Structural Brain Alterations Research Articles

A neuroimaging study of altered cortical and subcortical volume in adolescent methamphetamine users

Purpose: The aim of this study was is to compare brain structure volume, including cortical and subcortical regions of adolescents- methamphetamine users versus non-users.
 Materials and Methods: The study was designed to be cross-sectional, and structural magnetic resonance imaging scans were obtained from the participants, including ten methamphetamine users and nine non-users. volBrain program was used to evaluate the images. 
 Results: The results showed that methamphetamine users altered brain structures- temporal, parietal lobes, nucleus accumbens, amygdala, hippocampus, and thalamus volume. Also, the statistically significant difference in the volume between methamphetamine users and non-users was found in subcortical regions except putamen by age. Volumetric analysis of methamphetamine use in adolescents confirms a reduction in temporal lobes (methamphetamine users M±SD=3.43±0.18 non-users M±SD=3.48±0.22) and parietal lobes (methamphetamine users M±SD=2.23±0.24, non-users M±SD=2.37±0.33) in cortical regions in the brain as tissue volume. However, methamphetamine uses caused an increase in volume in the subcortical regions.
 Conclusion: Methamphetamine use appears to show decreased volume in the brain regions with age, which has adverse effects on cognitive, emotional, memory, and social abilities.

Changes in the superior longitudinal fasciculus and anterior thalamic radiation in the left brain are associated with developmental dyscalculia.

Developmental dyscalculia is a neurodevelopmental disorder specific to arithmetic learning even with normal intelligence and age-appropriate education. Difficulties often persist from childhood through adulthood lowering the individual's quality of life. However, the neural correlates of developmental dyscalculia are poorly understood. This study aimed to identify brain structural connectivity alterations in developmental dyscalculia. All participants were recruited from a large scale, non-referred population sample in a longitudinal design. We studied 10 children with developmental dyscalculia (11.3 ± 0.7 years) and 16 typically developing peers (11.2 ± 0.6 years) using diffusion-weighted magnetic resonance imaging. We assessed white matter microstructure with tract-based spatial statistics in regions-of-interest tracts that had previously been related to math ability in children. Then we used global probabilistic tractography for the first time to measure and compare tract length between developmental dyscalculia and typically developing groups. The high angular resolution diffusion-weighted magnetic resonance imaging and crossing-fiber probabilistic tractography allowed us to evaluate the length of the pathways compared to previous studies. The major findings of our study were reduced white matter coherence and shorter tract length of the left superior longitudinal/arcuate fasciculus and left anterior thalamic radiation in the developmental dyscalculia group. Furthermore, the lower white matter coherence and shorter pathways tended to be associated with the lower math performance. These results from the regional analyses indicate that learning, memory and language-related pathways in the left hemisphere might be related to developmental dyscalculia in children.

Obstructive sleep apnea and attention deficits: A systematic review of magnetic resonance imaging biomarkers and neuropsychological assessments.

Obstructive sleep apnea (OSA) is a common sleep disorder that causes intermittent hypoxia and sleep fragmentation, leading to attention impairment and other cognitive deficits. Magnetic resonance imaging (MRI) is a powerful modality that can reveal the structural and functional brain alterations associated with attention impairment in OSA patients. The objective of this systematic review is to identify and synthesize the evidence on MRI biomarkers and neuropsychological assessments of attention deficits in OSA patients. We searched the Scopus and PubMed databases for studies that used MRI to measure biomarkers related to attention alteration in OSA patients and reported qualitative and quantitative data on the association between MRI biomarkers and attention outcomes. We also included studies that found an association between neuropsychological assessments and MRI findings in OSA patients with attention deficits. We included 19 studies that met our inclusion criteria and extracted the relevant data from each study. We categorized the studies into three groups based on the MRI modality and the cognitive domain they used: structural and diffusion tensor imaging MRI findings, functional, perfusion, and metabolic MRI findings, and neuropsychological assessment findings. We found that OSA is associated with structural, functional, and metabolic brain alterations in multiple regions and networks that are involved in attention processing. Treatment with continuous positive airway pressure can partially reverse some of the brain changes and improve cognitive function in some domains and in some studies. This review suggests that MRI techniques and neuropsychological assessments can be useful tools for monitoring the progression and response to treatment of OSA patients.

