Most recent paper
Multiparametric MRI for the improved diagnostic accuracy of Alzheimer's disease and mild cognitive impairment: Research protocol of a case-control study design
PLoS One. 2021 Sep 21;16(9):e0252883. doi: 10.1371/journal.pone.0252883. eCollection 2021.
BACKGROUND: Alzheimer's disease (AD) is a major neurocognitive disorder identified by memory loss and a significant cognitive decline based on previous level of performance in one or more cognitive domains that interferes in the independence of everyday activities. The accuracy of imaging helps to identify the neuropathological features that differentiate AD from its common precursor, mild cognitive impairment (MCI). Identification of early signs will aid in risk stratification of disease and ensures proper management is instituted to reduce the morbidity and mortality associated with AD. Magnetic resonance imaging (MRI) using structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (1H-MRS) performed alone is inadequate. Thus, the combination of multiparametric MRI is proposed to increase the accuracy of diagnosing MCI and AD when compared to elderly healthy controls.
METHODS: This protocol describes a non-interventional case control study. The AD and MCI patients and the healthy elderly controls will undergo multi-parametric MRI. The protocol consists of sMRI, fMRI, DTI, and single-voxel proton MRS sequences. An eco-planar imaging (EPI) will be used to perform resting-state fMRI sequence. The structural images will be analysed using Computational Anatomy Toolbox-12, functional images will be analysed using Statistical Parametric Mapping-12, DPABI (Data Processing & Analysis for Brain Imaging), and Conn software, while DTI and 1H-MRS will be analysed using the FSL (FMRIB's Software Library) and Tarquin respectively. Correlation of the MRI results and the data acquired from the APOE genotyping, neuropsychological evaluations (i.e. Montreal Cognitive Assessment [MoCA], and Mini-Mental State Examination [MMSE] scores) will be performed. The imaging results will also be correlated with the sociodemographic factors. The diagnosis of AD and MCI will be standardized and based on the DSM-5 criteria and the neuropsychological scores.
DISCUSSION: The combination of sMRI, fMRI, DTI, and MRS sequences can provide information on the anatomical and functional changes in the brain such as regional grey matter volume atrophy, impaired functional connectivity among brain regions, and decreased metabolite levels specifically at the posterior cingulate cortex/precuneus. The combination of multiparametric MRI sequences can be used to stratify the management of MCI and AD patients. Accurate imaging can decide on the frequency of follow-up at memory clinics and select classifiers for machine learning that may aid in the disease identification and prognostication. Reliable and consistent quantification, using standardised protocols, are crucial to establish an optimal diagnostic capability in the early detection of Alzheimer's disease.
Correlation Analysis between Regional Homogeneity and Executive Dysfunction in Anti-N-methyl-D-aspartate receptor Encephalitis Patients
Eur J Neurol. 2021 Sep 21. doi: 10.1111/ene.15119. Online ahead of print.
BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by a range of cognitive impairments, especially in executive function. Our study aims to identify the abnormal regional homogeneity (ReHo) in anti-NMDAR encephalitis patients and its relationship with the executive function.
METHODS: Forty patients and forty-two healthy volunteers undertook the Attention Network Test (ATN) and resting-state fMRI scan. ReHo analysis was performed to investigate the neuronal activity synchronization in all subjects. Based on ReHo analysis, a multivariate pattern analysis (MVPA) was carried out to identify the brain regions that differed the most between the two groups.
RESULTS: Compared to controls, the patients had higher executive control (EC) scores (p < 0.05). The patients presented reduced ReHo values in the bilateral posterior cerebellar lobe, anterior cerebellar lobe, midbrain, bilateral caudate nucleus, right superior frontal gyrus, right middle temporal gyrus, bilateral inferior parietal lobule (IPL), and the left middle frontal gyrus. The ReHo values of bilateral IPL in patients were found to be negatively associated with the EC scores. The classification of patients and controls using MVPA had an accuracy of 76.83%,a sensitivity of 82.50%, a specificity of 71.43% and the area under the curve (AUC) was 0.83.
