Abnormal Alterations of Cortical Thickness in 16 Patients with Type 2 Diabetes Mellitus： A Pilot MRI Study

Objective The aim of this study is to investigate the cerebral cortical thickness changes in type 2 diabetes mellitus （T2DM） using a whole brain cortical thickness mapping system based on brain magnetic resonance imaging （MRI）. Methods High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 16 patients with T2DM, as well as from 16 normal controls. The whole brain cortical thickness maps were generated, and the cortical thickness of each brain region was calculated according to gyral based regions of interest （ROI） using an automated labeling system by the Freesurfer software. We compared mean cortical thickness at each brain region by the analysis of covariance with age and sex as covariates. The regional difference of the cortical thickness over the whole brain was compared by the analysis of surface-based cortical thickness. Results Mean cortical thicknesses analysis showed bilateral cerebrum in the patients with T2DM （left： 2.52±0.07 mm; right： 2.51±0.08 mm） were significant thinner than those in the normal controls （left： 2.56±0.09 mm; right： 2.56±0.09 mm） （both P〈0.05）. Regional cortical thinning in T2DM was demonstrated in the paracentral lobule, postcentral gyrus, lateral occipital gyrus, lingual gyrus, precuneus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus and posterior cingulate gyrus, compared to the normal controls. The cortical thickness of left middle cingulate and right inferior temporal gyrus were negatively correlated with the disease course. Conclusion A widespread cortical thinning was revealed in patients with T2DM by the analysis of brain cortical thickness on MR. Our finding supports the idea that T2DM could lead to subtle diabetic brain structural changes.

Longitudinal evolution of cortical thickness signature reflecting Lewy body dementia in isolated REM sleep behavior disorder:a prospective cohort study

Background The isolated rapid-eye-movement sleep behavior disorder(iRBD)is a prodromal condition of Lewy body disease including Parkinson’s disease and dementia with Lewy bodies(DLB).We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with iRBD.Methods We enrolled 22 DLB patients,44 healthy controls,and 50 video polysomnography-proven iRBD patients.Participants underwent 3-T magnetic resonance imaging(MRI)and clinical/neuropsychological evaluations.We characterized DLB-related whole-brain cortical thickness spatial covariance pattern(DLB-pattern)using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched controls.We analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD patients.With repeated MRI data during the follow-up in our prospective iRBD cohort,we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body dementia.Finally,we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD cohort.Results The DLB-pattern was characterized by thinning of the temporal,orbitofrontal,and insular cortices and relative preservation of the precentral and inferior parietal cortices.The DLB-pattern expression scores correlated with attentional and frontal executive dysfunction(Trail Making Test-A and B:R=−0.55,P=0.024 and R=−0.56,P=0.036,respectively)as well as visuospatial impairment(Rey-figure copy test:R=−0.54,P=0.0047).The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters(Pearson’s correlation,R=0.74,P=6.8×10−4)but no significant change in parkinsonism-first phenoconverters(R=0.0063,P=0.98).The mean value of the whole-brain cortical thickness predicted phenoconversion in iRBD patients with hazard ratio of 9.33[1.16-74.12].The increase in DLB-pattern expression score discriminated dementia-first from parkinsonism-first phenoconversions with 88.2%accuracy.Conclusion Cortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population.Replication studies would further validate the utility of this imaging marker in iRBD.

Association of Optic Radiation Integrity with Cortical Thickness in Children with Anisometropic Amblyopia

