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Dopamine Multilocus Genetic Profile, Spontaneous Activity of Left Superior Temporal Gyrus, and Early Therapeutic Effect in Major Depressive Disorder.

Sun, 01/10/2021 - 00:47
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Dopamine Multilocus Genetic Profile, Spontaneous Activity of Left Superior Temporal Gyrus, and Early Therapeutic Effect in Major Depressive Disorder.

Front Psychiatry. 2020;11:591407

Authors: Liu X, Hou Z, Yin Y, Xie C, Zhang H, Zhang H, Zhang Z, Yuan Y

Abstract
Objectives: This study aimed to examine the interactive effects of dopamine (DA) pathway gene and disease on spontaneous brain activity and further to explore the relationship between spontaneous brain activity and the early antidepressant therapeutic effect in patients with major depressive disorder (MDD). Methods: A total of 104 patients with MDD and 64 healthy controls (HCs) were recruited. The Hamilton Depression Scale-24 (HAMD-24) was used to measure the depression severity. Both groups were given resting-state functional magnetic resonance imaging (rs-fMRI) scan. The amplitude of low-frequency fluctuation (ALFF) was calculated to reflect the spontaneous brain activity based on the rs-fMRI data. After treatment for 2 weeks, depression severity was evaluated again, and HAMD-24 reductive rate was used to measure the therapeutic effect of antidepressants. Multilocus genetic profile scores (MGPS) were used to assess the multi-site cumulative effect of DA pathway gene. The interactive effects of MDD and DA pathway gene on the ALFF of regional brain areas were measured by the multivariate linear regression analysis. Finally, partial correlation analysis (age, sex, education, and illness durations as covariates) was performed to identify the relationship between regional ALFF and therapeutic effect. Results: MDD and DA-MGPS had interactive effects on the left fusiform gyrus (FG_L), right calcarine sulcus (CS_R), left superior temporal gyrus (STG_L), bilateral cerebellum posterior lobe (CPL), bilateral inferior frontal gyrus (IFG), and bilateral superior frontal gyrus (SFG). Partial correlation analysis revealed that the ALFF of STG_L had a significant negative correlation with 2-week HAMD-24 reductive rate (r = -0.211, P = 0.035). Conclusions: The spontaneous activity of STG_L may be a potential biomarker of antidepressant-related early therapeutic effect underlying the influence of DA pathway genes in MDD.

PMID: 33414733 [PubMed]

Menstrual Cycle Variations in Gray Matter Volume, White Matter Volume and Functional Connectivity: Critical Impact on Parietal Lobe.

Sun, 01/10/2021 - 00:47
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Menstrual Cycle Variations in Gray Matter Volume, White Matter Volume and Functional Connectivity: Critical Impact on Parietal Lobe.

Front Neurosci. 2020;14:594588

Authors: Meeker TJ, Veldhuijzen DS, Keaser ML, Gullapalli RP, Greenspan JD

Abstract
The role of gonadal hormones in neural plasticity remains unclear. This study aimed to examine the effects of naturally fluctuating hormone levels over the menstrual cycle in healthy females. Gray matter, functional connectivity (FC) and white matter changes over the cycle were assessed by using functional magnetic resonance imaging (fMRI), resting state fMRI, and structural MRIs, respectively, and associated with serum gonadal hormone levels. Moreover, electrocutaneous sensitivity was evaluated in 14 women in four phases of their menstrual cycle (menstrual, follicular, ovulatory, and luteal). Electrocutaneous sensitivity was greater during follicular compared to menstrual phase. Additionally, pain unpleasantness was lower in follicular phase than other phases while pain intensity ratings did not change over the cycle. Significant variations in cycle phase effects on gray matter volume were found in the left inferior parietal lobule (IPL) using voxel-based morphometry. Subsequent Freesurfer analysis revealed greater thickness of left IPL during the menstrual phase when compared to other phases. Also, white matter volume fluctuated across phases in left IPL. Blood estradiol was positively correlated with white matter volume both in left parietal cortex and whole cortex. Seed-driven FC between left IPL and right secondary visual cortex was enhanced during ovulatory phase. A seed placed in right IPL revealed enhanced FC between left and right IPL during the ovulatory phase. Additionally, we found that somatosensory cortical gray matter was thinner during follicular compared to menstrual phase. We discuss these results in the context of likely evolutionary pressures selecting for enhanced perceptual sensitivity across modalities specifically during ovulation.

PMID: 33414702 [PubMed]

Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer's disease.

