Global Functional Network Connectivity Disturbances in Parkinson’s Disease with Mild Cognitive Impairment by Resting-State Functional MRI

Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson’s disease(PD)with mild cognitive impairment(MCI)is a focus in resting-state functional MRI(rs-fMRI)studies.This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels:functional connectivity analysis within resting state networks(RSNs)and functional network connectivity(FNC)analysis.Using group independent component analysis(ICA)on rs-fMRI data acquired from 30 participants(14 healthy controls and 16 PD patients with MCI),16 RSNs were identified,and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups.Compared to controls,patients with PD showed decreased functional connectivity within putamen network,thalamus network,cerebellar network,attention network,and self-referential network,and increased functional connectivity within execution network.Globally disturbed,mostly increased functional connectivity of FNC was observed in PD group,and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs.Cerebellar network showed decreased functional connectivity with caudate network,insular network,and self-referential network.In general,decreased functional connectivity within RSNs and globally disturbed,mostly increased functional connectivity of FNC may be characteristics of PD.Increased functional connectivity within execution network may be an early marker of PD.The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN,contributing to the understanding of the neural mechanism of PD.

Age-related connectivity differences between attention deficit and hyperactivity disorder patients and typically developing subjects：a resting-state functional MRI study

Attention deficit and hyperactivity disorder（ADHD） is a disorder characterized by behavioral symptoms including hyperactivity/impulsivity among children,adolescents,and adults.These ADHD related symptoms are influenced by the complex interaction of brain networks which were under explored.We explored age-related brain network differences between ADHD patients and typically developing（TD） subjects using resting state f MRI（rs-f MRI） for three age groups of children,adolescents,and adults.We collected rs-f MRI data from 184 individuals（27 ADHD children and 31 TD children;32 ADHD adolescents and 32 TD adolescents;and 31 ADHD adults and 31 TD adults）.The Brainnetome Atlas was used to define nodes in the network analysis.We compared three age groups of ADHD and TD subjects to identify the distinct regions that could explain age-related brain network differences based on degree centrality,a well-known measure of nodal centrality.The left middle temporal gyrus showed significant interaction effects between disease status（i.e.,ADHD or TD） and age（i.e.,child,adolescent,or adult）（P 0.001）.Additional regions were identified at a relaxed threshold（P 0.05）.Many of the identified regions（the left inferior frontal gyrus,the left middle temporal gyrus,and the left insular gyrus） were related to cognitive function.The results of our study suggest that aberrant development in cognitive brain regions might be associated with age-related brain network changes in ADHD patients.These findings contribute to better understand how brain function influences the symptoms of ADHD.

A review of functional MRI application for brain research of Chinese language processing

As one of the most widely used languages in the world,Chinese language is distinct from most western languages in many properties,thus providing a unique opportunity for understanding the brain basis of human language and cognition.In recent years,non-invasive neuroimaging techniques such as magnetic resonance imaging(MRI)blaze a new trail to comprehensively study specific neural correlates of Chinese language processing and Chinese speakers.We reviewed the application of functional MRI(fMRI)in such studies and some essential findings on brain systems in processing Chinese.Specifically,for example,the application of task fMRI and resting-state fMRI in observing the process of reading and writing the logographic characters and producing or listening to the tonal speech.Elementary cognitive neuroscience and several potential research directions around brain and Chinese language were discussed,which may be informative for future research.

The development of brain functional connectivity networks revealed by resting-state functional magnetic resonance imaging

