Cortical Thinning In Patients Research Articles

Neurofilament Light Chain Levels Interact with Neurodegenerative Patterns and Motor Neuron Dysfunction in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving rapid motor neuron degeneration leading to brain, primarily precentral, atrophy. Neurofilament light chains are a robust prognostic biomarker highly specific to ALS, yet associations between neurofilament light chains and MR imaging outcomes are not well-understood. We investigated the role of neurofilament light chains as mediators among neuroradiologic assessments, precentral neurodegeneration, and disability in ALS. We retrospectively analyzed a prospective cohort of 29 patients with ALS (mean age, 56 [SD, 12] years; 18 men) and 36 controls (mean age, 49 [SD, 11] years; 18 men). Patients underwent 3T (n = 19) or 7T (n = 10) MR imaging, serum (n = 23) and CSF (n = 15) neurofilament light chains, and clinical (n = 29) and electrophysiologic (n = 27) assessments. The control group had equivalent 3T (n = 25) or 7T (n = 11) MR imaging. Two trained neuroradiologists performed blinded qualitative assessments of MR imaging anomalies (n = 29 patients, n = 36 controls). Associations between precentral cortical thickness and neurofilament light chains and clinical and electrophysiologic data were analyzed. We observed extensive cortical thinning in patients compared with controls. MR imaging analyses showed significant associations between precentral cortical thickness and bulbar or arm impairment following distributions corresponding to the motor homunculus. Finally, uncorrected results showed positive interactions among precentral cortical thickness, serum neurofilament light chains, and electrophysiologic outcomes. Qualitative MR imaging anomalies including global atrophy (P = .003) and FLAIR corticospinal tract hypersignal anomalies (P = .033), correlated positively with serum neurofilament light chains. Serum neurofilament light chains may be an important mediator between clinical symptoms and neuronal loss according to cortical thickness. Furthermore, MR imaging anomalies might have underestimated prognostic value because they seem to indicate higher serum neurofilament light chain levels.

Distinct spatiotemporal patterns of cortical thinning in Alzheimer’s disease-type cognitive impairment and subcortical vascular cognitive impairment

Previous studies on Alzheimer’s disease-type cognitive impairment (ADCI) and subcortical vascular cognitive impairment (SVCI) has rarely explored spatiotemporal heterogeneity. This study aims to identify distinct spatiotemporal cortical atrophy patterns in ADCI and SVCI. 1,338 participants (713 ADCI, 208 SVCI, and 417 cognitively unimpaired elders) underwent brain magnetic resonance imaging (MRI), amyloid positron emission tomography, and neuropsychological tests. Using MRI, this study measures cortical thickness in five brain regions (medial temporal, inferior temporal, posterior medial parietal, lateral parietal, and frontal areas) and utilizes the Subtype and Stage Inference (SuStaIn) model to predict the most probable subtype and stage for each participant. SuStaIn identifies two distinct cortical thinning patterns in ADCI (medial temporal: 65.8%, diffuse: 34.2%) and SVCI (frontotemporal: 47.1%, parietal: 52.9%) patients. The medial temporal subtype of ADCI shows a faster decline in attention, visuospatial, visual memory, and frontal/executive domains than the diffuse subtype (p-value < 0.01). However, there are no significant differences in longitudinal cognitive outcomes between the two subtypes of SVCI. Our study provides valuable insights into the distinct spatiotemporal patterns of cortical thinning in patients with ADCI and SVCI, suggesting the potential for individualized therapeutic and preventive strategies to improve clinical outcomes.

Valproate use associated with frontal and cerebellar gray matter volume reductions: A voxel-based morphometry study.