Sun, 01/10/2021 - 00:47
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Functional connectivity of the nucleus basalis of Meynert in Lewy body dementia and Alzheimer's disease.

Int Psychogeriatr. 2021 Jan 08;:1-6

Authors: Schumacher J, Thomas AJ, Peraza LR, Firbank M, O'Brien JT, Taylor JP

Abstract
Cholinergic deficits are a hallmark of Alzheimer's disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.

PMID: 33413710 [PubMed - as supplied by publisher]

Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine.

Sun, 01/10/2021 - 00:47
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Differential alteration of fMRI signal variability in the ascending trigeminal somatosensory and pain modulatory pathways in migraine.

J Headache Pain. 2021 Jan 07;22(1):4

Authors: Lim M, Jassar H, Kim DJ, Nascimento TD, DaSilva AF

Abstract
BACKGROUND: The moment-to-moment variability of resting-state brain activity has been suggested to play an active role in chronic pain. Here, we investigated the regional blood-oxygen-level-dependent signal variability (BOLDSV) and inter-regional dynamic functional connectivity (dFC) in the interictal phase of migraine and its relationship with the attack severity.
METHODS: We acquired resting-state functional magnetic resonance imaging from 20 migraine patients and 26 healthy controls (HC). We calculated the standard deviation (SD) of the BOLD time-series at each voxel as a measure of the BOLD signal variability (BOLDSV) and performed a whole-brain voxel-wise group comparison. The brain regions showing significant group differences in BOLDSV were used to define the regions of interest (ROIs). The SD and mean of the dynamic conditional correlation between those ROIs were calculated to measure the variability and strength of the dFC. Furthermore, patients' experimental pain thresholds and headache pain area/intensity levels during the migraine ictal-phase were assessed for clinical correlations.
RESULTS: We found that migraineurs, compared to HCs, displayed greater BOLDSV in the ascending trigeminal spinal-thalamo-cortical pathways, including the spinal trigeminal nucleus, pulvinar/ventral posteromedial (VPM) nuclei of the thalamus, primary somatosensory cortex (S1), and posterior insula. Conversely, migraine patients exhibited lower BOLDSV in the top-down modulatory pathways, including the dorsolateral prefrontal (dlPFC) and inferior parietal (IPC) cortices compared to HCs. Importantly, abnormal interictal BOLDSV in the ascending trigeminal spinal-thalamo-cortical and frontoparietal pathways were associated with the patient's headache severity and thermal pain sensitivity during the migraine attack. Migraineurs also had significantly lower variability and greater strength of dFC within the thalamo-cortical pathway (VPM-S1) than HCs. In contrast, migraine patients showed greater variability and lower strength of dFC within the frontoparietal pathway (dlPFC-IPC).
CONCLUSIONS: Migraine is associated with alterations in temporal signal variability in the ascending trigeminal somatosensory and top-down modulatory pathways, which may explain migraine-related pain and allodynia. Contrasting patterns of time-varying connectivity within the thalamo-cortical and frontoparietal pathways could be linked to abnormal network integrity and instability for pain transmission and modulation.

PMID: 33413090 [PubMed - in process]

Disruption of Rich club Connectivity in Cushing's Disease.

Sat, 01/09/2021 - 00:46
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Disruption of Rich club Connectivity in Cushing's Disease.

World Neurosurg. 2021 Jan 04;:

Authors: Xu CX, Jiang H, Zhao ZJ, Sun YH, Chen X, Sun BM, Sun QF, Bian LG

Abstract
OBJECTIVE: Cushing's disease (CD) is a rare clinical disease in which brain structural and function are impaired for excessive cortisol. However, little is known about rich club organization changes in CD patients, as visualized on resting state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aim to investigate whether the functional connectivity of rich club organization is affected, and whether any abnormal changes may reverse after TSS.
METHOD: In this study, 38 CD with active patients, 33 with remitted CD patients, and 41 age, sex and education matched healthy control participants underwent resting fMRI. Brain functional connectivity was constructed based on fMRI and rich club were calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich club connectivity based on fMRI.
RESULTS: We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich club connectivity showed significantly lower in active CD patients(P<0.001). Moreover, abnormal rich club connectivity improved to normal after TSS.
CONCLUSIONS: Our results reflect rich club organization was disrupted patients with active CD patients with excessive cortisol production. TSS can reverse the abnormal rich club connectivity. Rich club may be as new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in CD patients.

