Subsystem mechanisms of default mode network underlying white matter hyperintensity-related cognitive impairment.

Functional changes of default mode network (DMN) have been proven to be closely associated with white matter hyperintensity (WMH) related cognitive impairment (CI). However, subsystem mechanisms of DMN underlying WMH-related CI remain unclear. The present study recruited WMH patients (n = 206) with mild CI and normal cognition, as well as healthy controls (HC, n = 102). Static/dynamic functional connectivity (FC) of the DMN's three subsystems were calculated using resting-state functional MRI. K-means clustering analyses were performed to extract distinct dynamic connectivity states. Compared with the WMH-NC group, the WMH-MCI group displayed lower static FC within medial temporal lobe (MTL) and core subsystem, between core-MTL subsystem, as well as between core and dorsal medial prefrontal cortex subsystem. All these static alterations were positively associated with information processing speed (IPS). Regarding dynamic FC, the WMH-MCI group exhibited higher dynamic FC within MTL subsystem than the HC and WMH-NC groups. Altered dynamic FC within MTL subsystem mediated the relationship between WMH and memory span (indirect effect: -0.2251, 95% confidence interval [-0.6295, -0.0267]). Additionally, dynamic FCs of DMN subsystems could be clustered into two recurring states. For dynamic FCs within MTL subsystem, WMH-MCI subjects exhibited longer mean dwell time (MDT) and higher reoccurrence fraction (RF) in a sparsely connected state (State 2). Altered MDT and RF in State 2 were negatively associated with IPS. Taken together, these findings indicated static/dynamic FC of DMN subsystems can provide relevant information on cognitive decline from different aspects, which provides a comprehensive view of subsystem mechanisms of DMN underlying WMH-related CI.

Lower cerebrovascular reactivity in prefrontal cortex and weaker negative functional connectivity between prefrontal cortex and insula contribute to white matter hyperintensity-related anxiety or depression.

BACKGROUND: White matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms. METHODS: Participants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The CVR and FC maps were constructed from resting-state functional MRI. Two-way analysis of covariance with fixed factors A/D and WMH was performed to identify regional CVR abnormalities. Seed-based FC analyses were then conducted on regions with WMH × A/D interaction effects on CVR. Logistic regression models were constructed to examine the utility of these measurements for identifying WMH-related A/D. RESULTS: Participants with WMH related A/D exhibited significantly greater CVR in left insula and lower CVR in right superior frontal gyrus (SFG.R), and HAMA scores were negatively correlated with CVR in SFG.R (r = -0.156, P = 0.016). Insula-SFG.R negative FC was significantly weaker in WMH patients with suspected or definite A/D. A model including CVR plus FC changes identified WMH-associated A/D with highest sensitivity and specificity. In contrast, NCs with A/D exhibited greater CVR in prefrontal cortex and stronger FC within the default mode network (DMN) and between the DMN and executive control network. LIMITATIONS: This cross-sectional study requires validation by longitudinal and laboratory studies. CONCLUSIONS: Impaired CVR in SFG.R and weaker negative FC between prefrontal cortex and insula may contribute to WMH-related A/D, providing potential diagnostic imaging markers and therapeutic targets.

Stride length and cerebellar regulation: Key features of early gait disorder in cerebral small vessel disease.

OBJECTIVES: Gait disorder (GD) is a common problem in cerebral small vessel disease (CSVD). This study aimed to determine (1) the early characteristics of GD in CSVD, (2) cerebellar neuroimaging features related to GD in CSVD, and (3) the association of cognitive impairment with GD. METHODS: In total, 183 subjects were enrolled in this study: patients with CSVD with normal cognitive function (CSVD-NC) group (64 subjects), patients with CSVD with mild cognitive impairment (CSVD-MCI) group (66 subjects), and a healthy control (HC) group (53 subjects). The GD patterns were evaluated using the ReadyGo three-dimensional motion balance testing system. Meanwhile, we analyzed the cerebrum and cerebellum structurally and functionally. Correlation analyses were conducted among gait indicators, neuroimaging features, and neuropsychological tests. RESULTS: Both the CSVD-NC and CSVD-MCI groups had a reduced stride length, cortical atrophy in the left cerebellum VIIIb, and decreased functional connectivity between the left cerebellum VIIIb and left SFGmed compared with the HC group. In the correlation analysis, the gray matter probability of the left cerebellum VIIIb was closely related to stride length in the HC group. In the CSVD-MCI group, linguistic function, memory, and attention were significantly correlated with gait performance. CONCLUSION: Decreased stride length was the earliest characteristic of GD in CSVD. Structural and functional regulation of the left cerebellum VIIIb could play a particularly important role in early GD in CSVD.

