Lateral Orbital Cortex Research Articles

Cobalt microinjections into the infralimbic cortex of the anesthetized rat suppresses circulatory and respiratory reactions to the microelectrostimulation of the lateral orbital cortex

The central autonomous network that controls visceral systems, including circulatory and respiratory systems, includes the visceromotor infralimbic cortex (IL), which is one of the areas of the prefrontal cortex and is located on the medial surface of the large hemispheres. At the same time, there is evidence that areas of the prefrontal cortex located on the orbitofrontal surface, including the lateral orbital cortex (LO), can participate in the control of autonomous functions. The purpose of this work was to experimentally test the hypothesis according to which the participation of LO in the control of respiratory and circulatory functions is realized through IL. To this end, in acute experiments on laboratory rats anesthetized with urethane, the effect of microinjections of cobalt chloride solution (CoCl2) in IL on the reactions of circulatory and respiratory systems caused by microelectrostimulation of LO was investigated. It is known that Co2+ ions are non-specific blockers of synaptic transmission, therefore microinjections of CoCl2 solutions lead to disruption of conduction in the structures of the central nervous system. In the first, control series of experiments, micro-electrical stimulation of LO caused specific responses of the circulatory and respiratory systems, which were consistently reproduced throughout the experiment. In the second, experimental series, the introduction of CoCl2 solution into IL suppressed responses to micro-electrical stimulation of LO, and this effect turned out to be reversible. The obtained results confirmed the hypothesis put forward about the possible participation of IL in the implementation of autonomous LO functions. The elucidation of the mechanisms that ensure the interaction of LO and IL in the context of autonomous control should be the subject of further experimental research.

Does ‘portion size’ matter? Brain responses to food and non-food cues presented in varying amounts

Larger portions of food elicit greater intake than smaller portions of food, particularly when foods are high in energy density (kcal/g; ED). The neural mechanisms underlying this effect remain unclear. The present study used fMRI to assess brain activation to food (higher-ED, lower-ED) and non-food (office supplies) images presented in larger and smaller (i.e., age-appropriate) amounts in 61, 7-8-year-olds (29 male, 32 female) without obesity. Larger amounts of food increased activation in bilateral visual and right parahippocampal areas compared to smaller amounts; greater activation to food amount (larger > smaller) in this cluster was associated with smaller increases in food intake as portions increased. Activation to amount (larger > smaller) was stronger for food than office supplies in primary and secondary visual areas, but, for office supplies only, extended into bilateral parahippocampus, inferior parietal cortex, and additional visual areas (e.g., V7). Activation was greater for higher-vs. lower-ED food images in ventromedial prefrontal cortex for both larger and smaller amounts of food; however, this activation extended into left lateral orbital frontal cortex for smaller amounts only. Activation to food cues did not differ by familial risk for obesity. These results highlight potentially distinct neural pathways for encoding food energy content and quantity.

Association between physical frailty and cortical structure in middle-aged and elderly people: a Mendelian randomization study.

Physical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures. The Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran's Q test, and weighted median were employed. At the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable. The results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

Cobalt Microinjections into the Infralimbic Cortex of the Anesthetized Rat Suppresses Circulatory and Respiratory Reactions to the Electrical Microstimulation of the Lateral Orbital Cortex

Cobalt Microinjections into the Infralimbic Cortex of the Anesthetized Rat Suppresses Circulatory and Respiratory Reactions to the Electrical Microstimulation of the Lateral Orbital Cortex

The effect of dopamine replacement therapy on cortical structure in Parkinson's disease.