Recent morphometric magnetic resonance imaging (MRI) studies suggested the possibility that valproate (VPA) use is associated with parieto-occipital cortical thinning in patients with heterogeneous epilepsy syndromes. In this study, we examined the effect of VPA on the brain volume using a large number of homogenous patients with idiopathic generalized epilepsy. Voxel-based morphometry was used to compare regional gray matter (GM) volume between 112 patients currently taking VPA (VPA+ group), 81 patients not currently taking VPA (VPA- group), and 120 healthy subjects (control group). The VPA+ group showed a significant GM volume reduction in the bilateral cerebellum, hippocampus, insula, caudate nucleus, medial frontal cortex/anterior cingulate cortex, primary motor/premotor cortex, medial occipital cortex, and anteromedial thalamus, as compared to the control group. The VPA- group showed a significant GM volume reduction in the anteromedial thalamus and right hippocampus/temporal cortex, as compared to the control group. Compared to the VPA- group, the VPA+ group had a significant GM volume reduction in the bilateral cerebellum, primary motor/premotor cortex, and medial frontal cortex/anterior cingulate cortex. We have provided evidence that VPA use could result in GM volume reductions in the frontal cortex and cerebellum. Our findings should be acknowledged as a potential confounding factor in morphometric MRI studies that include subjects taking VPA.

Differential effects of parental socioeconomic status on cortical thickness in patients with schizophrenia spectrum disorders and healthy controls

ObjectivesWidespread changes in cortical thickness (CT) have been repeatedly reported in schizophrenia (SZ). The nature of the pathophysiologic process underlying such changes remains to be elucidated. The aims of the present study were to measure the CT; evaluate parent socioeconomic status (pSES), childhood trauma (ChT) and premorbid adjustment (PA) in patients with schizophrenia spectrum disorders (SSDs); and investigate group differences in CT (i.e., SSD vs. healthy controls (HCs)), pSES, PA, and/or ChT, as well as the interactions among these factors. Methods164 patients with SSD and 245 age-, sex- and education-matched healthy controls have participated. The pSES, ChT and PA were evaluated using Korean version of Polyenvironmental Risk Score, Early Trauma Inventory Self Report-Short Form and Premorbid Adjustment Scale, respectively. Vertex-wise measure of CT was estimated using the FreeSurfer. To investigate the main effects and interactions, multilevel regression was employed. ResultsWe found widespread cortical thinning in patients with SSDs compared to HCs. The cortical thinning was associated with ChT, symptom severity and chlorpromazine equivalent dose and duration of illness in patients. In multilevel regression, main effects of group and pSES and interaction between group and pSES were found whereas a significant interaction between ChT and CPZ equivalent was found in patients. ConclusionOur findings indicate that compared to HCs, patients with SSDs have cortical structural abnormalities, and that group and pSES interaction determines CT. Further studies are needed to explore the effects of psychosocial factors on brain structural and functional abnormalities in SZ.

Neuropsychological correlates of cerebellar volumes in multiple sclerosis: an MRI volumetric analysis study.

The hallmark of Multiple Sclerosis (MS) pathophysiology is the damage to the myelin sheath around axons. The cerebellum is a predilection site for demyelination with a well-recognized role in motor and a rather understudied contribution to cognitive functions. The aim of this study is to investigate patterns of cerebellar grey and white matter pathology, expressed as reduced volume, as well as cortical thickness and their potential contribution to cognitive performance and disability status of patients with MS. 24 patients with MS underwent extensive neuropsychological assessment using paper and pencil tests and the Brain Health Assessment (BHA) tablet-based battery. Cerebellar lobular volumes and thickness were calculated using a volumetric analysis with automated segmentation of the cerebellum and its lobules. The main findings are a reduction of cerebellar grey matter (CGMV) and white matter volumes (CWMV) in lobule X and a widespread cerebellar cortical thinning in patients. Overall disease severity and neurological disability, assessed with the Expanded Disability Status Severity Scale, was correlated with fatigue and information processing speed tasks, but not with CGMV and CWMV. CWMV and CGMV of lobule I-II was negatively correlated with information processing speed, as well as visuospatial memory tests and, finally, inverse cortical thinning associations were noted between the whole cerebellum, lobule I-II, lobule III, lobule VI, Crus I, lobule VIIIA and information processing speed and verbal fluency tasks. The inverse associations observed may represent a compensatory mechanism activated in MS engaging additional high-level cortical areas functionally interconnected with the damaged cerebellum, in order to cope with the cognitive demands of a task.

