Functional network disruption in the degenerative dementias.
paper
Cited
Public
- Authors
- Pievani, Michela; de Haan, Willem; Wu, Tao; Seeley, William W; Frisoni, Giovanni B
- Year
- 2011
- Journal
- The Lancet. Neurology
- PMID
- 21778116
- DOI
- 10.1016/S1474-4422(11)70158-2
- PMCID
- PMC3219874
Despite advances towards understanding the molecular pathophysiology of the neurodegenerative dementias, the mechanisms linking molecular changes to neuropathology and neuropathological changes to clinical symptoms remain largely obscure. Connectivity is a distinctive feature of the brain and the integrity of functional network dynamics is crucial for normal functioning. A better understanding of network disruption in the neurodegenerative dementias might help bridge the gap between molecular changes, pathological changes, and symptoms. Recent findings on functional network disruption as assessed with resting-state or intrinsic connectivity functional MRI and electroencephalography and magnetoencephalography have shown distinct patterns of network disruption across the major neurodegenerative diseases. These network abnormalities are somewhat specific to the clinical syndromes and, in Alzheimer's disease and frontotemporal dementia, network disruption tracks the pattern of pathological changes. These findings might have practical implications for diagnostic accuracy, allowing earlier detection of neurodegenerative diseases even at the presymptomatic stage, and tracking of disease progression.
The pathophysiological framework of neurodegenerative diseases: connectivity as an intermediate phenotype between pathology and symptoms. The case of AD.
Functional connectivity on resting-state fMRI in healthy subjects. ICA-derived resting-state fMRI networks (DMN, salience, left and right executive-control, visual and motor networks)26-28 of a healthy 33-year old male. Red-to-yellow colours indicate the strength of each voxel's connectivity to overall component time series (shown beneath each map).
Functional connectivity of resting-state EEG/MEG in healthy subjects. Headplot showing functional MEG network of a healthy 63-year old female in the alpha (8-13 Hz; left) and beta (13-30 Hz; right) frequency ranges.13 Coloured lines indicate different functional sub-networks (modules), black lines represent their interconnections (only visualized in beta band example). Background colours indicate connectivity strength (red indicates hub β i.e. highly connected -regions). SL=synchronization likelihood.13 A=Anterior; P=Posterior; L=Left; R=Right.
Structural connectivity assessed with DTI in a healthy (33-year old male) subject. DTI-tractography identifies long (mainly visible in sagittal view as green and blue colour-coded fibers) and short (mainly visible in axial and coronal views as red colour-coded fibers) WM connections. Specific tracts can be identified which subserve distinct cognitive and non-cognitive functions. The fornix and cingulum are mainly associated with memory and emotional processing, cortico-cortical association and intra-hemispheric tracts are associated with a broad range of cognitive processes, the corticospinal/cerebellar tracts are generally involved in motor disorders.36
Schematic representation of (B) βsmall-worldβ brain functional network and of (A) simulated βregularβ and (C) βrandomβ networks with the same number of nodes (n=35) and connections (n=120). (A) Regular networks have many connections among neighbouring regions (red lines) and few connections with distant nodes (light blue lines). (B) Small-world networks have less local connections and more long distance connections. (C) Random networks have few local connections and many connections among distant regions. Each network is shown overlaid onto a standard template (upper row) and in schematic representation (middle row). Nodes represent 35 cortical points of the left hemisphere drawn from the Automated Anatomical Labeling template, and edges represent functionally connected nodes. The real-world network was extracted from a single subject, the corresponding regular (A) and random (C) networks were simulated using the Brain Connectivity Toolbox.89 The corresponding theoretical Watts-Strogatz network models are also shown (lower row; adapted from ref 38). Reproduced from Nature Publishing Group (permission requested).
