Resting state functional connectome in breast cancer patients with fear of cancer recurrence.

This study aimed to investigate network-level brain functional changes in breast cancer patients and their relationship with fear of cancer recurrence (FCR). Resting-state functional MRI was collected from 43 patients with breast cancer and 40 healthy controls (HCs). Graph theory analyses, whole-brain voxel-wise functional connectivity strength (FCS) analyses and seed-based functional connectivity (FC) analyses were performed to identify connection alterations in breast cancer patients. Correlations between brain functional connections (i.e. FCS and FC) and FCR level were assessed to further reveal the neural mechanisms of FCR in breast cancer patients. Graph theory analyses indicated a decreased clustering coefficient in breast cancer patients compared to HCs (P = 0.04). Patients with breast cancer exhibited significantly higher FCS in both higher-order function networks (frontoparietal, default mode, and dorsal attention systems) and primary somatomotor networks. Among the hyperconnected regions in breast cancer, the left inferior frontal operculum demonstrated a significant positive correlation with FCR. Our findings suggest that breast cancer patients exhibit less segregation of brain function, and the left inferior frontal operculum is a key region associated with FCR. This study offers insights into the neural mechanisms of FCR in breast cancer patients at the level of brain connectome.

Altered Functional Connectivity Strength in Distinct Brain Networks of Children With Early-Onset Schizophrenia.

BACKGROUND: Schizophrenia is regarded as a brain network or connectome disorder that is associated with neurodevelopment. Children with early-onset schizophrenia (EOS) provide an opportunity to evaluate the neuropathology of schizophrenia at a very early stage without potential confounding factors. But dysfunction in brain networks of schizophrenia is inconsistent. PURPOSE: To identify abnormal functional connectivity (FC) in EOS patients and relationships with clinical symptoms, we aimed to reveal neuroimaging phenotypes of EOS. STUDY TYPE: Prospective, cross-sectional. POPULATION: Twenty-six female/22 male patients (age:14.3 ± 3.45 years) with first-episode EOS, 27 female/22 male age- and gender-matched healthy controls (HC) (age:14.1 ± 4.32). FIELD STRENGTH/SEQUENCE: 3-T, resting-state (rs) gradient-echo echo-planar imaging and three-dimensional magnetization-prepared rapid gradient-echo imaging. ASSESSMENT: Intelligence quotient (IQ) was measured by the Wechsler Intelligence Scale-Fourth edition for Children (WISC-IV). The clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS). FC strength (FCS) from rs functional MRI (rsfMRI) was used to investigate functional integrity of global brain regions. In addition, associations between regionally altered FCS and clinical symptoms in EOS patients were examined. STATISTICAL TESTS: Two-sample t-test controlling for sample size, diagnostic method, brain volume algorithm, and age of the subjects, Bonferroni correction, Pearson's correlation analysis. A P-value <0.05 with a minimum cluster size of 50 voxels was considered statistically significant. RESULTS: Compared with HC, EOS patients had significantly lower total IQ scores (IQ:91.5 ± 16.1), increased FCS in the bilateral precuneus, left dorsolateral prefrontal cortex, left thalamus, and left parahippocampus (paraHIP), and decreased FCS in the right cerebellum posterior lobe and right superior temporal gyrus. The PANSS total score of EOS patients (PANSS total score:74.30 ± 7.23) was found to be positively correlated to FCS in the left paraHIP (r = 0.45). DATA CONCLUSION: Our study revealed that disrupted FC of brain hubs illustrate multiple abnormalities in brain networks in EOS patients. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 2.

A common variant of the NOTCH4 gene modulates functional connectivity of the occipital cortex and its relationship with schizotypal traits.

