Measuring network disruption in neurodegenerative diseases: New approaches using signal analysis

Abstract

Advanced neuroimaging has increased understanding of the pathogenesis and spread of disease, and offered new therapeutic targets. MRI and positron emission tomography have shown that neurodegenerative diseases including Alzheimer’s disease (AD), Lewy body dementia (LBD), Parkinson’s disease (PD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) are associated with changes in brain networks. However, the underlying neurophysiological pathways driving pathological processes are poorly defined. The gap between what imaging can discern and underlying pathophysiology can now be addressed by advanced techniques that explore the cortical neural synchronisation, excitability and functional connectivity that underpin cognitive, motor, sensory and other functions. Transcranial magnetic stimulation can show changes in focal excitability in cortical and transcortical motor circuits, while electroencephalography and magnetoencephalography can now record cortical neural synchronisation and connectivity with good temporal and spatial resolution.Here we reflect on the most promising new approaches to measuring network disruption in AD, LBD, PD, FTD, MS, and ALS. We consider the most groundbreaking and clinically promising studies in this field. We outline the limitations of these techniques and how they can be tackled and discuss how these novel approaches can assist in clinical trials by predicting and monitoring progression of neurophysiological changes underpinning clinical symptomatology.

Patterned functional network disruption in amyotrophic lateral sclerosis

“…We have identified significant correlations between our observed neurophysiological changes in the frontoparietal and frontotemporal network and composite scores of executive and language function, respectively. phenotypes of disease that can be characterised by differential change in brain network architecture, are likely to be important in the evolution of a precision medicine approach towards treatments (McMackin, Muthuraman, et al, 2019). Our observed alterations in functional connectivity correlate with structural degeneration, and functional motor and cognitive measures.…”

Imaging of Nonlinear and Dynamic Functional Brain Connectivity Based on EEG Recordings With the Application on the Diagnosis of Alzheimer’s Disease

“…It is well recognised that the integrity of dynamically interacting widely distributed brain networks, supported by widespread anatomical interconnections, is a prerequisite for normal brain function and that neurodegenerative conditions, to include the dementias, are associated with distinct patterns of brain network disruption [26]. Since age is considered the most significant risk factor for the development of AD [27], resting state EEG recordings have been increasingly used to study and define the effect of normal ageing on brain network characteristics [28] and to distinguish it from pathological ageing and specifically AD.…”

Relevance of biomarkers across different neurodegenerative diseases

“…In line with this, pupillometry is being explored as a measure of noradrenergic activity and, thus, locus coeruleus integrity [52]. Signal analysis from transcranial magnetic stimulation, electroencephalography, or magnetoencephalography has also shown promise as a biomarker of functional connectivity and may be sensitive to early changes [86][87][88]. Other functional readouts, such as sleep polysomnography and app-based digital phenotyping assessments have been proposed as early biomarkers as well [89][90][91].…”