Most recent paper

A Series Registration Framework to Recover Resting-State Functional Magnetic Resonance Data Degraded By Motion.

AMIA Jt Summits Transl Sci Proc. 2020;2020:569-578

Authors: Schabdach JM, Ceschin R, Lee VK, Schmithorst V, Panigrahy A

Abstract
Data retention is a significant problem in the medical imaging domain. For example, resting-state functional magnetic resonance images (rs-fMRIs) are invaluable for studying neurodevelopment but are highly susceptible to corruption due to patient motion. The effects of patient motion can be reduced through post-acquisition techniques such as volume registration. Traditional volume registration minimizes the global differences between all volumes in the rs-fMRI sequence and a designated reference volume. We suggest using the spatiotemporal relationships between subsequent image volumes to inform the registration: they are used initialize each volume registration to reduce local differences between volumes while minimizing global differences. We apply both the traditional and novel registration methods to a set of healthy human neonatal rs-fMRIs with significant motion artifacts (N=17). Both methods impacted the mean and standard deviation of the image sequences' correlation ratio matrices similarly; however, the novel framework was more effective in meeting gold standard motion thresholds.

PMID: 32477679 [PubMed]

Classifying Autism Spectrum Disorder Using the Temporal Statistics of Resting-State Functional MRI Data With 3D Convolutional Neural Networks.

Front Psychiatry. 2020;11:440

Authors: Thomas RM, Gallo S, Cerliani L, Zhutovsky P, El-Gazzar A, van Wingen G

Abstract
Resting-state functional magnetic resonance imaging (rs-fMRI) data are 4-dimensional volumes (3-space + 1-time) that have been posited to reflect the underlying mechanisms of information exchange between brain regions, thus making it an attractive modality to develop diagnostic biomarkers of brain dysfunction. The enormous success of deep learning in computer vision has sparked recent interest in applying deep learning in neuroimaging. But the dimensionality of rs-fMRI data is too high (~20 M), making it difficult to meaningfully process the data in its raw form for deep learning experiments. It is currently not clear how the data should be engineered to optimally extract the time information, and whether combining different representations of time could provide better results. In this paper, we explored various transformations that retain the full spatial resolution by summarizing the temporal dimension of the rs-fMRI data, therefore making it possible to train a full three-dimensional convolutional neural network (3D-CNN) even on a moderately sized [~2,000 from Autism Brain Imaging Data Exchange (ABIDE)-I and II] data set. These transformations summarize the activity in each voxel of the rs-fMRI or that of the voxel and its neighbors to a single number. For each brain volume, we calculated regional homogeneity, the amplitude of low-frequency fluctuations, the fractional amplitude of low-frequency fluctuations, degree centrality, eigenvector centrality, local functional connectivity density, entropy, voxel-mirrored homotopic connectivity, and auto-correlation lag. We trained the 3D-CNN on a publically available autism dataset to classify the rs-fMRI images as being from individuals with autism spectrum disorder (ASD) or from healthy controls (CON) at an individual level. We attained results competitive on this task for a combined ABIDE-I and II datasets of ~66%. When all summary measures were combined the result was still only as good as that of the best single measure which was regional homogeneity (ReHo). In addition, we also applied the support vector machine (SVM) algorithm on the same dataset and achieved comparable results, suggesting that 3D-CNNs could not learn additional information from these temporal transformations that were more useful to differentiate ASD from CON.

PMID: 32477198 [PubMed]

Altered empathy-related resting-state functional connectivity in adolescents with early-onset schizophrenia and autism spectrum disorders.