Associations between parental depression and anxiety symptom severity and their Offspring's cortical thickness and subcortical volume

Depression and anxiety are associated with grey matter changes in subcortical regions in adults and adolescents. Parent psychopathology is associated with offspring brain structure, but it's unclear whether altered brain structure in children is associated with severity of parental depression and anxiety symptoms. We examined 123 youth (Mean age = 13.64; 62% female) with no clinically significant history of depression or anxiety and one parent diagnosed with current or past depressive or anxiety disorders. Parents completed the Mini International Neuropsychiatric Interview to assess diagnostic status and the Beck Depression Inventory-II, and the Generalized Anxiety Disorder-7 to assess current symptom severity. Youth underwent T1 weighted structural Magnetic Resonance Imaging scans. Bivariate analyses revealed higher parental depressive severity was not significantly associated with offspring grey matter. Parental anxiety severity was significantly associated with less left global surface area. When controlling for offspring age, sex and intracranial volume (ICV), offspring right surface area was negatively associated with parental depressive severity at a trend level. In previously depressed parents, greater parental depressive severity was significantly associated with offspring decreased left and right surface area. There were no significant associations between parental anxiety severity in previously depressed parents and offspring subcortical or cortical brain regions. These results highlight associations between parental depressive symptom severity and offspring brain structure and suggest that even within an already high-risk group of adolescents, there may be altered cortical surface area depending on parent symptom severity. This may help identify youth most at risk for developing a mood disorder and could help further early intervention and identification efforts.

Vascular Disease Is Associated With Differences in Brain Structure and Lower Cognitive Functioning in Inflammatory Bowel Disease: A Cross-Sectional Study.

Vascular disease and cognitive impairment have been increasingly documented in inflammatory bowel disease (IBD), and both have been individually correlated with changes in brain structure. This study aimed to determine if both macro- and microstructural brain changes are prevalent in IBD and whether alterations in brain structure mediate the relationship between vascular disease and cognitive functioning. Eighty-four IBD participants underwent multimodal magnetic resonance imaging. Volumetric and mean diffusivity measures of the thalamus, hippocampus, normal-appearing white matter, and white matter lesions were converted to age- and sex-adjusted z scores. Vascular comorbidity was assessed using a modified Framingham Risk Score and cognition was assessed using a battery of neuropsychological tests. Test scores were standardized using local regression-based norms. We generated summary statistics for the magnetic resonance imaging metrics and cognitive tests, and these were examined using canonical correlation analysis and linear regression modeling. Greater vascular comorbidity was negatively correlated with thalamic, normal-appearing white matter, and white matter lesion volumes. Higher Framingham Risk Score were also correlated with lower processing speed, learning and memory, and verbal fluency. Increased vascular comorbidity was predictive of poorer cognitive functioning, and this effect was almost entirely mediated (94.76%) by differences in brain structure. Vascular comorbidity is associated with deleterious effects on brain structure and lower cognitive functioning in IBD. These findings suggest that proper identification and treatment of vascular disease is essential to the overall management of IBD, and that certain brain areas may serve as critical targets for predicting the response to therapeutic interventions.

Epigenetics in migraine: A review

Genetic diseases are not only caused by direct mutations in "genes," but also consequences of heritable change other than mutation referred to as epigenetics and the science called epigenomics. In the present study, we aimed to review epigenetics, where we covered a quick overview of epigenetics, diseases that are caused by epigenetic modification, epigenetic as risk factors linked with migraine a cause leads to the neurodegenerative condition, and most accepted mechanisms of epigenetics. A structured research article and review of the literature was searched in the electronic databases of Google Scholar, PubMed, Springer, and Elsevier until Nov 2022 using multiple keywords. Aberrant DNA methylation pattern including hypermethylation in genes such as SLC6A5, SLC2A9, and SLC38A4, , DOCK6, COMT, GIT2, ZNF234, SOCS1. EZH2, a DNMTs enzyme is generally associated with the downregulation of gene expression but in the case of microglial, it is responsible for the upregulation of various genes including TRAF3IP2, BCL2L11, ITGAM, DAB2, NLRP12, WNT3, ADAM10. Increased expression of miRNAs such as miR-34a-5p, miR-29c-5p, miR-382-5p, miR-155, miR-126, Let-7g, hsa-miR-34a-5p, hsa-miR-375. Migraine is not only caused by non-genetic factors/ environmental factors or by brain structural alterations or genetic variations but also by alteration in epigenetics and their interaction too with other elements.

