Most recent paper
Aberrant dynamic functional network connectivity in vestibular migraine patients without peripheral vestibular lesion
Eur Arch Otorhinolaryngol. 2023 Jan 28. doi: 10.1007/s00405-023-07847-8. Online ahead of print.
PURPOSE: This study aimed to investigate changes in dynamic functional network connectivity (FNC) in patients with vestibular migraine (VM) and explore their relationship with clinical manifestations.
METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were scanned from 35 VM patients without peripheral vestibular lesion and 40 age-, sex- and education-matched healthy controls (HC). Independent component analysis (ICA), sliding window (SW) and k-means clustering analysis were performed to explore the difference in FNC and temporal characteristics between two groups. Additionally, Pearson's partial correlation analysis was adopted to investigate the relationship between clinical manifestations and rs-fMRI results in patients with VM.
RESULTS: Compared with HC, patients with VM showed increased FNC in pairs of extrastriate visual network (eVN)-ventral attention network (VAN), eVN-default mode network (DMN) and eVN-left frontoparietal network (lFPN), and exhibited decreased FNC in pairs of VAN-auditory network (AuN). The altered FNC was correlated with clinical manifestations of patients with VM. Additionally, we found increased mean dwell time and fractional windows in state 2 in VM patients compared with HC. Mean dwell time was positively correlated with headache impact test-6 (HIT-6) scores, fractional windows was positively associated with dizziness handicap inventory (DHI) scores.
CONCLUSION: Our results indicated that patients with VM showed altered FNC primarily between sensory networks and networks related to cognitive, emotional and attention implementation, with more time spent in a state characterized by positive FNC between sensor cortex system and dorsal attention network (DAN). These findings could help reinforce the understanding on the neural mechanisms of VM.
Impact of multidomain preventive strategies on functional brain connectivity in older adults with cognitive complaint: Subset from the Montpellier center of the ancillary MAPT-MRI study
Front Aging Neurosci. 2023 Jan 10;14:971220. doi: 10.3389/fnagi.2022.971220. eCollection 2022.
INTRODUCTION: The impact of multi-domain preventive interventions on older adults, in particular on those with higher risk to develop Alzheimer's disease (AD), could be beneficial, as it may delay cognitive decline. However, the precise mechanism of such positive impact is not fully understood and may involve brain reserve and adaptability of brain functional connectivity (FC).
METHODS: To determine the effect of multidomain interventions (involving physical activity, cognitive training, nutritional counseling alone or in combination with omega-3 fatty acid supplementation and vs. a placebo) on the brain, longitudinal FC changes were assessed after 36 months of intervention on 100 older adults (above 70 year-old) with subjective cognitive complaints.
RESULTS: No global change in FC was detected after uni or multidomain preventive interventions. However, an effect of omega-3 fatty acid supplementation dependent on cognitive decline status was underlined for frontoparietal, salience, visual and sensorimotor networks FC. These findings were independent of the cortical thickness and vascular burden.
DISCUSSION: These results emphasize the importance of patient stratification, based on risk factors, for preventive interventions.
Resting-state functional-MRI in iNPH: can default mode and motor networks changes improve patient selection and outcome? Preliminary report
Fluids Barriers CNS. 2023 Jan 26;20(1):7. doi: 10.1186/s12987-023-00407-6.
BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive and partially reversible form of dementia, characterized by impaired interactions between multiple brain regions. Because of the presence of comorbidities and a lack of accurate diagnostic and prognostic biomarkers, only a minority of patients receives disease-specific treatment. Recently, resting-state functional-magnetic resonance imaging (rs-fMRI) has demonstrated functional connectivity alterations in inter-hemispheric, frontal, occipital, default-mode (DMN) and motor network (MN) circuits. Herein, we report our experience in a cohort of iNPH patients that underwent cerebrospinal fluid (CSF) dynamics evaluation and rs-fMRI. The study aimed to identify functional circuits related to iNPH and explore the relationship between DMN and MN recordings and clinical modifications before and after infusion and tap test, trying to understand iNPH pathophysiology and to predict the best responders to ventriculoperitoneal shunt (VPS) implant.
