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Wendi Zhang,1 Zhaohui Chen1,2 1College of Acupuncture and Massage (Rehabilitation Medical College), Anhui University of Chinese Medicine, Hefei, People’s Republic of China; 2Department of Tendon Injury, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Zhaohui Chen, Email czhn007@163.comPurpose: The aim of the research was to observe the variations in brain activity between young cervical spondylosis patients with chronic neck pain (CNP) and healthy volunteers in the resting state and to investigate the central remodeling mechanisms in the patients.Patients and methods: Our study recruited 31 patients with chronic neck pain from cervical spondylosis and 30 healthy volunteers. Eventually, 29 patients (CNP group) and 29 healthy volunteers (HC group) completed the acquisition of clinical data and resting-state functional magnetic resonance (rs BOLD-fMRI) amplitude of low-frequency fluctuations (ALFF) data; in addition, we assessed the relationship between differentially active brain regions and clinical indicators.Results: The CNP group found greater ALFF values in the insula, cingulate gyrus, prefrontal lobe, and other brain regions. The occipital, parietal, and other brain regions had lower ALFF values. In addition, there was a negative connection between the duration of the sickness in the CNP group and the ALFF value of the right superior parietal gyrus (SPG.R). The level of tenderness threshold exhibited a negative correlation with the ALFF value of the left insula (INS.L). In addition, the NPQ score showed a negative association with the ALFF value of the ORBinf.R and a positive correlation with the ALFF value of the CC1.L. Finally, the HADS-A score exhibited a positive correlation with the ALFF value of the right anterior cingulate and paracingulate gyrus (ACG.R).Conclusion: Young patients with chronic neck pain show extensive central remodeling, with altered functional activity in pain-emotion brain areas (such as the cingulate gyrus and insula), pain-cognition brain areas (such as the prefrontal lobe), and other special sensory brain areas (such as the parietal and occipital lobes). These changes are linked to clinical tenderness, functional disability, and negative emotion indicators.Keywords: cervical spondylosis, chronic neck pain, central remodeling, resting-state functional magnetic resonance, young population

Deep neural networks (DNN) are increasingly being used in neuroimaging research for the diagnosis of brain disorders and understanding of human brain. Despite their impressive performance, their usage in medical applications will be limited unless there is more transparency on how these algorithms arrive at their decisions. We address this issue in the current report. A DNN classifier was trained to discriminate between healthy subjects and those with posttraumatic stress disorder (PTSD) using brain connectivity obtained from functional magnetic resonance imaging data. The classifier provided 90% accuracy. Brain connectivity features important for classification were generated for a pool of test subjects and permutation testing was used to identify significantly discriminative connections. Such heatmaps of significant paths were generated from 10 different interpretability algorithms based on variants of layer-wise relevance and gradient attribution methods. Since different interpretability algorithms make different assumptions about the data and model, their explanations had both commonalities and differences. Therefore, we developed a consensus across interpretability methods, which aligned well with the existing knowledge about brain alterations underlying PTSD. The confident identification of more than 20 regions, acknowledged for their relevance to PTSD in prior studies, was achieved with a voting score exceeding 8 and a family-wise correction threshold below 0.05. Our work illustrates how robustness and physiological plausibility of explanations can be achieved in interpreting classifications obtained from DNNs in diagnostic neuroimaging applications by evaluating convergence across methods. This will be crucial for trust in AI-based medical diagnostics in the future.