Asian J Psychiatr. 2020 May 16;53:102167

Authors: Shi LJ, Zhou HY, Wang Y, Shen YM, Fang YM, He YQ, Ou JJ, Li HB, Luo XR, Cheung EFC, Pantelis C, Chan RCK

Abstract
Empathy refers to the ability to understand other people's feelings and reacting emotionally to others. Impaired empathy has been reported in both individuals with schizophrenia and autism spectrum disorders (ASD). Despite overlaps, few studies have directly examined the neural mechanisms of impaired empathy in these two clinical groups. We used resting-state fMRI to investigate the neural correlates of empathic functioning in adolescents with ASD (N = 11), early-onset schizophrenia (EOS) (N = 20), and typically developing (TD) controls (N = 26). Their parents completed the Griffith Empathy Measure (GEM) to assess the adolescents' empathic capacity. We found that EOS and ASD participants both exhibited impaired empathy as measured by the GEM, especially in cognitive empathy (post-hoc ps < 0.05). Regions-of-interest-based functional connectivity revealed decreased connectivity between the salience network (SN) (i.e., the anterior insula and the anterior cingulate cortex) and core regions of the mentalizing network (e.g., the temporal-parietal junction and the precuneus), and among the SN and the bilateral superior temporal gyri (STG) and the left cerebellum in EOS participants. Subsequent comparisons revealed reduced grey matter volume in the STG bilaterally in both clinical groups. Increased resting-state functional connectivity within the social brain network was correlated with higher parent-reported scores of empathic capacity in TD adolescents, but such a brain-phenotype relationship was absent in the two clinical groups. These findings indicate that structural alterations and disturbed resting-state functional connectivity in the core empathy network may be the neural correlates of social cognitive deficits in individuals with EOS and ASD.

PMID: 32474345 [PubMed - as supplied by publisher]

Unravelling the effects of methylphenidate on the dopaminergic and noradrenergic functional circuits.

Neuropsychopharmacology. 2020 May 30;:

Authors: Dipasquale O, Martins D, Sethi A, Veronese M, Hesse S, Rullmann M, Sabri O, Turkheimer F, Harrison NA, Mehta MA, Cercignani M

Abstract
Functional magnetic resonance imaging (fMRI) can be combined with drugs to investigate the system-level functional responses in the brain to such challenges. However, most psychoactive agents act on multiple neurotransmitters, limiting the ability of fMRI to identify functional effects related to actions on discrete pharmacological targets. We recently introduced a multimodal approach, REACT (Receptor-Enriched Analysis of functional Connectivity by Targets), which offers the opportunity to disentangle effects of drugs on different neurotransmitters and clarify the biological mechanisms driving clinical efficacy and side effects of a compound. Here, we focus on methylphenidate (MPH), which binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET), to unravel its effects on dopaminergic and noradrenergic functional circuits in the healthy brain at rest. We then explored the relationship between these target-enriched resting state functional connectivity (FC) maps and inter-individual variability in behavioural responses to a reinforcement-learning task encompassing a novelty manipulation to disentangle the molecular systems underlying specific cognitive/behavioural effects. Our main analysis showed a significant MPH-induced FC increase in sensorimotor areas in the functional circuit associated with DAT. In our exploratory analysis, we found that MPH-induced regional variations in the DAT and NET-enriched FC maps were significantly correlated with some of the inter-individual differences on key behavioural responses associated with the reinforcement-learning task. Our findings show that main MPH-related FC changes at rest can be understood through the distribution of DAT in the brain. Furthermore, they suggest that when compounds have mixed pharmacological profiles, REACT may be able to capture regional functional effects that are underpinned by the same cognitive mechanism but are related to engagement of distinct molecular targets.

PMID: 32473593 [PubMed - as supplied by publisher]

Tumor grade-related language and control network reorganization in patients with left cerebral glioma.

Cortex. 2020 May 07;129:141-157

Authors: Yuan B, Zhang N, Yan J, Cheng J, Lu J, Wu J

Abstract
Language processing relies on both a functionally specialized language network and a domain-general cognitive control network. Yet, how the two networks reorganize after damage resulting from diffuse and progressive glioma remains largely unknown. To address this issue, 130 patients with left cerebral gliomas, including 77 patients with low-grade glioma (LGG, WHO grade Ⅰ/II), 53 patients with high-grade glioma (HGG, WHO grade III/IV) and 38 healthy controls (HC) were adopted. The changes in resting-state functional connectivity (rsFC) of the language network and the cingulo-opercular/fronto-parietal (CO-FP) network were examined using network-based statistics. We found that tumor grade negatively correlated with language scores and language network integrity. Compared with HCs, patients with LGGs exhibited slight language deficits, both decreased and increased changes in rsFC of language network, and nearly normal CO-FP network. Patients with HGGs had significantly lower language scores than those with LGG and exhibited more severe language and CO-FP network disruptions than HCs or patients with LGGs. Moreover, we found that in patients with HGGs, the decreased rsFCs of language network were positively correlated with language scores. Together, our findings suggest tumor grade-related network reorganization of both language and control networks underlie the different levels of language impairments observed in patients with gliomas.