BACKGROUND: Schizotypal traits are considered as inheritable traits and the endophenotype for schizophrenia. A common variant in the NOTCH4 gene, rs204993, has been linked with schizophrenia, but the neural underpinnings are largely unknown. METHODS: In present study, we compared the differences of brain functions between different genotypes of rs204993 and its relationship with schizotypal traits among 402 Chinese Han healthy volunteers. The brain function was evaluated with functional connectivity strength (FCS) using the resting-state functional magnetic resonance image(rs-fMRI). The schizotypal traits were measured by the schizotypal personality questionnaire (SPQ). RESULTS: Our results showed that carriers with the AA genotype showed reduced FCS in the left occipital cortex when compared with carriers with the AG and GG genotypes, and the carriers with the AG genotype showed reduced FCS in the left occipital cortex when compared with carriers with the GG genotype. The FCS values in the left occipital lobe were negatively associated with the SPQ scores and its subscale scores within the carriers with the GG genotype, but not within the carriers with AA or AG genotype. CONCLUSION: Our results suggested that the common variant in the NOTCH4 gene, rs204993, modulates the function of the occipital cortex, which may contribute to schizotypal traits. These findings provide insight for genetic effects on schizotypal traits and its potential neural substrate.

Individual identification for different age groups using functional connectivity strength.

BACKGROUND AND PURPOSE: Many studies demonstrate individual differences in functional network, especially those with age. Meanwhile, aging is one of the potential risk factors for Alzheimer's disease. Therefore, it is important to explore the discrepant pattern in aging population. METHODS: Most existing methods mostly target ancient atlas for the extraction of the classification features and not consider the effect of global signal. We use two novel atlases for the extraction of classification features and then use the whole and intra-hemispheric functional connectivity strength (FCS) as classification parameters to classify different age groups, respectively. Meanwhile, the regression of global signal or not during the preprocessing has been considered. Next, the support vector machine-recursive feature elimination (SVM-RFE) method is applied for feature selection and the SVM method is applied for classification. In addition, the receiver operating characteristic curve and area under the curve are drawn to evaluate the robustness of classifier. Finally, the discriminative features are related to the physiological mechanism of aging. RESULTS: The promising classification performance exhibits that the FCS can effectively distinguish different age groups. Moreover, the SVM-RFE method can increase the accuracy and extract the discriminative features. The classifiers constructed by the features derived from different atlas receive similar classification performance. CONCLUSION: This study successfully distinguishes the young group, middle-aged group, and elderly group through FCS parameter, indicating the functional pattern of the network exists difference between three groups. Moreover, the results received by the SVM-RFE method and SVM classifier have the very good robustness and not specific to particular atlas and not affected by global signal and appropriate for the FCS of the whole brain or intra-hemisphere, which suggests that we can apply them to disease diagnosis in the future.

Combined static and dynamic functional connectivity signatures differentiating bipolar depression from major depressive disorder.

OBJECTIVE: Bipolar disorder in the depressive phase (BDd) may be misdiagnosed as major depressive disorder (MDD), resulting in poor treatment outcomes. To identify biomarkers distinguishing BDd from MDD is of substantial clinical significance. This study aimed to characterize specific alterations in intrinsic functional connectivity (FC) patterns in BDd and MDD by combining whole-brain static and dynamic FC. METHODS: A total of 40 MDD and 38 BDd patients, and 50 age-, sex-, education-, and handedness-matched healthy controls (HCs) were included in this study. Static and dynamic FC strengths (FCSs) were analyzed using complete time-series correlations and sliding window correlations, respectively. One-way analysis of variance was performed to test group effects. The combined static and dynamic FCSs were then used to distinguish BDd from MDD and to predict clinical symptom severity. RESULTS: Compared with HCs, BDd patients showed lower static FCS in the medial orbitofrontal cortex and greater static FCS in the caudate, while MDD patients exhibited greater static FCS in the medial orbitofrontal cortex. BDd patients also demonstrated greater static and dynamic FCSs in the thalamus compared with both MDD patients and HCs, while MDD patients exhibited greater dynamic FCS in the precentral gyrus compared with both BDd patients and HCs. Combined static and dynamic FCSs yielded higher accuracy than either static or dynamic FCS analysis alone, and also predicted anhedonia severity in BDd patients and negative mood severity in MDD patients. CONCLUSION: Altered FC within frontal-striatal-thalamic circuits of BDd patients and within the default mode network/sensorimotor network of MDD patients accurately distinguishes between these disorders. These unique FC patterns may serve as biomarkers for differential diagnosis and provide clues to the pathogenesis of mood disorders.