Previous studies have indicated regional abnormalities of both gray and white matter in amblyopia. However, alterations of cortical thickness associated with changes in white matter integrity have rarely been reported. In this study, structural magnetic resonance imaging and diffusion tensor imaging （DTI） data were obtained from 15 children with anisometropic amblyopia and 15 age- and gender-matched children with normal sight. Combining DTI and surface-based morphometry, we examined a potential linkage between disrupted white matter integrity and altered cortical thickness. The fractional anisotropy （FA） values in the optic radiations （ORs） of children with anisometropic amblyopia were lower than in controls （P 〈 0.05）. The cortical thickness in amblyopic children was lower than controls in the following subregions： lin- gual cortex, lateral occipitotemporal gyrus, cuneus, occip- ital lobe, inferior parietal lobe, and temporal lobe （P 〈 0.05, corrected）, but was higher in the calcarine gyrus （P 〈 0.05, corrected）. Node-by-node correlation analysis of changes in cortical thickness revealed a significant association between a lower FA value in the OR and diminished cortical thickness in the following subregions： medial lingual cortex, lateral occipitotemporal gyrus, lat- eral, superior, and medial occipital cortex, and lunate cortex. We also found a relationship between changes of cortical thickness and white matter OR integrity in amblyopia. These findings indicate that developmental changes occur simultaneously in the OR and visual cortex in amblyopia, and provide key information on complex damage of brain networks in anisometropic amblyopia. Our results also support the hypothesis that the pathogenesis of anisometropic amblyopia is neurodevelopmental.

Abnormalcortical thickness in relapsing-remitting multiple sclerosis,correlations with cognition impairment,and effect of modified Bushenyisui decoction(补肾益髓汤)on cognitive function of multiple sclerosis

OBJECTIVE:To investigate the changes of subcortical gray matter volume and cortical thickness,andexplorethe correlations between regional abnormalities of cortical thickness and cognitive impairment and the effect of modified Bushenyisui decoction(补肾益髓汤,BSYSD)on the cognitive function of multiple sclerosis(MS).METHODS:This prospective study was approved by the institutional review board.92 subjects were recruited,including 46 relapsing-remitting multiple sclerosis(RRMS)patients and 46 healthy controls(HC).Of the 46 patients,22 patients experienced the treatment of BSYSD for half a year.A conventional three-dimensional T1-weighted sequence were acquired for all participants on a 3.0 tesla magnetic resonance system.Basic information,detailed cognitive scales Montreal Cognitive Assessment(MoCA),symbol digit modalities test(SDMT),immediate memory,delayed recall,and long-term recognition were evaluated.Subcortical gray matter volume and cortical thickness weremeasured by FreeSurfer.The correlations between cortical thickness which MS patients showed reduced with respect to HC and cognitive scales wereanalyzed by Pearson correlation in RRMS patients.The influence of modified BSYSD on MS patients'cognition was analyzed by paired T Test.RESULTS:MoCA,immediate memory,delayed recall,and long-term delayed recognition in RRMS were significantly decreased than those of HC.Gray matter atrophy measured by FreeSurfer showed mainly in thalamus and hippocampus of RRMS patients.Compared with HC,the cortical thickness of several regions in frontal lobe,parietal lobe,temporal lobe,hippocampal,cingulate gyrus,and fusiform gyrus of RRMS patients were decreased with significant difference.The regions of cortical thickness thinning related to MoCA,immediate memory,delayed recall,and long-term delayed recognition were temporal lobe and fusiform gyrus.Modified BSYSD could improve MoCA,SDMT,immediate memory,delayed recall,and long-term delayed recognition of MS patients,and it could promote the recovery of cognitive function in MS patients.CONCLUSIONS:Gray matter atrophy and cortical thickness thinning were validated in RRMS.Cortical thickness thinning of temporal lobe and fusiform gyrus strongly related to cognitive deficits in RRMS.The modified BSYSD could promote the recovery of cognitive function in MS.

Cortical thickness abnormalities in patients with first episode psychosis:a meta-analysis of psychoradiologic studies and replication in an independent sample

Background:Abnormalities of cortical thickness(CTh)in patients with their first episode psychosis(FEP)have been frequently reported,but findings are inconsistent.Objective:To define the most consistent CTh changes in patients with FEP by meta-analysis of publishedwholebrain studies.Methods:The meta-analysis used seed-based dmapping(SDM)software to obtain the most prominent regional CTh changes in FEP,and meta-regression analyses to explore the effects of demographics and clinical characteristics.The meta-analysis results were verified in an independent sample of 142 FEP patients and 142 age-and sex-matched healthy controls(HCs),using both a vertex-wise and a region of interest analysis,with multiple comparisons correction.Results:The meta-analysis identified lower CTh in the rightmiddle temporal cortex(MTC)extending to superior temporal cortex(STC),insula,and anterior cingulate cortex(ACC)in FEP compared with HCs.No significant correlations were identified between CTh alterations and demographic or clinical variables.These results were replicated in the independent dataset analysis.Conclusion:This study identifies a robust pattern of cortical abnormalities in FEP and extends understanding of gray matter abnormalities and pathological mechanisms in FEP.