PMID: 32473401 [PubMed - as supplied by publisher]

Volumetric and Functional Activity Lateralization in Healthy Subjects and Patients with Focal Epilepsy: Initial Findings in a 7T MRI Study.

J Neuroimaging. 2020 May 30;:

Authors: Canjels LPW, Backes WH, van Veenendaal TM, Vlooswijk MCG, Hofman PAM, Aldenkamp AP, Rouhl RPW, Jansen JFA

Abstract
BACKGROUND AND PURPOSE: In 30% of the patients with focal epilepsy, an epileptogenic lesion cannot be visually detected with structural MRI. Ultra-high field MRI may be able to identify subtle pathology related to the epileptic focus. We set out to assess 7T MRI-derived volumetric and functional activity lateralization of the hippocampus, hippocampal subfields, temporal and frontal lobe in healthy subjects and MRI-negative patients with focal epilepsy.
METHODS: Twenty controls and 10 patients with MRI-negative temporal or frontal lobe epilepsy (TLE and FLE, respectively) underwent a 7T MRI exam. T1 -weigthed imaging and resting-state fMRI was performed. T1 -weighted images were segmented to yield volumes, while from fMRI data, the fractional amplitude of low frequency fluctuations was calculated. Subsequently, volumetric and functional lateralization was calculated from left-right asymmetry.
RESULTS: In controls, volumetric lateralization was symmetric, with a slight asymmetry of the hippocampus and subiculum, while functional lateralization consistently showed symmetry. Contrarily, in epilepsy patients, regions were less symmetric. In TLE patients with known focus, volumetric lateralization in the hippocampus and hippocampal subfields was indicative of smaller ipsilateral volumes. These patients also showed clear functional lateralization, though not consistently ipsilateral or contralateral to the epileptic focus. TLE patients with unknown focus showed an obvious volumetric lateralization, facilitating the localization of the epileptic focus. Lateralization results in the FLE patients were less consistent with the epileptic focus.
CONCLUSION: MRI-derived volume and fluctuation amplitude are highly symmetric in controls, whereas in TLE, volumetric and functional lateralization effects were observed. This highlights the potential of the technique.

PMID: 32472965 [PubMed - as supplied by publisher]

Acute Alcohol Intake Produces Widespread Decreases in Cortical Resting Signal Variability in Healthy Social Drinkers.

Alcohol Clin Exp Res. 2020 May 29;:

Authors: Sevel L, Stennett B, Schneider V, Bush N, Nixon SJ, Robinson M, Boissoneault J

Abstract
BACKGROUND: Acute alcohol intoxication has wide-ranging neurobehavioral effects on psychomotor, attentional, inhibitory, and memory-related cognitive processes. These effects are mirrored in disruption of neural metabolism, functional activation, and functional network coherence. Metrics of intraregional neural dynamics such as regional signal variability (RSV) and brain entropy (BEN) may capture unique aspects of neural functional capacity in healthy and clinical populations; however, alcohol's influence on these metrics is unclear. The present study aimed to elucidate the influence of acute alcohol intoxication on RSV and to clarify these effects with subsequent BEN analyses.
METHODS: 26 healthy adults between 25 and 45 years of age (65.4% women) participated in two counterbalanced sessions. In one, participants consumed a beverage containing alcohol sufficient to produce a breath alcohol concentration of 0.08 g/dL. In the other, they consumed a placebo beverage. Approximately 35 minutes after beverage consumption, participants completed a 9-minute resting state fMRI scan. Whole brain, voxel-wise standard deviation was used to assess RSV, which was compared between sessions. Within clusters displaying alterations in RSV, sample entropy was calculated to assess BEN.
RESULTS: Compared to the placebo, alcohol intake resulted in widespread reductions in RSV in the bilateral middle frontal, right inferior frontal, right superior frontal, bilateral posterior cingulate, bilateral middle temporal, right supramarginal gyri, and bilateral inferior parietal lobule. Within these clusters, significant reductions in BEN were found in the bilateral middle frontal and right superior frontal gyri. No effects were noted in subcortical or cerebellar areas.
CONCLUSIONS: Findings indicate that alcohol intake produces diffuse reductions in RSV among structures associated with attentional processes. Within these structures, signal complexity was also reduced in a subset of frontal regions. Neurobehavioral effects of acute alcohol consumption may be partially driven by disruption of intraregional neural dynamics among regions involved in higher order cognitive and attentional processes.

