Gray Matter Volume Loss Research Articles

Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function.

Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss.

Progression of Structural Brain Changes in Patients With Chronic Pancreatitis and Its Association to Chronic Pain: A 7-Year Longitudinal Follow-up Study.

Temporal information about the structural brain changes in chronic pancreatitis (CP) and its relation to the clinical manifestations is lacking. This study investigated changes in morphological brain parameters over 7 years in painful CP patients, compared with controls. In this 7-year longitudinal magnetic resonance imaging study, we included 23 CP patients and 14 controls. Gray matter volume (GMV) and cortical thickness were examined using voxel-based and surface-based morphometry. In addition, patients completed pain questionnaires and diary. At baseline, patients had reduced GMV and cortical thickness in widespread brain areas compared with controls. After 7 years of follow-up, the GMV loss was more pronounced in patients compared with controls, particularly in precentral gyrus and putamen. Moreover, an increase in pain scores was associated with a less reduction of thalamic GMV (P = 0.046), whereas an increase in brief pain inventory score was associated with more reduction in cortical thickness of precentral (P = 0.005) and superior temporal gyri (P = 0.019), indicating that brain morphological alterations are associated with the pain. Chronic pancreatitis pain is associated with morphological brain changes over time in several areas, reflecting that brain plasticity may be a consequence of repeated long-term nociceptive signaling.

Regional White Matter Hyperintensity Influences Grey Matter Atrophy in Mild Cognitive Impairment.

The association between cerebrovascular disease pathology (measured by white matter hyperintensities, WMH) and brain atrophy in early Alzheimer's disease (AD) remain to be elucidated. Thus, we investigated how WMH influence neurodegeneration and cognition in prodromal and clinical AD. We examined 51 healthy controls, 35 subjects with mild cognitive impairment (MCI), and 30 AD patients. We tested how total and regional WMH is related to specific grey matter volume (GMV) reductions in MCI and AD compared to controls. Stepwise regression analysis was further performed to investigate the association of GMV and regional WMH volume with global cognition. We found that total WMH volume was highest in AD but showed the strongest association with lower GMV in MCI. Frontal and parietal WMH had the most extensive influence on GMV loss in MCI. Additionally, parietal lobe WMH volume (but not hippocampal atrophy) was significantly associated with global cognition in MCI while smaller hippocampal volume (but not WMH volume) was associated with lower global cognition in AD. Thus, although WMH volume was highest in AD subjects, it had a more pervasive influence on brain structure and cognitive impairment in MCI. Our study thus highlights the importance of early detection of cerebrovascular disease, as its intervention at the MCI stage might potentially slow down neurodegeneration.

Differential Gray Matter Vulnerability in the 1 Year Following a Clinically Isolated Syndrome.

Background and purpose: Whether some gray matter (GM) regions are differentially vulnerable at the early stages of MS is still unknown. The objective of this study is to investigate whether deep and cortical GM are differentially vulnerable after a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS).Methods: Fifty-six patients with CIS (PwCIS) and 38 healthy controls (HC) had conventional and diffusion tensor imaging (DTI) at baseline and 46 PwCIS and 20 HC were rescanned after 1 year. Deep GM (DGM) volumes, cortical thickness (CTh), and DTI metrics (FA: fractional anisotropy; MD: mean diffusivity) within these structures were calculated for each participant at each time-point and compared between PwCIS and HC. Linear regression models were used to investigate whether baseline DTI parameters could predict GM volume loss over time.Results: At baseline, GM volumes did not differ between PwCIS and HC, but hippocampal MD was higher in PwCIS than HC (p < 0.01). Over 1 year, GM alterations became more widespread with putamen and hippocampus volumes decreasing in PwCIS (p < 0.01), and cortical thinning in different parts of the cortex along with a significant increase of MD. Hippocampus MD at baseline could predict its volume loss (R2 = 0.159; p < 0.05) and cortical thinning was associated to microstructural damage (Spearman's rho ranging from −0.424 to −0.603 with p < 0.003).Conclusion: Along with MS being a diffuse inflammatory disease, GM showed a differential vulnerability at the early stage spreading from hippocampus to the cortex. Hippocampus volume loss could be predicted by its MD at baseline.