CONCLUSIONS: Our study provides evidence of abnormal cerebral function in anti-NMDAR encephalitis patients, which may contribute to unveil the neuropathological mechanisms of anti-NMDAR encephalitis and their influences on executive dysfunction. The MVPA classifier, based on ReHo, is helpful in identifying anti-NMDAR encephalitis patients from healthy controls.
Neuroimage Clin. 2021 Sep 11;32:102812. doi: 10.1016/j.nicl.2021.102812. Online ahead of print.
Beyond causing local ischemia and cell damage at the site of injury, stroke strongly affects long-range anatomical connections, perturbing the functional organization of brain networks. Several studies reported functional connectivity abnormalities parallelling both behavioral deficits and functional recovery across different cognitive domains. FC alterations suggest that long-range communication in the brain is altered after stroke. However, standard FC analyses cannot reveal the directionality and time scale of inter-areal information transfer. We used resting-state fMRI and covariance-based Granger causality analysis to quantify network-level information transfer and its alteration in stroke. Two main large-scale anomalies were observed in stroke patients. First, inter-hemispheric information transfer was significantly decreased with respect to healthy controls. Second, stroke caused inter-hemispheric asymmetries, as information transfer within the affected hemisphere and from the affected to the intact hemisphere was significantly reduced. Both anomalies were more prominent in resting-state networks related to attention and language, and they correlated with impaired performance in several behavioral domains. Overall, our findings support the hypothesis that stroke provokes asymmetries between the affected and spared hemisphere, with different functional consequences depending on which hemisphere is lesioned.
Treatment of upper limb spasticity with inhibitory repetitive transcranial magnetic stimulation: A randomized placebo-controlled trial
NeuroRehabilitation. 2021 Sep 13. doi: 10.3233/NRE-210088. Online ahead of print.
BACKGROUND: Upper limb dysfunction is a frequent complication after stroke impairing outcome. Inhibitory repetitive transcranial magnetic stimulation (rTMS) applied over the contralesional hemisphere is supposed to enhance the positive effects of conventional rehabilitative treatment.
OBJECTIVE: This double-blind randomized placebo-controlled trial investigated whether inhibitory rTMS as add-on to standard therapy improves upper limb spasticity.
METHODS: Twenty-eight patients (aged 44 to 80 years) with unilateral stroke in the middle cerebral artery territory were analyzed. Participants were randomly assigned to inhibitory, low-frequency (LF-) rTMS (n = 14) or sham-rTMS (n = 14). The primary outcome measure was the spasticity grade, which was assessed with the Modified Ashworth Scale (MAS). In addition, the Fugl-Meyer-Assessment (FMA) for the upper extremity (UE) and a resting-state fMRI were performed to measure motor functions and the sensorimotor network, respectively.
RESULTS: The MAS score was reduced in the LF-rTMS group only, whereas the FMA score improved in both groups over time. Regarding the fMRI data, both groups activated typical regions of the sensorimotor network. In the LF-rTMS group, however, connectivity to the left angular gyrus increased after treatment.
CONCLUSION: Changes in functional connectivity in patients receiving inhibitory rTMS over the contralesional motor cortex suggest that processes of neuronal plasticity are stimulated.
Multi-model Order ICA: A Data-driven Method for Evaluating Brain Functional Network Connectivity Within and Between Multiple Spatial Scales
Brain Connect. 2021 Sep 19. doi: 10.1089/brain.2021.0079. Online ahead of print.
BACKGROUND: While functional connectivity is widely studied, there has been little work studying functional connectivity at different spatial scales. Likewise, the relationship of functional connectivity between spatial scales is unknown.
METHODS: We proposed an independent component analysis (ICA) - based approach to capture information at multiple model orders (component numbers) and to evaluate functional network connectivity (FNC) both within and between model orders. We evaluated the approach by studying group differences in the context of a study of resting fMRI (rsfMRI) data collected from schizophrenia (SZ) individuals and healthy controls (HC). The predictive ability of FNC at multiple spatial scales was assessed using support vector machine (SVM)-based classification.