Background: The neuropathophysiological mechanisms of brain damage underlying hypothyroidism remain unclear. Fractional amplitude of low-frequency fluctuations (fALFF) has been established as a reliable indicator for investigation of abnormal spontaneous brain activity that occurs at specific frequencies in different types of mental disorder. However, the changes of fALFF in specific frequency bands in hypothyroidism have not yet been investigated. Methods: Fifty-three hypothyroid patients and 39 healthy controls (HCs) underwent thyroid-related hormone levels tests, neuropsychological assessment, and magnetic resonance imaging (MRI) scans. The fALFF in the standard band (0.01–0.1 Hz), slow-4 (0.027–0.073 Hz), and slow-5 bands (0.01–0.027 Hz) were analyzed. An analysis of Pearson correlation was conducted between fALFF, thyroid-related hormone levels, and neuropsychological scores in hypothyroid patients. Results: Compared to HCs, within the routine band, hypothyroidism group showed significantly decreased fALFF in left lingual gyrus, middle temporal gyrus (MTG), precentral gyrus, calcarine cortex, and right inferior occipital gyrus; within the slow-5 band, the hypothyroidism group exhibited decreased fALFF in left lingual gyrus, MTG, superior temporal gyrus, postcentral gyrus, and paracentral lobule, and increased fALFF in supplementary motor area (SMA) and right middle frontal gyrus; additionally, fALFF in the left lingual gyrus within the routine and slow-5 bands were negatively correlated with the level of thyroid stimulating hormone. Conclusions: In this study, the slow-5 frequency band exhibits better sensitivity than the standard band in detecting fALFF values. A decrease of fALFF values in the lingual gyrus and MTG was observed in both the standard and slow-5 bands and might present potential neuroimaging biomarkers for hypothyroidism. Clinical Trial Registration: No: ChiCTR2000028966. Registered 9 January, 2020, https://www.chictr.org.cn.

ObjectivesMigraine is often combined with vestibular dysfunction, particularly in patients with chronic migraine (CM). However, the pathogenesis of migraine chronification leading to vestibular dysfunction is not fully understood. The current study investigated whether structural or functional impairments to the brain during migraine chronification could be associated with vestibular dysfunction development.MethodsThe eligible participants underwent clinical assessment and magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) determined structural impairment by evaluating alterations in gray matter volume (GMV). Functional impairment was assessed by the mean amplitude of low-frequency fluctuation (mALFF). Furthermore, the resting-state functional connectivity (rsFC) of regions possessing impairment was examined with a seed-based approach. We also analyzed the correlations between altered neuroimaging features with clinical variables and performed multiple linear regression.ResultsEighteen CM patients, 18 episodic migraine (EM) patients, and 18 healthy controls (HCs) were included in this study. A one-way ANOVA indicated the group differences in mALFF. These were located within right supramarginal gyrus (SMG), left angular gyrus (AG), middle frontal gyrus (MFG), left middle occipital gyrus (MOG), right rolandic operculum (Rol) and left superior parietal gyrus (SPG). During rsFC analysis, the CM group had more enhanced rsFC of left SPG with left MOG than the EM and HC groups. The EM group revealed enhanced rsFC of left SPG with left AG than the CM and HC groups. In multiple linear regression, after controlling for age, body mass index (BMI) and disease duration, the rsFC of left SPG with left MOG (β = 48.896, p = 0.021) was found to predict the total Dizziness Handicap Inventory (DHI) score with an explained variance of 25.1%. Moreover, the rsFC of left SPG with left MOG (β = 1.253, p = 0.003) and right SMG (β = −1.571, p = 0.049) were significant predictors of migraine frequency, accounting for a total explained variance of 73.8%.ConclusionThe functional impairments due to migraine chronification are primarily concentrated in the multisensory integration-related brain regions. Additionally, the rsFC of SPG with MOG can predict the frequency of migraine and the degree of vestibular dysfunction. Therefore, these neuroimaging features could be potential mechanisms and therapeutic targets for developing vestibular dysfunction in migraine.

