Resting-state brain activity as a biomarker of chronic pain impairment and a mediator of its association with pain resilience.

Past cross-sectional chronic pain studies have revealed aberrant resting-state brain activity in regions involved in pain processing and affect regulation. However, there is a paucity of longitudinal research examining links of resting-state activity and pain resilience with changes in chronic pain outcomes over time. In this prospective study, we assessed the status of baseline (T1) resting-state brain activity as a biomarker of later impairment from chronic pain and a mediator of the relation between pain resilience and impairment at follow-up. One hundred forty-two adults with chronic musculoskeletal pain completed a T1 assessment comprising a resting-state functional magnetic resonance imaging scan based on regional homogeneity (ReHo) and self-report measures of demographics, pain characteristics, psychological status, pain resilience, pain severity, and pain impairment. Subsequently, pain impairment was reassessed at a 6-month follow-up (T2). Hierarchical multiple regression and mediation analyses assessed relations of T1 ReHo and pain resilience scores with changes in pain impairment. Higher T1 ReHo values in the right caudate nucleus were associated with increased pain impairment at T2, after controlling for all other statistically significant self-report measures. ReHo also partially mediated associations of T1 pain resilience dimensions with T2 pain impairment. T1 right caudate nucleus ReHo emerged as a possible biomarker of later impairment from chronic musculoskeletal pain and a neural mechanism that may help to explain why pain resilience is related to lower levels of later chronic pain impairment. Findings provide empirical foundations for prospective extensions that assess the status of ReHo activity and self-reported pain resilience as markers for later impairment from chronic pain and targets for interventions to reduce impairment. PRACTITIONER POINTS: Resting-state markers of impairment: Higher baseline (T1) regional homogeneity (ReHo) values, localized in the right caudate nucleus, were associated with exacerbations in impairment from chronic musculoskeletal pain at a 6-month follow-up, independent of T1 demographics, pain experiences, and psychological factors. Mediating role of ReHo values: ReHo values in the right caudate nucleus also mediated the relationship between baseline pain resilience levels and later pain impairment among participants. Therapeutic implications: Findings provide empirical foundations for research extensions that evaluate (1) the use of resting-state activity in assessment to identify people at risk for later impairment from pain and (2) changes in resting-state activity as biomarkers for the efficacy of treatments designed to improve resilience and reduce impairment among those in need.

Investigating mortality salience as a potential causal influence and moderator of responses to laboratory pain.

Background: Because pain can have profound ramifications for quality of life and daily functioning, understanding nuances in the interplay of psychosocial experiences with pain perception is vital for effective pain management. In separate lines of research, pain resilience and mortality salience have emerged as potentially important psychological correlates of reduced pain severity and increased tolerance of pain. However, to date, there has been a paucity of research examining potentially interactive effects of these factors on pain perception. To address this gap, the present experiment investigated mortality salience as a causal influence on tolerance of laboratory pain and a moderator of associations between pain resilience and pain tolerance within a Chinese sample. Methods: Participants were healthy young Chinese adults (86 women, 84 men) who first completed a brief initial cold pressor test (CPT) followed by measures of demographics and pain resilience. Subsequently, participants randomly assigned to a mortality salience (MS) condition completed two open-ended essay questions in which they wrote about their death as well as a death anxiety scale while those randomly assigned to a control condition completed analogous tasks about watching television. Finally, all participants engaged in a delay task and a second CPT designed to measure post-manipulation pain tolerance and subjective pain intensity levels. Results: MS condition cohorts showed greater pain tolerance than controls on the post-manipulation CPT, though pain intensity levels did not differ between groups. Moderator analyses indicated that the relationship between the behavior perseverance facet of pain resilience and pain tolerance was significantly stronger among MS condition participants than controls. Conclusions: This experiment is the first to document potential causal effects of MS on pain tolerance and Ms as a moderator of the association between self-reported behavior perseverance and behavioral pain tolerance. Findings provide foundations for extensions within clinical pain samples.