Impact of environmental factors and premorbid adjustment on the cortical thinning in patients with schizophrenia

Impact of environmental factors and premorbid adjustment on the cortical thinning in patients with schizophrenia

Integrated 18F-T807 Tau PET, Structural MRI, and Plasma Tau in Tauopathy Neurodegenerative Disorders.

Background and Objective: Tau-specific positron emission topography (PET) imaging enables in vivo assessment of Alzheimer's disease (AD). We aimed to investigate its performance in combination with plasma tau levels in patients with non-AD tauopathy.Methods: A total of 47 participants were enrolled, including 10 healthy controls, 16 with tauopathy parkinsonism syndromes (9 with corticobasal syndrome [CBS], 7 with progressive supranuclear palsy [PSP]), 9 with frontotemporal dementia (FTD), 4 with AD, and 8 with Parkinson's disease (PD). All participants underwent clinical assessments, 18F-T807 tau PET, brain MRI, and plasma tau assay.Results: The global cortical standard uptake value ratio (SUVR) of 18F-T807 PET was comparable between PD and control (p = 0.088). The cortical SUVR was significantly higher in AD group (p = 0.002) but was modestly increased in PSP group compared to the PD group (p = 0.044), especially in parietal and pallidal regions. Asymmetric 18F-T807 uptake at the pallidum was noted in patients with CBS and FTD. Cortical tau tracer uptake was associated with increased plasma total tau level (p = 0.016), especially in frontal and parietal regions. Regional tracer uptake was correlated with cortical thinning in patients with CBS and PSP (CBS: r = −0.092, p = 0.025; PSP: r = −0.114, p = 0.015).Conclusions: The 18F-T807 tau tracer uptake was only modestly increased in patients with PSP. Although the cortical tau tracer uptake correlated with regional cortical atrophy and plasma tau levels, a four-repeated tau-specific tracer is needed for future classifying tauopathy parkinsonism syndromes.

Temporal and extratemporal atrophic manifestation of temporal lobe epilepsy using voxel-based morphometry and corticometry: clinical application in lateralization of epileptogenic zone.

Advances in MRI acquisition and data processing have become important for revealing brain structural changes. Previous studies have reported widespread structural brain abnormalities and cortical thinning in patients with temporal lobe epilepsy (TLE), as the most common form of focal epilepsy. In this research, healthy control cases (n = 20) and patients with left TLE (n = 19) and right TLE (n = 14) were recruited, all underwent 3.0T MRI with magnetization-prepared rapid gradient echo sequence to acquire T1-weighted images. Morphometric alterations in gray matter were identified using voxel-based morphometry (VBM). Volumetric alterations in subcortical structures and cortical thinning were also determined. Patients with left TLE demonstrated more prevailing and widespread changes in subcortical volumes and cortical thickness than right TLE, mainly in the left hemisphere, compared to the healthy group. Both VBM analysis and subcortical volumetry detected significant hippocampal atrophy in ipsilateral compared to contralateral side in TLE group. In addition to hippocampus, subcortical volumetry found the thalamus and pallidum bilaterally vulnerable to the TLE. Furthermore, the TLE patients underwent cortical thinning beyond the temporal lobe, affecting gray matter cortices in frontal, parietal, and occipital lobes in the majority of patients, more prevalently for left TLE cases. Exploiting volume changes in individual patients in the hippocampus alone led to 63.6% sensitivity and 100% specificity for lateralization of TLE. Alteration of gray matter volumes in subcortical regions and neocortical temporal structures and also cortical gray matter thickness were evidenced as common effects of epileptogenicity, as manifested by the majority of cases in this study.

