Elsevier

Cortex

Volume 48, Issue 10, November–December 2012, Pages 1298-1309
Cortex

Research report
Brain networks in posterior cortical atrophy: A single case tractography study and literature review

https://doi.org/10.1016/j.cortex.2011.10.002Get rights and content

Abstract

Posterior cortical atrophy (PCA) is rare neurodegenerative dementia, clinically characterized by a progressive decline in higher-visual object and space processing. After a brief review of the literature on the neuroimaging in PCA, here we present a study of the brain structural connectivity in a patient with PCA and progressive isolated visual and visuo-motor signs. Clinical and cognitive data were acquired in a 58-years-old patient (woman, right-handed, disease duration 18 months). Brain structural and diffusion tensor (DT) Magnetic Resonance Imaging (MRI) were obtained. A voxel-based morphometry (VBM) study was performed to explore the pattern of gray matter (GM) atrophy, and a fully automatic segmentation was assessed to obtain the hippocampal volumes. DT MRI-based tractography was used to assess the integrity of long-range white matter (WM) pathways in the patient and in six sex- and age-matched healthy subjects. This PCA patient had a clinical syndrome characterized by left visual neglect, optic ataxia, and left limb apraxia, as well as mild visuo-spatial episodic memory impairment. VBM study showed bilateral posterior GM atrophy with right predominance; DT MRI tractography demonstrated WM damage to the right hemisphere only, including the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus, as compared to age-matched controls. The homologous left-hemisphere tracts were spared. No difference was found between left and right hippocampal volumes. These data suggest that selective visuo-spatial deficits typical of PCA might not result from cortical damage alone, but by a right-lateralized network-level dysfunction including WM damage along the major visual pathways.

Introduction

PCA is a rare, early-onset (usually before 65 years) neurodegenerative dementia, characterized by initially isolated, progressive impairment of higher order visual and visuo-spatial skills, which usually manifest as visual agnosia, prosopagnosia, environmental disorientation, elements of Balint’s syndrome and visual neglect (Andrade et al., 2010). While these deficits are hallmark features of the clinical syndrome, at presentation to specialized clinics, they can often be accompanied by deficits in praxis and language (e.g., dressing apraxia, transcortical sensory aphasia, and alexia) (Benson et al., 1988, Freedman et al., 1991, Mendez et al., 2002, Tang-Wai et al., 2004, McMonagle et al., 2006). Consistent with their clinical presentation, patients with PCA show gray matter (GM) loss in parieto-occipital and posterior temporal cortices, which is often more prominent in the right hemisphere (Galton et al., 2000, Whitwell et al., 2007). Positron emission topography (PET) studies have reported a prominent hypometabolism in the same posterior brain areas (Nestor et al., 2003, Schmidtke et al., 2005, Bokde et al., 2005). Although PCA patients do not meet clinical criteria for Alzheimer’s disease (AD), because of the lack of memory impairment as core of the syndrome, pathological series have found that the majority of PCA patients have senile plaques and neurofibrillary tangles, both hallmarks of AD, at autopsy (von Gunten et al., 2006, Renner et al., 2004, Tang-Wai et al., 2004, Alladi et al., 2007). In a recent study comparing clinical, biological and anatomical evidence between PCA and early-onset AD (age < 65) was directly performed (Migliaccio et al., 2009), voxel-based morphometry (VBM) results demonstrated a large region of overlapping atrophy between PCA and early-onset AD in the temporo-parietal regions. These regions are known to be preferentially affected in AD pathologically, structurally, and functionally, especially in younger patients (Yasuno et al., 1998, Frisoni et al., 2007, Rabinovici et al., 2010). Migliaccio et al. proposed that although location of atrophy is not an absolute marker of pathology, it does increase the probability of specific underlying pathologic processes, because different brain regions seem to be more vulnerable to specific diseases (Seeley et al., 2009). For these reasons and because of the early age at presentation (<65 years), the definition of “nontypical form of AD with an early age of onset” has been proposed for PCA (Migliaccio et al., 2009).

In PCA, the distribution of AD pathological changes is preponderant in occipital, parietal, and middle/inferior temporal cortices at the autopsy [see (von Gunten et al., 2006) for review]. However, recent studies conducted in vivo, using PET with [11C]-labeled Pittsburgh compound-B (Rosenbloom et al., 2011, de Souza et al., 2011), found no difference in the topography of fibrillar amyloid-β deposition between typical AD and PCA, and concluded that brain damage in PCA was not explained by the distribution of amyloid; if so, amyloid would not be the critical pathological change driving neurodegeneration in PCA.