Causal associations between blood lipids and brain structures: a Mendelian randomization study.

The potential causal association between dyslipidemia and brain structures remains unclear. Therefore, this study aimed to investigate whether circulating lipids are causally associated with brain structure alterations using Mendelian randomization analysis. Genome-wide association study summary statistics of blood lipids and brain structures were obtained from publicly available databases. Inverse-variance weighted method was used as the primary method to assess causality. In addition, four additional Mendelian randomization methods (MR-Egger, weighted median, simple mode, and weighted mode) were applied to supplement inverse-variance weighted. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses. After Bonferroni corrections, two causal associations were finally identified: elevated non-high-density lipoprotein cholesterol level leads to higher average cortical thickness (β = 0.0066mm, 95% confidence interval: 0.0045-0.0087mm, P = 0.001); and elevated high-density lipoprotein cholesterol level leads to higher inferior temporal surface area (β = 18.6077mm2, 95% confidence interval: 11.9835-25.2320mm2, P = 0.005). Four additional Mendelian randomization methods indicated parallel results. Sensitivity tests demonstrated the stability. Overall, the present study showed causal relationships between several lipid profiles and specific brain structures, providing new insights into the link between dyslipidemia and neurological disorders.

Early-in-life isoflurane exposure alters resting-state functional connectivity in juvenile non-human primates

BackgroundClinical studies suggest that anaesthesia exposure early in life affects neurobehavioural development. We designed a non-human primate (NHP) study to evaluate cognitive, behavioural, and brain functional and structural alterations after isoflurane exposure during infancy. These NHPs displayed decreased close social behaviour and increased astrogliosis in specific brain regions, most notably in the amygdala. Here we hypothesise that resting-state functional connectivity MRI can detect alterations in connectivity of brain areas that relate to these social behaviours and astrogliosis. MethodsImaging was performed in 2-yr-old NHPs under light anaesthesia, after early-in-life (postnatal days 6–12) exposure to 5 h of isoflurane either one or three times, or to room air. Brain images were segmented into 82 regions of interest; the amygdala and the posterior cingulate cortex were chosen for a seed-based resting-state functional connectivity MRI analysis. ResultsWe found differences between groups in resting-state functional connectivity of the amygdala and the auditory cortices, medial premotor cortex, and posterior cingulate cortex. There were also alterations in resting-state functional connectivity between the posterior cingulate cortex and secondary auditory, polar prefrontal, and temporal cortices, and the anterior insula. Relationships were identified between resting-state functional connectivity alterations and the decrease in close social behaviour and increased astrogliosis. ConclusionsEarly-in-life anaesthesia exposure in NHPs is associated with resting-state functional connectivity alterations of the amygdala and the posterior cingulate cortex with other brain regions, evident at the juvenile age of 2 yr. These changes in resting-state functional connectivity correlate with the decrease in close social behaviour and increased astrogliosis. Using resting-state functional connectivity MRI to study the neuronal underpinnings of early-in-life anaesthesia-induced behavioural alterations could facilitate development of a biomarker for anaesthesia-induced developmental neurotoxicity.

Severe Gross Hematuria Associated with Antithrombotic Drugs: Management and Impact on Prescription Thereafter

Anfibatide is a synthetic antiplatelet thrombolysin derived from snake venom and is proposed to treat ischemic stroke and cerebral ischemia-reperfusion injury. Current standard treatments for ischemic stroke include the administration of rt-PA, a thrombolytic agent, or endovascular removal of thrombi. However, the post-treatments are often associated with the occlusion of vessels due to a lack of antiplatelet and unrecovered vessel injury. Anfibatide, as a GPIba antagonist that interrupts the initiation of platelet aggregation caused by GPIba-vWF binding, becomes a potential novel candidate for treating ischemic stroke due to its antiplatelet and antithrombosis effects. Key findings show that Anfibatide can significantly reduce microthrombus formation in cerebral vessels and reduce neuron apoptosis due to the release of pro-inflammatory mediators caused by ischemia or Ischemia-Reperfusion (I/R) injury. Significant improvement in neurological scores and reversal of brain structure alterations are observed in the Anfibatide-treated ischemic animal models. To facilitate the clinical development of Anfibatide, this paper aims to summarize the completed preclinical studies and the Phase I clinical trial results of anfibatide to evaluate the risks and therapeutic potentials of Anfibatide in ischemic patients.