Previous studies on brain functional connectivity networks in children have mainly focused on changes in function in specific brain regions, as opposed to whole brain connectivity in healthy children. By analyzing the independent components of activation and network connectivity between brain regions, we examined brain activity status and development trends in children aged 3 and 5 years. These data could provide a reference for brain function rehabilitation in children with illness or abnormal function. We acquired functional magnetic resonance images from 15 3-year-old children and 15 5-year-old children under natural sleep cond让ions. The participants were recruited from five kindergartens in the Nanshan District of Shenzhen City, China. The parents of the participants signed an informed consent form with the premise that they had been fully informed regarding the experimental protocol. We used masked independent component analysis and BrainNet Viewer software to explore the independent components of the brain and correlation connections between brain regions. We identified seven independent components in the two groups of children, including the executive control network, the dorsal attention network, the default mode network, the left frontoparietal network, the right frontoparietal network, the salience network, and the motor network. In the default mode network, the posterior cingulate cortex, medial frontal gyrus, and inferior parietal lobule were activated in both 3- and 5-year-old children, supporting the "three-brain region theory” of the default mode network. In the frontoparietal network, the frontal and parietal gyri were activated in the two groups of children, and functional connectivity was strengthened in 5-year-olds compared with 3-year-olds, although the nodes and network connections were not yet mature. The high-correlation network connections in the default mode networks and dorsal attention networks had been significantly strengthened in 5-year-olds vs. 3-year-olds. Further, the salience network in the 3-year-old children included an activated insula/inferior frontal gyrus-anterior cingulate cortex network circu让 and an activated thalamus-parahippocampal-posterior cingulate cortex-subcortical regions network circuit. By the age of 5 years, no des and high-correlation network connections (edges) were reduced in the salience network. Overall, activation of the dorsal attention network, default mode network, left frontoparietal network, and right frontoparietal network increased (the volume of activation increased, the signals strengthened, and the high-correlation connections increased and strengthened) in 5-year-olds compared with 3-year-olds, but activation in some brain nodes weakened or disappeared in the salience network, and the network connections (edges) were reduced. Between the ages of 3 and 5 years, we observed a tendency for function in some brain regions to be strengthened and for the generalization of activation to be reduced, indicating that specialization begins to develop at this time. The study protocol was approved by the local ethics committee of the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences in China with approval No. SIAT-IRB- 131115-H0075 on November 15, 2013.

Effective doctor-patient communication skills training optimizes functional organization of intrinsic brain architecture:a restingstate functional MRI study

We studied the influence of doctor-patient communication skills training on brain functional architecture using resting-state functional MRI（rs-fMRI） with a regional homogeneity（ReHo） method. Ten medical students participated in the study. A 1-year long doctor-patient communication skills training program was conducted. RsfMRI data were collected at baseline, one month and one year after training. There was a significant increase in the communication skills test average scores between baseline and 1-month duration of training（P〈0.001）. After one month of communication skills training, medical students had decreased ReHo in the right superior temporal gyrus compared with the baseline. After one year of communication skills training, students had increased ReHo in multiple regions and decreased ReHo in several regions（P 〈0.05, Alphasim corrected）. The change of ReHo values in the superior temporal gyrus negatively correlated with the change of communication skills scale score between one month after communication skills training and baseline（r=-0.734, P= 0.036）. The training program we used can be an effective approach of improving doctor-patient communication skills, and the training resulted in functional plasticity of the brain’s architecture toward optimizing locally functional organization.

RESTplus: an improved toolkit for resting-state functional magnetic resonance imaging data processing

Resting-state functional magnetic resonance imaging (RS-fMRI)[1,2] provides relatively high spatial and temporal resolution for mapping spontaneous brain activity non-invasively. It has been widely used in cognitive neuroscience and clinical studies. A number of comprehensive software packages have been developed for RS-fMRI data analysis, among which a MATLAB package named REST (RESing-state fMRI data analysis Toolkit, released in October 2008 at http://www.restfmri.net)[3] is the earliest one dedicated to RS-fMRI analysis. REST focuses on RS-fMRI postprocessing metrics.