PMID: 32472620 [PubMed - as supplied by publisher]

Two nights of recovery sleep restores hippocampal connectivity but not episodic memory after total sleep deprivation.

Sci Rep. 2020 May 29;10(1):8774

Authors: Chai Y, Fang Z, Yang FN, Xu S, Deng Y, Raine A, Wang J, Yu M, Basner M, Goel N, Kim JJ, Wolk DA, Detre JA, Dinges DF, Rao H

Abstract
Sleep deprivation significantly impairs a range of cognitive and brain function, particularly episodic memory and the underlying hippocampal function. However, it remains controversial whether one or two nights of recovery sleep following sleep deprivation fully restores brain and cognitive function. In this study, we used functional magnetic resonance imaging (fMRI) and examined the effects of two consecutive nights (20-hour time-in-bed) of recovery sleep on resting-state hippocampal connectivity and episodic memory deficits following one night of total sleep deprivation (TSD) in 39 healthy adults in a controlled in-laboratory protocol. TSD significantly reduced memory performance in a scene recognition task, impaired hippocampal connectivity to multiple prefrontal and default mode network regions, and disrupted the relationships between memory performance and hippocampal connectivity. Following TSD, two nights of recovery sleep restored hippocampal connectivity to baseline levels, but did not fully restore memory performance nor its associations with hippocampal connectivity. These findings suggest that more than two nights of recovery sleep are needed to fully restore memory function and hippocampal-memory associations after one night of total sleep loss.

PMID: 32472075 [PubMed - as supplied by publisher]

Functional connectome analyses reveal the human olfactory network organization.

eNeuro. 2020 May 29;:

Authors: Arnold TC, You Y, Ding M, Zuo XN, de Araujo I, Li W

Abstract
The olfactory system is uniquely heterogeneous, performing multifaceted functions (beyond basic sensory processing) across diverse, widely distributed neural substrates. While knowledge of human olfaction continues to grow, it remains unclear how the olfactory network is organized to serve this unique set of functions. Leveraging a large and high-quality resting-state functional magnetic resonance imaging (rs-fMRI) dataset of nearly 900 participants from the Human Connectome Project (HCP), we identified a human olfactory network encompassing cortical and subcortical regions across the temporal and frontal lobes. Highlighting its reliability and generalizability, the connectivity matrix of this olfactory network mapped closely onto that extracted from an independent rs-fMRI dataset. Graph theoretical analysis further explicated the organizational principles of the network. The olfactory network exhibits a modular composition of three (i.e., the sensory, limbic, and frontal) subnetworks and demonstrates strong small-world properties, high in both global integration and local segregation (i.e., circuit specialization). This network organization thus ensures the segregation of local circuits, which are nonetheless integrated via connecting hubs (i.e., amygdala and anterior insula), thereby enabling the specialized, yet integrative, functions of olfaction. In particular, the degree of local segregation positively predicted olfactory discrimination performance in the independent sample, which we infer as a functional advantage of the network organization. In sum, an olfactory functional network has been identified through the large HCP dataset, affording a representative template of the human olfactory functional neuroanatomy. Importantly, the topological analysis of the olfactory network provides network-level insights into the remarkable functional specialization and spatial segregation of the olfactory system.Significance statement Olfaction is an intriguing multifunctional system, playing key roles in regulating emotions, autonomic tone, and feeding, beyond basic sensory perception. However, it is unclear how the neuroanatomy of olfaction is organized in humans to subserve these functions. Functional connectivity analysis of the HCP dataset combined with graph theoretical analysis revealed an optimized large-scale network consisting of three subnetworks-the sensory, limbic, and frontal subnetworks. Distributed across frontal and temporal lobes in well segregated fashion, these olfactory structures are also highly integrated, linked through hub nodes of the amygdala and anterior insula. Our independent dataset replicated the HCP-derived olfactory network and, importantly, highlighted a direct association between the degree of network segregation and olfactory perception.

