Skip to main content

Advertisement

SpringerLink
Log in

Altered cerebro-cerebellum resting-state functional connectivity in HIV-infected male patients

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

In addition to the role of planning and executing movement, the cerebellum greatly contributes to cognitive process. Numerous studies have reported structural and functional abnormalities in the cerebellum for HIV-infected patients, but little is known about the altered functional connectivity of particular cerebellar subregions and the cerebrum. Therefore, this study aimed to explore the resting-state functional connectivity (rsFC) changes of the cerebellum and further analyze the relationship between the rsFC changes and the neuropsychological evaluation. The experiment involved 26 HIV-infected men with asymptomatic neurocognitive impairment (ANI) and 28 healthy controls (HC). We selected bilateral hemispheric lobule VI and lobule IX as seed regions and mapped the whole-brain rsFC for each subregion. Results revealed that right lobule VI showed significant increased rsFC with the anterior cingulate cortex (ACC) in HIV-infected subjects. In addition, the correlation analysis on HIV-infected subjects illustrated the increased rsFC was negatively correlated with the attention/working memory score. Moreover, significantly increased cerebellar rsFCs were also observed in HIV-infected patients related to right inferior frontal gyrus (IFG) and right superior medial gyrus (SMG) while decreased rsFC was just found between right lobule VI and the left hippocampus (HIP). These findings suggested that, abnormalities of cerebro-cerebellar functional connectivity might be associated with cognitive dysfunction in HIV-infected men, particularly working memory impairment. It could also be the underlying mechanism of ANI, providing further evidence for early injury in the neural substrate of HIV-infected patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Allen LS, Gorski RA (1992) Sexual orientation and the size of the anterior commissure in the human brain. Proc Natl Acad Sci 89:7199–7202

    Article  CAS  Google Scholar 

  • Andrews-Hanna JR, Smallwood J, Spreng RN (2014) The default network and self-generated thought: component processes, dynamic control, and clinical relevance. Ann N Y Acad Sci 1316:29–52

    Article  Google Scholar 

  • Ann HW, Jun S, Shin NY, Han S, Ahn JY, Ahn MY, Jeon YD, Jung IY, Kim MH, Jeong WY, Ku NS, Kim JM, Smith DM, Choi JY (2016) Characteristics of resting-state functional connectivity in HIV-associated neurocognitive disorder. PLoS One 11:e0153493

    Article  Google Scholar 

  • Antinori A, Arendt G, Becker J, Brew B, Byrd D, Cherner M, Clifford D, Cinque P, Epstein L, Goodkin K (2007) Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69:1789–1799

    Article  CAS  Google Scholar 

  • Baddeley A (1996) Exploring the central executive. Q J Exp Psychol A Hum Exp Psychol 49:5–28

    Article  Google Scholar 

  • Caldwell JZ, Gongvatana A, Navia BA, Sweet LH, Tashima K, Ding M, Cohen RA (2014) Neural dysregulation during a working memory task in human immunodeficiency virus-seropositive and hepatitis C coinfected individuals. J Neuro-Oncol 20:398–411

    CAS  Google Scholar 

  • Castelo J, Sherman S, Courtney M, Melrose R, Stern C (2006) Altered hippocampal-prefrontal activation in HIV patients during episodic memory encoding. Neurology 66:1688–1695

    Article  CAS  Google Scholar 

  • Chang L, Løhaugen G, Douet V, Miller E, Skranes J, Ernst T (2016) Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial. Trials 17:62

    Article  CAS  Google Scholar 

  • Chang L, Speck O, Miller EN, Braun J, Jovicich J, Koch C, Itti L, Ernst T (2001) Neural correlates of attention and working memory deficits in HIV patients. Neurology 57:1001–1007

    Article  CAS  Google Scholar 

  • Chen SHA, Ho MHR, Desmond JE (2014) A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies. Hum Brain Mapp 35:593–615

    Article  Google Scholar 

  • Cooper DW (1958) The physiology and pathology of the cerebellum. Yale J Biol Med 31:108

    PubMed Central  Google Scholar 

  • Corrêa DG, Zimmermann N, Ventura N, Tukamoto G, Doring T, Leite SC, Fonseca RP, Bahia PR, Lopes FC, Gasparetto EL (2017) Longitudinal evaluation of resting-state connectivity, white matter integrity and cortical thickness in stable HIV infection: preliminary results. Neuroradiol J 30:535–545