White matter network alterations in patients with depersonalization/derealization disorder.

Depersonalization/derealization disorder (DPD) is a chronic and distressing condition characterized by detachment from oneself and/or the external world. Neuroimaging studies have associated DPD with structural and functional alterations in a variety of distinct brain regions. Such local neuronal changes might be mediated by altered interregional white matter connections. However, to our knowledge, no research on network characteristics in this patient population exists to date. We explored the structural connectome in 23 individuals with DPD and 23 matched, healthy controls by applying graph theory to diffusion tensor imaging data. Mean interregional fractional anisotropy (FA) was used to define the network weights. Group differences were assessed using network-based statistics and a link-based controlling procedure. Our main finding refers to lower FA values within left temporal and right temporoparietal regions in individuals with DPD than in healthy controls when using a link-based controlling procedure. These links were also associated with dissociative symptom severity and could not be explained by anxiety or depression scores. Using network-based statistics, no significant results emerged. However, we found a trend for 1 subnetwork that may support the model of frontolimbic dysbalance suggested to underlie DPD symptomatology. To ensure ecological validity, patients with certain comorbidities or psychotropic medication were included in the study. Confirmatory replications are necessary to corroborate the results of this explorative investigation. In patients with DPD, the structural connectivity between brain regions crucial for multimodal integration and emotion regulation may be altered. Aberrations in fibre tract communication seem to be not solely a secondary effect of local grey matter volume loss, but may present a primary pathophysiology in patients with DPD.

Gray matter atrophy in dementia with Lewy bodies with and without concomitant Alzheimer's disease pathology.

We aimed to study if patients with dementia with Lewy bodies (DLB) who have concomitant Alzheimer's disease (AD) pathology (detected antemortem by cerebrospinal fluid [CSF] biomarkers) have additional loss of gray matter volume. Ninety-eight DLB patients were divided into a "pure DLB" (DLB/AD-, n= 62) and a "mixed DLB" group (DLB/AD+, n= 36) and matched for age and symptom duration to 84 AD patients and 75 controls. We compared visual atrophy ratings, and in a subset, we analyzed cortical thickness and subcortical gray matter volumes. DLB/AD+ patients had more pronounced medial temporal lobe atrophy (MTA) compared to DLB/AD- (mean [total] MTA score 2.5 vs. 1.3, p= 0.02). Global and parietal atrophy scores were comparable between the 3 dementia groups and differed from controls. MTA score was associated with CSF Aβ-42, while posterior cortical and global atrophy scores were associated with CSF tau. Cortical thinning was found in DLB/AD-, DLB/AD+, and AD compared to controls. Concomitant AD pathology seems to cause additional (hippocampal) atrophy in DLB, and this may contribute to a more devastating disease course in DLB/AD+ patients.

Assessment of EEG Connectivity Patterns in Mild Cognitive Impairment Using Phase Slope Index.

Mild cognitive impairment (MCI) is a pathology characterized by an abnormal cognitive state. MCI patients are considered to be at high risk for developing dementia. The aim of this study is to characterize the changes that MCI causes in the patterns of brain information flow. For this purpose, spontaneous EEG activity from 41 MCI patients and 37 healthy controls was analyzed by means of an effective connectivity measure: the phase slope index (PSl). Our results showed statistically significant decreases in PSI values mainly at delta and alpha frequency bands for MCI patients, compared to the control group. These abnormal patterns may be due to the structural changes in the brain suffered by patients: decreased hippocampal volume, atrophy of the medial temporal lobe, or loss of gray matter volume. This study suggests the usefulness of PSI to provide further insights into the underlying brain dynamics associated with MCI.