To explore the cortical structural reorganization in Parkinson's disease (PD) patients under chronic dopamine replacement therapy (DRT) in cross-sectional and longitudinal data and determine whether these changes were associated with clinical alterations. A total of 61 DRT-treated, 60 untreated PD patients, and 61 normal controls (NC) were retrospectively included. Structural MRI scans and neuropsychological tests were conducted. Cortical thickness and volume were extracted based on FreeSurfer and were analyzed using general linear model to find statistically significant differences among three groups. Correlation analyses were performed among significant cortical areas, medication treatment (duration and dosage), and neuropsychological tests. Longitudinal cortical structural changes of patients who initiated DRT were analyzed using linear mixed-effect model. Significant cortical atrophy was primarily observed in the prefrontal cortex in treated patients, including the cortical thickness of right pars opercularis and the volume of bilateral superior frontal cortex (SFC), left rostral anterior cingulate cortex (rACC), right lateral orbital frontal cortex, right pars orbitalis, and right rostral middle frontal cortex. A negative correlation was detected between the left SFC volume and levodopa equivalent dose (LED) (r = -0.316, p = 0.016), as well as the left rACC volume and medication duration (r = -0.329, p = 0.013). In the patient group, the left SFC volume was positively associated with digit span forward score (r = 0.335, p = 0.017). The left SFC volume reduction was longitudinally correlated with increased LED (standardized coefficient = -0.077, p = 0.001). This finding provided insights into the influence of DRT on cortical structure and highlighted the importance of drug dose titration in DRT.

P049 Actigraphic rest-activity rhythms in older adults ‘at risk’ for dementia: associations with reduced cortical thickness in frontal, temporal and occipital cortices

Abstract Background Rest-activity rhythm disturbance is common in older adults ‘at risk’ for dementia. This may be an early marker of underlying disease pathology and risk of future decline. However, our understanding of how rest-activity rhythm relates to brain integrity remains unclear. Methods This study used vertex-wise analyses to examine the association between nonparametric actigraphy measures and cortical thickness in older adults ‘at risk’ for dementia. Primary measures of interest were intra-daily variability (IV), relative amplitude (RA), inter-daily stability (IS), and average activity during the least active 5-hour period (L5). Results 143 older adults ‘at risk’ for cognitive decline were included (mean age=67.41, SD=7.96). Higher IV was associated with lower cortical thickness in the right cuneus (CWP< 0.001), left middle frontal gyrus (CWP< 0.001) and lateral orbital frontal cortex (CWP=0.004). Higher L5 was linked with cortical thinning in the left superior temporal sulcus (CWP=0.004), superior middle temporal cortex (CWP=0.010) and middle temporal gyrus (CWP=0.013), as well as right inferior parietal lobe (CWP< 0.001). Lower IS was associated with cortical thinning in the left (CWP=0.002) and right (CWP< 0.001) superior frontal gyri, left superior temporal gyrus (CWP=0.043) and left post-central gyrus (CWP=0.033). Conclusions Markers of circadian rhythmicity are associated with reduced cortical thickness in frontal, temporal and occipital cortices in older adults ‘at risk’ for dementia. Future work is still required to delineate whether brain degeneration leads to altered daily rhythms and/or if circadian misalignment contributes to cognitive decline longitudinally.

Neuroanatomical correlates of aggressiveness: a case-control voxel- and surface-based morphometric study.

Aggression occurs across the population ranging on a symptom continuum. Most previous studies have used magnetic resonance imaging in clinical/forensic samples, which is associated with several confounding factors. The present study examined structural brain characteristics in two healthy samples differing only in their propensity for aggressive behavior. Voxel- and surface-based morphometry (SBM) analyses were performed on 29 male martial artists and 32 age-matched male controls. Martial artists had significantly increased mean gray matter volume in two frontal (left superior frontal gyrus and bilateral anterior cingulate cortex) and one parietal (bilateral posterior cingulate gyrus and precuneus) brain clusters compared to controls (whole brain: p < 0.001, cluster level: family-wise error (FWE)-corrected). SBM analyses revealed a trend for greater gyrification indices in martial artists compared to controls in the left lateral orbital frontal cortex and the left pars orbitalis (whole brain: p < 0.001, cluster level: FWE-corrected). The results indicate brain structural differences between martial artists and controls in frontal and parietal brain areas critical for emotion processing/inhibition of emotions as well as empathic processes. The present study highlights the importance of studying healthy subjects with a propensity for aggressive behavior in future structural MRI research on aggression.

The effects of physical exercise on structural, functional, and biochemical brain characteristics in individuals with chronic whiplash-associated disorder: A pilot randomized clinical trial.

