White Matter Network Research Articles

Baseline white matter function predicts short-term treatment response in first-episode schizophrenia.

The detection and characterization of functional activities in the gray matter of schizophrenia (SZ) have been widely explored. However, the relationship between resting-state functional signals in the white matter of first-episode SZ and short-term treatment response remains unclear. Thirty-six patients with first-episode SZ and 44 matched healthy controls were recruited in this study. Patients were classified as nonresponders and responders based on response to antipsychotic medication during a single hospitalization. The fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) of white matter were calculated. The relationships between functional changes and clinical features were analyzed. In addition, voxel-based morphometry was performed to analyze the white matter volume. One-way analysis of variance showed significant differences of fALFF and ReHo in the left posterior thalamic radiation and left cingulum (hippocampus) in the patient group, and the areas were regarded as seeds. The FC was calculated between seeds and other white matter networks. Compared with responders, nonresponders showed significantly increased FC between the left cingulum (hippocampus) and left posterior thalamic radiation, splenium of corpus callosum, and left tapetum, and were associated with the changes of clinical assessment. However, there was no difference in white matter volume between groups. Our work provides a novel insight that psycho-neuroimaging-based white matter function holds promise for influencing the clinical diagnosis and treatment of SZ.

Apathy in Patients With Cerebral Amyloid Angiopathy: A Multimodal Neuroimaging Study.

To analyze the prevalence and associated clinical characteristics of apathy in sporadic cerebral amyloid angiopathy and investigate whether apathy was associated with disease burden and disconnections of key structures in the reward circuit through a structural and functional multimodal neuroimaging approach. Thirty-seven participants with probable sporadic cerebral amyloid angiopathy without symptomatic intracranial hemorrhage or dementia (mean age, 73.3 ± 7.2 years, % male = 59.5%) underwent a detailed neuropsychological evaluation, including measures of apathy and depression, and a multimodal MR neuroimaging study. A multiple linear regression analysis was used to assess the association of apathy with conventional small vessel disease neuroimaging markers. A voxel-based morphometry with a small volume correction within regions previously associated with apathy and a whole-brain tract-based spatial statistics were performed to identify differences in the gray matter and white matter between the apathetic and nonapathetic groups. Gray matter regions significantly associated with apathy were further evaluated for their functional alterations as seeds in the seed-based resting-state functional connectivity analysis. Potential confounders, namely, age, sex, and measures of depression, were entered as covariates in all analyses. A higher composite small vessel disease marker score (CAA-SVD) was associated with a higher degree of apathy (standardized coefficient = 1.35 (0.07-2.62), adjusted R2 = 27.90, p = 0.04). Lower gray matter volume of the bilateral orbitofrontal cortices was observed in the apathetic group than in the nonapathetic group (F = 13.20, family-wise error-corrected p = 0.028). The apathetic group demonstrated a widespread decrease in white matter microstructural integrity compared with the nonapathetic group. These tracts connect key regions within and between related reward circuits. Finally, there were no significant functional alterations between the apathetic and nonapathetic groups. Our findings revealed the orbitofrontal cortex as a key region in the reward circuit associated with apathy in sporadic cerebral amyloid angiopathy, independent from depression. Apathy was shown to be associated with a higher CAA-SVD score and an extensive disruption of white matter tracts, which suggested that a higher burden of CAA pathology and the disruption in large-scale white matter networks may underlie manifestations of apathy.

Alterations in white matter integrity and network topological properties are associated with a decrease in global motion perception in older adults.

Previous studies have mainly explored the effects of structural and functional aging of cortical regions on global motion sensitivity in older adults, but none have explored the structural white matter (WM) substrates underlying the age-related decrease in global motion perception (GMP). In this study, random dot kinematogram and diffusion tensor imaging were used to investigate the effects of age-related reductions in WM fiber integrity and connectivity across various regions on GMP. We recruited 106 younger adults and 94 older adults and utilized both tract-based spatial statistics analysis and graph theoretical analysis to comprehensively investigate group differences in WM microstructural and network connections between older and younger adults at the microscopic and macroscopic levels. Moreover, partial correlation analysis was used to explore the relationship between alterations in WM and the age-related decrease in GMP. The results showed that decreased GMP in older adults was related to decreased fractional anisotropy (FA) of the inferior frontal-occipital fasciculus, inferior longitudinal fasciculus, anterior thalamic radiation, superior longitudinal fasciculus, and cingulum cingulate gyrus. Decreased global efficiency of the WM structural network and increased characteristic path length were closely associated with decreased global motion sensitivity. These results suggest that the reduced GMP in older adults may stem from reduced WM integrity in specific regions of WM fiber tracts as well as decreased efficiency of information integration and communication between distant cortical regions, supporting the "disconnection hypothesis" of cognitive aging.