White matter (WM) damage has attracted less interest. To date, only two single case studies (Yoshida et al., 2004, Duning et al., 2009) have assessed WM integrity in PCA by using diffusion tensor (DT) Magnetic Resonance Imaging (MRI) and a region of interest (ROI)-based approach. In one study (Duning et al., 2009), cognitive deterioration (over a period of 15 months) was associated with diffusivity changes of the occipito-parietal WM, rather than with overall GM and WM atrophy progression. In the other study (Yoshida et al., 2004), decreased fractional anisotropy (FA) was detected in the splenium of the corpus callosum (CC), possibly reflecting neuronal loss in caudal brain regions.

The lesional basis of PCA is not fully defined yet. Recent Single-photon emission computed tomography (SPECT) studies indicate a direct correlation between left inferior parietal hypoperfusion and acalculia, elements of Gerstmann’s syndrome, left–right disorientation and limb apraxia scores, whereas damage to the bilateral dorsal occipito-parietal regions appeared to be involved in Balint’s syndrome (Kas et al., 2011). In another study, structural MRI demonstrated a tendency toward a decreased cortical thickness in occipito-temporal and occipito-parietal cortices in PCA patients with predominant visuo-perceptual and visuo-spatial deficits, respectively (Lehmann et al., 2011). These results are consistent with the classical dichotomy between ventral (occipito-temporal) and dorsal (occipito-parietal) cortical visual streams (see Ungerleider and Mishkin, 1982).

It is to be noted, however, that the ventral–dorsal dichotomy may represent an oversimplification. Both the ventral and the dorsal streams are composed of several distinct pathways, which are starting to be defined both anatomically and functionally (Rizzolatti and Matelli, 2003, Schmahmann and Pandya, 2006, Kravitz et al., 2011, Thiebaut de Schotten et al., 2011). It is conceivable that different combinations of damage to these pathways give rise to distinct patterns of visual or visuo-motor impairment (Bartolomeo et al., 2007).

In neurodegenerative conditions, the prevalently cortical pathology usually inspires accounts of structure-function correlations based on strict cortical localization. Thus, neuropsychological deficits are conceived as resulting from cortical degeneration. However, in recent years a strict cortical localization approach for cognitive functions is changing toward more network-based hypotheses, according to which cognitive functions emerge from the interruption of the flow of information across large-scale networks linking different cortical regions (Catani and ffytche, 2005, Bartolomeo, 2011). The network-based approach contends that not only cortical lesions, but also damage to the WM connections between cortical areas can induce network dysfunction and, hence, cognitive disorders (Mesulam, 2009). On the other hand, WM abnormalities such as rarefaction, loss of axons, oligodendrocytes and reactive astrocytosis have also been reported in neurodegenerative conditions. However, it remains to be seen whether and to what extent damage to WM pathways can correlate with neuropsychological deficits.

A network approach to clinico-anatomical correlations seems particularly appropriate to degenerative disorders, in which neural damage does not distribute along vascular territories such as in stroke, but seem to follow neurofunctional systems implemented in large-scale brain networks. According to the network vulnerability target hypothesis, different networks show peculiar patterns of vulnerability in different neurodegenerative conditions (Seeley et al., 2009).

Section snippets

Case report

The present case report aims at exploring these open issues by taking advantage of detailed neuropsychological and neuroimaging studies, including DT MRI-based tractography of long-range WM tracts, which permits to explore microscopic changes undetected when using conventional MRI. Once specific tracts were identified, values of fiber integrity were obtained, such as mean diffusivity (MD), FA, parallel (λ//) and transverse (λ) diffusivities. These metrics have the potential to elucidate the

Neuropsychological study

The patient had moderate rightward deviation on both visual (19%) and tactile (25%) line bisection (Table 1), and pathological scores on landscape drawing copy (.5/4) and clock drawing test (0/4) (Fig. 2). Patient showed no auditory extinction (9/9), although she had some difficulty to identify auditory stimuli presented on the left side. There were rare left tactile extinctions on double stimulation (10/12).

Fig. 3 shows the setting of computerized assessment of optic ataxia (panel A) and the

Discussion

Neurodegenerative diseases are likely to progress along functionally and anatomically defined large-scale brain networks. These circuits may become the targets of specific neurodegenerative disorders (Seeley et al., 2009), consistent with the notion of selective vulnerability of anatomo-functional networks in neurodegenerative conditions (Mesulam, 2009). Long-range projections within functional neural circuits may thus play a critical role in brain–behavior relationships.

