Transient brain structure changes after high phenylalanine exposure in adults with phenylketonuria.

Phenylketonuria is a rare metabolic disease resulting from a deficiency of the enzyme phenylalanine hydroxylase. Recent cross-sectional evidence suggests that early-treated adults with phenylketonuria exhibit alterations in cortical grey matter compared to healthy peers. However, the effects of high phenylalanine exposure on brain structure in adulthood need to be further elucidated. In this double-blind, randomised, placebo-controlled crossover trial, we investigated the impact of a four-week high phenylalanine exposure on the brain structure and its relationship to cognitive performance and metabolic parameters in early-treated adults with phenylketonuria. Twenty-eight adult patients with early-treated classical phenylketonuria (19-48 years) underwent magnetic resonance imaging before and after the four-week phenylalanine and placebo interventions (four timepoints). Structural T1-weighted images were preprocessed and evaluated using DL+DiReCT, a deep-learning-based tool for brain morphometric analysis. Cortical thickness, white matter volume, and ventricular volume were compared between the phenylalanine and placebo periods. Brain phenylalanine levels were measured using 1H spectroscopy. Blood levels of phenylalanine, tyrosine, and tryptophan were assessed at each of the four timepoints, along with performance in executive functions and attention. Blood phenylalanine levels were significantly higher after the phenylalanine period (1441µmol/L) than after the placebo period (873µmol/L, P<0.001). Morphometric analyses revealed a statistically significant decrease in cortical thickness in 17 out of 60 brain regions after the phenylalanine period compared to placebo. The largest decreases were observed in the right pars orbitalis (point estimate=-0.095mm, P<0.001) and the left lingual gyrus (point estimate=-0.070mm, P<0.001). Bilateral white matter and ventricular volumes were significantly increased after the phenylalanine period. However, the structural alterations in the Phe-placebo group returned to baseline measures following the washout and placebo period. Additionally, elevated blood and brain phenylalanine levels were related to increased bilateral white matter volume (rs=0.43 to 0.51, P≤0.036) and decreased cortical thickness (rs=-0.62 to -0.39, not surviving FDR correction) after the phenylalanine and placebo periods. Moreover, decreased cortical thickness was correlated with worse cognitive performance after both periods (rs=-0.54 to -0.40, not surviving FDR correction). These findings provide evidence that a four-week high phenylalanine exposure in adults with phenylketonuria results in transient reductions of the cortical grey matter and increases in white matter volume. Further research is needed to determine the potential long-term impact of high phenylalanine levels on brain structure and function in adults with phenylketonuria.

Common and distinct cortical thickness alterations in youth with autism spectrum disorder and attention-deficit/hyperactivity disorder.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders with overlapping behavioral features and genetic etiology. While brain cortical thickness (CTh) alterations have been reported in ASD and ADHD separately, the degree to which ASD and ADHD are associated with common and distinct patterns of CTh changes is unclear. METHODS: We searched PubMed, Web of Science, Embase, and Science Direct from inception to 8 December 2023 and included studies of cortical thickness comparing youth (age less than 18) with ASD or ADHD with typically developing controls (TDC). We conducted a comparative meta-analysis of vertex-based studies to identify common and distinct CTh alterations in ASD and ADHD. RESULTS: Twelve ASD datasets involving 458 individuals with ASD and 10 ADHD datasets involving 383 individuals with ADHD were included in the analysis. Compared to TDC, ASD showed increased CTh in bilateral superior frontal gyrus, left middle temporal gyrus, and right superior parietal lobule (SPL) and decreased CTh in right temporoparietal junction (TPJ). ADHD showed decreased CTh in bilateral precentral gyri, right postcentral gyrus, and right TPJ relative to TDC. Conjunction analysis showed both disorders shared reduced TPJ CTh located in default mode network (DMN). Comparative analyses indicated ASD had greater CTh in right SPL and TPJ located in dorsal attention network and thinner CTh in right TPJ located in ventral attention network than ADHD. CONCLUSIONS: These results suggest shared thinner TPJ located in DMN is an overlapping neurobiological feature of ASD and ADHD. This alteration together with SPL alterations might be related to altered biological motion processing in ASD, while abnormalities in sensorimotor systems may contribute to behavioral control problems in ADHD. The disorder-specific thinner TPJ located in disparate attention networks provides novel insight into distinct symptoms of attentional deficits associated with the two neurodevelopmental disorders. TRIAL REGISTRATION: PROSPERO CRD42022370620. Registered on November 9, 2022.

