Significant Gray Matter Volume Reduction Research Articles

Changes of cerebral structure and perfusion in subtypes of systemic sclerosis: a brain magnetic resonance imaging study.

The characteristics of brain impairment in different subtypes of systemic sclerosis (SSc) (dcSSc, diffuse cutaneous SSc; lcSSc, limited cutaneous SSc) remain unclear. This study aimed to characterize cerebral structure and perfusion changes in different subtype of SSc patients using magnetic resonance (MR) imaging. Seventy SSc patients (46.0 ± 11.7 years, 62 females) and 30 healthy volunteers (44.8 ± 13.7 years, 24 females) were recruited and underwent brain MR imaging and Montreal Cognitive Assessment (MoCA) test. Gray matter (GM) volumes were measured using voxel-based morphometry analysis on T1-weighted images. Voxel-based and regional cerebral blood flow (CBF) was calculated on arterial spin labelling images. The cerebral structural and perfusion measurements by MR imaging were compared among dcSSc, lcSSc and healthy subjects using one-way ANOVA. The correlations between clinical characteristics and MR imaging measurements were also analyzed. The dcSSc patients exhibited a significant reduction in GM volume in the para-hippocampal region (cluster p < 0.01, FWE corrected) compared with healthy volunteers. Whereas, SSc patients, particularly lcSSc patients, showed elevated CBF in cerebellum, insula, cerebral cortex, and subcortical structures (regional analyses: all p < 0.05; voxel-based analyses: cluster p < 0.01, FWE corrected). Furthermore, clinical characteristics of modified Rodnan skin score (mRSS) (r value ranged from -0.29 to -0.45), MoCA scores (r = 0.40) and antinuclear antibody (ANA) positivity (r=-0.33) were significantly associated with CBF in some regions (all p < 0.05). The manifestations of brain involvement vary among different subtypes of SSc. In addition, severe skin sclerosis may indicate higher risk of brain involvement in SSc patients.

Cortical volume reductions in men transitioning to first-time fatherhood reflect both parenting engagement and mental health risk.

Perinatal reductions in gray matter volume have been observed in human mothers transitioning to parenthood, with preliminary evidence for similar changes in fathers. These reductions have been theorized to support adaptation to parenting, but greater investigation is needed. We scanned 38 first-time fathers during their partner's pregnancy and again after 6months postpartum, and collected self-report data prenatally and 3, 6, and 12months postpartum. Significant gray matter volume reductions were observed across the entire cortex but not the subcortex. Fathers who reported stronger prenatal bonding with the unborn infant, and planned to take more time off from work after birth, subsequently showed larger cortical volume decreases. Larger reductions in gray matter volume also emerged among fathers who reported stronger postpartum bonding with the infant, lower parenting stress, and more time spent with their infant. Larger volume reductions predicted more postpartum sleep problems and higher levels of postpartum depression, anxiety, and psychological distress, controlling for prenatal sleep and mental health. Volume reductions were smaller among fathers whose infants were older at the postpartum scan, indicating potential rebound. These results suggest that perinatal gray matter volume reductions might reflect not only greater parenting engagement but also increased mental health risk in new fathers.

Neural foundation of the diathesis-stress model: longitudinal gray matter volume changes in response to stressful life events in major depressive disorder and healthy controls.

Recurrences of depressive episodes in major depressive disorder (MDD) can be explained by the diathesis-stress model, suggesting that stressful life events (SLEs) can trigger MDD episodes in individuals with pre-existing vulnerabilities. However, the longitudinal neurobiological impact of SLEs on gray matter volume (GMV) in MDD and its interaction with early-life adversity remains unresolved. In 754 participants aged 18-65 years (362 MDD patients; 392 healthy controls; HCs), we assessed longitudinal associations between SLEs (Life Events Questionnaire) and whole-brain GMV changes (3 Tesla MRI) during a 2-year interval, using voxel-based morphometry in SPM12/CAT12. We also explored the potential moderating role of childhood maltreatment (Childhood Trauma Questionnaire) on these associations. Over the 2-year interval, HCs demonstrated significant GMV reductions in the middle frontal, precentral, and postcentral gyri in response to higher levels of SLEs, while MDD patients showed no such GMV changes. Childhood maltreatment did not moderate these associations in either group. However, MDD patients who had at least one depressive episode during the 2-year interval, compared to those who did not, or HCs, showed GMV increases in the middle frontal, precentral, and postcentral gyri associated with an increase in SLEs and childhood maltreatment. Our findings indicate distinct GMV changes in response to SLEs between MDD patients and HCs. GMV decreases in HCs may represent adaptive responses to stress, whereas GMV increases in MDD patients with both childhood maltreatment and a depressive episode during the 2-year interval may indicate maladaptive changes, suggesting a neural foundation for the diathesis-stress model in MDD recurrences.