PMID: 33412326 [PubMed - as supplied by publisher]

Anxiety in Parkinson's Disease: Abnormal resting activity and connectivity.

Sat, 01/09/2021 - 00:46
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Anxiety in Parkinson's Disease: Abnormal resting activity and connectivity.

Brain Res. 2021 Jan 04;:147235

Authors: Criaud M, Kim JH, Zurowski M, Lobaugh N, Chavez S, Houle S, Strafella AP

Abstract
Anxiety is a very common yet poorly understood symptom of Parkinson's disease. We investigated whether Parkinson's disease patients experiencing anxiety share neural mechanisms described in the general population with involvement of critical regions for the control of behaviour and movement. Thirty-nine patients with PD were recruited for this study, 20 with higher anxiety scores and 19 with lower anxiety scores. They all underwent a resting-state fMRI scan, while they were on medication. The amplitude of low-frequency fluctuation (ALFF) and seed-based connectivity were investigated to reveal the changes of the spontaneous activity and the interaction among different related regions. The results provided evidence that anxiety in Parkinson's disease is associated with the over-activation of the amygdala and impaired inter-relationship of regions involved in behavior (i.e. medial prefrontal cortex, insula) and motor control (i.e. basal ganglia).

PMID: 33412150 [PubMed - as supplied by publisher]

Revisiting correlation-based functional connectivity and its relationship with structural connectivity.

Sat, 01/09/2021 - 00:46
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Revisiting correlation-based functional connectivity and its relationship with structural connectivity.

Netw Neurosci. 2020;4(4):1235-1251

Authors: Liégeois R, Santos A, Matta V, Van De Ville D, Sayed AH

Abstract
Patterns of brain structural connectivity (SC) and functional connectivity (FC) are known to be related. In SC-FC comparisons, FC has classically been evaluated from correlations between functional time series, and more recently from partial correlations or their unnormalized version encoded in the precision matrix. The latter FC metrics yield more meaningful comparisons to SC because they capture 'direct' statistical dependencies, that is, discarding the effects of mediators, but their use has been limited because of estimation issues. With the rise of high-quality and large neuroimaging datasets, we revisit the relevance of different FC metrics in the context of SC-FC comparisons. Using data from 100 unrelated Human Connectome Project subjects, we first explore the amount of functional data required to reliably estimate various FC metrics. We find that precision-based FC yields a better match to SC than correlation-based FC when using 5 minutes of functional data or more. Finally, using a linear model linking SC and FC, we show that the SC-FC match can be used to further interrogate various aspects of brain structure and function such as the timescales of functional dynamics in different resting-state networks or the intensity of anatomical self-connections.

PMID: 33409438 [PubMed]

Coactivation pattern analysis reveals altered salience network dynamics in children with autism spectrum disorder.

Sat, 01/09/2021 - 00:46
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Coactivation pattern analysis reveals altered salience network dynamics in children with autism spectrum disorder.

Netw Neurosci. 2020;4(4):1219-1234

Authors: Marshall E, Nomi JS, Dirks B, Romero C, Kupis L, Chang C, Uddin LQ

Abstract
Brain connectivity studies of autism spectrum disorder (ASD) have historically relied on static measures of functional connectivity. Recent work has focused on identifying transient configurations of brain activity, yet several open questions remain regarding the nature of specific brain network dynamics in ASD. We used a dynamic coactivation pattern (CAP) approach to investigate the salience/midcingulo-insular (M-CIN) network, a locus of dysfunction in ASD, in a large multisite resting-state fMRI dataset collected from 172 children (ages 6-13 years; n = 75 ASD; n = 138 male). Following brain parcellation by using independent component analysis, dynamic CAP analyses were conducted and k-means clustering was used to determine transient activation patterns of the M-CIN. The frequency of occurrence of different dynamic CAP brain states was then compared between children with ASD and typically developing (TD) children. Dynamic brain configurations characterized by coactivation of the M-CIN with central executive/lateral fronto-parietal and default mode/medial fronto-parietal networks appeared less frequently in children with ASD compared with TD children. This study highlights the utility of time-varying approaches for studying altered M-CIN function in prevalent neurodevelopmental disorders. We speculate that altered M-CIN dynamics in ASD may underlie the inflexible behaviors commonly observed in children with the disorder.

PMID: 33409437 [PubMed]

Damage to the structural connectome reflected in resting-state fMRI functional connectivity.

Sat, 01/09/2021 - 00:46
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Damage to the structural connectome reflected in resting-state fMRI functional connectivity.