The pattern of cortical thickness underlying disruptive behaviors in Alzheimer’s disease

Background Disruptive behaviors,including agitation,disinhibition,irritability,and aberrant motor behaviors,are commonly observed in patients with Alzheimer’s disease(AD).However,the neuroanatomical basis of these disruptive behaviors is not fully understood.Objective To confirm the differences in cortical thickness and surface area between AD patients and healthy controls and to further investigate the features of cortical thickness and surface area associated with disruptive behaviors in patients with AD.Methods One hundred seventy-four participants(125 AD patients and 49 healthy controls)were recruited frommemory clinics at the Peking University Institute of Sixth Hospital.Disruptive behaviors,including agitation/aggression,disinhibition,irritability/lability,and aberrant motor activity subdomain scores,were evaluated using the Neuropsychiatry Inventory.Both whole-brain vertex-based and region-of-interest-based cortical thickness and surface area analyses were automatically conducted with the CIVET pipeline based on structural magnetic resonance images.Both group-based statistical comparisons and brain-behavior association analyses were performed using general linear models,with age,sex,and education level as covariables.Results Compared with healthy controls,the AD patients exhibited widespread reduced cortical thickness,with the most significant thinning located in the medial and lateral temporal and parietal cortex,and smaller surface areas in the left fusiform and left inferior temporal gyrus.High total scores of disruptive behaviors were significantly associated with cortical thinning in several regions that are involved in sensorimotor processing,language,and expression functions.The total score of disruptive behaviors did not show significant associations with surface areas.ConclusionWe highlight that disruptive behaviors in patientswith AD are selectively associated with cortical thickness abnormalities in sensory,motor,and language regions,which provides insights into neuroanatomical substrates underlying disruptive behaviors.These findings could lead to sensory,motor,and communication interventions for alleviating disruptive behaviors in patients with AD.

Cross-sectional associations between cortical thiclmess and physical activity in older adults with spontaneous memory complaints:The MAPT Study

Background:Age-related changes in brain structure may constitute the starting point for cerebral function alteration.Physical activity(PA)demonstrated favorable associations with total brain volume,but its relationship with cortical thickness(CT)remains unclear.We investigated the cross-sectional associations between PA level and CT in community-dwelling people aged 70 years and older.Methods:A total of 403 older adults aged 74.8±4.0 years(mean±SD)who underwent a baseline magnetic resonance imaging examination and who had data on PA and confounders were included.PA was assessed with a questionnaire.Participants were categorized according to PA levels.Multiple linear regressions were used to compare the brain CT(mm)of the inactive group(no PA at all)with 6 active groups(growing PA levels)in 34 regions of interest.Results:Compared with inactive persons,people who achieved PA at a level of 1500-1999 metabolic equivalent task-min/week(i.e.,about6-7 h of brisk walking for exercise) and those who achieved it at 2000-2999 metabolic equivalent task-min/week(i.e.,8-11 h of brisk walking for exercise)had higher CT in the fusiform gyrus and the temporal pole.Additionally,dose-response associations between PA and CT were found in the fusiform gyrus(B=0.011,SE=0.004,adj.p=0.035),the temporal pole(B=0.026,SE=0.009,adj.p=0.048),and the caudal middle frontal gyrus,the entorhinal,medial orbitofrontal,lateral occipital,and insular cortices.Conclusion:This study demonstrates a positive association between PA level and CT in temporal areas such as the fusiform gyrus,a brain region often associated to Alzheimer’s disease in people aged 70 years and older.Future investigations focusing on PA type may help to fulfil remaining knowledge gaps in this field.