Pattern of cortical thinning in patients with mild cognitive impairment associated with obstructive sleep apnea compared to patients with age‐associated mild cognitive impairment

AbstractBackgroundObstructive sleep apnea (OSA) is a reversible cause of mild cognitive impairment (MCI). There are evidences that OSA associated with decline of brain cortex. The pattern of cortical thinning in OSA associated MCI has not been well characterized. This study sought to assess pattern of cortical thinning in MCI patients with OSA (MCI‐OSA).MethodWe analyzed magnetic resonance images (MRI) of MCI‐OSA and age associated (MCI‐AA) to determine difference in cortical atrophy pattern between two groups. Firstly, cortical surfaces were reconstructed from each patient’s MRI. Cortical thickness measurement was then processed on these surfaces. At last, thickness comparison between the two groups was performed using vertex‐by‐vertex general linear model (GLM) and standard t‐test.ResultSubjects were consecutively recruited including 22 MCI‐OSA patients and 20 MCI‐AA patients. Compared to MCI‐AA, MCI‐OSA patients has larger brain volume (p=0.002). Using GLM, we found 3 large clusters in the left anterior cingulate, the left and right lateral occipital cortices that were significantly thinner in MCI‐OSA (p&lt;0.001, p=0.005, p=0.001, respectively). Using t‐test, we found 11 cortical regions with different thicknesses between the two groups. Only the left anterior cingulate cortex remained significantly thinner in the MCI‐OSA group using both methods.ConclusionWe demonstrated that MCI‐OSA patients had significant thinning of left anterior cingulate gyrus as compared to MCI‐AA despite having larger brain volume.

Long term cortical thickness changes after a first episode of non- affective psychosis: The 10 year follow-up of the PAFIP cohort

Cortical thickness has been widely studied in individuals with schizophrenia and, in particular, first-episode psychosis. Abnormalities have been described, although there is, to date, a lack of consensus regarding changes across time and correlations with clinical and functional outcomes of the illness.One hundred and twenty-three first-episode psychosis patients and 74 healthy volunteers were subjected to magnetic resonance imaging scans and clinical and functional assessments by different scales at four consecutive visits during a 10 year follow-up period. Linear mixed effects models were applied to our data to compute cortical thickness changes over time in (1) schizophrenia patients versus healthy controls and (2) in patients with good versus poor functional outcome. The associations between cortical thickness percentage changes and clinical and functional status at 10 years were also assessed.The patients presented a thinner cortex than the controls at baseline (b's = −0.06; q ≤ 0.00023) with non-significant coefficients for the interaction term (follow-up time x group) (b's = −0.001; q ≥ 0.681). Poor functioning patients presented statistically significant coefficients for the interaction term (follow-up time x functionality) (left: b = −0.005, q = 0.019; right: b = −0.005, q = 0.022). In contrast, no correlations were found between cortical thickness measurements and clinical variables at 10 years.Overall, there were widespread thickness anomalies in first-episode psychosis patients across cortical regions that remained stable across time. Progressive thickness changes were related to patient functional outcomes, with progressive and steeper cortical thinning in patients with worse functional outcomes and a stabilization in those with better outcomes.