Glymphatic abnormality in systemic lupus erythematosus detected by diffusion tensor image analysis along the perivascular space.

OBJECTIVES: This study aimed to evaluate the activity of the glymphatic system in systemic lupus erythematosus (SLE) by a diffusion-based method termed "Diffusion Tensor Image Analysis aLong the Perivascular Space (DTI-ALPS)", and examined its correlations with morphological changes in the brain. METHODS: In this cross-sectional study, forty-five female patients with SLE and thirty healthy controls (HCs) were included. Voxel-based and surface-based morphometric analyses were performed to examine T1 weighted images, and diffusion tensor images were acquired to determine diffusivity along the x-, y-, and z-axes in the plane of the lateral ventricle body. The ALPS-index was calculated. The differences in values between SLE patients and HC group were compared using the independent samples t test or Mann-Whitney U test. For the correlations between the ALPS-index and brain morphological parameters, partial correlation analysis and Pearson's correlation analysis were conducted. RESULTS: SLE patients showed lower values for the ALPS-index in left (1.543 ± 0.141 vs 1.713 ± 0.175, p < 0.001), right (1.428 ± 0.142 vs 1.556 ± 0.139, p < 0.001) and whole (1.486 ± 0.121 vs 1.635 ± 0.139, p < 0.001) brain compared with the HC group. The reduced ALPS-index showed significant positive correlations with gray matter loss. CONCLUSION: The non-invasive ALPS-index could serve as a sensitive and effective neuroimaging biomarker for individually quantifying glymphatic activity in patients with SLE. Glymphatic system abnormality may be involved in the pathophysiologic mechanism underlying central nervous system damage in SLE patients.

Distinctive cortical morphological patterns in primary trigeminal neuralgia: a cross-sectional clinical study.

PURPOSE: The characteristics of surface-based morphological patterns to primary trigeminal neuralgia (PTN) are still not well understood. This study aims to screen the useful cortical indices for the prediction of PTN and the quantification of pain severity. METHODS: Fifty PTN patients and 48 matched healthy subjects enrolled in the study from March 2016 to August 2021. High-resolution T1 data were performed at 3.0 Tesla scanner and were analyzed with FreeSurfer software to detect the abnormalities of cortical mean curve (CMC), cortical thickness (CT), surface area (SA), and cortical volume (CV) in PTN patients compared to healthy controls. Logistic regression analysis was conducted to determine whether certain morphological patterns could predict PTN disorder. Then, the relationships of cortical indices to the pain characteristics in patient group were examined using linear regression model. RESULTS: Distinctive cortical alterations were discovered through surface-based analysis, including increased temporal CMC, decreased insular CT and fusiform SA, along with decreased CV in several temporal and occipital areas. Moreover, the difference of temporal CMC was greater than other cortical parameters between the two groups, and the combination of certain morphological indices was of good value in the diagnosis for PTN. Besides, CT of left insula was negatively associated with the pain intensity in PTN patients. CONCLUSION: The patients with PTN demonstrate distinctive morphological patterns in several cortical regions, which may contribute to the imaging diagnosis of this refractory disorder and be useful for the quantification of the orofacial pain. CLINICAL TRIALS: The registry name of this study in https://clinicaltrials.gov/ : Magnetic Resonance Imaging Study on Patients with Trigeminal Neuralgia (MRI-TN) https://clinicaltrials.gov/ ID: NCT02713646 A link to the full application: https://clinicaltrials.gov/ct2/results?cond=&term=NCT02713646&cntry=&state=&city=&dist= The first patient with primary trigeminal neuralgia was recruited on November 28, 2016.