Cognition and motion dysfunction-associated brain functional network disruption in diabetic peripheral neuropathy.

Neuroimaging studies have demonstrated extensive brain functional alterations in cognitive and motor functional areas in Type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN), suggesting potential alterations in large-scale brain networks related to DPN and associated cognition and motor dysfunction. In this study, using resting-state functional connectivity (FC) and graph theory computational approaches, we investigated the topological disruptions of brain functional networks in 28 DPN, 43 T2DM without DPN (NDPN), and 32 healthy controls (HCs) and examined the correlations between altered network topological metrics and cognitive/motor function parameters in T2DM. For global topology, NDPN exhibited a significantly decreased shortest path length compared with HCs, suggesting increased efficient global integration. For regional topology, DPN and NDPN had separated topological reorganization of functional hubs compared with HCs. In addition, DPN showed significantly decreased nodal efficiency (Enodal ), mainly in the bilateral superior occipital gyrus (SOG), right cuneus, middle temporal gyrus (MTG), and left inferior parietal gyrus (IPL), compared with NDPN, whereas NDPN showed significantly increased Enodal compared with HCs. Intriguingly, in T2DM patients, the Enodal of the right SOG was significantly negatively correlated with Toronto Clinical Scoring System scores, while the Enodal of the right postcentral gyrus (PoCG) and MTG were significantly positively correlated with Montreal Cognitive Assessment scores. Conclusively, DPN and NDPN patients had segregated disruptions in the brain functional network, which were related to cognition and motion dysfunctions. Our findings provide a theoretical basis for understanding the neurophysiological mechanism of DPN and its effective prevention and treatment in T2DM.

Disrupted brain structural networks associated with depression and cognitive dysfunction in cerebral small vessel disease with microbleeds.

Emerging evidence highlights cerebral microbleeds (CMBs) as hallmarks of cerebral small vessel disease (CSVD) underlying depression and cognitive dysfunction. This study aimed to reveal how depression and cognition-related white matter (WM) abnormalities are topologically presented, and the network-level structural disruptions associated with CMBs in CSVD. We used probabilistic diffusion tractography and graph theory to investigate brain WM network topology in CSVD patients with (n = 64, CSVD-c) and without (n = 138, CSVD-n) CMBs and 90 healthy controls. Then we evaluated the Pearson's correlations between disrupted network metrics and neuropsychological parameters. For global topology, the CSVD-c group exhibited significantly decreased global (Eglob) and local (Eloc) efficiency and increased shortest path length compared with the controls, while no significant difference was found between the CSVD-c and CSVD-n groups. For regional topology, although all groups showed highly similar hub distributions, compare with control group, the CSVD-c group exhibited significantly decreased nodal efficiency mainly in the bilateral supplementary motor area (SMA), median cingulate gyrus (DCG) and right orbital middle frontal gyrus, while the CSVD-n group showed significantly decreased nodal efficiency only in the right SMA. Notably, Eglob, Eloc and nodal efficiency of the right anterior cingulate gyrus, DCG, middle temporal gyrus and left insula showed significantly negative correlations with depression score, significantly positive correlations with Rey auditory verbal learning test and symbol digit modalities test scores in CSVD-n group, as well as significantly negative correlations with Stroop color-word test scores in CSVD-c group. The WM networks of CSVD patients are characterized by decreased global integration and local specialization, and decreased nodal efficiency highly related to depression and cognitive dysfunction in the attention, default mode network and sensorimotor regions. These findings provide new insight into the neurobiological mechanisms of CSVD and concomitant affective and cognitive disorders.

Decreased Local Specialization of Brain Structural Networks Associated with Cognitive Dysfuntion Revealed by Probabilistic Diffusion Tractography for Different Cerebral Small Vessel Disease Burdens.

