Gray Matter Volume Reduction Research Articles

Immune-Related Genetic Overlap Between Regional Gray Matter Reductions and Psychiatric Symptoms in Adolescents, and Gene-Set Validation in a Translational Model.

Adolescence is a period of vulnerability for the maturation of gray matter (GM) and also for the onset of psychiatric disorders such as major depressive disorder (MDD), bipolar disorder and schizophrenia. Chronic neuroinflammation is considered to play a role in the etiology of these illnesses. However, the involvement of neuroinflammation in the observed link between regional GM volume reductions and psychiatric symptoms is not established yet. Here, we investigated a possible common immune-related genetic link between these two phenomena in european adolescents recruited from the community. Hippocampal and medial prefrontal cortex (mPFC) were defined a priori as regions of interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from the IMAGEN database. We found a set of 26 SNPs that correlated with the hippocampal volumes and 29 with the mPFC volumes at age 14. We formed two ROI-Related Immune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampal GM volume and to mPFC GM volume. The predictive ability of both RRIs with regards to the presence of psychiatric symptoms at age 18 was investigated by correlating the RRIs with psychometric questionnaires obtained at age 18. The RRIs (but not control scores constructed with random SNPs) correlated with the presence of depressive symptoms, positive psychotic symptoms, and externalizing symptoms in later adolescence. In addition, the effect of childhood maltreatment, one of the major environmental risk factors for depression and other mental disorders, interacted with the RRI effect. We next sought to validate this finding by investigating our set of inflammatory genes in a translational animal model of early life adversity. Mice were subjected to a protocol of maternal separation at an early post-natal age. We evaluated depressive behaviors in separated and non-separated mice at adolescence and their correlations with the concomitant expression of our genes in whole blood samples. We show that in mice, early life adversity affected the expression of our set of genes in peripheral blood, and that levels of expression correlated with symptoms of negative affect in adolescence. Overall, our translational findings in adolescent mice and humans provide a novel validated gene-set of immune-related genes for further research in the early stages of mood disorders.

Convergent and divergent brain structural and functional abnormalities associated with developmental dyslexia.

Brain abnormalities in the reading network have been repeatedly reported in individuals with developmental dyslexia (DD); however, it is still not totally understood where the structural and functional abnormalities are consistent/inconsistent across languages. In the current multimodal meta-analysis, we found convergent structural and functional alterations in the left superior temporal gyrus across languages, suggesting a neural signature of DD. We found greater reduction in grey matter volume and brain activation in the left inferior frontal gyrus in morpho-syllabic languages (e.g. Chinese) than in alphabetic languages, and greater reduction in brain activation in the left middle temporal gyrus and fusiform gyrus in alphabetic languages than in morpho-syllabic languages. These language differences are explained as consequences of being DD while learning a specific language. In addition, we also found brain regions that showed increased grey matter volume and brain activation, presumably suggesting compensations and brain regions that showed inconsistent alterations in brain structure and function. Our study provides important insights about the etiology of DD from a cross-linguistic perspective with considerations of consistency/inconsistency between structural and functional alterations.

Complex Regional Pain Syndrome: Thalamic GMV Atrophy and Associations of Lower GMV With Clinical and Sensorimotor Performance Data.

Results on gray matter alterations in complex regional pain syndrome (CRPS) showed heterogeneous findings. Since CRPS is a rare disease, most studies included only small and heterogeneous samples resulting in a low reliability of findings between studies. We investigated 24 CRPS patients with right upper limb affection in the chronic stage of disease using structural MRI and clinical testing. We focused on gray matter volume (GMV) alterations of the brain in comparison to 33 age matched healthy controls, their association to clinical characteristics (duration of pain syndrome and pain intensity ratings) and sensorimotor performance (finger dexterity and spatiotactile resolution). When applying an explorative whole brain analysis CRPS patients showed lower GMV in the bilateral medial thalamus. No other areas showed a relevant GMV difference for the group comparisons. When applying a region of interest driven approach using anatomical masks of the thalamus, ACC/mPFC, putamen, and insula we found relevant associations of clinical and behavioral data in ACC and insula. Whereas, the GMV in ACC showed negative associations with pain intensity and CRPS duration, the GMV of the left posterior insula was negatively associated with sensorimotor performance of the affected hand side. Overall, our results are in accordance to results of others describing a thalamic reduction of GMV in patients with neuropathic pain and are also in accordance with associations of pain intensity and duration with reduced ACC in general in patients with chronic pain syndromes. Sensorimotor performance seems to be related to posterior insula GMV reduction, which has not been described yet for other patient groups.