RESULTS: In addition to consistent predictive patterns at both multiple-model orders and single model orders, unique predictive information was seen at multiple-model orders and in the interaction between model orders. We observed that the FNC between model order 25 and 50 maintained the highest predictive information between HC and SZ. Results highlighted the predictive ability of the somatomotor and visual domains both within and between model orders compared to other functional domains. Also, subcortical-somatomotor, temporal-somatomotor, and temporal-subcortical FNCs had relatively high weights in predicting SZ.
CONCLUSIONS: In sum, multi-model order ICA provides a more comprehensive way to study FNC, produces meaningful and interesting results which are applicable to future studies. We shared the spatial templates from this work at different model orders to provide a reference for the community, which can be leveraged in regression-based or fully automated (spatially constrained) ICA approaches.
Neural Plast. 2021 Sep 8;2021:3741104. doi: 10.1155/2021/3741104. eCollection 2021.
BACKGROUND: Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear.
METHODS: A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier.
RESULTS: Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%.
CONCLUSION: Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.
A Treatment-Response Comparison Study of Resting-State Functional Magnetic Resonance Imaging Between Standard Treatment of SSRI and Standard Treatment of SSRI Plus Non-dominant Hand-Writing Task in Patients With Major Depressive Disorder
Front Psychiatry. 2021 Sep 3;12:698954. doi: 10.3389/fpsyt.2021.698954. eCollection 2021.
Background: Researches have recently shifted from functional/structural imaging studies to functional connectivity (FC) studies in major depressive disorder (MDD). We aimed to compare treatment response of two treatment groups before and after treatment, in terms of both with psychiatric evaluation scales and resting-state functional connectivity (RSFC) changes in order to objectively demonstrate the possible contribution of the non-dominant hand-writing exercise (NHE) effect on depression treatment. Methods: A total of 26 patients who were right-handed women with similar sociodemographic characteristics were enrolled. Their pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychiatric tests were recorded, and then, patients were divided into two groups randomly. A standard treatment (ST) (fix sertraline 50 mg/day) was given to both groups. One randomly selected group was given the NHE in addition to the ST. After 8 weeks of treatment, all patients were reevaluated with rs-fMRI and neuropsychiatric tests. Pre- and post-treatment FC changes within the groups and post-treatment connectivity changes between groups were evaluated. Results: Post-treatment neuropsychiatric tests were significantly different in both groups. Post-treatment, two brain regions' connectivity changed in the ST group, whereas 10 brain regions' connectivity changed significantly in the ST + NHE group. When treatment groups were compared with each other after the treatment, the FC of 13 regions changed in the ST + NHE group compared to the ST group (p-unc/p-PFD <0.05). The density of connectivity changes in the frontal and limbic regions, especially connectivities shown to change in depression treatment, in the ST + NHE group indicates a positive contribution to depression treatment, which is also supported by neuropsychiatric scale changes. Conclusion: NHE, which we developed with inspiration from the Eye Movement Desensitization and Reprocessing (EMDR) method, showed significantly more connecitivity changes related with MDD treatment. Beyond offering a new additional treatment method, our study will also contribute to the current literature with our efforts to evaluate all brain regions and networks that may be related to MDD and its treatment together, without being limited to a few regions. Trial Registration: The rs-fMRI and treatment registers were recorded in the BizMed system, which is the patient registration system of Bezmialem Vakif University Medicine Faculty, under the BAP support project approval code and the registration number 3.2018/8.
Aberrant Intraregional Brain Activity and Functional Connectivity in Patients With Diarrhea-Predominant Irritable Bowel Syndrome
Front Neurosci. 2021 Sep 3;15:721822. doi: 10.3389/fnins.2021.721822. eCollection 2021.
