Most recent paper

Intrinsic Cerebro-Cerebellar Functional Connectivity Reveals the Function of Cerebellum VI in Reading-Related Skills.

Front Psychol. 2020;11:420

Authors: Ang C, Zhang J, Chu M, Li H, Tian M, Feng X, Zhang M, Liu L, Meng X, Ding G

Abstract
The engagement of the cerebellum VI in reading was reported in both typically developing and dyslexic readers. However, it is still not clear how the cerebellum VI contributes to reading. Here we have examined the correlation of intrinsic cerebro-cerebellar functional connectivity with two critical reading-related skills-phonological awareness (PA) and rapid automatized naming (RAN)-with fMRI technology. Specifically, we tested the hypothesis that the cerebellum may contribute to reading either by phonological skills or by automatizing skills. We chose the left and right cerebellum VI as ROIs, and we calculated the intrinsic cerebro-cerebellar functional connectivity during a resting state. We further explored whether and how cerebro-cerebellar resting state functional connectivity (RSFC) is associated with individuals' reading-related skills including PA and RAN. The results showed that the functional connectivity between the left supramarginal gyrus and bilateral cerebellum VI was related to RAN, and the connectivity between the left insula and right cerebellum VI was related to PA. However, the effect of PA did not survive after the RAN was regressed out. Control analyses further confirmed that it was the intrinsic cerebro-cerebellar functional connectivity rather than the local cerebellar functionality that associated with phonological awareness ability and rapid automatized naming ability. For the first time, the relationship between cerebro-cerebellar resting state functional connectivity and specific reading-related skills has been explored, and this has deepened our understanding of the way the cerebellum VI is involved in reading.

PMID: 32265778 [PubMed]

High-Frequency rTMS of the Motor Cortex Modulates Cerebellar and Widespread Activity as Revealed by SVM.

Front Neurosci. 2020;14:186

Authors: Wang J, Deng XP, Wu YY, Li XL, Feng ZJ, Wang HX, Jing Y, Zhao N, Zang YF, Zhang J

Abstract
Functional magnetic resonance imaging (fMRI) studies have shown that the effect of repetitive transcranial magnetic stimulation (rTMS) can induce changes in remote brain regions. In the stimulated regions, low-frequency (≤1 Hz) rTMS induces inhibitory effects, while high-frequency (≥5 Hz) stimulation induces excitatory effects. However, these stereotypical effects arising from low- and high-frequency stimulation are based on measurements of motor evoked potentials (MEPs) induced by pulsed stimulation. To test the effects of rTMS on remote brain regions, the current study recruited 31 young healthy adults who participated in three rTMS sessions (10 Hz high frequency, 1 Hz low frequency, and sham) on three separate days. The stimulation target was based on individual fMRI activation in the motor cortex evoked by a finger movement task. Pre- and post-rTMS resting-state fMRI (RS-fMRI) were acquired. Regional homogeneity (ReHo) and degree centrality (DC) were calculated to measure the local and global connectivity, respectively. Compared with the sham session, high-frequency (10 Hz) rTMS significantly increased ReHo and DC in the right cerebellum, while low-frequency (1 Hz) stimulation did not significantly alter ReHo or DC. Then, using a newly developed PAIR support vector machine (SVM) method, we achieved accuracy of 93.18-97.24% by split-half validation for pairwise comparisons between conditions for ReHo or DC. While the univariate analyses suggest that high-frequency rTMS of the left motor cortex could affect distant brain activity in the right cerebellum, the multivariate SVM results suggest that both high- and low-frequency rTMS significantly modulated widespread brain activity. The current findings are useful for increasing the understanding of the mechanisms of rTMS, as well as guiding precise individualized rTMS treatment of movement disorders.