Exercise for people with whiplash associated disorder (WAD) induces hypoalgesic effects in some, but hyperalgesic effects in others. We investigated the exercise-induced neurobiological effects of aerobic and strengthening exercise in individuals with chronic WAD. Sixteen participants (8 WAD, 8 pain-free [CON]) were randomised to either aerobic or strengthening exercise. MRI for brain morphometry, functional MRI for brain connectivity, and magnetic resonance spectroscopy for brain biochemistry, were used at baseline and after the 8-week intervention. There were no differences in brain changes between exercise groups in either the WAD or CON group, therefore aerobic and strengthening data were combined to optimise sample size. After the exercise intervention, the CON group demonstrated increased cortical thickness (left parahippocampus: mean difference = 0.04, 95% CI = 0.07-0.00, p = 0.032; and left lateral orbital frontal cortex: mean difference = 0.03, 95% CI = 0.00-0.06, p = 0.048). The WAD group demonstrated an increase in prefrontal cortex (right medial orbital frontal) volume (mean difference = 95.57, 95% CI = 2.30-192.84, p = 0.046). Functional changes from baseline to follow-up between the default mode network and the insula, cingulate cortex, temporal lobe, and somatosensory and motor cortices, were found in the CON group, but not in the WAD group. There were no changes post-exercise in brain biochemistry. Aerobic and strengthening exercises did not exert differential effects on brain characteristics, however differences in structural and functional changes were found between WAD and CON groups. This suggests that an altered central pain modulatory response may be responsible for differential effects of exercise in individuals with chronic WAD.

Structural equation modeling of treatment-related changes in neural connectivity for youth with PTSD

BackgroundPrevious studies suggest that improvement in symptoms of posttraumatic stress disorder (PTSD) is accompanied by changes in neural connectivity, however, few studies have investigated directional (effective) connectivity. The current study assesses treatment-related changes in effective connectivity in youth with PTSD undergoing Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). MethodsFunctional MRI scans before and after 16 weeks of TF-CBT for 20 youth with PTSD, or the same time interval for 20 healthy controls (HC) were included in the analysis. Structural equation modeling was used to model group differences in directional connectivity at baseline, and changes in connectivity from pre- to post-treatment. ResultsAt baseline, the PTSD group, relative to the HC group, had significantly greater connectivity in the path from dorsal cingulate to anterior cingulate and from dorsal cingulate to posterior cingulate corticies. From pre- to post-treatment, connectivity in these paths decreased significantly in the PTSD group, as did connectivity from right hippocampus to left superior temporal gyrus. Connectivity from the left amygdala to the lateral orbital frontal cortex was significantly lower in PTSD vs HC at baseline, but did not change from pre- to post-treatment. ConclusionAlthough based on a small sample, these results converge with previous studies in suggesting a central role for the dorsal cingulate cortex in PTSD symptoms. The direction of this connectivity suggests that the dorsal cingulate is the source of modulation of anterior and posterior cingulate cortex during trauma-focused cognitive behavioral therapy.

Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction

ObjectivesTo explore the neuropsychological profile and the integrity of the olfactory network in patients with COVID-19-related persistent olfactory dysfunction (OD). MethodsPatients with persistent COVID-19-related OD underwent olfactory assessment with Sniffin’ Sticks and neuropsychological evaluation. Additionally, both patients and a control group underwent brain MRI, including T1-weighted and resting-state functional MRI (rs-fMRI) sequences on a 3 T scanner. Morphometrical properties were evaluated in olfaction-associated regions; the rs-fMRI data were analysed using graph theory at the whole-brain level and within a standard parcellation of the olfactory functional network. All the MR-derived quantities were compared between the two groups and their correlation with clinical scores in patients were explored. ResultsWe included 23 patients (mean age 37 ± 14 years, 12 females) with persistent (mean duration 11 ± 5 months, range 2–19 months) COVID-19-related OD (mean score 23.63 ± 5.32/48, hyposmia cut-off: 30.75) and 26 sex- and age-matched healthy controls. Applying population-derived cut-off values, the two cognitive domains mainly impaired were visuospatial memory and executive functions (17 % and 13 % of patients). Brain MRI did not show gross morphological abnormalities. The lateral orbital cortex, hippocampus, and amygdala volumes exhibited a reduction trend in patients, not significant after the correction for multiple comparisons. The olfactory bulb volumes did not differ between patients and controls. Graph analysis of the functional olfactory network showed altered global and local properties in the patients’ group (n = 19, 4 excluded due to artifacts) compared to controls. Specifically, we detected a reduction in the global modularity coefficient, positively correlated with hyposmia severity, and an increase of the degree and strength of the right thalamus functional connections, negatively correlated with short-term verbal memory scores. DiscussionPatients with persistent COVID-19-related OD showed an altered olfactory network connectivity correlated with hyposmia severity and neuropsychological performance. No significant morphological alterations were found in patients compared with controls.

