Aged; Aged, 80 and over; Brain/diagnostic imaging/metabolism; Female; Hallucinations/diagnostic imaging/etiology/metabolism; Humans; Lewy Body Disease/complications/diagnostic imaging/metabolism; Male; Neuropsychological Tests; Positron-Emission Tomography; 18F-FDG-PET; Dementia with Lewy bodies; Metabolic connectivity; NPI; Visual hallucinations
Abstract :
[en] Visual hallucinations (VH) are a core clinical feature of dementia with Lewy bodies (DLB), but their specific neural substrate remains elusive. We used (18)F-FDG-PET to study the neural dysfunctional signature of VH in a group of 38 DLB patients (mean age±SD 72.9 ± 7.5) with available anamnestic records, cognitive and neurological examination and NeuroPsychiatric Inventory assessing VH. We tested the voxel-wise correlation between (18)F-FDG-PET hypometabolism and VH NPI scores at the whole-group level, then adopting inter-regional correlation analysis to explore the resting-state networks (RSNs) metabolic connectivity in DLB patients with and without visual hallucinations, as compared to N = 38 age-matched healthy controls (HCs) (mean age±SD 71.5 ± 6.9). At the whole-group level, we found a negative correlation between VH NPI scores and (18)F-FDG-PET hypometabolism in the right occipito-temporal cortex (p < .001 uncorrected, p < .05 Family-Wise Error cluster-corrected). Then, splitting the group according to VH presence, we found that DLB non-hallucinators presented a pattern of connectivity seeding from this occipito-temporal cluster and extending to the ventral visual stream. At difference, the DLB hallucinators showed a metabolic connectivity pattern limited to the occipital-dorsal parietal regions. As for RSNs, both the DLB subgroups showed a markedly reduced extent of attention and visual networks compared to HCs, with a variable alteration in the topography. DLB-VH patients showed a more pronounced shrinkage of the primary visual network, which was disconnected from the higher visual hubs, at difference with both HC and DLB non-hallucinators. These findings suggest that an altered brain metabolic connectivity within and beyond visual systems may promote VH in DLB. These results support the most recent neurocognitive models interpreting VH as the result of an inefficient recruitment of the ventral visual stream and of a large-scale multi-network derangement.
Agosta, F., Galantucci, S., Filippi, M., Advanced magnetic resonance imaging of neurodegenerative diseases. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 38:1 (2017), 41–51 http://doi.org/10.1007/s10072-016-2764-x.
Auning, E., Rongve, A., Fladby, T., Booij, J., Hortobágyi, T., Siepel, F.J., et al. Early and presenting symptoms of dementia with lewy bodies. Dementia and Geriatric Cognitive Disorders 32:3 (2011), 202–208 http://doi.org/10.1159/000333072.
Cagnin, A., Gnoato, F., Jelcic, N., Favaretto, S., Zarantonello, G., Ermani, M., et al. Clinical and cognitive correlates of visual hallucinations in dementia with Lewy bodies. Journal of Neurology, Neurosurgery and Psychiatry 84:5 (2013), 505–510 http://doi.org/10.1136/jnnp-2012-304095.
Caminiti, S.P., Tettamanti, M., Sala, A., Presotto, L., Iannaccone, S., Cappa, S.F., et al. Metabolic connectomics targeting brain pathology in dementia with Lewy bodies. Journal of Cerebral Blood Flow and Metabolism 37:4 (2017), 1311–1325 http://doi.org/10.1177/0271678X16654497.
Collerton, D., Perry, E., McKeith, I., Why people see things that are not there: A novel perception and attention deficit model for recurrent complex visual hallucinations. Behavioral and Brain Sciences, 28(06), 2005 http://doi.org/10.1017/s0140525x05000130.
Crutch, S.J., Schott, J.M., Rabinovici, G.D., Murray, M., Snowden, J.S., van der Flier, W.M., et al. Consensus classification of posterior cortical atrophy. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 13:8 (2017), 870–884 http://doi.org/10.1016/j.jalz.2017.01.014.
