Differential cortical gray matter changes in early- and late-onset patients with amyotrophic lateral sclerosis.

Age at onset may be an important feature associated with distinct subtypes of amyotrophic lateral sclerosis (ALS). Little is known about the neuropathological mechanism of early-onset ALS (EO-ALS) and late-onset ALS (LO-ALS). Ninety ALS patients were divided into EO-ALS and LO-ALS group, and 128 healthy controls were matched into young controls(YCs) and old controls (OCs). A voxel-based morphometry approach was employed to investigate differences in gray matter volume (GMV). Significant age at onset-by-diagnosis interactions were found in the left parietal operculum, left precentral gyrus, bilateral postcentral gyrus, right occipital gyrus, and right orbitofrontal cortex. Post hoc analysis revealed a significant decrease in GMV in all affected regions of EO-ALS patients compared with YCs, with increased GMV in 5 of the 6 brain regions, except for the right orbitofrontal cortex, in LO-ALS patients compared with OCs. LO-ALS patients had a significantly increased GMV than EO-ALS patients after removing the aging effect. Correspondingly, GMV of the left postcentral gyrus correlated with disease severity in the 2 ALS groups. Our findings suggested that the pathological mechanisms in ALS patients with different ages at onset might differ. These findings provide unique insight into the clinical and biological heterogeneity of the 2 ALS subtypes.

Structural and functional abnormalities in first-episode drug-naïve pediatric idiopathic generalized epilepsy.

The aim of this study was to investigate brain structure and corresponding static and dynamic functional connectivity (sFC & dFC) abnormalities in untreated, first-episode pediatric idiopathic generalized epilepsy (IGE), with the goal of better understanding the underlying pathological mechanisms of IGE. Thirty-one children with IGE and 31 age-matched healthy controls (HC) were recruited. Structural magnetic resonance imaging (sMRI) data were acquired, and voxel-based morphometry (VBM) analysis were performed to reveal abnormal gray matter volume (GMV). Moreover, sFC and dFC analyses were conducted using the brain areas exhibiting abnormal GMV as seed regions to explore abnormal functional couplings. Compared to HC, the IGE group exhibited increased GMV in left middle cingulate cortex (MCC) and right parahippocampus (ParaHipp). In addition, the analyses of dFC and sFC with MCC and ParaHipp as seeds revealed more extensive functional connectivity (FC) changes in dFC. Notably, the structurally and functionally abnormal brain areas were primarily localized in the default mode network (DMN). However, our study did not find any significant associations between these altered neuroimaging measurements and clinical outcomes. This study uncovered microstructural changes as well as corresponding sFC and dFC changes in patients with new-onset, untreated pediatric IGE. The affected brain regions were primarily located within the DMN, highlighting the DMN's crucial role in the development of pediatric IGE.

Neural mechanisms of sentence production: a volumetric study of primary progressive aphasia.

Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task. Verb retrieval deficits partly mediated the relationship between L IFG/MFG and performance on the NAVS-SPPT. These findings underscore the importance of L IFG/MFG for sentence production and suggest that this relationship is partly accounted for by verb retrieval deficits, but not phonological loop integrity. In contrast, it is possible that the posterior temporal cortex is associated with auditory short-term memory ability, to the extent that DSF performance is a valid measure of this in aphasia.

Brain functional gradient and structure features in adolescent and adult autism spectrum disorders.

Understanding how function and structure are organized and their coupling with clinical traits in individuals with autism spectrum disorder (ASD) is a primary goal in network neuroscience research for ASD. Atypical brain functional networks and structures in individuals with ASD have been reported, but whether these associations show heterogeneous hierarchy modeling in adolescents and adults with ASD remains to be clarified. In this study, 176 adolescent and 74 adult participants with ASD without medication or comorbidities and sex, age matched healthy controls (HCs) from 19 research groups from the openly shared Autism Brain Imaging Data Exchange II database were included. To investigate the relationship between the functional gradient, structural changes, and clinical symptoms of brain networks in adolescents and adults with ASD, functional gradient and voxel-based morphometry (VBM) analyses based on 1000 parcels defined by Schaefer mapped to Yeo's seven-network atlas were performed. Pearson's correlation was calculated between the gradient scores, gray volume and density, and clinical traits. The subsystem-level analysis showed that the second gradient scores of the default mode networks and frontoparietal network in patients with ASD were relatively compressed compared to adolescent HCs. Adult patients with ASD showed an overall compression gradient of 1 in the ventral attention networks. In addition, the gray density and volumes of the subnetworks showed no significant differences between the ASD and HC groups at the adolescent stage. However, adults with ASD showed decreased gray density in the limbic network. Moreover, numerous functional gradient parameters, but not VBM parameters, in adolescents with ASD were considerably correlated with clinical traits in contrast to those in adults with ASD. Our findings proved that the atypical changes in adolescent ASD mainly involve the brain functional network, while in adult ASD, the changes are more related to brain structure, including gray density and volume. These changes in functional gradients or structures are markedly correlated with clinical traits in patients with ASD. Our study provides a novel understanding of the pathophysiology of the structure-function hierarchy in ASD.