Age and sex differentially shape brain networks in Parkinson's disease.

Age and sex are important individual factors modifying the clinical symptoms of patients with Parkinson's disease (PD). Our goal is to evaluate the effects of age and sex on brain networks and clinical manifestations of PD patients. Parkinson's disease participants (n=198) receiving functional magnetic resonance imaging from Parkinson's Progression Markers Initiative database were investigated. Participants were classified into lower quartile group (age rank: 0%~25%), interquartile group (age rank: 26%~75%), and upper quartile group (age rank: 76%~100%) according to their age quartiles to examine how age shapes brain network topology. The differences of brain network topological properties between male and female participants were also investigated. Parkinson's disease patients in the upper quartile age group exhibited disrupted network topology of white matter networks and impaired integrity of white matter fibers compared to lower quartile age group. In contrast, sex preferentially shaped the small-world topology of gray matter covariance network. Differential network metrics mediated the effects of age and sex on cognitive function of PD patients. Age and sex have diverse effects on brain structural networks and cognitive function of PD patients, highlighting their roles in the clinical management of PD.

Disrupted white matter network of brain structural connectomes in bipolar disorder patients revealed by q-ball imaging

BackgroundStructural and functional brain changes have been found to be associated with altered emotion and cognition in patients with bipolar disorder (BD). Widespread microstructural white matter abnormalities have been observed using traditional structural imaging in BD. q-Ball imaging (QBI) and graph theoretical analysis (GTA) improve the specificity and sensitivity and high accuracy of fiber tracking. We applied QBI and GTA to investigate and compare the structural connectivity alterations and network alterations in patients with and without BD. MethodsSixty-two patients with BD and 62 healthy controls (HCs) completed a MR scan. We evaluated the group differences in generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values by voxel-based statistical analysis with QBI. We also evaluated the group differences in topological parameters of GTA and subnetwork interconnections in network-based statistical analysis (NBS). ResultsThe QBI indices in the BD group were significantly lower than those in the HC group in the corpus callosum, cingulate gyrus, and caudate. The GTA indices indicated that the BD group demonstrated less global integration and higher local segregation than the HC group, but they retained small-world properties. NBS evaluation showed that the majority of the more connected subnetworks in BD occurred in thalamo-temporal/parietal connectivity. ConclusionOur findings supported white matter integrity with network alterations in BD.

Dynamic cortical and tractography atlases of proactive and reactive alpha and high-gamma activities.