PMID: 32471848 [PubMed - as supplied by publisher]

Trait-related changes in brain network topology in premenstrual dysphoric disorder.

Horm Behav. 2020 May 26;:104782

Authors: Dan R, Reuveni I, Canetti L, Weinstock M, Segman R, Goelman G, Bonne O

Abstract
The female predominance in the prevalence of depression is partially accounted by reactivity to hormonal fluctuations. Premenstrual dysphoric disorder (PMDD) is a reproductive subtype of depression characterized by cyclic emotional and somatic symptoms that recur before menstruation. Despite the growing understanding that most psychiatric disorders arise from dysfunctions in distributed brain circuits, the brain's functional connectome and its network properties of segregation and integration were not investigated in PMDD. To this end, we examined the brain's functional network organization in PMDD using graph theoretical analysis. 24 drug naïve women with PMDD and 27 controls without premenstrual symptoms underwent 2 resting-state fMRI scans, during the mid-follicular and late-luteal menstrual cycle phases. Functional connectivity MRI, graph theory metrics and levels of sex hormones were computed during each menstrual phase. Altered network topology was found in PMDD across symptomatic and remitted stages in major graph metrics (characteristic path length, clustering coefficient, transitivity, local and global efficiency, centrality), indicating decreased functional network segregation and increased functional network integration. In addition, PMDD patients exhibited hypoconnectivity of the anterior temporal lobe and hyperconnectivity of the basal ganglia and thalamus, across menstrual phases. Furthermore, the relationship between difficulties in emotion regulation and PMDD was mediated by specific patterns of functional connectivity, including connections of the striatum, thalamus and prefrontal cortex. The shifts in the functional connectome and its topology in PMDD may suggest trait vulnerability markers of the disorder.

PMID: 32470339 [PubMed - as supplied by publisher]

Alterations of functional and structural connectivity in patients with brain metastases.

PLoS One. 2020;15(5):e0233833

Authors: Hua B, Ding X, Xiong M, Zhang F, Luo Y, Ding J, Ding Z

Abstract
Metastases are the most prevalent tumors in the brain and are commonly associated with high morbidity and mortality. Previous studies have suggested that brain tumors can induce a loss of functional connectivity and alter the brain network architecture. Little is known about the effect of brain metastases on whole-brain functional and structural connectivity networks. In this study, 14 patients with brain metastases and 16 healthy controls underwent resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). We constructed functional connectivity network using rs-fMRI signal correlations and structural connectivity network using DTI tractography. Graph theoretical analysis was employed to calculate network properties. We further evaluated the performance of brain networks after metastases resection by a simulated method. Compared to healthy controls, patients with brain metastases showed an altered "small-world" architecture in both functional and structural connectivity networks, shifting to a more randomness organization. Besides, the coupling strength of functional-structural connectivity was decreased in patients. After removing nodes infiltrated by metastases, aggravated disruptions were found in both functional and structural connectivity networks, and the alterations of network properties correlated with the removed hubs number. Our findings suggest that brain metastases interfere with the optimal network organization and relationship of functional and structural connectivity networks, and tumor resection involving hubs could cause a worse performance of brain networks. This study provides neuroimaging guidance for neurosurgical planning and postoperative assessment of brain metastases from the aspect of brain networks.

PMID: 32470024 [PubMed - as supplied by publisher]

Endogenous cortisol-related alterations of right anterior insula functional connectivity under acute stress.