To reveal the network-level structural disruptions associated with cognitive dysfunctions in different cerebral small vessel disease (CSVD) burdens, we used probabilistic diffusion tractography and graph theory to investigate the brain network topology in 67 patients with a severe CSVD burden (CSVD-s), 133 patients with a mild CSVD burden (CSVD-m) and 89 healthy controls. We used one-way analysis of covariance to assess the altered topological measures between groups, and then evaluated their Pearson correlation with cognitive parameters. Both the CSVD and control groups showed efficient small-world organization in white matter (WM) networks. However, compared with CSVD-m patients and controls, CSVD-s patients exhibited significantly decreased local efficiency, with partially reorganized hub distributions. For regional topology, CSVD-s patients showed significantly decreased nodal efficiency in the bilateral anterior cingulate gyrus, caudate nucleus, right opercular inferior frontal gyrus (IFGoperc), supplementary motor area (SMA), insula and left orbital superior frontal gyrus and angular gyrus. Intriguingly, global/local efficiency and nodal efficiency of the bilateral caudate nucleus, right IFGoperc, SMA and left angular gyrus showed significant correlations with cognitive parameters in the CSVD-s group, while only the left pallidum showed significant correlations with cognitive metrics in the CSVD-m group. In conclusion, the decreased local specialization of brain structural networks in patients with different CSVD burdens provides novel insights into understanding the brain structural alterations in relation to CSVD severity. Cognitive correlations with brain structural network efficiency suggest their potential use as neuroimaging biomarkers to assess the severity of CSVD.

Diffusion kurtosis imaging tractography reveals disrupted white matter structural networks in children with obstructive sleep apnea syndrome.

To assess the disruptions of brain white matter (WM) structural network in children with obstructive sleep apnea (OSA) using diffusion kurtosis imaging (DKI). We use DKI tractography to construct individual whole-brain, region-level WM networks in 40 OSA and 28 healthy children. Then, we apply graph theory approaches to analyze whether OSA children would show altered global and regional network topological properties and whether these alterations would significantly correlate with the clinical characteristics of OSA. We found that both OSA and healthy children showed an efficient small-world organization and highly similar hub distributions in WM networks. However, characterized by kurtosis fractional anisotropy (KFA) weighted networks, OSA children exhibited decreased global and local efficiency, increased shortest path length compared with healthy children. For regional topology, OSA children exhibited significant decreased nodal betweenness centrality (BC) in the bilateral medial orbital superior frontal gyrus (ORBsupmed), right orbital part superior frontal gyrus (ORBsup), insula, postcentral gyrus, left middle temporal gyrus (MTG), and increased nodal BC in the superior parietal gyrus, pallidum. Intriguingly, the altered nodal BC of multiple regions (right ORBsupmed, ORBsup and left MTG) within default mode network showed significant correlations with sleep parameters for OSA patients. Our results suggest that children with OSA showed decreased global integration and local specialization in WM networks, typically characterized by DKI tractography and KFA metric. This study may advance our current understanding of the pathophysiological mechanisms of impaired cognition underlying OSA.

Depression- and anxiety-associated disrupted brain structural networks revealed by probabilistic tractography in thyroid associated ophthalmopathy.