Interactions between monoamine oxidase A rs1137070 and smoking on brain structure and function in male smokers.

The monoamine oxidase A (MAOA) enzyme metabolizes monoamine neurotransmitters such as dopamine, serotonin and norepinephrine, and its genetic polymorphism (rs1137070) influences its activity level and is associated with smoking behaviors. However, the underlying neural mechanisms of the gene × environment interactions remain largely unknown. In this study, we aimed to explore the interactive effects of the rs1137070 and cigarette smoking on gray matter volume (GMV) and functional connectivity strength (FCS). A total of 81 smokers and 42 nonsmokers were enrolled in the present study. Voxel-based morphometry analysis showed a significant rs1137070 genotype × smoking effect on the GMV of the left orbitofrontal cortex (OFC), such that individuals with risk allele had greater GMV among nonsmokers but not smokers. Meanwhile, rs1137070 variant and nicotine dependence interactively altered the FCS of the right hippocampus, the left inferior parietal lobule (IPL), the left dorsolateral prefrontal cortex and bilateral OFC. In addition, the FCS in the left IPL was correlated with smoking initiation and smoking years in smokers with the risk allele. These findings suggest that MAOA rs1137070 contributes to the susceptibility to nicotine dependence through its influence on brain circuits involved in reward and attention, and interacts with smoking in the progression.

Effects of sound therapy on resting-state functional brain networks in patients with tinnitus: A graph-theoretical-based study.

BACKGROUND: Tinnitus is considered to be triggered by aberrant neural activity in the brain. Sound therapy is regarded as a reasonable management option for tinnitus treatment and has been applied in the clinical setting for decades. HYPOTHESIS: We hypothesized that sound therapy, a commonly used tinnitus treatment method, would alter the functional connectivity (FC) of brain regions in tinnitus models. STUDY TYPE: Longitudinal. POPULATION: Resting-state functional MRI data were collected from 27 tinnitus patients before and after 12 weeks of sound therapy. Twenty-seven age- and sex-matched healthy controls were also longitudinally scanned at the 12-week timepoint. FIELD STRENGTH: 3.0T MRI system and echo planar imaging (EPI) sequence, 3D brain volume imaging (BRAVO) sequence. ASSESSMENT: Functional connectivity strength (FCS), a graph-theoretical-based analytic method, was applied to analyze the FC features in the whole brain. STATISTICAL TESTS: Student's t-test and chi-square test were used for analyses between two groups. A two-way analysis of covariance (ANCOVA) followed by post-hoc analyses was performed to determine differences of FC. RESULTS: The interaction effect between the two groups and two scans on FCS was observed in the bilateral thalami and left anterior cingulate cortex (ACC). The fitted FCS values in the bilateral thalami were significantly higher in tinnitus patients at baseline and decreased to a relatively normal range after sound therapy compared with healthy controls. Conversely, the fitted FCS values in the left ACC were within the normal range, but increased after treatment (1.08 ± 0.29, P < 0.02); however, there was no change in the control group. Importantly, significant correlations were observed between the FCS changes in the right thalamus (P = 0.028), the FC of the right thalamus-right inferior frontal gyrus (P = 0.015), and symptomatic improvement. DATA CONCLUSION: Sound therapy may modulate the brain network by altering the gating function of the thalamus as well as enhancing the tinnitus-canceling system. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:1731-1741.

Spatially Overlapping Regions Show Abnormal Thalamo-frontal Circuit and Abnormal Precuneus in Disorders of Consciousness.