BACKGROUND AND PURPOSE: The appearance and aggravation of diarrhea-predominant irritable bowel syndrome (IBS-D) have proven to be closely related to psychosocial factors. We aimed to measure altered spontaneous brain activity and functional connectivity (FC) in patients with IBS-D using resting-state functional magnetic resonance imaging (RS-fMRI) and to analyze the relationship between these parameters and emotional symptoms.
METHODS: Thirty-six adult IBS-D patients and thirty-six demographic-matched healthy controls (HCs) underwent RS-fMRI scans. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of the two groups were compared. The abnormal regions were selected as the regions of interest to compare whole-brain seed-based FC between the groups. The relationships between RS-fMRI data and mood and gastrointestinal symptoms were analyzed using correlation and mediation analyses.
RESULTS: Compared with HCs, IBS-D patients showed increased ALFF in the right cerebellum posterior lobe, the right lingual gyrus/calcarine, the right postcentral gyrus, the right superior frontal gyrus (SFG), and middle frontal gyrus (MFG), with decreased ALFF in the right inferior parietal lobule, the right striatum, the right anterior cingulated cortex, the right insula, the right hippocampus, the right thalamus, the right midbrain, and the left precuneus. IBS-D patients showed increased ReHo in the bilateral lingual gyrus/calcarine, the bilateral SFG, the right MFG, and the right postcentral gyrus, with decreased ReHo in the orbital part of the left inferior frontal gyrus and the right supplementary motor area. Patients showed enhanced FC between the left precuneus and the bilateral orbitofrontal cortex (OFC). There was a positive correlation between increased ALFF values in the right midbrain and anxiety-depression symptoms in IBS-D patients, and the mediating effect of gastrointestinal symptoms indirectly caused this correlation.
CONCLUSION: IBS-D patients had dysregulated spontaneous activity and FC in regions related to pain regulation and emotional arousal involved in prefrontal-limbic-midbrain circuit and somatosensory processing. The development of mood disorders in IBS-D patients may be partly related to the dysfunction of components in the dopamine pathway (especially the midbrain, OFC) due to visceral pain.
Individual localization value of resting-state fMRI in epilepsy presurgical evaluation: A combined study with stereo-EEG
Clin Neurophysiol. 2021 Aug 30:S1388-2457(21)00707-0. doi: 10.1016/j.clinph.2021.07.028. Online ahead of print.
OBJECTIVE: To examine the individual-patient-level localization value of resting-state functional MRI (rsfMRI) metrics for the seizure onset zone (SOZ) defined by stereo-electroencephalography (SEEG) in patients with medically intractable focal epilepsies.
METHODS: We retrospectively included 19 patients who underwent SEEG implantation for epilepsy presurgical evaluation. Voxel-wise whole-brain analysis was performed on 3.0 T rsfMRI to generate clusters for amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC), which were co-registered with the SEEG-defined SOZ to evaluate their spatial overlap. Subgroup and correlation analyses were conducted for various clinical characteristics.
RESULTS: ALFF demonstrated concordant clusters with SEEG-defined SOZ in 73.7% of patients, with 93.3% sensitivity and 77.8% PPV. The concordance rate showed no significant difference when subgrouped by lesional/non-lesional MRI, SOZ location, interictal epileptiform discharges on scalp EEG, pathology or seizure outcomes. No significant correlation was seen between ALFF concordance rate and epilepsy duration, seizure-onset age, seizure frequency or number of antiseizure medications. ReHo and DC did not achieve favorable concordance results (10.5% and 15.8%, respectively). All concordant clusters showed regional activation, representing increased neural activities.
CONCLUSION: ALFF had high concordance rate with SEEG-defined SOZ at individual-patient level.
SIGNIFICANCE: ALFF activation on rsfMRI can add localizing information for the noninvasive presurgical workup of intractable focal epilepsies.
Where in the brain is "the other's" hand? Mapping dysfunctional neural networks in somatoparaphrenia
Neuroscience. 2021 Sep 16:S0306-4522(21)00459-0. doi: 10.1016/j.neuroscience.2021.09.007. Online ahead of print.
