Longitudinal evaluation of resting-state connectivity,white matter integrity and cortical thickness in stable HIV infection: Preliminary results

Abstract

Purpose

The objectives of this study were to determine if HIV-infected patients treated with highly active antiretroviral therapy (HAART), without dementia, suffer from longitudinal gray matter (GM) volume loss, changes in white matter (WM) integrity and deterioration in functional connectivity at rest, in an average interval of 30 months.

Methods

Clinically stable HIV-positive patients (on HAART, CD4 + T lymphocyte > 200 cells/μl, and viral loads <50 copies/μl) were recruited. None of them had HIV-associated dementia. Each patient underwent two scans, performed in a 1.5-T magnetic resonance imaging (MRI) scanner. FreeSurfer was used to perform cortical volumetric reconstruction and segmentation of GM structures. WM integrity was assessed using tract-based spatial statistics to post-process diffusion tensor imaging data, and FMRIB's Software Library tools were used to post-process resting-state functional magnetic resonance imaging (RS-fMRI).

Results

There were no significant differences in cortical thickness, deep GM volumes, or diffusivity parameters between the scans at the two time points. Five resting-state networks were identified in our patients. In the second MRI, HIV-positive patients presented increased areas of functional connectivity in visual pathways, frontoparietal and cerebellar networks, compared with the first MRI (considering p < 0.05).

Conclusions

RS-fMRI revealed potentially compensatory longitudinal alterations in the brains of HIV-positive patients, attempting to compensate for brain damage related to the infection.

Keywords

HIV cortical thickness diffusion tensor imaging resting-state functional imaging longitudinal follow-up

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References

Maartens

Celum

Lewin

. HIV infection: Epidemiology, pathogenesis, treatment, and prevention. Lancet 2014; 384: 258–271.

Deeks

Phillips

. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 2009; 338: a3172.

Spudich

. HIV and neurocognitive dysfunction. Curr HIV/AIDS Rep 2013; 10: 235–243.

Simioni

Cavassini

Annoni

et al.

Cognitive dysfunction in HIV patients despite long-standing suppression of viremia. AIDS 2010; 24: 1243–1250.

Dong

Welsh

Chenevert

et al.

Clinical applications of diffusion tensor imaging. J Magn Reson Imaging 2004; 19: 6–18.

Ragin

Storey

Cohen

et al.

Whole brain diffusion tensor imaging in HIV-associated cognitive impairment. AJNR Am J Neuroradiol 2004; 25: 195–200.

Leite

Corrêa

Doring

et al.

Diffusion tensor MRI evaluation of the corona radiata, cingulate gyri, and corpus callosum in HIV patients. J Magn Reson Imaging 2013; 38: 1488–1493.

Corrêa

Zimmermann

Doring

et al.

Diffusion tensor MR imaging of white matter integrity in HIV-positive patients with planning deficits. Neuroradiology 2015; 57: 475–482.

Thompson

Dutton

Hayashi

et al.

Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4 + T lymphocyte decline. Proc Natl Acad Sci U S A 2005; 102: 15647–15652.

10.

Ragin

Ochs

et al.

Structural brain alterations can be detected early in HIV infection. Neurology 2012; 79: 2328–2334.

11.

Corrêa

Zimmermann

Netto

et al.

Regional cerebral gray matter volume in HIV-positive patients with executive function deficits. J Neuroimaging 2016; 26: 450–457.

12.

Lee

Smyser CD and Shimony

. Resting-state fMRI: A review of methods and clinical applications. AJNR Am J Neuroradiol 2013; 34: 1866–1872.

13.

Smitha

Akhil Raja

Arun

et al.

Resting state fMRI: A review on methods in resting state connectivity analysis and resting state networks. Neuroradiol J 2017; 30: 305–317.

14.

Guha

Wang

Tanenbaum

et al.

Intrinsic network connectivity abnormalities in HIV-infected individuals over age 60. J Neurovirol 2016; 22: 80–87.

15.

Ortega

Brier

Ances

. Effects of HIV and combination antiretroviral therapy on cortico-striatal functional connectivity. AIDS 2015; 29: 703–712.

16.

Thomas

Brier

Snyder

et al.

Pathways to neurodegeneration: Effects of HIV and aging on resting-state functional connectivity. Neurology 2013; 80: 1186–1193.

17.

Antinori

Arendt

Becker

et al.

Updated research nosology for HIV-associated neurocognitive disorders. Neurology 2007; 69: 1789–1799.

18.

Fischl

Salat

Busa

et al.

Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron 2002; 33: 341–355.

19.

Desikan

Ségonne

Fischl

et al.

An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 2006; 31: 968–980.

20.

Smith

Jenkinson

Woolrich

et al.

Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004; 23(Suppl 1): S208–S219.

21.

Smith

Jenkinson

Johansen-Berg

et al.

Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. Neuroimage 2006; 31: 1487–1505.

22.

Roosendaal

Schoonheim

Hulst

et al.

Resting state networks change in clinically isolated syndrome. Brain 2010; 133(Pt 6): 1612–1621.

23.

Beckmann

DeLuca

Devlin

et al.

Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci 2005; 360: 1001–1013.

24.

Mwanza

Nyamabo

Tylleskär

et al.

Neuro-ophthalmological disorders in HIV infected subjects with neurological manifestations. Br J Ophthalmol 2004; 88: 1455–1459.

25.

Vincent

Kahn

Snyder

et al.

Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J Neurophysiol 2008; 100: 3328–3342.

26.

Woods

Moore

Weber

et al.

Cognitive neuropsychology of HIV-associated neurocognitive disorders. Neuropsychol Rev 2009; 19: 152–168.