Netw Neurosci. 2020;4(4):1197-1218

Authors: Wodeyar A, Cassidy JM, Cramer SC, Srinivasan R

Abstract
The relationship between structural and functional connectivity has been mostly examined in intact brains. Fewer studies have examined how differences in structure as a result of injury alters function. In this study we analyzed the relationship of structure to function across patients with stroke among whom infarcts caused heterogenous structural damage. We estimated relationships between distinct brain regions of interest (ROIs) from functional MRI in two pipelines. In one analysis pipeline, we measured functional connectivity by using correlation and partial correlation between 114 cortical ROIs. We found fMRI-BOLD partial correlation was altered at more edges as a function of the structural connectome (SC) damage, relative to the correlation. In a second analysis pipeline, we limited our analysis to fMRI correlations between pairs of voxels for which we possess SC information. We found that voxel-level functional connectivity showed the effect of structural damage that we could not see when examining correlations between ROIs. Further, the effects of structural damage on functional connectivity are consistent with a model of functional connectivity, diffusion, which expects functional connectivity to result from activity spreading over multiple edge anatomical paths.

PMID: 33409436 [PubMed]

Individualized Prediction of PTSD Symptom Severity in Trauma Survivors From Whole-Brain Resting-State Functional Connectivity.

Sat, 01/09/2021 - 00:46
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Individualized Prediction of PTSD Symptom Severity in Trauma Survivors From Whole-Brain Resting-State Functional Connectivity.

Front Behav Neurosci. 2020;14:563152

Authors: Suo X, Lei D, Li W, Yang J, Li L, Sweeney JA, Gong Q

Abstract
Previous studies have demonstrated relations between spontaneous neural activity evaluated by resting-state functional magnetic resonance imaging (fMRI) and symptom severity in post-traumatic stress disorder. However, few studies have used brain-based measures to identify imaging associations with illness severity at the level of individual patients. This study applied connectome-based predictive modeling (CPM), a recently developed data-driven and subject-level method, to identify brain function features that are related to symptom severity of trauma survivors. Resting-state fMRI scans and clinical ratings were obtained 10-15 months after the earthquake from 122 earthquake survivors. Symptom severity of post-traumatic stress disorder features for each survivor was evaluated using the Clinician Administered Post-traumatic Stress Disorder Scale (CAPS-IV). A functionally pre-defined atlas was applied to divide the human brain into 268 regions. Each individual's functional connectivity 268 × 268 matrix was created to reflect correlations of functional time series data across each pair of nodes. The relationship between CAPS-IV scores and brain functional connectivity was explored in a CPM linear model. Using a leave-one-out cross-validation (LOOCV) procedure, findings showed that the positive network model predicted the left-out individual's CAPS-IV scores from resting-state functional connectivity. CPM predicted CAPS-IV scores, as indicated by a significant correspondence between predicted and actual values (r = 0.30, P = 0.001) utilizing primarily functional connectivity between visual cortex, subcortical-cerebellum, limbic, and motor systems. The current study provides data-driven evidence regarding the functional brain features that predict symptom severity based on the organization of intrinsic brain networks and highlights its potential application in making clinical evaluation of symptom severity at the individual level.

PMID: 33408617 [PubMed]

Recognition of Cognitive Impairment in Adult Moyamoya Disease: A Classifier Based on High-Order Resting-State Functional Connectivity Network.

Sat, 01/09/2021 - 00:46
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Recognition of Cognitive Impairment in Adult Moyamoya Disease: A Classifier Based on High-Order Resting-State Functional Connectivity Network.

Front Neural Circuits. 2020;14:603208

Authors: Lei Y, Chen X, Su JB, Zhang X, Yang H, Gao XJ, Ni W, Chen L, Yu JH, Gu YX, Mao Y