Cortical and subcortical grey matter correlates of psychopathic traits in a Japanese community sample of young adults: sex and configurations of factors' level matter!

While neuroimaging research has examined the structural brain correlates of psychopathy predominantly in clinical/forensic male samples from western countries, much less is known about those correlates in non-western community samples. Here, structural magnetic resonance imaging data were analyzed using voxel- and surface-based morphometry to investigate the neuroanatomical correlates of psychopathic traits in a mixed-sex sample of 97 well-functioning Japanese adults (45 males, 21-39 years; M = 27, SD = 5.3). Psychopathic traits were assessed using the Self-Report Psychopathy Scale (SRP-SF; 4th Edition). Multiple regression analysis showed greater Factor 1 scores were associated with higher gyrification in the lingual gyrus, and gray matter volume in the anterior cingulate cortex and amygdala/hippocampus border. Total psychopathy and Factor 1 scores interacted with sex to, respectively, predict cortical thickness in the precuneus and gyrification in the superior temporal gyrus. Finally, Factor 1 and Factor 2 traits interacted to predict gyrification in the posterior cingulate cortex. These preliminary data suggest that, while there may be commonalities in the loci of structural brain correlates of psychopathic traits in clinical/forensic and community samples, the nature of that association might be different (i.e. positive) and may vary according to sex and configurations of factors' level.

Cortical changes in the brain of patients with hemifacial spasm.

OBJECTIVE: Hemifacial spasm (HFS) is a movement disorder characterized by involuntary muscle contractions on one side of the face. It is associated with disturbances in the brain's functional architecture. Despite this, the structural alterations in the brain related to HFS remain poorly understood. In this study, we investigated the cortical morphology changes in patients with HFS compared to healthy controls (HCs). METHODS: We analyzed 3D T1-weighted MRI images from 33 patients with left-sided primary HFS and 33 age- and sex-matched HCs. Measurements of cortical thickness (CTh), sulcal depth, local gyrification index (lGI), and fractal dimension were taken using a computational anatomy toolbox. A general linear model, accounting for age, gender, and total brain volume, was applied for statistical analyses. Significant clusters were then assessed for correlations with clinical parameters. RESULTS: The HFS patients displayed several cortical abnormalities when compared to HCs, including reduced CTh in the contralateral precentral gyrus and left orbitofrontal cortex, decreased sulcal depth in the left orbitofrontal cortex, and increased lGI in the right insula and superior temporal cortex. However, fractal dimension did not differ significantly between the groups. Additionally, in HFS patients, a notable negative correlation was found between the sulcal depth in the left orbitofrontal cortex and the Beck Depression Inventory-II scores. CONCLUSIONS: Our findings reveal that HFS is associated with specific surface-based morphological changes in the brain. These alterations contribute to a deeper understanding of the neurophysiological mechanisms involved in HFS and may have implications for future research and treatment strategies.

Distinct biological property of tau in tau-first cognitive proteinopathy: Evidence by longitudinal clinical neuroimaging profiles and compared with late-onset Alzheimer disease.

BACKGROUND: Tau-first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. AIM: We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late-onset AD (LOAD). METHOD: We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three-dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow-up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed-effects model. RESULTS: The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short-term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. DISCUSSION: The biological properties of tau and the longitudinal cognitive-imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short-term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau.

Morphological alterations of contralesional hemisphere relate to functional outcomes after stroke.