Measurement of Cortical Bone Thickness in Adults by Cone-beam Computerized Tomography for Orthodontic Miniscrews Placement

The purpose of this study was to investigate the cortical bone thickness of the inter-dental area of both jaws for orthodontic miniscrew placement. The cone-beam computerized tomography images of 32 non-orthodontic adults with normal occlusion were taken to measure the cortical bone thick- ness in both.jaws. One-way analysis of variance （ANOVA） was used to analyze the differences in cortical bone thickness. Buccal cortical bone in the mandible was thicker than that in the maxilla. In the maxilla, cortical bone thickness was thicker in the buccal side than in the palatal side. Buccal cortical bone thickness in the mandible was thickest at the site distal to the first molar, and in the maxilla it was thickest at the site mesial to the first molar, while in the palatal side of maxilla it was thickest at the site mesial to the second premolar. The changing pattern of cortical bone thickness varies at different sites. In the buccal side of maxilla, the thinnest cortical bone thickness was lbund to be at 4 mm level from the alveolar crest, while the thickest was at 10 mm level （except for the site mesial to the first premolar）. The buccal cortical bone thickness at the sites mesial or distal to the first molar in the mandible and palatal cortical bone thickness of maxilla tended to increase with increasing distance from the alveolar bone.

Correlation between cerebral cortex changes and clinical features in patients with neuromyelitis optica spectrum disorder with normal-appearing brain tissue:a case-control study

Neuro myelitis optica spectrum disorder(NMOSD) is an inflammatory demyelinating disease of the central nervous system.However,whether and how cortical changes occur in NMOSD with normal-appearing brain tissue,or whether any cortical changes correlate with clinical chara cteristics,is not completely clear.The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age,sex,and educational background from December 2020 to February 2022.A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness,sulcal depth,and gyrification index.Analysis showed that cortical thickness in the bilate ral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants.Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes,those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus,superior parietal co rtex,and pericalcarine co rtex.Correlation analysis indicated that co rtical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale.These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue,and that the degree of thinning is correlated with clinical disability and cognitive function.These findings will help im prove our understanding of the imaging chara cteristics in NMOSD and their potential clinical significance.

A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

Surface-based map plasticity of brain regions related to sensory motor and pain information processing after osteonecrosis of the femoral head

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical positioning of functional data.The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,20 patients with osteonecrosis of the femoral head(12 males and 8 females,aged 56.80±13.60 years)and 20 healthy controls(9 males and 11 females,aged 54.56±10.23 years)were included in this study.Data of resting-state functional magnetic resonance imaging were collected.The results revealed that compared with healthy controls,compared with the healthy controls,patients with osteonecrosis of the femoral head(ONFH)showed significantly increased surface-based regional homogeneity(Re Ho)in areas distributed mainly in the left dorsolateral prefrontal cortex,frontal eye field,right frontal eye field,and the premotor cortex and decreased surface-based Re Ho in the right primary motor cortex and primary sensory cortex.Regions showing significant differences in surfacebased Re Ho values between the healthy controls and patients with ONFH were defined as the regions of interests.Seed-based functional connectivity was performed to investigate interregional functional synchronization.When the areas with decreased surface-based Re Ho in the frontal eye field and right premotor cortex were used as the regions of interest,compared with the healthy controls,the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex.Compared with healthy controls,patients with ONFH showed significantly decreased cortical thickness in the para-insular area,posterior insular area,anterior superior temporal area,frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens.These findings suggest that hip disorder patients showed cortical plasticity changes,mainly in sensorimotor-and pain-related regions.This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine(approval No.2018-041)on August 1,2018.

Structural remodeling in related brain regions in patients with facial synkinesis

Facial synkinesis is a troublesome sequelae of facial nerve malfunction.It is difficult to recover from synkinesis,despite improved surgical techniques for isolating the peripheral facial nerve branches.Furthermore,it remains unclear whether long-term dysfunction of motor control can lead to irreversible plasticity-induced structural brain changes.This case-control study thus investigated the structural brain alterations associated with facial synkinesis.The study was conducted at Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China.Twenty patients with facial synkinesis(2 male and 18 female,aged 33.35±6.97 years)and 19 healthy volunteers(2 male and 17 female,aged 33.21±6.75 years)underwent magnetic resonance imaging,and voxel-based and surface-based morphometry techniques were used to analyze data.There was no significant difference in brain volume between patients with facial synkinesis and healthy volunteers.Patients with facial synkinesis exhibited a significantly reduced cortical thickness in the contralateral superior and inferior temporal gyri and a reduced sulcal depth of the ipsilateral precuneus compared with healthy volunteers.In addition,sulcal depth of the ipsilateral precuneus was negatively correlated with the severity of depression.These findings suggest that there is a structural remodeling of gray matter in patients with facial synkinesis after facial nerve malfunction.This study was approved by the Ethics Review Committee of the Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China(approval No.2017-365-T267)on September 13,2017,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR1800014630)on January 25,2018.