METHODS: We prospectively collected data regarding clinical assessment, neuroradiological findings, lumbar infusion and tap test of thirty-two iNPH patients who underwent VPS implant. Rs-fMRI was performed using MELODIC-ICA both before and after the tap test. Rs-fMRI data of thirty healthy subjects were also recorded.
RESULTS: At the baseline, reduced z-DMN and z-MN scores were recorded in the iNPH cohort compared with controls. Higher z-scores were recorded in more impaired patients. Both z-scores significantly improved after the tap test except in subjects with a low resistance to outflow value and without a significant clinical improvement after the test. A statistically significant difference in mean MN connectivity scores for tap test responders and non-responders was demonstrated both before (p = 0.0236) and after the test (p = 0.00137). A statistically significant main effect of the tap test on DMN connectivity after CSF subtraction was recorded (p = 0.038).
CONCLUSIONS: Our results suggest the presence of a partially reversible plasticity functional mechanism in DMN and MN. Low values compensate for the initial stages of the disease, while higher values of z-DMN were recorded in older patients with a longer duration of symptoms, suggesting an exhausted plasticity compensation. The standardization of this technique could play a role as a non-invasive biomarker in iNPH disease, suggesting the right time for surgery. Trial Registration Prot. IRB 090/2021.
AJNR Am J Neuroradiol. 2023 Jan 26. doi: 10.3174/ajnr.A7778. Online ahead of print.
BACKGROUND AND PURPOSE: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy.
MATERIALS AND METHODS: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps.
RESULTS: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices.
CONCLUSIONS: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.
Midbrain structure volume, estimated myelin and functional connectivity in idiopathic generalised epilepsy
Epilepsy Behav. 2023 Jan 24;140:109084. doi: 10.1016/j.yebeh.2023.109084. Online ahead of print.
BACKGROUND: Structural and functional neuroimaging studies often overlook lower basal ganglia structures located in and adjacent to the midbrain due to poor contrast on clinically acquired T1-weighted scans. Here, we acquired T1-weighted, T2-weighted, and resting-state fMRI scans to investigate differences in volume, estimated myelin content and functional connectivity of the substantia nigra (SN), subthalamic nuclei (SubTN) and red nuclei (RN) of the midbrain in IGE.
METHODS: Thirty-three patients with IGE (23 refractory, 10 non-refractory) and 39 age and sex-matched healthy controls underwent MR imaging. Midbrain structures were automatically segmented from T2-weighted images and structural volumes were calculated. The estimated myelin content for each structure was determined using a T1-weighted/T2-weighted ratio method. Resting-state functional connectivity analysis of midbrain structures (seed-based) was performed using the CONN toolbox.
RESULTS: An increased volume of the right RN was found in IGE and structural volumes of the right SubTN differed between patients with non-refractory and refractory IGE. However, no volume findings survived corrections for multiple comparisons. No myelin alterations of midbrain structures were found for any subject groups. We found functional connectivity alterations including significantly decreased connectivity between the left SN and the thalamus and significantly increased connectivity between the right SubTN and the superior frontal gyrus in IGE.
CONCLUSIONS: We report volumetric and functional connectivity alterations of the midbrain in patients with IGE. We postulate that potential increases in structural volumes are due to increased iron deposition that impacts T2-weighted contrast. These findings are consistent with previous studies demonstrating pathophysiological abnormalities of the lower basal ganglia in animal models of generalised epilepsy.
Sex differences in effects of tDCS and language treatments on brain functional connectivity in primary progressive aphasia
Neuroimage Clin. 2023 Jan 20;37:103329. doi: 10.1016/j.nicl.2023.103329. Online ahead of print.
Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or language treatment(s). In the current study, we compared sex differences, induced by active-tDCS and language therapy alone, in the default mode and language networks, acquired during resting-state fMRI in 36 PPA patients. Using a novel statistical method, the covariate-assisted-principal-regression (CAPs) technique, we found sex and age differences in FC changes following active-tDCS. In the default mode network (DMN): (1) men (in both conditions) showed greater FC in DMN than women. (2) men who received active-tDCS showed greater FC in the DMN than men who received language-treatment only. In the language network: (1) women who received active-tDCS showed significantly greater FC across the language network than women who received sham-tDCS. As age increases, regardless of sex and treatment condition, FC in language regions decreases. The current findings suggest active-tDCS treatment in PPA alters network-specific FC in a sex-dependent manner.
Preoperative Detection of Subtle Focal Cortical Dysplasia in Children by Combined Arterial Spin Labeling, Voxel-Based Morphometry, Electroencephalography-Synchronized Functional MRI, Resting-State Regional Homogeneity, and 18F-fluorodeoxyglucose...
Neurosurgery. 2022 Dec 22. doi: 10.1227/neu.0000000000002310. Online ahead of print.
BACKGROUND: Focal cortical dysplasia (FCD) causes drug-resistant epilepsy in children that can be cured surgically, but the lesions are often unseen by imaging.
OBJECTIVE: To assess the efficiency of arterial spin labeling (ASL), voxel-based-morphometry (VBM), fMRI electroencephalography (EEG), resting-state regional homogeneity (ReHo), 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their combination in detecting pediatric FCD.
METHODS: We prospectively included 10 children for whom FCD was localized by surgical resection. They underwent 3T MR acquisition with concurrent EEG, including ASL perfusion, resting-state BOLD fMRI (allowing the processing of EEG-fMRI and ReHo), 3D T1-weighted images processed using VBM, and FDG PET-CT coregistered with MRI. Detection was assessed visually and by comparison with healthy controls (for ASL and VBM).
RESULTS: Eight children had normal MRI, and 2 had asymmetric sulci. Using MR techniques, FCD was accurately detected by ASL for 6/10, VBM for 5/10, EEG-fMRI for 5/8 (excluding 2 with uninterpretable results), and ReHo for 4/10 patients. The combination of ASL, VBM, and ReHo allowed correct FCD detection for 9/10 patients. FDG PET alone showed higher accuracy than the other techniques (7/9), and its combination with VBM allowed correct FCD detection for 8/9 patients. The detection efficiency was better for patients with asymmetric sulci (2/2 for all techniques), but advanced MR techniques and PET were useful for MR-negative patients (7/8).
CONCLUSION: A combination of multiple imaging techniques, including PET, ASL, and VBM analysis of T1-weighted images, is effective in detecting subtle FCD in children.
The value of brain MRI functional connectivity data in a machine learning classifier for distinguishing migraine from persistent post-traumatic headache
Front Pain Res (Lausanne). 2023 Jan 9;3:1012831. doi: 10.3389/fpain.2022.1012831. eCollection 2022.
BACKGROUND: Post-traumatic headache (PTH) and migraine often have similar phenotypes. The objective of this exploratory study was to develop classification models to differentiate persistent PTH (PPTH) from migraine using clinical data and magnetic resonance imaging (MRI) measures of brain structure and functional connectivity (fc).
METHODS: Thirty-four individuals with migraine and 48 individuals with PPTH attributed to mild TBI were included. All individuals completed questionnaires assessing headache characteristics, mood, sensory hypersensitivities, and cognitive function and underwent brain structural and functional imaging during the same study visit. Clinical features, structural and functional resting-state measures were included as potential variables. Classifiers using ridge logistic regression of principal components were fit on the data. Average accuracy was calculated using leave-one-out cross-validation. Models were fit with and without fc data. The importance of specific variables to the classifier were examined.
RESULTS: With internal variable selection and principal components creation the average accuracy was 72% with fc data and 63.4% without fc data. This classifier with fc data identified individuals with PPTH and individuals with migraine with equal accuracy.
CONCLUSION: Multivariate models based on clinical characteristics, fc, and brain structural data accurately classify and differentiate PPTH vs. migraine suggesting differences in the neuromechanism and clinical features underlying both headache disorders.