Structural Neuroimaging and Molecular Signatures of Drug‐Naive Depression With Melancholic Features

Objectives: Melancholic depression (MD) is a common subtype of major depressive disorder (MDD). It is difficult to treat because its neurobiological basis is poorly understood. Therefore, to investigate whether MD patients have any structural changes in gray matter (GM) and the molecular foundation of these changes, we combined voxel‐based morphometry (VBM) analysis with neurotransmitter system‐derived mapping from public data.Methods: 137 drug‐naive MDD patients and 75 healthy controls (HCs) were recruited for structural magnetic resonance imaging. The imaging results were analyzed using VBM analysis. MDD patients were then divided into MD and nonmelancholic depression (NMD) subgroups according to their scores on the Montgomery–Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale. Next, we analyzed the spatial correlation between the changes in the gray matter volume (GMV) maps and the neurotransmitter receptor/transporter protein density maps provided by the JuSpace toolbox.Results: Compared to HCs, patients with MD had significant GMV reduction in the bilateral hippocampus, bilateral thalamus, right amygdala, and right posterior cingulate cortex (PCC)/precuneus. Compared to patients with NMD, MD patients had significant GMV reduction in the bilateral PCC/precuneus and lateral occipital cortex. Moreover, compared to HCs, changes in GMV introduced by MD were spatially associated with the serotonin transporter, cannabinoid receptor, and μ‐opioid receptor. Compared to NMD patients, changes in GMV introduced by MD were spatially associated with the vesicular acetylcholine transporter.Conclusion: The present study discovered abnormal GMV alterations in patients with subtypes of depression. We also found a series of neurotransmitter receptors that may be associated with the alterations. The findings of the current study may provide a more comprehensive understanding of the molecular mechanisms underlying the structural abnormalities in subtypes of depression and potentially offer new insights into developing new therapeutic strategies.

Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations

BackgroundPrevious longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. MethodsA Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. ResultsAt baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. ConclusionsBrain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.

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

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

Structural brain networks in schizophrenia based on nonnegative matrix factorization.

Schizophrenia is a severe mental disease with significant morphometric reductions in gray matter volume and cortical thickness in a variety of brain regions. However, most studies only focused on the voxel level alterations in specific cerebral regions and ignored the spatial relationship between voxels. In the present study, we used a novel, data-driven technique-nonnegative matrix factorization (NMF) to group voxels with similar information into a network, and studied the structural covariance at the network level in schizophrenia. Our sample included 36 patients with schizophrenia and 21 healthy controls. Compared with healthy controls, patients with schizophrenia showed significant gray matter volume reductions in six structural covariance networks (dorsal striatum, thalamus, hippocampus-parahippocampus, supplementary motor area-fusiform, middle/inferior temporal network, frontal-parietal-occipital network). Our findings confirmed the assumption of a disturbance in the cortical-subcortical circuit in schizophrenia and suggested that NMF is a useful multivariate method to identify brain networks, which provides a new perspective to study the neural mechanism in schizophrenia.

Structural changes in the thalamus and its subregions in regulating different symptoms of posttraumatic stress disorder

