Changes In Cortical Structure Research Articles

Retraction and replacement: Assessing the cortical microstructure in contralesional sensorimotor areas after stroke

Abstract Cortical thickness analyses have provided valuable insights into changes in cortical brain structure after stroke and their association with recovery. Across studies though, relationships between cortical structure and function show inconsistent results. Recent developments in diffusion-weighted imaging of the cortex have paved the way to uncover hidden aspects of stroke-related alterations in cortical microstructure, going beyond cortical thickness as a surrogate for cortical macrostructure. Animal data obtained in rats and monkeys have evidenced that contralesional motor areas undergo degenerative alterations in their microstructure which are accompanied by compensatory changes as well. We hypothesized that cortical diffusion imaging can detect similar changes in human stroke survivors. We re-analysed clinical and imaging data of 42 well-recovered chronic stroke patients from two independent cohorts (mean age 64 years, 4 left-handed, 71% male, 16 right-sided strokes) and 33 healthy controls of similar age and gender. Cortical fractional anisotropy, axial diffusivity, radial diffusivity and cortical thickness values were obtained for six key sensorimotor areas of the contralesional hemisphere. The regions included the primary motor cortex, dorsal and ventral premotor cortex, supplementary and pre-supplementary motor areas and primary somatosensory cortex. Linear models were estimated for group comparisons between patients and controls and for correlations between cortical fractional anisotropy, axial diffusivity, radial diffusivity and cortical thickness and clinical scores. Against our hypothesis, we did not find any significant alterations in contralesional cortical microstructure after stroke. Likewise, we did not detect any correlations between cortical microstructure and behavioural scores. Future analyses are warranted to investigate whether such alterations might occur in different populations, e.g. in later stages of recovery, in more severely impaired patients, or only in the ipsilesional hemisphere in patients with specific lesion patterns.

Causal association of COVID-19 with brain structure changes: Findings from a non-overlapping 2-sample Mendelian randomization study

Recent cohort studies suggested that SARS-CoV-2 infection is associated with changes in brain structure. However, the potential causal relationship remains unclear. We performed a two-sample Mendelian randomization analysis to determine whether genetic susceptibility of COVID-19 is causally associated with changes in cortical and subcortical areas of the brain. This 2-sample MR (Mendelian Randomization) study is an instrumental variable analysis of data from the COVID-19 Host Genetics Initiative (HGI) meta-analyses round 5 excluding UK Biobank participants (COVID-19 infection, N = 1,348,701; COVID-19 severity, N = 1,557,411), the Enhancing NeuroImaging Genetics through Meta Analysis (ENIGMA) Global and regional cortical measures, N = 33,709; combined hemispheric subcortical volumes, N = 38,851), and UK Biobank (left/right subcortical volumes, N = 19,629). A replication analysis was performed on summary statistics from different COVID-19 GWAS study (COVID-19 infection, N = 80,932; COVID-19 severity, N = 72,733). We found that the genetic susceptibility of COVID-19 was not significantly associated with changes in brain structures, including cortical and subcortical brain structure. Similar results were observed for different (1) MR estimates, (2) COVID-19 GWAS summary statistics, and (3) definitions of COVID-19 infection and severity. This study suggests that the genetic susceptibility of COVID-19 is not causally associated with changes in cortical and subcortical brain structure.

Systolic blood pressure is associated with abnormal alterations in brain cortical structure: Evidence from a Mendelian randomization study

BackgroundHypertension has been recognized as a significant risk factor for cerebrovascular diseases and cognitive decline. However, the specific impact of hypertension, systolic/diastolic blood pressure, pulse pressure (PP) and mean arterial pressure (MAP) on brain cortical structure remains unclear. Mendelian randomization (MR) provides a robust approach to investigate the causal relationship between blood pressure components and brain cortical changes. MethodsIn this MR study, data from large-scale genome-wide association studies for blood pressure components and neuroimaging were utilized to conduct our analyses. We leveraged genetic variants associated specifically with hypertension (122,620 cases and 332,683 controls), systolic (469,767 individuals), diastolic (490,469 individuals) blood pressure, PP (810,865 individuals) and MAP (over 1 million individuals) to evaluate their effects on brain cortex surficial area (51,665 individuals) and cortex thickness (51,665 individuals). ResultsOur findings revealed a significant correlation between systolic blood pressure and abnormal reduction in brain cortex surficial area (β=-1330.69, 95% confident interval [CI]: -2655.35 to -6.02, p = 0.0489); however, no significant relationship was found between systolic blood pressure and brain cortex thickness (β=-0.0078, 95% CI: -0.0178 to 0.0022, p = 0.1287). Additionally, no significant associations were observed between hypertension (β=-200.05, p = 0.6884; β=-0.0051, p = 0.1179, respectively), diastolic blood pressure (β=-460.63, p = 0.5160; β=0.0047, p = 0.2448, respectively), PP (β=1041.84, p = 0.3725; β=-0.0112, p = 0.2212, respectively), MAP (β=-18.84, p = 0.8841; β=0.0002, p = 0.7654, respectively) and both brain cortex surficial area and brain cortex thickness. ConclusionOur MR study provides evidence supporting the hypothesis that systolic blood pressure, rather than diastolic blood pressure, PP or MAP, is associated with abnormal changes in brain cortical structure.