Functional MRI study of mild Alzheimer＇s disease using amplitude of low frequency fluctuation analysis

Background Previous studies have shown that the functional brain activity in the resting state is impaired in Alzheimer＇s disease （AD） patients. However, most studies focused on the relationship between different brain areas, rather than the amplitude or strength of the regional brain activity. The purpose of this study was to explore the functional brain changes in AD patients by measuring the amplitude of the blood oxygenation level dependent （BOLD） functional MRI （fMRI） signals.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression

Background:Late-onset depression(LOD)and early-onset depression(EOD)exhibit different pathological mechanisms and clinical phenotypes,including different extents of olfactory dysfunction.However,the brain abnormalities underlying the differences in ol-factory dysfunction between EOD and LOD remain unclear.Objective:The aim of this study was to compare the functional connectivity(FC)patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function.Methods:One hundred and five patients with EOD,101 patients with LOD and 160 normal controls(NCs)were recruited for the present study.Participants underwent clinical assessment,olfactory testing,cognitive assessments,and magnetic resonance imaging.Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC.Results:Patients with LOD exhibited decreased odor identification(OI)compared with patients with EOD and NCs.The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest(the piriform cortex,lateral entorhinal cortex,and orbital-frontal cortex).Additionally,these abnormal olfactory FCs were associated with decreased cognitive function scores and OI,and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI.Conclusion:Overall,patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD,and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment.The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear.In this study,rats were randomly divided into middle cerebral occlusion model(MCAO)and paired associated magnetic stimulation(PAMS)groups.The MCAO rat model was produced by middle cerebral artery embolization.The PAMS group received PAMS on days 3 to 20 post MCAO.The MCAO group received sham stimulation,three times every week.Within 18 days after ischemia,rats were subjected to behavioral experiments—the foot-fault test,the balance beam walking test,and the ladder walking test.Balance ability was improved on days 15 and 17,and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group.Western blot assay showed that the expression levels of brain derived neurotrophic factor,glutamate receptor 2/3,postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21.Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere,but decreased in the contralateral hemisphere on day 20.By finite element simulation,the electric field distribution showed a higher intensity,of approximately 0.4 A/m^2,in the ischemic cortex compared with the contralateral cortex in the template.Together,our findings show that PAMS upregulates neuroplasticity-related proteins,increases regional brain activity,and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model.The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.

Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies

Searching for effective biomarkers is one of the most challenging tasks in the research ？eld of Autism Spectrum Disorder（ASD）. Magnetic resonance imaging（MRI） provides a non-invasive and powerful tool for investigating changes in the structure, function, maturation,connectivity, and metabolism of the brain of children with ASD. Here, we review the more recent MRI studies in young children with ASD, aiming to provide candidate biomarkers for the diagnosis of childhood ASD. The review covers structural imaging methods, diffusion tensor imaging, resting-state functional MRI, and magnetic resonance spectroscopy. Future advances in neuroimaging techniques, as well as cross-disciplinary studies and largescale collaborations will be needed for an integrated approach linking neuroimaging, genetics, and phenotypic data to allow the discovery of new, effective biomarkers.

Cortico–subcortical spatiotemporal dynamics in Parkinson’s disease can be modulated by transcranial alternating current stimulation

Objective:We investigated changes in cortico–subcortical spatiotemporal dynamics to explore the treatment mechanisms oftranscranial alternating current stimulation(tACS)in patientswith Parkinson’s disease(PD).Methods:Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 20 patients with PD and 20 normal controls(NC).Each patient with PD received successivemultidisciplinary intensive rehabilitation treatment and tACStreatment over a one-year interval.Individual functional brain network mapping and co-activation pattern(CAP)analysis were performed to characterize cortico–subcortical dynamics.Results:The same tACS electrode placement stimulated different proportions of functional brain networks across the participants.CAP analysis revealed that the visual network,attentional network,and default mode network co-activated with the thalamus,accumbens,and amygdala,respectively.The pattern characterized by thede-activation of the visual network and the activation of the thalamus showed a significantly low amplitude in the patients with PD than inNCs,and this amplitude increased after tACS treatment.Furthermore,the co-occurrence of cortico–subcortical CAPs was significantly higherin patients with PD than in NCs and decreased after tACS treatment.Conclusions:This study investigated cortico–subcortical spatiotemporaldynamics in patients with PD and further revealed the tACS treatmentmechanism.These findings contribute to understanding cortico–subcortical dynamics and exploring noninvasive neuromodulationtargets of cortico–subcortical circuits in brain diseases,such as PD,Alzheimer’s disease,and depression.