Abstract
Objective: Vascular cognitive impairment (VCI) is a common complication in adult patients with moyamoya disease (MMD), and is reversible by surgical revascularization in its early stage of mild VCI. However, accurate diagnosis of mild VCI is difficult based on neuropsychological examination alone. This study proposed a method of dynamic resting-state functional connectivity (FC) network to recognize global cognitive impairment in MMD. Methods: For MMD, 36 patients with VCI and 43 patients with intact cognition (Non-VCI) were included, as well as 26 normal controls (NCs). Using resting-state fMRI, dynamic low-order FC networks were first constructed with multiple brain regions which were generated through a sliding window approach and correlated in temporal dimension. In order to obtain more information of network interactions along the time, high-order FC networks were established by calculating correlations among each pair of brain regions. Afterwards, a sparse representation-based classifier was constructed to recognize MMD (experiment 1) and its cognitive impairment (experiment 2) with features extracted from both low- and high-order FC networks. Finally, the ten-fold cross-validation strategy was proposed to train and validate the performance of the classifier. Results: The three groups did not differ significantly in demographic features (p > 0.05), while the VCI group exhibited the lowest MMSE scores (p = 0.001). The Non-VCI and NCs groups did not differ significantly in MMSE scores (p = 0.054). As for the classification between MMD and NCs, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the classifier reached 90.70, 88.57, 93.67, and 73.08%, respectively. While for the classification between VCI and Non-VCI, the AUC, accuracy, sensitivity, and specificity of the classifier reached 91.02, 84.81, 80.56, and 88.37%, respectively. Conclusion: This study not only develops a promising classifier to recognize VCI in adult MMD in its early stage, but also implies the significance of time-varying properties in dynamic FC networks.

PMID: 33408614 [PubMed - in process]

Decreased Functional Connectivity Between the Right Precuneus and Middle Frontal Gyrus Is Related to Attentional Decline Following Acute Sleep Deprivation.

Sat, 01/09/2021 - 00:46
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Decreased Functional Connectivity Between the Right Precuneus and Middle Frontal Gyrus Is Related to Attentional Decline Following Acute Sleep Deprivation.

Front Neurosci. 2020;14:530257

Authors: Li B, Zhang L, Zhang Y, Chen Y, Peng J, Shao Y, Zhang X

Abstract
Objectives: Acute sleep deprivation (SD) seriously affects cognitive functions, such as attention, memory, and response inhibition. Previous neuroimaging studies have demonstrated a close relationship between the functional activities of the precuneus (PC) and the function of alert attention. However, the specific effect of the PC on attention decline after acute SD has not been elucidated. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to study the relationship between the changes of the PC functional connectivity and alertness decline after total SD.
Methods: Thirty healthy, right-handed adult men participated in the experiment. Alert attention and functional connectivity were assessed by the Psychomotor Vigilance Test and a resting-state fMRI scan before and after total SD. The region of interest to region of interest ("ROI-to-ROI") correlation was employed to analyze the relationship between the PC and other brain regions after acute SD.
Results: Participants showed decreased alert attention after total SD. In addition, SD induced decreased functional connectivity between the right PC and the right middle frontal gyrus (MFG). Moreover, there was a significant correlation between the decreased PC functional connectivity and alertness decline after total SD.
Conclusion: Our findings suggest that the interruption of the connection between the right PC and the right MFG is related to the observed decline in alert attention after acute SD. These results provide evidence further elucidating the cognitive impairment model of SD.

PMID: 33408600 [PubMed]

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging.

Sat, 01/09/2021 - 00:46
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A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging.

Acta Neuropathol Commun. 2021 Jan 06;9(1):2

Authors: To XV, Nasrallah FA

Abstract
Concussion or mild traumatic brain injury is the most common form of traumatic brain injury with potentially long-term consequences. Current objective diagnosis and treatment options are limited to clinical assessment, cognitive rest, and symptom management, which raises the real danger of concussed patients being released back into activities where subsequent and cumulative injuries may cause disproportionate damages. This study conducted a cross-sectional multi-modal examination investigation of the temporal changes in behavioural and brain changes in a mouse model of concussion using magnetic resonance imaging. Sham and concussed mice were assessed at day 2, day 7, and day 14 post-sham or injury procedures following a single concussion event for motor deficits, psychological symptoms with open field assessment, T2-weighted structural imaging, diffusion tensor imaging (DTI), neurite orientation density dispersion imaging (NODDI), stimulus-evoked and resting-state functional magnetic resonance imaging (fMRI). Overall, a mismatch in the temporal onsets and durations of the behavioural symptoms and structural/functional changes in the brain was seen. Deficits in behaviour persisted until day 7 post-concussion but recovered at day 14 post-concussion. DTI and NODDI changes were most extensive at day 7 and persisted in some regions at day 14 post-concussion. A persistent increase in connectivity was seen at day 2 and day 14 on rsfMRI. Stimulus-invoked fMRI detected increased cortical activation at day 7 and 14 post-concussion. Our results demonstrate the capabilities of advanced MRI in detecting the effects of a single concussive impact in the brain, and highlight a mismatch in the onset and temporal evolution of behaviour, structure, and function after a concussion. These results have significant translational impact in developing methods for the detection of human concussion and the time course of brain recovery.