Cortical structure and the risk of amyotrophic lateral sclerosis: A bidirectional Mendelian randomization study

BackgroundCurrent observational studies indicate progressive brain atrophy is closely associated with the clinical feature of amyotrophic lateral sclerosis. However, it is unclear whether the changes in cortical structure are the cause or result of ALS. Our study aimed to investigate the causal relationship between cortical structure and ALS risk using a bidirectional two-sample MR study. MethodsWe collected publicly available genome-wide association studies' summary statistics for cortical structure from UK Biobank and ENIGMA consortium (n = 33,992) and ALS from the Project MinE (n = 138,086). We used the inverse variance weighted method (IVW) as primary analysis in order to evaluate the causal effects. In addition, the weighted median and MR Egger methods were performed to ensure the robustness and reliability of the IVW results. ResultsWe found the decreased surface of the paracentral lobule and thickness of the frontal pole and middle temporal lobe were suggestively associated with an increased risk of ALS as well as the increased surface of medial orbitofrontal and middle temporal lobe. In another aspect, the causalities between the susceptibility to ALS and the volume of the transverse temporal gyrus and superior temporal gyrus were negative. Besides, the susceptibility to ALS might also contribute to an increased thickness of the postcentral gyrus and superior parietal gyrus. ConclusionIn this two-sample MR analysis, we observed that multiple cortical brain regions are associated with a higher ALS risk. Further research into the underlying mechanisms is required to back up our findings.

Brain imaging and neuropsychological assessment of individuals recovered from a mild to moderate SARS-CoV-2 infection

As severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections have been shown to affect the central nervous system, the investigation of associated alterations of brain structure and neuropsychological sequelae is crucial to help address future health care needs. Therefore, we performed a comprehensive neuroimaging and neuropsychological assessment of 223 nonvaccinated individuals recovered from a mild to moderate SARS-CoV-2 infection (100 female/123 male, age [years], mean ± SD, 55.54 ± 7.07; median 9.7mo after infection) in comparison with 223 matched controls (93 female/130 male, 55.74 ± 6.60) within the framework of the Hamburg City Health Study. Primary study outcomes were advanced diffusion MRI measures of white matter microstructure, cortical thickness, white matter hyperintensity load, and neuropsychological test scores. Among all 11 MRI markers tested, significant differences were found in global measures of mean diffusivity (MD) and extracellular free water which were elevated in the white matter of post-SARS-CoV-2 individuals compared to matched controls (free water: 0.148 ± 0.018 vs. 0.142 ± 0.017, P< 0.001; MD [10-3mm2/s]: 0.747 ± 0.021 vs. 0.740 ± 0.020, P< 0.001). Group classification accuracy based on diffusion imaging markers was up to 80%. Neuropsychological test scores did not significantly differ between groups. Collectively, our findings suggest that subtle changes in white matter extracellular water content last beyond the acute infection with SARS-CoV-2. However, in our sample, a mild to moderate SARS-CoV-2 infection was not associated with neuropsychological deficits, significant changes in cortical structure, or vascular lesions several months after recovery. External validation of our findings and longitudinal follow-up investigations are needed.

Altered microstructure of the contralesional ventral premotor cortex and motor output after stroke.