Long-term global and focal cerebral atrophy in perimesencephalic subarachnoid hemorrhage-a case-control study.

Non-aneurysmal perimesencephalic subarachnoid hemorrhage (PmSAH) represents 6.8% of spontaneous subarachnoid hemorrhage, and usually has a benign clinical course. However, patients might have early cerebral ischemic lesions and long-term neurocognitive complaints. Cerebral atrophy has been described in patients after aneurysmal SAH, but not in PmSAH. We aimed to investigate if PmSAH associates with increased brain volume loss. In this prospective study, we included consecutive patients with PmSAH that performed MR in the first 10days after hemorrhage, and follow-up MR 6-7years later. Automated volumetric measurements of intracranial, white matter, gray matter, whole brain, lateral ventricles, hippocampus, and amygdala volumes were performed. Volumes were compared to a normal population, matched for age. Eight patients with PmSAH were included, with a mean age of 51.5 (SE 3.6) at baseline. The control group included 22 patients with a mean age of 56.3 (SE 2.0). A relative reduction of all volumes was found in both groups; however, PmSAH patients had significant reductions in intracranial, white and gray matter, whole brain, and hippocampal volumes when compared to controls. These changes had a higher magnitude in whole brain volume, with a significant absolute decrease of 6.5% in PmSAH patients (versus 1.9% in controls), and a trend for an increase in lateral ventricle volume (absolute 21.3% increase, versus 3.9% in controls). Our cohort of PmSAH patients showed significant long-term parenchymal atrophy, and higher global and focal parenchymal volume loss rates when compared to a non-SAH population.

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.

Fronto-Parietal Gray Matter Volume Loss Is Associated with Decreased Working Memory Performance in Adolescents with a First Episode of Psychosis.

Cognitive maturation during adolescence is modulated by brain maturation. However, it is unknown how these processes intertwine in early onset psychosis (EOP). Studies examining longitudinal brain changes and cognitive performance in psychosis lend support for an altered development of high-order cognitive functions, which parallels progressive gray matter (GM) loss over time, particularly in fronto-parietal brain regions. We aimed to assess this relationship in a subsample of 33 adolescents with first-episode EOP and 47 matched controls over 2 years. Backwards stepwise regression analyses were conducted to determine the association and predictive value of longitudinal brain changes over cognitive performance within each group. Fronto-parietal GM volume loss was positively associated with decreased working memory in adolescents with psychosis (frontal left (B = 0.096, p = 0.008); right (B = 0.089, p = 0.015); parietal left (B = 0.119, p = 0.007), right (B = 0.125, p = 0.015)) as a function of age. A particular decrease in frontal left GM volume best predicted a significant amount (22.28%) of the variance of decreased working memory performance over time, accounting for variance in age (14.9%). No such association was found in controls. Our results suggest that during adolescence, EOP individuals seem to follow an abnormal neurodevelopmental trajectory, in which fronto-parietal GM volume reduction is associated with the differential age-related working memory dysfunction in this group.

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.

Genes associated with grey matter volume reduction in multiple sclerosis.

There is extensive grey matter volume (GMV) reduction in multiple sclerosis (MS), which may account for cognitive impairment in this disabling disorder. Although genome-wide association studies (GWASs) have identified hundreds of genes associated with MS, we know little about which genes associated with GMV reduction and cognitive decline in MS. In the present study, we aimed to uncover genes associated with GMV reduction in MS by performing cross-sample (1473 brain tissue samples) partial least squares regression between gene expression from 6 postmortem brains and case-control GMV difference of MS from a meta-analysis of 1391 patients and 1189 controls (discovery phase) and from the intergroup comparison between 69 patients and 70 controls (replication phase). We identified 623 genes whose brain spatial expression profiles were significantly associated with GMV reduction in MS. These genes showed significant enrichment for MS-related genes identified by GWAS; were functionally associated with ion channel, synaptic transmission, axon and neuron projection; and showed more significant cell type-specific expression in neurons than other cell types. More importantly, the identified genes showed significant enrichment for those genes with downregulated rather than upregulated expression in MS. The spatial distribution patterns of the expression of the identified genes showed more significant correlations with brain activation patterns of memory and language tasks. These findings indicate that grey matter atrophy in MS may be resulted from the joint effects of multiple genes that are associated with this disorder, especially genes with downregulated expression in MS.