Understanding the neural mechanisms of disorders of consciousness (DOC) is essential for estimating the conscious level and diagnosing DOC patients. Although previous studies reported brain functional connectivity (FC) and spontaneous neural activity patterns associated with consciousness, the relationship between them remains unclear. In this study, we identified the abnormal brain regions in DOC patients by performing voxel-wise FC strength (FCS) and fractional amplitude of low-frequency fluctuations (fALFF) analyses on resting-state functional magnetic resonance imaging data of 15 DOC patients and 24 healthy controls. Furthermore, we detected spatial intersections between two measures and estimated the correlations between either the FCS or the fALFF and the subscales of the Coma Recovery Scale-Revised (CRS-R). We found that the right superior frontal gyrus, left thalamus and right precuneus in which the DOC patients had a lower local FCS and fALFF than healthy controls, are coincident with regions of the mesocircuit model. In the right precuneus, the local FCS/fALFF was significantly positively correlated with the oromotor and motor scores/motor score of the CRS-R. Our findings may indicate that the co-occurrent pattern of spontaneous neural activity and functional connectivity in the thalamo-frontal circuit and the precuneus are associated with motor function in DOC patients.

Altered cerebellar functional connectivity in remitted bipolar disorder: A resting-state functional magnetic resonance imaging study.

OBJECTIVES: Several recent studies have reported a strong association between the cerebellar structural and functional abnormalities and psychiatric disorders. However, there are no studies to investigate possible changes in cerebellar functional connectivity in bipolar disorder. This study aimed to examine the whole-brain functional connectivity pattern of patients with remitted bipolar disorder II, in particular in the cerebellum. METHODS: A total of 25 patients with remitted bipolar disorder II and 25 controls underwent resting-state functional magnetic resonance imaging and neuropsychological tests. Voxel-wise whole-brain connectivity was analyzed using a graph theory approach: functional connectivity strength. A seed-based resting-state functional connectivity analysis was further performed to investigate abnormal functional connectivity pattern of those regions with changed functional connectivity strength. RESULTS: Remitted bipolar disorder II patients had significantly decreased functional connectivity strength in the bilateral posterior lobes of cerebellum (mainly lobules VIIb/VIIIa). The seed-based functional connectivity analyses revealed decreased functional connectivity between the right posterior cerebellum and the default mode network (i.e. right posterior cingulate cortex/precuneus and right superior temporal gyrus), bilateral hippocampus, right putamen, left paracentral lobule and bilateral posterior cerebellum and decreased functional connectivity between the left posterior cerebellum and the right inferior parietal lobule and bilateral posterior cerebellum in patients with remitted bipolar disorder II. CONCLUSION: Our results suggest that cerebellar dysconnectivity, in particular distributed cerebellar-cerebral functional connectivity, might be associated with the pathogenesis of bipolar disorder.

Impact of previous episodes of hepatic encephalopathy on short-term brain function recovery after liver transplantation: a functional connectivity strength study.

Neuropsychological studies have documented an incomplete reversal of pre-existing cognitive dysfunction in cirrhotic patients after liver transplantation (LT) and have found this is more severe in patients with hepatic encephalopathy (HE). In this study, we aimed to investigate the impact of prior HE episodes on post-transplantation brain function recovery. Resting-state functional magnetic resonance imaging data was collected from 30 healthy controls and 33 cirrhotic patients (HE, n = 15 and noHE, n = 18) before and one month after LT. Long- and short-range functional connectivity strength (FCS) analysis indicated that before transplantation both noHE and HE groups showed diffuse FCS abnormalities relative to healthy controls. For the noHE group, the abnormal FCS found before LT largely returned to normal levels after LT, except for in the cerebellum, precuneus, and orbital middle frontal gyrus. However, the abnormal FCS prior to LT was largely preserved in the HE group, including high-level cognition-related (frontal and parietal lobes) and vision-related areas (occipital lobe, cuneus, and precuneus). In addition, comparisons between HE and noHE groups revealed that weaker FCS in default mode network (DMN) in HE group persisted from pre- to post- LT. Correlation analysis showed that changes in FCS in the left postcentral and right middle frontal gyrus correlated with alterations in neuropsychological performance and ammonia levels. In conclusion, the findings in this study demonstrate potential adverse effects of pre-LT episode of HE on post-LT brain function recovery, and reveal that DMN may be the most affected brain region by HE episodes, which can't be reversed by LT.