27.

Stoodley

Schmahmann

. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 2010; 46: 831–844.

28.

Kwakwa

Ghobrial

. Primary cerebellar degeneration and HIV. Arch Intern Med 2001; 161: 1555–1556.

29.

Becker

Maruca

Kingsley

et al.

Factors affecting brain structure in men with HIV disease in the post-HAART era. Neuroradiology 2012; 54: 113–121.

30.

Towgood

Pitkanen

Kulasegaram

et al.

Mapping the brain in younger and older asymptomatic HIV-1 men: Frontal volume changes in the absence of other cortical or diffusion tensor abnormalities. Cortex 2012; 48: 230–241.

31.

Ances

Ortega

Vaida

et al.

Independent effects of HIV, aging, and HAART on brain volumetric measures. J Acquir Immune Defic Syndr 2012; 59: 469–477.

32.

Stout

Ellis

Jernigan

et al.

Progressive cerebral volume loss in human immunodeficiency virus infection: A longitudinal volumetric magnetic resonance imaging study. Arch Neurol 1998; 55: 161–168.

33.

Kuhn

Schonfeld

Sayegh

et al.

The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study. Hum Brain Mapp 2017; 38: 1025–1037.

34.

Pfefferbaum

Rogosa

Rosenbloom

et al.

Accelerated aging of selective brain structures in human immunodeficiency virus infection: A controlled, longitudinal magnetic resonance imaging study. Neurobiol Aging 2014; 35: 1755–1768.

35.

Seider

Gongvatana

Woods

et al.

Age exacerbates HIV-associated white matter abnormalities. J Neurovirol 2016; 22: 201–212.

36.

Chang

Wong

Nakama

et al.

Greater than age-related changes in brain diffusion of HIV patients after 1 year. J Neuroimmune Pharmacol 2008; 3: 265–274.

37.

Corrêa

Zimmermann

Tukamoto

et al.

Longitudinal assessment of subcortical gray matter volume, cortical thickness, and white matter integrity in HIV-positive patients. J Magn Reson Imaging 2016; 44: 1262–1269.

38.

Ann

Jun

Shin

et al.

Characteristics of resting-state functional connectivity in HIV-associated neurocognitive disorder. PLoS One 2016; 11: e0153493.

39.

Wang

Foryt

Ochs

et al.

Abnormalities in resting-state functional connectivity in early human immunodeficiency virus infection. Brain Connect 2011; 1: 207–217.

40.

Seeley

Menon

Schatzberg

et al.

Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 2007; 27: 2349–2356.

41.

Chang

Holt

Yakupov

et al.

Lower cognitive reserve in the aging human immunodeficiency virus-infected brain. Neurobiol Aging 2013; 34: 1240–1253.

42.

Ernst

Yakupov

Nakama

et al.

Declined neural efficiency in cognitively stable human immunodeficiency virus patients. Ann Neurol 2009; 65: 316–325.

43.

Bell

Arango

Anthony

. Neurobiology of multiple insults: HIV-1-associated brain disorders in those who use illicit drugs. J Neuroimmune Pharmacol 2006; 1: 182–191.

44.

Brandies

Yehuda

. The possible role of retinal dopaminergic system in visual performance. Neurosci Biobehav Rev 2008; 32: 611–656.

45.

Störmer

Passow

Biesenack

et al.

Dopaminergic and cholinergic modulations of visual-spatial attention and working memory: Insights from molecular genetic research and implications for adult cognitive development. Dev Psychol 2012; 48: 875–889.

46.

Wang

Chang

Volkow

et al.

Decreased brain dopaminergic transporters in HIV-associated dementia patients. Brain 2004; 127: 2452–2458.

47.

Chang

Yakupov

Nakama

et al.

Antiretroviral treatment is associated with increased attentional load-dependent brain activation in HIV patients. J Neuroimmune Pharmacol 2008; 3: 95–104.

48.

Ances

Roc

Korczykowski

et al.

Combination antiretroviral therapy modulates the blood oxygen level-dependent amplitude in human immunodeficiency virus-seropositive patients. J Neurovirol 2008; 14: 418–424.

49.

Ernst

Chang

Jovicich

et al.

Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology 2002; 59: 1343–1349.

50.

Melrose

Tinaz

Castelo

et al.

Compromised fronto-striatal functioning in HIV: An fMRI investigation of semantic event sequencing. Behav Brain Res 2008; 188: 337–347.

51.

Clifford

Ances

. HIV-associated neurocognitive disorder. Lancet Infect Dis 2013; 13: 976–986.

52.

Wonderlick

Ziegler

Hosseini-Varnamkhasti

et al.

Reliability of MRI-derived cortical and subcortical morphometric measures: Effects of pulse sequence, voxel geometry, and parallel imaging. Neuroimage 2009; 44: 1324–1333.

53.

Inano

Takao

Hayashi

et al.

Effects of age and gender on neuroanatomical volumes. J Magn Reson Imaging 2013; 37: 1072–1076.

54.

Madden

Spaniol

Costello

et al.

Cerebral white matter integrity mediates adult age differences in cognitive performance. J Cogn Neurosci 2009; 21: 289–302.

55.

Damoiseaux

Beckmann

Arigita

et al.

Reduced resting-state brain activity in the “default network” in normal aging. Cereb Cortex 2008; 18: 1856–1864.

56.

Beckmann

DeLuca

Devlin

et al.

Investigations into resting-state connectivity using independent component analysis. Philos Trans R Soc Lond B Biol Sci 2005; 360: 1001–1013.