Structural and functional brain alterations in subthreshold depression: A multimodal coordinate-based meta-analysis.

Imaging studies of subthreshold depression (StD) have reported structural and functional abnormalities in a variety of spatially diverse brain regions. However, there is no consensus among different studies. In the present study, we applied a multimodal meta-analytic approach, the Activation Likelihood Estimation (ALE), to test the hypothesis that StD exhibits spatially convergent structural and functional brain abnormalities compared to healthy controls. A total of 31 articles with 25 experiments were included, collectively representing 1001 subjects with StD. We found consistent differences between StD and healthy controls mainly in the left insula across studies with various neuroimaging methods. Further exploratory analyses found structural atrophy and decreased functional activities in the right pallidum and thalamus in StD, and abnormal spontaneous activity converged to the middle frontal gyrus. Coordinate-based meta-analysis found spatially convergent structural and functional impairments in StD. These findings provide novel insights for understanding the neural underpinnings of subthreshold depression and enlighten the potential targets for its early screening and therapeutic interventions in the future.

Gray matter alterations in Huntington's disease: A meta-analysis of VBM neuroimaging studies.

Increasing neuroimaging studies have attempted to identify biomarkers of Huntington's disease (HD) progression. Here, we conducted voxel-based meta-analyses of voxel-based morphometry (VBM) studies on HD to investigate the evolution of gray matter volume (GMV) alterations and explore the effects of genetic and clinical features on GMV changes. A systematic review was performed to identify the relevant studies. Meta-analyses of whole-brain VBM studies were performed to assess the regional GMV changes in all HD mutation carriers, in presymptomatic HD (pre-HD), and in symptomatic HD (sym-HD). A quantitative comparison was performed between pre-HD and sym-HD. Meta-regression analyses were used to explore the effects of genetic and clinical features on GMV changes. Twenty-eight studies were included, comparing a total of 1811 HD mutation carriers [including 1150 pre-HD and 560 sym-HD] and 969 healthy controls (HCs). Pre-HD showed decreased GMV in the bilateral caudate nuclei, putamen, insula, anterior cingulate/paracingulate gyri, middle temporal gyri, and left dorsolateral superior frontal gyrus compared with HCs. Compared with pre-HD, GMV decrease in sym-HD extended to the bilateral median cingulate/paracingulate gyri, Rolandic operculum and middle occipital gyri, left amygdala, and superior temporal gyrus. Meta-regression analyses found that age, mean lengths of CAG repeats, and disease burden were negatively associated with GMV atrophy of the bilateral caudate and right insula in all HD mutation carriers. This meta-analysis revealed the pattern of GMV changes from pre-HD to sym-HD, prompting the understanding of HD progression. The pattern of GMV changes may be biomarkers for disease progression in HD.

Altered gray matter volume and functional connectivity in lung cancer patients with bone metastasis pain.