We studied a

Acknowledgments

We thank our patient Dr. B.N. for her willingness, will-power, and interest in our research. We also thank Bastien Oliveiro, Sophie Ferrieux and Elisabetta Pagani for their useful support. The authors acknowledge the support of the French Agence Nationale de la Recherche (ANR-07-LVIE-002-01 – Biomage study). Dr. Migliaccio was funded by the Neuropole de Recherche Francilien (NeRF) and the European Neurological Society (ENS).

References (79)

  • K.M. Heilman et al.

    The disconnection apraxias

    Cortex

    (2008)
  • S.R. Jackson et al.

    Where the eye looks, the hand follows; limb-dependent magnetic misreaching in optic ataxia

    Current Biology

    (2005)
  • J.A. McNab et al.

    High resolution diffusion-weighted imaging in fixed human brain using diffusion-weighted steady state free precession

    NeuroImage

    (2009)
  • M. Mesulam

    Defining neurocognitive networks in the BOLD new world of computed connectivity

    Neuron

    (2009)
  • C. Pierpaoli et al.

    Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture

    NeuroImage

    (2001)
  • L. Pisella et al.

    Optic ataxia and Balint’s syndrome: Neuropsychological and neurophysiological prospects

    Handbook of Clinical Neurology

    (2008)
  • L. Pisella et al.

    Optic ataxia and the function of the dorsal stream: Contributions to perception and action

    Neuropsychologia

    (2009)
  • W.W. Seeley et al.

    Neurodegenerative diseases target large-scale human brain networks

    Neuron

    (2009)
  • T. Shallice et al.

    Right posterior cortical functions in a tumour patient series

    Cortex

    (2010)
  • N.H. Stricker et al.

    Decreased white matter integrity in late-myelinating fiber pathways in Alzheimer’s disease supports retrogenesis

    NeuroImage

    (2009)
  • A. von Gunten et al.

    Neural substrates of cognitive and behavioral deficits in atypical Alzheimer’s disease

    Brain Research Reviews

    (2006)
  • V.J. Wedeen et al.

    Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers

    NeuroImage

    (2008)
  • J.L. Whitwell et al.

    Imaging correlates of posterior cortical atrophy

    Neurobiology of Aging

    (2007)
  • F. Agosta et al.

    Language networks in semantic dementia

    Brain

    (2010)
  • S. Alladi et al.

    Focal cortical presentations of Alzheimer’s disease

    Brain

    (2007)
  • K. Andrade et al.

    Visual neglect in posterior cortical atrophy

    BMC Neurology

    (2010)
  • P. Azouvi et al.

    A battery of tests for the quantitative assessment of unilateral neglect

    Restorative Neurology and Neuroscience

    (2006)
  • P. Bartolomeo

    Visual neglect

    Current Opinion in Neurology

    (2007)
  • P. Bartolomeo et al.

    Left unilateral neglect as a disconnection syndrome

    Cerebral Cortex

    (2007)
  • C. Beaulieu

    The basis of anisotropic water diffusion in the nervous system – a technical review

    NMR in Biomedicine

    (2002)
  • D.F. Benson et al.

    Posterior cortical atrophy

    Archives of Neurology

    (1988)
  • A.L. Bokde et al.

    Association between cognitive performance and cortical glucose metabolism in patients with mild Alzheimer’s disease

    Dementia and Geriatric Cognitive Disorders

    (2005)
  • L. Bronge et al.

    Postmortem MRI and histopathology of white matter changes in Alzheimer brains. A quantitative, comparative study

    Dementia and Geriatric Cognitive Disorders

    (2002)
  • A. Brun et al.

    A white matter disorder in dementia of the Alzheimer type: A pathoanatomical study

    Annals of Neurology

    (1986)
  • M. Catani et al.

    Symmetries in human brain language pathways correlate with verbal recall

    Proceedings of the National Academy of Sciences USA

    (2007)
  • M. Catani et al.

    The rises and falls of disconnection syndromes

    Brain

    (2005)
  • M. Chupin et al.

    Fully automatic hippocampus segmentation and classification in Alzheimer’s disease and mild cognitive impairment applied on data from ADNI

    Hippocampus

    (2009)
  • J.S. Damoiseaux et al.

    White matter tract integrity in aging and Alzheimer’s disease

    Human Brain Mapping

    (2009)
  • L.C. de Souza et al.

    Similar amyloid-beta burden in posterior cortical atrophy and Alzheimer’s disease

    Brain

    (2011)
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