Somatoparaphrenia refers to the delusional belief, typically observed in right brain-damaged patients, that the contralesional limbs belong to someone else. Here, we aimed to uncover the neural activity associated with this productive, i.e. confabulatory, component in a patient, S.P.P., with a large right-sided lesion of both cortical and subcortical gray and white matter. He claimed that his left paralyzed hand belonged to his mother. In a block-design functional magnetic resonance (fMRI) experiment, S.P.P. imagined that the mother would move her (i.e. his left) hand (condition "mother"). Subtraction of the activity elicited by control conditions (imagery of self-generated movement of either left or right hand) from that in the "mother" condition resulted in the focal activation of the pars opercularis of the right inferior frontal gyrus (rIFG). In a separate, resting-state fMRI experiment with S.P.P. and 21 healthy controls, we examined the functional connectivity of the rIFG and the affected hand somatosensory network to the rest of the brain. We found a negative correlation between the activity in the rIFG and that of Broca area and the temporo-parietal junction in the left hemisphere. Furthermore, the affected hand somatosensory network was disconnected from the left secondary somatosensory cortex. Our results link the productive component of somatoparaphrenia to the activity of crucial hubs for integrating the multimodal signals of the affected hand. Furthermore, they provide the first direct evidence supporting the "left narrator model", proposed by Halligan et al. (1995), according to which the confabulations of somatoparaphrenia are due to a disconnection of left hemisphere language areas from right hemisphere parieto-temporal cortex.
Semin Ultrasound CT MR. 2021 Oct;42(5):507-522. doi: 10.1053/j.sult.2021.07.007. Epub 2021 Aug 1.
A comprehensive mapping of the structural and functional circuitry of the brain is a major unresolved problem in contemporary neuroimaging research. Diffusion-weighted and functional MRI have provided investigators with the capability to assess structural and functional connectivity in-vivo, driven primarily by methods of white matter tractography and resting-state fMRI, respectively. These techniques have paved the way for the construction of the functional and structural connectomes, which are quantitative representations of brain architecture as neural networks, comprised of nodes and edges. The connectomes, typically depicted as matrices or graphs, possess topological properties that inherently characterize the strength, efficiency, and organization of the connections between distinct brain regions. Graph theory, a general mathematical framework for analyzing networks, can be implemented to derive metrics from the connectomes that are sensitive to changes in brain connectivity associated with age, sex, cognitive function, and disease. These quantities can be assessed at either the global (whole brain) or local levels, allowing for the identification of distinct regional connectivity hubs and associated localized brain networks, which together serve crucial roles in establishing the structural and functional architecture of the brain. As a result, structural and functional connectomes have each been employed to study the brain circuitry underlying early brain development, neuroplasticity, developmental disorders, psychopathology, epilepsy, aging, neurodegenerative disorders, and traumatic brain injury. While these studies have yielded important insights into brain structure, function, and pathology, a precise description of the innate relationship between functional and structural networks across the brain remains unachieved. To date, connectome research has merely scratched the surface of potential clinical applications and related characterizations of brain-wide connectivity. Continued advances in diffusion and functional MRI acquisition, the delineation of functional and structural networks, and the quantification of neural network properties in specific brain regions, will be invaluable to future progress in neuroimaging science.
Disturbance of functional and effective connectivity of the salience network involved in attention deficits in right temporal lobe epilepsy
Epilepsy Behav. 2021 Sep 15;124:108308. doi: 10.1016/j.yebeh.2021.108308. Online ahead of print.