Cortical thickness analyses have provided valuable insights into changes in cortical brain structure after stroke and their association with recovery. Across studies though, relationships between cortical structure and function show inconsistent results. Recent developments in diffusion-weighted imaging of the cortex have paved the way to uncover hidden aspects of stroke-related alterations in cortical microstructure, going beyond cortical thickness as a surrogate for cortical macrostructure. We re-analysed clinical and imaging data of 42 well-recovered chronic stroke patients from 2 independent cohorts (mean age 64 years, 4 left-handed, 71% male, 16 right-sided strokes) and 33 healthy controls of similar age and gender. Cortical fractional anisotropy and cortical thickness values were obtained for six key sensorimotor areas of the contralesional hemisphere. The regions included the primary motor cortex, dorsal and ventral premotor cortex, supplementary and pre-supplementary motor areas, and primary somatosensory cortex. Linear models were estimated for group comparisons between patients and controls and for correlations between cortical fractional anisotropy and cortical thickness and clinical scores. Compared with controls, stroke patients exhibited a reduction in fractional anisotropy in the contralesional ventral premotor cortex (P = 0.005). Fractional anisotropy of the other regions and cortical thickness did not show a comparable group difference. Higher fractional anisotropy of the ventral premotor cortex, but not cortical thickness, was positively associated with residual grip force in the stroke patients. These data provide novel evidence that the contralesional ventral premotor cortex might constitute a key sensorimotor area particularly susceptible to stroke-related alterations in cortical microstructure as measured by diffusion MRI and they suggest a link between these changes and residual motor output after stroke.

Analysis of Mouse Brain Sections by Live-cell Time-lapse Confocal Microscopy.

The developing cerebral cortex of mammals is generated from nascent pyramidal neurons, which radially migrate from their birthplace in the ventral part of the neural tube to the cortical surface. Subtle aberrations in this process may cause significant changes in cortical structure and lead to developmental neurological disorders. During pyramidal neuron migration, we recently showed that the migrating neuron, which bypasses its last preceding neuron, is critical for its proper positioning and contributes to cerebral cortex thickness. Studying this process requires an imaging system with single-cell resolution and a prolonged observation window. Therefore, we built a system to maintain an organotypic brain slice on the stage of a Leica SP5 confocal microscope, which facilitated high-resolution imaging over a 12-hour time-lapse observation period of cellular events during neuron migration. Here, we share our protocol along with guidelines for overcoming difficulties during the setup. This protocol facilitates the observation of, but is not limited to, neurodevelopmental and pathological processes occurring during neuron migration.

Early deprivation alters structural brain development from middle childhood to adolescence.

Hypotheses concerning the biologic embedding of early adversity via developmental neuroplasticity mechanisms have been proposed on the basis of experimental studies in animals. However, no studies have demonstrated a causal link between early adversity and neural development in humans. Here, we present evidence from a randomized controlled trial linking psychosocial deprivation in early childhood to changes in cortical development from childhood to adolescence using longitudinal data from the Bucharest Early Intervention Project. Changes in cortical structure due to randomization to foster care were most pronounced in the lateral and medial prefrontal cortex and in white matter tracts connecting the prefrontal and parietal cortex. Demonstrating the causal impact of exposure to deprivation on the development of neural structure highlights the importance of early placement into family-based care to mitigate lasting neurodevelopmental consequences associated with early-life deprivation.

Menopause-related cortical loss of the humeral head region mainly occurred in the greater tuberosity.

AimsProximal humerus fractures are commonly observed in postmenopausal women. The goal of this study was to investigate menopause-related changes in cortical structure of the humeral head.Materials and methodsClinical computed tomography (CT) scans of 75 healthy women spanning a wide range of ages (20–72 years) were analyzed. For each subject, cortical bone mapping (CBM) was applied to create a color three-dimensional (3D) thickness map for the proximal humerus. Nine regions of interest (ROIs) were defined in three walls of the humeral head. Cortical parameters, including the cortical thickness (CTh), cortical mass surface density (CM), and the endocortical trabecular density (ECTD), were measured.ResultsCompared to premenopausal women, postmenopausal women were characterized by a significantly lower CTh and CM value in the lateral part of the greater tuberosity. Similar changes were only found in ROI 4, but not in ROIs 5–6 in the lesser tuberosity. Linear regression analysis revealed that the CTh and CM value of ROIs 1, 3, and 4 were negatively associated with age. These results showed that menopause-related loss in CTh and CM was mainly in the greater tuberosity besides the proximal part of the lesser tuberosity. Trabecular bone variable measured as ECTD showed a notably lower value in ROIs 1–9 in postmenopausal vs. premenopausal group. Inverse linear associations for ECTD and age were found in ROIs 2, 3, 5, 6, 7, and 9, indicating no site-specific differences of endocortical trabecular bone loss between the greater and lesser tuberosity.ConclusionsMenopause-related cortical loss of the humeral head mainly occurred in the lateral part of the greater tuberosity. The increased rate of humeral bone loss in the greater tuberosity may contribute materially to complex proximal humerus fractures.