Abnormal functional connectivity strength in patients with adolescent-onset schizophrenia: a resting-state fMRI study.

Structural and functional abnormalities were reported in the brain of patients with adolescent-onset schizophrenia (AOS). However, evidence of abnormal functional connectivity of the brain in AOS patients is limited. Thus, we analyzed the resting-state functional magnetic resonance scans of 48 drug-naive AOS patients and 31 healthy controls to determine their functional connectivity strength (FCS) and examined if FCS abnormalities were correlated with clinical characteristics. Compared with healthy controls, AOS patients showed significantly increased FCS in the left cerebellum VI and right inferior frontal gyrus/insula. A positive correlation was observed between FCS values in the right inferior frontal gyrus/insula and general psychopathology scores of positive and negative syndrome scale. Results suggest that functional connectivity pattern is disrupted in drug-naive AOS patients. The FCS values in this abnormal region have potential for evaluating the disease severity.

Whole brain functional connectivity in clinically isolated syndrome without conventional brain MRI lesions.

OBJECTIVE: To investigate brain functional connectivity (FC) alterations in patients with clinically isolated syndromes (CIS) presenting without conventional brain MRI lesions, and to identify the FC differences between the CIS patients who converted to multiple sclerosis (MS) and those not converted during a 5-year follow-up. METHODS: We recruited 20 CIS patients without conventional brain lesions, 28 patients with MS and 28 healthy controls (HC). Normalized voxel-based functional connectivity strength (nFCS) was determined using resting-state fMRI (R-fMRI) and compared among groups. Furthermore, 5-years clinical follow-up of the CIS patients was performed to examine the differences in nFCS between converters and non-converters. RESULTS: Compared to HC, CIS patients showed significantly decreased nFCS in the visual areas and increased nFCS in several brain regions predominately in the temporal lobes. MS patients revealed more widespread higher nFCS especially in deep grey matter (DGM), compared to CIS and HC. In the four CIS patients converting to MS, significantly higher nFCS was found in right anterior cingulate gyrus (ACC) and fusiform gyrus (FG), compared to non-converted patients. CONCLUSION: We demonstrated both functional impairment and compensation in CIS by R-fMRI. nFCS alteration in ACC and FG seems to occur in CIS patients at risk of developing MS. KEY POINTS: • Both functional impairment and compensation occur in CIS without conventional brain lesions. • MS patients revealed more widespread higher nFCS especially in deep grey matter. • nFCS alteration may help stratifying CIS at risk of developing MS.

Functional cortical reorganization in cases of cervical spondylotic myelopathy and changes associated with surgery.