Progressive Cortical Thinning in Patients With Focal Epilepsy

It is controversial whether epilepsy is a static or progressive disease. Evidence of progressive gray matter loss in epilepsy would support early diagnosis, rapid treatment, and early referral for surgical interventions. To demonstrate progressive cortical thinning in patients with focal epilepsy distinct from cortical thinning associated with normal aging. A case-control neuroimaging study was conducted from August 3, 2004, to January 26, 2016, among 190 patients with focal epilepsy at a tertiary epilepsy referral center (epilepsy data) and 3 independent comparison cohorts matched for age and sex (healthy volunteer data; n = 141). Two or more high-resolution T1-weighted magnetic resonance imaging scans at least 6 months apart (mean [SD] interval, 2.5 [1.6] years). Global and vertexwise rate of progressive cortical thinning. A total of 190 people with focal epilepsy (99 women and 91 men; mean [SD] age, 36 [11] years; 396 magnetic resonance imaging scans) were compared with 141 healthy volunteers (76 women and 65 men; mean [SD] age, 35 [17] years; 282 magnetic resonance imaging scans). Widespread highly significant progressive cortical thinning exceeding normal aging effects, mainly involving the bilateral temporal lobes, medial parietal and occipital cortices, pericentral gyri, and opercula, was seen in 146 individuals with epilepsy (76.8%; 95% CI, 58%-95%). The mean (SD) annualized rate of global cortical thinning in patients with epilepsy was twice the rate of age-associated thinning observed in healthy volunteers (0.024 [0.061] vs 0.011 [0.029] mm/y; P = .01). Progression was most pronounced in adults older than 55 years and during the first 5 years after the onset of seizures. Areas of accelerated cortical thinning were detected in patients with early onset of epilepsy and in patients with hippocampal sclerosis. Accelerated thinning was not associated with seizure frequency, history of generalized seizures, or antiepileptic drug load and did not differ between patients with or without ongoing seizures. Progressive atrophy in temporal (n = 101) and frontal (n = 28) lobe epilepsy was most pronounced ipsilaterally to the epileptic focus but also affected a widespread area extending beyond the focus and commonly affected the contralateral hemisphere. For patients with temporal lobe epilepsy, accelerated cortical thinning was observed within areas structurally connected with the ipsilateral hippocampus. Widespread progressive cortical thinning exceeding that seen with normal aging may occur in patients with focal epilepsy. These findings appear to highlight the need to develop epilepsy disease-modifying treatments to disrupt or slow ongoing atrophy. Longitudinal cortical thickness measurements may have the potential to serve as biomarkers for such studies.

Cortical thinning in patients with REM sleep behavior disorder is associated with clinical progression

The aim of this study is to determine whether structural MRI measures are associated with clinical impairment and progression to a Lewy body disease in patients with idiopathic REM sleep behavior disorder (iRBD). Twenty-seven patients with iRBD in addition to patients with de novo PD and healthy controls were included from the Parkinson’s Progression Markers Initiative. Patients with iRBD were followed for up to 3 years. Clinical and MRI measures were compared across groups and the association between clinical features and structural MRI was assessed in iRBD patients. Cox regression analyses were applied to identify risk factors for progressing to a Lewy body disease in iRBD. Our results showed that, at baseline, iRBD patients showed parietal and occipital cortical thinning, compared to controls. They also showed worse motor and non-motor abilities, some of which correlated with motor, frontal or temporal cortical thinning. At follow-up, six (22%) iRBD patients were diagnosed with a Lewy body disorder. These patients showed cortical thinning in frontal, occipital and parietal areas compared to iRBD non-converters. Cortical thinning was a significant predictor for future development of a Lewy body disorder (HR: 0.784; 95% CI: 0.640–0.960; p = 0.02). We conclude that cortical thinning is associated with worse motor and non-motor abilities, and predicts conversion to a Lewy body disorder in iRBD, suggesting it could be used to select candidates for clinical trials to delay the onset of neurodegenerative disease.

Evidence for a genetic effect in altered cortical surface area but not in cortical thinning in siblings of patients with mesial temporal lobe epilepsy: Commentary on: "Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study".