Cummings, J.L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D.A., Gornbein, J., The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology 44:12 (1994), 2308–2314.
Della Rosa, P.A., Cerami, C., Gallivanone, F., Prestia, A., Caroli, A., Castiglioni, I., et al. A standardized [18F]-FDG-PET template for spatial normalization in statistical parametric mapping of dementia. Neuroinformatics 12:4 (2014), 575–593 http://doi.org/10.1007/s12021-014-9235-4.
Delli Pizzi, S., Maruotti, V., Taylor, J.-P., Franciotti, R., Caulo, M., Tartaro, A., et al. Relevance of subcortical visual pathways disruption to visual symptoms in dementia with Lewy bodies. Cortex 59 (2014), 12–21 http://doi.org/10.1016/j.cortex.2014.07.003.
Eickhoff, S.B., Paus, T., Caspers, S., Grosbras, M.-H., Evans, A.C., Zilles, K., et al. Assignment of functional activations to probabilistic cytoarchitectonic areas revisited. NeuroImage 36:3 (2007), 511–521 http://doi.org/10.1016/j.neuroimage.2007.03.060.
ffytche, D.H., Creese, B., Politis, M., Chaudhuri, K.R., Weintraub, D., Ballard, C., et al. The psychosis spectrum in Parkinson disease. Nature Reviews Neurology 13:2 (2017), 81–95 http://doi.org/10.1038/nrneurol.2016.200.
Firbank, M.J., Lloyd, J., O'Brien, J.T., The relationship between hallucinations and FDG-PET in dementia with Lewy bodies. Brain Imaging and Behavior 10:3 (2016), 636–639 http://doi.org/10.1007/s11682-015-9434-0.
Fulford, J., Milton, F., Salas, D., Smith, A., Simler, A., Winlove, C., et al. The neural correlates of visual imagery vividness – an fMRI study and literature review. Cortex, 105, 2018, 26–40 http://doi.org/10.1016/j.cortex.2017.09.014.
Goedert, M., Spillantini, M.G., Del Tredici, K., Braak, H., 100 years of Lewy pathology. Nature reviews Neurology 9:1 (2013), 13–24 http://doi.org/10.1038/nrneurol.2012.242.
Harding, A.J., Broe, G.A., Halliday, G.M., Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain 125:Pt 2 (2002), 391–403.
Horwitz, B., Duara, R., Rapoport, S.I., Intercorrelations of glucose metabolic rates between brain-regions - application to healthy-males in a state of reduced sensory input. Journal of Cerebral Blood Flow and Metabolism 4:4 (1984), 484–499 http://doi.org/10.1038/jcbfm.1984.73.
Imamura, T., Ishii, K., Hirono, N., Hashimoto, M., Tanimukai, S., Kazuai, H., et al. Visual hallucinations and regional cerebral metabolism in dementia with Lewy bodies (DLB). NeuroReport 10:9 (1999), 1903–1907.
Josephs, K.A., Whitwell, J.L., Boeve, B.F., Knopman, D.S., Tang-Wai, D.F., Drubach, D.A., et al. Visual hallucinations in posterior cortical atrophy. Archives of Neurology 63:10 (2006), 1427–1432 http://doi.org/10.1001/archneur.63.10.1427.
Kantarci, K., Avula, R., Senjem, M.L., Samikoglu, A.R., Zhang, B., Weigand, S.D., et al. Dementia with Lewy bodies and Alzheimer disease: neurodegenerative patterns characterized by DTI. Neurology 74:22 (2010), 1814–1821 http://doi.org/10.1212/WNL.0b013e3181e0f7cf.
Kenny, E.R., Blamire, A.M., Firbank, M.J., O'Brien, J.T., Functional connectivity in cortical regions in dementia with Lewy bodies and Alzheimer's disease. Brain 135:2 (2011), 569–581 http://doi.org/10.1093/brain/awr327.
