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      Changes in resting-state functional brain activity are associated with waning cognitive functions in HIV-infected children

      research-article
      Author(s): a , * , b , a , a , c , d , b , c , e , a , f , a , g
      Publication date (Electronic):
      Journal: NeuroImage : Clinical
      Publisher: Elsevier
      Keywords: Human immunodeficiency virus, Resting-state functional imaging, Magnetic resonance imaging, Amplitude of low frequency fluctuations, Functional connectivity, HIV, Human immunodeficiency virus, ALFF, Amplitude of Low frequency fluctuations, FC, Functional connectivity, rs-fMRI, Resting-state functional magnetic resonance imaging, NPT, Neuropsychological test, CNS, Central nervous system, HAART, Highly-active-antiretroviral-therapy, MRI, Magnetic resonance imaging, 1H-MRS, Proton magnetic resonance spectroscopy, SNA, Spontaneous neural activity, ELISA, Enzyme-linked-immunosorbent-assay, RAKIT, Revisie Amsterdamse Kinder Intelligentie Test, BRAVO, Brain volume imaging, TR, Repetition time, TE, Echo time, FOV, Field of view, TI, Inversion time, FA, Flip angle, FLAIR, Fluid-attenuated-inversion recovery, FWHM, Full-width at half-maximum, cART, Combination antiretroviral therapy

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          Abstract

          Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment.

          Highlights

          • •

            Resting-state fMRI and cognitive assessment were performed in HIV-infected children.

          • •

            HIV-infected children showed abnormal spontaneous neural activity (SNA) and functional connectivity (FC).

          • •

            Lower cognitive scores were significantly associated with SNA and FC in HIV-infected children.

          • •

            HIV infection may have significant impact on neurodevelopment and cognitive performance.

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          Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

          Yu-Feng Zang, Yong Qing He, Chao-Zhe Zhu … (2007)
          In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.
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            Changes in hippocampal connectivity in the early stages of Alzheimer's disease: evidence from resting state fMRI.

            Liang Wang, Yufeng Zang, Yong Zhu He … (2006)
            A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in "default mode network" previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.
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              Impaired long distance functional connectivity and weighted network architecture in Alzheimer's disease.

              Ed Bullmore, Bing Liu, Yunyun Duan … (2014)
              Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting-state fMRI measures as biomarkers or predictors of disease progression in AD.
              Article 0 comments Cited 104 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Santosh K. Yadav
                Journal
                Journal ID (nlm-ta): Neuroimage Clin
                Journal ID (iso-abbrev): Neuroimage Clin
                Title: NeuroImage : Clinical
                Publisher: Elsevier
                ISSN (Electronic): 2213-1582
                Publication date PMC-release: 29 October 2018
                Publication date Collection: 2018
                Publication date (Electronic): 29 October 2018
                Volume: 20
                Pages: 1204-1210
                Affiliations
                [a ]Division of Translational Medicine, Research Branch, Sidra Medicine, Doha, Qatar
                [b ]Department of Radiology and Imaging, Fortis Memorial Research Institute, Gurgaon, India
                [c ]Department of Neurology, King George Medical University, Lucknow, India
                [d ]Department of Microbiology, King George Medical University, Lucknow, India
                [e ]Department of Pediatric Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
                [f ]Department of Psychiatry, Sidra Medicine/Weill Cornell Medicine-Qatar, Doha, Qatar
                [g ]Laboratory Animal Research Center, Qatar University, Doha, Qatar
                Author notes
                [* ]Corresponding author at: Division of Translational Medicine, Sidra Medicine, Doha, Qatar, P.O. Box 26999, Doha, Qatar. syadav@ 123456sidra.org
                Article
                Publisher ID: S2213-1582(18)30338-3
                DOI: 10.1016/j.nicl.2018.10.028
                PMC ID: 6224323
                PubMed ID: 30391858
                SO-VID: 58e074ed-9f12-471b-a10a-c5a4d0a7b19a
                Copyright © © 2018 The Authors. Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 2 May 2018
                Date revision received : 22 October 2018
                Date accepted : 26 October 2018
                Categories
                Subject: Regular Article

                Keywords: human immunodeficiency virus,resting-state functional imaging,magnetic resonance imaging,amplitude of low frequency fluctuations,functional connectivity,hiv, human immunodeficiency virus,alff, amplitude of low frequency fluctuations,fc, functional connectivity,rs-fmri, resting-state functional magnetic resonance imaging,npt, neuropsychological test,cns, central nervous system,haart, highly-active-antiretroviral-therapy,mri, magnetic resonance imaging,1h-mrs, proton magnetic resonance spectroscopy,sna, spontaneous neural activity,elisa, enzyme-linked-immunosorbent-assay,rakit, revisie amsterdamse kinder intelligentie test,bravo, brain volume imaging,tr, repetition time,te, echo time,fov, field of view,ti, inversion time,fa, flip angle,flair, fluid-attenuated-inversion recovery,fwhm, full-width at half-maximum,cart, combination antiretroviral therapy
                Data availability:
                Keywords: human immunodeficiency virus, resting-state functional imaging, magnetic resonance imaging, amplitude of low frequency fluctuations, functional connectivity, hiv, human immunodeficiency virus, alff, amplitude of low frequency fluctuations, fc, functional connectivity, rs-fmri, resting-state functional magnetic resonance imaging, npt, neuropsychological test, cns, central nervous system, haart, highly-active-antiretroviral-therapy, mri, magnetic resonance imaging, 1h-mrs, proton magnetic resonance spectroscopy, sna, spontaneous neural activity, elisa, enzyme-linked-immunosorbent-assay, rakit, revisie amsterdamse kinder intelligentie test, bravo, brain volume imaging, tr, repetition time, te, echo time, fov, field of view, ti, inversion time, fa, flip angle, flair, fluid-attenuated-inversion recovery, fwhm, full-width at half-maximum, cart, combination antiretroviral therapy

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