Microelectrostimulation of the Rat Lateral Orbital Cortex Causes Specific Reactions of the Circulation and Respiration

Microelectrostimulation of the Rat Lateral Orbital Cortex Causes Specific Reactions of the Circulation and Respiration

Projections from the five divisions of the orbital cortex to the thalamus in the rat.

The orbital cortex (ORB) of the rat consists of five divisions: the medial (MO), ventral (VO), ventrolateral (VLO), lateral (LO), and dorsolateral (DLO) orbital cortices. No previous report has comprehensively examined and compared projections from each division of the ORB to the thalamus. Using the anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we describe the efferent projections from the five divisions of the ORB to the thalamus in the rat. We demonstrated that, with some overlap, each division of the ORB distributed in a distinct (and unique) manner to nuclei of the thalamus. Overall, ORB projected to a relatively restricted number of sites in the thalamus, and strikingly distributed entirely to structures of the medial/midline thalamus, while completely avoiding lateral regions or principal nuclei of the thalamus. The main termination sites in the thalamus were the paratenial nucleus (PT) and nucleus reuniens (RE) of the midline thalamus, the medial (MDm) and central (MDc) divisions of the mediodorsal nucleus, the intermediodorsal nucleus, the central lateral, paracentral, and central medial nuclei of the rostral intralaminar complex and the submedial nucleus (SM). With some exceptions, medial divisions of the ORB (MO, VO) mainly targeted "limbic-associated" nuclei such as PT, RE, and MDm, whereas lateral division (VLO, LO, DLO) primarily distributed to "sensorimotor-associated" nuclei including MDc, SM, and the rostral intralaminar complex. As discussed herein, the medial/midline thalamus may represent an important link (or bridge) between the orbital cortex and the hippocampus and between the ORB and medial prefrontal cortex. In summary, the present results demonstrate that each division of the orbital cortex projects in a distinct manner to nuclei of the thalamus which suggests unique functions for each division of the orbital cortex.

Relationship between CSF tau biomarkers and structural brain MRI measures in frontotemporal lobar degeneration

BackgroundRecently in the field neurodegenerative diseases increasing attention has been pointed to CSF biomarkers and their integration with neuroimaging (1). Frontotemporal lobar degeneration (FTLD) refers to a heterogeneous group of clinical syndromes with different underlying proteinopathies including tau pathology. CSF biomarkers have been proposed as diagnostic and prognostic factors. Aim of our study was to evaluate the relationship between CSF tau biomarkers and structural MRI brain measures in FTLD. MethodsWe included early FTLD patient. All included patients underwent lumbar puncture to evaluate amyloid, total-tau (t-tau), phospho-tau 181 (p-tau); p-tau/t-tau ratio was also calculated; brain MRI was performed to estimate whole brain volume, volume of principal deep grey matter structures and regional cortical thickness. ResultsDemographic characteristics of the 28 included patients were as follows: female/male: 9/19; mean ± SD age: 68.1 ± 7.8 years. The p-tau/t-tau ratio was significantly correlated with whole brain volume (r = 0.69; p: 0.001), left putamen volume (r = 0.55 p: 0.009), left pallidum volume (r = 0.41; p: 0.01), right accumbens area (r = 0.47; p: 0.02). P-tau/t tau ratio showed also a significant correlation with cortical thickness of left temporal lobe (r = 0.74; p: 0.001) and right lateral orbital frontal cortex (r = 0.45; p: 0.03). Linear regression showed a significant relationship between p-tau/t-tau ratio and left temporal pole (p = 0.01; r2: 0.60) and brain volume (p:0.002; r2: 0.56) after controlling for age and gender. ConclusionsOur data suggest that CSF biomarkers, especially p-tau/t-tau ratio, could play a role as prognostic factor in FTLD. Further longitudinal investigations are needed to confirm these findings.