Bone metastasis pain (BMP) is a severe chronic pain condition. Our previous studies on BMP revealed functional brain abnormalities. However, the potential effect of BMP on brain structure and function, especially gray matter volume (GMV) and related functional networks, have not yet been clearly illustrated. Voxel-based morphometry and functional connectivity (FC) analysis methods were used to investigate GMV and intrinsic FC differences in 45 right-handed lung cancer patients with BMP(+), 37 lung cancer patients without BMP(-), and 45 healthy controls (HCs). Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. Compared to HCs, BMP(+) group exhibited decreased GMV in medial frontal gyrus (MFG) and right middle temporal gyrus (MTG). Compared with BMP(-) group, BMP(+) group exhibited reduced GMV in cerebelum_6_L and left lingual gyrus. However, no regions with significant GMV differences were found between BMP(-) and HCs groups. Receiver operating characteristic analysis indicated the potential classification power of these aberrant regions. Correlation analysis revealed that GMV in the right MTG was positively associated with anxiety in BMP(+) group. Further FC analysis demonstrated enhanced interactions between MFG/right MTG and cerebellum in BMP(+) patients compared with HCs. These results showed that BMP was closely associated with cerebral alterations, which may induce the impairment of pain moderation circuit, deficits in cognitive function, dysfunction of emotional control, and sensorimotor processing. These findings may provide a fresh perspective and further neuroimaging evidence for the possible mechanisms of BMP. Furthermore, the role of the cerebellum in pain processing needs to be further investigated.

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.

Larger putamen in individuals at risk and with manifest bipolar disorder.

BACKGROUND: Individuals at risk for bipolar disorder (BD) have a wide range of genetic and non-genetic risk factors, like a positive family history of BD or (sub)threshold affective symptoms. Yet, it is unclear whether these individuals at risk and those diagnosed with BD share similar gray matter brain alterations. METHODS: In 410 male and female participants aged 17-35 years, we compared gray matter volume (3T MRI) between individuals at risk for BD (as assessed using the EPIbipolar scale; n = 208), patients with a DSM-IV-TR diagnosis of BD (n = 87), and healthy controls (n = 115) using voxel-based morphometry in SPM12/CAT12. We applied conjunction analyses to identify similarities in gray matter volume alterations in individuals at risk and BD patients, relative to healthy controls. We also performed exploratory whole-brain analyses to identify differences in gray matter volume among groups. ComBat was used to harmonize imaging data from seven sites. RESULTS: Both individuals at risk and BD patients showed larger volumes in the right putamen than healthy controls. Furthermore, individuals at risk had smaller volumes in the right inferior occipital gyrus, and BD patients had larger volumes in the left precuneus, compared to healthy controls. These findings were independent of course of illness (number of lifetime manic and depressive episodes, number of hospitalizations), comorbid diagnoses (major depressive disorder, attention-deficit hyperactivity disorder, anxiety disorder, eating disorder), familial risk, current disease severity (global functioning, remission status), and current medication intake. CONCLUSIONS: Our findings indicate that alterations in the right putamen might constitute a vulnerability marker for BD.

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

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

The vmPFC-IPL functional connectivity as the neural basis of future self-continuity impacted procrastination: the mediating role of anticipated positive outcomes.

Procrastination is universally acknowledged as a problematic behavior with wide-ranging consequences impacting various facets of individuals' lives, including academic achievement, social accomplishments, and mental health. Although previous research has indicated that future self-continuity is robustly negatively correlated with procrastination, it remains unknown about the neural mechanisms underlying the impact of future self-continuity on procrastination. To address this issue, we employed a free construction approach to collect individuals' episodic future thinking (EFT) thoughts regarding specific procrastination tasks. Next, we conducted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analysis to explore the neural substrates underlying future self-continuity. Behavior results revealed that future self-continuity was significantly negatively correlated with procrastination, and positively correlated with anticipated positive outcome. The VBM analysis showed a positive association between future self-continuity and gray matter volumes in the right ventromedial prefrontal cortex (vmPFC). Furthermore, the RSFC results indicated that the functional connectivity between the right vmPFC and the left inferior parietal lobule (IPL) was positively correlated with future self-continuity. More importantly, the mediation analysis demonstrated that anticipated positive outcome can completely mediate the relationship between the vmPFC-IPL functional connectivity and procrastination. These findings suggested that vmPFC-IPL functional connectivity might prompt anticipated positive outcome about the task and thereby reduce procrastination, which provides a new perspective to understand the relationship between future self-continuity and procrastination.

Grey matter structure within the visual networks in migraine with aura: multivariate and univariate analyses.