BACKGROUND: Patients with thyroid-associated opthalmopathy (TAO) have widespread white matter (WM) abnormalities in the emotional and cognitive functional regions. However, the topological representation of these WM abnormalities and the network-level structural aberrations underlying TAO and concomitant affective disorders are still unclear. METHODS: We used probabilistic diffusion tractography and graph theory to investigate brain network topology in 37 active, 35 inactive TAO patients and 23 healthy controls. Then, we evaluated the partial correlations between network topological metrics and clinical parameters. RESULTS: For global topology, only active TAO patients exhibited significantly decreased global (Eglob) and local (Eloc) efficiency compared with controls, while no significant difference was observed between active and inactive TAO patients. For regional topology, we found a significantly decreased nodal efficiency in the left orbital superior frontal gyrus (ORBsup), medial orbital superior frontal gyrus (ORBsupmed), hippocampus and amygdala in active TAO patients compared with inactive ones. Intriguingly, Eglob, Eloc, and nodal efficiency of left ORBsup, ORBsupmed, olfactory cortex, gyrus rectus, hippocampus, right parahippocampal gyrus and amygdala had significantly positive correlations with anxiety/depression scores, bilateral exophthalmos and intraocular pressure in active TAO patients, while no significant correlation was observed in inactive TAO patients. LIMITATIONS: No longitudinal follow-up. CONCLUSIONS: WM networks of TAO are characterized by decreased local specialization and global integration in the active phase, and decreased nodal efficiency highly related to anxiety and depression in the emotional and cognitive regions. Our findings provide new insight regarding the neurobiological mechanisms of TAO and contribute to the treatment of concomitant affective disorders.

Comparisons are Odious? The neural basis of in-group and out-group social comparison among game players: An fMRI study.

Social comparison is an important way for individuals to define their social characteristics. Online games with a large amount of social information provide a convenient platform for social comparison between players. However, few studies have examined the neural basis of different social comparisons in game players. This study aims to explore the activation of brain regions triggered by social comparison in different contexts and the possible moderating effect of group identity. A total of 26 subjects participated in our experiment. We referred to the minimum group paradigm to evoke group identity and used the dot estimation paradigm to generate in-group or out-group social comparisons. The activation of brain regions was measured and analyzed. Compared to upward comparison, the fusiform gyrus, putamen, lentiform nucleus, precuneus, and precentral gyrus were significantly activated in downward comparison when the group identity of the comparison object was the same as that of the player. When the two had different identities, downward comparison significantly activated the angular gyrus, middle frontal gyrus, and superior frontal gyrus. However, the moderating effect of group identity was not significant. Further functional connectivity analysis based on the brain region activation results was performed. Our study has shown that social comparison in group contexts leads to the activation of different brain regions and provides neurophysiological evidence of social interaction among game players.

Disrupted Gray Matter Networks Associated with Cognitive Dysfunction in Cerebral Small Vessel Disease.

This study aims to investigate the disrupted topological organization of gray matter (GM) structural networks in cerebral small vessel disease (CSVD) patients with cerebral microbleeds (CMBs). Subject-wise structural networks were constructed from GM volumetric features of 49 CSVD patients with CMBs (CSVD-c), 121 CSVD patients without CMBs (CSVD-n), and 74 healthy controls. The study used graph theory to analyze the global and regional properties of the network and their correlation with cognitive performance. We found that both the control and CSVD groups exhibited efficient small-world organization in GM networks. However, compared to controls, CSVD-c and CSVD-n patients exhibited increased global and local efficiency (Eglob/Eloc) and decreased shortest path lengths (Lp), indicating increased global integration and local specialization in structural networks. Although there was no significant global topology change, partially reorganized hub distributions were found between CSVD-c and CSVD-n patients. Importantly, regional topology in nonhub regions was significantly altered between CSVD-c and CSVD-n patients, including the bilateral anterior cingulate gyrus, left superior parietal gyrus, dorsolateral superior frontal gyrus, and right MTG, which are involved in the default mode network (DMN) and sensorimotor functional modules. Intriguingly, the global metrics (Eglob, Eloc, and Lp) were significantly correlated with MoCA, AVLT, and SCWT scores in the control group but not in the CSVD-c and CSVD-n groups. In contrast, the global metrics were significantly correlated with the SDMT score in the CSVD-s and CSVD-n groups but not in the control group. Patients with CSVD show a disrupted balance between local specialization and global integration in their GM structural networks. The altered regional topology between CSVD-c and CSVD-n patients may be due to different etiological contributions, which may offer a novel understanding of the neurobiological processes involved in CSVD with CMBs.

Disrupted topological organization of white matter structural networks in high myopia patients revealed by diffusion kurtosis imaging and tractography.