Gray matter volume reduction with different disease duration in trigeminal neuralgia.

PurposeStructural magnetic resonance imaging is widely used to explore brain gray and white matter structure in trigeminal neuralgia (TN) but has yielded conflicting findings. This study investigated the relationship between disease duration as a clinical feature of TN and changes in brain structure.MethodsWe divided 49 TN patients into three groups (TN1–TN3) based on disease duration (TN1 = 1.1 ± 0.7 (0–2) years, TN2 = 4.8 ± 1.5 (3–7) years, TN3 = 15.1 ± 5.5 (10–30) years). We used voxel-based morphometry (VBM) to compare the gray matter volume (GMV) across groups and between TN patients and 18 matched healthy control subjects.ResultsThe TN1 group showed reduced GMV of pain-related regions in the cerebellum; the TN2 group showed reduced GMV in the thalamus and the motor/sensory cortex; and the TN3 group showed reduced GMV in the emotional and reward circuits compared with healthy controls. Similar brain regions, including bilateral hippocampi, caudate, left insular cortex, and medial superior frontal cortex, were affected in TN2 and TN3 compared with TN1.ConclusionDisease duration can explain differences in structural alterations—especially in pain-related brain regions—in TN. These results highlight the advanced structural neuroimaging method that are valuable tools to assess the trigeminal system in TN and may further our current understanding of TN pathology.

Recognition Memory is Associated with Distinct Patterns of Regional Gray Matter Volumes in Young and Aged Monkeys.

Cognitive aging varies tremendously across individuals and is often accompanied by regionally specific reductions in gray matter (GM) volume, even in the absence of disease. Rhesus monkeys provide a primate model unconfounded by advanced neurodegenerative disease, and the current study used a recognition memory test (delayed non-matching to sample; DNMS) in conjunction with structural imaging and voxel-based morphometry (VBM) to characterize age-related differences in GM volume and brain-behavior relationships. Consistent with expectations from a long history of neuropsychological research, DNMS performance in young animals prominently correlated with the volume of multiple structures in the medial temporal lobe memory system. Less anticipated correlations were also observed in the cingulate and cerebellum. In aged monkeys, significant volumetric correlations with DNMS performance were largely restricted to the prefrontal cortex and striatum. Importantly, interaction effects in an omnibus analysis directly confirmed that the associations between volume and task performance in the MTL and prefrontal cortex are age-dependent. These results demonstrate that the regional distribution of GM volumes coupled with DNMS performance changes across the lifespan, consistent with the perspective that the aged primate brain retains a substantial capacity for structural reorganization.

Lower regional gray matter volume in the absence of higher cortical amyloid burden in late-life depression

Late-life depression (LLD) is associated with a risk of developing Alzheimer’s disease (AD). However, the role of AD-pathophysiology in LLD, and its association with clinical symptoms and cognitive function are elusive. In this study, one hundred subjects underwent amyloid positron emission tomography (PET) imaging with [18F]-flutemetamol and structural MRI: 48 severely depressed elderly subjects (age 74.1 ± 7.5 years, 33 female) and 52 age-/gender-matched healthy controls (72.4 ± 6.4 years, 37 female). The Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) were used to assess the severity of depressive symptoms and episodic memory function respectively. Amyloid deposition was quantified using the standardized uptake value ratio. Whole-brain voxel-wise comparisons of amyloid deposition and gray matter volume (GMV) between LLD and controls were performed. Multivariate analysis of covariance was conducted to investigate the association of regional differences in amyloid deposition and GMV with clinical factors, including GDS and RAVLT. As a result, there were no significant group differences in amyloid deposition. In contrast, LLD showed significant lower GMV in the left temporal and parietal region. GMV reduction in the left temporal region was associated with episodic memory dysfunction, but not with depression severity. Regional GMV reduction was not associated with amyloid deposition. LLD is associated with lower GMV in regions that overlap with AD-pathophysiology, and which are associated with episodic memory function. The lack of corresponding associations with amyloid suggests that lower GMV driven by non-amyloid pathology may play a central role in the neurobiology of LLD presenting as a psychiatric disorder.Trial registration: European Union Drug Regulating Authorities Clinical Trials identifier: EudraCT 2009-018064-95.