Brain network modularity predicts changes in cortical thickness in children involved in a physical activity intervention.

Individual differences in brain network modularity at baseline can predict improvements in cognitive performance after cognitive and physical interventions. This study is the first to explore whether brain network modularity predicts changes in cortical brain structure in 8- to 9-year-old children involved in an after-school physical activity intervention (N=62), relative to children randomized to a wait-list control group (N=53). For children involved in the physical activity intervention, brain network modularity at baseline predicted greater decreases in cortical thickness in the anterior frontal cortex and parahippocampus. Further, for children involved in the physical activity intervention, greater decrease in cortical thickness was associated with improvements in cognitive efficiency. The relationships among baseline modularity, changes in cortical thickness, and changes in cognitive performance were not present in the wait-list control group. Our exploratory study has promising implications for the understanding of brain network modularity as a biomarker of intervention-related improvements with physical activity.

Effect of Age on Bone Structure Parameters in Laying Hens.

Simple SummaryLaying hens supply calcium to their eggshells via a process of dynamic bone formation and resorption called remodeling. As hens age, their bone becomes weak and brittle due to an imbalance in remodeling, resulting in bone disorders. Osteoporosis, characterized by bone mass loss and increased risk of fractures, is a serious problem in the egg industry, affecting both productivity and animal welfare. Nonetheless, the mechanisms of age-related osteoporosis remain unknown. We evaluated differences in bone structure between age groups, using microscopy and 3D imaging. Bone quality was reduced by an increase in porosity, with loss of volume, contributing to age-related osteoporosis.Changes in medullary and cortical bone structure with age remain unclear. Twenty Hy-Line W36 hens, 25 or 52 weeks of age, were euthanized, and both tibiae were collected when an egg was present in the magnum. Serial cross sections of the tibiae were stained with Alcian blue. The bones were scanned using micro-computed tomography. Trabecular width (Tb.Wi) was significantly higher (p < 0.05) in 25-week-old hens, whereas medullary bone tissue volume (TV) was significantly higher (p < 0.01) in 52-week-old hens. 25-week-old hens had significantly higher (p < 0.01) bone volume fraction (BVF = calcified tissue / TV). Moreover, the cortical bone parameters were significantly higher (TV and bone mineral content (BMC) at p < 0.05, and bone volume (BV) and BVF at p < 0.01) in younger hens. Open porosity and total porosity, which indicate less density, were significantly higher (p < 0.01) in older hens. Older hens showed significantly higher (p < 0.01) tibial diaphysis TV than younger hens. Younger hens had significantly higher (p < 0.01) BV, BVF and bone mineral density (BMD) of the tibial diaphysis. These findings reveal that reductions in medullary bone quality might be associated with age-related low estrogen levels and stimulation of osteoclastic bone resorption by parathyroid hormone. Cortical bone quality decreased with enlargement of the Haversian canals and loss of volume, with a longer egg-laying period leading to osteoporosis.

Fetal Rhesus Monkey First Trimester Zika Virus Infection Impacts Cortical Development in the Second and Third Trimesters

AbstractZika virus is a teratogen similar to other neurotropic viruses, notably cytomegalovirus and rubella. The goal of these studies was to address the direct impact of Zika virus on fetal development by inoculating early gestation fetal rhesus monkeys using an ultrasound-guided approach (intraperitoneal vs. intraventricular). Growth and development were monitored across gestation, maternal samples collected, and fetal tissues obtained in the second trimester or near term. Although normal growth and anatomical development were observed, significant morphologic changes were noted in the cerebral cortex at 3-weeks post-Zika virus inoculation including massive alterations in the distribution, density, number, and morphology of microglial cells in proliferative regions of the fetal cerebral cortex; an altered distribution of Tbr2+ neural precursor cells; increased diameter and volume of blood vessels in the cortical proliferative zones; and a thinner cortical plate. At 3-months postinoculation, alterations in morphology, distribution, and density of microglial cells were also observed with an increase in blood vessel volume; and a thinner cortical plate. Only transient maternal viremia was observed but sustained maternal immune activation was detected. Overall, these studies suggest persistent changes in cortical structure result from early gestation Zika virus exposure with durable effects on microglial cells.

Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth.

Cortical neuron atrophy is a hallmark of depression and includes neurite retraction, dendritic spine loss, and decreased synaptic density. Psychoplastogens, small molecules capable of rapidly promoting cortical neuron growth, have been hypothesized to produce long-lasting positive effects on behavior by rectifying these deleterious structural and functional changes. Here we demonstrate that ketamine and LSD, psychoplastogens from two structurally distinct chemical classes, promote sustained growth of cortical neurons after only short periods of stimulation. Furthermore, we show that psychoplastogen-induced cortical neuron growth can be divided into two distinct epochs: an initial stimulation phase requiring TrkB activation and a growth period involving sustained mTOR and AMPA receptor activation. Our results provide important temporal details concerning the molecular mechanisms by which next-generation antidepressants produce persistent changes in cortical neuron structure, and they suggest that rapidly excreted psychoplastogens might still be effective neurotherapeutics with unique advantages over compounds like ketamine and LSD.

The Degree of Nesting between Spindles and Slow Oscillations Modulates Neural Synchrony.

Spindles and slow oscillations (SOs) both appear to play an important role in memory consolidation. Spindle and SO "nesting," or the temporal overlap between the two events, is believed to modulate consolidation. However, the neurophysiological processes modified by nesting remain poorly understood. We thus recorded activity from the primary motor cortex of 4 male sleeping rats to investigate how SO and spindles interact to modulate the correlation structure of neural firing. During spindles, primary motor cortex neurons fired at a preferred phase, with neural pairs demonstrating greater neural synchrony, or correlated firing, during spindle peaks. We found a direct relationship between the temporal proximity between SO and spindles, and changes to the distribution of neural correlations; nesting was associated with narrowing of the distribution, with a reduction in low- and high-correlation pairs. Such narrowing may be consistent with greater exploration of neural states. Interestingly, after animals practiced a novel motor task, pairwise correlations increased during nested spindles, consistent with targeted strengthening of functional interactions. These findings may be key mechanisms through which spindle nesting supports memory consolidation.SIGNIFICANCE STATEMENT Our analysis revealed changes in cortical spiking structure that followed the waxing and waning of spindles; firing rates increased, spikes were more phase-locked to spindle-band local field potential, and synchrony across units peaked during spindles. Moreover, we showed that the degree of nesting between spindles and slow oscillations modified the correlation structure across units by narrowing the distribution of pairwise correlations. Finally, we demonstrated that engaging in a novel motor task increased pairwise correlations during nested spindles. These phenomena suggest key mechanisms through which the interaction of spindles and slow oscillations may support sensorimotor learning. More broadly, this work helps link large-scale measures of population activity to changes in spiking structure, a critical step in understanding neuroplasticity across multiple scales.

Altered cortical morphology in patients with chronic shoulder pain

Shoulder pain is a common condition associated with slow recovery and high recurrence rates. Persistent pain may lead to structural brain changes that may further promote pain chronification. The present study addressed whether abnormal changes in cortical surface structure exist in patients with chronic shoulder pain of myofascial origin and whether such changes would be related to pain measures. Brain structural MRIs were obtained in 22 patients with chronic pain in the bilateral upper trapezius muscles and in 22 healthy controls. Cortical thickness, gyrification index and sulcal depth were assessed together with pain measures. Shallower sulcal depth was found in patients in the right central sulcus, posterior insula, inferior frontal and dorsomedial prefrontal cortices, precuneus, and the middle temporal cortex, and in the left medial orbitofrontal cortex. Negative correlations were found between the right central sulcus and pain intensity and between the left medial orbitofrontal cortex and pain affect. Cortical thickness or gyrification index did not differ significantly between the two groups. The afflicted cortical regions constitute interacting networks responsible for sensory, affective and cognitive dimensions of the pain experience.

Time-lagged associations between cognitive and cortical development from childhood to early adulthood.