J Affect Disord. 2020 May 23;274:231-238

Authors: Zhu Y, Wang Y, Yang Z, Wang L, Hu X

Abstract
BACKGROUND: Previous studies have suggested that the right anterior insula (rAI) plays a vital role in salience processing and stress-related disorders. In this study, we aimed to investigate the relationship between rAI functional connectivity changes and individual differences in cortisol responses after acute stress, in order to provide insights into psychiatric illness vulnerabilities.
METHODS: Thirty-five young men were enrolled in a randomized, counterbalanced two-session study, with aversive movie clip combined with electrical shocks as stress stimulation and the neutral movie clip as control stimulation. Resting-state fMRI data was acquired after movie exposure. The rAI was chosen as seed for functional connectivity analysis. We then examined the effect of acute stress on rAI functional connectivity and its association with individuals' cortisol response.
RESULTS: We found decreased rAI functional connectivity in the fronto-parietal regions, but increased functional connectivity in the visual and somatosensory areas following acute stress. Moreover, stress-induced cortisol response was significantly positively correlated with the rAI functional connectivity in the medial prefrontal cortex, and negatively correlated with the orbital-frontal cortex, lingual gyrus, and middle temporal gyrus.
LIMITATIONS: Only young Chinese males without any trauma experience were recruited in this study.
CONCLUSIONS: The results suggested tight link between specific rAI functional connectivity alterations and individual stress reactivity, which may help elucidate the potential neurobiological mechanism underlying vulnerability to stress-related disorders.

PMID: 32469811 [PubMed - as supplied by publisher]

Dynamic Reconfiguration, Fragmentation, and Integration of Whole-Brain Modular Structure across Depths of Unconsciousness.

Cereb Cortex. 2020 May 29;:

Authors: Standage D, Areshenkoff CN, Nashed JY, Hutchison RM, Hutchison M, Heinke D, Menon RS, Everling S, Gallivan JP

Abstract
General anesthetics are routinely used to induce unconsciousness, and much is known about their effects on receptor function and single neuron activity. Much less is known about how these local effects are manifest at the whole-brain level nor how they influence network dynamics, especially past the point of induced unconsciousness. Using resting-state functional magnetic resonance imaging (fMRI) with nonhuman primates, we investigated the dose-dependent effects of anesthesia on whole-brain temporal modular structure, following loss of consciousness. We found that higher isoflurane dose was associated with an increase in both the number and isolation of whole-brain modules, as well as an increase in the uncoordinated movement of brain regions between those modules. Conversely, we found that higher dose was associated with a decrease in the cohesive movement of brain regions between modules, as well as a decrease in the proportion of modules in which brain regions participated. Moreover, higher dose was associated with a decrease in the overall integrity of networks derived from the temporal modules, with the exception of a single, sensory-motor network. Together, these findings suggest that anesthesia-induced unconsciousness results from the hierarchical fragmentation of dynamic whole-brain network structure, leading to the discoordination of temporal interactions between cortical modules.

PMID: 32469053 [PubMed - as supplied by publisher]

An Examination of Psychomotor Disturbance in Current and Remitted MDD: An RDoC Study.

J Psychiatr Brain Sci. 2020;5:

Authors: Shankman SA, Mittal VA, Walther S

Abstract
Major depressive disorder (MDD) is a serious public health problem that has, at best, modest treatment response-potentially due to its heterogeneous clinical presentation. One way to parse the heterogeneity is to investigate the role of particular features of MDD, an endeavor that can also help identify novel and focal targets for treatment and prevention efforts. Our R01 focuses on the feature of psychomotor disturbance (e.g., psychomotor agitation (PmA) and retardation (PmR)), a particularly pernicious feature of MDD, that has not been examined extensively in MDD. Aim 1 is comparing three groups of individuals-those with current MDD (n = 100), remitted MDD (n = 100), and controls (n = 50)-on multiple measures of PmR and PmA (assessed both in the lab and in the subjects' natural environment). Aim 2 is examining the structural (diffusion MRI) and functional (resting state fMRI) connectivity of motor circuitry of the three groups as well as the relation between motor circuitry and the proposed indicators of PmR and PmA. Aim 3 is following up with subjects three times over 18 months to evaluate whether motor symptoms change in tandem with overall depressive symptoms and functioning over time and/or whether baseline PmR/PmA predicts course of depression and functioning. Aim 3 is particularly clinically significant. Finding that motor functioning and overall depression severity co-vary over time, or that motor variables predict subsequent change in overall depression severity, would support the potential clinical utility of these novel, reliable, and easily administered motor assessments.