18F]AV1451 PET IN RELATION TO ATROPHY ACROSS THE ALZHEIMER’S DISEASE SPECTRUM

Neuropathological Braak staging of neurofibrillary tangles has been introduced to capture the spatial spreading of tau. Using [18F]AV1451 PET, it is now possible to visualize these Braak stages in vivo. The aim of this study was to investigate whether and how specific [18F]AV1451 binding in ascending Braak stages relates to regional atrophy patterns across the Alzheimer's disease (AD) spectrum. We included 70 subjects (35 subjective cognitive decline [SCD], 6 mild cognitive impairment [MCI] and 29 AD dementia) who underwent a 130-minute dynamic [18F]AV1451 PET scan and structural MRI (table1). For [18F]AV1451, receptor parametric mapping (RPM) with cerebellar grey matter as reference region was used to calculate binding potential (BPND). Separate regional values for 1) Braak stage I/II (enthorinal), 2) Braak stage III/IV (limbic) and 3) Braak stage V/VI (neocortical) (Schöll et al, 2016) were extracted (figure 1). T1-weighted MR images were used to assess grey matter (GM) volumes. We performed whole-brain voxelwise analyses using the 3 regional Braak [18F]AV1451 BPND as independent variables, and GM volumes as the dependent variable, adjusting for age, sex and total intracranial volume, with a threshold of p<0.001 (uncorrected for multiple comparisons). These analyses were repeated using region-of-interest analyses for both [18F]AV1451 BPND and GM volumes. [18F]AV1451 BPND values per Braak region, according to diagnosis. Abbreviations: BPND= binding potential, SCD = subjective cognitive decline, MCI = Mild Cognitive Impairment, AD = Alzheimer's Disease. In the MCI/AD group, [18F]AV1451 BPND in Braak stage I/II showed limited associations with GM volumes. Greater [18F]AV1451 BPND in Braak stage III/IV, however, was associated with lower GM volumes in temporal, parietal and frontal cortices (figure2). These associations were similar for [18F]AV1451 BPND in Braak stage V/VI, although slightly less widespread (figure2). For SCD, only subtle associations between [18F]AV1451 BPND in Braak III/IV and GM volumes were observed (figure3). Region-of-interest analyses were in line with these findings (table2, figure4). Associations between regional [18F]AV1451 BPND and voxelwise brain GM volumes in MCI/AD. Analyses were adjusted for age, sex and TIV. Displayed are p-values, thresholded at an uncorrected p<0.001. Associations between regional [18F]AV1451 BPND and voxelwise brain GM volumes in SCD. Analyses were adjusted for age, sex and TIV. Displayed are p-values, thresholded at an uncorrected p<0.001. Relationships between [18F]AVIASI BPND and gray matter ROIs. Displayed are relationships between [18F]AV1451 BPND in Braak 1-2 (panel A,D), Braak 3-4 (panel B,E) and Braak 5-6 (panel C,F) and gray matter in medial temporal lobe (panel A-C) and temporoparietal lobe (panel D-F). Data are shown for SCD in blue and MCI/AD in red. Beta coefficients and p-values are displayed in blue boxes for SCD and in red boxs for MCI/AD. Abbreviations: BPND = binding potential GM = gray matter; ROI = region of interest, SCD = subjective cognitive decline, MCI = mild cognitive decline, AD = Alzheimer's disease These data suggest that tau pathology in Braak stages III/IV is most strongly associated with gray matter volume loss in patients with MCI and AD. Higher tau specific binding in Braak stage V/VI is not related to more extensive atrophy. In SCD and in Braak stage I/II in MCI/AD, only subtle associations between tau pathology and gray matter were observed. These findings could possibly be influenced by partial volume effects.

