Within-patient correspondence of amyloid-β and intrinsic network connectivity in Alzheimer’s disease

“The dissociation between heteromodal and primary networks is in line with findings that primary sensory and sensorimotor regions are relatively spared in earlier stages of Alzheimer’s disease (Braak and Braak, 1991).”

“…MRI image (using affine registration), and normalized to a template in the stereotactic space of the Montreal Neurological Institute (MNI) with the ‘segment’ function (SPM5), which uses an iterative combination of non-linear registration and cortical segmentation (Ashburner and Friston, 2005).”

“Framewise displacement (Power et al., 2012) or the root-mean-”

“Aberrant clearance of amyloid-b precursor protein is thought to be a critical initial event in the disease’s pathogenesis, leading to amyloid-b peptide accumulation and plaque formation 20 to 30 years before cognitive symptoms arise (Selkoe, 2002; Jack et al., 2010; Bateman et al., 2012).”

“Prodromal Alzheimer’s disease has recently been defined by the coincidence of both mild cognitive impairment and the presence of at least one of five supportive biological signs for Alzheimer’s disease, such as medial temporal lobe atrophy or significant PiB uptake (Dubois et al., 2007).”

“…participant included medical history, neurological examination, informant interview (Morris, 1993), neuropsychological assessment by the neuropsychological assessment battery of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD, Morris et al., 1989), structural MRI and PiB-PET.”

“Given that significant PiB-uptake is measurable in the DMN even in early preclinical stages of Alzheimer’s disease (Jack et al., 2010; Bateman et al., 2012), where conventional measures of connectivity do not report robust connectivity reductions, the method presented here may help detect early, subtle reductions in c…”

“…et al., 2009; Bero et al., 2012; Zhou et al., 2012); and that (ii) amyloid-b pathology is accelerated by local stress caused by a lifetime of increased metabolism and intrinsic activity and connectivity (Greicius et al., 2004; Buckner et al., 2005, 2009; Bero et al., 2011; Drzezga et al., 2011).”

“…et al., 2009; Bero et al., 2012; Zhou et al., 2012); and that (ii) amyloid-b pathology is accelerated by local stress caused by a lifetime of increased metabolism and intrinsic activity and connectivity (Greicius et al., 2004; Buckner et al., 2005, 2009; Bero et al., 2011; Drzezga et al., 2011).”

“…previous studies, which tested amyloid-b-propagation models in healthy controls and compared them with patient atrophy data (Buckner et al., 2009; Seeley et al., 2009; Raj et al., 2012; Zhou et al., 2012), or which correlated amyloid-b plaques with DMN connectivity across subjects (Drzezga et…”

“In turn, the stronger accumulation leads to an increased reduction in connectivity.”

“…et al., 2009; Bero et al., 2012; Zhou et al., 2012); and that (ii) amyloid-b pathology is accelerated by local stress caused by a lifetime of increased metabolism and intrinsic activity and connectivity (Greicius et al., 2004; Buckner et al., 2005, 2009; Bero et al., 2011; Drzezga et al., 2011).”

“Searchlight approaches (Kriegeskorte et al., 2006) are multivariate analysis methods that step through all voxels of interest in sequence (in our case, all voxels in a given network) and examine voxel values in a ‘searchlight’ region of interest surrounding the current voxel.”

“…it allowed us to confirm previous studies done in animal models (e.g. Bero et al., 2011, 2012) or using intrinsic connectivity estimates from healthy controls (e.g. Buckner et al., 2009, Seeley et al., 2009, Zhou et al., 2012) that may not necessarily replicate in patients (Huang and Mucke, 2012).”

“The estimation of independent component analysis across both groups was in line with previous research (e.g. Filippini et al., 2009) and ensured a better correspondence of network maps between groups.”

“, 2012), the DMN and so-called attentional networks were of a priori interest (Allen et al., 2011).”

“On the one hand, animal studies have linked amyloid-b to reduced intrinsic activity and connectivity (Busche et al., 2008; Bero et al., 2011), a finding that has been repeatedly corroborated in the human DMN (Sheline et al., 2010; Mormino et al., 2011; for a review see Sheline and Raichle, 2013).”

“This approach has been used to remove zero-lag correlations when connectivity is calculated in magnetoencephalographic data (see Brookes et al., 2011; Hipp et al., 2012).”

“05 FWE cluster corrected for multiple comparisons) only in posterior parietal regions of the posterior DMN and right attention networks, replicating previous results (e.g. Sorg et al., 2007; see Supplementary Fig.”

“Typically, the deposition of plaques has been associated with the default mode network (DMN; Buckner et al., 2005; Sperling et al., 2009), a set of frontal and parietal midline structures with high metabolic activity that are coupled through high intrinsic functional connectivity (i.e. synchronous…”

“rather than to spatially contiguous but less connected neighbours (He et al., 2008; Seeley et al., 2009; Bero et al., 2012; Zhou et al., 2012); and that (ii) amyloid-b pathology is accelerated by local”

“Resulting network connectivity scores were then submitted to two-way mixed-effects ANOVA with factors group and network.”

“On the one hand, animal studies have linked amyloid-b to reduced intrinsic activity and connectivity (Busche et al., 2008; Bero et al., 2011), a finding that has been repeatedly corroborated in the human DMN (Sheline et al., 2010; Mormino et al., 2011; for a review see Sheline and Raichle, 2013).”