A Review of Anfibatide Studies in Animal Models with Ischemic Stroke and Cerebral Ischemia-Reperfusion Injury and in Healthy Human

Anfibatide is a synthetic antiplatelet thrombolysin derived from snake venom and is proposed to treat ischemic stroke and cerebral ischemia-reperfusion injury. Current standard treatments for ischemic stroke include the administration of rt-PA, a thrombolytic agent, or endovascular removal of thrombi. However, the post-treatments are often associated with the occlusion of vessels due to a lack of antiplatelet and unrecovered vessel injury. Anfibatide, as a GPIba antagonist that interrupts the initiation of platelet aggregation caused by GPIba-vWF binding, becomes a potential novel candidate for treating ischemic stroke due to its antiplatelet and antithrombosis effects. Key findings show that Anfibatide can significantly reduce microthrombus formation in cerebral vessels and reduce neuron apoptosis due to the release of pro-inflammatory mediators caused by ischemia or Ischemia-Reperfusion (I/R) injury. Significant improvement in neurological scores and reversal of brain structure alterations are observed in the Anfibatide-treated ischemic animal models. To facilitate the clinical development of Anfibatide, this paper aims to summarize the completed preclinical studies and the Phase I clinical trial results of anfibatide to evaluate the risks and therapeutic potentials of Anfibatide in ischemic patients.

Brain morphology and functional connectivity alterations in patients with severe obstructive sleep apnea

BackgroundIt has been demonstrated that widespread structural and functional brain alterations influence the development of cognitive impairment in patients with obstructive sleep apnea (OSA). However, the literature has limited evidence regarding the neuropathophysiological mechanisms behind these impairments. This research aimed to investigate brain morphologic and functional connectivity (FC) abnormalities related to neurocognitive function in OSA. MethodsFifty treatment-naïve males, newly diagnosed patients with severe OSA, and 50 well-matched healthy controls (HCs) were enrolled prospectively. All subjects underwent an MRI scan, cognitive psychological and sleep scale assessment. The differences of brain morphological and seed-based FC between the two groups were compared. The correlation analysis and receiver operating characteristic curve were performed for further analysis. ResultsCompared with HCs, the right brainstem, left dorsal-lateral superior frontal gyrus (SFGdor), and superior temporal gyrus (STG) exhibited atrophy in the OSA group. In addition, FC between the left SFGdor and the right postcentral gyrus (PoCG) was increased, which was positively correlated with disease duration (r = 0.312, FDR-corrected P = 0.027). The Jacobian values of the brainstem were negatively correlated with MoCA and recall scores (r = −0.449, FDR-corrected P = 0.0025; r = −0.416, FDR-corrected P = 0.005). Furthermore, the Jacobian values of the left SFGdor demonstrated a relatively high diagnostic performance (sensitivity: 86%, specificity: 56%, AUC: 0.740, 95% CI: 0.643–0.836, P < 0.0001). ConclusionsStructural atrophy in brainstem and frontotemporal lobe and altered FC may be the neurobiological hallmark of brain impairment in OSA. Notably, brainstem atrophy has been associated with cognitive impairment, which may provide new insights into understanding the neuropathophysiological mechanisms of cognitive impairment in OSA patients.

Detecting schizophrenia with 3D structural brain MRI using deep learning

Schizophrenia is a chronic neuropsychiatric disorder that causes distinct structural alterations within the brain. We hypothesize that deep learning applied to a structural neuroimaging dataset could detect disease-related alteration and improve classification and diagnostic accuracy. We tested this hypothesis using a single, widely available, and conventional T1-weighted MRI scan, from which we extracted the 3D whole-brain structure using standard post-processing methods. A deep learning model was then developed, optimized, and evaluated on three open datasets with T1-weighted MRI scans of patients with schizophrenia. Our proposed model outperformed the benchmark model, which was also trained with structural MR images using a 3D CNN architecture. Our model is capable of almost perfectly (area under the ROC curve = 0.987) distinguishing schizophrenia patients from healthy controls on unseen structural MRI scans. Regional analysis localized subcortical regions and ventricles as the most predictive brain regions. Subcortical structures serve a pivotal role in cognitive, affective, and social functions in humans, and structural abnormalities of these regions have been associated with schizophrenia. Our finding corroborates that schizophrenia is associated with widespread alterations in subcortical brain structure and the subcortical structural information provides prominent features in diagnostic classification. Together, these results further demonstrate the potential of deep learning to improve schizophrenia diagnosis and identify its structural neuroimaging signatures from a single, standard T1-weighted brain MRI.