PMID: 32265624 [PubMed]

Decoding task-specific cognitive states with slow, directed functional networks in the human brain.

eNeuro. 2020 Apr 06;:

Authors: Ajmera S, Jain H, Sundaresan M, Sridharan D

Abstract
Flexible functional interactions among brain regions mediate critical cognitive functions. Such interactions can be measured using functional magnetic resonance imaging (fMRI) data either with instantaneous (zero-lag) or lag-based (time-lagged) functional connectivity. Because the fMRI hemodynamic response is slow, and sampled at a timescale (seconds) several orders of magnitude slower than the underlying neural dynamics (milliseconds), simulation studies have shown that lag-based fMRI functional connectivity, measured with approaches like Granger-Geweke causality (GC), provides spurious and unreliable estimates of underlying neural interactions. Experimental verification of this claim is challenging because neural ground truth connectivity is, often, unavailable concurrently with fMRI recordings. Here we demonstrate that, despite these widely-held caveats, GC networks estimated from fMRI recordings contain useful information for classifying task specific cognitive states. We estimated instantaneous and lag-based GC functional connectivity networks using fMRI data from 1000 participants (Human Connectome Project database). A linear classifier, trained on either instantaneous or lag-based GC, reliably discriminated among seven different task and resting brain states, with over 80% cross-validation accuracy. With network simulations, we demonstrate that instantaneous and lag-based GC exploited interactions at fast and slow timescales, respectively, to achieve robust classification. With human fMRI data, instantaneous and lag-based GC identified complementary, task-core networks. Finally, variations in GC connectivity explained inter-individual variations in a variety of cognitive scores. Our findings show that instantaneous and lag-based methods reveal complementary aspects of functional connectivity in the brain, and suggest that slow, directed functional interactions, estimated with fMRI, may provide useful markers of behaviorally relevant cognitive states.Significance statement Functional MRI is a leading, non-invasive technique for mapping functionally connected networks in the human brain. The fMRI hemodynamic response is slow, noisy and sampled far more slowly (seconds) than the timescale of neuronal spikes (milliseconds). fMRI data is, therefore, considered unsuitable for mapping directed, time-lagged functional connectivity among brain regions. Here, we apply machine learning to fMRI data from 1000 human participants and show that directed connectivity, estimated with Granger-Geweke Causality from fMRI data, accurately predicts task-specific cognitive states, and individual subjects' behavioral scores. Moreover, directed connectivity robustly identifies network configurations that may be challenging to identify with conventional, correlation-based approaches. Directed functional connectivity, as measured with fMRI, may be relevant for a complete understanding of brain function.

PMID: 32265196 [PubMed - as supplied by publisher]

Shifted hub regions in the brain network of rat neuropathic pain model after electroacupuncture therapy.

J Integr Neurosci. 2020 Mar 30;19(1):65-75

Authors: Wu J, Wang S, Lu Y, Zheng M, Hua X, Xu J

Abstract
Electroacupuncture has been considered an effective neurorehabilitative approach to relieve neuropathic pain originating in the central nervous system. However, the neural mechanism underlying the effect of electroacupuncture on pain-relief remains largely unknown. The objective of this study was to investigate the alteration of hub configurations of brain networks caused by the sustained impact of electroacupuncture on a clinically relevant animal model of neuropathic pain. Rats were divided into four groups: normal, model, electroacupuncture, and sham-electroacupuncture. Rats of the last three groups received complete brachial plexus avulsion to evoke neuropathic pain. Electroacupuncture was conducted continuously for three months on the electroacupuncture group, while the sham intervention was performed on the sham-electroacupuncture group. Mechanical withdrawal thresholds were evaluated at the end of the first and third month of intervention. Graph theoretical network analysis compared the regional topological parameters and explored hub configurations of brain networks by longitudinal resting-state fMRI. Three-months electroacupuncture showed a significant pain-relief effect. Not the spatial distribution of hubs, but the hubness distribution showed a significant difference among groups after a three-month intervention. The proportion of more highly connected hub regions was significantly higher in the model rats than the normal rats, while that of the electroacupuncture group was considerably lower than the model group. Additionally, regional parameter changes showed a very similar distribution of hub proportions. It was concluded that long-term electroacupuncture might restore an adaptive equilibrium to a disrupted network and suppress maladaptive plastic changes that follow neuropathic pain. This may provide an important avenue for future strategies appropriate for therapeutic interventions.

PMID: 32259887 [PubMed - as supplied by publisher]

The Modulation of Reward and Habit Systems by Acupuncture in Adolescents with Internet Addiction.