Evaluation of altered brain activity in type 2 diabetes using various indices of brain function: A resting-state functional magnetic resonance imaging study
Front Hum Neurosci. 2023 Jan 9;16:1032264. doi: 10.3389/fnhum.2022.1032264. eCollection 2022.
BACKGROUND: Type 2 diabetes mellitus (T2DM) has been identified as a risk factor that increases the rate of cognitive decline. Previous studies showed that patients with T2DM had brain function alterations based on a single index of resting-state functional magnetic resonance imaging (rs-fMRI). The present study aimed to explore spontaneous brain activity in patients with T2DM by comparing various rs-fMRI indices, and to determine the relationship between these changes and cognitive dysfunction.
METHODS: A total of 52 patients with T2DM and age- and sex-matched control participants were included in this study. The amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and voxel-mirrored homotopic connectivity (VMHC) values were calculated to represent the status of spontaneous neural activity. The Montreal Cognitive Assessment (MoCA) was used for the rapid evaluation of cognition in all subjects. Pearson correlation and mediation analyses were conducted to investigate the relationship between rs-fMRI indices and clinical parameters such as fasting glucose, disease duration, and MoCA.
RESULTS: Patients with T2DM had alterations of concordant spontaneous brain activity in brain areas including the bilateral cerebellum posterior lobe, the left inferior temporal gyrus (ITG.L), the parahippocampal gyrus, and the left supplementary motor area (SMA.L). The indices were significantly correlated to each other in most of the detected brain areas. Positive correlations were observed between fasting glucose and neural activity in the surrounding areas of the left insula and the inferior frontal gyrus. MoCA scores were negatively correlated with the ReHo values extracted from the left anterior occipital lobe and the superior cerebellar cortex and were positively correlated with VMHC values extracted from the left caudate and the precentral gyrus (PreCG). No significant mediation effect of abnormal brain activity was found in the relationship between clinical parameters and MoCA scores.
CONCLUSION: The current study demonstrated the functional concordance of abnormal brain activities in patients with T2DM by comparing ALFF, ReHo, and VMHC measurements. Widespread abnormalities mainly involved in motor and sensory processing functions may provide insight into examining T2DM-related neurological pathophysiology.
Identification of chronic mild traumatic brain injury using resting state functional MRI and machine learning techniques
Front Neurosci. 2023 Jan 9;16:1099560. doi: 10.3389/fnins.2022.1099560. eCollection 2022.
Mild traumatic brain injury (mTBI) is a major public health concern that can result in a broad spectrum of short-term and long-term symptoms. Recently, machine learning (ML) algorithms have been used in neuroscience research for diagnostics and prognostic assessment of brain disorders. The present study aimed to develop an automatic classifier to distinguish patients suffering from chronic mTBI from healthy controls (HCs) utilizing multilevel metrics of resting-state functional magnetic resonance imaging (rs-fMRI). Sixty mTBI patients and forty HCs were enrolled and allocated to training and testing datasets with a ratio of 80:20. Several rs-fMRI metrics including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), degree centrality (DC), voxel-mirrored homotopic connectivity (VMHC), functional connectivity strength (FCS), and seed-based FC were generated from two main analytical categories: local measures and network measures. Statistical two-sample t-test was employed comparing between mTBI and HCs groups. Then, for each rs-fMRI metric the features were selected extracting the mean values from the clusters showing significant differences. Finally, the support vector machine (SVM) models based on separate and multilevel metrics were built and the performance of the classifiers were assessed using five-fold cross-validation and via the area under the receiver operating characteristic curve (AUC). Feature importance was estimated using Shapley additive explanation (SHAP) values. Among local measures, the range of AUC was 86.67-100% and the optimal SVM model was obtained based on combined multilevel rs-fMRI metrics and DC as a separate model with AUC of 100%. Among network measures, the range of AUC was 80.42-93.33% and the optimal SVM model was obtained based on the combined multilevel seed-based FC metrics. The SHAP analysis revealed the DC value in the left postcentral and seed-based FC value between the motor ventral network and right superior temporal as the most important local and network features with the greatest contribution to the classification models. Our findings demonstrated that different rs-fMRI metrics can provide complementary information for classifying patients suffering from chronic mTBI. Moreover, we showed that ML approach is a promising tool for detecting patients with mTBI and might serve as potential imaging biomarker to identify patients at individual level.