Cortical Morphology in Cannabis Use Disorder: Implications for Transcranial Direct Current Stimulation Treatment.

Transcranial direct current stimulation (tDCS) has been studied as an adjunctive treatment option for substance use disorders (SUDs). Alterations in brain structure following SUD may change tDCS-induced electric field (EF) and subsequent responses; however, group-level differences between healthy controls (HC) and participants with SUDs in terms of EF and its association with cortical architecture have not yet been modeled quantitatively. This study provides a methodology for group-level analysis of computational head models to investigate the influence of cortical morphology metrics on EFs. Whole-brain surface-based morphology was conducted, and cortical thickness, volume, and surface area were compared between participants with cannabis use disorders (CUD) (n=20) and age-matched HC (n=22). Meanwhile, EFs were simulated for bilateral tDCS over the dorsolateral prefrontal cortex. The effects of structural alterations on EF distribution were investigated based on individualized computational head models. Regarding EF, no significant difference was found within the prefrontal cortex; however, EFs were significantly different in left-postcentral and right-superior temporal gyrus (P<0.05) with higher levels of variance in CUD compared to HC [F(39, 43)=5.31, P<0.0001, C=0.95]. Significant differences were observed in cortical area (caudal anterior cingulate and rostral middle frontal), thickness (lateral orbitofrontal), and volume (paracentral and fusiform) between the two groups. Brain morphology and tDCS-induced EFs may be changed following CUD; however, differences between CUD and HCs in EFs do not always overlap with brain areas that show structural alterations. To sufficiently modulate stimulation targets, whether individuals with CUD need different stimulation doses based on tDCS target location should be checked.

Understanding the impact of radical changes in diet and the gut microbiota on brain function and structure: rationale and design of the EMBRACE study.

Bariatric surgery leads to profound changes in gut microbiota and dietary patterns, both of which may interact to impact gut-brain communication. Though cognitive function improves postsurgery, there is a large variability in outcomes. How bariatric surgery-induced modifications in the gut microbiota and dietary patterns influence the variability in cognitive function is still unclear. To elucidate the associations between bariatric surgery-induced changes in dietary and gut microbiota patterns with cognition and brain structure. University hospital. A total of 120 adult patients (≥30 years) scheduled to undergo a primary bariatric surgery along with 60 age-, sex-, and body mass index-matched patients on the surgery waitlist will undergo assessments 3-months presurgery and 6- and 12-month postsurgery (or an equivalent time for the waitlist group). Additionally, 60 age-and sex-matched nonbariatric surgery eligible individuals will complete the presurgical assessments only. Evaluations will include sociodemographic and health behavior questionnaires, physiological assessments (anthropometrics, blood-, urine-, and fecal-based measures), neuropsychological cognitive tests, and structural magnetic resonance imaging. Cluster analyses of the dietary and gut microbiota changes will define the various dietary patterns and microbiota profiles, then using repeated measures mixed models, their associations with global cognitive and structural brain alterations will be explored. The coordinating study site (Centre intégré universitaire de santé et de services sociaux du Nord-de-l'Île-de-Montréal, QC, Canada), provided the primary ethical approval (Research Ethics Board#: MP-32-2022-2412). The insights generated from this study can be used to develop individually-targeted neurodegenerative disease prevention strategies, as well as providing critical mechanistic information.

Endotype Characterization Reveals Mechanistic Differences Across Brain Regions in Sporadic Alzheimer's Disease.

