Zhujing Shen

Influence of regional iron on the motor impairments of Parkinson's disease: A quantitative susceptibility mapping study

Because the roles of striatal‐thalamo‐cortical and cerebello‐thalamo‐cortical circuits in the heterogeneous motor impairments of Parkinsons disease (PD) are becoming recognized, this study was designed to investigate the relationships between regional iron in the cardinal subcortical nuclei in these circuits and the different motor impairments.

Severity of dependence modulates smokers’ functional connectivity in the reward circuit: a preliminary study

RationaleNicotine dependence is characterized as a neural circuit dysfunction, particularly with regard to the reward circuit. Although dependence severity moderates cue reactivity in the brain regions involved in reward processing, the direction of its influence remains controversial.ObjectivesInvestigating the functional organization of the reward circuit may provide complementary information. Here, we used resting-state functional connectivity (rsFC) to evaluate the integrity of the reward circuit in smokers with different severities of nicotine dependence.MethodsTotals of 65 smokers and 37 non-smokers underwent resting-state functional magnetic resonance imaging (fMRI). The smokers were divided into low-dependent (FTND < 5, n = 26) and high-dependent smoker groups (FTND ≥ 5, n = 39) based on their nicotine-dependence severity (as measured by the Fagerström test for nicotine dependence [FTND]). The region of interest (ROI)-wise rsFC within the reward circuit was compared between smokers and non-smokers as well as between low-dependent and high-dependent smokers and then correlated with smokers’ FTND scores.ResultsWidespread rsFC attenuation was observed in the reward circuit of smokers compared with non-smokers. Compared with low-dependent smokers, high-dependent smokers showed greater rsFC between the right amygdala and the left nucleus accumbens (NAcc) as well as between the bilateral hippocampus. Furthermore, a positive correlation between the inter-hippocampus rsFC and the severity of nicotine dependence (FTND) was detected among all smokers (r = 0.416, p = 0.001).ConclusionsOur results indicate a dysfunction of the reward circuit in nicotine-dependent individuals. Moreover, our study improves the understanding of the neuroplastic changes that occur during the development of nicotine dependence.

Altered human brain anatomy in chronic smokers: a review of magnetic resonance imaging studies

Cigarette smoking is becoming more prevalent in developing countries, such as China, and is the largest single cause of preventable death worldwide. New emerging reports are highlighting how chronic cigarette smoking plays a role in neural dysfunctions, such as cognitive decline. Basic animal experimental studies have shown that rats undergo persistent pathological brain changes after being given chronic levels of nicotine. What is perhaps less appreciated is the fact that chronic cigarette smoking induces subtle anatomical changes in the human brain. Consequently, this chapter aims to summarize and integrate the existing magnetic resonance imaging studies on both gray- and white-matter marcostructural and microstructural changes. The reviewed studies demonstrate that chronic cigarette smoking results in discrete and localized alterations in brain region tissue (both the gray and white matter of different brain regions), which may, in part, be responsible for different neural dysfunctions. In addition, we further discuss the possible pathological and neurobiological mechanisms of these nicotinic effects on the brain tissue. We will also address the limitations of the current studies on this issue and identify opportunities for future research.

Increased network centrality as markers of relapse risk in nicotine-dependent individuals treated with varenicline

ABSTRACT Identifying smokers at high risk of relapse could improve the effectiveness of cessation therapies. Although altered regional brain function in smokers has been reported, whether the whole‐brain functional organization differs smokers with relapse vulnerability from others remains unclear. Thus, the goal of this study is to investigate the baseline functional connectivity differences between relapsers and quitters. Using resting‐state fMRI, we acquired images from 57 smokers prior to quitting attempts. After 12‐week treatment with varenicline, smokers were divided into relapsers (n = 36) and quitters (n = 21) (quitter: continuously abstinent for weeks 9–12). The smoking cessation outcomes were cross‐validated by self‐reports and expired carbon monoxide. We then used eigenvector centrality (EC) mapping to identify the functional connectivity differences between relapsers and quitters. When compared to quitters, increased EC in the right dorsolateral prefrontal cortex (DLPFC), left middle temporal gyrus (MTG) and cerebellum anterior lobe was observed in relapsers. In addition, a logistic regression analysis of EC data (with DLPFC, MTG and cerebellum included) predicted relapse with 80.7% accuracy. These findings suggest that the DLPFC, MTG and cerebellum may be important substrates of smoking relapse vulnerability. The data also suggest that relapse‐vulnerable smokers can be identified before quit attempts, which could enable personalized treatment and improve smoking cessation outcomes. HIGHLIGHTSSmokers who relapse in smoking cessation showed higher functional connectivity in the right DLPFC, left MTG and cerebellum.The functional connectivity in DLPFC, MTG and cerebellum were predictors of smoking relapse.These results may aid to understand the mechanism of smoking relapse and improve cessation treatment.

Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study

Objective It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data. Method There were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years’ follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimers disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD. Results We found that APOE ε4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE ε4 carriers had significantly decreased Aβ1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and ε4 allele was related with declining trend of cognition. Conclusion Our findings suggested APOE ε4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and ε4 allele can exert long-term detrimental effects on individuals trajectory of cognition.

Decreased Inter-Hemispheric Functional Connectivity in Cognitively Intact Elderly APOE ɛ4 Carriers: A Preliminary Study

The apolipoprotein E (APOE) ɛ4 allele is the best-known genetic risk factor for developing sporadic Alzheimers disease (AD). According to neuroimaging studies, the APOE ɛ4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE ɛ4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between inter-hemispheric homotopic regions in cognitively intact, elderly APOE ɛ4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE ɛ4 carriers (with at least one copy of APOE ɛ4 allele) and 22 well-matched ɛ3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with ɛ3 homozygotes, APOE ɛ4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE ɛ4 carriers, the inter-hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p <  0.05; r = 0.65, p <  0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p <  0.05). In our study, the presence of the APOE ɛ4 allele was linked with decreased inter-hemispheric RSFC, which was attributed to memory performance in carriers.