Alpha waves-posterior dominant rhythms at 8-12 Hz reactive to eye opening and closure-are among the most fundamental EEG findings in clinical practice and research since Hans Berger first documented them in the early 20th century. Yet, the exact network dynamics of alpha waves in regard to eye movements remains unknown. High-gamma activity at 70-110 Hz is also reactive to eye movements and a summary measure of local cortical activation supporting sensorimotor or cognitive function. We aimed to build the first-ever brain atlases directly visualizing the network dynamics of eye movement-related alpha and high-gamma modulations, at cortical and white matter levels. We studied 28 patients (age: 5-20 years) who underwent intracranial EEG and electro-oculography recordings. We measured alpha and high-gamma modulations at 2167 electrode sites outside the seizure onset zone, interictal spike-generating areas and MRI-visible structural lesions. Dynamic tractography animated white matter streamlines modulated significantly and simultaneously beyond chance, on a millisecond scale. Before eye-closure onset, significant alpha augmentation occurred at the occipital and frontal cortices. After eye-closure onset, alpha-based functional connectivity was strengthened, while high gamma-based connectivity was weakened extensively in both intra-hemispheric and inter-hemispheric pathways involving the central visual areas. The inferior fronto-occipital fasciculus supported the strengthened alpha co-augmentation-based functional connectivity between occipital and frontal lobe regions, whereas the posterior corpus callosum supported the inter-hemispheric functional connectivity between the occipital lobes. After eye-opening offset, significant high-gamma augmentation and alpha attenuation occurred at occipital, fusiform and inferior parietal cortices. High gamma co-augmentation-based functional connectivity was strengthened, whereas alpha-based connectivity was weakened in the posterior inter-hemispheric and intra-hemispheric white matter pathways involving central and peripheral visual areas. Our results do not support the notion that eye closure-related alpha augmentation uniformly reflects feedforward or feedback rhythms propagating from lower to higher order visual cortex, or vice versa. Rather, proactive and reactive alpha waves involve extensive, distinct white matter networks that include the frontal lobe cortices, along with low- and high-order visual areas. High-gamma co-attenuation coupled to alpha co-augmentation in shared brain circuitry after eye closure supports the notion of an idling role for alpha waves during eye closure. These normative dynamic tractography atlases may improve understanding of the significance of EEG alpha waves in assessing the functional integrity of brain networks in clinical practice; they also may help elucidate the effects of eye movements on task-related brain network measures observed in cognitive neuroscience research.

The effect of damage to the white matter network and premorbid intellectual ability on postoperative verbal short-term memory and functional outcome in patients with brain lesions.

Cognitive reserve is the capacity to cope with cognitive decline due to brain damage caused by neurological diseases. Premorbid IQ has been investigated as a proxy for cognitive reserve. To date, no study has focused on the effects of premorbid IQ in patients with brain tumors, considering the damage to white matter tracts. We investigated whether a higher premorbid IQ has a beneficial impact on postoperative verbal short-term memory and functional outcomes in patients with brain tumors. A total of 65 patients with brain tumors (35 right and 30 left hemisphere lesions) and 65 healthy subjects participated in the study. We used multiple regression analysis to examine whether white matter tract damage and premorbid IQ affect postoperative verbal short-term memory, and the interaction effects of premorbid IQ with damage to white matter tract on postoperative verbal short-term memory. Path analysis was used to investigate the relationship between damage to the white matter tract and premorbid IQ on postoperative functional ability. Our results showed that damage to the left arcuate fasciculus affected postoperative functional ability through verbal short-term memory, working memory, and global cognition in patients with left hemisphere lesions. In the right hemisphere lesion group, high premorbid IQ had a positive effect on functional ability by mediating verbal short-term memory, verbal working memory, and global cognition. We found that damage to the eloquent pathway affected postoperative verbal short-term memory regardless of the premorbid IQ level. However, a higher premorbid IQ was associated with better postoperative verbal short-term memory and functional outcomes when the brain lesions were not located in a crucial pathway. Our findings suggest that premorbid IQ and damage to the white matter tracts should be considered predictors of postoperative functional outcomes.

Anxious Brains: A Combined Data Fusion Machine Learning Approach to Predict Trait Anxiety from Morphometric Features.

Trait anxiety relates to the steady propensity to experience and report negative emotions and thoughts such as fear and worries across different situations, along with a stable perception of the environment as characterized by threatening stimuli. Previous studies have tried to investigate neuroanatomical features related to anxiety mostly using univariate analyses and thus giving rise to contrasting results. The aim of this study is to build a predictive model of individual differences in trait anxiety from brain morphometric features, by taking advantage of a combined data fusion machine learning approach to allow generalization to new cases. Additionally, we aimed to perform a network analysis to test the hypothesis that anxiety-related networks have a central role in modulating other networks not strictly associated with anxiety. Finally, we wanted to test the hypothesis that trait anxiety was associated with specific cognitive emotion regulation strategies, and whether anxiety may decrease with ageing. Structural brain images of 158 participants were first decomposed into independent covarying gray and white matter networks with a data fusion unsupervised machine learning approach (Parallel ICA). Then, supervised machine learning (decision tree) and backward regression were used to extract and test the generalizability of a predictive model of trait anxiety. Two covarying gray and white matter independent networks successfully predicted trait anxiety. The first network included mainly parietal and temporal regions such as the postcentral gyrus, the precuneus, and the middle and superior temporal gyrus, while the second network included frontal and parietal regions such as the superior and middle temporal gyrus, the anterior cingulate, and the precuneus. We also found that trait anxiety was positively associated with catastrophizing, rumination, other- and self-blame, and negatively associated with positive refocusing and reappraisal. Moreover, trait anxiety was negatively associated with age. This paper provides new insights regarding the prediction of individual differences in trait anxiety from brain and psychological features and can pave the way for future diagnostic predictive models of anxiety.