Altered gray matter volume and functional connectivity in patients with herpes zoster and postherpetic neuralgia

Numerous neuroimaging studies on postherpetic neuralgia (PHN) and herpes zoster (HZ) have revealed abnormalities in brain structure/microstructure and function. However, few studies have focused on changes in gray matter (GM) volume and intrinsic functional connectivity (FC) in the transition from HZ to PHN. This study combined voxel-based morphometry and FC analysis methods to investigate GM volume and FC differences in 28 PHN patients, 25 HZ patients, and 21 well-matched healthy controls (HCs). Compared to HCs, PHN patients exhibited a reduction in GM volume in the bilateral putamen. Compared with HZ patients, PHN patients showed decreased GM volume in the left parahippocampal gyrus, putamen, anterior cingulate cortex, and right caudate and increased GM volume in the right thalamus. However, no regions with significant GM volume changes were found between the HZ and HC groups. Correlation analysis revealed that GM volume in the right putamen was positively associated with illness duration in PHN patients. Furthermore, lower FCs between the right putamen and right middle frontal gyrus/brainstem were observed in PHN patients than in HCs. These results indicate that aberrant GM volumes and FC in several brain regions, especially in the right putamen, are closely associated with chronification from HZ to PHN; moreover, these changes profoundly affect multiple dimensions of pain processing. These findings may provide new insights into the pathophysiological mechanisms of PHN.

Obesity and Gray Matter Volume Assessed by Neuroimaging: A Systematic Review.

Obesity has become a major public and individual health problem due to its high worldwide prevalence and its relation with comorbid conditions. According to previous studies, obesity is related to an increased risk of cognitive impairment and dementia. This systematic review aims to further examine the present state of the art about the association between obesity and gray matter volume (GMV) as assessed by magnetic resonance imaging (MRI). A search was conducted in Pubmed, SCOPUS and Cochrane of those studies released before 1 February 2021 including MRIs to assess the GMVs in obese participants. From this search, 1420 results were obtained, and 34 publications were finally included. Obesity was mainly measured by the body mass index, although other common types of evaluations were used (e.g., waist circumference, waist-to-hip ratio and plasma leptin levels). The selected neuroimaging analysis methods were voxel-based morphometry (VBM) and cortical thickness (CT), finding 21 and 13 publications, respectively. There were 30 cross-sectional and 2 prospective longitudinal studies, and 2 articles had both cross-sectional and longitudinal designs. Most studies showed a negative association between obesity and GMV. This would have important public health implications, as obesity prevention could avoid a potential risk of GMV reductions, cognitive impairment and dementia.

Common and Distinct Alterations of Cognitive Function and Brain Structure in Schizophrenia and Major Depressive Disorder: A Pilot Study

Objective: Numerous studies indicate that schizophrenia (SCZ) and major depressive disorder (MDD) share pathophysiological characteristics. Investigating the neurobiological features of psychiatric-affective disorders may facilitate the diagnosis of psychiatric disorders. Hence, we aimed to explore whether patients with SCZ and patients with MDD had the similar or distinct cognitive impairments and GMV alterations to further understand their underlying pathophysiological mechanisms.Methods: We recruited a total of 52 MDD patients, 64 SCZ patients, and 65 healthy controls (HCs). The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery was used to assess cognitive functions. In addition, voxel-based morphometry (VBM) analysis was used to evaluate the gray matter volume (GMV) by using MRI scanning. One-way ANOVA and post-hoc tests were used to find the differences among the MDD, SCZ, and HCs. Finally, we explored the correlation between structural alterations and cognitive functions.Results: Compared with that of HCs, processing speed was impaired in both patients with SCZ and patients with MDD (F = 49.505, p < 0.001). SCZ patients displayed impaired cognitive performance in all dimensions of cognitive functions compared with HCs (p < 0.001, except social cognition, p = 0.043, Bonferroni corrected). Whole-brain VBM analysis showed that both SCZ and MDD groups had reductions of GMV in the medial superior frontal cortex (cluster-level FWE p < 0.05). Patients with SCZ exhibited declining GMV in the anterior cingulate cortex and right middle frontal cortex (MFC) compared with HCs and MDD patients (cluster-level FWE p < 0.05). The mean values of GMV in the right MFC had a positive correlation with the attention/vigilance function in patients with MDD (p = 0.014, partial. r = 0.349, without Bonferroni correction).Conclusions: In total, our study found that MDD and SCZ groups had common cognitive impairments and brain structural alterations, but the SCZ group exhibited more severe impairment than the MDD group in both fields. The above findings may provide a potential support for recognizing the convergent and divergent brain neural pathophysiological mechanisms between MDD and SCZ.