As a key center for sensory information processing and transmission, the thalamus plays a crucial role in the development of posttraumatic stress disorder (PTSD). However, the changes in the thalamus and its role in regulating different PTSD symptoms remain unclear. In this study, fourteen PTSD patients and eighteen healthy controls (HCs) were recruited. All subjects underwent whole-brain T1-weighted three-dimensional Magnetization Prepared Rapid Gradient Echo Imaging scans. Gray matter volume (GMV) in the thalamus and its subregions were estimated using voxel-based morphometry (VBM). Compared to HCs, PTSD patients exhibited significant GMV reduction in the left thalamus and its subregions, including anterior, mediodorsal, ventral-lateral-dorsal (VLD), ventral-anterior, and ventral-lateral-ventral (VLV). Among the significantly reduced thalamic subregions, we found positive correlations between the GMV values of the left VLD and VLV and the re-experiencing symptoms score, arousal symptoms score, and total CAPS score. When using the symptom-related GMV values of left VLV and VLD in combination as a predictor, receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for binary classification reached 0.813. This study highlights the neurobiological mechanisms of PTSD related to thalamic changes and may provide potential imaging markers for diagnosis and therapy targets.

Brain structural changes in alternating hemiplegia of childhood using single-case voxel-based morphometry analysis.

Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by ATP1A3 mutations. Using voxel-based morphometry (VBM) analysis, we compared an AHC patient cohort with controls. Additionally, with single-case VBM analysis, we assessed the associations between clinical severity and brain volume in patients with AHC. To investigate structural brain changes in gray matter (GM) and white matter (WM) volumes between 9 patients with AHC and 20 age-matched controls, VBM analysis was performed using three-dimensional T1-weighted magnetic resonance imaging. Single-case VBM analysis was also performed on nine patients with AHC to investigate the associations between the respective volumes of GM/WM differences and the motor level, cognitive level, and status epilepticus severity in patients with AHC. Compared with controls, patients with AHC showed significant GM volume reductions in both hippocampi and diffuse cerebellum, and there were WM reductions in both cerebral hemispheres. In patients with AHC, cases with more motor dysfunction, the less GM/WM volume of cerebellum was shown. Three of the six cases with cognitive dysfunction showed a clear GM volume reduction in the insulae. Five of the six cases with status epilepticus showed the GM volume reduction in hippocampi. One case had severe status epilepticus without motor dysfunction and showed no cerebellar atrophy. With single-case VBM analysis, we could show the association between region-specific changes in brain volume and the severity of various clinical symptoms even in a small sample of subjects.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.

Brain structural and perfusion changes in amyotrophic lateral sclerosis-frontotemporal dementia patients with cognitive and motor onset: a preliminary study

Amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) is rare but exhibits worse prognosis than either ALS or FTD alone. However, cognitive onset ALS-FTD (ALS-FTD-C) confers significantly better patient survival than does motor onset ALS-FTD (ALS-FTD-M), underscoring a meager understanding of pathological group differences. This study aimed to assess disparities in cortical atrophy and perfusion shown by patients with the above disease variants. A total of 38 participants (ALS-FTD-C, 8; ALS-FTD-M, 6; simultaneous-onset ALS-FTD [ALS-FTD-S], 4; healthy controls [HC], 20) qualified for the study and underwent magnetic resonance imaging scan. Three-dimensional T1-weighted structural brain imaging and 3D-pseudocontinuous arterial spin-labeled imaging were routinely collected. Gray matter volume (GMV) and cerebral blood flow (CBF) in ALS-FTD-C and ALS-FTD-M were compared through voxel-based analysis. Correlations between imaging parameters and clinical data were also assessed. Compared with HC, ALS-FTD had significant GMV reduction mainly in bilateral limbic system. GMV reduction in ALS-FTD-C was similar in pattern but less widespread, whereas ALS-FTD-M lacked any significant GMV reduction. In CBF analyses, ALS-FTD displayed hypoperfusion in bilateral motor cortex, frontotemporal lobe, and left basal ganglia. Hypoperfusion involved bilateral temporal lobe, prefrontal cortex, and putamen in ALS-FTD-C but was limited to left parahippocampal gyrus in ALS-FTD-M. Correlations between clinical data and GMV/CBF changes in specific regions were also identified in ALS-FTD. Group-specific patterns of cortical atrophy and perfusion were evident in ALS-FTD-C and ALS-FTD-M. ALS-FTD-C showed pronounced cortical atrophy and hypoperfusion, which were otherwise minimal in ALS-FTD-M. Above findings preliminarily revealed the pathological group differences that may help in classifying patients with ALS-FTD.

Patterns of Gray and White Matter Volume Alterations in Patients With Post-Traumatic Anosmia: A Voxel-Based Morphometry Study.

