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Updated: Jun 22, 2025
Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
Published on: June 9, 2018
The phase coherence of the neurovascular unit is reduced in Huntington's disease
Juliane Bjerkan1, Jan Kobal2, Gemma Lancaster1
1Department of Physics, Lancaster University, Lancaster LA1 4YB, UK.
Insights
Huntington's disease impairs neurovascular unit function even before symptoms appear, affecting brain oxygenation and neuronal activity. This study offers a non-invasive method to track disease progression and treatment effectiveness.
Area of Science:
- Neuroscience
- Medical Research
- Systems Biology
Background:
- Huntington's disease (HD) is a neurodegenerative disorder characterized by chorea and cognitive decline, linked to expanded CAG repeats in the huntingtin gene.
- While structural and molecular changes in HD are known, neurovascular dysfunction's role remains unclear.
- The neurovascular unit is increasingly recognized as critical in neurodegenerative diseases, with mutant huntingtin affecting its components in HD patients.
Purpose of the Study:
- To investigate neurovascular interactions in presymptomatic and symptomatic Huntington's disease (HD) participants non-invasively.
- To assess alterations in brain oxygen transport dynamics and neuronal activity using advanced signal analysis.
- To establish a potential method for monitoring HD progression and treatment efficacy.
Main Methods:
- Simultaneous recording of functional near-infrared spectroscopy (fNIRS), ECG, and respiration effort to assess oxygen transport dynamics.
- Electroencephalography (EEG) was used to measure neuronal activity.
- Time-series analysis, including wavelet transform power and phase coherence, was applied to discern multiscale dynamics.
Main Results:
- Reduced neurovascular phase coherence around 0.1 Hz was observed in both presymptomatic and symptomatic HD groups.
- Presymptomatic HD participants showed lower oxygenation oscillation power, while symptomatic participants exhibited lower spatial coherence.
- EEG phase coherence, particularly in the alpha band, decreased in both HD groups, more significantly in the symptomatic stage.
Conclusions:
- The neurovascular unit is less efficient in Huntington's disease (HD) at both presymptomatic and symptomatic stages.
- Early-stage HD involves significant vascular impairment, potentially leading to compensatory vascular remodeling.
- Declining alpha and gamma coherence suggests progressive neuronal activity deterioration, raising questions about the sequence of vascular versus neuronal functional changes.
Abstract:
Huntington's disease is a neurodegenerative disorder in which neuronal death leads to chorea and cognitive decline. Individuals with ≥40 cytosine-adenine-guanine repeats on the interesting transcript 15 gene develop Huntington's disease due to a mutated huntingtin protein. While the associated structural and molecular changes are well characterized, the alterations in neurovascular function that lead to the symptoms are not yet fully understood. Recently, the neurovascular unit has gained attention as a key player in neurodegenerative diseases. The mutant huntingtin protein is known to be present in the major parts of the neurovascular unit in individuals with Huntington's disease. However, a non-invasive assessment of neurovascular unit function in Huntington's disease has not yet been performed. Here, we investigate neurovascular interactions in presymptomatic (N = 13) and symptomatic (N = 15) Huntington's disease participants compared to healthy controls (N = 36). To assess the dynamics of oxygen transport to the brain, functional near-infrared spectroscopy, ECG and respiration effort were recorded. Simultaneously, neuronal activity was assessed using EEG. The resultant time series were analysed using methods for discerning time-resolved multiscale dynamics, such as wavelet transform power and wavelet phase coherence. Neurovascular phase coherence in the interval around 0.1 Hz is significantly reduced in both Huntington's disease groups. The presymptomatic Huntington's disease group has a lower power of oxygenation oscillations compared to controls. The spatial coherence of the oxygenation oscillations is lower in the symptomatic Huntington's disease group compared to the controls. The EEG phase coherence, especially in the α band, is reduced in both Huntington's disease groups and, to a significantly greater extent, in the symptomatic group. Our results show a reduced efficiency of the neurovascular unit in Huntington's disease both in the presymptomatic and symptomatic stages of the disease. The vasculature is already significantly impaired in the presymptomatic stage of the disease, resulting in reduced cerebral blood flow control. The results indicate vascular remodelling, which is most likely a compensatory mechanism. In contrast, the declines in α and γ coherence indicate a gradual deterioration of neuronal activity. The results raise the question of whether functional changes in the vasculature precede the functional changes in neuronal activity, which requires further investigation. The observation of altered dynamics paves the way for a simple method to monitor the progression of Huntington's disease non-invasively and evaluate the efficacy of treatments.