| # | Section | Preview |
|---|---|---|
| 20 | 3. Disruption of functional networks is associated with clinical impairment β 3.1 Alzheimer's Disease | Graph theoretical analysis of network organization in AD has shown a loss of small-world structureβ¦ |
| 21 | 3. Disruption of functional networks is associated with clinical impairment β 3.2 Frontotemporal dementia | FTD refers to a group of clinical syndromes associated with underlying frontotemporal lobarβ¦ |
| 22 | 3. Disruption of functional networks is associated with clinical impairment β 3.2 Frontotemporal dementia | Recent work has revealed that bvFTD syndrome, like typical AD, reflect the progressive degenerationβ¦ |
| 23 | 3. Disruption of functional networks is associated with clinical impairment β 3.2 Frontotemporal dementia | network alone,58 suggesting that network-based patterns which are sensitive to decreases andβ¦ |
| 24 | 3. Disruption of functional networks is associated with clinical impairment β 3.2 Frontotemporal dementia | Neurophysiological literature on functional networks in FTLD is almost non-existent. Oneβ¦ |
| 25 | 3. Disruption of functional networks is associated with clinical impairment β 3.2 Frontotemporal dementia | Whether the underlying FTD molecular class can be identified by its impact on network-specificβ¦ |
| 26 | 3. Disruption of functional networks is associated with clinical impairment β 3.3 Parkinson's Disease and Dementia with Lewy bodies | PD and DLB are two neurodegenerative syndromes associated with deposition ofβ¦ |
| 27 | 3. Disruption of functional networks is associated with clinical impairment β 3.3 Parkinson's Disease and Dementia with Lewy bodies | Available evidence suggests that PD and DLB are associated with distinct patterns of functionalβ¦ |
| 28 | 3. Disruption of functional networks is associated with clinical impairment β 3.3 Parkinson's Disease and Dementia with Lewy bodies | study of patients in early, drug-naive stages showed an increase in alpha band (8-10 Hz)β¦ |
| 29 | 3. Disruption of functional networks is associated with clinical impairment β 3.3 Parkinson's Disease and Dementia with Lewy bodies | In PD and DLB, a clear correspondence between structural and functional connectivity changes inβ¦ |
| 30 | 3. Disruption of functional networks is associated with clinical impairment β 3.3 Parkinson's Disease and Dementia with Lewy bodies | show reduced connectivity between fronto-temporal and fronto-occipital regions compared toβ¦ |
| 31 | 3. Disruption of functional networks is associated with clinical impairment β 3.3 Parkinson's Disease and Dementia with Lewy bodies | Graph theory studies of network organization in PD, PDD and DLB are scarce. One study investigatedβ¦ |
| 32 | 3. Disruption of functional networks is associated with clinical impairment β 3.4 Neurobiological and clinical implications of network disruption | Research findings reviewed here demonstrate that functional neuroimaging is able to detect distinctβ¦ |
| 33 | 3. Disruption of functional networks is associated with clinical impairment β 3.4 Neurobiological and clinical implications of network disruption | Important network differences have emerged from comparisons between PD, PDD and DLB, with anβ¦ |
| 34 | 3. Disruption of functional networks is associated with clinical impairment β 3.4 Neurobiological and clinical implications of network disruption | From a clinical perspective, further pursuit of network-based strategies may lead to the developmentβ¦ |
| 35 | 3. Disruption of functional networks is associated with clinical impairment β 3.4 Neurobiological and clinical implications of network disruption | such as PET and cerebrospinal fluid sampling. In general, these techniques are non-invasive andβ¦ |
| 36 | 4. Conclusions β 4.1 Connectivity studies in the larger context | Brain connectivity studies allow to address questions that have so far escaped a convincing answer.β¦ |
| 37 | 4. Conclusions β 4.1 Connectivity studies in the larger context | neurons from fetal donors only to develop Lewy bodies within those neurons a few years afterβ¦ |
| 38 | 4. Conclusions β 4.1 Connectivity studies in the larger context | Finally, although the mechanisms noted above are built around the idea that networks constrain andβ¦ |
| 39 | 4. Conclusions β 4.2 Technical issues and limitations | The analysis of functional networks is a multi-step procedure, in which methodological choices andβ¦ |
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