Introduction: High myopia (HM) is a public health issue that can lead to severe visual impairment. Previous studies have exhibited widespread white matter (WM) integrity damage in HM patients. However, how these WM damages are topologically related, and the network-level structural disruptions underlying HM has not been fully defined. We aimed to assess the alterations of brain WM structural networks in HM patients using diffusion kurtosis imaging (DKI) and tractography in the present study. Methods: Individual whole-brain and ROI-level WM networks were constructed using DKI tractography in 30 HM patients and 33 healthy controls. Graph theory analysis was then applied to explore the altered global and regional network topological properties. Pearson correlations between regional properties and disease duration in the HM group were also assessed. Results: For global topology, although both groups showed a small-world network organization, HM patients exhibited significant decreased local efficiency and clustering coefficient compared with controls. For regional topology, HM patients and controls showed highly similar hub distributions, except for three additional hub regions in HM patients including left insula, anterior cingulate and paracingulate gyri (ACG), and median cingulate and paracingulate gyri (DCG). In addition, HM patients showed significantly altered nodal betweenness centrality (BC) mainly in the bilateral inferior occipital gyrus (IOG), left superior occipital gyrus (SOG), caudate nucleus, rolandic operculum and right putamen, pallidum, and gyrus rectus compared with controls. Intriguingly, the nodal BC of left IOG was negatively correlated with disease duration in HM patients. Discussion: Our findings suggest that HM exhibited alterations in WM structural networks as indicated by decreased local specialization. This study may advance the current understanding of the pathophysiological mechanisms underlying HM.

Abnormal whole-brain voxelwise structure-function coupling and its association with cognitive dysfunction in patients with different cerebral small vessel disease burdens.

Cerebral small vessel disease (CSVD) is a universal neurological disorder in older adults that occurs in connection with cognitive dysfunction and is a chief risk factor for dementia and stroke. While whole-brain voxelwise structural and functional abnormalities in CSVD have been heavily explored, the degree of structure-function coupling abnormality possible in patients with different CSVD burdens remains largely unknown. This study included 53 patients with severe CSVD burden (CSVD-s), 108 patients with mild CSVD burden (CSVD-m) and 76 healthy controls. A voxelwise coupling metric of low frequency fluctuations (ALFF) and voxel-based morphometry (VBM) was used to research the important differences in whole-brain structure-function coupling among groups. The correlations between ALFF/VBM decoupling and cognitive parameters in CSVD patients were then investigated. We found that compared with healthy controls, CSVD-s patients presented notably decreased ALFF/VBM coupling in the bilateral caudate nuclei and increased coupling in the right inferior temporal gyrus (ITG). In addition, compared with the CSVD-m group, the CSVD-s group demonstrated significantly decreased coupling in the bilateral caudate nuclei, right putamen and inferior frontal gyrus (IFG) and increased coupling in the left middle frontal gyrus and medial superior frontal gyrus. Notably, the ALFF/VBM decoupling values in the caudate, IFG and ITG not only showed significant correlations with attention and executive functions in CSVD patients but also prominently distinguished CSVD-s patients from CSVD-m patients and healthy controls in receiver operating characteristic curve research. Our discoveries demonstrated that decreased ALFF/VBM coupling in the basal ganglia and increased coupling in the frontotemporal lobes were connected with more severe burden and worse cognitive decline in CSVD patients. ALFF/VBM coupling might serve as a novel effective neuroimaging biomarker of CSVD burden and provide new insights into the pathophysiological mechanisms of the clinical development of CSVD.