The salience network (SN) acts as a switch that generates transient control signals to regulate the executive control network (ECN) and the default mode network (DMN) and has been implicated in cognitive processes. Temporal lobe epilepsy (TLE) is usually accompanied by different types of cognitive deficits, but whether it is associated with dysfunctional connectivity of the SN remains unknown. To address this, thirty-six patients with right TLE (rTLE) and thirty-six healthy controls (HCs) were recruited for the present study. All of the participants were subjected to attention network test (ANT) and resting-state functional resonance imaging (rs-fMRI) scanning. The patient group showed deficits in attention performance. Moreover, the functional connectivity (FC) and effective connectivity (EC) were analyzed based on key SN hubs (the anterior cingulate cortex (ACC) and the bilateral anterior insula (AI)). When compared with those in the HC group, the ACC showed increased FC with the left middle frontal gyrus and the left precentral gyrus, and the right AI showed decreased FC with the right precuneus and the right superior occipital gyrus in the patient group. The EC analysis revealed an increased inflow of information from the left middle temporal gyrus to the ACC and the right AI and an increased outflow of information from the bilateral AI to the left middle frontal gyrus. Furthermore, in the correlation analysis, the abnormal EC from the right AI to the left middle temporal gyrus was positively correlated with the executive control effect. These findings demonstrated aberrant modulation of the SN in rTLE, which was particularly characterized by dysfunctional connectivity between the SN and key brain regions in the DMN and ECN. Elucidation of this effect may further contribute to the comprehensive understanding of the neural mechanisms of the SN in regard to attention deficits in patients with TLE.
The resting-state cerebro-cerebellar function connectivity and associations with verbal working memory performance
Behav Brain Res. 2021 Sep 15:113586. doi: 10.1016/j.bbr.2021.113586. Online ahead of print.
The cerebellum plays an important role in cognitive functions through connecting with the cerebral areas. However, the relationship between the resting-state functional connectivity (FC) pattern of human cerebro-cerebellar circuits and cognition is not fully understood. The present study investigated the FC pattern of human cerebro-cerebellar circuits and their associations with verbal working memory performance (an n-back task with three subtasks: 0-back, 1-back, and 2-back) through resting-state functional magnetic resonance imaging (fMRI) data from 37 healthy subjects. The whole-brain connectivity analysis was used to identify the cortical hubs as regions of interest (ROI). Then ROI-based FC analysis was performed to investigate the connectivity characteristics within the key cortical hubs and their associations with n-back task performance. The results showed that the bilateral cerebellar lobule VI as central hubs had increased FC with the default mode network (DMN) node (e.g., right posterior cingulate cortex) and salient network (SN) node (e.g., right anterior cingulate cortex), while decreased FC with the executive control network (ECN) node (e.g., the bilateral superior frontal gyrus). Furthermore, FC values of the cerebellum lobule VI with DMN and ECN nodes correlated with verbal working memory performance (response time of 2-back task). The results suggest that the cerebro-cerebellar circuits involve the underlying neural basis of verbal working memory processing during the resting state.
Peripheral inflammation is associated with micro-structural and functional connectivity changes in depression-related brain networks
Mol Psychiatry. 2021 Sep 17. doi: 10.1038/s41380-021-01272-1. Online ahead of print.
Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density-a plausible marker of extracellular oedema-and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.
Resting-state functional connectivity predictors of treatment response in schizophrenia - A systematic review and meta-analysis
Schizophr Res. 2021 Sep 15;237:153-165. doi: 10.1016/j.schres.2021.09.004. Online ahead of print.
We aimed to systematically synthesize and quantify the utility of pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI) in predicting antipsychotic response in schizophrenia. We searched the PubMed/MEDLINE database for studies that examined the magnitude of association between baseline rs-fMRI assessment and subsequent response to antipsychotic treatment in persons with schizophrenia. We also performed meta-analyses for quantifying the magnitude and accuracy of predicting response defined continuously and categorically. Data from 22 datasets examining 1280 individuals identified striatal and default mode network functional segregation and integration metrics as consistent determinants of treatment response. The pooled correlation coefficient for predicting improvement in total symptoms measured continuously was ~0.47 (12 datasets; 95% CI: 0.35 to 0.59). The pooled odds ratio of predicting categorically defined treatment response was 12.66 (nine datasets; 95% CI: 7.91-20.29), with 81% sensitivity and 76% specificity. rs-fMRI holds promise as a predictive biomarker of antipsychotic treatment response in schizophrenia. Future efforts need to focus on refining feature characterization to improve prediction accuracy, validate prediction models, and evaluate their implementation in clinical practice.
