impairments of gray matter in MRI-negative epileptic patients with different seizure types

Objective: To investigate the damage of gray matter structure in MRI-negative epilepsy patients with different symptoms by voxel-based morphometry (VBM). Methods: From June, 2009 to October, 2016, ninety MRI-negative epilepsy patients and thirty-five healthy volunteers underwent the 3T magnetic resonance imaging scan in Nanjing General Hospital. The patients were divided into three groups, including idiopathic generalized tonic-clonic seizure (I-GTCS), secondarily generalized tonic-clonic seizure (S-GTCS), and partial seizure (PS) according to different symptoms. The three-dimensional high-resolution T1 structural MRI data was obtained for the voxel-based morphometry. Data of gray matter structure from four groups were compared using one-way analysis of variance (ANOVA). An independent-sample t test was performed in order to compare gray matter volume of the three patient groups with controls respectively. According the results of ANOVA, impaired brain regions were selected as regions of interest in order to carry out correlation analysis between gray matter volume and disease duration. Results: ANOVA showed significant differences in gray matter structure of bilateral thalamus and frontal lobe between four groups (alphasim correction, P<0.01). Independent-sample t test showed that the volume of bilateral thalamus and frontal lobe decreased in all three patients groups (alphasim correction, P<0.01) .The volume of bilateral thalamus showed significantly negatively correlation with disease duration in I-GTCS patients (r=-0.466, P<0.01). Conclusions: Generalized seizures and partial seizures all can cause damage to the gray matter structure, especially in thalamus and frontal lobe. The impairments of thalamus and frontal lobe in patients with different seizure types are different with the progression of disease, which suggests that influences of different epilepsy seizures on the thalamo-cortical network are different.

Structural and Biophysical Analysis of the Soluble DHH/DHHA1-Type Phosphodiesterase TM1595 from Thermotoga maritima

The concentration of messenger molecules in bacterial cells needs to be tightly regulated. This can be achieved by either controlling the synthesis rate, degradation, or export by specific transporters, respectively. The regulation of the essential second messenger c-di-AMP is achieved by modulation of the diadenylate cyclase activity as well as by specific phosphodiesterases that hydrolyze c-di-AMP in the cell. We provide here structural and biochemical data on the DHH-type phosphodiesterase TmPDE (TM1595) from Thermotoga maritima. Our analysis shows that TmPDE is preferentially degrading lineardinucleotides, such as 5'-pApA, 5'-pGpG, and 5'-pApG, compared with cyclic dinucleotide substrates. The high-resolution structural data provided here describe all steps of the PDE reaction: the ligand-free enzyme, two substrate-bound states, and three post-reaction states. We can furthermore show that Pde2 from Streptococcus pneumoniae shares both structural features and substrate specificity based on small-angle X-ray scattering data and biochemical assays.

Structural brain abnormalities in 12 persons with aniridia.

Background: Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the PAX6 gene, which is a transcriptional regulator necessary for normal eye and brain development. The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well. Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter. However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge. Methods: Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia. The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects. Results: We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm. The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of the other structures examined were present in at least one individual. Conclusions: Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific. These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.

Structural brain abnormalities in 12 persons with aniridia

Background: Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the PAX6 gene, which is a transcriptional regulator necessary for normal eye and brain development. The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well. Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter. However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge. Methods: Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia. The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects. Results: We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm. The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of the other structures examined were present in at least one individual. Conclusions: Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific. These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.

Hippocampal maturity promotes memory distinctiveness in childhood and adolescence

Adaptive learning systems need to meet two complementary and partially conflicting goals: detecting regularities in the world versus remembering specific events. The hippocampus (HC) keeps a fine balance between computations that extract commonalities of incoming information (i.e., pattern completion) and computations that enable encoding of highly similar events into unique representations (i.e., pattern separation). Histological evidence from young rhesus monkeys suggests that HC development is characterized by the differential development of intrahippocampal subfields and associated networks. However, due to challenges in the in vivo investigation of such developmental organization, the ontogenetic timing of HC subfield maturation remains controversial. Delineating its course is important, as it directly influences the fine balance between pattern separation and pattern completion operations and, thus, developmental changes in learning and memory. Here, we relate in vivo, high-resolution structural magnetic resonance imaging data of HC subfields to behavioral memory performance in children aged 6-14 y and in young adults. We identify a multivariate profile of age-related differences in intrahippocampal structures and show that HC maturity as captured by this pattern is associated with age differences in the differential encoding of unique memory representations.