The present study aimed to investigate poststroke morphological alterations contralesionally and correlations with functional outcomes. Structural magnetic resonance images were obtained from 27 poststroke patients (24 males, 50.21 ± 10.97 years) and 20 healthy controls (13 males, 46.63 ± 12.18 years). Voxel-based and surface-based morphometry analysis were conducted to detect alterations of contralesional grey matter volume (GMV), cortical thickness (CT), gyrification index (GI), sulcus depth (SD), and fractal dimension (FD) in poststroke patients. Partial correlation analysis was used to explore the relationship between regions with significant structural differences and scores of clinical assessments, including Modified Barthel Index (MBI), Berg Balance Scale (BBS), Fugl-Meyer Assessment of Upper Extremity (FMA-UE), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Correction for multiplicity was conducted within each parameter and for all tests. GMV significantly decreased in the contralesional motor-related, occipital and temporal cortex, limbic system, and cerebellum lobe (P < 0.01, family-wise error [FWE] correction). Lower CT was found in the contralesional precentral and lingual gyrus (P < 0.01, FWE correction), while lower GI found in the contralesional superior temporal gyrus and insula (P < 0.01, FWE correction). There were significant correlations between GMV of contralesional lingual gyrus and MBI (P = 0.031, r = 0.441), and BBS (P = 0.047, r = 0.409) scores, and GMV of contralesional hippocampus and FMA-UE scores (P = 0.048, r = 0.408). In conclusion, stroke patients exhibited wide grey matter loss and cortical morphological changes in the contralesional hemisphere, which correlated with sensorimotor functions and the ability of daily living.

Different neuroanatomical correlates for temporal and spectral supra-threshold auditory tasks and speech in noise recognition in older adults with hearing impairment.

Varying degrees of pure-tone hearing loss in older adults are differentially associated with cortical volume (CV) and thickness (CT) within and outside of the auditory pathway. This study addressed the question to what degree supra-threshold auditory performance (i.e., temporal compression and frequency selectivity) as well as speech in noise (SiN) recognition are associated with neurostructural correlates in a sample of 59 healthy older adults with mild to moderate pure-tone hearing loss. Using surface-based morphometry on T1-weighted MRI images, CT, CV, and surface area (CSA) of several regions-of-interest were obtained. The results showed distinct neurostructural patterns for the different tasks in terms of involved regions as well as morphometric parameters. While pure-tone averages (PTAs) positively correlated with CT in a right hemisphere superior temporal sulcus and gyrus cluster, supra-threshold auditory perception additionally extended significantly to CV and CT in left and right superior temporal clusters including Heschl's gyrus and sulcus, the planum polare and temporale. For SiN recognition, we found significant correlations with an auditory-related CT cluster and furthermore with language-related areas in the prefrontal cortex. Taken together, our results show that different auditory abilities are differently associated with cortical morphology in older adults with hearing impairment. Still, a common pattern is that greater PTAs and poorer supra-threshold auditory performance as well as poorer SiN recognition are all related to cortical thinning and volume loss but not to changes in CSA. These results support the hypothesis that mostly CT undergoes alterations in the context of auditory decline, while CSA remains stable.

Neuroanatomical markers of familial risk in adolescents with conduct disorder and their unaffected relatives.

BACKGROUND: Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD. METHODS: Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12-18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures. RESULTS: The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes. CONCLUSIONS: These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.

MRI Assessment of the Relationship Between Cortical Morphological Features and Hemiparetic Motor-Related Outcomes in Chronic Subcortical Stroke Patients.