    Article  Google Scholar 

  • Cox RW, Chen G, Glen DR, Reynolds RC, Taylor PA (2017) FMRI clustering in AFNI: false-positive rates redux. Brain Connect 7:152–171

    Article  Google Scholar 

  • Desmond JE, Chen S, Shieh PB (2005) Cerebellar transcranial magnetic stimulation impairs verbal working memory. Ann Neurol 58:553–560

    Article  Google Scholar 

  • Desmond JE, Fiez JA (1998) Neuroimaging studies of the cerebellum: language, learning and memory. Trends Cogn Sci 2:355–362

    Article  CAS  Google Scholar 

  • Diedrichsen J (2006) A spatially unbiased atlas template of the human cerebellum. NeuroImage 33:127–138

    Article  Google Scholar 

  • Elsheikh BH, Maher WE, Kissel JT (2010) Cerebellar atrophy associated with human immunodeficiency virus infection. Arch Neurol 67:634–635

    Article  Google Scholar 

  • Ernst T, Chang L, Jovicich J, Ames N, Arnold S (2002) Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology 59:1343–1349

    Article  CAS  Google Scholar 

  • Ernst T, Yakupov R, Nakama H, Crocket G, Cole M, Watters M, Ricardo-Dukelow ML, Chang L (2009) Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 65:316–325

    Article  Google Scholar 

  • Fletcher P, McKenna P, Friston K, Frith C, Dolan R (1999) Abnormal cingulate modulation of fronto-temporal connectivity in schizophrenia. NeuroImage 9:337–342

    Article  CAS  Google Scholar 

  • Fling BW, Cohen RG, Mancini M, Carpenter SD, Fair DA, Nutt JG, Horak FB (2014) Functional reorganization of the locomotor network in Parkinson patients with freezing of gait. PLoS One 9:e100291

    Article  Google Scholar 

  • Gardini S, Venneri A, Sambataro F, Cuetos F, Fasano F, Marchi M, Crisi G, Caffarra P (2015) Increased functional connectivity in the default mode network in mild cognitive impairment: a maladaptive compensatory mechanism associated with poor semantic memory performance. J Alzheimers Dis 45:457–470

    Article  Google Scholar 

  • Grant I, Franklin DR, Deutsch R, Woods SP, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson J, Collier AC (2014) Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology 82:2055–2062

    Article  CAS  Google Scholar 

  • Greicius MD, Krasnow B, Reiss AL, Menon V (2003) Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci 100:253–258

    Article  CAS  Google Scholar 

  • Guha A, Wang L, Tanenbaum A, Esmaeili-Firidouni P, Wendelken LA, Busovaca E, Clifford K, Desai A, Ances BM, Valcour V (2016) Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60. J Neurovirol 22:80–87

    Article  CAS  Google Scholar 

  • Guo W, Liu F, Zhang Z, Liu G, Liu J, Yu L, Xiao C, Zhao J (2015) Increased cerebellar functional connectivity with the default-mode network in unaffected siblings of schizophrenia patients at rest. Schizophr Bull 41:1317–1325

    Article  Google Scholar 

  • Habas C, Kamdar N, Nguyen D, Prater K, Beckmann CF, Menon V, Greicius MD (2009) Distinct cerebellar contributions to intrinsic connectivity networks. J Neurosci 29:8586–8594

    Article  CAS  Google Scholar 

  • Hakkers CS, Arends JE, Barth RE, Du Plessis S, Hoepelman AI, Vink M (2017) Review of functional MRI in HIV: effects of aging and medication. J Neuro-Oncol 23:20–32

    CAS  Google Scholar 

  • Hawellek DJ, Hipp JF, Lewis CM, Corbetta M, Engel AK (2011) Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis. Proc Natl Acad Sci 108:19066–19071

    Article  CAS  Google Scholar 

  • Heaton RK, Grant I, Butters N, White DA, Kirson D, Atkinson JH, McCutchan JA, Taylor MJ, Kelly MD, Ellis RJ, Wolfson T, Velin R, Marcotte TD, Hesselink JR, Jernigan TL, Chandler J, Wallace M, Abramson I (2009) The HNRC 500-neuropsychology of HIV infection at different disease stages. J Int Neuropsychol Soc 1:231

    Article  Google Scholar 

  • Keren-Happuch E, Chen S-HA, Ho M-HR, Desmond JE (2014) A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies. Hum Brain Mapp 35:593–615

    Article  Google Scholar 

  • Kipping JA, Grodd W, Kumar V, Taubert M, Villringer A, Margulies DS (2013) Overlapping and parallel cerebello-cerebral networks contributing to sensorimotor control: an intrinsic functional connectivity study. NeuroImage 83:837–848