Computational Prediction of Position Effects of Apparently Balanced Human Chromosomal Rearrangements

Interpretation of variants of uncertain significance, especially chromosomal rearrangements in non-coding regions of the human genome, remains one of the biggest challenges in modern molecular diagnosis. To improve our understanding and interpretation of such variants, we used high-resolution three-dimensional chromosomal structural data and transcriptional regulatory information to predict position effects and their association with pathogenic phenotypes in 17 subjects with apparently balanced chromosomal abnormalities. We found that the rearrangements predict disruption of long-range chromatin interactions between several enhancers and genes whose annotated clinical features are strongly associated with the subjects' phenotypes. We confirm gene-expression changes for a couple of candidate genes to exemplify the utility of our analysis of position effect. These results highlight the important interplay between chromosomal structure and disease and demonstrate the need to utilize chromatin conformational data for the prediction of position effects in the clinical interpretation of non-coding chromosomal rearrangements.

The role of geological structure and weathering in contaminant fate and transport in fractured bedrock at two sites in the UK

Case studies are presented of two superficially similar fractured bedrock sites in the UK affected by chlorinated solvents. Site investigation used high-resolution site characterization techniques that have allowed a detailed understanding of the distribution of contaminant mass in the source areas, and the development of advanced conceptual site models at both sites. Differences in the amount of weathering, the geological structural style and the amount of organic carbon present meant that the contaminant fate and transport at each site is completely different. At one site deep, pervasive weathering had increased matrix porosity and permeability, whereas clay-infilled fractures in the underlying fresh shale prevented the contaminants from entering fractures at depth and produced a shallow and relatively short plume. At the second site there were very thin soils over a low-grade slate with almost no weathering, and solvent had penetrated to greater depths and diffused into the matrix. A lack of pore space, carbon and biodegradation has produced a deep, long, fast-moving and highly concentrated plume that is affecting a nearby surface water receptor. The decision to obtain high-resolution structural logging and chemical sampling data was the most important choice in the development of the conceptual site model.

Improved T*₂ determination in 23Na, 35Cl, and 17O MRI using iterative partial volume correction based on 1H MRI segmentation.

Functional parameters can be measured with the help of quantitative non-proton MRI where exact relaxometry parameters are needed. Investigation of [Formula: see text] is often biased by strong partial volume (PV) effects. Hence, in this work a PV correction algorithm approach was evaluated that uses iteratively adapted [Formula: see text]-values and high-resolution structural 1H data to determine transverse relaxation in non-proton MRI more accurately. Simulations, a phantom study and in vivo 23Na, 17O and 35Cl MRI measurements of five healthy volunteers were performed to evaluate the algorithm. [Formula: see text] values of grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) were obtained. Data were acquired at B 0 =7T with nominal spatial resolutions of (4-7mm)3 using a density-adapted radial sequence. The resulting transverse relaxation times were used for quantification of 17O data. The conducted simulations and phantom study verified the correction performance of the algorithm. For in vivo measured [Formula: see text] values, the correction of PV effects leads to an increase in CSF and to a decrease in GM/WM (23Na MRI: long/short GM, WM [Formula: see text]: 36.4±3.1/5.4±0.2, 23.3±2.6/3.5±0.1ms; 35Cl MRI: 8.9±1.4/1.0±0.4, 5.9±0.3/0.4±0.1ms; 17O MRI: 2.5±0.1, 2.8±0.1ms). Iteratively corrected in vivo [Formula: see text] values of the 17O study resulted in improved water content quantification. The proposed iterative algorithm for PV correction leads to more accurate [Formula: see text] values and, thus, can improve accuracy in quantitative non-proton MRI.

Atypical callosal morphology in developmental language disorder

IntroductionDevelopmental language disorder (DLD) is common, yet the neurobiology of DLD is poorly understood. A key hypothesis suggests atypical functional lateralization of language, which might be accompanied structurally by a deficit in inter-hemispheric connectivity of language-related regions. Indeed, aberrations of the corpus callosum have been associated with language deficits in children with frank neurological lesions and/or born pre-term. In contrast, studies examining the corpus callosum in children with DLD remain elusive.ObjectiveWe aimed to expand this largely understudied field by comparing callosal morphology between 17 children with DLD and 17 typically developing children carefully matched for sex and age.MethodsWe analyzed high-resolution structural magnetic resonance imaging data applying a well-validated computational approach, which captures the thickness of the corpus callosum with a high regional specificity at 100 equidistant points.ResultsAs shown in Fig. 1, we observed a significantly thinner corpus callosum, particularly in the splenium, in children with DLD compared to typically developing controls (DLD &lt; CTL).ConclusionsThese findings indicating pronounced aberrations in the brain's largest whiter matter tract make an important contribution to an understudied field of research and support the theory that DLD is accompanied by atypical lateralization of language function.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Structural brain abnormalities in 12 persons with aniridia

Background: Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the PAX6 gene, which is a transcriptional regulator necessary for normal eye and brain development. The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well. Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter. However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge. Methods: Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia. The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects. Results: We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm. The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of other structures examined were present in at least one individual. Conclusions: Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific. These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.