Neural Plast. 2020;2020:7409417

Authors: Wang Y, Qin Y, Li H, Yao D, Sun B, Li Z, Li X, Dai Y, Wen C, Zhang L, Zhang C, Zhu T, Luo C

Abstract
Purpose: Acupuncture is an effective therapy for Internet addiction (IA). However, the underlying mechanisms of acupuncture in relieving compulsive Internet use remain unknown. Neuroimaging studies have demonstrated the role of the ventral striatum (VS) in the progress of IA; hence, the aim of this study was to explore the effects of acupuncture on the resting-state functional connectivity (rsFC) and relevant network of VS in IA.
Methods: Twenty-seven IA individuals and 30 demographically matched healthy control subjects (HCs) were recruited in this study. We acquired the functional magnetic resonance imaging (fMRI) data in IA subjects before and after 40 days of acupuncture treatment. Seed-to-voxel and ROI-to-ROI analyses were applied to detect the rsFC alterations of the VS and related network in IA subjects and to investigate the modulation effect of acupuncture on the rsFC.
Results: Compared with HCs, IA subjects exhibited enhanced rsFC of the right ventral rostral putamen (VRP) with the left orbitofrontal cortex (OFC), premotor cortex (PMC), cerebellum, and right ventromedial prefrontal cortex (vmPFC). In the network including these five ROIs, IA also showed increased ROI-to-ROI rsFC. Using a paired t-test in IA subjects before and after 40 days of acupuncture, the increased ROI-to-ROI rsFC was decreased (normalized to HC) with acupuncture, including the rsFC of the right VRP with the left OFC, PMC, and cerebellum, and the rsFC of the left cerebellum with the left OFC, PMC, and right vmPFC. Furthermore, the change in rsFC strength between the right VRP and left cerebellum in IA individuals was found positively correlated with the Internet craving alleviation after acupuncture.
Conclusions: These findings verified the modulation effect of acupuncture on functional connectivity of reward and habit systems related to the VS in IA individuals, which might partly represent the underlying mechanisms of acupuncture on IA.

PMID: 32256558 [PubMed - as supplied by publisher]

Acute and Chronic Effects of Betel Quid Chewing on Brain Functional Connectivity.

Front Psychiatry. 2020;11:198

Authors: Sariah A, Guo S, Zuo J, Pu W, Liu H, Rolls ET, Xue Z, Liu Z, Huang X

Abstract
Background: The active alkaloid in Betel quid is arecoline. Consumption of betel quid is associated with both acute effects and longer-term addictive effects. Despite growing evidence that betel quid use is linked with altered brain function and connectivity, the neurobiology of this psychoactive substance in initial acute chewing, and long-term dependence, is not clear.
Methods: In this observational study, functional magnetic resonance imaging in a resting-state was performed in 24 male betel quid-dependent chewers and 28 male controls prior to and promptly after betel quid chewing. Network-based statistics were employed to determine significant differences in functional connectivity between brain networks for both acute effects and in long-term betel users versus controls. A support vector machine was employed for pattern classification analysis.
Results: Before chewing betel quid, higher functional connectivity in betel quid-dependent chewers than in controls was found between the temporal, parietal and frontal brain regions (right medial orbitofrontal cortex, right lateral orbital frontal cortex, right angular gyrus, bilateral inferior temporal gyrus, superior parietal gyrus, and right medial superior frontal gyrus). In controls, the effect of betel quid chewing was significantly increased functional connectivity between the subcortical regions (caudate, putamen, pallidum, and thalamus), and the visual cortex (superior occipital gyrus and right middle occipital gyrus).
Conclusion: These findings show that individuals who chronically use betel quid have higher functional connectivity than controls of the orbitofrontal cortex, and inferior temporal and angular gyri. Acute effects of betel quid are to increase the functional connectivity of some visual cortical areas (which may relate to the acute symptoms) and the basal ganglia and thalamus.

PMID: 32256411 [PubMed - as supplied by publisher]

Longitudinal Changes in Whole-Brain Functional Connectivity Strength Patterns and the Relationship With the Global Cognitive Decline in Older Adults.

Front Aging Neurosci. 2020;12:71

Authors: Li Q, Dong C, Liu T, Chen X, Perry A, Jiang J, Cheng J, Niu H, Kochan NA, Brodaty H, Sachdev PS, Wen W

Abstract
Aging is associated with changes in brain functional patterns as well as cognition. The present research sought to investigate longitudinal changes in whole brain functional connectivity strength (FCS) and cognitive performance scores in very old cognitively unimpaired individuals. We studied 34 cognitively normal elderly individuals at both baseline and 4-year follow-up (baseline age = 78 ± 3.14 years) with resting-state functional magnetic resonance imaging (r-fMRI), structural MRI scans, and neuropsychological assessments conducted. Voxel-based whole brain FCS was calculated and we found that bilateral superior parietal and medial frontal regions showed decreased FCS, while the supplementary motor area (SMA) and insula showed increased FCS with age, along with a decrease in bilateral prefrontal cortical thickness. The changes of FCS in left precuneus were associated with an aging-related decline in global cognition. Taken together, our results suggest changes in FCS with aging with the precuneus as a hub and this may underlie changes in global cognition that accompany aging. These findings help better understand the normal aging mechanism.

