Schoonheim, M. M. | bioRxiv Science

bioRxiv2021

Structural (dys)connectivity associates with cholinergic cell density of the nucleus basalis of Meynert in Alzheimer's disease

Cognitive deficits in Alzheimers disease, specifically amnestic (memory dominant) deficits, are associated with cholinergic degeneration in the basal forebrain. The cholinergic nucleus within the basal forebrain, the nucleus basalis of Meynert, exhibits local atrophy and reduced cortical tract integrity on MRI, and reveals amyloid-{beta} and phosphorylated-tau pathology at autopsy. To better understand the pathophysiology of nucleus basalis of Meynert atrophy and its neocortical projections in Alzheimers disease, we utilized a combined post-mortem in-situ MRI and histopathology approach. A total of 19 Alzheimers disease (10 amnestic and 9 non-amnestic) and 9 non-neurological control donors underwent 3T T1-weighted MRI for anatomical delineation and volume assessment of the nucleus basalis of Meynert, and diffusion-weighted imaging for microstructural assessment of the nucleus and its projections. At subsequent brain autopsy, tissue dissection and immunohistochemistry were performed for amyloid-{beta}, phosphorylated-tau and choline acetyltransferase. Compared to controls, we observed an MRI-derived volume reduction and altered microstructural integrity of the nucleus basalis of Meynert in Alzheimers disease donors. Furthermore, decreased cholinergic cell density was associated with reduced integrity of the nucleus and its tracts to the temporal lobe, specifically to the temporal pole of the superior temporal gyrus, and the parahippocampal gyrus. The association between cholinergic cell density and alteration to cortical tracts was specific for amnestic, compared to non-amnestic Alzheimers disease donors. Our study illustrates that the nucleus basalis of Meynert is severely affected in amnestic Alzheimers disease, both in terms of pathology within the nucleus, but also in terms of damage to its cortical projections, specifically to the temporal lobe, which may contribute to the observed cognitive deterioration.

neuroscience↗

bioRxiv2021

Multimodal multilayer network centrality relates to executive functioning

Executive functioning is a higher-order cognitive process that is thought to depend on a brain network organization facilitating network integration across specialized subnetworks. The frontoparietal network (FPN), a subnetwork that has diverse connections to other brain modules, seems pivotal to this integration, and a more central role of regions in the FPN has been related to better executive functioning. Brain networks can be constructed using different modalities: diffusion MRI (dMRI) can be used to reconstruct structural networks, while resting-state fMRI (rsfMRI) and magnetoencephalography (MEG) yield functional networks. These networks are often studied in a unimodal way, which cannot capture potential complementary or synergistic modal information. The multilayer framework is a relatively new approach that allows for the integration of different modalities into one network of networks. It has already yielded promising results in the field of neuroscience, having been related to e.g. cognitive dysfunction in Alzheimers disease. Multilayer analyses thus have the potential to help us better understand the relation between brain network organization and executive functioning. Here, we hypothesized a positive association between centrality of the FPN and executive functioning, and we expected that multimodal multilayer centrality would supersede unilayer centrality in explaining executive functioning. We used dMRI, rsfMRI, MEG, and neuropsychological data obtained from 33 healthy adults (age range 22-70 years) to construct eight modality-specific unilayer networks (dMRI, fMRI, and six MEG frequency bands), as well as a multilayer network comprising all unilayer networks. Interlayer links in the multilayer network were present only between a nodes counterpart across layers. We then computed and averaged eigenvector centrality of the nodes within the FPN for every uni- and multilayer network and used multiple regression models to examine the relation between uni- or multilayer centrality and executive functioning. We found that higher multilayer FPN centrality, but not unilayer FPN centrality, was related to better executive functioning. To further validate multilayer FPN centrality as a relevant measure, we assessed its relation with age. Network organization has been shown to change across the life span, becoming increasingly efficient up to middle age and regressing to a more segregated topology at higher age. Indeed, the relation between age and multilayer centrality followed an inverted-U shape. These results show the importance of FPN integration for executive functioning as well as the value of a multilayer framework in network analyses of the brain. Multilayer network analysis may particularly advance our understanding of the interplay between different brain network aspects in clinical populations, where network alterations differ across modalities. HighlightsO_LIMultimodal neuroimaging and neurophysiology data were collected in healthy adults C_LIO_LIMultilayer frontoparietal centrality was positively associated with executive functioning C_LIO_LIUnilayer (unimodal) centralities were not associated with executive functioning C_LIO_LIThere was an inverted-U relationship between multilayer centrality and age C_LI

neuroscience↗