Regular paperCortical asymmetries in normal, mild cognitive impairment, and Alzheimer's disease
Introduction
The human brain exhibits hemispheric dominance for specific cognitive cortical functions. The left hemisphere is more specialized for language function, while the right hemisphere is more involved in visuospatial tasks, musical abilities, attention, and many aspects of emotion (Geschwind and Galaburda, 1985). In line with this functional asymmetry, there are also structural asymmetries between the left and right hemispheres. For example, earlier studies have shown that the left hemisphere has a longer lateral fissure and a wider occipital lobe than the right hemisphere, while the right hemisphere has a wider frontal lobe than the left hemisphere (LeMay, 1977, Toga and Thompson, 2003). In addition, the left hemisphere has a larger planum temporale, while the right hemisphere has a larger hippocampus (Allen et al., 2008, Dorsaint-Pierre et al., 2006, Geschwind and Levitsky, 1968).
With the advent of imaging techniques, there have been cortical asymmetry studies in healthy people using computerized imaging analysis of magnetic resonance imaging (MRI) such as voxel-based morphometry (VBM) (Good et al., 2001, Luders et al., 2004, Watkins et al., 2001) or “computational cortical pattern matching methods” (CCPMM) (Luders et al., 2006). More recently, resting state functional MRI has been employed to investigate the hemispheric asymmetry of functional networks (Tian et al., 2011). However, there have not been studies that investigated cortical asymmetry using surface based morphometry (SBM) that is known to be 1 of the most sensitive methods to measure cortical thickness (Kabani et al., 2001, MacDonald et al., 2000).
Despite many studies of cortical asymmetries in healthy individuals, there have been only a few studies on alterations of regional asymmetries of cortical thickness in Alzheimer's disease (AD) (Barnes et al., 2005, Thompson et al., 2003). Human cortical asymmetry may represent degree of specialization of specific cognitive functions. Prior studies suggested that the gain or loss of cognitive traits are associated with changes in cerebral asymmetry (Herbert et al., 2005, Illingworth and Bishop, 2009, Luders et al., 2004, Shaw et al., 2009). Therefore, cortical asymmetry of AD patients would be altered as disease progresses from normal cognition to AD. Previous studies suggest that there are many factors that can contribute to human cortical asymmetry such as handedness, gender, and interaction of nature and nurture (Hirnstein et al., 2010, Nadeau, 2010). However, 1 of the factors that contribute to regional cortical asymmetry in AD may be corticocortical connections. According to Terry et al., the most robust structural correlate of cognitive deficits associated with AD is the loss of synapses, and most of the synaptic loss in the neocortex is from neuronal networks that are rich in corticocortical connections (Terry et al., 1991). Galaburda et al. also stated that the magnitudes and directions of neocortical asymmetries are related to the numbers of neurons that comprise architectonic homologues in the left and right hemisphere as well as the density of intrahemispheric connections (Galaburda et al., 1990). In regard to corticocortical connectivity in the neocortex, the neurons in primary cortical areas or modality-specific sensory association areas lack this corticocortical connectivity compared with heteromodal (polymodal and supramodal) areas that are connected with a rich variety of modality-specific association areas, as well as with each other and paralimbic areas. Within the neocortex, AD appears to involve layer II (the external granular layer) and layer IV (the internal granular layer) before involving other layers (Hyman et al., 1984) and these affected cell layers are important for interconnecting cortical regions (corticocortical connections). Because patterns of cortical thickness are dependent in part on corticocortical connectivity, and areas of high connectivity are often most deteriorated in patients with AD, cortical regions with the greatest corticocortical connectivity are more likely to change in the cortical asymmetry patterns observed in healthy individuals during the course of AD.
In this study, we investigate the hemispheric neocortical asymmetries of participants with normal cognition (NC), mild cognitive impairment of amnestic type (aMCI), mild AD, and moderate to severe AD, using a relatively recently developed and very accurate SBM method called constrained Laplacian anatomic segmentation using proximity constrained Laplacian-based automated segmentation with proximities (CLASP) (Kim et al., 2005).
Section snippets
Participants
The subjects tested in this study included 152 individuals with NC, 101 with aMCI, and 207 with probable AD. All participants were right-handed as determined by the Edinburg Handedness Inventory (Oldfield, 1971). We defined right-handedness if the score of the Edinburgh Handedness Inventory was from +71 to +100 according to the cutoff score used in a previous study (Dragovic, 2004). These participants had visited the Memory Disorder Clinic of Samsung Medical Center from October 1999 through
Topography of cortical asymmetry in normal controls
The cortical asymmetry patterns in NC, aMCI, mild AD, and moderate-to-severe AD are shown in Fig. 1A. In NC, the areas with leftward asymmetric areas were the medial frontal lobe, medial orbitofrontal cortex including the rectal gyrus, inferior parts of pre- and postcentral gyri, superior and inferior parietal lobule, superior and middle temporal, and anterior tip of inferior temporal gyri. The rightward asymmetric areas were the middle and inferior frontal gyri, lateral orbitofrontal cortex,
Discussion
This study revealed that in normal elderly individuals, with reference to the precentral sulcus, the neocortical cortical thickness asymmetries of the medial and lateral sides of the right and left hemispheres were opposite of each other. The lateral portions of the cerebral hemisphere in the frontal areas, anterior to the precentral sulcus, exhibited rightward asymmetry of cortical thickness, but the lateral temporoparietal areas posterior to the precentral sulcus exhibited leftward asymmetry (
Disclosure statement
Dr. Heilman receives research support from the state of Florida, NIDCD/NIH (T-32 grant, 1T32DC008768-01), VA-Merit Review (#114-30-4813), University of Florida Opportunity Fund and NIH (R21 DC009247). Also, he was sponsored by Myriad, Novartis, Esai, and Pfizer Pharmaceuticals, Inc., for drug studies. The remaining authors report no disclosures.
The study was approved by the Institutional Review Board.
Acknowledgements
This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health, Welfare, and Family Affairs, Republic of Korea (A050079).
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