PMID: 32256339 [PubMed - as supplied by publisher]

Structural and Functional Hippocampal Changes in Subjective Cognitive Decline From the Community.

Front Aging Neurosci. 2020;12:64

Authors: Liang L, Zhao L, Wei Y, Mai W, Duan G, Su J, Nong X, Yu B, Li C, Mo X, Wilson G, Deng D, Kong J

Abstract
Background: Recently, subjective cognitive decline (SCD) has been described as the earliest at-risk state of Alzheimer's disease (AD), and drawn attention of investigators. Studies suggested that SCD-community individuals may constitute a more vulnerable population than SCD-clinic patients, therefore, to investigate the early changes of the brain may provide guidance for treatment of the disease. We sought to investigate the changes of structure and functional connectivity alternation of the hippocampus in individuals with SCD recruited from the community using structural and resting-state functional MRI (fMRI).
Methods: Thirty-five SCD patients and 32 healthy controls were recruited. Resting-state fMRI data and high-resolution T1-weighted images were collected. Whole-brain voxel-based morphometry was used to examine the brain structural changes. We also used the hippocampal tail and the whole hippocampus as seeds to investigate functional connectivity alternation in SCD.
Results: Individuals with SCD showed significant gray matter volume decreases in the bilateral hippocampal tails and enlargement of the bilateral paracentral lobules. We also found that individuals with SCD showed decreased hippocampal tail resting-state functional connectivity (rsFC) with the right medial prefrontal cortex (mPFC) and the left temporoparietal junction (TPJ), and decreased whole hippocampus rsFC with the bilateral mPFC and TPJ. These brain region and FC showing significant differences also showed significantly correlation with Montreal Cognitive Assessment (MoCA) scores.
Conclusion: Individuals with SCD recruited from the community is associated with structural and functional changes of the hippocampus, and these changes may serve as potential biomarkers of SCD.
Clinical Trial Registration: The Declaration of Helsinki, and the study was registered in http://www.chictr.org.cn. The Clinical Trial Registration Number was ChiCTR-IPR-16009144.

PMID: 32256336 [PubMed - as supplied by publisher]

Cerebellar-cortical dysconnectivity in resting-state associated with sensorimotor tasks in schizophrenia.

Hum Brain Mapp. 2020 Apr 06;:

Authors: Kim DJ, Moussa-Tooks AB, Bolbecker AR, Apthorp D, Newman SD, O'Donnell BF, Hetrick WP

Abstract
Abnormalities of cerebellar function have been implicated in the pathophysiology of schizophrenia. Since the cerebellum has afferent and efferent projections to diverse brain regions, abnormalities in cerebellar lobules could affect functional connectivity with multiple functional systems in the brain. Prior studies, however, have not examined the relationship of individual cerebellar lobules with motor and nonmotor resting-state functional networks. We evaluated these relationships using resting-state fMRI in 30 patients with a schizophrenia-spectrum disorder and 37 healthy comparison participants. For connectivity analyses, the cerebellum was parcellated into 18 lobular and vermal regions, and functional connectivity of each lobule to 10 major functional networks in the cerebrum was evaluated. The relationship between functional connectivity measures and behavioral performance on sensorimotor tasks (i.e., finger-tapping and postural sway) was also examined. We found cerebellar-cortical hyperconnectivity in schizophrenia, which was predominantly associated with Crus I, Crus II, lobule IX, and lobule X. Specifically, abnormal cerebellar connectivity was found to the cerebral ventral attention, motor, and auditory networks. This cerebellar-cortical connectivity in the resting-state was differentially associated with sensorimotor task-based behavioral measures in schizophrenia and healthy comparison participants-that is, dissociation with motor network and association with nonmotor network in schizophrenia. These findings suggest that functional association between individual cerebellar lobules and the ventral attentional, motor, and auditory networks is particularly affected in schizophrenia. They are also consistent with dysconnectivity models of schizophrenia suggesting cerebellar contributions to a broad range of sensorimotor and cognitive operations.