Mindful attention promotes control of brain network dynamics for self-regulation and discontinues the past from the present

Mindful attention is characterized by acknowledging the present experience as a transient mental event. Early stages of mindfulness practice may require greater neural effort for later efficiency. Early effort may self-regulate behavior and focalize the present, but this understanding lacks a computational explanation. Here we used network control theory as a model of how external control inputs-operationalizing effort-distribute changes in neural activity evoked during mindful attention across the white matter network. We hypothesized that individuals with greater network controllability, thereby efficiently distributing control inputs, effectively self-regulate behavior. We further hypothesized that brain regions that utilize greater control input exhibit shorter intrinsic timescales of neural activity. Shorter timescales characterize quickly discontinuing past processing to focalize the present. We tested these hypotheses in a randomized controlled study that primed participants to either mindfully respond or naturally react to alcohol cues during fMRI and administered text reminders and measurements of alcohol consumption during 4 wk postscan. We found that participants with greater network controllability moderated alcohol consumption. Mindful regulation of alcohol cues, compared to one's own natural reactions, reduced craving, but craving did not differ from the baseline group. Mindful regulation of alcohol cues, compared to the natural reactions of the baseline group, involved more-effortful control of neural dynamics across cognitive control and attention subnetworks. This effort persisted in the natural reactions of the mindful group compared to the baseline group. More-effortful neural states had shorter timescales than less effortful states, offering an explanation for how mindful attention promotes being present.

Periventricular and juxtacortical characterization of UManitoba-JHU functionally defined human white matter atlas networks.

The open-access UManitoba-JHU functionally defined human white matter (WM) atlas contains specific WM pathways and general WM regions underlying 12 functional brain networks in ICBM152 template space. However, it is not known whether any of these WM networks are disproportionately co-localized with periventricular and/or juxtacortical WM (PVWM and JCWM), which could potentially impact their ability to infer network-specific effects in future studies-particularly in patient populations expected to have disproportionate PVWM and/or JCWM damage. The current study therefore identified intersecting regions of PVWM and JCWM (defined as WM within 5 mm of the ventricular and cortical boundaries) and: (1) the ICBM152 global WM mask, and (2) all 12 UManitoba-JHU WM networks. Dice Similarity Coefficient (DSC), Jaccard Similarity Coefficient (JSC), and proportion of volume (POV) values between PVWM (and JCWM) and each functionally defined WM network were then compared to corresponding values between PVWM (and JCWM) and global WM. Between the 12 WM networks and PVWM, 8 had lower DSC, JSC, and POV; 1 had lower DSC and JSC, but higher POV; and 3 had higher DSC, JSC, and POV compared to global WM. For JCWM, all 12 WM networks had lower DSC, JSC, and POV compared to global WM. The majority of UManitoba-JHU functionally defined WM networks exhibited lower than average spatial similarity with PVWM, and all exhibited lower than average spatial similarity with JCWM. This suggests that they can be used to explore network-specific WM changes, even in patient populations with known predispositions toward PVWM and/or JCWM damage.

Deep Learning Classifies Low- and High-Grade Glioma Patients with High Accuracy, Sensitivity, and Specificity Based on Their Brain White Matter Networks Derived from Diffusion Tensor Imaging.