Connectome gradient dysfunction contributes to white matter hyperintensity-related cognitive decline.

BACKGROUND: Although white matter hyperintensity (WMH) is closely associated with cognitive decline, the precise neurobiological mechanisms underlying this relationship are not fully elucidated. Connectome studies have identified a primary-to-transmodal gradient in functional brain networks that support the spectrum from sensation to cognition. However, whether connectome gradient structure is altered as WMH progresses and how this alteration is associated with WMH-related cognitive decline remain unknown. METHODS: A total of 758 WMH individuals completed cognitive assessment and resting-state functional MRI (rs-fMRI). The functional connectome gradient was reconstructed based on rs-fMRI by using a gradient decomposition framework. Interrelations among the spatial distribution of WMH, functional gradient measures, and specific cognitive domains were explored. RESULTS: As the WMH volume increased, the executive function (r = -0.135, p = 0.001) and information-processing speed (r = -0.224, p = 0.001) became poorer, the gradient range (r = -0.099, p = 0.006), and variance (r = -0.121, p < 0.001) of the primary-to-transmodal gradient reduced. A narrower gradient range (r = 0.131, p = 0.001) and a smaller gradient variance (r = 0.136, p = 0.001) corresponded to a poorer executive function. In particular, the relationship between the frontal/occipital WMH and executive function was partly mediated by gradient range/variance of the primary-to-transmodal gradient. CONCLUSIONS: These findings indicated that WMH volume, the primary-to-transmodal gradient, and cognition were interrelated. The detrimental effect of the frontal/occipital WMH on executive function was partly mediated by the decreased differentiation of the connectivity pattern between the primary and transmodal areas.

Altered neuroimaging patterns of cerebellum and cognition underlying the gait and balance dysfunction in cerebral small vessel disease.

Background: The mechanism of gait and balance dysfunction (GBD) in cerebral small vessel disease (CSVD) remains unclear. Evidence supports cognition engages in GBD of CSVD. The cerebellum is important in motor and cognition, while little is known about the influence of the cerebellum on GBD in CSVD. Methods: This study is a retrospective cohort study. All participants of this study were enrolled from the CSVD individuals in Nanjing Drum Tower Hospital from 2017 to 2021. The GBD of CSVD patients was defined as Tinetti Test score ≤ 23. Cerebral cortical thickness, cerebellar gray matter volume, the amplitude of low-frequency fluctuation, functional connectivity, and modular interaction were calculated to determine the cortical atrophy and activity patterns of CSVD patients with GBD. The effect of cognitive domains during GBD in CSVD patients was explored by correlation analyses. Results: A total of 25 CSVD patients were recruited in CSVD patients with GBD group (Tinetti Test score ≤ 23, mean age ± standard deviation: 70.000 ± 6.976 years), and 34 CSVD patients were recruited in CSVD patients without GBD group (Tinetti Test score > 23, mean age ± standard deviation: 64.029 ± 9.453 years). CSVD patients with GBD displayed worse cognitive performance and cortical atrophy in the right cerebellum VIIIa and bilateral superior temporal gyrus than those without GBD. The right postcentral gyrus, left inferior temporal gyrus, right angular gyrus, right supramarginal gyrus and right middle frontal gyrus were functionally overactivated and showed decreased modular interaction with the right cerebellum. Tinetti Test scores were negatively related to the volume of the right cerebellum VIIIa in CSVD patients with GBD. Notably, memory, especially visuospatial memory, was greatly associated with GBD in CSVD. Conclusion: The cortical atrophy and altered functional activity in sensorimotor area and ventral attention network in the cerebellum and cerebrum may underlying the GBD in CSVD. Memory might be critically cognitively responsible for GBD in CSVD.

Intracranial Atherosclerotic Stenosis Is Associated with Cognitive Impairment in Patients with Nondisabling Ischemic Stroke: A pCASL-Based Study.

Background: Intracranial atherosclerotic stenosis (ICAS) is a key risk factor for vascular cognitive impairment. Cerebral blood flow (CBF) and the spatial coefficient of variation (sCoV) of CBF images (based on pseudocontinuous arterial spin labeling) are used to explore abnormal cerebral perfusion. We aimed to probe the mechanisms underlying cognitive impairment in patients with nondisabling anterior circulation macrovascular disease. Methods: This study included 47 patients with ICAS or occlusion and 40 controls. All participants underwent global and individual neuropsychology assessments and magnetic resonance imaging scan. The correlations between cognitive function and abnormal perfusion were explored. Results: The CBF in the ipsilateral middle cerebral artery (MCA) territory of the lesion side decreased significantly, while it increased on the contralateral side. CBF value had a significant correlation with the memory function in the right cerebral artery lesion group. The sCoV in both gray matter (GM) and the ipsilateral MCA territory of the lesion increased significantly. The sCoV value based on the GM territory or MCA territory was significantly correlated with global cognitive function, memory function, and executive function in patients with ICAS. Conclusions: The cognitive function of patients with severe ICAS or occlusion in anterior circulation was significantly impaired. sCoV could be a better indicator of cognitive impairment than CBF. Interventions to relieve vascular stenosis or occlusion and delay cognitive impairment or improve cognitive function should be actively considered.