Frequency and amplitude modulation of resting-state fMRI signals and their functional relevance in normal aging

The intrinsic composition and functional relevance of resting-state blood oxygen level-dependent signals are fundamental in research using functional magnetic resonance imaging (fMRI). Using the Hilbert-Huang Transform to estimate high-resolution time-frequency spectra, we investigated the instantaneous frequency and amplitude modulation of resting-state fMRI signals, as well as their functional relevance in a large normal-aging cohort (n= 420, age= 21-89years). We evaluated the cognitive function of each participant and recorded respiratory signals during fMRI scans. The results showed that the Hilbert-Huang Transform effectively categorized resting-state fMRI power spectra into high (0.087-0.2Hz), low (0.045-0.087Hz), and very-low (≤0.045Hz) frequency bands. The high-frequency power was associated with respiratory activity, and the low-frequency power was associated with cognitive function. Furthermore, within the cognition-related low-frequency band (0.045-0.087Hz), we discovered that aging was associated with the increased frequency modulation and reduced amplitude modulation of the resting-state fMRI signal. These aging-related changes in frequency and amplitude modulation of resting-state fMRI signals were unaccounted for by the loss of gray matter volume and were consistently identified in the default mode and salience network. These findings indicate that resting-state fMRI signal modulations are dynamic during the normal aging process. In summary, our results refined the functionally related blood oxygen level-dependent frequency band in a considerably narrow band at a low-frequency range (0.045-0.087Hz) and challenged the current method of resting-fMRI preprocessing by using low-frequency filters with a relatively wide range below 0.1Hz.

Early Gray Matter Volume Loss in MAPT H1H1 de Novo PD Patients: A Possible Association With Cognitive Decline.

The MAPT H1 haplotype has been identified as a predictor of cognitive decline in Parkinson's disease (PD). However, its underlying pathological mechanisms have not been fully established. In this work, using a cohort of 120 de novo PD patients with preserved cognition from the Parkinson's Progression Markers Initiative (PPMI) database, we found that patients who were homozygous for MAPT H1 had less gray matter volume (GMV) and greater 1-year GMV loss than patients without this genetic profile. Importantly, these changes were associated with a longitudinal worsening of cognitive indicators. Our findings suggest that early GMV loss in MAPT H1H1 PD patients increases their risk to develop cognitive decline.

Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure

Childhood lead exposure has been correlated to acts of delinquency and criminal behavior; however, little research has been conducted to examine its potential long term influence on behavioral factors such as personality, specifically psychopathic personality. Neuroimaging studies have demonstrated that the effects of childhood lead exposure persist into adulthood, with structural abnormalities found in gray and white matter regions involved in behavioral decision making. The current study examined whether measurements of adult psychopathy were associated with neuroanatomical differences in structural brain volumes for a longitudinal cohort with measured childhood lead exposure. We hypothesized that increased total psychopathy scores and increased blood lead concentration at 78 months of age (PbB78) would be inversely associated with volumetric measures of gray and white matter brain structures responsible for executive and emotional processing. Analyses did not display a direct effect between total psychopathy score and gray matter volume; however, reduced white matter volume in the cerebellum and brain stem in relation to increased total psychopathy scores was observed. An interaction between sex and total psychopathy score was also detected. Females displayed increased gray matter volume in the frontal, temporal, and parietal lobes associated with increased total psychopathy score, but did not display any white matter volume differences. Males primarily displayed reductions in frontal gray and white matter brain volume in relation to increased total psychopathy scores. Additionally, reduced gray and white matter volume was associated with increased blood lead levels in the frontal lobes; reduced white matter volume was also observed in the parietal and temporal lobes. Females demonstrated gray and white matter volume loss associated with increased PbB78 values in the right temporal lobe, as well as reduced gray matter volume in the frontal lobe. Males displayed reduced white matter volumes associated with increased PbB78 values in the frontal, temporal, and parietal lobes. Comparison of the two primary models revealed a volumetric decrease in the white matter of the left prefrontal cortex associated with increased total psychopathy scores and increased blood lead concentration in males. The results of this study suggested that increased psychopathy scores in this cohort may be attributable to the neuroanatomical abnormalities observed and that childhood lead exposure may be influential to these outcomes.