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.

Altered Gray Matter Volume and Functional Connectivity in Patients With Vestibular Migraine

SubjectsVestibular migraine (VM) is the most common neurological cause of vertigo in adults. Previous neuroimaging studies have reported structural alterations in areas associated with pain and vestibular processing. However, it is unclear whether altered resting-state functional connectivity (FC) exists in brain regions with structural abnormalities in patients with VM.MethodsResting-state functional magnetic resonance imaging (MRI) and three-dimensional T1-weighed MRI were performed in 30 patients with VM and 30 healthy controls (HCs). Patients underwent an evaluation of migraine and dizziness severity. FC and voxel-based morphometry (VBM) were performed using DPABI 4.3 and CAT12, respectively. The association between changes in gray matter (GM) volume or FC and clinical parameters was also analyzed.ResultsCompared with HCs, patients with VM demonstrated a reduced GM volume in the bilateral parietoinsular vestibular cortex (PIVC), right middle frontal gyrus, and precuneus. The GM volume of the left PIVC was negatively associated with Dizziness Handicap Inventory score in patients with VM. Taking this region as a seed region, we further observed increased FC between the left primary somatosensory cortex (S1)/inferior parietal lobule (IPL) and the left PIVC in patients with VM.ConclusionFC between regions with a decline in GM volume (the PIVC and S1/IPL) is altered in patients with VM, suggesting that abnormalities in vestibular cortical network could be useful for understanding the underlying mechanisms of VM.

Symptom-Based Profiling and Multimodal Neuroimaging of a Large Preteenage Population Identifies Distinct Obsessive-Compulsive Disorder–like Subtypes With Neurocognitive Differences

BackgroundObsessive-compulsive disorder (OCD) is characterized by both internalizing (anxiety) and externalizing (compulsivity) symptoms. Currently, little is known about their interrelationships and their relative contributions to disease heterogeneity. Our goal is to resolve affective and cognitive symptom heterogeneity related to internalized and externalized symptom dimensions by determining subtypes of children with OCD symptoms, and to identify any corresponding neural differences. MethodsA total of 1269 children with OCD symptoms screened using the Child Behavior Checklist Obsessive-Compulsive Symptom scale and 3987 matched control subjects were obtained from the Adolescent Brain Cognitive Development (ABCD) Study. Consensus hierarchical clustering was used to cluster children with OCD symptoms into distinct subtypes. Ten neurocognitive task scores and 20 Child Behavior Checklist syndrome scales were used to characterize cognitive/behavioral differences. Gray matter volume, fractional anisotropy of major white matter fiber tracts, and functional connectivity among networks were used in case-control studies. ResultsWe identified two subgroups with contrasting patterns in internalized and externalized dimensions. Group 1 showed compulsive thoughts and repeated acts but relatively low anxiety symptoms, whereas group 2 exhibited higher anxiety and perfectionism and relatively low repetitive behavior. Only group 1 had significant cognitive impairments and gray matter volume reductions in the bilateral inferior parietal lobe, precentral gyrus, and precuneus gyrus, and had white matter tract fractional anisotropy reductions in the corticostriatal fasciculus. ConclusionsChildren with OCD symptoms are heterogeneous at the level of symptom clustering and its underlying neural basis. Two subgroups represent distinct patterns of externalizing and internalizing symptoms, suggesting that anxiety is not its major predisposing factor. These results may have implications for the nosology and treatment of preteenage OCD.