While Alzheimer's disease (AD) pathology is associated with altered brain structure, it is not clear whether gene expression changes mirror the onset and evolution of pathology in distinct brain regions. Deciphering the mechanisms which cause the differential manifestation of the disease across different regions has the potential to help early diagnosis. We aimed to identify common and unique endotypes and their regulation in tangle-free neurons in sporadic AD (SAD) across six brain regions: entorhinal cortex (EC), hippocampus (HC), medial temporal gyrus (MTG), posterior cingulate (PC), superior frontal gyrus (SFG), and visual cortex (VCX). To decipher the states of tangle-free neurons across different brain regions in human subjects afflicted with AD, we performed analysis of the neural transcriptome. We explored changes in differential gene expression, functional and transcription factor target enrichment, and co-expression gene module detection analysis to discern disease-state transcriptomic variances and characterize endotypes. Additionally, we compared our results to tangled AD neuron microarray-based study and the Allen Brain Atlas. We identified impaired neuron function in EC, MTG, PC, and VCX resulting from REST activation and reversal of mature neurons to a precursor-like state in EC, MTG, and SFG linked to SOX2 activation. Additionally, decreased neuron function and increased dedifferentiation were linked to the activation of SUZ12. Energetic deficit connected to NRF1 inactivation was found in HC, PC, and VCX. Our findings suggest that SAD manifestation varies in scale and severity in different brain regions. We identify endotypes, such as energetic shortfalls, impaired neuronal function, and dedifferentiation.

Progressive reduction in basal ganglia explains and predicts cerebral structural alteration in type 2 diabetes

Type 2 diabetes is consistently reported to be associated with reduced gray matter, mainly in the cortical-striatal-limbic networks. However, little is known about how the progression of diabetes affects cerebral gray matter. To investigate, we collected 543 age- and sex-matched participants of nondiabetes, prediabetes, and diabetes. Voxel-based morphometry using a linear trend model was performed to reveal brain regions associated with disease progression. The Granger causal network of structural covariance was used to assess the causal relationships of brain structural alterations according to disease progression. Multivariate pattern analysis was applied for the stage-specific predictions of hyperglycemia. We detected a linear trend of gray matter volume reduction in the basal ganglia with disease progression (P < 0.05, FWER corrected), which caused a reduction in bilateral temporal gyri, frontal pole, parahippocampus, and bilateral posterior cingulate/precuneus volumes. In addition, the gray matter pattern of the basal ganglia could predict patients with diabetes (accuracy 60.12%, p = 0.002). In conclusion, the basal ganglia is the brain area with progressive gray matter reduction as diabetes progress. The reduced volume in the basal ganglia causes widespread gray matter reductions throughout diabetes progression. These findings indicate that the basal ganglia play a key role in diabetes by affecting the cortical-striatal-limbic network.

Practitioner Review: Neurobiological consequences of childhood maltreatment - clinical and therapeutic implications for practitioners.

Childhood maltreatment is one of the most important preventable risk factors for a wide variety of psychiatric disorders. Further, when psychiatric disorders emerge in maltreated individuals they typically do so at younger ages, with greater severity, more psychiatric comorbid conditions, and poorer response to established treatments, resulting in a more pernicious course with an increased risk for suicide. Practitioners treating children, adolescents, and young adults with psychiatric disorders will likely encounter the highest prevalence of clients with early-onset maltreatment-associated psychiatric disorders. These may be some of their most challenging cases. In this report, we explore key validated alterations in brain structure, function, and connectivity associated with exposure to childhood maltreatment as potential mechanisms behind their patients' clinical presentations. We then summarize key behavioral presentations likely associated with neurobiological alterations and propose a toolkit of established trauma and skills-based strategies that may help diminish symptoms and foster recovery. We also discuss how some of these alterations may serve as latent vulnerability factors for the possible development of future psychopathology. Research on the neurobiological consequences of childhood adversity provides a vastly enriched biopsychosocial understanding of the developmental origins of health and pathology that will hopefully lead to fundamental advances in clinical psychology and psychiatry.

Decreased Local Specialization of Brain Structural Networks Associated with Cognitive Dysfuntion Revealed by Probabilistic Diffusion Tractography for Different Cerebral Small Vessel Disease Burdens