In vivo relationship between serotonin 1A receptor binding and gray matter volume in the healthy brain and in major depressive disorder.

Serotonin 1A (5-HT1A) receptors mediate serotonin trophic role in brain neurogenesis. Gray matter volume (GMV) loss and 5-HT1A receptor binding alterations have been identified in major depressive disorder (MDD). Here we investigated the relationship between 5-HT1A receptor binding and GMV in 40 healthy controls (HCs) and, for the first time, 47 antidepressant-free MDD patients using Voxel-Based Morphometry and [11C]WAY100635 Positron Emission Tomography. Values of GMV and 5-HT1A binding (expressed as BPF, one of the types of binding potentials that refer to displaceable or specific binding that can be quantified in vivo with PET) were obtained in 13 regions of interest, including raphe, and at the voxel level. We used regression analysis within each group to predict GMV from BPF, while covarying for age, sex, total gray matter volume and medication status. In the HCs group, we found overall a positive correlation between terminal field 5-HT1A receptor binding and GMV, which reached statistical significance in regions such as hippocampus, insula, orbital prefrontal cortex, and parietal lobe. We observed a trend towards inverse correlation between raphe 5-HT1A autoreceptor binding and anterior cingulate GMV in both groups, and a statistically significant positive correlation between raphe 5-HT1A binding and temporal GMV in MDD. Analysis of covariance at the voxel-level revealed a trend towards interaction between diagnosis and raphe 5-HT1A binding in predicting GMV in cerebellum and supramarginal gyrus (higher correlation in HCs compared with MDD). Our results replicated previous findings in the normative brain, but did not extend them to the brain in MDD, and indicated a trend towards dissociation between MDD and HCs in the relationship of raphe 5-HT1A binding with postsynaptic GMV. These results suggest that 5-HT1A receptors contribute to altered neuroplasticity in MDD, possibly via effects predating depression onset.

Cerebral gray matter volume losses in essential tremor: A case-control study using high resolution tissue probability maps

IntroductionEssential tremor (ET) is increasingly recognized as a multi-dimensional disorder with both motor and non-motor features. For this reason, imaging studies are more broadly examining regions outside the cerebellar motor loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized processing, adapted to high-resolution magnetic resonance imaging (MRI). We investigated cerebral GM volume loss in ET cases using automated segmentation of MRI T1-weighted images. MethodsMRI was acquired on 47 ET cases and 36 controls. Automated segmentation and voxel-wise comparisons of volume were performed using Statistical Parametric Mapping (SPM) software. To improve upon standard protocols, the high-resolution International Consortium for Brain Mapping (ICBM) 2009a atlas and tissue probability maps were used to process each subject image. Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH) vs. Controls, and severe ET vs. Controls. An analysis of variance (ANOVA) was performed between ET with and without head tremor and controls. Age, sex, and Montreal Cognitive Assessment (MoCA) score were regressed out from each comparison. ResultsWe were able to consistently identify regions of cerebral GM volume loss in ET and in ET subgroups in the posterior insula, superior temporal gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal regions. There were no significant increases in GM volume in ET in any comparisons with controls. ConclusionThis study, which uses improved methodologies, provides evidence that GM volume loss in ET is present beyond the cerebellum, and in fact, is widespread throughout the cerebrum as well.

Grey-matter network disintegration as predictor of cognitive and motor function with aging