Morphometric changes in the cortex following acute mild traumatic brain injury

Morphometric changes in cortical thickness(CT),cortical surface area(CSA),and cortical volume(CV) can reflect pathological changes after acute mild traumatic brain injury(m TBI).Most previous studies focused on changes in CT,CSA,and CV in subacute or chronic m TBI,and few studies have examined changes in CT,CSA,and CV in acute m TBI.Furthermore,acute m TBI patients typically show transient cognitive impairment,and few studies have reported on the relationship between cerebral morphological changes and cognitive function in patients with m TBI.This prospective cohort study included 30 patients with acute m TBI(15 males,15 females,mean age 33.7 years) and 27 matched healthy controls(12 males,15 females,mean age 37.7 years) who were recruited from the Second Xiangya Hospital of Central South University between September and December 2019.High-resolution T1-weighted images were acquired within 7 days after the onset of m TBI.The results of analyses using Free Surfer software revealed significantly increased CSA and CV in the right lateral occipital gyrus of acutestage m TBI patients compared with healthy controls,but no significant changes in CT.The acute-stage m TBI patients also showed reduced executive function and processing speed indicated by a lower score in the Digital Symbol Substitution Test,and reduced cognitive ability indicated by a longer time to complete the Trail Making Test-B.Both increased CSA and CV in the right lateral occipital gyrus were negatively correlated with performance in the Trail Making Test part A.These findings suggest that cognitive deficits and cortical alterations in CSA and CV can be detected in the acute stage of m TBI,and that increased CSA and CV in the right lateral occipital gyrus may be a compensatory mechanism for cognitive dysfunction in acute-stage m TBI patients.This study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University,China(approval No.086) on February 9,2019.

Sex differences of brain cortical structure in major depressive disorder

Background:Major depressive disorder(MDD)has different clinical presentations in males and females.However,the neuroanatom-ical mechanisms underlying these sex differences are not fully understood.Objective:The purpose of present study was to explore the sex differences in brain cortical thickness(CT)and surface area(SA)of MDD and the relationship between these differences and clinical manifestations in different gender.Methods:High-resolution T1-weighted images were acquired from 61 patients with MDD and 61 healthy controls(36 females and 25 males,both).The sex differences in CT and SA were obtained using the FreeSurfer software and compared between every two groups by post hoc test.Spearman correlation analysis was also performed to explore the relationships between these regions and clinical characteristics.Results:In male patients with MDD,the CT of the right precentral was thinner compared to female patients,although this did not survive Bonferroni correction.The SA of several regions,including right superior frontal,medial orbitofrontal gyrus,inferior frontal gyrus triangle,superior temporal,middle temporal,lateral occipital gyrus,and inferior parietal lobule in female patients with MDD was smaller than that in male patients(P<0.01 after Bonferroni correction).In female patients,the SA of the right superior temporal(r=0.438,P=0.008),middle temporal(r=0.340,P=0.043),and lateral occipital gyrus(r=0.372,P=0.025)were positively correlated with illness duration.Conclusion:The current study provides evidence of sex differences in CT and SA in patients with MDD,which may improve our understanding of the sex-specific neuroanatomical changes in the development of MDD.

Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment

Grey matter(GM)alterations may contribute to cognitive decline in individuals with white matter hyperintensities(WMH)but no consensus has yet emerged.Here,we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment(WMH-MCI),43 WMH patients without cognitive impairment,and 55 healthy controls.Both WMH groups showed GM atrophy in the bilateral thalamus,fronto-insular cortices,and several parietal-temporal regions,and the WMH-MCI group showed more extensive and severe GM atrophy.The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients.Furthermore,the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses.These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment.