Glymphatic Dysfunction Mediates the Influence of White Matter Hyperintensities on Episodic Memory in Cerebral Small Vessel Disease.

Glymphatic dysfunction has been linked to cognitive decline in several neurodegenerative diseases. In cerebral small vessel disease (CSVD), the mechanism of white matter hyperintensities (WMH)-related cognitive impairment (CI) is still under investigation. The diffusion tensor image (DTI) analysis along the perivascular space (ALPS) method has been considered to be a reliable parameter to evaluate glymphatic function. Therefore, we applied the ALPS-index to determine the influence of glymphatic function on CI in CSVD. In total, 137 CSVD patients (normal cognitive group, mild CI group, and dementia group) and 52 normal controls were included in this study. The ALPS-index was calculated based on the DTI. Correlation analyses and mediation analysis were conducted to examine the relationship between glymphatic function and cognition. Remarkable differences in the ALPS-index were observed between subjects with and without CI. The ALPS-index was negatively correlated with age, WMH volume, and general cognitive function in all CSVD patients. In the mild CI group, the ALPS-index was independently positively related to episodic memory, and mediated the relationship between WMH volume and episodic memory. In conclusion, the ALPS-index is a potential marker for early recognition of CI in CSVD. Glymphatic dysfunction mediates the relationship between WMH and CI in CSVD.

Using the Chinese Smell Identification Test to explore olfactory function in Parkinson's disease.

Introduction: The Chinese Smell Identification Test (CSIT) was developed specifically for Chinese populations. This work investigated the utility of this test in detecting Parkinson's disease (PD). Olfactory dysfunction is a common non-motor symptom of PD. There are different opinions on the efficacy of drugs for anosmia in PD.Objective: To investigate the olfactory function of Chinese PD patients, verify the effectiveness of the CSIT, and further detect the effects of dopaminergic drugs on anosmia.Methods: In total, 149 PD patients were recruited from the First Affiliated Hospital of Anhui Medical University and 149 healthy comparison participants (HCP) were recruited from the Institute of Psychology of the Chinese Academy of Sciences. The CSIT was used for olfactory function testing in all participants.Results: CSIT scores were significantly lower in the PD group than in the HCP group (t(296) = -12.797, P < 0.001, d = 1.48). Receiver operating characteristic curve analysis showed that the optimal threshold value for the olfactory recognition test was 22.5, which had a sensitivity and specificity of 71.1% and 89.3%, respectively, for the detection of Parkinson's disease. Sex showed a significant influence on CSIT score (t = -3.552, P = 0.001), with males being more likely to develop olfactory dysfunction. We found CSIT scores of the non-medication group and the group with medication were lower than those of the HCP group, and the difference was statistically significant (t(82) = -7.116, P < 0.0167, d = 1.59; t(82) = -4.907, P < 0.0167, d = 1.10). CSIT scores of the group with medication were significantly higher than those of the non-medication group (t(41) = -3.067, P < 0.0167, d = 0.41).Conclusions: In China, the CSIT is recommended to improve the sensitivity of PD detection. The olfactory function of PD patients was improved after treatment with dopaminergic drugs.

Enhanced cerebro-cerebellar functional connectivity reverses cognitive impairment following electroconvulsive therapy in major depressive disorder.

Electroconvulsive therapy (ECT), a rapidly acting and effective treatment for major depressive disorder (MDD), is frequently accompanied by cognitive impairment. Recent studies have documented that ECT reorganizes dysregulated inter/intra- connected cerebral networks, including the affective network, the cognitive control network(CCN) and default mode network (DMN).Moreover, cerebellum is thought to play an important role in emotion regulation and cognitive processing. However, little is known about the relationship between cerebro-cerebellar connectivity alterations following ECT and antidepressant effects or cognitive impairment. We performed seed-based resting-state functional connectivity (RSFC) analyses in 28 MDD patients receiving ECT and 20 healthy controls to identify cerebro-cerebellar connectivity differences related to MDD and changes induced by ECT. Six seed regions (three per hemisphere) in the cerebrum were selected for RSFC, corresponding to the affective network, CCN and DMN, to establish cerebro-cerebellar functional connectivity with cerebellum. MDD patients showed increased RSFC between left sgACC and left cerebellar lobule VI after ECT. Ggranger causality analyses (GCA) identified the causal interaction is from left cerebellar lobule VI to left sgACC. Furthermore, increased effective connectivity from left cerebellar lobule VI to left sgACC exhibited positively correlated with the change in verbal fluency test (VFT) score following ECT (r = 0.433, p = 0.039). Our findings indicate that the enhanced cerebro-cerebellar functional connectivity from left lobule VI to left sgACC may ameliorate cognitive impairment induced by ECT. This study identifies a potential neural pathway for mitigation of cognitive impairment following ECT.