BACKGROUND: It is unclear which cortical regions are specific to or commonly associated with the impairments of the upper/lower limbs and the activities of daily life (ADL) in stroke patients. PURPOSE: To investigate the relationships between MRI-assessed surface-based morphometry (SBM) features and motor function as well as ADL in participants with chronic stroke. STUDY TYPE: Prospective. SUBJECTS: Thirty-five participants with subcortical stroke more than 3 months from the first-onset (age: 56.44 ± 9.56 years; 32 male). FIELD STRENGTH/SEQUENCE: T1 -weighted images, 3.0 T, three-dimensional fast field-echo sequence. ASSESSMENT: FreeSurfer (6.0) was used to parcellate each hemisphere into 34 regions based on the Desikan-Killiany atlas and to extract the surface area, volume, thickness, and curvature. The motor function and ADL were assessed by the Fugl-Meyer Assessment for the Upper/Lower Extremity (FMA-UE/FMA-LE) and the Chinese version of the Modified Barthel Index (MBI-C), respectively. STATISTICAL TESTS: A linear mixed-effect model was applied to evaluate the relationship between the morphological features and the FMA-UE, FMA-LE, and MBI-C. A false discovery rate corrected P value < 0.05 was considered statistically significant. RESULTS: Correlations between the size of stroke lesion and MRI measurements did not pass the FDR correction (adjusted P > 0.05). SBM features in motor-related and high-order cognitive cortical regions showed significant correlations with FMA-UE and FMA-LE, respectively. Moreover, the thickness in the prefrontal cortex significantly positively correlated, while the surface area in the right supramarginal gyrus significantly negatively correlated, with both FMA-UE, FMA-LE, and MBI-C. The thickness in the left frontal lobe significantly positively correlated with both FMA-UE and MBI-C. DATA CONCLUSION: This study's findings suggest that different hemiparetic motor-related outcomes in participants with subcortical stroke which suffered a corticospinal tract-related injury show specific, but also share common, associations with several cortical regions. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Structural Correlates of Lifetime Voice-Hearing in Patients with Borderline Personality Disorder: A Pilot Study.

INTRODUCTION: Auditory verbal hallucinations (AVH) are transdiagnostic phenomena that can occur in several mental disorders, including borderline personality disorder (BPD). Despite the transdiagnostic relevance of these symptoms, very little is known about neural signatures of AVH in BPD. METHODS: We used structural magnetic resonance imaging to investigate multiple markers of brain morphology in BPD patients presenting with a lifetime history of AVH (AVH, n = 6) versus BPD patients without AVH (nAVH, n = 10) and healthy controls (HC, n = 12). The Computational Anatomy Toolbox (CAT12) was used for surface-based morphometric analyses that considered cortical thickness (CTh), gyrification (CG), and complexity of cortical folding (CCF). Factorial models were used to explore differences between AVH patients and HC, as well as between the patient groups. RESULTS: Compared to HC, AVH patients showed distinct abnormalities in key regions of the language network, i.e., aberrant CTh and CG in right superior temporal gyrus and abnormal CCF in left inferior frontal gyrus. Further abnormalities were found in right prefrontal cortex (CTh) and left orbitofrontal cortex (CCF). Compared to nAVH patients, individuals with AVH showed abnormal CTh in right prefrontal cortex, along with CCF differences in right transverse temporal, superior parietal, and parahippocampal gyri. CG differences between the patient groups were found in left orbitofrontal cortex. CONCLUSION: The data suggest a transdiagnostic neural signature of voice-hearing that converges on key regions involved in speech generation and perception, memory and executive control. It is possible that cortical features of distinct evolutionary and genetic origin, i.e., CTh and CG/CCF, differently contribute to AVH vulnerability in BPD.

Cortical morphological changes in multiple sclerosis patients: a study of cortical thickness, sulcal depth, and local gyrification index.