Kiuchi, K., Morikawa, M., Taoka, T., Kitamura, S., Nagashima, T., Makinodan, M., et al. White matter changes in dementia with Lewy bodies and Alzheimer's disease: A tractography-based study. Journal of Psychiatric Research 45:8 (2011), 1095–1100 http://doi.org/10.1016/j.jpsychires.2011.01.011.
Kobeleva, X., Firbank, M., Peraza, L., Gallagher, P., Thomas, A., Burn, D.J., et al. Divergent functional connectivity during attentional processing in Lewy body dementia and Alzheimer's disease. Cortex 92 (2017), 8–18 http://doi.org/10.1016/j.cortex.2017.02.016.
Lee, D.S., Kang, H., Kim, H., Park, H., Oh, J.S., Lee, J.S., et al. Metabolic connectivity by interregional correlation analysis using statistical parametric mapping (SPM) and FDG brain PET; methodological development and patterns of metabolic connectivity in adults. European Journal of Nuclear Medicine and Molecular Imaging 35:9 (2008), 1681–1691 http://doi.org/10.1007/s00259-008-0808-z.
Lowther, E.R., O'Brien, J.T., Firbank, M.J., Blamire, A.M., Lewy body compared with Alzheimer dementia is associated with decreased functional connectivity in resting state networks. Psychiatry Research: Neuroimaging 223:3 (2014), 192–201 http://doi.org/10.1016/j.pscychresns.2014.06.004.
McKeith, I.G., Boeve, B.F., Dickson, D.W., Halliday, G., Taylor, J.-P., Weintraub, D., et al. Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology 89:1 (2017), 88–100 http://doi.org/10.1212/WNL.0000000000004058.
Mosimann, U.P., Rowan, E.N., Partington, C.E., Collerton, D., Littlewood, E., O'Brien, J.T., et al. Characteristics of visual hallucinations in Parkinson disease dementia and dementia with lewy bodies. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry 14:2 (2006), 153–160 http://doi.org/10.1097/01.JGP.0000192480.89813.80.
Mueller, C., Ballard, C., Corbett, A., Aarsland, D., The prognosis of dementia with Lewy bodies. The Lancet Neurology 16:5 (2017), 390–398 http://doi.org/10.1016/S1474-4422(17)30074-1.
Passow, S., Specht, K., Adamsen, T.C., Biermann, M., Brekke, N., Craven, A.R., et al. Default-mode network functional connectivity is closely related to metabolic activity. Human Brain Mapping 36:6 (2015), 2027–2038 http://doi.org/10.1002/hbm.22753.
Perani, D., FDG-PET and amyloid-PET imaging: the diverging paths. Current Opinion in Neurology 27:4 (2014), 405–413 http://doi.org/10.1097/WCO.0000000000000109.
Perani, D., Della Rosa, P.A., Cerami, C., Gallivanone, F., Fallanca, F., Vanoli, E.G., et al. Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting. NeuroImage: Clinical 6 (2014), 445–454 http://doi.org/10.1016/j.nicl.2014.10.009.
Peraza, L.R., Kaiser, M., Firbank, M., Graziadio, S., Bonanni, L., Onofrj, M., et al. fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies. NeuroImage: Clinical 4 (2014), 558–565 http://doi.org/10.1016/j.nicl.2014.03.013.
Perneczky, R., Drzezga, A., Boecker, H., Förstl, H., Kurz, A., Häussermann, P., Cerebral metabolic dysfunction in patients with dementia with Lewy bodies and visual hallucinations. Dementia and Geriatric Cognitive Disorders 25:6 (2008), 531–538 http://doi.org/10.1159/000132084.
Sanchez-Castaneda, C., Rene, R., Ramirez-Ruiz, B., Campdelacreu, J., Gascon, J., Falcon, C., et al. Frontal and associative visual areas related to visual hallucinations in dementia with Lewy bodies and Parkinson's disease with dementia. Movement Disorders 25:5 (2010), 615–622 http://doi.org/10.1002/mds.22873.