Role of the PB2 627 Domain in Influenza A Virus Polymerase Function.

ABSTRACTThe RNA genome of influenza A viruses is transcribed and replicated by the viral RNA-dependent RNA polymerase, composed of the subunits PA, PB1, and PB2. High-resolution structural data revealed that the polymerase assembles into a central polymerase core and several auxiliary highly flexible, protruding domains. The auxiliary PB2 cap-binding and the PA endonuclease domains are both involved in cap snatching, but the role of the auxiliary PB2 627 domain, implicated in host range restriction of influenza A viruses, is still poorly understood. In this study, we used structure-guided truncations of the PB2 subunit to show that a PB2 subunit lacking the 627 domain accumulates in the cell nucleus and assembles into a heterotrimeric polymerase with PB1 and PA. Furthermore, we showed that a recombinant viral polymerase lacking the PB2 627 domain is able to carry out cap snatching, cap-dependent transcription initiation, and cap-independent ApG dinucleotide extension in vitro, indicating that the PB2 627 domain of the influenza virus RNA polymerase is not involved in core catalytic functions of the polymerase. However, in a cellular context, the 627 domain is essential for both transcription and replication. In particular, we showed that the PB2 627 domain is essential for the accumulation of the cRNA replicative intermediate in infected cells. Together, these results further our understanding of the role of the PB2 627 domain in transcription and replication of the influenza virus RNA genome.IMPORTANCE Influenza A viruses are a major global health threat, not only causing disease in both humans and birds but also placing significant strains on economies worldwide. Avian influenza A virus polymerases typically do not function efficiently in mammalian hosts and require adaptive mutations to restore polymerase activity. These adaptations include mutations in the 627 domain of the PB2 subunit of the viral polymerase, but it still remains to be established how these mutations enable host adaptation on a molecular level. In this report, we characterize the role of the 627 domain in polymerase function and offer insights into the replication mechanism of influenza A viruses.

Characterizing the Structure and Oligomerization of Major Royal Jelly Protein 1 (MRJP1) by Mass Spectrometry and Complementary Biophysical Tools.

Royal jelly (RJ) triggers the development of female honeybee larvae into queens. This effect has been attributed to the presence of major royal jelly protein 1 (MRJP1) in RJ. MRJP1 isolated from royal jelly is tightly associated with apisimin, a 54-residue α-helical peptide that promotes the noncovalent assembly of MRJP1 into multimers. No high-resolution structural data are available for these complexes, and their binding stoichiometry remains uncertain. We examined MRJP1/apisimin using a range of biophysical techniques. We also investigated the behavior of deglycosylated samples, as well as samples with reduced apisimin content. Our mass spectrometry (MS) data demonstrate that the native complexes predominantly exist in a (MRJP14 apisimin4) stoichiometry. Hydrogen/deuterium exchange MS reveals that MRJP1 within these complexes is extensively disordered in the range of residues 20-265. Marginally stable secondary structure (likely antiparallel β-sheet) exists around residues 266-432. These weakly structured regions interchange with conformers that are extensively unfolded, giving rise to bimodal (EX1) isotope distributions. We propose that the native complexes have a "dimer of dimers" quaternary structure in which MRJP1 chains are bridged by apisimin. Specifically, our data suggest that apisimin acts as a linker that forms hydrophobic contacts involving the MRJP1 segment 316VLFFGLV322. Deglycosylation produces large soluble aggregates, highlighting the role of glycans as aggregation inhibitors. Samples with reduced apisimin content form dimeric complexes with a (MRJP12 apisimin1) stoichiometry. The information uncovered in this work will help pave the way toward a better understanding of the unique physiological role played by MRJP1 during queen differentiation.

Novel Molecular Mechanism of Excitatory Neurotransmitter Transport Inhibition

Human members of the solute carrier 1 (SLC1) family of transporters take up excitatory neurotransmitters in the brain, mainly glutamate, and amino acids in peripheral organs. Dysregulation of their functions is associated to neurodegenerative disorders and cancer. Here we present recent high-resolution structural and dynamic data obtained from a thermostable human glutamate transporter. In particular, combining X-ray crystallography and hydrogen-deuterium exchange mass spectrometry, we have now revealed architectural features of human SLC1 proteins and a novel allosteric mechanism of transport inhibition, opening new venues for drug design targeting SLC1 transporters.

The crystal structure of PD1, a Haemophilus surface fibril domain.

The Haemophilus surface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains of H. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel `hairpin-like' architecture, the characterization of Hsf has been limited to in silico modelling and electron micrographs, with no high-resolution structural data available. Here, the crystal structure of Hsf putative domain 1 (PD1) is reported at 3.3 Å resolution. The structure corrects the previous domain annotation by revealing the presence of an unexpected N-terminal TrpRing domain. PD1 represents the first Hsf domain to be solved, and thus paves the way for further research on the `hairpin-like' hypothesis.