CLINICAL TRIAL REGISTRATION: [clinicaltrials.gov], identifier [NCT03241732].
Assessing atypical brain functional connectivity development: An approach based on generative adversarial networks
Front Neurosci. 2023 Jan 9;16:1025492. doi: 10.3389/fnins.2022.1025492. eCollection 2022.
Generative Adversarial Networks (GANs) are promising analytical tools in machine learning applications. Characterizing atypical neurodevelopmental processes might be useful in establishing diagnostic and prognostic biomarkers of psychiatric disorders. In this article, we investigate the potential of GANs models combined with functional connectivity (FC) measures to build a predictive neurotypicality score 3-years after scanning. We used a ROI-to-ROI analysis of resting-state functional magnetic resonance imaging (fMRI) data from a community-based cohort of children and adolescents (377 neurotypical and 126 atypical participants). Models were trained on data from neurotypical participants, capturing their sample variability of FC. The discriminator subnetwork of each GAN model discriminated between the learned neurotypical functional connectivity pattern and atypical or unrelated patterns. Discriminator models were combined in ensembles, improving discrimination performance. Explanations for the model's predictions are provided using the LIME (Local Interpretable Model-Agnostic) algorithm and local hubs are identified in light of these explanations. Our findings suggest this approach is a promising strategy to build potential biomarkers based on functional connectivity.
Front Neurosci. 2023 Jan 9;16:1070911. doi: 10.3389/fnins.2022.1070911. eCollection 2022.
OBJECTIVE: This study aims to explore the changes in the structure, perfusion, and function of the bilateral hippocampus in type 2 diabetes mellitus (T2DM) applying multimodal MRI methods, hoping to provide reliable neuroimaging evidence for the diagnosis of hippocampus-related brain injury in T2DM.
METHODS: We recruited 30 T2DM patients and 45 healthy controls (HCs), on which we performed 3D T1-weighted images, resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) sequences, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, fractional ALFF (fALFF) value, coherence-based regional homogeneity (Cohe-ReHo) value, and degree centrality (DC) values of the bilateral hippocampus.
RESULTS: In the T2DM group, the bilateral hippocampal volumes and the CBF value of the right hippocampus were lower than those in the HCs, while the ALFF value, fALFF value, and Cohe-ReHo value of the bilateral hippocampus were higher than those in the HCs. Correlation analysis showed that fasting blood glucose (FBG) was negatively correlated with the residuals of left hippocampal volume (r = -0.407, P = 0.025) and right hippocampal volume (r = -0.420, P = 0.021). The residual of the auditory-verbal learning test (AVLT) (immediate) score was positively correlated with the residual of right hippocampal volume (r = 0.369, P = 0.045).
CONCLUSION: This study indicated that the volume and perfusion of the hippocampus are decreased in T2DM patients that related to chronic hyperglycemia. Local spontaneous neural activity and coordination are increased in the hippocampus of T2DM patients, possibly as an adaptive compensation for cognitive decline.
Front Aging Neurosci. 2023 Jan 9;14:1037347. doi: 10.3389/fnagi.2022.1037347. eCollection 2022.
BACKGROUND: Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. In view of our rapidly aging population, there is an urgent need to identify Alzheimer's disease (AD) at an early stage. A potential way to do so is by assessing the functional connectivity (FC), i.e., the statistical dependency between two or more brain regions, through novel analysis techniques.
METHODS: In the present study, we assessed the static and dynamic FC using different approaches. A resting state (rs)fMRI dataset from the Alzheimer's disease neuroimaging initiative (ADNI) was used (n = 128). The blood-oxygen-level-dependent (BOLD) signals from 116 regions of 4 groups of participants, i.e., healthy controls (HC; n = 35), early mild cognitive impairment (EMCI; n = 29), late mild cognitive impairment (LMCI; n = 30), and Alzheimer's disease (AD; n = 34) were extracted and analyzed. FC and dynamic FC were extracted using Pearson's correlation, sliding-windows correlation analysis (SWA), and the point process analysis (PPA). Additionally, graph theory measures to explore network segregation and integration were computed.