PMID: 32467859 [PubMed]

Transdiagnostic and disease-specific abnormalities in the default-mode network hubs in psychiatric disorders: A meta-analysis of resting-state functional imaging studies.

Eur Psychiatry. 2020 May 29;:1-17

Authors: Doucet GE, Janiri D, Howard R, O'Brien M, Andrews-Hanna JR, Frangou S

PMID: 32466812 [PubMed - as supplied by publisher]

A longitudinal, multi-parametric functional MRI study to determine age-related changes in the rodent brain.

Neuroimage. 2020 May 25;:116976

Authors: Crofts A, Trotman-Lucas M, Janus J, Kelly M, Gibson CL

Abstract
As the population ages, the incidence of age-related neurological diseases and cognitive decline increases. To further understand disease-related changes in brain function it is advantageous to examine brain activity changes in healthy aging rodent models to permit mechanistic investigation. Here, we examine the suitability, in rodents, of using a novel, minimally invasive anaesthesia protocol in combination with a functional MRI protocol to assess alterations in neuronal activity due to physiological aging. 11 Wistar Han female rats were studied at 7, 9, 12, 15 and 18 months of age. Under an intravenous infusion of propofol, animals underwent functional magnetic resonance imaging (fMRI) and functional magnetic resonance spectroscopy (fMRS) with forepaw stimulation to quantify neurotransmitter activity, and resting cerebral blood flow (CBF) quantification using arterial spin labelling (ASL) to study changes in neurovascular coupling over time. Animals showed a significant decrease in size of the active region with age (P < 0.05). fMRS results showed a significant decrease in glutamate change with stimulation (ΔGlu) with age (P < 0.05), and ΔGlu became negative from 12 months onwards. Global CBF remained constant for the duration of the study. This study shows age related changes in the blood oxygen level dependent (BOLD) response in rodents that correlate with those seen in humans. The results also suggest that a reduction in synaptic glutamate turnover with age may underlie the reduction in the BOLD response, while CBF is preserved.

PMID: 32464290 [PubMed - as supplied by publisher]

An analytical workflow for seed-based correlation and independent component analysis in interventional resting-state fMRI studies.

Neurosci Res. 2020 May 25;:

Authors: Seewoo BJ, Joos AC, Feindel KW

Abstract
Resting-state functional MRI (rs-fMRI) is a task-free method of detecting spatially distinct brain regions with correlated activity, which form organised networks known as resting-state networks (RSNs). The two most widely used methods for analysing RSN connectivity are seed-based correlation analysis (SCA) and independent component analysis (ICA) but there is no established workflow of the optimal combination of analytical steps and how to execute them. Rodent rs-fMRI data from our previous longitudinal brain stimulation studies were used to investigate these two methods using FSL. Specifically, we examined: (1) RSN identification and group comparisons in ICA, (2) ICA-based denoising compared to nuisance signal regression in SCA, and (3) seed selection in SCA. In ICA, using a baseline-only template resulted in greater functional connectivity within RSNs and more sensitive detection of group differences than when an average pre/post stimulation template was used. In SCA, the use of an ICA-based denoising method in the preprocessing of rs-fMRI data and the use of seeds from individual functional connectivity maps in running group comparisons increased the sensitivity of detecting group differences by preventing the reduction in signals of interest. Accordingly, when analysing animal and human rs-fMRI data, we infer that the use of baseline-only templates in ICA and ICA-based denoising and individualised seeds in SCA will improve the reliability of results and comparability across rs-fMRI studies.

PMID: 32464181 [PubMed - as supplied by publisher]

Alterations of local functional connectivity in lifespan: A resting-state fMRI study.