    Article  Google Scholar 

  • Kirschen MP, Chen SA, Schraedley-Desmond P, Desmond JE (2005) Load-and practice-dependent increases in cerebro-cerebellar activation in verbal working memory: an fMRI study. NeuroImage 24:462–472

    Article  Google Scholar 

  • Law WA, Martin A, Mapou RL, Roller TL, Salazar AM, Temoshok LR, Rundell JR (1994) Working memory in individuals with HIV infection. J Clin Exp Neuropsychol 16:173–182

    Article  CAS  Google Scholar 

  • LeVay S (1991) A difference in hypothalamic structure between heterosexual and homosexual men. Science 253:1034–1037

    Article  CAS  Google Scholar 

  • Luks TL, Simpson GV, Feiwell RJ, Miller WL (2002) Evidence for anterior cingulate cortex involvement in monitoring preparatory attentional set. NeuroImage 17:792–802

    Article  Google Scholar 

  • Marcotte TD, Ghate M, Deutsch R, Letendre S, Meyer RA, Godbole, Risbud A, Thakar M, Grant I, Mehendale S (2012) Earlier initiation of antiretroviral therapy results in better neurocognitive functioning. In: Paper presented at the 19th conference on retroviruses and opportunistic infections, Seattle, WA, March 5-8. http://www.natap.org/2012/CROI/croi_155.htm

  • Meoded A, Morrissette AE, Katipally R, Schanz O, Gotts SJ, Floeter MK (2015) Cerebro-cerebellar connectivity is increased in primary lateral sclerosis. NeuroImage: Clinical 7:288–296

    Article  Google Scholar 

  • Middleton F, Strick P (1994) Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function. Science 266:458–461

    Article  CAS  Google Scholar 

  • Onuki Y, Van Someren EJ, De Zeeuw CI, Van der Werf YD (2013) Hippocampal–cerebellar interaction during spatio-temporal prediction. Cereb Cortex 25:313–321

    Article  Google Scholar 

  • Osaka M, Osaka N, Kondo H, Morishita M, Fukuyama H, Aso T, Shibasaki H (2003) The neural basis of individual differences in working memory capacity: an fMRI study. NeuroImage 18:789–797

    Article  Google Scholar 

  • Heaton RK, Clifford M, Franklin J, Woods P, Ake P, Vaida P, Ellis M, Letendre M, Marcotte P, Atkinson M, Rivera-Mindt P, Vigil M, Taylor P, Collier M, Marra M, Gelman M, McArthur M, Morgello M, Simpson M, McCutchan M, Abramson P, Gamst P, Fennema-Notestine P, Jernigan P, Wong M, Grant M, For the CHARTER Group (2010) HIV-associated neurocognitive disorders persist in the era of potent antiretroviral therapy. Neurology 75(23):2087–2096

    Article  CAS  Google Scholar 

  • Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL (2001) A default mode of brain function. Proc Natl Acad Sci 98:676–682

    Article  CAS  Google Scholar 

  • Reyes E, Mohar A, Mallory M, Miller A, Masliah E (1994) Hippocampal involvement associated with human immunodeficiency virus encephalitis in Mexico. Arch Pathol Lab Med 118:1130–1134

    CAS  PubMed  Google Scholar 

  • Riedel MC, Ray KL, Dick AS, Sutherland MT, Hernandez Z, Fox PM, Eickhoff SB, Fox PT, Laird AR (2015) Meta-analytic connectivity and behavioral parcellation of the human cerebellum. NeuroImage 117:327–342

    Article  Google Scholar 

  • Rochefort C, Arabo A, André M, Poucet B, Save E, Rondi-Reig L (2011) Cerebellum shapes hippocampal spatial code. Science 334:385–389

    Article  CAS  Google Scholar 

  • Sang L, Qin W, Liu Y, Han W, Zhang Y, Jiang T, Yu C (2012) Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures. NeuroImage 61:1213–1225

    Article  Google Scholar 

  • Savic I, Lindström P (2008) PET and MRI show differences in cerebral asymmetry and functional connectivity between homo-and heterosexual subjects. Proc Natl Acad Sci 105:9403–9408

    Article  CAS  Google Scholar 

  • Schmahmann JD (1991) An emerging concept: the cerebellar contribution to higher function. Arch Neurol 48:1178–1187