BACKGROUND: The visual cortex is involved in the generation of migraine aura. Voxel-based multivariate analyses applied to this region may provide complementary information about aura mechanisms relative to the commonly used mass-univariate analyses. METHODS: Structural images constrained within the functional resting-state visual networks were obtained in migraine patients with (n = 50) and without (n = 50) visual aura and healthy controls (n = 50). The masked images entered a multivariate analysis in which Gaussian process classification was used to generate pairwise models. Generalizability was assessed by five-fold cross-validation and non-parametric permutation tests were used to estimate significance levels. A univariate voxel-based morphometry analysis was also performed. RESULTS: A multivariate pattern of grey matter voxels within the ventral medial visual network contained significant information related to the diagnosis of migraine with visual aura (aura vs. healthy controls: classification accuracy = 78%, p < 0.001; area under the curve = 0.84, p < 0.001; migraine with aura vs. without aura: classification accuracy = 71%, p < 0.001; area under the curve = 0.73, p < 0.003). Furthermore, patients with visual aura exhibited increased grey matter volume in the medial occipital cortex compared to the two other groups. CONCLUSIONS: Migraine with visual aura is characterized by multivariate and univariate patterns of grey matter changes within the medial occipital cortex that have discriminative power and may reflect pathological mechanisms.

Frontal deficits and atrophy in a patient with familial encephalopathy with neuroserpin inclusion bodies detected by single-case voxel-based morphometry: a case report.

BACKGROUND: Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare genetic disorder characterized by progressive cognitive decline and myoclonic epilepsy, caused by pathogenic variants of SERPINI1. We reported a case of genetically confirmed FENIB with de novo H338R mutation in the SERPINI1, in which frontal deficits including inattention and disinhibition, and relevant atrophy in the vmPFC on brain MRI were observed in the early stage of the disease. CASE PRESENTATION: A 23-year-old Japanese man presented with progressive inattention and disinhibition over 4 years followed by myoclonic epilepsy. The whole-genome sequencing and filtering analysis showed de novo heterozygous H338R mutation in the SERPINI1, confirming the diagnosis of FENIB. Single-case voxel-based morphometry using brain magnetic resonance imaging obtained at the initial visit revealed focal gray matter volume loss in the ventromedial prefrontal cortices, which is presumed to be associated with inattention and disinhibition. CONCLUSION: Frontal deficits including inattention and disinhibition can be the presenting symptoms of patients with FENIB. Single-case voxel-based morphometry may be useful for detecting regional atrophy of the frontal lobe in FENIB. Detecting these abnormalities in the early stage of disease may be key findings for differentiating FENIB from other causes of progressive myoclonic epilepsy.

Supplementary motor area driving changes of structural brain network in blepharospasm.

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural MRI was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis and functional decoding were subsequently performed to map the causal effect of grey matter change pattern, hierarchical topography and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater grey matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased grey matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater grey matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased grey matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of grey matter abnormalities.

Identification of biopsychological trait markers in functional neurological disorders.

Stress is a well-known risk factor to develop a functional neurological disorder, a frequent neuropsychiatric medical condition in which patients experience a variety of disabling neurological symptoms. Only little is known about biological stress regulation, and how it interacts with predisposing biological and psychosocial risk factors. Dysregulation of the hypothalamic-pituitary-adrenal axis in patients with functional neurological disorders has been postulated, but its relationship to preceding psychological trauma and brain anatomical changes remains to be elucidated. We set out to study the hypothalamic-pituitary-adrenal axis analysing the cortisol awakening response and diurnal baseline cortisol in 86 patients with mixed functional neurological symptoms compared to 76 healthy controls. We then examined the association between cortisol regulation and the severity and duration of traumatic life events. Finally, we analysed volumetric brain alterations in brain regions particularly sensitive to psychosocial stress, acting on the assumption of the neurotoxic effect of prolonged cortisol exposure. Overall, patients had a significantly flatter cortisol awakening response (P < 0.001) and reported longer (P = 0.01) and more severe (P < 0.001) emotional neglect as compared to healthy controls. Moreover, volumes of the bilateral amygdala and hippocampus were found to be reduced in patients. Using a partial least squares correlation, we found that in patients, emotional neglect plays a role in the multivariate pattern between trauma history and hypothalamic-pituitary-adrenal axis dysfunction, while cortisol did not relate to reduced brain volumes. This suggests that psychological stress acts as a precipitating psychosocial risk factor, whereas a reduced brain volume rather represents a biological predisposing trait marker for the disorder. Contrarily, an inverse relationship between brain volume and cortisol was found in healthy controls, representing a potential neurotoxic effect of cortisol. These findings support the theory of reduced subcortical volumes representing a predisposing trait factor in functional neurological disorders, rather than a state effect of the illness. In summary, this study supports a stress-diathesis model for functional neurological disorders and showed an association between different attributes of trauma history and abnormalities in hypothalamus-pituitary-adrenal axis function. Moreover, we suggest that reduced hippocampal and amygdalar volumes represent a biological 'trait marker' for functional neurological disorder patients, which might contribute to a reduced resilience to stress.