Although studies have shown cortical and subcortical changes in first-degree relatives of patients with familial forms of temporal lobe epilepsy, few studies have addressed extrahippocampal morphology changes in unaffected siblings of patients with sporadic mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Alhusaini et al1 described subtle reduced cortical volumes in the anteromedial temporal cortex of asymptomatic siblings of sporadic MTLE-HS patients, suggesting that such localized traits are possibly heritable. In this issue of Epilepsia, Yaakub et al2 replicated these findings in first-degree asymptomatic relatives of patients with MTLE-HS.2 A positive history of simple febrile convulsions before the age of 4 years was present in two relatives in this study.2 Both these relatives had values above the median of the relative group for the reduced surface area in the anteromedial temporal cortex, further strengthening the possibility that these subtle morphological changes are inherited.2 Limitations of this study include the small number of subjects studied and that they side-flipped the images to increase power to detect differences, thus treating both hemispheres as if they were equal, which is not the case, as shown recently by Kong et al.3 The study by Alhusaini et al1 showed that the alterations of cortical morphology found in anteromedial regions of unaffected siblings of subjects with left MTLE-HS (more in the left entorhinal cortex and parahippocampal gyrus) differed from those found in unaffected siblings of subjects with right MTLE-HS (more in the right entorhinal cortex and temporal pole). It is of relevance that both studies1, 2 used FreeSurfer (http://surfer.nmr.mgh.harvard.edu), which measures cortical volume as a product of two distinct aspects of the cortical architecture: cortical thickness and surface area.4 Cortical thickness and surface area measurements appear to represent different early neurodevelopmental events with distinct genetic influences, as shown by Panizzon et al5 in a magnetic resonance imaging study of twins. They found that, although cortical thickness and surface area are both highly heritable (>0.80), they are mostly unrelated genetically (genetic correlation = 0.08).5 These results suggest some independence of these two surface-based measures, and potentially, their asymmetry patterns. A recent study that mapped cortical brain asymmetry in 17 141 healthy individuals showed regions with different asymmetrical patterns in cortical thickness and surface area and a significant heritability of these asymmetry characteristics.3 Effect sizes of cortical thickness and surface area were independent, and the asymmetry was generally more prominent for surface area compared with that of cortical thickness.3 Most regions showed significant asymmetry in surface area, although with no clear directional pattern affecting neighboring regions, or along the anterior-posterior axis, as they observed for cortical thickness.3 Widespread cerebral cortical thinning has been identified in patients with MTLE as compared to healthy controls within several cortical regions, including the mesiotemporal, limbic, and central sensorimotor cortices.6 This pattern of cortical thinning appeared progressive in patients with medically refractory epilepsy,6 but also to a lesser degree in MTLE patients under seizure control.7 Less attention has been paid to cortical surface area in studies of MTLE patients. Interestingly, both Alhusaini et al1 and Yaakub et al2 found reduced cortical surface areas in anteromedial temporal regions of asymptomatic siblings of sporadic MTLE-HS patients, but no significant changes in cortical thickness. This lack of cortical thickness changes has been confirmed in 127 asymptomatic first-degree relatives of MTLE-HS patients from three independent cohorts, each with a healthy control group.8 These findings altogether indicate that the previously characterized progressive cortical thinning in patients with MTLE-HS is not heritable and is likely driven by disease-related factors, whereas changes in the cortical surface area may represent an inherited trait that preceded seizure onset. This hypothesis needs to be confirmed in further studies with multiple large cohorts, also taking into account the asymmetric nature of cerebral hemispheres. The author has no conflict of interest to disclose. I confirm that I have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

A five-year longitudinal study reveals progressive cortical thinning in narcolepsy and faster cortical thinning in relation to early-onset.

Narcolepsy with cataplexy is characterized by excessive daytime sleepiness, cataplexy, and other REM sleep phenomena. Previous MRI studies were cross-sectional in design and could not adequately address if disease progression leads the brain structural abnormalities in narcolepsy. Our analysis in patients using longitudinally collected brain MRIs (n = 17; 2 scans per patient; scan interval: 4.7 ± 1.9years) revealed widespread progressive cortical thinning in bilateral dorsolateral frontal and fusiform cortices, right anterior cingulate (corrected p < 0.05). Cross-sectional analyses showed faster progressive cortical thinning in patients than controls (n = 83, one scan per subject available), which we confirmed significant in the analysis of a small-set of longitudinal control data (n = 10). The pattern of progressive thinning in patients was overlapped well with those found in structural and functional studies of narcolepsy. We also found a faster progression of cortical thinning and worse disease severity (decreased sleep efficiency, increased sleep latency and arousal index) over time in a subgroup of patients with earlier disease onset (n = 9, onset age: 15.9 ± 2.5years old) compared to later disease onset (n = 8, 25.3 ± 4.9). The faster progressive cortical thinning and worse disease severity over time in the patients with early-onset suggest compelling evidence of disease progression existing in this phenotype of narcolepsy syndrome. Our result based on a small dataset, however, demands a more careful investigation of the underlying mechanism.