Association of adverse childhood experiences and precuneus volume with intrusive reexperiencing in autism spectrum disorder.

Compared to typically developing (TD) children, people with autism spectrum disorder (ASD) have an increased risk of adverse childhood experiences (ACEs). Exposure to ACEs is associated with adult ASD psychological comorbidities, such as posttraumatic stress disorder (PTSD). Occurrence of intrusive event reexperiencing, characteristic of PTSD, often causes social dysfunction in adults with ASD, but its pathological basis is unclear. This study examined brain regions related to the severity of intrusive reexperiencing and explored whether ACE severity was associated with that of intrusive reexperiencing and/or extracted regional gray matter volume. Forty-six individuals with ASD and 41 TD subjects underwent T1-weighted magnetic resonance imaging and evaluation of ACEs and intrusive reexperiencing. Brain regions related to the severity of intrusive reexperiencing in both groups were identified by voxel-based whole brain analyses. Associations among the severity of intrusive reexperiencing, that of ACEs, and gray matter volume were examined in both groups. The severities of intrusive reexperiencing and ACEs were significantly associated with reduced gray matter volume in the right precuneus in individuals with ASD but not in TD subjects. Although the right precuneus gray matter volume was smaller in individuals with ASD and severe ACEs than in those with mild ACEs or TD subjects, it was similar in the latter two groups. However, ACE-dependent gray matter volume reduction in the right precuneus led to intrusive reexperiencing in individuals with ASD. This suggests that exposure to ACEs is associated with right precuneus gray matter reduction, which is critical for intrusive reexperiencing in adults with ASD. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) are at increased risk of adverse childhood experiences (ACEs) and of subsequent manifestation of intrusive reexperiencing of stressful life events. The present study found that reduced gray matter volume in the right precuneus of the brain was associated with more severe intrusive reexperiencing of ACEs by individuals with ASD. These results suggest that ACEs affect neural development in the precuneus, which is the pathological basis of intrusive event reexperiencing in ASD.

Memory for public events in amnestic mild cognitive impairment: The role of hippocampus and ventro-medial prefrontal cortex.

Current theories assume that retrograde memory deficits for semantic information in amnestic mild cognitive impairment (aMCI) are temporally graded and partially sparing most remote memories. Moreover, these models assume a prevalent role of the hippocampus in early phases of memory consolidation and of the prefrontal mesial neocortical areas in permanent consolidation of traces. To explore the relationship between hippocampus and memory accuracy for the most recent public events and between the ventro-medial prefrontal cortex (vmPFC) and memory accuracy irrespective of the memory age, we investigated in aMCI patients the retrograde memory for public events and its relationship with grey matter volume reductions in the hippocampus and vmPFC. 18 aMCI patients and 13 healthy subjects (HS) underwent a modified version of the Famous Events questionnaire (FEq) to assess their memory performance for public events. Patients underwent 3T-MRI scanning to assess correlations between FEq's scores and grey matter volumes. aMCI showed significantly reduced performances on FEq compared to HS in the recollection of most recent events, while no significant difference was observed for more remote memories, thus demonstrating a temporal gradient. Moreover, hippocampal volumes predicted accuracy scores for most recent, but not older, public events. Finally, an area in the subcallosal portion of the vmPFC, corresponding to BA32, predicted accuracy scores on FEq irrespective of the period examined. Pathological changes in a neural circuit linking hippocampal to medial prefrontal cortical regions are responsible for impaired recollection of retrograde memories in aMCI.

Common abnormality of gray matter integrity in substance use disorder and obsessive-compulsive disorder: A comparative voxel-based meta-analysis.

The objective of the current study is to determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case‐control studies examining gray matter volume (GMV) alterations in substance use disorders (SUD) and obsessive‐compulsive disorder (OCD). Voxel‐based meta‐analysis within the individual disorders and conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta‐analytic coordinates and signed brain volumetric maps determining directed (reduced/increased) GMV alterations between the disorder groups and controls served as the primary outcome. The separate meta‐analysis demonstrated that SUD and OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology. Together the findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.