RESULTS: Our results showed a longer characteristic path length and a decreased degree of EMCI in comparison to the other groups. Additionally, an increased FC in several regions in LMCI and AD in contrast to HC and EMCI was detected. These results suggest a maladaptive short-term mechanism to maintain cognition.
CONCLUSION: The increased pattern of FC in several regions in LMCI and AD is observable in all the analyses; however, the PPA enabled us to reduce the computational demands and offered new specific dynamic FC findings.
Alzheimers Dement (N Y). 2023 Jan 18;9(1):e12371. doi: 10.1002/trc2.12371. eCollection 2023.
BACKGROUND: Mild behavioral impairment (MBI) is a syndrome that uses later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting-state functional magnetic resonance imaging (rs-fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI-).
METHODS: From two harmonized dementia-free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI- individuals were identified (mean age: 71.7 years; 54.7% female). Seed-based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p-value of .05 considered significant.
RESULTS: For the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI-. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula.
CONCLUSION: MBI in dementia-free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers.
HIGHLIGHTS: Resting-state functional magnetic resonance imaging was completed in 95 dementia-free persons from FAVR and COMPASS-ND studies.Participants were stratified by informant-rated Mild Behavioral Impairment Checklist (MBI-C) score, ≥6 for MBI+.MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network.These FC changes are consistent with those seen in early-stage Alzheimer's disease.MBI may help identify persons with early-stage neurodegenerative disease.
MRI texture-based radiomics analysis for the identification of altered functional networks in alcoholic patients and animal models
Comput Med Imaging Graph. 2023 Jan 21;104:102187. doi: 10.1016/j.compmedimag.2023.102187. Online ahead of print.
Alcohol use disorder (AUD) is a complex condition representing a leading risk factor for death, disease and disability. Its high prevalence and severe health consequences make necessary a better understanding of the brain network alterations to improve diagnosis and treatment. The purpose of this study was to evaluate the potential of resting-state fMRI 3D texture features as a novel source of biomarkers to identify AUD brain network alterations following a radiomics approach. A longitudinal study was conducted in Marchigian Sardinian alcohol-preferring msP rats (N = 36) who underwent resting-state functional and structural MRI before and after 30 days of alcohol or water consumption. A cross-sectional human study was also conducted among 33 healthy controls and 35 AUD patients. The preprocessed functional data corresponding to control and alcohol conditions were used to perform a probabilistic independent component analysis, identifying seven independent components as resting-state networks. Forty-three radiomic features extracted from each network were compared using a Wilcoxon signed-rank test with Holm correction to identify the network most affected by alcohol consumption. Features extracted from this network were then used in the machine learning process, evaluating two feature selection methods and six predictive models within a nested cross-validation structure. The classification was evaluated by computing the area under the ROC curve. Images were quantized using different numbers of gray-levels to test their influence on the results. The influence of ageing, data preprocessing, and brain iron accumulation were also analyzed. The methodology was validated using structural scans. The striatal network in alcohol-exposed msP rats presented the most significant number of altered features. The radiomics approach supported this result achieving good classification performance in animals (AUC = 0.915 ± 0.100, with 12 features) and humans (AUC = 0.724 ± 0.117, with 9 features) using a random forest model. Using the structural scans, high accuracy was achieved with a multilayer perceptron in both species (animals: AUC > 0.95 with 2 features, humans: AUC > 0.82 with 18 features). The best results were obtained using a feature selection method based on the p-value. The proposed radiomics approach is able to identify AUD patients and alcohol-exposed rats with good accuracy, employing a subset of 3D features extracted from fMRI. Furthermore, it can help identify relevant networks in drug addiction.
Long-term ANT-DBS effects in pilocarpine-induced epileptic rats: A combined 9.4T MRI and histological study
J Neurosci Res. 2023 Jan 25. doi: 10.1002/jnr.25169. Online ahead of print.