ObjectiveTraumatic brain injury is one of the major causes of human olfactory dysfunction and leads to brain structure alterations, mainly in the cortical olfactory regions. Our study aimed to investigate volume changes in the gray matter (GM) and white matter (WM) in patients with post-traumatic anosmia and then to explore the relationship between GM volume and olfactory function.MethodsEthics committee approved prospective studies which included 22 patients with post-traumatic anosmia and 18 age- and gender-matched healthy volunteers. Olfactory function was assessed using the Sniffin' Sticks. High-resolution 3-dimensional T1 MRIs of the participants were acquired on a 3T scanner and the data were collected for voxel-based morphometry (VBM) analysis. Furthermore, the GM and WM volumes of the whole brain regions were compared and correlated with olfactory function.ResultsThe analysis revealed significant GM volume reduction in the orbitofrontal cortex (OFC), gyrus rectus (GR), olfactory cortex, insula, parahippocampal, temporal pole, and cerebellum (all P < 0.001) in patients. Besides, WM volume loss was also found in the OFC, GR, and insula (all P < 0.001) in patients. All WM atrophy areas were connected to areas of GM volume loss spatially. Correlation analysis showed the olfactory scores were significantly positively correlated with the GM volume of the occipital cortex (P < 0.001, and PFWE < 0.05), while no significant correlation was found between the Sniffin' Sticks test scores and the WM volume in patients.ConclusionThe reduction of GM and WM volume in olfactory-related regions was responsible for olfactory dysfunction in post-traumatic patients. The occipital cortex may play a compensation mechanism to maintain the residual olfactory function. To our knowledge, we report here for the first time on white matter volume alterations specifically in post-traumatic patients with anosmia.

Differential alterations in brain structural network organization during addiction between adolescents and adults.

The adolescent brain may be susceptible to the influences of illicit drug use. While compensatory network reorganization is a unique developmental characteristic that may restore several brain disorders, its association with methamphetamine (MA) use-induced damage during adolescence is unclear. Using independent component (IC) analysis on structural magnetic resonance imaging data, spatially ICs described as morphometric networks were extracted to examine the effects of MA use on gray matter (GM) volumes and network module connectivity in adolescents (51 MA users v. 60 controls) and adults (54 MA users v. 60 controls). MA use was related to significant GM volume reductions in the default mode, cognitive control, salience, limbic, sensory and visual network modules in adolescents. GM volumes were also reduced in the limbic and visual network modules of the adult MA group as compared to the adult control group. Differential patterns of structural connectivity between the basal ganglia (BG) and network modules were found between the adolescent and adult MA groups. Specifically, adult MA users exhibited significantly reduced connectivity of the BG with the default network modules compared to control adults, while adolescent MA users, despite the greater extent of network GM volume reductions, did not show alterations in network connectivity relative to control adolescents. Our findings suggest the potential of compensatory network reorganization in adolescent brains in response to MA use. The developmental characteristic to compensate for MA-induced brain damage can be considered as an age-specific therapeutic target for adolescent MA users.

Structural and functional deficits and couplings in the cortico-striato-thalamo-cerebellar circuitry in social anxiety disorder

Although functional and structural abnormalities in brain regions involved in the neurobiology of fear and anxiety have been observed in patients with social anxiety disorder (SAD), the findings have been heterogeneous due to small sample sizes, demographic confounders, and methodological differences. Besides, multimodal neuroimaging studies on structural-functional deficits and couplings are rather scarce. Herein, we aimed to explore functional network anomalies in brain regions with structural deficits and the effects of structure-function couplings on the SAD diagnosis. High-resolution structural magnetic resonance imaging (MRI) and resting-state functional MRI images were obtained from 49 non-comorbid patients with SAD and 53 demography-matched healthy controls. Whole-brain voxel-based morphometry analysis was conducted to investigate structural alterations, which were subsequently used as seeds for the resting-state functional connectivity analysis. In addition, correlation and mediation analyses were performed to probe the potential roles of structural-functional deficits in SAD diagnosis. SAD patients had significant gray matter volume reductions in the bilateral putamen, right thalamus, and left parahippocampus. Besides, patients with SAD demonstrated widespread resting-state dysconnectivity in cortico-striato-thalamo-cerebellar circuitry. Moreover, dysconnectivity of the putamen with the cerebellum and the right thalamus with the middle temporal gyrus/supplementary motor area partially mediated the effects of putamen/thalamus atrophy on the SAD diagnosis. Our findings provide preliminary evidence for the involvement of structural and functional deficits in cortico-striato-thalamo-cerebellar circuitry in SAD, and may contribute to clarifying the underlying mechanisms of structure-function couplings for SAD. Therefore, they could offer insights into the neurobiological substrates of SAD.