Food Allergy-Induced Autism-Like Behavior is Associated with Gut Microbiota and Brain mTOR Signaling.

PurposeFood allergy-induced autism-like behavior has been increasing for decades, but the causal drivers of this association are unclear. We sought to test the association of gut microbiota and mammalian/mechanistic target of rapamycin (mTOR) signaling with cow’s milk allergy (CMA)-induced autism pathogenesis.MethodsMice were sensitized intragastrically with whey protein containing cholera toxin before sensitization on intraperitoneal injection with whey-containing alum, followed by intragastric allergen challenge to induce experimental CMA. The food allergic immune responses, ASD-like behavioral tests and changes in the mTOR signaling pathway and gut microbial community structure were performed.ResultsCMA mice showed autism-like behavioral abnormalities and several distinct biomarkers. These include increased levels of 5-hydroxymethylcytosine (5-hmC) in the hypothalamus; c-Fos were predominantly located in the region of the lateral orbital prefrontal cortex (PFC), but not ventral; decreased serotonin 1A in amygdala and PFC. CMA mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial genera, including the Lactobacillus. Interestingly, the changes were accompanied by promoted mTOR signaling in the brain of CMA mice.ConclusionWe found that disease-associated microbiota and mTOR activation may thus play a pathogenic role in the intestinal, immunological, and psychiatric Autism Spectrum Disorder (ASD)-like symptoms seen in CAM associated autism. However, this is only a preliminary study, and their mechanisms require further investigation.

Effects of Maternal Deprivation on the Prefrontal Cortex of Male Rats: Cellular, Neurochemical, and Behavioral Outcomes.

Stressful events experienced during early life are associated with increased vulnerability of developing psychopathology in adulthood. In the present study, we exposed 9-day-old Wistar rats to 24 h maternal deprivation (MD) with the aim to investigate the impact of early life stress (ELS) on morphological, biochemical, and functional aspects of the prefrontal cortex (PFC), a brain region particularly sensitive to stress. We found that in the superficial medial orbital cortex (MO), young adult male rats had reduced density of GAD67 and CCK immunopositive cells, while the rostral part of the ventral lateral orbital cortex (roVLO) showed a decrease in the density of GAD67 immunopositive cells in both superficial and deep layers. In addition, the superficial rostral part of area 1 of the cingulate cortex (roCg1) and deep prelimbic cortex (PrL) was also affected by MD indicated by the reduction in PV immunopositive cellular density. Furthermore, MD induced upregulation of brain-derived neurotrophic factor (BDNF), while it did not affect the overall expression of Iba1 in neonatal or young adult PFC as measured by Western blot, however, microglial activation in young adult MD rats was detected immunohistochemically in deep layers of MO and infralimbic cortex (IL). Interestingly, when young adult male rats were subjected to a behavioral flexibility test in a T-maze, MD rats showed a subtle impairment in T-maze reversal learning indicating a mildly affected PFC function. Taken together, our findings demonstrated that MD reduced the density of interneurons and induced microglial activation, in particular, PFC areas at young adulthood, and could alter synaptic plasticity accompanied by PFC dysfunction.

In vivo microdialysis shows differential effects of prenatal protein malnutrition and stress on norepinephrine, dopamine, and serotonin levels in rat orbital frontal cortex.