PMID: 33407949 [PubMed - in process]

Distinct network topology in Alzheimer's disease and behavioral variant frontotemporal dementia.

Sat, 01/09/2021 - 00:46
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Distinct network topology in Alzheimer's disease and behavioral variant frontotemporal dementia.

Alzheimers Res Ther. 2021 Jan 06;13(1):13

Authors: Ng ASL, Wang J, Ng KK, Chong JSX, Qian X, Lim JKW, Tan YJ, Yong ACW, Chander RJ, Hameed S, Ting SKS, Kandiah N, Zhou JH

Abstract
BACKGROUND: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) cause distinct atrophy and functional disruptions within two major intrinsic brain networks, namely the default network and the salience network, respectively. It remains unclear if inter-network relationships and whole-brain network topology are also altered and underpin cognitive and social-emotional functional deficits.
METHODS: In total, 111 participants (50 AD, 14 bvFTD, and 47 age- and gender-matched healthy controls) underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological assessments. Functional connectivity was derived among 144 brain regions of interest. Graph theoretical analysis was applied to characterize network integration, segregation, and module distinctiveness (degree centrality, nodal efficiency, within-module degree, and participation coefficient) in AD, bvFTD, and healthy participants. Group differences in graph theoretical measures and empirically derived network community structures, as well as the associations between these indices and cognitive performance and neuropsychiatric symptoms, were subject to general linear models, with age, gender, education, motion, and scanner type controlled.
RESULTS: Our results suggested that AD had lower integration in the default and control networks, while bvFTD exhibited disrupted integration in the salience network. Interestingly, AD and bvFTD had the highest and lowest degree of integration in the thalamus, respectively. Such divergence in topological aberration was recapitulated in network segregation and module distinctiveness loss, with AD showing poorer modular structure between the default and control networks, and bvFTD having more fragmented modules in the salience network and subcortical regions. Importantly, aberrations in network topology were related to worse attention deficits and greater severity in neuropsychiatric symptoms across syndromes.
CONCLUSIONS: Our findings underscore the reciprocal relationships between the default, control, and salience networks that may account for the cognitive decline and neuropsychiatric symptoms in dementia.

PMID: 33407913 [PubMed - in process]

Brain activity of benzoate, a D-amino acid oxidase inhibitor, in patients with mild cognitive impairment in a randomized, double-blind, placebo controlled clinical trial.

Fri, 01/08/2021 - 00:46

Brain activity of benzoate, a D-amino acid oxidase inhibitor, in patients with mild cognitive impairment in a randomized, double-blind, placebo controlled clinical trial.

Int J Neuropsychopharmacol. 2021 Jan 06;:

Authors: Lane HY, Tu CH, Lin WC, Lin CH

Abstract
BACKGROUND: Current anti-dementia drugs cannot benefit mild cognitive impairment (MCI). Sodium benzoate (a D-amino acid oxidase [DAO] inhibitor) has been found to improve the cognitive function of patients with early-phase Alzheimer's disease (AD) (mild AD or MCI). However, its effect on brain function remains unknow. This study aimed to evaluate the influence of benzoate on fMRI in patients with amnestic MCI.
METHODS: This was a 24-week randomized, double-blind, placebo-controlled trial, which enrolled 21 patients with aMCI and allocated them randomly to either of 2 treatment groups: (1) benzoate group (250-1500 mg/day); (2) placebo group. We assessed the patients' working memory, verbal learning and memory, and resting-state fMRI and regional homogeneity (ReHo) maps at baseline and endpoint.
RESULTS: Resting-state ReHo decreased in right orbitofrontal cortex after benzoate treatment, but didn't change after placebo. Moreover, after benzoate treatment, the change in working memory was positively correlated and the change in ReHo in right precentral gyrus and right middle occipital gyrus; and the change in verbal learning and memory was positively correlated with the change in ReHo in left precuneus. In contrast, after placebo treatment, the change in working memory or in verbal learning and memory was not correlated with the change in ReHo in any brain region.
CONCLUSION: The current study is the first to demonstrate that a DAO inhibitor, sodium benzoate herein, can alter brain activity as well as cognitive functions in the MCI individuals. The preliminary finding lends supports for DAO inhibition as a novel approach for early dementing processes.

PMID: 33406269 [PubMed - as supplied by publisher]

A Review of the Default Mode Network in Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder.