IntroductionLumbar disc herniation, a chronic degenerative disease, is one of the major contributors to chronic low back pain and disability. Although many studies have been conducted in the past on brain function in chronic low back pain, most of these studies did not classify chronic low back pain (cLBP) patients according to their etiology. The lack of etiologic classification may lead to inconsistencies between findings, and the correlation between differences in brain activation and clinical symptoms in patients with cLBP was less studied in the past.MethodsIn this study, 36 lumbar disc herniation patients with chronic low back pain (LDHCP) and 36 healthy controls (HCs) were included to study brain activity abnormalities in LDHCP. Visual analogue scale (VAS), oswestry disability index (ODI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) were used to assess clinical symptoms.ResultsThe results showed that LDHCP patients exhibited abnormally increased and diminished activation of brain regions compared to HCs. Correlation analysis showed that the amplitude of low frequency fluctuations (ALFF) in the left middle frontal gyrus is negatively correlated with SAS and VAS, while the right superior temporal gyrus is positively correlated with SAS and VAS, the dorsolateral left superior frontal gyrus and the right middle frontal gyrus are negatively correlated with VAS and SAS, respectively.ConclusionLDHCP patients have brain regions with abnormally increased and abnormally decreased activation compared to healthy controls. Furthermore, some of the abnormally activated brain regions were correlated with clinical pain or emotional symptoms.

PurposeWe aimed to evaluate the spontaneous neuronal activity and functional connectivity pattern variations using resting-state functional magnetic resonance imaging (rs-fMRI) measures, such as amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and functional connectivity (FC), in patients with thyroid-associated ophthalmopathy (TAO).MethodA total of 24 active TAO patients, 26 inactive TAO patients, and 27 matched healthy controls (HCs) were included. First, ALFF and fALFF were used to detect local neural activity changes, the MRI data were analyzed, and regions with group differences were taken as seeds. Second, FC analysis was performed to explore the altered connection between seeds and other brain regions. A correlation analysis was performed to assess the relationship between functional brain activity and clinical indices and neuropsychiatric behaviors.ResultsCompared to HCs, both active and inactive TAO patients exhibited significantly lower ALFF values in the right calcarine (Calcarine_R) and left postcentral gyrus (Postcentral_L). Active TAO patients also showed significantly higher ALFF values in the left caudate nucleus (Caudate_L) and increased fALFF values in the superior lobe of the right cerebellum (Cerebelum_Crus1_R). Moreover, both active and inactive TAO patients demonstrated decreased FC within the left postcentral gyrus (Postcentral_L) compared to HCs. Additionally, active TAO patients exhibited lower FC compared to inactive TAO patients. The ALFF values in the Calcarine_R of active TAO patients positively correlated with disease duration (r = 0.5892, p = 0.0049) and the Hamilton Anxiety Rating Scale (HARS; r = 0.5377, p = 0.0119). Furthermore, the ALFF value in the Calcarine_R of inactive TAO patients negatively correlated with visual functioning (r = −0.5449, p = 0.0072), while the ALFF values in the Caudate_L of active TAO patients positively correlated with visual functioning (r = 0.6496, p = 0.0014).ConclusionWe found that the Caudate_L and Cerebelum_Crus1_R related to motor control and coordination in active TAO patients exhibit significant compensatory mechanisms; whereas, the Calcarine_R and Postcentral_L related to visual and somatosensory cortices show varying degrees of impairment. Our findings complement the functional neural mechanism of TAO.

ObjectiveEpilepsy is considered as a neural network disorder. Seizure activity in epilepsy may disturb brain networks and damage brain functions. We propose using resting-state functional magnetic resonance imaging (rs-fMRI) data to characterize connectivity patterns in drug-resistant epilepsy.MethodsThis study enrolled 47 participants, including 28 with drug-resistant epilepsy and 19 healthy controls. Functional and effective connectivity was employed to assess drug-resistant epilepsy patients within resting state networks. The resting state functional connectivity (FC) analysis was performed to assess connectivity between each patient and healthy controls within the default mode network (DMN) and the dorsal attention network (DAN). In addition, dynamic causal modeling was used to compute effective connectivity (EC). Finally, a statistical analysis was performed to evaluate our findings.ResultsThe FC analysis revealed significant connectivity changes in patients giving 64.3% (18/28) and 78.6% (22/28) for DMN and DAN, respectively. Statistical analysis of FC was significant between the medial prefrontal cortex, posterior cingulate cortex, and bilateral inferior parietal cortex for DMN. For DAN, it was significant between the left and the right intraparietal sulcus and the frontal eye field. For the DMN, the patient group showed significant EC connectivity in the right inferior parietal cortex and the medial prefrontal cortex for the DMN. There was also bilateral connectivity between the medial prefrontal cortex and the posterior cingulate cortex, as well as between the left and right inferior parietal cortex. For DAN, patients showed significant connectivity in the right frontal eye field and the right intraparietal sulcus. Bilateral connectivity was also found between the left frontal eye field and the left intraparietal sulcus, as well as between the right frontal eye field and the right intraparietal sulcus. The statistical analysis of the EC revealed a significant result in the medial prefrontal cortex and the right intraparietal cortex for the DMN. The DAN was found significant in the left frontal eye field, as well as the left and right intraparietal sulcus.ConclusionOur results provide preliminary evidence to support that the combination of functional and effective connectivity analysis of rs-fMRI can aid in diagnosing epilepsy in the DMN and DAN networks.