Throughout childhood and adolescence, humans experience marked changes in cortical structure and cognitive ability. Cortical thickness and surface area, in particular, have been associated with cognitive ability. Here we ask the question: What are the time-related associations between cognitive changes and cortical structure maturation. Identifying a developmental sequence requires multiple measurements of these variables from the same individuals across time. This allows capturing relations among the variables and, thus, finding whether (a) developmental cognitive changes follow cortical structure maturation, (b) cortical structure maturation follows cognitive changes, or (c) both processes influence each other over time. Four hundred and thiry children and adolescents (age range = 6.01-22.28 years) completed the Wechsler Abbreviated Scale of Intelligence battery and were MRI scanned at 3 time points separated by ≈2 years (Mage T1 = 10.60, SD = 3.58; Mage T2 = 12.63, SD = 3.62; Mage T3 = 14.49, SD = 3.55). Latent change score models were applied to quantify age-related relationships among the variables of interest. Our results indicate that cortical and cognitive changes related to each other reciprocally. Specifically, the magnitude or rate of the change in each variable at any occasion-and not the previous level-was predictive of later changes. These results were replicated for brain regions selected according to the coordinates identified in the Basten et al.'s (2015) meta-analysis, to the parieto-frontal integration theory (Jung & Haier, 2007) and to the whole cortex. Potential implications regarding brain plasticity and cognitive enhancement are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

FV10. Gastric-bypass surgery induced widespread neural plasticity of the obese human brain

Bariatric surgery has become the gold standard for the treatment of morbid obesity (body mass index (BMI) ⩾ 40 kg/m2), but its plastic influences on the obese brain remain largely unexplored. Here, we combined structural and functional magnetic resonance brain imaging (MRI) in twenty-seven patients (BMI 47.8 ± 5.5 kg/m2) undergoing gastric-bypass surgery and fourteen non-obese controls (BMI 24.7 ± 3.4 kg/m2). Over the first year after surgery, patients presented changes in gray matter density (GMD) in the cerebral cortex of all lobes, subcortical structures as well as the cerebellum, but no changes in white matter water diffusivity throughout the brain. Related to the BMI loss, we identified altered GMD in the hypothalamus, the brain’s homeostatic control site, the lateral orbitofrontal cortex, assumed to host reward and gustatory processes, as well as bilateral abdominal representations in somatosensory cortex. Voxel-by-voxel regression analyses revealed that all GMD changes were associated with elevated regional homogeneity of spontaneous neural activity (ReHo) in blood-oxygenation level-dependent signals. Spatial–temporal integration of structural and functional MRI suggests that gastric-bypass surgery induced widespread plastic changes in cortical structure that concurrently homogenized the functional profile of the cortex.

Metabolic and Electrophysiological Changes Associated to Clinical Improvement in Two Severely Traumatized Subjects Treated With EMDR—A Pilot Study

Neuroimaging represents a powerful tool to investigate the neurobiological correlates of Eye Movements Desensitization and Reprocessing (EMDR). The impact of EMDR on cortical and sub-cortical brain regions has been proven by several investigations demonstrating a clear association between symptoms disappearance and changes in cortical structure and functionality. The aim of this study was to assess by electroencephalography (EEG) and for the first time by positron emission tomography (PET) the changes occurring after EMDR therapy in two cases of psychological trauma following brain concussion and comatose state due to traffic accident. A 28 and a 29 years old men underwent extensive neuropsychological examination, which investigated: (i) categorical and phonological verbal fluency; (ii) episodic verbal memory; (iii) executive functions; (iv) visuospatial abilities; (v) attention and working memory as well as clinical assessment by means of psychopathological tests (CAPS, IES, BDI, SCL90R, and DES). They were then treated by eight sessions of EMDR. During the first session EEG monitoring was continuously performed and 18F-FDG PET scans, depicting brain metabolism, were acquired at rest within a week (T0). After the last session, in which the two clients were considered to be symptoms-free, neuropsychological, clinical, and PET assessment were repeated (T1). PET data were semi-quantitatively compared to a group of 18 normal controls, as for EEG the preferential cortical activations were disclosed by thresholding the individual z-score to a p < 0.05. There was a significant improvement in clinical condition for both clients associated with a significant decrease in CAPS scores. IES and BDI were found to be pathological at T0 and improved at T1 in only one subject. Visuo-constructive abilities and abstract reasoning improved after EMDR in both subjects. As for EEG, the most striking changes occurred in fronto-temporal-parietal cortex in subject 1 while subject 2 showed only minor changes. PET showed more pronounced metabolism in orbito-frontal and prefrontal cortex at T1 as compared to T0 in both subjects. In conclusion both clients had a clear clinical improvement in PTSD symptoms associated with metabolic and electrophysiological changes in limbic and associative cortex, respectively, highlighting the value of EMDR also in such extreme pathological conditions.