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures in animals and humans however, its therapeutic mechanisms remain elusive. This study aimed to combine 9.4T multimodal magnetic resonance imaging (MRI) with histology to investigate the longitudinal effects of long-term ANT-DBS in pilocarpine-induced epileptic rats. Status epilepsy (SE) was induced by LiCl-pilocarpine injection in 11 adult male Sprague-Dawley rats. Four weeks after SE, chronic epileptic rats underwent either ANT-DBS (n = 6) or sham-DBS (n = 5) surgery. Electroencephalography (EEG) and spontaneous recurrent seizures (SRS) were recorded for 1 week. The T2-weighted image and images from resting-state functional MRI (rs-fMRI) were acquired at three states: before SE, at 4 weeks post-SE, and at 5 weeks post-DBS. Volumes of the hippocampal subregions and hippocampal-related functional connectivity (FC) were compared longitudinally. Finally, antibodies against neuronal nuclei (NeuN) and glial fibrillary acidic proteins were used to evaluate neuronal loss and astrogliosis in the hippocampus. Long-term ANT-DBS significantly reduced seizure generalization in pilocarpine-induced epileptic rats. By analyzing the gray matter volume using T2-weighted images, long-term ANT-DBS displayed morphometric restoration of the hippocampal subregions. Neuronal protection of the hippocampal subregions and inhibition of astrogliosis in the hippocampal subregions were observed in the ANT-DBS group. ANT-DBS caused reversible regulation of FC in the insula-hippocampus and subthalamic nucleus-hippocampus. Long-term ANT-DBS provides comprehensive protection of hippocampal histology, hippocampal morphometrics, and hippocampal-related functional networks.
Intrinsic hippocampal connectivity is associated with individual differences in retrospective duration processing
Brain Struct Funct. 2023 Jan 25. doi: 10.1007/s00429-023-02612-3. Online ahead of print.
The estimation of incidentally encoded durations of time intervals (retrospective duration processing) is thought to rely on the retrieval of contextual information associated with a sequence of events, automatically encoded in medial temporal lobe regions. "Time cells" have been described in the hippocampus (HC), encoding the temporal progression of events and their duration. However, whether the HC supports explicit retrospective duration judgments in humans, and which neural dynamics are involved, is still poorly understood. Here we used resting-state fMRI to test the relation between variations in intrinsic connectivity patterns of the HC, and individual differences in retrospective duration processing, assessed using a novel task involving the presentation of ecological stimuli. Results showed that retrospective duration discrimination performance predicted variations in the intrinsic connectivity of the bilateral HC with the right precentral gyrus; follow-up exploratory analyses suggested a role of the CA1 and CA4/DG subfields in driving the observed pattern. Findings provide insights on neural networks associated with implicit processing of durations in the second range.
Examining the usefulness of the brain network marker program using fMRI for the diagnosis and stratification of major depressive disorder: a non-randomized study protocol
BMC Psychiatry. 2023 Jan 24;23(1):63. doi: 10.1186/s12888-023-04560-y.
BACKGROUND: Although many studies have reported the biological basis of major depressive disorder (MDD), none have been put into practical use. Recently, we developed a generalizable brain network marker for MDD diagnoses (diagnostic marker) across multiple imaging sites using resting-state functional magnetic resonance imaging (rs-fMRI). We have planned this clinical trial to establish evidence for the practical applicability of this diagnostic marker as a medical device. In addition, we have developed generalizable brain network markers for MDD stratification (stratification markers), and the verification of these brain network markers is a secondary endpoint of this study.
METHODS: This is a non-randomized, open-label study involving patients with MDD and healthy controls (HCs). We will prospectively acquire rs-fMRI data from 50 patients with MDD and 50 HCs and anterogradely verify whether our diagnostic marker can distinguish between patients with MDD and HCs. Furthermore, we will longitudinally obtain rs-fMRI and clinical data at baseline and 6 weeks later in 80 patients with MDD treated with escitalopram and verify whether it is possible to prospectively distinguish MDD subtypes that are expected to be effectively responsive to escitalopram using our stratification markers.
