Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

Pini, Lorenzo; Jacquemot, Charlotte; Cagnin, Annachiara; Meneghello, Francesca; Semenza, Carlo; Mantini, Dante; Vallesi, Antonino

doi:10.1002/hbm.24790

Cited by 56 publications

(51 citation statements)

References 78 publications

(158 reference statements)

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“…Cortical sensory processing is not well-studied in HD mouse models; however, changes in cortical regions involved in sensory processing have been reported on structural MRI from prodromal HD gene-expansion carriers 24 . We are interested in mapping cortical network activity on a wide scale, and began by measuring the cortical response to a sensory stimulus because it is time-locked and can be analyzed with fast techniques such as in vivo electrophysiology and voltage-sensitive dye imaging to compare genotype responses with precision.…”

Section: Resultsmentioning

confidence: 99%

Altered cortical processing of sensory input in Huntington disease mouse models

Sepers

Mackay

Koch

et al. 2021

Preprint

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Huntington disease (HD), a hereditary neurodegenerative disorder, manifests as progressively impaired movement and cognition. Although early abnormalities of neuronal activity in striatum are well established in HD models, there are fewer in vivo studies of the cortex. Here, we record local field potentials (LFPs) in YAC128 HD model mice versus wild-type mice. In multiple cortical areas, limb sensory stimulation evokes a greater change in LFP power in YAC128 mice. Mesoscopic imaging using voltage-sensitive dyes reveal more extensive spread of evoked sensory signals across the cortical surface in YAC128 mice. YAC128 layer 2/3 sensory cortical neurons ex vivo show increased excitatory events, which could contribute to enhanced sensory responses in vivo. Cortical LFP responses to limb stimulation, visual and auditory input are also significantly increased in zQ175 HD mice. Results presented here extend knowledge of HD beyond ex vivo studies of individual neurons to the intact cortical network.

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Section: Resultsmentioning

confidence: 99%

Altered cortical processing of sensory input in Huntington disease mouse models

Sepers

Mackay

Koch

et al. 2021

Preprint

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“…Likewise, healthy slow wave sleep requires both local cortical and brain-wide synchrony of neuronal oscillatory activity. It may, therefore, also be that the widespread cortical pathology of HD, which affects connectivity even from presymptomatic stages [ 83 ], accounts for deficits in slow wave sleep. Moreover, recent evidence has identified a possible role of the striatum in governing arousability during sleep, and the generation of periodic limb movements [ 43 , 84 , 85 ].…”

Section: Sleep and Circadian Abnormalities In Huntington’s Disease: Evidence To Datementioning

confidence: 99%

The sleep and circadian problems of Huntington’s disease: when, why and their importance

2020

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Introduction Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases. Findings This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington’s disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface. Conclusions Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer’s and Parkinson’s as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.

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“…For example, if NREM sleep-promoting pathways (such as the melanin-concentrating hormone) that inhibit wake-promoting pathways are impaired early in HD, then this may result in abnormal transition dynamics without a change in the length of the sleep episode. Alternatively, given that both neuronal function and connectivity are impaired in HD [ 66 , 67 ] it is possible that the ability of the cortical neurons to produce and propagate slow waves [ 68 ] is altered in HD, making it easier for them to quickly transition from the hyperpolarised sleep-like state (cortical OFF state) to a depolarised wake-like state (cortical ON state).…”

Section: Discussionmentioning

confidence: 99%

Abnormally abrupt transitions from sleep-to-wake in Huntington’s disease sheep (Ovis aries) are revealed by automated analysis of sleep/wake transition dynamics

et al. 2021

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Sleep disturbance is a common and disruptive symptom of neurodegenerative diseases such as Alzheimer’s and Huntington’s disease (HD). In HD patients, sleep fragmentation appears at an early stage of disease, although features of the earliest sleep abnormalities in presymptomatic HD are not fully established. Here we used novel automated analysis of quantitative electroencephalography to study transitions between wake and non-rapid eye movement sleep in a sheep model of presymptomatic HD. We found that while the number of transitions between sleep and wake were similar in normal and HD sheep, the dynamics of transitions from sleep-to-wake differed markedly between genotypes. Rather than the gradual changes in EEG power that occurs during transitioning from sleep-to-wake in normal sheep, transition into wake was abrupt in HD sheep. Furthermore, transitions to wake in normal sheep were preceded by a significant reduction in slow wave power, whereas in HD sheep this prior reduction in slow wave power was far less pronounced. This suggests an impaired ability to prepare for waking in HD sheep. The abruptness of awakenings may also have potential to disrupt sleep-dependent processes if they are interrupted in an untimely and disjointed manner. We propose that not only could these abnormal dynamics of sleep transitions be useful as an early biomarker of HD, but also that our novel methodology would be useful for studying transition dynamics in other sleep disorders.

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Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

Cited by 56 publications

References 78 publications

Altered cortical processing of sensory input in Huntington disease mouse models

Altered cortical processing of sensory input in Huntington disease mouse models

The sleep and circadian problems of Huntington’s disease: when, why and their importance

Abnormally abrupt transitions from sleep-to-wake in Huntington’s disease sheep (Ovis aries) are revealed by automated analysis of sleep/wake transition dynamics

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