Structural and functional brain alterations in patients with myasthenia gravis.

Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 ± 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 ± 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail.

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder.

The present study was aimed to investigate the relationships between serum thyroid hormones (THs), frontal gray matter volume, and executive function in selected patients with major depressive disorder (MDD). One hundred and four MDD patients and seventy-five healthy controls (HCs) were subjected to thyroid-stimulating hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), and executive function tests and underwent structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis was performed to compare group differences in the gray matter for the frontal lobe. Furthermore, mediation analysis was used to investigate whether gray matter volumes of the frontal gyrus mediated the relationship between serum THs and executive function in MDD patients. MDD patients exhibited significant gray matter volume reduction in several brain regions, including the left rectus, right middle frontal cortex, and left middle frontal cortex. Serum TSH levels are positively associated with altered regional gray matter volume patterns within MFG and executive function. Importantly, gray matter in the right MFG was a significant mediator between serum TSH levels and executive function. These findings expand our understanding of how thyroid function affects brain structure changes and executive function in MDD patients.

Maternal Immune Activation during Pregnancy Alters Postnatal Brain Growth and Cognitive Development in Nonhuman Primate Offspring.

Human epidemiological studies implicate exposure to infection during gestation in the etiology of neurodevelopmental disorders. Animal models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant offspring brain and behavior development. Here we evaluate neurodevelopment of male rhesus monkeys (Macaca mulatta) born to MIA-treated dams (n = 14) injected with a modified form of the viral mimic polyinosinic:polycytidylic acid at the end of the first trimester. Control dams received saline injections at the same gestational time points (n = 10) or were untreated (n = 4). MIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature, and inflammatory cytokines. Although offspring born to control or MIA-treated dams did not differ on measures of physical growth and early developmental milestones, the MIA-treated animals exhibited subtle changes in cognitive development and deviated from species-typical brain growth trajectories. Longitudinal MRI revealed significant gray matter volume reductions in the prefrontal and frontal cortices of MIA-treated offspring at 6 months that persisted through the final time point at 45 months along with smaller frontal white matter volumes in MIA-treated animals at 36 and 45 months. These findings provide the first evidence of early postnatal changes in brain development in MIA-exposed nonhuman primates and establish a translationally relevant model system to explore the neurodevelopmental trajectory of risk associated with prenatal immune challenge from birth through late adolescence.SIGNIFICANCE STATEMENT Women exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental disorder. Preclinical maternal immune activation (MIA) models have demonstrated that the effects of maternal infection on fetal brain development are mediated by maternal immune response. Since the majority of MIA models are conducted in rodents, the nonhuman primate provides a unique system to evaluate the MIA hypothesis in a species closely related to humans. Here we report the first longitudinal study conducted in a nonhuman primate MIA model. MIA-exposed offspring demonstrate subtle changes in cognitive development paired with marked reductions in frontal gray and white matter, further supporting the association between prenatal immune challenge and alterations in offspring neurodevelopment.

Association between cytomegalovirus infection, reduced gray matter volume, and resting-state functional hypoconnectivity in major depressive disorder: a replication and extension