    Article  CAS  Google Scholar 

  • Smith EE, Jonides J (1999) Storage and executive processes in the frontal lobes. Science 283:1657–1661

    Article  CAS  Google Scholar 

  • Stoodley CJ, Schmahmann JD (2009) Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. NeuroImage 44:489–501

    Article  Google Scholar 

  • Stout JC, Salmon D, Butters N, Taylor M, Peavy G, Heindel W, Delis D, Ryan L, Atkinson J, Chandler J (1995) Decline in working memory associated with HIV infection. Psychol Med 25:1221–1232

    Article  CAS  Google Scholar 

  • Sundermann B, Pfleiderer B (2012) Functional connectivity profile of the human inferior frontal junction: involvement in a cognitive control network. BMC Neurosci 13:119

    Article  Google Scholar 

  • Swaab DF, Hofman MA (1990) An enlarged suprachiasmatic nucleus in homosexual men. Brain Res 537:141–148

    Article  CAS  Google Scholar 

  • Tagliati M, Simpson D, Morgello S, Clifford D, Schwartz R, Berger J (1998) Cerebellar degeneration associated with human immunodeficiency virus infection. Neurology 50:244–251

    Article  CAS  Google Scholar 

  • Thomas JB, Brier MR, Snyder AZ, Vaida FF, Ances BM (2013) Pathways to neurodegeneration effects of HIV and aging on resting-state functional connectivity. Neurology 80:1186–1193

    Article  Google Scholar 

  • Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L (2017) Cerebellar granule cells encode the expectation of reward. Nature 544:96–100

    Article  CAS  Google Scholar 

  • Wang L, Zou F, Shao Y, Ye E, Jin X, Tan S, Hu D, Yang Z (2014) Disruptive changes of cerebellar functional connectivity with the default mode network in schizophrenia. Schizophr Res 160:67–72

    Article  Google Scholar 

  • Wiley CA, Soontornniyomkij V, Radhakrishnan L, Masliah E, Mellors J, Hermann SA, Dailey P, Achim CL (1998) Distribution of brain HIV load in AIDS. Brain Pathol 8:277–284

    Article  CAS  Google Scholar 

  • Woods SP, Moore DJ, Weber E, Grant I (2009) Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 19:152–168

    Article  Google Scholar 

  • Yu W, Krook-Magnuson E (2015) Cognitive collaborations: bidirectional functional connectivity between the cerebellum and the hippocampus. Front Syst Neurosci 9:177

    Article  Google Scholar 

  • Zheng W, Liu X, Song H, Li K, Wang Z (2017) Altered functional connectivity of cognitive-related cerebellar subregions in Alzheimer’s disease. Front Aging Neurosci 9:143

    Article  Google Scholar 

  • Zhuo C, Wang C, Wang L, Guo X, Xu Q, Liu Y, Zhu J (2017) Altered resting-state functional connectivity of the cerebellum in schizophrenia. Brain Imaging Behav 12(2):383–389

    Article  Google Scholar 

Download references

Funding

This study was supported by the Fundamental Research Funds for the Central Universities (WK 2100230016 to XW), the National Natural Science Foundation of China (91432301), the National Natural Science Foundation of China (81701665), the National Nature Science Foundation of China (81571634, 81771806), the Beijing Municipal Administration of Hospitals Incubating Program (PX2016036), the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (No. ZYLX201511), and the Capital Medical University Research and Incubation Funding (PYZ2017124).

Author information

Author notes

  1. Huijuan Wang and Ruili Li contributed equally to this work.

Authors and Affiliations

  1. Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, 230026, China

    Huijuan Wang, Yawen Zhou, Yanming Wang, Jin Cui, Benedictor Alexander Nguchu, Bensheng Qiu & Xiaoxiao Wang

  2. Department of Radiology, Beijing Youan Hospital, Capital Medical University, No.8, Xi Tou Tiao, Youanmen Wai, Feng Tai District, Beijing, 10069, China

    Ruili Li & Hongjun Li

Authors
  1. Huijuan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ruili Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yawen Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yanming Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jin Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Benedictor Alexander Nguchu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bensheng Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaoxiao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hongjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiaoxiao Wang or Hongjun Li.

Ethics declarations

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the research ethics committee of the Beijing Youan Hospital, Capital Medical University, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Li, R., Zhou, Y. et al. Altered cerebro-cerebellum resting-state functional connectivity in HIV-infected male patients. J. Neurovirol. 24, 587–596 (2018). https://doi.org/10.1007/s13365-018-0649-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13365-018-0649-x

Keywords

Search

Navigation