Brain structure-function coupling associated with cognitive impairment in cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is a common chronic and progressive disease that can lead to mental and cognitive impairment. Damage to brain structure and function may play an important role in the neuropsychiatric disorders of patients with CSVD. Increasing evidence suggests that functional changes are accompanied by structural changes in corresponding brain regions. Thus, normal structure-function coupling is essential for optimal brain performance, and disrupted structure-function coupling can be found in many neurological and psychiatric disorders. To date, most studies on patients with CSVD have focused on separate structures or functions, including reductions in white matter volume and blood flow, which lead to cognitive dysfunction. However, there are few studies on brain structure-function coupling in patients with CSVD. In recent years, with the rapid development of multilevel (voxel-wise, neurovascular, regional level, and network level) brain structure-functional coupling analysis methods based on multimodal magnetic resonance imaging (MRI), new evidence has been provided to reveal the correlation between brain function and structural abnormalities and cognitive impairment. Therefore, studying brain structure-function coupling has a potential significance in the exploration and elucidation of the neurobiological mechanism of cognitive impairment in patients with CSVD. This article mainly describes the currently popular brain structure-function coupling analysis technology based on multimodal MRI and the important research progress of these coupling technologies on CSVD and cognitive impairment to provide a perspective for the study of the pathogenesis and early diagnosis of CSVD.

A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Decreased gray matter volume in the right middle temporal gyrus associated with cognitive dysfunction in preeclampsia superimposed on chronic hypertension.

Introduction: The effects of preeclampsia superimposed on chronic hypertension (CHTN-PE) on the structure and function of the human brain are mostly unknown. The purpose of this study was to examine altered gray matter volume (GMV) and its correlation with cognitive function in pregnant healthy women, healthy non-pregnant individuals, and CHTN-PE patients. Methods: Twenty-five CHTN-PE patients, thirty-five pregnant healthy controls (PHC) and thirty-five non-pregnant healthy controls (NPHC) were included in this study and underwent cognitive assessment testing. A voxel-based morphometry (VBM) approach was applied to investigate variations in brain GMV among the three groups. Pearson's correlations between mean GMV and the Stroop color-word test (SCWT) scores were calculated. Results: Compared with the NPHC group, the PHC and CHTN-PE groups showed significantly decreased GMV in a cluster of the right middle temporal gyrus (MTG), and the GMV decrease was more significant in the CHTN-PE group. There were significant differences in the Montreal Cognitive Assessment (MoCA) and Stroop word scores among the three groups. Notably, the mean GMV values in the right MTG cluster were not only significantly negatively correlated with Stroop word and Stroop color scores but also significantly distinguished CHTN-PE patients from the NPHC and PHC groups in receiver operating characteristic curve analysis. Discussion: Pregnancy may cause a decrease in local GMV in the right MTG, and the GMV decrease is more significant in CHTN-PE patients. The right MTG affects multiple cognitive functions, and combined with the SCWT scores, it may explain the decline in speech motor function and cognitive flexibility in CHTN-PE patients.

Characterisation of brain microstructural alterations in children with obstructive sleep apnea syndrome using diffusion kurtosis imaging.

Obstructive sleep apnea (OSA) is a common chronic sleep-related breathing disorder in children. Previous studies showed widespread alterations in white matter (WM) in children with OSA mainly by using diffusion tensor imaging (DTI), while diffusional kurtosis imaging (DKI) extended DTI and exhibited improved sensitivity in detecting developmental and pathological changes in neural tissues. Therefore, we conducted whole-brain DTI and DKI analyses and compared the differences in kurtosis and diffusion parameters within the skeleton between 41 children with OSA and 32 healthy children. Between-group differences were evaluated by tract-based spatial statistics (TBSS) analysis (p < 0.05, TFCE corrected), and partial correlations between DKI metrics and sleep parameters were assessed considering age and gender as covariates. Compared with the controls, children with OSA showed significantly decreased kurtosis fractional anisotropy (KFA) mainly in white matter regions with a complex fibre arrangement including the posterior corona radiate (PCR), superior longitudinal fasciculus (SLF), and inferior fronto-occipital fasciculus (IFOF), while decreased FA in white matter regions with a coherent fibre arrangement including the posterior limb of internal capsule (PLIC), anterior thalamic radiation (ATR), and corpus callosum (CC). Notably, the receiver operating characteristic (ROC) curve analysis demonstrated the KFA value in complex tissue regions significantly (p < 0.001) differentiated children with OSA from the controls. In addition, the KFA value in the left PCR, SLF, and IFOF showed significant partial correlations to the sleep parameters for children with OSA. Combining DKI derived kurtosis and diffusion parameters can provide complementary neuroimaging biomarkers for assessing white matter alterations, and reveal pathological changes and monitor disease progression in paediatric OSA.