Fri, 01/08/2021 - 00:46

A Review of the Default Mode Network in Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder.

Brain Connect. 2021 Jan 06;:

Authors: Harikumar A, Evans DW, Dougherty CC, Carpenter KLH, Michael A

Abstract
Functional magnetic resonance imaging (fMRI) has been widely used to examine the relationships between brain function and phenotypic features in neurodevelopmental disorders. Techniques such as resting state functional connectivity (FC) have enabled the identification of the primary networks of the brain. One fMRI network in particular, the default mode network, (DMN), has been implicated in social-cognitive deficits in Autism Spectrum Disorders (ASD) and attentional deficits in Attentional Deficit Hyperactivity Disorder (ADHD). Given the significant clinical and genetic overlap between ASD and ADHD, surprisingly, no reviews have compared the clinical, developmental, and genetic correlates of DMN in ASD and ADHD and here we address this knowledge gap. We find that, compared to matched controls, ASD studies show a mixed pattern of both stronger and weaker FC in the DMN and ADHD studies mostly show stronger FC. Factors such as age, IQ, medication status, and heredity affect DMN FC in both ASD and ADHD. We also note that most DMN studies make ASD versus ADHD group comparisons and fail to consider ASD+ADHD comorbidity. We conclude, by identifying areas for improvement and by discussing the importance of using transdiagnostic approaches such as the Research Domain Criteria (RDoC) to fully account for the phenotypic and genotypic heterogeneity and overlap of ASD and ADHD.

PMID: 33403915 [PubMed - as supplied by publisher]

Functional Neural Architecture Supporting Highly Superior Autobiographical Memory.

Fri, 01/08/2021 - 00:46

Functional Neural Architecture Supporting Highly Superior Autobiographical Memory.

Brain Connect. 2021 Jan 06;:

Authors: Mazzoni G, De Marco M, Venneri A, Manca R

Abstract
BACKGROUND: The neural mechanisms of Highly Superior Autobiographical Memory are poorly understood. To shed light on the fMRI-informed neurobiology of this condition, in this study we characterise for the first time the neurofunctional architecture of a 20-year old individual (BB) with Highly Superior Autobiographical Memory and no concurrent neurological/psychiatric or other clinical conditions.
METHOD: Relying on t-test inferential models comparing a single observation with a control group, we processed BB's resting-state fMRI signal and compared it with the neurofunctional architecture of 16 young adults with normal autobiographical memory. Specifically, we analysed large-scale brain networks, region-to-region functional connectivity and connectivity indices informed by graph theory.
RESULTS: BB showed higher expression of large-scale and region-to-region connectivity, larger segregation of the pallidum and enhanced centrality of the temporal pole, orbitofrontal cortex and cerebellar lobule IX.
CONCLUSION: These findings indicate that Highly Superior Autobiographical Memory is associated with increased expression of neural pathways that support memory encoding, retrieval and elaboration, but also with reduced expression of patterns typically involved in information control and metacognition, the use of which would be minimised thanks to automatic and accurate memory processing.

PMID: 33403914 [PubMed - as supplied by publisher]

Interhemispheric Parietal-Frontal Connectivity Predicts the Ability to Acquire a Non-Dominant Hand Skill.

Fri, 01/08/2021 - 00:46

Interhemispheric Parietal-Frontal Connectivity Predicts the Ability to Acquire a Non-Dominant Hand Skill.

Brain Connect. 2021 Jan 06;:

Authors: Philip B, McAvoy M, Frey SH

Abstract
INTRODUCTION: After chronic impairment of the right dominant hand, some individuals are able to compensate with increased performance with the intact left non-dominant hand. This process may depend on the non-dominant (right) hemisphere's ability to access dominant (left) hemisphere mechanisms. To predict or modulate patients' ability to compensate with the left hand, we must understand the neural mechanisms and connections that underpin this process.
METHODS: We studied 17 right-handed healthy adults who underwent resting state functional connectivity (FC) MRI scans before 10 days of training on a left hand precision drawing task. We sought to identify right-hemisphere areas where FC from left hemisphere seeds (primary motor cortex, intraparietal sulcus, inferior parietal lobule) would predict left hand skill learning or magnitude.
RESULTS: Left hand skill learning was predicted by convergent FC from left primary motor cortex and left intraparietal sulcus onto the same small region (0.31 cm3) in the right superior parietal lobule.
DISCUSSION: For patients who must compensate with the left hand, the right superior parietal lobule may play a key role in integrating left-hemisphere mechanisms that typically control the right hand. Our study provides the first model of how interhemispheric functional connections in the human brain may support compensation after chronic injury to the right hand.