Aging and Spaceflight: Catalase targeted to mitochondria alters skeletal structure and responses to musculoskeletal disuse

Accumulation of oxidative damage from excess reactive oxygen species (ROS) contributes to aging and also may mediate adverse tissue responses to the space environment. We aim to explore the importance of cellular redox defense for physiological adaptation and tissue degeneration during spaceflight or prolonged bedrest on Earth. To begin to test this, transgenic mice (male, 16 weeks of age) with human catalase targeted to mitochondria (mCAT), and wildtype (WT) littermates were analysed for responsiveness to a combination of hindlimb unloading (to simulate weightlessness) and a single dose of ionizing radiation (137Cs, 0.83 Gy/min, 2Gy); mCAT mice are known to display improved longevity and reduced age‐related diseases compared to WT mice (Schriner et al. 2005, Dai et al. 2010). After 2 weeks, bones were recovered for analysis of cell behavior (osteoblast and osteoclast differentiation ex vivo from bone marrow cells), oxidative lipid damage (malondialdehyde, 4‐hydroxynonenol) and structure (3D microcomputed tomography). mCAT mice expressed the catalase transgene in skeletal tissues, and in cultured marrow‐derived osteoblasts and pre‐osteoclasts. Treatment with unloading and radiation led to increased lipid oxidative damage markers in bones from WT mice but not mCAT mice, showing that transgene expression effectively mitigated oxidative damage. Ex vivo osteoblast colony growth rate was 95% greater in mCAT mice than WT, and correlated with catalase activity levels (P&lt;0.005, r=0.6679), though terminal differentiation of osteoblasts (mineralization) and osteoclasts (resorption pit formation) remained unaffected. Microarchitectural analysis of high turnover, cancellous tissue revealed diminished size of mCAT bones compared to WT (−16% bone volume/total volume mCAT/WT), and no genotype‐dependent difference in cancellous bone loss caused by treatment. Similarly, slow‐turnover, cortical bones were smaller in control mCAT mice (−7% cortical area), although treatment of mCAT mice showed an unexpected and rapid stimulation of radial expansion (+8% cortical area, +22% moment of inertia, mCAT:Treated/Control), which was not observed in WT mice. Thus, quenching of mitochondrial ROS by over‐expression of catalase appeared to stimulate growth but not differentiation of osteoprogenitors ex vivo; nonetheless, the smaller size of mCAT bones showed that mitochondrial ROS signaling was important for the acquisition of adult bone structure. Further, we conclude that transgene expression led to changes in cortical structure following treatment that are similar to those that occur during aging, indicative of a role for mitochondrial ROS in coordinating skeletal remodeling in response to challenge.Support or Funding InformationGrant funding from NASA Space Biology program (NNH14ZTT001N) and the National Space Biomedical Research Institute through NCC 9–58, Project MA02501. A.S. Schreurs was supported by a NASA Space Biology Postdoctoral Program Fellowship award.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Brain TSPO imaging and gray matter volume in schizophrenia patients and in people at ultra high risk of psychosis: An [11C]PBR28 study

Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure. MethodsFourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [11C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan. We investigated the relationship between the volume changes of cortical regions and microglial activation in cortical GM (as indexed by [11C]PBR28 distribution volume ratio (DVR). ResultsThe total cortical GM volume was significantly lower in SCZ than the controls [mean (SD)/cm3: SCZ=448.83 (39.2) and controls=499.6 (59.2) (p=0.02) but not in UHR (mean (SD)=503.06 (57.9) and controls=524.46 (45.3) p=0.3). Regression model fitted the total cortical GM DVR values with the cortical regional volumes in SCZ (r=0.81; p<0.001) and in UHR (r=0.63; p=0.02). We found a significant negative correlation between the TSPO signal and total cortical GM volume in SCZ with the highest absolute correlation coefficient in the right superior-parietal cortex (r=−0.72; p=0.006). ConclusionsThese findings suggest that microglial activity is related to the altered cortical volume seen in schizophrenia. Longitudinal investigations are required to determine whether microglial activation leads to cortical gray matter loss.