PMID: 32250008 [PubMed - as supplied by publisher]

Robust prediction of individual personality from brain functional connectome.

Soc Cogn Affect Neurosci. 2020 Apr 04;:

Authors: Cai H, Zhu J, Yu Y

Abstract
Neuroimaging studies have linked inter-individual variability in the brain to individualized personality traits. However, only one or several aspects of personality have been effectively predicted based on brain imaging features. The objective of this study was to construct a reliable prediction model of personality in a large sample by using connectome-based predictive modeling (CPM), a recently developed machine learning approach. High-quality resting-state fMRI data of 810 healthy young participants from the Human Connectome Project dataset were used to construct large-scale brain networks. Personality traits of the five-factor model (FFM) were assessed by the NEO Five Factor Inventory. We found that CPM successfully and reliably predicted all the FFM personality factors (agreeableness, openness, conscientiousness and neuroticism) other than extraversion in novel individuals. At the neural level, we found that the personality-associated functional networks mainly included brain regions within default-mode, frontoparietal executive-control, visual, and cerebellar systems. Although different feature selection thresholds and parcellation strategies did not significantly influence the prediction results, some findings lost significance after controlling for confounds including age, gender, intelligence, and head motion. Our finding of robust personality prediction from an individual's unique functional connectome may help advance the translation of 'brain connectivity fingerprinting' into real-world personality psychological settings.

PMID: 32248238 [PubMed - as supplied by publisher]

Within-network brain connectivity in Crohn's disease patients with gadolinium deposition in the cerebellum.

Neuroradiology. 2020 Apr 04;:

Authors: Mallio CA, Piervincenzi C, Carducci F, Quintiliani L, Parizel PM, Pantano P, Quattrocchi CC

Abstract
PURPOSE: Patients with Crohn's disease (CD) undergo multiple gadolinium-based contrast agent injections across their lifespan to enhance signal intensity of the intestinal wall and differentiate active from quiescent inflammatory disease. Thus, CD patients are prone to gadolinium accumulation in the brain and represent a non-neurological population to explore gadolinium-related brain toxicity. Possible effects are expected to be greater on the cerebellar network due to the high propensity of the dentate nucleus to accumulate gadolinium. Herein, we provide a whole-brain network analysis of resting-state fMRI dynamics in long-term quiescent CD patients with normal renal function and MRI evidence of gadolinium deposition in the brain.
METHODS: Fifteen patients with CD and 16 healthy age- and gender-matched controls were enrolled in this study. Relevant resting-state networks (RSNs) were identified using independent component analysis (ICA) from functional magnetic resonance imaging data. An unpaired two-sample t test (with age and sex as nuisance variables) was used to investigate between different RSNs. Clusters were determined by using threshold-free cluster enhancement and a family-wise error corrected cluster significance threshold of p < 0.05.
RESULTS: Patients showed significantly decreased resting-state functional connectivity (p < 0.05, FWE corrected) of several regions of the right frontoparietal (FPR) and the dorsal attention (DAN) RSNs. No differences between the two groups were found in the functional connectivity maps of all the other RSNs, including the cerebellar network.
CONCLUSION: Our findings suggest a non-significant impact of gadolinium deposition on within-network cerebellar functional connectivity of long-term quiescent CD patients.

PMID: 32246178 [PubMed - as supplied by publisher]

Effective brain connectivity at rest is associated with choice-induced preference formation.

Hum Brain Mapp. 2020 Apr 03;:

Authors: Voigt K, Murawski C, Speer S, Bode S

Abstract
Preferences can change as a consequence of making hard decisions whereby the value of chosen options increases and the value of rejected options decreases. Such choice-induced preference changes have been associated with brain areas detecting choice conflict (anterior cingulate cortex, ACC), updating stimulus value (dorsolateral prefrontal cortex, dlPFC) and supporting memory of stimulus value (hippocampus and ventromedial prefrontal cortex, vmPFC). Here we investigated whether resting-state neuronal activity within these regions is associated with the magnitude of individuals' preference updates. We fitted a dynamic causal model (DCM) to resting-state neuronal activity in the spectral domain (spDCM) and estimated the causal connectivity among core regions involved in preference formation following hard choices. The extent of individuals' choice-induced preference changes were found to be associated with a diminished resting-state excitation between the left dlPFC and the vmPFC, whereas preference consistency was related to a higher resting-state excitation from the ACC to the left hippocampus and vmPFC. Our results point to a model of preference formation during which the dynamic network configurations between left dlPFC, ACC, vmPFC and left hippocampus at rest are linked to preference change or stability.