Classifying low-grade glioma (LGG) patients from high-grade glioma (HGG) is one of the most challenging tasks in planning treatment strategies for brain tumor patients. Previous studies derived several handcrafted features based on the tumor's texture and volume from magnetic resonance images (MRI) to classify LGG and HGG patients. The accuracy of classification was moderate. We aimed to classify LGG from HGG with high accuracy using the brain white matter (WM) network connectivity matrix constructed using diffusion tensor tractography. We obtained diffusion tensor images (DTI) of 44 LGG and 48 HGG patients using routine clinical imaging. Fiber tractography and brain parcellation were performed for each patient to obtain the fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity weighted connectivity matrices. We used a deep convolutional neural network (DNN) for classification and the gradient class activation map (GRAD-CAM) technique to identify the neural connectivity features focused on by the DNN. DNN could classify both LGG and HGG with 98% accuracy. The sensitivity and specificity values were above 0.98. GRAD-CAM analysis revealed a distinct WM network pattern between LGG and HGG patients in the frontal, temporal, and parietal lobes. Our results demonstrate that glioma affects the WM network in LGG and HGG patients differently.

Spotlight on the December 13 Issue

![Graphic][1]</img>#### Notable in Neurology This Week This issue features an article that examines the association of striatal dopamine depletion pattern and white matter networks in Parkinson disease; another investigates the prevalence and patterns of interfacility transfers after seizure-related emergency department visits. A featured Contemporary Issues in Practice, Education, & Research article presents a progress report of the National Institute of Neurological Disorders and Stroke's 2021–2026 Strategic Plan. ### Longitudinal Brain Atrophy Rates in Presymptomatic Carriers of Genetic Frontotemporal Dementia ![Graphic][2]</img> Identifying the timing of brain changes in genetic frontotemporal dementia (FTD) may improve diagnostics, care, … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif

Mapping white matter structural and network alterations in betel quid-dependent chewers using high angular resolution diffusion imaging.

To evaluate brain white matter diffusion characteristics and anatomical network alterations in betel quid dependence (BQD) chewers using high angular resolution diffusion imaging (HARDI). The current study recruited 53 BQD chewers and 37 healthy controls (HC) in two groups. We explored regional diffusion metrics alternations in the BQD group compared with the HC group using automated fiber quantification (AFQ). We further employed the white matter (WM) anatomical network of HARDI to explore connectivity alterations in BQD chewers using graph theory. BQD chewers presented significantly lower FA values in the left and right cingulum cingulate, the left and right thalamic radiation, and the right uncinate. The BQD has a significantly higher RD value in the right uncinate fasciculus than the HC group. At the global WM anatomical network level, global network efficiency (p = 0.008) was poorer and Lp (p = 0.016) was greater in the BQD group. At the nodal WM anatomical network level, nodal efficiency (p < 0.05) was lower in the BQD group. Our findings provide novel morphometric evidence that brain structural changes in BQD are characterized by white matter diffusivity and anatomical network connectivity among regions of the brain, potentially leading to the enhanced reward system and impaired inhibitory control.

Neurobiological mechanisms of psychosis in epilepsy: Findings from neuroimaging studies.

Despite the high prevalence and clinical importance of comorbid psychosis in epilepsy, its neurobiological mechanisms remain understudied. This narrative mini-review aims to provide an overview of recent updates in in vivo neuroimaging studies on psychosis in epilepsy, including structural and diffusion magnetic resonance imaging (MRI) and functional and molecular imaging, and to discuss future directions in this field. While the conventional morphological analysis of structural MRI has provided relatively inconsistent results, advanced methods, including brain network analysis, hippocampal subregion volumetry, and machine learning models, have recently provided novel findings. Diffusion MRI, for example, has revealed a reduction in white matter integrity mainly in the frontal and temporal lobes, as well as a disruption of brain white matter networks. Functional neuroimaging, such as perfusion single-photon emission computed tomography (SPECT) or fluorodeoxyglucose positron emission tomography (FDG-PET), often identifies hyperactivity in various brain regions. The current limitations of these more recent studies may include small and sometimes heterogeneous samples, insufficient control groups, the effects of psychoactive drugs, and the lack of longitudinal analysis. Further investigations are required to establish novel treatments and identify clinical diagnostic or disease-monitoring biomarkers in psychosis in epilepsy.