Characterization of white matter microstructural abnormalities associated with cognitive dysfunction in cerebral small vessel disease with cerebral microbleeds.

BACKGROUND: Diffusion tensor imaging (DTI) is recommended as a sensitive method to explore white matter (WM) microstructural alterations. Cerebral small vessel disease (CSVD) may be accompanied by extensive WM microstructural deterioration, while cerebral microbleeds (CMBs) are an important factor affecting CSVD. METHODS: Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 49 CSVD patients with CMBs (CSVD-c), 114 CSVD patients without CMBs (CSVD-n), and 83 controls were analyzed using DTI-derived tract-based spatial statistics to detect WM diffusion changes among groups. RESULTS: Compared with the CSVD-n and control groups, the CSVD-c group showed a significant FA decrease and AD, RD and MD increases mainly in the cognitive and sensorimotor-related WM tracts. There was no significant difference in any diffusion metric between the CSVD-n and control groups. Furthermore, the widespread regional diffusion alterations among groups were significantly correlated with cognitive parameters in both the CSVD-c and CSVD-n groups. Notably, we applied the multiple kernel learning technique in multivariate pattern analysis to combine multiregion and multiparameter diffusion features, yielding an average accuracy >77 % for three binary classifications, which showed a considerable improvement over the single modality approach. LIMITATIONS: We only grouped the study according to the presence or absence of CMBs. CONCLUSIONS: CSVD patients with CMBs have extensive WM microstructural deterioration. Combining DTI-derived diffusivity and anisotropy metrics can provide complementary information for assessing WM alterations associated with cognitive dysfunction and serve as a potential discriminative pattern to detect CSVD at the individual level.

Altered Intrinsic Brain Activity Related to Neurologic and Motor Dysfunction in Diabetic Peripheral Neuropathy Patients.

CONTEXT: Brain functional alterations in type 2 diabetes with diabetic peripheral neuropathy (DPN) related to motor dysfunction remain largely unknown. OBJECTIVE: We aimed to explore intrinsic resting brain activity in DPN. METHODS: A total of 28 patients with DPN, 43 patients with diabetes and without DPN (NDPN), and 32 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging. We calculated the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo). One-way analysis of covariance was applied to evaluate the above indicators among the 3 groups, and the mean ALFF/fALFF/ReHo values of altered brain regions were then correlated with clinical features of patients. RESULTS: Compared with the NDPN group, the DPN group showed significantly decreased ALFF values in the right orbital superior frontal gyrus (ORBsup) and medial superior frontal gyrus (SFGmed), and increased ALFF values in the left inferior temporal gyrus (ITG) and decreased fALFF values in the right SFGmed. Compared with HCs, the NDPN group showed increased ALFF values in the right ORBsup, middle frontal gyrus, and left orbital middle frontal gyrus, and decreased fALFF values in the right middle temporal gyrus. Notably, the mean ALFF values of the right ORBsup were significantly negatively correlated with Toronto Clinical Scoring System scores and gait speed in diabetics. The mean ALFF/fALFF values of right SFGmed and the mean ALFF values of left ITG and right ORBsup were significantly differentiated between DPN and patients witht NDPN in receiver operating characteristic curve analysis. CONCLUSION: Patients with DPN have abnormal brain activity in sensorimotor and cognitive brain areas, which may implicate the underlying neurophysiological mechanisms in intrinsic brain activity.