Persistent alterations in gray matter in COVID-19 patients experiencing sleep disturbances:a 3-month longitudinal study

Sleep disturbances are among the most prevalent neuropsychiatric symptoms in individuals who have recovered from severe acute respiratory syndrome coronavirus 2 infections.Previous studies have demonstrated abnormal brain structures in patients with sleep disturbances who have recovered from coronavirus disease 2019(COVID-19).However,neuroimaging studies on sleep disturbances caused by COVID-19 are scarce,and existing studies have primarily focused on the long-term effects of the virus,with minimal acute phase data.As a result,little is known about the pathophysiology of sleep disturbances in the acute phase of COVID-19.To address this issue,we designed a longitudinal study to investigate whether alterations in brain structure occur during the acute phase of infection,and verified the results using 3-month follow-up data.A total of 26 COVID-19 patients with sleep disturbances(aged 51.5±13.57 years,8 women and 18 men),27 COVID-19 patients without sleep disturbances(aged 47.33±15.98 years,9 women and 18 men),and 31 age-and gender-matched healthy controls(aged 49.19±17.51 years,9 women and 22 men)were included in this study.Eleven COVID-19 patients with sleep disturbances were included in a longitudinal analysis.We found that COVID-19 patients with sleep disturbances exhibited brain structural changes in almost all brain lobes.The cortical thicknesses of the left pars opercularis and left precuneus were significantly negatively correlated with Pittsburgh Sleep Quality Index scores.Additionally,we observed changes in the volume of the hippocampus and its subfield regions in COVID-19 patients compared with the healthy controls.The 3-month follow-up data revealed indices of altered cerebral structure(cortical thickness,cortical grey matter volume,and cortical surface area)in the frontal-parietal cortex compared with the baseline in COVID-19 patients with sleep disturbances.Our findings indicate that the sleep disturbances patients had altered morphology in the cortical and hippocampal structures during the acute phase of infection and persistent changes in cortical regions at 3 months post-infection.These data improve our understanding of the pathophysiology of sleep disturbances caused by COVID-19.

Association between intercellular adhesion molecule-1 to depression and blood-brain barrier penetration in cerebellar vascular disease

BACKGROUND Cerebral small vessel disease(CSVD)is a prevalent cerebrovascular disease in clinical practice that is often associated with macrovascular disease.A clear understanding of the underlying causes of CSVD remains elusive.AIM To explore the association between intercellular adhesion molecule-1(ICAM-1)and blood-brain barrier(BBB)penetration in CSVD.METHODS This study included patients admitted to Fuyang People’s Hospital and Fuyang Community(Anhui,China)between December 2021 and March 2022.The study population comprised 142 patients,including 80 in the CSVD group and 62 in the control group.Depression was present in 53 out of 80 patients with CSVD.Multisequence magnetic resonance imaging(MRI)and dynamic contrast-enhanced MRI were applied in patients to determine the brain volume,cortical thickness,and cortical area of each brain region.Moreover,neuropsychological tests including the Hamilton depression scale,mini-mental state examination,and Montreal cognitive assessment basic scores were performed.RESULTS The multivariable analysis showed that age[P=0.011;odds ratio(OR)=0.930,95%confidence interval(CI):0.880-0.983]and ICAM-1 levels(P=0.023;OR=1.007,95%CI:1.001-1.013)were associated with CSVD.Two regions of interest(ROIs;ROI3 and ROI4)in the white matter showed significant(both P<0.001;95%CI:0.419-0.837 and 0.366-0.878)differences between the two groups,whereas only ROI1 in the gray matter showed signi-ficant difference(P=0.046;95%CI:0.007-0.680)between the two groups.ICAM-1 was significantly correlated(all P<0.05)with cortical thickness in multiple brain regions in the CSVD group.CONCLUSION This study revealed that ICAM-1 levels were independently associated with CSVD.ICAM-1 may be associated with cortical thickness in the brain,predominantly in the white matter,and a significant increase in BBB permeability,proposing the involvement of ICAM-1 in BBB destruction.