Hypometabolic and hypermetabolic brain regions in patients with ALS-FTD show distinct patterns of grey and white matter degeneration: A pilot multimodal neuroimaging study

BackgroundUp to 50% of amyotrophic lateral sclerosis (ALS) patients develop some degree of cognitive dysfunction and a small proportion of these develop frontotemporal dementia (FTD). Non-invasive techniques of magnetic resonance imaging (MRI) and [18F]-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET) have demonstrated structural and metabolic abnormalities, respectively, in the brains of such patients with ALS-FTD. Although initial 18F-FDG PET studies in ALS patients showed only hypometabolism of motor and extramotor brain regions, subsequent studies have demonstrated hypermetabolic changes as well. Such contrasting findings prompted us to hypothesize that hypo- and hypermetabolic brain regions in ALS-FTD patients are associated with divergent degeneration of structural grey matter (GM) and white matter (WM). MethodsCerebral glucose metabolic rate (CMRglc), cortical thickness (CT), fractal dimension (FD), and graph theory WM network analyses were performed on clinical MRI and 18F-FDG PET images from 8 ALS-FTD patients and 14 neurologic controls to explore the relationship between GM-WM degeneration and hypo- and hypermetabolic brain regions. ResultsCMRglc revealed significant hypometabolism in frontal and precentral gyrus brain regions, with hypermetabolism in temporal, occipital and cerebellar regions. Cortical thinning was noted in both hypo- and hypermetabolic brain areas. Unlike CT, FD did not reveal widespread GM degeneration in hypo- and hypermetabolic brain regions of ALS-FTD patients. Graph theory analysis showed severe WM degeneration in hypometabolic but not hypermetabolic areas, especially in the right hemisphere. ConclusionOur multimodal MRI-PET study provides insights into potentially differential pathophysiological mechanisms between hypo- and hypermetabolic brain regions of ALS-FTD patients.

Structural brain connectivity predicts early acute pain after mild traumatic brain injury.

Mild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision. We extracted white matter structural connectivity networks and used a machine learning approach to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamiccortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in 2 independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6 months after the collision still predicted mTBI pain at that timepoint (n = 36). These white matter connections were associated with 2 nociceptive psychophysical outcomes tested at a remote body site-namely, conditioned pain modulation and magnitude of suprathreshold pain-and with pain sensitivity questionnaire scores. Our findings demonstrate a stable white matter network, the properties of which determine an important amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.

Investigation of white matter functional networks underlying different behavioral profiles in attention-deficit/hyperactivity disorder.

Cortical functional network alterations have been widely accepted as the neural basis of attention-deficit/hyperactivity disorder (ADHD). Recently, white matter has also been recognized as a novel neuroimaging marker of psychopathology and has been used as a complement to cortical functional networks to investigate brain-behavior relationships. However, disorder-specific features of white matter functional networks (WMFNs) are less well understood than those of gray matter functional networks. In the current study, we constructed WMFNs using a new strategy to characterize behavior-related network features in ADHD. We recruited 46 drug-naïve boys with ADHD and 46 typically developing (TD) boys, and used clustering analysis on resting-state functional magnetic resonance imaging data to generate WMFNs in each group. Intrinsic activity within each network was extracted, and the associations between network activity and behavior measures were assessed using correlation analysis. Nine WMFNs were identified for both ADHD and TD participants. However, boys with ADHD showed a splitting of the inferior corticospinal-cerebellar network and lacked a cognitive control network. In addition, boys with ADHD showed increased activity in the dorsal attention network and somatomotor network, which correlated positively with attention problems and hyperactivity symptom scores, respectively, while they presented decreased activity in the frontoparietal network and frontostriatal network in association with poorer performance in response inhibition, working memory, and verbal fluency. We discovered a dual pattern of white matter network activity in drug-naïve ADHD boys, with hyperactive symptom-related networks and hypoactive cognitive networks. These findings characterize two distinct types of WMFN in ADHD psychopathology.

Altered controllability of white matter networks and related brain function changes in first-episode drug-naive schizophrenia.

Understanding how structural connectivity alterations affect aberrant dynamic function using network control theory will provide new mechanistic insights into the pathophysiology of schizophrenia. The study included 140 drug-naive schizophrenia patients and 119 healthy controls (HCs). The average controllability (AC) quantifying capacity of brain regions/networks to shift the system into easy-to-reach states was calculated based on white matter connectivity and was compared between patients and HCs as well as functional network topological and dynamic properties. The correlation analysis between AC and duration of untreated psychosis (DUP) were conducted to characterize the controllability progression pattern without treatment effects. Relative to HCs, patients exhibited reduced AC in multiple nodes, mainly distributed in default mode network (DMN), visual network (VN), and subcortical regions, and increased AC in somatomotor network. These networks also had impaired functional topology and increased temporal variability in dynamic functional connectivity analysis. Longer DUP was related to greater reductions of AC in VN and DMN. The current study highlighted potential structural substrates underlying altered functional dynamics in schizophrenia, providing a novel understanding of the relationship of anatomic and functional network alterations.