Brain Behav. 2020 May 27;:e01652

Authors: Wen X, He H, Dong L, Chen J, Yang J, Guo H, Luo C, Yao D

Abstract
INTRODUCTION: As aging attracted attention globally, revealing changes in brain function across the lifespan was largely concerned. In this study, we aimed to reveal the changes of functional networks of the brain (via local functional connectivity, local FC) in lifespan and explore the mechanism underlying them.
MATERIALS AND METHODS: A total of 523 healthy participants (258 males and 265 females) aged 18-88 years from part of the Cambridge Center for Ageing and Neuroscience (CamCAN) were involved in this study. Next, two data-driven measures of local FC, local functional connectivity density (lFCD) and four-dimensional spatial-temporal consistency of local neural activity (FOCA), were calculated, and then, general linear models were used to assess the changes of them in lifespan.
RESULTS: Local functional connectivity (lFCD and FOCA) within visual networks (VN), sensorimotor network (SMN), and default mode network (DMN) decreased across the lifespan, while within basal ganglia network (BGN), local connectivity was increased across the lifespan. And, the fluid intelligence decreased within BGN while increased within VN, SMN, and DMN.
CONCLUSION: These results might suggest that the decline of executive control and intrinsic cognitive ability in the aging population was related to the decline of functional connectivity in VN, SMN, and DMN. Meanwhile, BGN might play a regulatory role in the aging process to compensate for the dysfunction of other functional systems. Our findings may provide important neuroimaging evidence for exploring the brain functional mechanism in lifespan.

PMID: 32462815 [PubMed - as supplied by publisher]

The compensatory phenomenon of the functional connectome related to pathological biomarkers in individuals with subjective cognitive decline.

Transl Neurodegener. 2020 May 27;9(1):21

Authors: Chen H, Sheng X, Luo C, Qin R, Ye Q, Zhao H, Xu Y, Bai F, Alzheimer’s Disease Neuroimaging Initiative

Abstract
BACKGROUND: Subjective cognitive decline (SCD) is a preclinical stage along the Alzheimer's disease (AD) continuum. However, little is known about the aberrant patterns of connectivity and topological alterations of the brain functional connectome and their diagnostic value in SCD.
METHODS: Resting-state functional magnetic resonance imaging and graph theory analyses were used to investigate the alterations of the functional connectome in 66 SCD individuals and 64 healthy controls (HC). Pearson correlation analysis was computed to assess the relationships among network metrics, neuropsychological performance and pathological biomarkers. Finally, we used the multiple kernel learning-support vector machine (MKL-SVM) to differentiate the SCD and HC individuals.
RESULTS: SCD individuals showed higher nodal topological properties (including nodal strength, nodal global efficiency and nodal local efficiency) associated with amyloid-β levels and memory function than the HC, and these regions were mainly located in the default mode network (DMN). Moreover, increased local and medium-range connectivity mainly between the bilateral parahippocampal gyrus (PHG) and other DMN-related regions was found in SCD individuals compared with HC individuals. These aberrant functional network measures exhibited good classification performance in the differentiation of SCD individuals from HC individuals at an accuracy up to 79.23%.
CONCLUSION: The findings of this study provide insight into the compensatory mechanism of the functional connectome underlying SCD. The proposed classification method highlights the potential of connectome-based metrics for the identification of the preclinical stage of AD.

PMID: 32460888 [PubMed - in process]

Functional connectivity in chronic non-bothersome tinnitus following acoustic trauma: a seed-based resting state fMRI study.

Brain Connect. 2020 May 27;:

Authors: Job A, Jaroszynski C, Kavounoudias A, Jaillard A, Delon-Martin C

Abstract
BACKGROUND: Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. While most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic, non-bothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus.
METHODS: A seed-based resting-state MRI study explored the functional connectivity in an acoustic trauma group presenting slight to mild, non-bothersome, chronic tinnitus and compared it to a control group.
RESULTS: Group-differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror-regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group.
CONCLUSION: These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

PMID: 32458713 [PubMed - as supplied by publisher]