To reveal the network-level structural disruptions associated with cognitive dysfunctions in different cerebral small vessel disease (CSVD) burdens, we used probabilistic diffusion tractography and graph theory to investigate the brain network topology in 67 patients with a severe CSVD burden (CSVD-s), 133 patients with a mild CSVD burden (CSVD-m) and 89 healthy controls. We used one-way analysis of covariance to assess the altered topological measures between groups, and then evaluated their Pearson correlation with cognitive parameters. Both the CSVD and control groups showed efficient small-world organization in white matter (WM) networks. However, compared with CSVD-m patients and controls, CSVD-s patients exhibited significantly decreased local efficiency, with partially reorganized hub distributions. For regional topology, CSVD-s patients showed significantly decreased nodal efficiency in the bilateral anterior cingulate gyrus, caudate nucleus, right opercular inferior frontal gyrus (IFGoperc), supplementary motor area (SMA), insula and left orbital superior frontal gyrus and angular gyrus. Intriguingly, global/local efficiency and nodal efficiency of the bilateral caudate nucleus, right IFGoperc, SMA and left angular gyrus showed significant correlations with cognitive parameters in the CSVD-s group, while only the left pallidum showed significant correlations with cognitive metrics in the CSVD-m group. In conclusion, the decreased local specialization of brain structural networks in patients with different CSVD burdens provides novel insights into understanding the brain structural alterations in relation to CSVD severity. Cognitive correlations with brain structural network efficiency suggest their potential use as neuroimaging biomarkers to assess the severity of CSVD.

A Shared Multivariate Brain-Behavior Relationship in a Transdiagnostic Sample of Adolescents

BackgroundInternalizing and externalizing psychopathology typically present in early childhood and can have negative implications on general functioning and quality of life. Prior work has linked increased psychopathology symptoms with altered brain structure. Multivariate analysis such as partial least squares correlation can help identify patterns of covariation between brain regions and psychopathology symptoms. This study examined the relationship between gray matter volume (GMV) and psychopathology symptoms in adolescents with various psychiatric diagnoses. MethodsStructural magnetic resonance imaging data were collected from 490 participants with various internalizing and externalizing diagnoses (197 female/293 male; age = 14.68 ± 2.35 years; IQ = 104.05 ± 13.11). Cortical and subcortical volumes were parcellated using the Desikan-Killiany atlas. Partial least squares correlation was used to identify multivariate linear relationships between GMV and the Strength and Difficulties Questionnaire difficulties domains (emotional, peer, conduct, and hyperactivity issues). Resampling approaches were used to determine significance (permutation test), stability (bootstrap resampling), and reproducibility (split-half resampling) of identified relationships. ResultsWe found a significant, stable, and largely reproducible dimension that linked lower Strength and Difficulties Questionnaire scores (less impairment) across all difficulties domains with greater widespread GMV (singular value = 1.17, accounts for 87.1% of the covariance; p < .001). This dimension emphasized the relationship between lower conduct problems and greater GMV in frontotemporal regions. ConclusionsOur results indicate that the most significant and stable brain-behavior relationship in a transdiagnostic sample is a domain-general relationship, linking lower psychopathology symptom scores to greater global GMV. This finding suggests that a shared brain-behavior relationship may be present across adolescents with and without clinically significant psychopathology symptoms.

Predicting long-term outcome in anorexia nervosa: a machine learning analysis of brain structure at different stages of weight recovery.

Anorexia nervosa (AN) is characterized by sizable, widespread gray matter (GM) reductions in the acutely underweight state. However, evidence for persistent alterations after weight-restoration has been surprisingly scarce despite high relapse rates, frequent transitions to other psychiatric disorders, and generally unfavorable outcome. While most studies investigated brain regions separately (univariate analysis), psychiatric disorders can be conceptualized as brain network disorders characterized by multivariate alterations with only subtle local effects. We tested for persistent multivariate structural brain alterations in weight-restored individuals with a history of AN, investigated their putative biological substrate and relation with 1-year treatment outcome. We trained machine learning models on regional GM measures to classify healthy controls (HC) (N = 289) from individuals at three stages of AN: underweight patients starting intensive treatment (N = 165, used as baseline), patients after partial weight-restoration (N = 115), and former patients after stable and full weight-restoration (N = 89). Alterations after weight-restoration were related to treatment outcome and characterized both anatomically and functionally. Patients could be classified from HC when underweight (ROC-AUC = 0.90) but also after partial weight-restoration (ROC-AUC = 0.64). Alterations after partial weight-restoration were more pronounced in patients with worse outcome and were not detected in long-term weight-recovered individuals, i.e. those with favorable outcome. These alterations were more pronounced in regions with greater functional connectivity, not merely explained by body mass index, and even increases in cortical thickness were observed (insula, lateral orbitofrontal, temporal pole). Analyzing persistent multivariate brain structural alterations after weight-restoration might help to develop personalized interventions after discharge from inpatient treatment.