PMID: 32243689 [PubMed - as supplied by publisher]

Breakdown of the affective-cognitive network in functional dystonia.

Hum Brain Mapp. 2020 Apr 03;:

Authors: Canu E, Agosta F, Tomic A, Sarasso E, Petrovic I, Piramide N, Svetel M, Inuggi A, D Miskovic N, Kostic VS, Filippi M

Abstract
Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.

PMID: 32243055 [PubMed - as supplied by publisher]

Obesogenic Diet-Associated C-Reactive Protein Predicts Reduced Central Dopamine and Corticostriatal Functional Connectivity in Female Rhesus Monkeys.

Brain Behav Immun. 2020 Mar 30;:

Authors: Godfrey JR, Pincus M, Kovacs-Balint Z, Feczko E, Earl E, Miranda-Dominguez O, Fair DA, Jones SR, Locke J, Sanchez MM, Wilson ME, Michopoulos V

Abstract
Alterations in dopamine (DA) signaling and reductions in functional connectivity (FC; a measure of temporal correlations of activity between different brain regions) within dopaminergic reward pathways are implicated in the etiology of psychopathology and have been associated with increased concentrations of inflammatory markers, including C-reactive protein. Peripheral and central inflammatory cytokines that have been shown to disrupt DA signaling and corticostriatal FC are associated with C-reactive protein, an acute phase reactant that is used translationally as a marker of systemic inflammation. One factor that can significantly increase systemic inflammation to produce neuroadaptations in reward pathways is a diet that results in fat mass accumulation (e.g. obesogenic diet). The current study in female rhesus monkeys maintained in a standard laboratory chow (n=18) or on obesogenic diet (n=16) for 12-months tested the hypothesis that an obesogenic diet would alter central DA and homovanillic acid (HVA) concentrations, and be associated with increased CRP concentrations and decreased FC between corticostriatal regions at 12-months following dietary intervention. We specifically assessed FC between the nucleus accumbens (NAcc) and two sub-regions of the prefrontal cortex (PFC) previously associated with CRP concentrations, the ventromedial PFC (vmPFC) and the orbitofrontal cortex (OFC), which are also involved in emotional and motivational salience assessment, and in goal-directed behavior, impulse control and the salience/value of food, respectively. Results showed that CSF DA concentrations were decreased (p=0.002), HVA:DA ratios were increased (p=0.016), and body mass index was increased (p=0.047) over the 12-months of consuming an obesogenic diet. At 12-months, females maintained in the obesogenic diet exhibited higher CRP concentrations than females consuming chow-only (p=0.008). Linear regression analyses revealed significant CRP by dietary condition interactions on DA concentrations (β=-5.10; p=0.017) and HVA:DA ratios (β=5.14; p=0.029). Higher CRP concentrations were associated with lower CSF DA concentrations (r=-0.69; p=0.004) and greater HVA:DA ratios only in females maintained in the obesogenic dietary condition (r=0.58; p=0.024). Resting-state magnetic resonance neuroimaging (rs-fMRI) in a subset of females from each diet condition (n=8) at 12-months showed that higher CRP concentrations were associated decreased FC between the NAcc and subregions of the prefrontal cortex (PFC; p's<0.05). Decreased FC between the NAcc and PFC subregions were also associated with lower concentrations of DA and greater HVA:DA ratios (p's<0.05). Overall, these data suggest that increased inflammatory signaling driving heightened CRP levels may mediate the adverse consequences of obesogenic diets on DA neurochemistry and corticostriatal connectivity.

PMID: 32240763 [PubMed - as supplied by publisher]

Weight loss reduces head motion: Revisiting a major confound in neuroimaging.