Probing the excitonic landscape of the Chlorobaculum tepidum Fenna-Matthews-Olson (FMO) complex: a mutagenesis approach

In this paper we report the steady-state optical properties of a series of site-directed mutants in the Fenna-Matthews-Olson (FMO) complex of Chlorobaculum tepidum, a photosynthetic green sulfur bacterium. The FMO antenna complex has historically been used as a model system for energy transfer due to the water-soluble nature of the protein, its stability at room temperature, as well as the availability of high-resolution structural data. Eight FMO mutants were constructed with changes in the environment of each of the bacteriochlorophyll a pigments found within each monomer of the homotrimeric FMO complex. Our results reveal multiple changes in low temperature absorption, as well as room temperature CD in each mutant compared to the wild-type FMO complex. These datasets were subsequently used to model the site energies of each pigment in the FMO complex by employing three different Hamiltonians from the literature. This enabled a basic approximation of the site energy shifts imparted on each pigment by the changed amino acid residue. These simulations suggest that, while the three Hamiltonians used in this work provide good fits to the wild-type FMO absorption spectrum, further efforts are required to obtain good fits to the mutant minus wild-type absorption difference spectra. This demonstrates that the use of FMO mutants can be a valuable tool to refine and iterate the current models of energy transfer in this system.

Common and Specific Abnormalities in Cortical Thickness in Patients with Major Depressive and Bipolar Disorders

Major depressive disorder (MDD) and bipolar disorder (BD) are severe psychiatric diseases with overlapping symptomatology. Although previous studies reported abnormal brain structures in MDD or BD patients, the disorder-specific underlying neural mechanisms remain poorly understood. The purpose of this study was to investigate the whole-brain gray matter morphological patterns in unmedicated patients with MDD or BD and to identify the shared and disease-specific brain morphological alterations in these two disorders.We acquired high-resolution brain structural MRI data from a sample of 36 MDD patients, 32 BD patients, and 30 healthy controls. Using FreeSurfer, we estimated their brain cortical thickness (CT) and compared between-group difference in multiple locations across the continuous cortical surface.Compared to the healthy controls, both the MDD and BD patient groups showed significantly reduced CT in the left inferior temporal cortex (ITC). However, compared to the MDD patients, the BD patients showed a significantly thinner CT in the left rostral middle frontal region. In addition, compared to the healthy controls, the BD patients displayed thinner CT in the left ITC, left frontal pole (FPO), left superior frontal, right lateral occipital, right pars triangularis (PTRI) and right lateral orbitofrontal regions. Further analysis revealed a significantly positive correlation between the mean CT in the left FPO and the onset age, but a negative correlation between the mean CT in the right PTRI and the number of episodes, in the BD patients.Our findings revealed that the BD and MDD patients had variations in CT that were in common, but many more that were distinct, suggesting potential differences in their neural mechanisms.

Radiation-induced abnormal cortical thickness in patients with nasopharyngeal carcinoma after radiotherapy

Conventional MRI studies showed that radiation-induced brain necrosis in patients with nasopharyngeal carcinoma (NPC) in years after radiotherapy (RT) could involve brain gray matter (GM) and impair brain function. However, it is still unclear the radiation-induced brain morphological changes in NPC patients with normal-appearing GM in the early period after RT. In this study, we acquired high-resolution brain structural MRI data from three groups of patients, 22 before radiotherapy (pre-RT) NPC patients with newly diagnosed but not yet medically treated, 22 NPC patients in the early-delayed stage after radiotherapy (post-RT-ED), and 20 NPC patients in the late-delayed stage after radiotherapy (post-RT-LD), and then analyzed the radiation-induced cortical thickness alteration in NPC patients after RT. Using a vertex-wise surface-based morphometry (SBM) approach, we detected significantly decreased cortical thickness in the precentral gyrus (PreCG) in the post-RT-ED group compared to the pre-RT group. And the post-RT-LD group showed significantly increased cortical thickness in widespread brain regions, including the bilateral inferior parietal, left isthmus of the cingulate, left bank of the superior temporal sulcus and left lateral occipital regions, compared to the pre-RT group, and in the bilateral PreCG compared to the post-RT-ED group. Similar analysis with ROI-wise SBM method also found the consistent results. These results indicated that radiation-induced brain injury mainly occurred in the post-RT-LD group and the cortical thickness alterations after RT were dynamic in different periods. Our findings may reflect the pathogenesis of radiation-induced brain injury in NPC patients with normal-appearing GM and an early intervention is necessary for protecting GM during RT.