PMID: 33403906 [PubMed - as supplied by publisher]

Seizure frequency is associated with effective connectivity of the hippocampal-diencephalic-cingulate in epilepsy with unilateral mesial temporal sclerosis.

Fri, 01/08/2021 - 00:46

Seizure frequency is associated with effective connectivity of the hippocampal-diencephalic-cingulate in epilepsy with unilateral mesial temporal sclerosis.

Brain Connect. 2021 Jan 06;:

Authors: Shih YC, Lin FH, Liou HH, Tseng WI

Abstract
BACKGROUND: Temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) is a common intractable epilepsy. To seek neural correlates of seizure recurrence, this study investigated aberrant intrinsic effective connectivity (iEC) in TLE with unilateral MTS and their associations with seizure frequency.
METHODS: Thirty patients with unilateral MTS (left/right MTS = 14/16) and 37 age-matched healthy controls underwent resting-state functional magnetic resonance imaging (rsfMRI) on a 3-Tesla magnetic resonance imaging (MRI) system. The structural equation modeling was employed to estimate the iEC of the three candidate epilepsy models, including the Papez circuit, hippocampal-diencephalic-cingulate (HDC) model, and simplified HDC model. After comparing the performance of model-fitting, the best model was selected to compare iEC among the study groups. The linear regression analysis was performed to associate abnormal iEC with seizure frequency.
RESULTS: The simplified HDC model was the best model to estimate iEC across the three study groups (p < 0.05), and it comprised of the 26 interconnected pathway between the mesial temporal lobe, thalamus, and cingulate cortices. The linear regression analysis revealed a significant relationship between the shared iEC alterations in both patient groups and seizure frequency (adjusted-R2 = 0.350; p = 0.037), including the 3 paths of mammillary body → bilateral anterior thalamic nuclei (left: standardized β-value = 0.580, p = 0.013; right: standardized β-value = -0.711, p = 0.006) and right hippocampus → mammillary body (standardized β-value = 0.541, p = 0.045).
CONCLUSIONS: our findings provide new insights into neurophysiological significance relevant to seizure recurrence. Aberrant iEC on the neural paths connected to the mammillary body can be a potential imaging marker, aiding the therapeutic management in TLE with unilateral MTS.

PMID: 33403892 [PubMed - as supplied by publisher]

Chemotherapy-Induced Brain Effects in Small-Cell Lung Cancer Patients: A Multimodal MRI Study.

Fri, 01/08/2021 - 00:46
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Chemotherapy-Induced Brain Effects in Small-Cell Lung Cancer Patients: A Multimodal MRI Study.

Brain Topogr. 2021 Jan 05;:

Authors: Mentzelopoulos A, Gkiatis K, Karanasiou I, Karavasilis E, Papathanasiou M, Efstathopoulos E, Kelekis N, Kouloulias V, Matsopoulos GK

Abstract
The golden standard of treating Small Cell Lung Cancer (SCLC) entails application of platinum-based chemotherapy, is often accompanied by Prophylactic Cranial Irradiation (PCI), which have been linked to neurotoxic side-effects in cognitive functions. The related existing neuroimaging research mainly focuses on the effect of PCI treatment in life quality and expectancy, while little is known regarding the distinct adverse effects of chemotherapy. In this context, a multimodal MRI analysis based on structural and functional brain data is proposed in order to evaluate chemotherapy-specific effects on SCLC patients. Data from 20 patients (after chemotherapy and before PCI) and 14 healthy controls who underwent structural MRI, DTI and resting state fMRI were selected in this study. From a structural aspect, the proposed analysis included volumetry and thickness measurements on structural MRI data for assessing gray matter dissimilarities, as well as deterministic tractography and Tract-Based Spatial Statistics (TBSS) on DTI data, aiming to investigate potential white matter abnormalities. Functional data were also processed on the basis of connectivity analysis, evaluating brain network parameters to identify potential manifestation of functional inconsistencies. By comparing patients to healthy controls, the obtained results revealed statistically significant differences, with the patients' brains presenting reduced volumetry/thickness and fractional anisotropy values, accompanied by prominent differences in functional connectivity measurements. All above mentioned findings were observed in patients that underwent chemotherapy.

PMID: 33403560 [PubMed - as supplied by publisher]