Childhood emotional neglect (CEN) has a relatively high incidence rate and substantially adverse effects. Many studies have found that CEN is closely related to emotion regulation and depression symptoms. Besides, the functional activity of the prefrontal lobe may also be related to them. However, the relationships between the above variables have not been thoroughly studied. This study recruited two groups of college students, namely, those with primary CEN (neglect group) and those without childhood trauma (control group), to explore the relationships among CEN, adulthood emotion regulation, depressive symptoms, and prefrontal resting functional connections. The methods used in this study included the Childhood Trauma Questionnaire (CTQ), Emotion Regulation Questionnaire (ERQ), Beck Depression Inventory-II (BDI-II) and resting-state functional magnetic resonance imaging (rs-fMRI). The results showed that compared with the control group, the neglect group utilized the reappraisal strategy less frequently and displayed more depressive symptoms. The prefrontal functional connections with other brain regions in the neglect group were more robust than those in the control group using less stringent multiple correction standards. Across the two groups, the functional connection strength between the right orbitofrontal gyrus and the right middle frontal gyrus significantly negatively correlated with the ERQ reappraisal score and positively correlated with the BDI-II total score; the ERQ reappraisal score wholly mediated the relationship between the functional connection strength and the BDI-II total score. It suggests that primary CEN may closely correlate with more depressive symptoms in adulthood. Furthermore, the more robust spontaneous activity of the prefrontal lobe may also be closely associated with more depressive symptoms by utilizing a reappraisal strategy less frequently.

ObjectiveTo study the dynamic changes of local metrics in patients with toothache (TA, Toothache) in the resting state, in order to further understand the changes of central neural mechanism in patients with dental pain and its effect on cognition and emotion.MethodsThirty patients with TA and thirty matched healthy (HC) control volunteers were recruited, and resting-state functional magnetic resonance (rs-MRI) scans were performed on all subjects, and data were analyzed to compare group differences in three dynamic local indices: dynamic regional homogeneity (dReHO), dynamic low-frequency fluctuation amplitude (dALFF) and dynamic fractional low-frequency fluctuation amplitude (dfALFF). In addition, the association between dynamic local metrics in different brain regions of TA patients and scores on the Visual Analog Scale (VAS) and the Hospital Anxiety and Depression Scale (HADS) was investigated by Pearson correlation analysis.ResultsIn this study, we found that The local metrics of TA patients changed with time Compared with the HC group, TA patients showed increased dReHo values in the left superior temporal gyrus, middle frontal gyrus, precentral gyrus, precuneus, angular gyrus, right superior frontal gyrus, middle temporal gyrus, postcentral gyrus and middle frontal gyrus, increased dALFF values in the right superior frontal gyrus, and increased dfALFF values in the right middle temporal gyrus, middle frontal gyrus and right superior occipital gyrus (p < 0.01, cluster level P < 0.05). Pearson correlation analysis showed that dReHo values of left precuneus and left angular gyrus were positively correlated with VAS scores in TA group. dReHo value of right posterior central gyrus was positively correlated with HADS score (P < 0.05).ConclusionThere are differences in the patterns of neural activity changes in resting-state brain areas of TA patients, and the brain areas that undergo abnormal changes are mainly pain processing brain areas, emotion processing brain areas and pain cognitive modulation brain areas, which help to reveal their underlying neuropathological mechanisms. In the hope of further understanding its effects on cognition and emotion.