PURPOSE: Multiple sclerosis (MS) is a disease that progresses not only with demyelination but also with neurodegeneration. One of the goals of drug treatment in MS is to prevent neurodegeneration. Cortical thickness (CT), sulcal depth (SD), and local gyrification index (LGI) are indicators related to neurodegeneration. The aim of this study is to investigate changes in CT, SD, and LGI in patients with relapsing-remitting MS (RRMS). METHODS: T1 images of 74 RRMS patients and 65 healthy controls were used. T1 hypointense areas in RRMS patients were corrected using fully automated methods. CT, SD, and LGI were calculated for each patient. RESULTS: RRMS patients showed widespread cortical thinning, especially in bilateral temporoparietal areas, decreased SD in bilateral supramarginal gyrus, superior temporal gyrus, postcentral gyrus, and transverse temporal gyrus, and decreased LGI, especially in the left posterior cingulate gyrus and insula. The decrease in cortical thickness was associated with the number of attacks and lesion volume. EDSS was related to CT in the right lingual, inferior temporal, and fusiform gyrus. The LGI was correlated with T2 lesion volume in bilateral insula, with EDSS in the right insula and transverse and superior temporal gyri, and with the number of attacks in the right paracentral gyrus and pre-cuneus. However, SD did not show any correlation with EDSS, T2 lesion volume, or the number of attacks. CONCLUSION: Our results demonstrate widespread cortical thinning, decreased sulcal depth in local areas, and decreased gyrification in folds in RRMS patients, which are related to clinical parameters.

Altered Somatosensory Cortical Activity Is Associated with Cortical Thickness in Adults with Cerebral Palsy: Multimodal Evidence from MEG/sMRI.

Somatosensory cortical activity is altered in individuals with cerebral palsy (CP). However, previous studies have focused on the lower extremities in children with CP and have given less attention to structural changes that may contribute to these alterations. We used a multimodal neuroimaging approach to investigate the relationship between somatosensory cortical activity and cortical thickness in 17 adults with CP (age = 32.8 ± 9.3 years) and 18 healthy adult controls (age = 30.7 ± 9.8 years). Participants performed a median nerve paired-pulse stimulation paradigm while undergoing magnetoencephalography (MEG) to investigate somatosensory cortical activity and sensory gating. Participants also underwent magnetic resonance imaging to evaluate cortical thickness within the area of the somatosensory cortex that generated the MEG response. We found that the somatosensory responses were attenuated in the adults with CP (P = 0.004). The adults with CP also hypergated the second stimulation (P = 0.030) and had decreased cortical thickness in the somatosensory cortex (P = 0.015). Finally, the strength of the somatosensory response was significantly correlated with the cortical thickness (P = 0.023). These findings demonstrate that the aberrant somatosensory cortical activity in adults with CP extends to the upper extremities and appears to be related to cortical thickness.

Abnormal neuroanatomical patterns as potential diagnostic biomarkers for cocaine use disorder.

Cocaine use disorder (CUD) is a global health problem with serious consequences for both individuals and society. Previous studies on abnormal anatomical patterns in CUD have mainly used voxel-based morphometry to investigate grey matter volume changes, while surface-based morphometry (SBM) has been found to provide detail information on cortical thickness (CT), surface area and cortical meancurve, which can contribute to a better understanding of structural brain changes associated with CUD. In this study, SBM was conducted to investigate abnormal neuroanatomical patterns in CUD and whether these abnormal patterns could be used as potential diagnostic biomarkers for CUD. Sixty-eight CUD individuals and 52 matched healthy controls were enrolled, and all participants performed once MRI scanning and clinical assessments. We found that CUD individuals exhibited altered morphological indicators across widespread brain regions and these abnormal anatomical alterations were significantly predictive of CUD status. Furthermore, the CT reduction of right insula was significantly associated with years of cocaine use in CUD. These findings revealed the association of abnormal anatomical patterns in specific brain regions in CUD, which further improve the understanding of CUD pathophysiology and provide the alternative diagnostic biomarkers for CUD.

Aberrant gray matter structure in neurosyphilis without conventional MRI abnormality: a pilot study with voxel and surface-based morphology.