Prenatal protein malnutrition (PPM) alters the developing brain including changes in monoaminergic systems and attention. In the present study, we used in vivo microdialysis to examine the relationship between PPM, acute stress, and extracellular serotonin (5HT), dopamine (DA) and norepinephrine (NE) in both hemispheres of lateral orbital frontal cortices (lOFC) in the adult rat. We hypothesized that prenatal protein malnutrition would alter extracellular concentrations of cortical monoamines. The effects of an acute restraint stress were also assessed because PPM alters the brain's response to stress. We used adult male, Long-Evans rats [10 prenatally malnourished (6% casein) and 10 prenatally well-nourished (25% casein)]. Samples were collected from the left and right hemispheres of the lOFC every 20 min for 6 hr total and quantified using high-performance liquid chromatography (HPLC). After 2 hr of sampling, animals were exposed to a 40-min restraint stress. Extracellular levels of NE were significantly higher in PPM animals than in well-nourished controls across both hemispheres at all time-points. In contrast, baseline levels of 5HT and DA levels did not differ between nutritional groups. 5HT levels, but not NE or DA levels, were elevated compared to baseline levels in both nutritional groups and in both hemispheres during the first 20 min of stress exposure. These data highlight the impact of PPM on neuromodulatory systems and the profile of changes in response to acute stress. Additional studies are needed to determine how these basal and stress-related responses impact cognitive performance and whether these differences persist during cognitive testing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Neural basis responsible for self-control association with procrastination: Right MFC and bilateral OFC functional connectivity with left dlPFC

Converging theory and evidence highlights procrastination as a form of self-control failure. However, the underlying neural correlates of how self-control is associated with procrastination remains unclear. As such we investigated the neural basis for self-control association with procrastination using voxel-based morphometry (VBM) and resting-state functional connectivity (FC) approaches. The VBM results showed a positive correlation between self-control and the gray matter volume of left dorsolateral prefrontal cortex (dlPFC). Then the FC of left dlPFC to lateral orbital frontal cortex (lOFC) and right dorsal medial frontal cortex (dMFC) were all negatively correlated to procrastination and showed a mediating effect. This indicates that brain functional communication involves in emotion regulation and valuation processing may account for the association between self-control and procrastination.

Systematic volumetric analysis predicts response to CSF drainage and outcome to shunt surgery in idiopathic normal pressure hydrocephalus

ObjectivesIdiopathic normal pressure hydrocephalus (INPH) is a neurodegenerative disorder characterized by excess cerebrospinal fluid (CSF) in the ventricles, which can be diagnosed by invasive CSF drainage test and treated by shunt placement. Here, we aim to investigate the diagnostic and prognostic power of systematic volumetric analysis based on brain structural MRI for INPH.MethodsWe performed a retrospective study with a cohort of 104 probable INPH patients who underwent CSF drainage tests and another cohort of 41 INPH patients who had shunt placement. High-resolution T1-weighted images of the patients were segmented using an automated pipeline into 283 structures that are grouped into different granularity levels for volumetric analysis. Volumes at multi-granularity levels were used in a recursive feature elimination model to classify CSF drainage responders and non-responders. We then used pre-surgical brain volumes to predict Tinetti and MMSE scores after shunting, based on the least absolute shrinkage and selection operator.ResultsThe classification accuracy of differentiating the CSF drainage responders and non-responders increased as the granularity increased. The highest diagnostic accuracy was achieved at the finest segmentation with a sensitivity/specificity/precision/accuracy of 0.89/0.91/0.84/0.90 and an area under the curve of 0.94. The predicted post-surgical neurological scores showed high correlations with the ground truth, with r = 0.80 for Tinetti and r = 0.88 for MMSE. The anatomical features that played important roles in the diagnostic and prognostic tasks were also illustrated.ConclusionsWe demonstrated that volumetric analysis with fine segmentation could reliably differentiate CSF drainage responders from other INPH-like patients, and it could accurately predict the neurological outcomes after shunting.Key Points• We performed a fully automated segmentation of brain MRI at multiple granularity levels for systematic volumetric analysis of idiopathic normal pressure hydrocephalus (INPH) patients.• We were able to differentiate patients that responded to CSF drainage test with an accuracy of 0.90 and area under the curve of 0.94 in a cohort of 104 probable INPH patients, as well as to predict the post-shunt gait and cognitive scores with a coefficient of 0.80 for Tinetti and 0.88 for MMSE.• Feature analysis showed the inferior lateral ventricle, bilateral hippocampus, and orbital cortex are positive indicators of CSF drainage responders, whereas the posterior deep white matter and parietal subcortical white matter were negative predictors.