BackgroundApathy is among the most prevalent and incapacitating non-motor symptoms of Parkinson’s disease (PD). PD patients with apathy (PD-A) have been reported to have abnormal spontaneous brain activity mainly in 0.01–0.08 Hz. However, the frequency-dependence of brain activity in PD-A remains unclear. Therefore, this study aimed to examine whether abnormalities in PD-A are associated with specific frequency bands.Materials and methodsOverall, 28 patients with PD-A, 19 PD patients without apathy (PD-NA), and 32 gender-, age-matched healthy controls (HCs) were enrolled. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data, demographic information, and neuropsychological assessments, including apathy, depression, anxiety and cognitive function for every participant. The amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) were calculated in the conventional (0.01–0.08 Hz), slow-4 (0.027–0.073 Hz), and slow-5 (0.01–0.027 Hz) frequency bands based on statistical parametric mapping (SPM12) and RESTplus V1.25. Two-sample t-tests were performed to compare the differences among the three groups.ResultsPD-A reduced ALFF in the right anterior cingulate gyri in the slow-5 band and decreased fALFF in the right middle frontal gyrus in the conventional band, compared to patients with PD-NA. However, PerAF, ReHo, and DC could not distinguish PD-A from PD-NA in the three bands. PD-A had higher ALFF and fALFF in the left middle occipital gyrus and lower fALFF in the bilateral insula in the slow-5 band compared to the HCs. Furthermore, abnormal DC value in hippocampus and parahippocampus was observed separately in the conventional band and in the slow-4 band between PD-A and HCs. Moreover, PD-A and PD-NA showed lower ReHo in cerebellum in the three bands compared to the HCs.ConclusionOur study revealed that PD-A and PD-NA might have different neurophysiological mechanisms. Concurrently, the ALFF in the slow-5 band and fALFF in the conventional band were sensitive in differentiating PD-A from PD-NA. The influence of apathy on the disease can be considered in the future research on PD, with the effects of frequency band taken into account when analyzing spontaneous brain activities in PD-A.

Abstract Background Although several brain networks play important roles in cervical dystonia (CD) patients, regional homogeneity (ReHo) changes in CD patients have not been clarified. We investigated to explore ReHo in CD patients at rest and analyzed its correlations with symptom severity as measured by Tsui scale. Methods A total of 19 CD patients and 21 gender-, age-, and education-matched healthy controls underwent fMRI scans at rest state. Data were analyzed by ReHo method. Results Patients showed increased ReHo in the right cerebellum crus I and decreased ReHo in the right superior medial prefrontal cortex (MPFC). Moreover, the right precentral gyrus, right insula, and bilateral middle cingulate gyrus also showed increased ReHo values. A significantly positive correlation was observed between ReHo value in the right cerebellum crus I and symptom severity (p

Background and ObjectiveWhile evidence has demonstrated that the default-mode network (DMN) plays a key role in the broad-scale cognitive problems that occur in right temporal lobe epilepsy (rTLE), little is known about alterations in the network homogeneity (NH) of the DMN in TLE. In this study, we used the NH method to investigate the NH of the DMN in TLE at rest, and an support vector machine (SVM) method for the diagnosis of rTLE.MethodsA total of 43 rTLE cases and 42 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Imaging data were analyzed with the NH and SVM methods.ResultsrTLE patients have a decreased NH in the right inferior temporal gyrus (ITG) and left middle temporal gyrus (MTG), but increased NH in the bilateral precuneus (PCu) and right inferior parietal lobe (IPL), compared with HCs. We found that rTLE had a longer performance reaction time (RT). No significant correlation was found between abnormal NH values and clinical variables of the patients. The SVM results showed that increased NH in the bilateral PCu as a diagnostic biomarker distinguished rTLE from HCs with an accuracy of 74.12% (63/85), a sensitivity 72.01% (31/43), and a specificity 72.81% (31/42).ConclusionThese findings suggest that abnormal NH of the DMN exists in rTLE, and highlights the significance of the DMN in the pathophysiology of cognitive problems occurring in rTLE, and the bilateral PCu as a neuroimaging diagnostic biomarker for rTLE.