Alteration of regional homogeneity and white matter hyperintensities in amnestic mild cognitive impairment subtypes are related to cognition and CSF biomarkers

Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified. Regional homogeneity (ReHo) was employed to analyze regional synchronization. Periventricular white matter hyperintensities (PWMH) and deep WMH (DWMH) volume of each participant was quantitatively assessed. AD biomarkers from CSF were also measured. SD-aMCI showed decreased ReHo in medial temporal gyrus (MTG), and increased ReHo in lingual gyrus (LG) and superior temporal gyrus (STG) relative to controls. MD-aMCI showed decreased ReHo, mostly located in precuneus (PCu), LG and postcentral gyrus (PCG), relative to SD-aMCI and controls. As for microvascular disease, MD-aMCI patients had more PWMH burden than SD-aMCI and controls. Correlation analyses indicated mean ReHo in differenced regions were related with memory, language, and executive function in aMCI patients. However, no significant associations between PWMH and behavioral data were found. The Aβ level was related with the ReHo value of STG in SD-aMCI. MD-aMCI displayed different patterns of abnormal regional synchronization and more severe PWMH burden compared with SD-aMCI. Therefore aMCI is not a uniform disease entity, and MD-aMCI group may show more complicated pathologies than SD-aMCI group.

Longitudinal Alterations of Local Spontaneous Brain Activity in Parkinson’s Disease

Abstract We used resting-state fMRI to evaluate longitudinal alterations in local spontaneous brain activity in Parkinson’s disease (PD) over a 2-year period. Data were acquired from 23 PD patients at baseline and follow-up, and 27 age- and sex-matched normal controls. Regional homogeneity (ReHo) and voxel-based-morphometry (VBM) were used to identify differences in local spontaneous brain activity and grey matter volume. With disease progression, we observed a progressive decrease in ReHo in the sensorimotor cortex, default-mode network, and left cerebellum, but increased ReHo in the supplementary motor area, bilateral temporal gyrus, and hippocampus. Moreover, there was a significant positive correlation between the rates of ReHo change in the left cerebellum and the rates of change in the Unified Parkinson’s Disease Rating Scale-III scores. VBM revealed no significant differences in the grey matter volume among the three sets of acquisitions. We conclude that ReHo may be a suitable non-invasive marker of progression in PD.

Altered spontaneous activity of posterior cingulate cortex and superior temporal gyrus are associated with a smoking cessation treatment outcome using varenicline revealed by regional homogeneity

Compared to nonsmokers, smokers exhibit a number of potentially important differences in regional brain function. However, little is known about the associations between the local spontaneous brain activity and smoking cessation treatment outcomes. In the present analysis, we aimed to evaluate whether the local features of spontaneous brain activity prior to the target quit date was associated with the smoking cessation outcomes. All the participants underwent magnetic resonance imaging scans and smoking-related behavioral assessments. After a 12-week treatment with varenicline, 23 smokers succeeded in quitting smoking and 32 failed. Smokers underwent functional magnetic resonance imaging (fMRI) scanning prior to an open label smoking cessation treatment trial. Regional homogeneity (ReHo) was used to measure spontaneous brain activity, and whole-brain voxel-wise comparisons of ReHo were performed to detect brain regions with altered spontaneous brain activity between relapser and quitter groups. After controlling for potentially confounding factors including years of education, years smoked, cigarettes smoked per day and FTND score as covariates, compared to quitters, relapsers displayed significantly decreased ReHo in bilateral posterior cingulate cortex (PCC), as well as increased ReHo in left superior temporal gyrus (STG). These preliminary results suggest that regional brain function variables may be promising predictors of smoking relapse. This study provided novel insights into the neurobiological mechanisms underlying smoking relapse. A deeper understanding of the neurobiological mechanisms associated with relapse may result in novel pharmacological and behavioral interventions.

Disrupted Brain Network in Progressive Mild Cognitive Impairment Measured by Eigenvector Centrality Mapping is Linked to Cognition and Cerebrospinal Fluid Biomarkers

Mild cognitive impairment (MCI) is a heterogeneous condition associated with a high risk of progressing to Alzheimers disease (AD). Although functional brain network alterations have been observed in progressive MCI (pMCI), the underlying pathological mechanisms of network alterations remain unclear. In the present study, we evaluated neuropsychological, imaging, and cerebrospinal fluid (CSF) data at baseline across a cohort of: 21 pMCI patients, 33 stable MCI (sMCI) patients, and 29 normal controls. Fast eigenvector centrality mapping (fECM) based on resting-state functional MRI (rsfMRI) was used to investigate brain network organization differences among these groups, and we further assessed its relation to cognition and AD-related pathology. Our results demonstrated that pMCI had decreased eigenvector centrality (EC) in left temporal pole and parahippocampal gyrus, and increased EC in left middle frontal gyrus compared to sMCI. In addition, compared to normal controls, patients with pMCI showed decreased EC in right hippocampus and bilateral parahippocampal gyrus, and sMCI had decreased EC in right middle frontal gyrus and superior parietal lobule. Correlation analysis showed that EC in the left temporal pole was related to Wechsler Memory Scale-Revised Logical Memory (WMS-LM) delay score (r = 0.467, p = 0.044) and total tau (t-tau) level in CSF (r = -0.509, p = 0.026) in pMCI. Our findings implicate EC changes of different brain network nodes in the prognosis of pMCI and sMCI. Importantly, the association between decreased EC of brain network node and pathological changes may provide a deeper understanding of the underlying pathophysiology of pMCI.