The phase coherence of the neurovascular unit is reduced in Huntington's disease.

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.

Aging affects the phase coherence between spontaneous oscillations in brain oxygenation and neural activity.

The risk of neurodegenerative disorders increases with age, due to reduced vascular nutrition and impaired neural function. However, the interactions between cardiovascular dynamics and neural activity, and how these interactions evolve in healthy aging, are not well understood. Here, the interactions are studied by assessment of the phase coherence between spontaneous oscillations in cerebral oxygenation measured by fNIRS, the electrical activity of the brain measured by EEG, and cardiovascular functions extracted from ECG and respiration effort, all simultaneously recorded. Signals measured at rest in 21 younger participants (31.1 ± 6.9 years) and 24 older participants (64.9 ± 6.9 years) were analysed by wavelet transform, wavelet phase coherence and ridge extraction for frequencies between 0.007 and 4 Hz. Coherence between the neural and oxygenation oscillations at ∼ 0.1 Hz is significantly reduced in the older adults in 46/176 fNIRS-EEG probe combinations. This reduction in coherence cannot be accounted for in terms of reduced power, thus indicating that neurovascular interactions change with age. The approach presented promises a noninvasive means of evaluating the efficiency of the neurovascular unit in aging and disease.