The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities.

OBJECTIVE: White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances. METHODS: A total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored. RESULTS: The analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs. CONCLUSION: Our study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.

Abnormal Degree Centrality in White Matter Hyperintensities: A Resting-State Functional Magnetic Resonance Imaging Study.

Background: White matter hyperintensities (WMHs) are a common occurrence with aging and are associated with cognitive impairment. However, the neurobiological mechanisms of WMHs remain poorly understood. Functional magnetic resonance imaging (fMRI) is a prominent tool that helps in non-invasive examinations and is increasingly used to diagnose neuropsychiatric diseases. Degree centrality (DC) is a common and reliable index in fMRI, which counts the number of direct connections for a given voxel in a network and reflects the functional connectivity within brain networks. We explored the underlying mechanism of cognitive impairment in WMHs from the perspective of DC. Methods: A total of 104 patients with WMHs and 37 matched healthy controls (HCs) were enrolled in the current study. All participants underwent individual and overall cognitive function tests and resting-state fMRI (rs-fMRI). WMHs were divided into three groups (39 mild WMHs, 37 moderate WMHs, and 28 severe WMHs) according to their Fazekas scores, and the abnormal DC values in the WMHs and HCs groups were analyzed. Results: There was a significant difference in the right inferior frontal orbital gyrus and left superior parietal gyrus between the WMHs and HCs groups. The functional connectivity between the right inferior frontal orbital gyrus and left inferior temporal gyrus, left superior parietal gyrus, and left parietal inferior gyrus was also different in the WMHs group. Conclusion: The change in DC value may be one of the underlying mechanisms of cognitive impairment in individuals with WMHs, which provides us with a new approach to delaying cognitive impairment in WMHs.

Bifrontal electroconvulsive therapy changed regional homogeneity and functional connectivity of left angular gyrus in major depressive disorder.

Electroconvulsive therapy (ECT) is a rapid and effective treatment for MDD. However, the mechanism of ECT for MDD has not been clarified. In this study, we used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the mechanism of ECT. Two groups of subjects were recruited: healthy controls (HCs) and MDD patients who received bifrontal ECT. MDD patients and HCs underwent rs-fMRI scans and clinical assessments (Hamilton Depression Rating Scale, Rey-Auditory Verbal Learning Test (RAVLT), and the verbal fluency test). Regional homogeneity (ReHo) and functional connectivity were evaluated for the analysis of rs-fMRI data. The results showed that ReHo values in the left angular gyrus (LAG) significantly increased in MDD patients after ECT, and the functional connectivity of the LAG with bilateral inferior temporal gyrus, bilateral middle frontal gyrus, left superior frontal gyrus, left middle temporal gyrus, left precuneus, left posterior cingulate gyrus, and right angular gyrus was found to be strengthened after ECT. The scores of delayed recall trial in the RAVLT of MDD patients were related to the functional connectivity of the LAG with the left inferior temporal gyrus and the left posterior cingulate gyrus. It indicated LAG palyed an important role in the mechanism of ECT in MDD.

Automatic Construction and Global Optimization of a Multisentiment Lexicon.

Manual annotation of sentiment lexicons costs too much labor and time, and it is also difficult to get accurate quantification of emotional intensity. Besides, the excessive emphasis on one specific field has greatly limited the applicability of domain sentiment lexicons (Wang et al., 2010). This paper implements statistical training for large-scale Chinese corpus through neural network language model and proposes an automatic method of constructing a multidimensional sentiment lexicon based on constraints of coordinate offset. In order to distinguish the sentiment polarities of those words which may express either positive or negative meanings in different contexts, we further present a sentiment disambiguation algorithm to increase the flexibility of our lexicon. Lastly, we present a global optimization framework that provides a unified way to combine several human-annotated resources for learning our 10-dimensional sentiment lexicon SentiRuc. Experiments show the superior performance of SentiRuc lexicon in category labeling test, intensity labeling test, and sentiment classification tasks. It is worth mentioning that, in intensity label test, SentiRuc outperforms the second place by 21 percent.