Hum Brain Mapp. 2020 Apr 02;:

Authors: Beyer F, Prehn K, Wüsten KA, Villringer A, Ordemann J, Flöel A, Witte AV

Abstract
Head motion during magnetic resonance imaging (MRI) induces image artifacts that affect virtually every brain measure. In parallel, cross-sectional observations indicate a correlation of head motion with age, psychiatric disease status and obesity, raising the possibility of a systematic artifact-induced bias in neuroimaging outcomes in these conditions, due to the differences in head motion. Yet, a causal link between obesity and head motion has not been tested in an experimental design. Here, we show that a change in body mass index (BMI) (i.e., weight loss after bariatric surgery) systematically decreases head motion during MRI. In this setting, reduced imaging artifacts due to lower head motion might result in biased estimates of neural differences induced by changes in BMI. Overall, our finding urges the need to rigorously control for head motion during MRI to enable valid results of neuroimaging outcomes in populations that differ in head motion due to obesity or other conditions.

PMID: 32239733 [PubMed - as supplied by publisher]

Functional Connectivity of Hippocampal CA3 Predicts Neurocognitive Aging via CA1-Frontal Circuit.

Cereb Cortex. 2020 Apr 02;:

Authors: Liang X, Hsu LM, Lu H, Ash JA, Rapp PR, Yang Y

Abstract
The CA3 and CA1 principal cell fields of the hippocampus are vulnerable to aging, and age-related dysfunction in CA3 may be an early seed event closely linked to individual differences in memory decline. However, whether the differential vulnerability of CA3 and CA1 is associated with broader disruption in network-level functional interactions in relation to age-related memory impairment, and more specifically, whether CA3 dysconnectivity contributes to the effects of aging via CA1 network connectivity, has been difficult to test. Here, using resting-state fMRI in a group of aged rats uncontaminated by neurodegenerative disease, aged rats displayed widespread reductions in functional connectivity of CA3 and CA1 fields. Age-related memory deficits were predicted by connectivity between left CA3 and hippocampal circuitry along with connectivity between left CA1 and infralimbic prefrontal cortex. Notably, the effects of CA3 connectivity on memory performance were mediated by CA1 connectivity with prefrontal cortex. We additionally found that spatial learning and memory were associated with functional connectivity changes lateralized to the left CA3 and CA1 divisions. These results provide novel evidence that network-level dysfunction involving interactions of CA3 with CA1 is an early marker of poor cognitive outcome in aging.

PMID: 32239141 [PubMed - as supplied by publisher]

Increased intrinsic default-mode network activity as a compensatory mechanism in aMCI: a resting-state functional connectivity MRI study.

Aging (Albany NY). 2020 Apr 01;12:

Authors: Liang J, Li Y, Liu H, Zhang S, Wang M, Chu Y, Ye J, Xi Q, Zhao X

Abstract
Numerous studies have investigated the differences in the mean functional connectivity (FC) strength between amnestic mild cognitive impairment (aMCI) patients and normal subjects using resting-state functional magnetic resonance imaging. However, whether the mean FC is increased, decreased or unchanged in aMCI patients compared to normal controls remains unclear. Two factors might lead to inconsistent results: the determination of regions of interest and the reliability of the FC.We explored differences in FC and the degree centrality (Dc) constructed by the bootstrap method, between and within networks (default-mode network (DN), frontoparietal control network (CN), dorsal attention network (AN)), and resulting from a hierarchical-clustering algorithm.The mean FC within the DN and CN was significantly increased (P < 0.05, uncorrected) in patients. Significant increases (P < 0.05, uncorrected) in the mean FC were found in patients between DN and CN and between DN and AN. Five pairs of FC (false discovery rate corrected) and the Dc of six regions (Bonferroni corrected) displayed a significant increase in patients. Lower cognitive ability was significantly associated with a greater increase in the Dc of the left superior temporal sulcus.Our results demonstrate that the early dysfunctions in aMCI disease are mainly compensatory impairments.

PMID: 32238610 [PubMed - as supplied by publisher]

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice.

Microbiome. 2020 Apr 01;8(1):44

Authors: Tengeler AC, Dam SA, Wiesmann M, Naaijen J, van Bodegom M, Belzer C, Dederen PJ, Verweij V, Franke B, Kozicz T, Arias Vasquez A, Kiliaan AJ

Abstract
BACKGROUND: The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging (MRI), and studied mouse behavior in a behavioral test battery.
RESULTS: Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test.
CONCLUSIONS: Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals' behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders. Video abstract.