OBJECTIVE The physiological mechanisms underlying the recovery of motor function after cervical spondylotic myelopathy (CSM) surgery are poorly understood. Neuronal plasticity allows neurons to compensate for injury and disease and to adjust their activities in response to new situations or changes in their environment. Cortical reorganization as well as improvement in corticospinal conduction happens during motor recovery after stroke and spinal cord injury. In this study the authors aimed to understand the cortical changes that occur due to CSM and following CSM surgery and to correlate these changes with functional recovery by using blood oxygen level-dependent (BOLD) functional MRI (fMRI). METHODS Twenty-two patients having symptoms related to cervical cord compression due to spondylotic changes along with 12 age- and sex-matched healthy controls were included in this study. Patients underwent cervical spine MRI and BOLD fMRI at 1 month before surgery (baseline) and 6 months after surgery. RESULTS Five patients were excluded from analysis because of technical problems; thus, 17 patients made up the study cohort. The mean overall modified Japanese Orthopaedic Association score improved in patients following surgery. Mean upper-extremity, lower-extremity, and sensory scores improved significantly. In the preoperative patient group the volume of activation (VOA) was significantly higher than that in controls. The VOA after surgery was reduced as compared with that before surgery, although it remained higher than that in the control group. In the preoperative patient group, activations were noted only in the left precentral gyrus (PrCG). In the postoperative group, activations were seen in the left postcentral gyrus (PoCG), as well as the PrCG and premotor and supplementary motor cortices. In postoperative group, the VOA was higher in both the PrCG and PoCG as compared with those in the control group. CONCLUSIONS There is over-recruitment of sensorimotor cortices during nondexterous relative to dexterous movements before surgery. After surgery, there was recruitment of other cortical areas such as the PoCG and premotor and supplementary motor cortices, which correlated with improvement in dexterity, but activation in these areas was greater than that found in controls. The results show that improvement in dexterity and finer movements of the upper limbs is associated with recruitment areas other than the premotor cortex to compensate for the damage in the cervical spinal cord.

Increased functional connectivity strength of right inferior temporal gyrus in first-episode, drug-naive somatization disorder.

BACKGROUND: Evidence of brain structural and functional alterations have been implicated in patients with somatization disorder (SD). However, little is known about brain functional connectivity in SD. In the present study, resting-state functional magnetic resonance imaging (fMRI) and graph theory were used to obtain a comprehensive view of whole-brain functional connectivity and to investigate the changes of voxel-wise functional networks in patients with SD. METHODS: Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex- and education-matched healthy controls (HCs) underwent resting-state fMRI. The graph theory approach was employed to analyze the data. RESULTS: Compared to the HCs, patients with SD showed significantly increased functional connectivity strength in the right inferior temporal gyrus (ITG). There is a significant positive correlation between the z-values of the cluster in the right ITG and Hamilton Anxiety Scale scores. CONCLUSIONS: Our findings indicate that there is a disruption of the functional connectivity pattern in the right ITG in first-episode, treatment-naive patients with SD, which bears clinical significance.

Individualized functional connectome abnormalities obtained using two normative model unveil neurophysiological subtypes of obsessive compulsive disorder.

The high heterogeneity observed among patients with obsessive-compulsive disorder (OCD) underscores the need to identify neurophysiological OCD subtypes to facilitate personalized diagnosis and treatment. In this study, our aim was to identify potential OCD subtypes based on individualized functional connectome abnormalities. We recruited a total of 99 patients with OCD and 104 healthy controls (HCs) matched for demographic characteristics. Individualized functional connectome abnormalities were obtained using normative models of functional connectivity strength (FCS) and used as features to unveil OCD subtypes. Sensitivity analyses were conducted to assess the reproducibility and robustness of the clustering outcomes. Patients exhibited significant intersubject heterogeneity in individualized functional connectome abnormalities. Two subtypes with distinct patterns of FCS abnormalities relative to HCs were identified. Subtype 1 patients primarily exhibited significantly decreased FCS in regions including the frontal gyrus, insula, hippocampus, and precentral/postcentral gyrus, whereas subtype 2 patients demonstrated increased FCS in widespread brain regions. When all patients were combined, no significant differences were observed. Additionally, the identified subtypes showed significant differences in age of onset. Furthermore, sensitivity analyses confirmed the reproducibility of our subtyping results. In conclusion, the identified OCD subtypes shed new light on the taxonomy and neurophysiological heterogeneity of OCD.

Resting-state functional MRI study of conventional MRI-negative intractable epilepsy in children.