White matter structural and network topological changes in moyamoya disease with limb paresthesia: A study based on diffusion kurtosis imaging

To investigate the structural and network topological changes in the white matter (WM) in MMD patients with limb paresthesia by performing diffusion kurtosis imaging (DKI). A total of 151 MMD patients, including 46 with left-limb paresthesia (MLP), 52 with right-limb paresthesia (MRP), and 53 without paresthesia (MWP), and 28 healthy controls (HCs) underwent whole-brain DKI, while the surgical patients were reexamined 3-4 months after revascularization. The data were preprocessed to calculate the fractional anisotropy (FA) and mean kurtosis (MK) values. Voxel-wise statistics for FA and MK images were obtained by using tract-based spatial statistics (TBSS). Next, the whole-brain network was constructed, and global and local network parameters were analyzed using graph theory. All parameters were compared among the HC, MWP, MLP, and MRP groups, and changes in the MMD patients before and after revascularization were also compared. The TBSS analysis revealed significant reductions in FA and MK in extensive WM regions in the three patient groups. In comparison with the MWP group, the MLP group showed reductions in FA and MK in both right and left WM, mainly in the right WM, while the MRP group mainly showed a reduction in FA in the left WM region and demonstrated no significant change in MK. The graph theoretical analysis showed decreased global network efficiency, increased characteristic path length, and increased sigma in the MWP, MRP, and MLP groups in comparison with the HC group. Among local network parameters, the nodal efficiency decreased in the bilateral MFG and IFGtriang, while the degree decreased in the MFG.L and bilateral IFGtriang. Patients with right-limb paresthesia showed the lowest nodal efficiency and degree in MFG.L and IFGtriang.L, while those with left-limb paresthesia showed the lowest nodal efficiency in MFG.R and IFGtriang.R and the lowest degree in IFGtriang.R. A DKI-based whole-brain structural and network analysis can be used to detect changes in WM damage and network topological changes in MMD patients with limb paresthesia. FA is more sensitive than MK in detecting WM injury, while MFG and IFGtriang are the key nodes related to the development of acroparesthesia.

Association Between White Matter Networks and the Pattern of Striatal Dopamine Depletion in Patients With Parkinson Disease.

Individual variability in nigrostriatal dopaminergic denervation is an important factor underlying clinical heterogeneity in Parkinson disease (PD). This study aimed to explore whether the pattern of striatal dopamine depletion was associated with white matter (WM) networks in PD. A total of 240 newly diagnosed patients with PD who underwent 18F-FP-CIT PET scans and brain diffusion tensor imaging at initial assessment were enrolled in this study. We measured 18F-FP-CIT tracer uptake as an indirect marker for striatal dopamine depletion. Factor analysis-derived striatal dopamine loss patterns were estimated in each patient to calculate the composite scores of 4 striatal subregion factors (caudate, more-affected and less-affected sensorimotor striata, and anterior putamen) based on the availability of striatal dopamine transporter. The WM structural networks that were correlated with the composite scores of each striatal subregion factor were identified using a network-based statistical analysis. A higher composite score of caudate (i.e., relatively preserved dopaminergic innervation in the caudate) was associated with a strong structural connectivity in a single subnetwork comprising the left caudate and left frontal gyri. Selective dopamine loss in the caudate was associated with strong connectivity in the structural subnetwork whose hub nodes were bilateral thalami and left insula, which were connected to the anterior cingulum. However, no subnetworks were correlated with the composite scores of other striatal subregion factors. The connectivity strength of the network with a positive correlation with the composite score of caudate affected the frontal/executive function either directly or indirectly through the mediation of dopamine depletion in the caudate. Our findings indicate that different patterns of striatal dopamine depletion are closely associated with WM structural alterations, which may contribute to heterogeneous cognitive profiles in individuals with PD.