A multimodal imaging study of brain structural correlates of schizotypy dimensions using the MSS

Schizotypy is a multidimensional construct of subclinical schizophrenia-like behavioural traits and cognition. The recently developed multidimensional schizotypy scale (MSS) provides an improved psychometric assessment of the three main dimensions (positive, negative, and disorganised). We tested the hypothesis that the three dimensions are related to brain structural variation in the precuneus and fronto-thalamo-striatal system in a new non-clinical healthy cohort to support a dimensional model of the psychosis spectrum. We analysed data from 104 subjects with Multidimensional Schizotypy Scale (MSS) phenotyping and 3 Tesla magnetic resonance images using voxel-based morphometry (VBM) applying CAT12 software, and diffusion-tensor imaging (DTI) with TBSS in FSL to test for correlations with MSS scores. MSS subscales and total score were negatively associated with GMV in brain areas including the medial prefrontal cortex, anterior cingulate cortex, and lateral prefrontal and orbital cortex. MSS schizotypy was associated with white matter integrity in anterior thalamic radiation, uncinate fasciculus, and superior longitudinal fasciculus. Our findings provide first direct evidence for an association of schizotypy (as a psychosis risk phenotype) and the fronto-thalamo-striatal system, in both grey and white matter with regionally diverging effects across single dimensions. This provides new evidence arguing for the fronto-striatal system (rather than precuneus) in schizotypy.

Depression Mediated By Inflammatory Responses To Chronic Stress

BackgroundMajor depressive disorder (MDD) is a chronic debilitating illness affecting yearly 350 million people worldwide. Although the mechanisms underlying depression are still not defined, it has been suggested that inflammation acts as depression mediator promoting glial and neuronal dysfunction. Microglia, as the resident innate immune cells of the brain, can be activated by both immune (i.e. infection) and nonimmune challenges (i.e. psychosocial stress), and contribute to the regulation of neurological and neuropsychiatric disorders. The aim of the present study is to characterize the inflammatory responses during chronic social stress and determine their effects on neuronal homeostasis and depression in a rodent depression model.MethodsThe Repeated Social Defeat Stress (RSDS) paradigm (10 days) was utilized to study the post RSDS stages [(10+5 days (D15) and 10+15 days (D25)] in 2–4 months old male C57BL/6J, CX3CR1‐GFP+ mice. At the beginning of the RSDS paradigm the mice were fed with chow containing the Csf1R inhibitors PLX5622 [passes blood brain barrier (BBB) and specifically targets microglia] or PLX73086 (does not cross BBB and targets peripheral monocytes) or control chow. In addition, all groups were administered BrdU (5‐bromo‐2’‐deoxyuridine) ad libitum to monitor cell proliferation. Behavioral tasks for social interaction, anxiety, anhedonia and despair behavioral (BH1 &amp; BH2) were performed to categorize the defeated mice to susceptible (S; depressive‐like) and resilient (R; non‐depressive) to stress groups. The study focuses on the MDD‐affected Prefrontal (mPFC), Ventral or Lateral Orbital (VO/LO) Cortex areas. Cell quantification and data analysis were partially blinded and performed by 3 investigators.ResultsInflammation was observed in all areas at D15, depicted by the presence of activated Iba1+ cells [reactive morphology (CD68+) and inflammatory markers (TSPO, CD206, CD86, iNOS, Arg‐1)] in the S groups. Given the increased microglial numbers, microglial proliferation capacity was also examined after chronic stress, revealing a small increase in the S groups. Peripheral macrophage numbers (FACS; CD11b+CD45+high) were comparable at D15 in C, S and R groups. Remarkably, after microglial ablation (PLX5622), mice did not exhibit depressive behaviors, or altered cellular markers (c‐Fos, MAP2). This was altered after PLX withdrawal. Interestingly, PLX73086 chow also resulted in significant resilience to chronic stress, which was reversed to susceptibility after chow withdrawal, suggesting that PLX leaked into the CNS parenchyma, potentially a result of cerebrovascular compromise observed during chronic stress.ConclusionsOur data suggest that chronic stress induces microglial activation and recruitment, swiftly compromising neuronal homeostasis, leading to depressive‐like behavior in mice. Microglial elimination during psychosocial stress protected against the psychological and physical effects, pointing to the significance of microglia in modulating depression disorder.Support or Funding InformationThis work was supported by: American Heart Association #19PRE34370044 and Scholars in BioMedical Sciences Program T32GM127253.Graphical abstract of experimental outline.Figure 1