Loss of grey-matter volume with advancing age affects the entire cortex. It has been suggested that atrophy occurs in a network-dependent manner with advancing age rather than in independent brain areas. The relationship between networks of structural covariance (SCN) disintegration and cognitive functioning during normal aging is not fully explored. We, therefore, aimed to (1) identify networks that lose GM integrity with advancing age, (2) investigate if age-related impairment of integrity in GM networks associates with cognitive function and decreasing fine motor skills (FMS), and (3) examine if GM disintegration is a mediator between age and cognition and FMS. T1-weighted scans of n = 257 participants (age range: 20–87) were used to identify GM networks using independent component analysis. Random forest analysis was implemented to examine the importance of network integrity as predictors of memory, executive functions, and FMS. The associations between GM disintegration, age and cognitive performance, and FMS were assessed using mediation analyses. Advancing age was associated with decreasing cognitive performance and FMS. Fourteen of 20 GM networks showed integrity changes with advancing age. Next to age and education, eight networks (fronto-parietal, fronto-occipital, temporal, limbic, secondary somatosensory, cuneal, sensorimotor network, and a cerebellar network) showed an association with cognition and FMS (up to 15.08%). GM networks partially mediated the effect between age and cognition and age and FMS. We confirm an age-related decline in cognitive functioning and FMS in non-demented community-dwelling subjects and showed that aging selectively affects the integrity of GM networks. The negative effect of age on cognition and FMS is associated with distinct GM networks and is partly mediated by their disintegration.

Brain gray matter alterations in Chinese patients with chronic knee osteoarthritis pain based on voxel-based morphometry.

Altered cerebral gray matter volume (GMV) is commonly found in patients with chronic pain. Chronic pain is the prominent characteristic of knee osteoarthritis (KOA), yet little is known about its morphological changes in the brain. Here an MRI study was performed to examine the structural brain abnormalities in 30 KOA patients with knee pain and age-matched healthy subjects. We detected that the patients exhibited significant almost 2-fold age-related decreases of GMV compared to healthy controls. Moreover, KOA patients also had significant loss of regional GMV including in the bilateral orbital frontal cortex (OFC), the right lateral prefrontal cortex (lPFC), and precentral and postcentral cortices. In addition, a high proportion of KOA patients exerted abnormal scores of Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Mini Mental State examination (MMSE), and Montreal Cognitive Assessment (MoCA) compare to controls. Our results imply that chronic pain conditions which preferentially involve PFC might consider as a “cognitive state.” And emotion and cognitive function about chronic pain should be highly regarded.

Deep gray matter volume loss drives disability worsening in multiple sclerosis.

ObjectiveGray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS.MethodsWe analyzed 3,604 brain high‐resolution T1‐weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing‐remitting [RRMS], 128 secondary‐progressive [SPMS], and 125 primary‐progressive [PPMS]), over an average follow‐up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow‐up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time‐to‐EDSS progression.ResultsSPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time‐to‐EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow‐up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (–1.45%), PPMS (–1.66%), and RRMS (–1.34%) than CIS (–0.88%) and HCs (–0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (–1.21%) was significantly faster than RRMS (–0.76%), CIS (–0.75%), and HCs (–0.51%). Similarly, the rate of parietal GM atrophy in SPMS (–1.24‐%) was faster than CIS (–0.63%) and HCs (–0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001).InterpretationThis large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210–222

Standard chemoradiation in combination with VEGF targeted therapy for glioblastoma results in progressive gray and white matter volume loss.

Standard chemoradiation in combination with VEGF targeted therapy for glioblastoma results in progressive gray and white matter volume loss.

Gray Matter Volume Changes over the Whole Brain in the Bulbar- and Spinal-onset Amyotrophic Lateral Sclerosis: a Voxel-based Morphometry Study.