Degree Centrality of a Brain Network Is Altered by Stereotype Threat: Evidences From a Resting-State Functional Magnetic Resonance Imaging Study
Front Psychol. 2021 Aug 31;12:705363. doi: 10.3389/fpsyg.2021.705363. eCollection 2021.
Previous studies have found the effects of stereotype threat (ST) on cognitive processes, emotions, and motivations which could account for the underperformance in domain tasks. Efficient brain function does not require the function of different brain regions during specific tasks, but it does require the brain networks on which information is transported. Based on these, the effects of ST on the degree centrality under the resting state of brain regions related to these processes were investigated under math-related ST. The results showed that RSDC was decreased in the left hippocampus and left middle occipital gyrus (MOC), while RSDC was increased in the left precuneus, the right angular gyrus (AG), and the right superior parietal gyrus (SPG) under ST. Interestingly, we also found that the right-left anterior temporal lobe (ATL) and the right hippocampus were negatively correlated with manipulation check (MC) score in the ST group, while the right-left ATL and the right hippocampus were positively correlated with MC score in the control group. These results might reflect those individuals who attempted to inhibit the negative emotions induced by the negative stereotypes under ST conditions while increasing the self-relevant processes by retrieving episodic memory or autobiographical memory.
Proc SPIE Int Soc Opt Eng. 2021 Feb 15;11596:115961X. doi: 10.1117/12.2580771.
Resting-state functional MRI (rsfMRI) provides important information for studying and mapping the activities and functions of the brain. Conventionally, rsfMRIs are often registered to structural images in the Euclidean space without considering cortical surface geometry. Meanwhile, a surface-based representation offers a relaxed coordinate chart, but this still requires surface registration for group-wise data analysis. In this work, we investigate the performance of two existing surface registration methods in a surface-based rsfMRI analysis framework: FreeSurfer and Hierarchical Spherical Deformation (HSD). To minimize registration bias, we establish shape correspondence using both methods in a group-wise manner that estimates the unbiased average of a given cohort. To evaluate their performance, we focus on neuroanatomical alignment as well as the amount of distortion that can potentially bias surface tessellation for secondary level rsfMRI data analyses. In the pilot analysis, we examine a single timepoint of imaging data from 100 subjects out of an aging cohort. Overall, HSD establishes improved shape correspondence with reduced mean curvature deviation (10.94% less on average per subject, paired t-test: p <10-10) and reduced registration distortion (FreeSurfer: average 41.91% distortion per subject, HSD: 18.63%, paired t-test: p <10-10). Furthermore, HSD introduces less distortion than FreeSurfer in the areas identified in the individual components that were extracted by surface-based independent component analysis (ICA) after spatial smoothing and time series normalization. Consequently, we show that FreeSurfer capture individual components with globally similar but locally different patterns in ICA in visual inspection.
Hippocampal connectivity with retrosplenial cortex is linked to neocortical tau accumulation and memory function
J Neurosci. 2021 Sep 15:JN-RM-0990-21. doi: 10.1523/JNEUROSCI.0990-21.2021. Online ahead of print.