White and Gray Matter Abnormalities in Young Adult Females with Dependent Personality Disorder: A Diffusion-Tensor Imaging and Voxel-Based Morphometry Study.

We applied diffusion-tensor imaging (DTI) including measurements of fractional anisotropy (FA), a parameter of neuronal fiber integrity, mean diffusivity (MD), a parameter of brain tissue integrity, as well as voxel-based morphometry (VBM), a measure of gray and white matter volume, to provide a basis to improve our understanding of the neurobiological basis of dependent personality disorder (DPD). DTI was performed on young girls with DPD (N = 17) and young female healthy controls (N = 17). Tract-based spatial statistics (TBSS) were used to examine microstructural characteristics. Gray matter volume differences between the two groups were investigated using voxel-based morphometry (VBM). The Pearson correlation analysis was utilized to examine the relationship between distinct brain areas of white matter and gray matter and the Dy score on the MMPI. The DPD had significantly higher fractional anisotropy (FA) values than the HC group in the right retrolenticular part of the internal capsule, right external capsule, the corpus callosum, right posterior thalamic radiation (include optic radiation), right cerebral peduncle (p < 0.05), which was strongly positively correlated with the Dy score of MMPI. The volume of gray matter in the right postcentral gyrus and left cuneus in DPD was significantly increased (p < 0.05), which was strongly positively correlated with the Dy score of MMPI (r1,2= 0.467,0.353; p1,2 = 0.005,0.04). Our results provide new insights into the changes in the brain structure in DPD, which suggests that alterations in the brain structure might implicate the pathophysiology of DPD. Possible visual and somatosensory association with motor nerve circuits in DPD.

Neural basis of writing in prodromal to mild dementia with lewy bodies.

OBJECTIVES: We have previously demonstrated difficulties in written production in dementia with Lewy bodies (DLB) patients. We now aim to determine the neural correlates of writing production in DLB, combining clinical data and structural MRI measures. METHOD: Sixteen prodromal to mild DLB patients were selected to participate in the study. The GREMOTS test was used to assess writing production. Using three-dimensional T1 brain MRI images, correlations between the GREMOTS test and grey matter (GM) volume were performed using voxel-based morphometry (VBM; SPM12, XjView and Matlab R2021b softwares). RESULTS: VBM analysis (p < 0.001, uncorrected) revealed a positive and significant correlation between both left anterior insula and left supramarginal gyrus GM volumes and DLB patients' ability to write logatoms using the phonological route. The handwriting deficit was negatively and significantly correlated to the supplementary motor area. The parkinsonism-like characteristics of agraphia were negatively and significantly correlated with both right anterior and right posterior cerebellum GM volumes. Our study also revealed a negative and significant correlation between grammatical spelling impairments and an area of the orbitofrontal gyrus, and a negative and significant correlation between supramarginal gyrus and general slowness in dictation tasks. CONCLUSION: Writing disorders in early DLB patients appears to be GM decreases in several brain regions, such as the left anterior insula, the left supramaginal gyrus, as well as two areas of the right cerebellum.

Removing outliers from the normative database improves regional atrophy detection in single-subject voxel-based morphometry.