“Our independent component analysis approach consisted of a series of wellestablished analysis steps (Kiviniemi et al., 2003; Erhardt et al., 2011).”

“05. automatically spatially normalized to the MNI-template in SPM5 using warping parameters derived from previous individual structural MRI normalization (Mosconi et al., 2008).”

“atrophy data (Buckner et al., 2009; Seeley et al., 2009; Raj et al., 2012; Zhou et al., 2012), or which correlated amyloid-b plaques with DMN connectivity across subjects (Drzezga et al.”

“…models in healthy controls and compared them with patient atrophy data (Buckner et al., 2009; Seeley et al., 2009; Raj et al., 2012; Zhou et al., 2012), or which correlated amyloid-b plaques with DMN connectivity across subjects (Drzezga et al., 2011), here we developed a…”

“analysis framework (Calhoun et al., 2001), which is implemented”

“Following previous findings of aberrant medial and lateral heteromodal frontoparietal networks in early Alzheimer’s disease (Sorg et al., 2007, 2009; Neufang et al., 2011; Agosta et al., 2012), the DMN and so-called attentional networks were of a priori interest (Allen et al.”

“This finding is in line with results of previous studies, which found intersubject correlations between amyloid-b load and intrinsic connectivity in the DMN in individuals with significant plaque pathology (Hedden et al., 2009; Sheline et al., 2010; Mormino et al., 2011).”

“This finding is in line with results of previous studies, which found intersubject correlations between amyloid-b load and intrinsic connectivity in the DMN in individuals with significant plaque pathology (Hedden et al., 2009; Sheline et al., 2010; Mormino et al., 2011).”

“This association is mostly due to the apparent spatial overlap between the DMN and the average deposition of amyloid across the cortex (e.g. Buckner et al., 2005, 2009; Vlassenko et al., 2010; Mormino et al., 2011).”

“In contrast, rGLOBAL did not correlate with mean intrinsic connectivity in any network of either group (all uncorrected P4 0.12), indicating that the correlation was mainly driven by variability in PiB-uptake.”

“15, consistent with cut-off values used in previous PiB-PET studies (Drzezga et al., 2011).”

“Our independent component analysis approach consisted of a series of wellestablished analysis steps (Kiviniemi et al., 2003; Erhardt et al., 2011).”

“This association is mostly due to the apparent spatial overlap between the DMN and the average deposition of amyloid across the cortex (e.g. Buckner et al., 2005, 2009; Vlassenko et al., 2010; Mormino et al., 2011).”

“2A and B), with the highest load in the posterior DMN. Generally, the correlation between plaques and connectivity was higher in networks of higher median plaque load (Fig.”

“Our finding provides strong evidence for the previously stated hypothesis (Jagust and Mormino, 2011) that high levels of connectivity in heteromodal areas are associated with increased levels of amyloidb pathology, potentially due to nodal stress incurred by a lifetime of increased intrinsic…”

“…spreading to functionally connected areas rather than to spatially contiguous but less connected neighbours (He et al., 2008; Seeley et al., 2009; Bero et al., 2012; Zhou et al., 2012); and that (ii) amyloid-b pathology is accelerated by local stress caused by a lifetime of increased metabolism…”

“…deficits in functional connectivity of other intrinsic networks covering heteromodal areas (Sorg et al., 2007; Brier et al., 2012; Li et al., 2012; see also Sorg et al., 2012), the latter point has been reformulated in a model that supposes effects of amyloid-b in hetermodal…”

“As described previously (Sorg et al., 2013), the preprocessed data were decomposed into spatially independent components reflecting intrinsic networks in a group-independent component analysis framework (Calhoun et al., 2001), which is implemented in the GIFT software (http://icatb.sourceforge.net).”

“Since our model predicts that the same mechanism governs amyloid-b-related neurodegeneration, irrespective of the affected network, it should also apply to other variants of Alzheimer’s disease, such as posterior cortical atrophy or logopenic primary progressive aphasia (Lehmann et al., 2013a, b).”

“Given the widespread and well-known distribution of amyloid-b outside the DMN (Lehmann et al., 2013a, b; Sepulcre et al., 2013), and the well-characterized deficits in functional connectivity of other intrinsic networks covering heteromodal areas (Sorg et al.”

“Following previous findings of aberrant medial and lateral heteromodal frontoparietal networks in early Alzheimer’s disease (Sorg et al., 2007, 2009; Neufang et al., 2011; Agosta et al., 2012), the DMN and so-called attentional networks were of a priori interest (Allen et al.”

“Following previous findings of aberrant medial and lateral heteromodal frontoparietal networks in early Alzheimer’s disease (Sorg et al., 2007, 2009; Neufang et al., 2011; Agosta et al., 2012), the DMN and so-called attentional networks were of a priori interest (Allen et al., 2011).”

“…in functional connectivity of other intrinsic networks covering heteromodal areas (Sorg et al., 2007; Brier et al., 2012; Li et al., 2012; see also Sorg et al., 2012), the latter point has been reformulated in a model that supposes effects of amyloid-b in hetermodal (i.e. fronto-parietal)…”