Linking Cortical and Connectional Pathology in Schizophrenia.

Schizophrenia is associated with cortical thickness (CT) deficits and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relationship between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration. Structural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy controls to map CT and fractional anisotropy in regionally adjacent infracortical white matter at various cortical depths. We found a robust and reproducible relationship between thickness and anisotropy deficits, which were inversely correlated across cortical regions (r = -.5, P < .0001): the most anisotropic infracortical white matter was found adjacent to regions with extensive cortical thinning. This pattern was evident in early (20 y: r = -.3, P = .005) and middle life (30 y: r = -.4, P = .004, 40 y: r = -.3, P = .04), but not beyond 50 years (P > .05). Frontal pathology contributed most to this pattern, with cortical thinning in patients compared to controls at all ages (P < .05); in contrast to initially elevated frontal white matter anisotropy in patients at 30 years, followed by rapid white matter decline with age (rate of annual decline; patients: 0.0012, controls 0.0006, P < .001). Our findings point to pathological dependencies between gray and white matter in a large sample of schizophrenia patients. We argue that elevated frontal anisotropy reflects regionally-specific, compensatory responses to cortical thinning, which are eventually overwhelmed with increasing illness duration.

Amyloid-β-related and unrelated cortical thinning in dementia with Lewy bodies.

Coexisting Alzheimer's disease (AD) pathology is common in patients with dementia with Lewy bodies (DLB). To evaluate the cortical thinning in patients with DLB considering the effect of amyloid-β (Aβ), we compared the regional cortical thickness between control subjects and patients with DLB with abnormal dopamine transporter imaging. Seventeen (43.6%) of 39 patients with DLB and no control subjects had significant Aβ deposition on 18F-florbetaben positron emission tomography. Compared to control (n= 15), Aβ-negative DLB group (n= 21) had cortical thinning in the bilateral insula, entorhinal, basal frontal, and occipito-parietal cortices. Compared to Aβ-negative DLB, Aβ-positive DLB group (n= 15) had a lower cortical thickness in the AD-prone brain regions in addition to the bilateral occipital, basal frontal, and somatomotor cortices. After controlling for the amount of Aβ deposition, DLB group had cortical thinning in the same regions affected in the Aβ-negative DLB group. In summary, patients with DLB had an Aβ-independent cortical thinning, while Aβ was associated with additional cortical thinning in the AD-prone brain regions and the aggravation of DLB-specific cortical thinning.

O6.5. LINKING CORTICAL AND CONNECTIONAL PATHOLOGY IN SCHIZOPHRENIA

BackgroundSchizophrenia is associated with cortical thinning and breakdown in white matter microstructure. Whether these pathological processes are related remains unclear. We used multimodal neuroimaging to investigate the relation between regional cortical thinning and breakdown in adjacent infracortical white matter as a function of age and illness duration.MethodsStructural magnetic resonance and diffusion images were acquired in 218 schizophrenia patients and 167 age-matched healthy controls to map cortical thickness (CT) and fractional anisotropy (FA) in regionally adjacent infracortical white matter at various cortical depths.ResultsBetween-group differences in CT and infracortical FA were inversely correlated across cortical regions (r=−0.5, p<0.0001), such that the most anisotropic infracortical white matter was found adjacent to regions with extensive cortical thinning. This pattern was evident in early (20 years: r=−0.3, p=0.005) and middle life (30 years: r=−0.4, p=0.004, 40 years: r=−0.3, p=0.04), but not beyond 50 years (p>0.05). Frontal pathology contributed most to this pattern, with extensive cortical thinning in patients compared to controls at all ages (p<0.05); in contrast to initially increased frontal infracortical FA in patients at 30 years, followed by rapid decline in frontal FA with age (rate of annual decline; patients: 0.0012, controls 0.0006, p<0.001).DiscussionCortical thinning and breakdown in white matter anisotropy are inversely related in young schizophrenia patients, with abnormally elevated white matter myelination found adjacent to frontal regions with extensive cortical thinning. We argue that elevated frontal anisotropy reflects regionally-specific, compensatory responses to cortical thinning, which are eventually overwhelmed with increasing illness duration.