Savica, R., Grossardt, B.R., Bower, J.H., Boeve, B.F., Ahlskog, J.E., Rocca, W.A., Incidence of dementia with Lewy bodies and Parkinson disease dementia. JAMA Neurology 70:11 (2013), 1396–1402 http://doi.org/10.1001/jamaneurol.2013.3579.
Savio, A., Fünger, S., Tahmasian, M., Rachakonda, S., Manoliu, A., Sorg, C., et al. Resting-state networks as simultaneously measured with functional MRI and PET. Journal of Nuclear Medicine 58:8 (2017), 1314–1317 http://doi.org/10.2967/jnumed.116.185835.
Shine, J.M., Muller, A.J., O'Callaghan, C., Hornberger, M., Halliday, G.M., Lewis, S.J., Abnormal connectivity between the default mode and the visual system underlies the manifestation of visual hallucinations in Parkinson's disease: a task-based fMRI study. NPJ Parkinson's Disease, 1, 2015, 15003 http://doi.org/10.1038/npjparkd.2015.3.
Shine, J.M., O'Callaghan, C., Halliday, G.M., Lewis, S.J.G., Tricks of the mind: Visual hallucinations as disorders of attention. Progress in Neurobiology 116 (2014), 58–65 http://doi.org/10.1016/j.pneurobio.2014.01.004.
Shirer, W.R., Ryali, S., Rykhlevskaia, E., Menon, V., Greicius, M.D., Decoding subject-driven cognitive states with whole-brain connectivity patterns. Cerebral Cortex (New York, N.Y.: 1991) 22:1 (2012), 158–165 http://doi.org/10.1093/cercor/bhr099.
Smith, S.M., Jenkinson, M., Woolrich, M.W., Beckmann, C.F., Behrens, T.E.J., Johansen-Berg, H., et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage 23 (2004), S208–S219 http://doi.org/10.1016/j.neuroimage.2004.07.051.
Sourty, M., Thoraval, L., Roquet, D., Armspach, J.-P., Foucher, J., Blanc, F., Identifying dynamic functional connectivity changes in dementia with lewy bodies based on product hidden markov models. Frontiers in Computational Neuroscience, 10, 2016, 60 http://doi.org/10.3389/fncom.2016.00060.
Taylor, J.-P., Firbank, M., O'Brien, J.T., Visual cortical excitability in dementia with Lewy bodies. The British Journal of Psychiatry: The Journal of Mental Science 208:5 (2016), 497–498 http://doi.org/10.1192/bjp.bp.114.152736.
Tiraboschi, P., Hansen, L.A., Alford, M., Sabbagh, M.N., Schoos, B., Masliah, E., et al. Cholinergic dysfunction in diseases with Lewy bodies. Neurology 54:2 (2000), 407–411.
Tomasi, D., Volkow, N.D., Association between functional connectivity hubs and brain networks. Cerebral Cortex (New York, N.Y.: 1991) 21:9 (2011), 2003–2013 http://doi.org/10.1093/cercor/bhq268.
Trotta, N., Baete, K., Van Laere, K., Goldman, S., De Tiège, X., Wens, V., Letter to the editor: Neurometabolic resting-state networks derived from seed-based functional connectivity analysis. Journal of Nuclear Medicine, 2018 http://doi.org/10.2967/jnumed.118.212878.
Waters, F., Fernyhough, C., Hallucinations: A systematic review of points of similarity and difference across diagnostic classes. Schizophrenia Bulletin 43:1 (2017), 32–43 http://doi.org/10.1093/schbul/sbw132.
Winton-Brown, T.T., Ting, A., Mocellin, R., Velakoulis, D., Gaillard, F., Distinguishing neuroimaging features in patients presenting with visual hallucinations. AJNR. American Journal of Neuroradiology 37:5 (2016), 774–781 http://doi.org/10.3174/ajnr.A4636.
Xia, M., Wang, J., He, Y., BrainNet Viewer: a network visualization tool for human brain connectomics. PloS One, 8(7), 2013, e68910 http://doi.org/10.1371/journal.pone.0068910.