DISCUSSION: In this study, we will confirm that sufficient accuracy of the diagnostic marker could be reproduced for data from a prospective clinical study. Using longitudinally obtained data, we will also examine whether the "brain network marker for MDD diagnosis" reflects treatment effects in patients with MDD and whether treatment effects can be predicted by "brain network markers for MDD stratification". Data collected in this study will be extremely important for the clinical application of the brain network markers for MDD diagnosis and stratification.
TRIAL REGISTRATION: Japan Registry of Clinical Trials ( jRCTs062220063 ). Registered 12/10/2022.
Altered brain activity and functional connectivity in migraine without aura during and outside attack
Neurol Res. 2023 Jan 24:1-7. doi: 10.1080/01616412.2023.2170938. Online ahead of print.
BACKGROUND: Migraine is commonly seen as a cyclic disorder with variable cortical excitability at different phases. Herein, we investigated the cortical excitability in migraine without aura patients during an attack (MWoA-DA) and interictal period (MWoA-DI) and further explored the functional connectivity (FC) in brain regions with cortical excitability abnormalities in patients.
METHODS: Seven MWoA-DA patients, twenty-seven MWoA-DI patients, and twenty-nine healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuations (ALFF) was assessed to identify spontaneous brain activity. Then, brain regions showing significant differences across groups were identified as regions of interest (ROI) in FC analysis.
RESULTS: Compared with MWoA-DI patients and HC, the ALFF in the trigeminocervical complex (TCC) was higher in the MWoA-DA patients. Decreased FC in MWoA-DA patients was found between TCC and left postcentral gyrus compared with MWoA-DI patients. Compared with HC, ALFF was lower in the right cuneus but higher in the right rolandic operculum of MWoA-DI patients. Additionally, the ALFF in the right cuneus was negatively correlated with the Migraine Disability Assessment Scale (MIDAS) in MWoA-DI patients.
CONCLUSIONS: The trigeminovascular system and impairments in descending pain modulatory pathways participate in the pathophysiology of migraine during the ictal period. The defense effect exists in the interictal phase, and the dysfunction in the cuneus may be related to the disease severity. This dynamic change in different brain regions could deepen our understanding of the physiopathology underlying migraine.
Heliyon. 2022 Dec 16;9(1):e12372. doi: 10.1016/j.heliyon.2022.e12372. eCollection 2023 Jan.
Migraine is a recurrent disease in which the cumulative effect of repeated pain attacks over a long period of time causes changes in brain function. Although there are some studies focusing on the interictal period of migraine, the reproducibility of these results is poor. Therefore, we intend to use a data-driven functional connectivity (FC) approach to probe the alterations in cerebral functional activity during the interictal period, as well as underlying no-task mechanisms of inducing headache attack in migraine patients. In the current research, 24 episodic migraine patients and 23 healthy controls (HCs) were recruited. By analyzing the magnitude of regional homogeneity (ReHo) and low-frequency fractional fluctuation (fALFF), We identified alterations in spontaneous brain activity in migraineurs, including the bilateral middle frontal gyrus, left postcentral, and right lingual gyrus. Thereafter such abnormalities were selected as seeds (ROIs) for FC analysis to further explore the underlying changes between ROIs and the whole brain areas. Compared with HCs, FC between the right middle frontal gyrus with the left precuneus cortex, and bilateral thalamus were enhanced in migraineurs. In addition, increased FC has been showed between the left postcentral gyrus with the bilateral thalamus. Furthermore, negative correlation existed between fALFF values of the left middle frontal gyrus and the pain intensity of migraine attacks (r = -0.4578, p = 0.0245). In summary, abnormal FC between the bilateral thalamus and right middle frontal gyrus, or the left retrocentral gyrus may occur between attacks in migraineurs, which may be the basis for sensory integration and pain regulation dysfunction. Thus, this could become a promising biomarker for the early diagnosis and evaluation of migraine in the interictal period, and provide a novel view for further investigation of the pathogenesis and etiology of recurrent migraine.