BACKGROUND: The underlying mechanism of neurosyphilis was not fully understood. PURPOSE: To assess gray matter (GM) microstructure in patients with early-stage neurosyphilis without overt conventional magnetic resonance imaging (MRI) abnormality using voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses. MATERIAL AND METHODS: Three-dimensional high-resolution T1-weighted imaging data from 19 individuals with neurosyphilis and 19 healthy controls were analyzed. A battery of neuropsychological tests was performed before each MRI examination. The differences of GM volume and cerebral cortical morphological data between the two groups were compared. The correlations between MRI metrics and neuropsychology/laboratory tests in the patient group were investigated. RESULTS: Regional decreased GM volumes in patients with neurosyphilis were found in the left frontal cortices (Rolandic operculum, middle frontal, and precentral) and bilateral temporal/occipital cortices (bilateral middle temporal, left lingual, and right middle occipital) (P < 0.05, FDR correction). SBM analysis showed significant cortical thickness reduction in the right medial orbitofrontal lobe, and reduced gyrification index in the left insula in patients with neurosyphilis (P < 0.05, FDR correction). Additionally, in the patient group, the GM volume in the middle frontal gyrus, the cortical thickness of right medial orbitofrontal lobe, and the gyrification index in the left insula were negatively correlated to the number connection test-A scores. The gyrification index was also negatively correlated to cerebrospinal fluid white blood cell count. CONCLUSION: Early-stage neurosyphilis without conventional MRI abnormality presented regional GM volume reduction and cortical morphological changes, which might be related to cognitive impairment and intra-cranial infection. VBM and SBM analyses might be useful for understanding the underlying neural trait of neurosyphilis.

Alteration of the cortical morphology in classical trigeminal neuralgia: voxel-, deformation-, and surface-based analysis.

OBJECTIVE: This study aimed to combine voxel-based morphometry, deformation-based morphometry, and surface-based morphometry to analyze gray matter volume and cortex shape in classical trigeminal neuralgia patients. METHODS: This study included 79 classical trigeminal neuralgia patients and age- and sex-matched 81 healthy controls. The aforementioned three methods were used to analyze brain structure in classical trigeminal neuralgia patients. Spearman correlation analysis was used to analyze the correlation of brain structure with the trigeminal nerve and clinical parameters. RESULTS: The bilateral trigeminal nerve was atrophied, and the ipsilateral trigeminal nerve volume was smaller than the contralateral volume in the classical trigeminal neuralgia. The gray matter volume of Temporal_Pole_Sup_R and Precentral_R was found to be decreased using voxel-based morphometry. The gray matter volume of Temporal_Pole_Sup_R had a positive correlation with disease duration and a negative correlation with the cross-section area of the compression point and the quality-of-life score in trigeminal neuralgia. The gray matter volume of Precentral_R was negatively correlated with the ipsilateral volume of the trigeminal nerve cisternal segment, cross-section area of compression point, and visual analogue scale. The gray matter volume of Temporal_Pole_Sup_L was found to be increased using deformation-based morphometry and had a negative correlation with the self-rating anxiety scale. The gyrification of the middle temporal gyrus_L increased and the Postcentral_L thickness decreased, as detected using surface-based morphometry. CONCLUSIONS: The gray matter volume and cortical morphology of pain-related brain regions were correlated with clinical and trigeminal nerve parameters. voxel-based morphometry, deformation-based morphometry, and surface-based morphometry complemented each other in analyzing the brain structures of patients with classical trigeminal neuralgia and provided a basis for studying the pathophysiology of classical trigeminal neuralgia.

Patterns of a structural covariance network associated with dispositional optimism during late adolescence.

Dispositional optimism (hereinafter, optimism), as a vital character strength, reflects the tendency to hold generalized positive expectancies for future outcomes. A great number of studies have consistently shown the importance of optimism to a spectrum of physical and mental health outcomes. However, less attention has been given to the intrinsic neurodevelopmental patterns associated with interindividual differences in optimism. Here, we investigated this important question in a large sample comprising 231 healthy adolescents (16-20 years old) via structural magnetic resonance imaging and behavioral tests. We constructed individual structural covariance networks based on cortical gyrification using a recent novel approach combining probability density estimation and Kullback-Leibler divergence and estimated global (global efficiency, local efficiency and small-worldness) and regional (betweenness centrality) properties of these constructed networks using graph theoretical analysis. Partial correlations adjusted for age, sex and estimated total intracranial volume showed that optimism was positively related to global and local efficiency but not small-worldness. Partial least squares correlations indicated that optimism was positively linked to a pronounced betweenness centrality pattern, in which twelve cognition-, emotion-, and motivation-related regions made robust and reliable contributions. These findings remained basically consistent after additionally controlling for family socioeconomic status and showed significant correlations with optimism scores from 2.5 years before, which replicated the main findings. The current work, for the first time, delineated characteristics of the cortical gyrification covariance network associated with optimism, extending previous neurobiological understandings of optimism, which may navigate the development of interventions on a neural network level aimed at raising optimism.