Neurofilament light chain is increased in the parahippocampal cortex and associates with pathological hallmarks in Parkinson’s disease dementia

Background Increased neurofilament levels in biofluids are commonly used as a proxy for neurodegeneration in several neurodegenerative disorders.In this study,we aimed to investigate the distribution of neurofilaments in the cerebral cortex of Parkinson’s disease(PD),PD with dementia(PDD)and dementia with Lewy bodies(DLB)donors,and its association with pathology load and MRI measures of atrophy and diffusivity.Methods Using a within-subject post-mortem MRI-pathology approach,we included 9 PD,12 PDD/DLB and 18 age-matched control donors.Cortical thickness and mean diffusivity(MD)metrics were extracted respectively from 3DT1 and DTI at 3T in-situ MRI.After autopsy,pathological hallmarks(pSer129-αSyn,p-tau and amyloid-βload)together with neurofilament light-chain(NfL)and phosphorylated-neurofilament medium-and heavy-chain(p-NfM/H)immunoreactivity were quantified in seven cortical regions,and studied in detail with confocal-laser scanning microscopy.The correlations between MRI and pathological measures were studied using linear mixed models.Results Compared to controls,p-NfM/H immunoreactivity was increased in all cortical regions in PD and PDD/DLB,whereas NfL immunoreactivity was increased in the parahippocampal and entorhinal cortex in PDD/DLB.NfL-positive neurons showed degenerative morphological features and axonal fragmentation.The increased p-NfM/H correlated with p-tau load,and NfL correlated with pSer129-αSyn but more strongly with p-tau load in PDD/DLB.Lastly,neuro-filament immunoreactivity correlated with cortical thinning in PD and with increased cortical MD in PDD/DLB.Conclusions Taken together,increased neurofilament immunoreactivity suggests underlying axonal injury and neurofilament accumulation in morphologically altered neurons with increased pathological burden.Importantly,we demonstrate that such neurofilament markers at least partly explain MRI measures that are associated with the neurodegenerative process.

Aberrant single-subject morphological brain networks in first-episode,treatment-naive adolescents with major depressive disorder

Background:Neuroimaging-based connectome studies have indicated that major depressive disorder(MDD)is associated with dis-rupted topological organization of large-scale brain networks.However,the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD.Objective:To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD.Methods:Twenty-five first-episode,treatment-naive adolescents with MDD and 19 healthy controls(HCs)underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests.Single-subject morphological brain networks were constructed separately based on cortical thickness,fractal dimension,gyrification index,and sulcus depth,and topologically characterized by graph-based approaches.Between-group differences were inferred by permutation testing.For significant alterations,partial correla-tions were used to examine their associations with clinical and neuropsychological variables in the patients.Finally,a support vector machine was used to classify the patients from controls.Results:Compared with the HCs,the patients exhibited topological alterations only in cortical thickness-based networks character-ized by higher nodal centralities in parietal(left primary sensory cortex)but lower nodal centralities in temporal(left parabelt complex,right perirhinal ectorhinal cortex,right area PHT and right ventral visual complex)regions.Moreover,decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients.These results were largely reproducible for binary and weighted network analyses.Finally,topological properties of the cortical thickness-based net-works were able to distinguish the MDD adolescents from HCs with 87.6%accuracy.Conclusion:Adolescent MDD is associated with disrupted topological organization of morphological brain networks,and the disrup-tions provide potential biomarkers for diagnosing and monitoring the disease.

A Systematic Characterization of Structural Brain Changes in Schizophrenia

A systematic characterization of the similarities and differences among different methods for detecting structural brain abnormalities in schizophrenia,such as voxel-based morphometry(VBM),tensor-based morphometry(TBM),and projection-based thickness(PBT),is important for understanding the brain pathology in schizophrenia and for developing effective biomarkers for a diagnosis of schizophrenia.However,such studies are still lacking.Here,we performed VBM,TBM,and PBT analyses on T1-weighted brain MR images acquired from 116 patients with schizophrenia and 116 healthy controls.We found that,although all methods detected wide-spread structural changes,different methods captured different information-only 10.35%of the grey matter changes in cortex were detected by all three methods,and VBM only detected 11.36%of the white matter changes detected by TBM.Further,pattern classification between patients and controls revealed that combining different measures improved the classification accuracy(81.9%),indicating that fusion of different structural measures serves as a better neuroimaging marker for the objective diagnosis of schizophrenia.