PURPOSE: Single-subject voxel-based morphometry (VBM) compares an individual T1-weighted MRI to a sample of normal MRI in a normative database (NDB) to detect regional atrophy. Outliers in the NDB might result in reduced sensitivity of VBM. The primary aim of the current study was to propose a method for outlier removal ("NDB cleaning") and to test its impact on the performance of VBM for detection of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). METHODS: T1-weighted MRI of 81 patients with biomarker-confirmed AD (n = 51) or FTLD (n = 30) and 37 healthy subjects with simultaneous FDG-PET/MRI were included as test dataset. Two different NDBs were used: a scanner-specific NDB (37 healthy controls from the test dataset) and a non-scanner-specific NDB comprising 164 normal T1-weighted MRI from 164 different MRI scanners. Three different quality metrics based on leave-one-out testing of the scans in the NDB were implemented. A scan was removed if it was an outlier with respect to one or more quality metrics. VBM maps generated with and without NDB cleaning were assessed visually for the presence of AD or FTLD. RESULTS: Specificity of visual interpretation of the VBM maps for detection of AD or FTLD was 100% in all settings. Sensitivity was increased by NDB cleaning with both NDBs. The effect was statistically significant for the multiple-scanner NDB (from 0.47 [95%-CI 0.36-0.58] to 0.61 [0.49-0.71]). CONCLUSION: NDB cleaning has the potential to improve the sensitivity of VBM for the detection of AD or FTLD without increasing the risk of false positive findings.

Network dysfunction of sadness facial expression processing and morphometry in euthymic bipolar disorder.

Facial emotion recognition (FER), including sadness, is altered in bipolar disorder (BD). However, the relationship between this impairment and the brain structure in BD is relatively unexplored. Furthermore, its association with clinical variables and with the subtypes of BD remains to be clarified. Twenty euthymic patients with BD type I (BD-I), 28 BD type II (BD-II), and 45 healthy controls completed a FER test and a 3D-T1-weighted magnetic resonance imaging. Gray matter volume (GMV) of the cortico-limbic regions implicated in emotional processing was estimated and their relationship with FER performance was investigated using network analysis. Patients with BD-I had worse total and sadness-related FER performance relative to the other groups. Total FER performance was significantly negatively associated with illness duration and positively associated with global functioning in patients with BD-I. Sadness-related FER performance was also significantly negatively associated with the number of previous manic episodes. Network analysis showed a reduced association of the GMV of the frontal-insular-occipital areas in patients with BD-I, with a greater edge strength between sadness-related FER performance and amygdala GMV relative to controls. Our results suggest that FER performance, particularly for facial sadness, may be distinctively impaired in patients with BD-I. The pattern of reduced interrelationship in the frontal-insular-occipital regions and a stronger positive relationship between facial sadness recognition and the amygdala GMV in BD may reflect altered cortical modulation of limbic structures that ultimately predisposes to emotional dysregulation. Future longitudinal studies investigating the effect of mood state on FER performance in BD are warranted.

A multimodal meta-analysis of regional functional and structural brain abnormalities in obsessive-compulsive disorder.

Numerous neuroimaging studies of resting-state functional imaging and voxel-based morphometry (VBM) have revealed abnormalities in specific brain regions in obsessive-compulsive disorder (OCD), but results have been inconsistent. We conducted a whole-brain voxel-wise meta-analysis on resting-state functional imaging and VBM studies that investigated differences of functional activity and gray matter volume (GMV) between patients with OCD and healthy controls (HCs) using seed-based d mapping (SDM) software. A total of 41 independent studies (51 datasets) for resting-state functional imaging and 42 studies (46 datasets) for VBM were included by a systematic literature search. Overall, patients with OCD displayed increased spontaneous functional activity in the bilateral inferior frontal gyrus (IFG) (extending to the bilateral insula) and bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), as well as decreased spontaneous functional activity in the bilateral paracentral lobule, bilateral cerebellum, left caudate nucleus, left inferior parietal gyri, and right precuneus cortex. For the VBM meta-analysis, patients with OCD displayed increased GMV in the bilateral thalamus (extending to the bilateral cerebellum), right striatum, and decreased GMV in the bilateral mPFC/ACC and left IFG (extending to the left insula). The conjunction analyses found that the bilateral mPFC/ACC, left IFG (extending to the left insula) showed decreased GMV with increased intrinsic function in OCD patients compared to HCs. This meta-analysis demonstrated that OCD exhibits abnormalities in both function and structure in the bilateral mPFC/ACC, insula, and IFG. A few regions exhibited only functional or only structural abnormalities in OCD, such as the default mode network, striatum, sensorimotor areas, and cerebellum. It may provide useful insights for understanding the underlying pathophysiology of OCD and developing more targeted and efficacious treatment and intervention strategies.