Background: Increasing evidence from modern neuroimaging has confirmed that cervical dystonia (CD) is caused by network abnormalities. Specific brain networks are known to be crucial in patients suffering from CD. However, changes in network homogeneity (NH) in CD patients have not been characterized. Therefore, the purpose of this study was to investigate the NH of patients with CD.Methods: An automated NH method was used to analyze resting-state functional magnetic resonance (fMRI) data from 19 patients with CD and 21 gender- and age-matched healthy controls (HC). Correlation analysis were conducted between NH, illness duration and symptom severity measured by the Tsui scale.Results: Compared with the HC group, CD patients showed a lower NH in the right superior medial frontal gyrus. No significant correlations were found between abnormal NH values and illness duration or symptom severity.Conclusion: Our findings suggest the existence of abnormal NH in the default mode network (DMN) of CD patients, and thereby highlight the importance of the DMN in the pathophysiology of CD.

BackgroundSmoking is a modifiable risk factor for Alzheimer’s disease (AD). However, smoking-related effects on intrinsic brain activity in high-risk AD population are still unclear.ObjectiveWe aimed to explore differences in smoking effects on brain function between healthy elderly and amnestic mild cognitive impairment (aMCI) patients using ReHo mapping.MethodsWe identified 64 healthy elderly controls and 116 aMCI patients, including 98 non-smoking and 18 smoking aMCI. Each subject underwent structural and resting-state functional MRI scanning and neuropsychological evaluations. Regional homogeneity (ReHo) mapping was used to assess regional brain synchronization. After correction for age, gender, education, and gray matter volume, we explored the difference of ReHo among groups in a voxel-wise way based on analysis of covariance (ANCOVA), followed by post hoc two-sample analyses (p < 0.05, corrected). Further, we correlated the mean ReHo with neuropsychological scales.ResultsThree groups were well-matched in age, gender, and education. Significant ReHo differences were found among three groups, located in the left supramarginal gyrus (SMG) and left angular gyrus (AG). Specifically, non-smoking aMCI had lower ReHo in SMG and AG than smoking aMCI and controls. By contrast, smoking aMCI had greater AG ReHo than healthy controls (p < 0.05). Across groups, correlation analyses showed that left AG ReHo correlated with MMSE (r = 0.18, p = 0.015), clock drawing test (r = 0.20, p = 0.007), immediate recall (r = 0.36, p < 0.001), delayed recall (r = 0.34, p < 0.001), and auditory verbal learning test (r = 0.20, p = 0.007).ConclusionSmoking might pose compensatory or protective effects on intrinsic brain activity in aMCI patients.

BackgroundAnxious depression (AD), which is generally recognized as a common clinical subtype of major depressive disorder (MDD), holds distinctive features compared with unanxious depression (UAD). However, the neural mechanism of AD still remains unrevealed. To give insight to it, we compared resting-state functional magnetic resonance amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) between AD and UAD patients.MethodThe data were collected from 60 AD patients, 38 UAD patients, and 60 matched healthy controls. The ALFF and seed-based FC were examined. Pearson correlations were computed between ALFF/FC and clinical measures.ResultsIn Comparison with the UAD group, the ALFF value of the right orbital part of middle frontal gyrus (RO-MFG) decreased in AD group. Specifically, the ALFF values of the RO-MFG were negatively correlated with retardation factor scores in AD group (r = -0.376, p = 0.003).ConclusionsAD patients exhibited disturbed intrinsic brain function compared with UAD patients. The decreased activity of the RO-MFG is indicative of the alterations involved in the neural basis of AD.