The mechanisms underlying accumulation of Alzheimer's disease (AD)-related tau pathology outside of the medial temporal lobe (MTL) in older adults are unknown but crucial to understanding cognitive decline. A growing body of evidence from human and animal studies strongly implicates neural connectivity in the propagation of tau in humans, but the pathways of neocortical tau spread and its consequences for cognitive function are not well understood. Using resting state fMRI and tau PET imaging from a sample of 97 male and female cognitively normal older adults, we examined MTL structures involved in medial parietal tau accumulation and associations with memory function. Functional connectivity between hippocampus and retrosplenial cortex, a key region of the medial parietal lobe, was associated with tau in medial parietal lobe. By contrast, connectivity between entorhinal and retrosplenial cortices did not correlate with medial parietal lobe tau. Further, greater hippocampal-retrosplenial connectivity was associated with a stronger correlation between MTL and medial parietal lobe tau. Finally, an interaction between connectivity strength and medial parietal tau was associated with episodic memory performance, particularly in the visuospatial domain. This pattern of tau accumulation thus appears to reflect pathways of neural connectivity, and propagation of tau from entorhinal cortex to medial parietal lobe via the hippocampus may represent a critical process in the evolution of cognitive dysfunction in aging and AD.SIGNIFICANCE STATEMENTThe accumulation of tau pathology in the neocortex is a fundamental process underlying Alzheimer's disease. Here, we use functional connectivity in cognitively normal older adults to track the accumulation of tau in the medial parietal lobe, a key region for memory processing that is affected early in the progression of AD. We show that the strength of connectivity between the hippocampus and retrosplenial cortex is related to medial parietal tau burden, and that these tau and connectivity measures interact to associate with episodic memory performance. These findings establish the hippocampus as the origin of medial parietal tau and implicate tau pathology in this region as a crucial marker of the beginnings of Alzheimer's disease.
Hum Brain Mapp. 2021 Sep 16. doi: 10.1002/hbm.25662. Online ahead of print.
Aging is closely associated with cognitive decline affecting attention, memory and executive functions. The hippocampus is the core brain area for human memory, learning, and cognition processing. To delineate the individual functional patterns of hippocampus is pivotal to reveal the neural basis of aging. In this study, we developed a group-guided individual parcellation approach based on semisupervised affinity propagation clustering using the resting-state functional magnetic resonance imaging to identify individual functional subregions of hippocampus and to identify the functional patterns of each subregion during aging. A three-way group parcellation was yielded and was taken as prior information to guide individual parcellation of hippocampus into head, body, and tail in each subject. The superiority of individual parcellation of hippocampus is validated by higher intraregional functional similarities by compared to group-level parcellation results. The individual variations of hippocampus were associated with coactivation patterns of three typical functions of hippocampus. Moreover, the individual functional connectivities of hippocampus subregions with predefined target regions could better predict age than group-level functional connectivities. Our study provides a novel framework for individual brain functional parcellations, which may facilitate the future individual researches for brain cognitions and brain disorders and directing accurate neuromodulation.
Reversed patterns of resting state functional connectivity for females vs. males in posttraumatic stress disorder
Neurobiol Stress. 2021 Sep 1;15:100389. doi: 10.1016/j.ynstr.2021.100389. eCollection 2021 Nov.
BACKGROUND: Posttraumatic stress disorder (PTSD) is twice as prevalent among females as compared to males following potentially traumatic events. While there is evidence for aberrant functional connectivity between hubs of the central executive network (CEN), salience network (SN), and the default mode network (DMN) in PTSD, little is known regarding sex-specificity of this connectivity. The current study aims to directly examine sex-specific resting-state functional connectivity (rs-FC) in trauma exposed males and females, with and without PTSD.
METHODS: One hundred and seventy-eight individuals underwent functional magnetic resonance imaging (fMRI) at rest, of them 85 females (45 with PTSD) and 93 males (57 with PTSD). We conducted whole-brain seed-based analysis using CEN (lateral prefrontal cortex [lPFC]), SN (anterior cingulate cortex [ACC], insula, amygdala [AMG]), and DMN (medial prefrontal cortex [mPFC], posterior parietal cortex [PCC], and hippocampus [HIP]) hubs as seed regions. Group-by-Sex ANOVA was conducted.
RESULTS: The amygdala-precuneus, ACC-precuneus, and hippocampus-precuneus pathways exhibited significant group-by-sex interaction effects, with females with PTSD consistently differing in connectivity patterns from males with PTSD and from trauma-exposed healthy females.
CONCLUSIONS: Sex-specific neural connectivity patterns were found within and between key nodes of the CEN, DMN, and the SN, suggesting opposite patterns of connectivity in PTSD and trauma-exposed controls as a function of sex as a biological variable (SABV). This may point to mechanistic sex differences in adaptation following trauma and may inform differential neural targets for treatment of females and males with PTSD.