Objective: The study aimed at investigating functional connectivity strength (FCS) changes in children with MRI-negative intractable epilepsy (ITE) and evaluating correlations between aberrant FCS and both disease duration and intelligence quotient (IQ). Methods: Fifteen children with ITE, 24 children with non-intractable epilepsy (nITE) and 25 matched healthy controls (HCs) were subjected to rs-fMRI. IQ was evaluated by neuropsychological assessment. Voxelwise analysis of covariance was conducted in the whole brain, and then pairwise comparisons were made across three groups using Bonferroni corrections. Results: FCS was significantly different among three groups. Relative to HCs, ITE patients exhibited decreased FCS in right temporal pole of the superior temporal gyrus, middle temporal gyrus, bilateral precuneus, etc and increased FCS values in left triangular part of the inferior frontal gyrus, parahippocampal gyrus, supplementary motor area, caudate and right calcarine fissure and surrounding cortex and midbrain. The nITE patients presented decreased FCS in right orbital superior frontal gyrus, precuneus etc and increased FCS in bilateral fusiform gyri, parahippocampal gyri, etc. In comparison to nITE patients, the ITE patients presented decreased FCS in right medial superior frontal gyrus and left inferior temporal gyrus and increased FCS in right middle temporal gyrus, inferior temporal gyrus and calcarine fissure and surrounding cortex. Correlation analysis indicated that FCS in left caudate demonstrated correlation with verbal IQ (VIQ) and disease duration. Conclusion: ITE patients demonstrated changed FCS values in the temporal and prefrontal cortices relative to nITE patients, which may be related to drug resistance in epilepsy. FCS in the left caudate nucleus associated with VIQ, suggesting the caudate may become a key target for improving cognitive impairment and seizures in children with ITE.

Distance-specific functional connectivity strength alterations in human immunodeficiency virus asymptomatic neurocognitive impairment patients: a cross-sectional study.

Background: Asymptomatic neurocognitive impairment (ANI) is the mildest form of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs), and functional connectivity strength (FCS) alternations have been observed in the ANI stage. However, it is not clear whether the FCS alterations are influenced by the anatomical distance. This study sought to investigate distance-specific FCS changes in HIV ANI patients. Methods: In total, 29 patients with HAND and 32 healthy controls (HCs) were enrolled in the study. Between-group differences were detected for short, middle and long range anatomical distance FCS. A correlation analysis was performed to examine the relationship between distance-specific FCS and immunological parameters and neuropsychological tests. A receiver operating characteristic (ROC) analysis was conducted to examine the discriminative performance for HIV ANI patients. Results: In comparison to the HCs, the HAND patients showed increased short-range FCS in the left inferior parietal lobule (IPL), middle-range FCS in the superior temporal gyrus (STG), long-range FCS in the left precuneus (PCC), and decreased FCS in the right postcentral gyrus (PCG) (cluster P<0.05, voxel significance P<0.001). Further, the long-range FCS in the right PCG was negatively correlated with the CD4/CD8 ratio (r=-0.479, 95% confidence interval (CI): -0.735 to -0.104, P=0.015), and the distance-specific FCS also showed good classification performance between the HAND patients and HCs. The left IPL, left STG, right PCG, and left PCC had areas under the curve (AUCs) of 0.875 [95% confidence interval (CI): 0.758-0.949, P<0.0001], 0.806 (95% CI: 0.677-0.900, P<0.0001), 0.855 (95% CI: 0.734-0.935, P<0.0001), and 0.852 (95% CI: 0.754-0.950, P<0.0001), respectively. There was no significant relationship between the distance-specific FCS and the neuropsychological tests. Conclusions: Distance-specific FCS could be used to examine subtle alternations in HIV-infected patients in the ANI stage and help to explain the possible neurophysiological mechanism of HAND.

Aberrant Neurovascular Coupling in Diabetic Retinopathy Using Arterial Spin Labeling (ASL) and Functional Magnetic Resonance Imaging (fMRI) methods.