Impaired Ocular Tracking and Cortical Atrophy in Idiopathic Rapid Eye Movement Sleep Behavior Disorder.

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of synucleinopathies. Patients with synucleinopathies frequently display eye movement abnormalities. However, whether patients with iRBD have eye movement abnormalities remains unknown. OBJECTIVE: The aim of this study was to assess eye movement abnormalities and related gray matter alterations and explore whether such abnormalities can serve as biomarkers to indicate phenoconversion to synucleinopathies in iRBD. METHODS: Forty patients with iRBD with early disease progression and 35 healthy control subjects participated in a 15-minute ocular-tracking task that evaluated their control of eye movement abilities. They also underwent clinical assessments for olfactory function, nonmotor symptoms, and autonomic symptoms, all of which are biomarkers to predict phenoconversion to synucleinopathies in iRBD. A subgroup of the participants (20 patients with iRBD and 20 healthy control subjects) also participated in structural magnetic resonance imaging. RESULTS: The ocular-tracking ability in patients with iRBD was inferior to that of healthy control subjects in two aspects: pursuit initiation and steady-state tracking. Cortical thinning in the right visual area V4 in patients with iRBD is coupled with impaired pursuit initiation. Furthermore, prolonged pursuit initiation in patients with iRBD exhibits a trend of correlation with olfactory loss, the earliest biomarker that develops prior to other prodromal biomarkers. CONCLUSIONS: We found ocular-tracking abnormalities in patients with iRBD even early in their disease progression that have not been reported before. These abnormalities are coupled with atrophy of brain areas involved in the perception of object motion and might indicate phenoconversion to synucleinopathies in iRBD. © 2022 International Parkinson and Movement Disorder Society.

Brain structural correlates of schizotypal signs and subclinical schizophrenia nuclear symptoms in healthy individuals.

BACKGROUND: Subclinical psychotic-like experiences (PLE), resembling key symptoms of psychotic disorders, are common throughout the general population and possibly associated with psychosis risk. There is evidence that such symptoms are also associated with structural brain changes. METHODS: In 672 healthy individuals, we assessed PLE and associated distress with the symptom-checklist-90R (SCL-90R) scales 'schizotypal signs' (STS) and 'schizophrenia nuclear symptoms' (SNS) and analysed associations with voxel- and surfaced-based brain structural parameters derived from structural magnetic resonance imaging at 3 T with CAT12. RESULTS: For SNS, we found a positive correlation with the volume in the left superior parietal lobule and the precuneus, and a negative correlation with the volume in the right inferior temporal gyrus [p < 0.05 cluster-level Family Wise Error (FWE-corrected]. For STS, we found a negative correlation with the volume of the left and right precentral gyrus (p < 0.05 cluster-level FWE-corrected). Surface-based analyses did not detect any significant clusters with the chosen statistical threshold of p < 0.05. However, in exploratory analyses (p < 0.001, uncorrected), we found a positive correlation of SNS with gyrification in the left insula and rostral middle frontal gyrus and of STS with the left precuneus and insula, as well as a negative correlation of STS with gyrification in the left temporal pole. CONCLUSIONS: Our results show that brain structures in areas implicated in schizophrenia are also related to PLE and its associated distress in healthy individuals. This pattern supports a dimensional model of the neural correlates of symptoms of the psychotic spectrum.