Objective To investigate cerebral structural signatures of the bulbar- and spinal-onset amyotrophic lateral sclerosis (ALS) using voxel-based morphometry on magnetic resonance imaging. Methods The MR structural images of the brain were obtained from 65 ALS patients (15 bulbar-onset, 50 spinal-onset) and 65 normal controls (NC) on a 3.0T MRI system. Gray matter (GM) volume changes were investigated by voxel-based morphometry, and the distribution of the brain regions with volume changes was compared between ALS and normal controls, as well as between bulbar-onset and spinal-onset ALS based on Neuromorphometrics atlas. Result On voxel-level the decreased volume of brain regions in ALS patients was located in the right precentral gyrus (rPrcGy) and right middle frontal gyrus compared with that in NC. The bulbar-onset ALS presented extra-motor cortex atrophy (fronto-temporal pattern), including left medial orbital gyrus, left inferior temporal gyrus and right middle temporal gyrus; the spinal-onset ALS suffered from motor cortex atrophy (rPrcGy dominance) and extra-motor cortex atrophy (fronto-temporal and extra-fronto-temporal pattern) compared with NC. The spinal-onset ALS featured by GM volume loss of left postcentral gyrus and bulbar-onset ALS featured by GM volume loss of left middle temporal gyrus compared with each other. Conclusions The asymmetric GM atrophy of the motor cortex and extra-motor cortex represents the common MRI structural signatures of spinal-onset ALS, and sole extra-motor cortex atrophy represents the structural signatures of bulbar-onset ALS. The present study also demonstrated that the pattern of GM damage is likely to distribute wider in spinal-onset ALS than in bulbar-onset ALS.

Test-retest variability of resting-state networks in healthy aging and prodromal Alzheimer's disease.

In recent years, changes in resting-state networks (RSN), identified by functional magnetic resonance imaging (fMRI), have gained increasing attention as potential biomarkers and trackers of neurological disorders such as Alzheimer's disease (AD). Intersession reliability of RSN is fundamental to this approach.In this study, we investigated the test-retest reliability of three memory related RSN (i.e., the default mode, salience, and executive control network) in 15 young, 15 healthy seniors (HS), and 15 subjects affected by mild cognitive impairment (MCI) with positive biomarkers suggestive of incipient AD (6 females each). FMRI was conducted on three separate occasions. Independent Component Analysis decomposed the resting-state data into RSNs. Comparisons of variation in functional connectivity between groups were made applying different thresholds in an explorative approach. Intersession test-retest reliability was evaluated by intraclass correlation coefficient (ICC) comparisons. To assess the effect of gray matter volume loss, motion, cerebrospinal fluid based biomarkers and the time gap between sessions on intersession variation, the former four were correlated separately with the latter.Data showed that i) young subjects ICCs (relative to HS/MCI-subjects) had higher intersession reliability, ii) stringent statistical thresholds need to be applied to prevent false-positives, iii) both HS and MCI-subjects (relative to young) showed significantly more clusters of intersession variation in all three RSN, iv) while intersession variation was highly correlated with head motion, it was also correlated with biomarkers (especially phospho-tau), the time gap between sessions and local GMV. Results indicate that time gaps between sessions should be kept constant and that head motion must be taken into account when using RSN to assess aging and neurodegeneration. In patients with prodromal AD, re-test reliability may be increased by accouting for overall disease burden by including biomarkers of neuronal injury (especially phospho-tau) in statistical analyses. Local atrophy however, does not seem to play a major role in regards to reliability, but should be used as covariate depending on the research question.

Olfactory cortex and Olfactory bulb volume alterations in patients with post-infectious Olfactory loss.

Upper respiratory tract infection (URI) is one of the most common etiology of olfactory loss. Previous studies demonstrated that both olfactory bulb (OB) volume and sulcus (OS) depth decreased in patients with post-infectious olfactory loss (PIOL) compared to normal controls. The aim of our study was to observe alterations of central olfactory pathways in patients with PIOL. T1 weighted magnetic resonance images were acquired in 19 PIOL patients and 19 age- and sex-matched control subjects on a 3T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. We also analyzed OB volume in coronal T2-weighted images. Whole-brain analysis revealed a significant gray matter volume loss in the right orbitofrontal cortex (OFC) in patients group. Further analysis with region of interest exhibited a significant negative correlation between gray matter volume in right OFC as well as OB volume and the duration of olfactory loss in these patients (r = -0.566 and r = -0.535 both P < 0.05, respectively). In conclusion, the morphological alterations in the right OFC and OB might contribute to the pathogenic mechanism of olfactory dysfunction after upper respiratory tract infection.