Background: Previous imaging studies have demonstrated that diabetic retinopathy (DR) is linked to structural and functional abnormalities in the brain. However, the extent to which DR patients exhibit abnormal neurovascular coupling remains largely unknown. Methods: Thirty-one patients with DR and 31 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) to calculate functional connectivity strength (FCS) and arterial spin-labeling imaging (ASL) to calculate cerebral blood flow (CBF). The study compared CBF-FCS coupling across the entire grey matter and CBF/FCS ratios (representing blood supply per unit of connectivity strength) per voxel between the two groups. Additionally, a support vector machine (SVM) method was employed to differentiate between diabetic retinopathy (DR) patients and healthy controls (HC). Results: In DRpatients compared to healthy controls, there was a reduction in CBF-FCS coupling across the entire grey matter. Specifically, DR patients exhibited elevated CBF/FCS ratios primarily in the primary visual cortex, including the right calcarine fissure and surrounding cortex. On the other hand, reduced CBF/FCS ratios were mainly observed in premotor and supplementary motor areas, including the left middle frontal gyrus. Conclusion: An elevated CBF/FCS ratio suggests that patients with DR may have a reduced volume of gray matter in the brain. A decrease in its ratio indicates a decrease in regional CBF in patients with DR. These findings suggest that neurovascular decoupling in the visual cortex, as well as in the supplementary motor and frontal gyrus, may represent a neuropathological mechanism in diabetic retinopathy.

Treatment effects of N-acetyl cysteine on resting-state functional MRI and cognitive performance in patients with chronic mild traumatic brain injury: a longitudinal study.

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups including controls (CN, n = 25), and patients receiving treatment with N-acetyl cysteine (NAC, n = 25). NAC group received 50 mg/kg intravenous (IV) medication once a day per week. In the rest of the week, they took one 500 mg NAC tablet twice per day. Each patient underwent rs-fMRI scanning at two timepoints including the baseline and 3 months later at follow-up, while the NAC group received a combination of oral and IV NAC over that time. Three rs-fMRI metrics were measured including fractional amplitude of low frequency fluctuations (fALFF), degree centrality (DC), and functional connectivity strength (FCS). Neuropsychological tests were also assessed at the same day of scanning for each patient. The alteration of rs-fMRI metrics and cognitive scores were measured over 3 months treatment with NAC. Then, the correlation analysis was executed to estimate the association of rs-fMRI measurements and cognitive performance over 3 months (p < 0.05). Two significant group-by-time effects demonstrated the changes of rs-fMRI metrics particularly in the regions located in the default mode network (DMN), sensorimotor network, and emotional circuits that were significantly correlated with cognitive function recovery over 3 months treatment with NAC (p < 0.05). NAC appears to modulate neural activity and functional connectivity in specific brain networks, and these changes could account for clinical improvement. This study confirmed the short-term therapeutic efficacy of NAC in chronic mTBI patients that may contribute to understanding of neurophysiological effects of NAC in mTBI. These findings encourage further research on long-term neurobehavioral assessment of NAC assisting development of therapeutic plans in mTBI.

Altered resting-state neurovascular coupling in patients with pontine infarction.

The risk for motor and cognitive impairment is increased in patients with chronic pontine infarction (PI). In this study, we attempted to explore the alterations of neurovascular coupling (NVC) in order to understand the neural basis of behavioral impairment after PI. Three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied in 49 patients with unilateral PI (left-sided, n = 26; right-sided, n = 23) and 30 matched normal subjects to assess whole-brain cerebral blood flow (CBF) and functional connectivity strength (FCS). We evaluated NVC in each subject by calculating the correlation coefficient between the whole-brain CBF and FCS (CBF-FCS coupling) and the ratio between voxel-wise CBF and FCS (CBF/FCS ratio). The FCS maps were then divided into long-range and short-range FCS to identify the influence of connection distance. The results indicated that the CBF-FCS coupling in the whole-brain level was significantly interrupted in PI patients, and the CBF/FCS ratio in cognition-related brain regions was abnormal. Distance-dependent results demonstrated that PI had a more serious effect on long-range neurovascular coupling. Correlation analysis revealed that the changes in neurovascular coupling were correlated with working memory scores. These findings imply that disruption of neurovascular coupling in the remote-infarction brain regions may underlie the impaired cognitive functions in chronic PI.