PMID: 32238191 [PubMed - as supplied by publisher]

A review on epileptic foci localization using resting-state functional magnetic resonance imaging.

Math Biosci Eng. 2020 Feb 26;17(3):2496-2515

Authors: Shi Y, Zhang X, Yang CL, Ren JC, Li ZM, Wang Q

Abstract
Epilepsy is a brain syndrome caused by synchronous abnormal discharge of brain neurons. As an effective treatment for epilepsy, successful surgical resection requires accurate localization of epileptic foci to avoid iatrogenic disability. Previous studies have demonstrated the potential of restingstate functional magnetic resonance imaging (rs-fMRI) technique to localize epileptic foci though clinical applications of rs-fMRI are still at an early stage of development. fMRI data analysis approaches seek pre-defined regressors modeling contributions to the voxel time series, including the BOLD response following neuronal activation. In present study, localization strategies of epileptic foci in rs-fMRI technology were classified and summarized. To begin with, data-driven approaches attempting to determine the intrinsic structure of the data were discussed in detail. Then, as novel fMRI data analysis methods, deconvolution algorithms such as total activation (TA) and blind deconvolution were discussed, which were applied to explore the underlying activity-inducing signal of the BOLD signal. Lastly, effective connectivity approaches such as autocorrelation function method and Pearson correlation coefficient have also been proposed to identify the brain regions driving the generation of seizures within the epileptic network. In the future, fMRI technology can be used as a supplement of intraoperative subdural electrode method or combined with traditional epileptic focus localization technologies, which is one of the most attractive aspect in clinic. It may also play an important role in providing diagnostic information for epilepsy patients.

PMID: 32233551 [PubMed - in process]

Multimodal analysis using [11C]PiB-PET/MRI for functional evaluation of patients with Alzheimer's disease.

EJNMMI Res. 2020 Mar 30;10(1):30

Authors: Okazawa H, Ikawa M, Jung M, Maruyama R, Tsujikawa T, Mori T, Rahman MGM, Makino A, Kiyono Y, Kosaka H

Abstract
BACKGROUND: Multimodal PET/MRI image data simultaneously obtained from patients with early-stage of Alzheimer's disease (eAD) were assessed in order to observe pathophysiologic and functional changes, as well as alterations of morphology and connectivity in the brain. Fifty-eight patients with mild cognitive impairment and early dementia (29 males, 69 ± 12 years) underwent [11C]Pittsburgh compound-B (PiB) PET/MRI with 70-min PET and MRI scans. Sixteen age-matched healthy controls (CTL) (9 males, 68 ± 11 years) were also studied with the same scanning protocol. Cerebral blood flow (CBF) was calculated from the early phase PET images using the image-derived input function method. A standardized uptake value ratio (SUVr) was calculated from 50 to 70 min PET data with a reference region of the cerebellar cortex. MR images such as 3D-T1WI, resting-state functional MRI (RS-fMRI), diffusion tensor image (DTI), and perfusion MRI acquired during the dynamic PET scan were also analyzed to evaluate various brain functions on MRI.
RESULTS: Twenty-seven of the 58 patients were determined as eAD based on the results of PiB-PET and clinical findings, and a total of 43 subjects' data including CTL were analyzed in this study. PiB SUVr values in all cortical regions of eAD were significantly greater than those of CTL. The PiB accumulation intensity was negatively correlated with cognitive scores. The regional PET-CBF values of eAD were significantly lower in the bilateral parietal lobes and right temporal lobe compared with CTL, but not in MRI perfusion; however, SPM showed regional differences on both PET- and MRI-CBF. SPM analysis of RS-fMRI delineated regional differences between the groups in the anterior cingulate cortex and the left precuneus. VBM analysis showed atrophic changes in the AD group in a part of the bilateral hippocampus; however, analysis of fractional anisotropy calculated from DTI data did not show differences between the two groups.
CONCLUSION: Multimodal analysis conducted with various image data from PiB-PET/MRI scans showed differences in regional CBF, cortical volume, and neuronal networks in different regions, indicating that pathophysiologic and functional changes in the AD brain can be observed from various aspects of neurophysiologic parameters. Application of multimodal brain images using PET/MRI would be ideal for investigating pathophysiologic changes in patients with dementia and other neurodegenerative diseases.

PMID: 32232573 [PubMed]