Human cytomegalovirus (HCMV) is a neurotropic herpes virus known to cause neuropathology in patients with impaired immunity. Previously, we reported a reduction in the gray matter volume (GMV) of several brain regions in two independent samples of participants who were seropositive for HCMV (HCMV+) compared to matched participants who were seronegative for HCMV (HCMV−). In addition to an independent replication of the GMV findings, this study aimed to examine whether HCMV+ was associated with differences in resting-state functional connectivity (rsfMRI-FC). After balancing on 11 clinical/demographic variables using inverse probability of treatment weighting (IPTW), GMV and rsfMRI-FC were obtained from 99 participants with major depressive disorder (MDD) who were classified into 42 HCMV+ and 57 HCMV− individuals. Relative to the HCMV− group, the HCMV+ group showed a significant reduction of GMV in nine cortical regions. Volume reduction in the right lateral orbitofrontal cortex (standardized beta coefficient (SBC) = −0.32, [95%CI, −0.62 to −0.02]) and the left pars orbitalis (SBC = −0.34, [95%CI, −0.63 to −0.05]) in the HCMV+ group was also observed in the previous study. Regardless of the parcellation method or analytical approach, relative to the HCMV− group, the HCMV+ group showed hypoconnectivity between the hubs of the sensorimotor network (bilateral postcentral gyrus) and the hubs of the salience network (bilateral insula) with effect sizes ranging from SBC = −0.57 to −0.99. These findings support the hypothesis that a positive HCMV serostatus is associated with altered connectivity of regions that are important for stress and affective processing and further supports a possible etiological role of HCMV in depression.

Neuroanatomical Correlates of Impulsive Choices and Risky Decision Making in Young Chronic Tobacco Smokers: A Voxel-Based Morphometry Study.

Introduction: Impairments in the multifaceted neuropsychological construct of cognitive impulsivity are a main feature of chronic tobacco smokers. According to the literature, these cognitive impairments are relevant for the initiation and maintenance of the smoking behavior. However, the neuroanatomical correlates of cognitive impulsivity in chronic smokers remain under-investigated.Methods: A sample of 28 chronic smokers (mean age = 28 years) not affected by polysubstance dependence and 24 matched non-smoker controls was recruited. Voxel Based Morphometry (VBM) was employed to assess Gray Matter (GM) volume differences between smokers and non-smokers. The relationships between GM volume and behavioral manifestations of impulsive choices (5 trial adjusting delay discounting task, ADT-5) and risky decision making (Cambridge Gambling Task, CGT) were also investigated.Results: VBM results revealed GM volume reductions in cortical and striatal brain regions of chronic smokers compared to non-smokers. Additionally, smokers showed heightened impulsive choices (p < 0.01, Cohen's f = 0.50) and a riskier decision- making process (p < 0.01, Cohen's f = 0.40) compared to non-smokers. GM volume reductions in the left Anterior Cingulate Cortex (ACC) correlated with impaired impulsive and risky choices, while GM volume reductions in the left Ventrolateral Prefrontal Cortex (VLPFC) and Caudate correlated with heightened impulsive choices. Reduced GM volume in the left VLPFC correlated with younger age at smoking initiation (mean = 16 years).Conclusion: Smokers displayed significant GM volume reductions and related cognitive impulsivity impairments compared to non-smoker individuals. Longitudinal studies would be required to assess whether these impairments underline neurocognitive endophenotypes or if they are a consequence of tobacco exposure on the adolescent brain.

P 44. Structural and functional brain alterations in patients with myasthenia gravis

Introduction. Myasthenia gravis (MG) is an autoimmune disease affecting the peripheral nervous system and causes skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described (Gilhus et al., 2019). Here, we investigate structural and functional brain changes in MG patients. Materials & Methods. Eleven MG patients (age: 70.64 ± 9.27; 11 male) were compared to age-, sex- and education-matched healthy controls (age: 70.18 ± 8.98). All patients received cholinesterase inhibitors. Structural brain changes were determined with voxel-based morphometry (VBM) using high-resolution T1-weighted MPRAGE sequences. Functional brain changes were accesed wih a neuropsychological test battery that probed cognitive deficits (MMST), attention, memory and executive functions. Results. MG patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, MG patients showed significant lower results in working memory (Spatial Span, p = .034, |d| = 1.466) and verbal episodic memory (VLMT, p = .003, |d| = 1.463). Discussion. Our results indicate that MG is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Future research is needed to replicate this finding in a larger sample size and to investigate structural and functional brain changes in a longitudinal study. Reference Gilhus, Nils Erik; Tzartos, Socrates; Evoli, Amelia; Palace, Jacqueline; Burns, Ted M.; Verschuuren, Jan J. G. M. (2019): Myasthenia gravis. In: Nature reviews. Disease primers 5 (1), S. 30. DOI: 10.1038/s41572-019-0079-y.