Focal cortical thinning in patients with stable relapsing-remitting multiple sclerosis: cross-sectional-based novel estimation of gray matter kinetics.

The aim of our study is to identify radiological patterns of cortical gray matter atrophy (CGMA) that correlate with disease duration in patients with relapsing-remitting multiple sclerosis (RRMS). RRMS patients were randomly selected from the Sheba Multiple Sclerosis (MS) center computerized data registry based on stratification of disease duration up to 10years. Patients were scanned by 3.0T (Signa, GE) MRI, using a T1 weighted 3D high resolution, FSPGR, MS protocol. Neurological disability was assessed by the Expanded Disability Status Scale (EDSS). FreeSurfer was used to obtain brain volumetric segmentation and to perform cortical thickness surface-based analysis. Clusters of change in cortical thickness with correlation to disease duration were produced. Two hundred seventy-one RRMS patients, mean ± SD age 33.0 ± 7.0years, EDSS 1.6 ± 1.2, disease duration 5.0 ± 3.4years. Cortical thickness analysis demonstrated focal areas of cerebral thinning that correlated with disease duration. Seven clusters accounting for 11.7% of the left hemisphere surface and eight clusters accounting for 10.6% of the right hemisphere surface were identified, with cluster-wise probability of p < 0.002 and p < 0.02, respectively.The clusters included bilateral involvement of areas within the cingulate, precentral, postcentral, paracentral, superior-parietal, superior-frontal gyri and insular cortex. Mean and cluster-wise cortical thickness negatively correlated with EDSS score, p < 0.001, with stronger Spearman rho for cluster-wise measurements. We identified CGMA patterns in sensitive brain regions which give insight and better understanding of the progression of cortical gray matter loss in relation to dissemination in space and time. These patterns may serve as markers to modulate therapeutic interventions to improve the management of MS patients.

Negative correlation of cortical thickness with the severity and duration of abdominal pain in Asian women with irritable bowel syndrome.

Background & aimsIrritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain–gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS.MethodsThirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics.ResultsThe left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain.ConclusionsSome of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

Effects of environmental risks and polygenic loading for schizophrenia on cortical thickness

There are established differences in cortical thickness (CT) in schizophrenia (SCZ) and bipolar (BD) patients when compared to healthy controls (HC). However, it is unknown to what extent environmental or genetic risk factors impact on CT in these populations. We have investigated the effect of Environmental Risk Scores (ERS) and Polygenic Risk Scores for SCZ (PGRS-SCZ) on CT.Structural MRI scans were acquired at 3T for patients with SCZ or BD (n=57) and controls (n=41). Cortical reconstructions were generated in FreeSurfer (v5.3). The ERS was created by determining exposure to cannabis use, childhood adverse events, migration, urbanicity and obstetric complications. The PGRS-SCZ were generated, for a subset of the sample (Patients=43, HC=32), based on the latest PGC GWAS findings. ANCOVAs were used to test the hypotheses that ERS and PGRS-SCZ relate to CT globally, and in frontal and temporal lobes.An increase in ERS was negatively associated with CT within temporal lobe for patients. A higher PGRS-SCZ was also related to global cortical thinning for patients. ERS effects remained significant when including PGRS-SCZ as a fixed effect. No relationship which survived FDR correction was found for ERS and PGRS-SCZ in controls.Environmental risk for SCZ was related to localised cortical thinning in patients with SCZ and BD, while increased PGRS-SCZ was associated with global cortical thinning. Genetic and environmental risk factors for SCZ appear therefore to have differential effects. This provides a mechanistic means by which different risk factors may contribute to the development of SCZ and BD.