Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: A three-year follow-up study

Odish, Omar F. F.; Berg-Huysmans, Annette A. van den; Bogaard, Simon J.A. van den; Dumas, Eve M.; Hart, Ellen P.; Rombouts, Serge A.R.B.; Grond, Jeroen van der; Roos, Raymund A.C.

doi:10.1002/hbm.22616

Cited by 36 publications

(38 citation statements)

References 47 publications

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“…Other studies on pre‐HD and early‐onset patients reported reduced rsFC . However, a longitudinal study of pre‐HD over a period of 3 years didn't detect change in rsFC despite a significantly higher rate of striatal atrophy . This is different from recently suggested correlated patterns of structural atrophy within resting state network deficits in several neurodegenerative diseases .…”

Section: Introductioncontrasting

confidence: 79%

Connectomic imaging reveals Huntington‐related pathological and pharmaceutical effects in a mouse model

et al. 2018

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Recent studies suggest that neurodegenerative diseases could affect brain structure and function in disease‐specific network patterns; however, how spontaneous activity affects structural covariance network (SC) is not clear. We hypothesized that hyper‐excitability in Huntington disease (HD) disrupts the coordinated structural and functional connectivity, and treatment with memantine helps to reduce excitotoxicity and normalize the connectivity. MRI was conducted to measure somatosensory activation, resting‐state functional‐connectivity (rsFC), SC, amplitude of low frequency fluctuation (ALFF) and ALFF covariance (ALFFC) in the YAC128 mouse model of HD. We found somatosensory activation was unchanged but the subcortical ALFF was increased in HD mice, indicating subcortical but not cortical hyperactivity. The reduced sensorimotor rsFC but spared hippocampal and default mode networks in the HD mice was consistent with the more pronounced impairment in motor function compared with cognitive performance. The disease suppressed SC globally and reduced ALFFC in the basal ganglia network as well as its anti‐correlation with the default mode network. By comparing these connectivity measures, we found that the originally coupled rsFC‐SC relationship was impaired whereas SC‐ALFFC correlation was increased by HD, suggesting disease facilitated covariation of brain volume and activity amplitude but not neural synchrony. The comparison with mono‐synaptic axonal projection supports the hypothesis that rsFC, but not SC or ALFFC, is highly dependent on structural connectivity under healthy conditions. Treatment with memantine had a strong effect on normalizing the SC and reducing ALFF while slightly increasing other connectivity measures and restoring the rsFC‐SC coupling, which is consistent with its effect on alleviating hyper‐excitability and improving the coordinated neural growth. These results indicate that HD affects the cerebral structure–function relationship which could be partially reverted by NMDA antagonism. These connectivity measures provide unique insights into pathological and pharmaceutical effects in brain circuitry, and could be translatable biomarkers for evaluating drug effect and refining its efficacy.

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Section: Introductioncontrasting

confidence: 79%

Connectomic imaging reveals Huntington‐related pathological and pharmaceutical effects in a mouse model

et al. 2018

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“…VIS impairment prior to motor symptom onset is less clear. Most of the studies in pre‐HD did not report changes within this network compared to HC (Coppen et al, ; Odish et al, ; Poudel et al, ). Only Dumas et al () showed reduced connectivity in the medial VIS, in brain regions positioned outside the canonical visual mask (i.e., left frontal and right parietal lobules), leaving it unknown whether this connectivity pattern could reflect early changes within the VIS.…”

Section: Resultsmentioning

confidence: 99%

“…The auditory network did not show selective vulnerability at rest in either manifest or pre‐HD (Dumas et al, ; Odish et al, ; Poudel et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Similarly, increased synchronization in the right hippocampus and left dorsolateral prefrontal clusters of FPN was reported in manifest HD compared to the presymptomatic phase of the disease, showing positive correlation with disease burden score (Poudel et al, ). However, in pre‐HD individuals several studies failed to report changes in FPN (Dumas et al, ; Odish et al, ; Poudel et al, ), leaving the question related to its involvement in early HD stage still unsettled.…”

Section: Resultsmentioning

confidence: 99%

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

Pini

Jacquemot

Cagnin

et al. 2019

Human Brain Mapping

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Resting‐state functional magnetic resonance imaging (rs‐fMRI) has the potential to shed light on the pathophysiological mechanisms of Huntington's disease (HD), paving the way to new therapeutic interventions. A systematic literature review was conducted in three online databases according to PRISMA guidelines, using keywords for HD, functional connectivity, and rs‐fMRI. We included studies investigating connectivity in presymptomatic (pre‐HD) and manifest HD gene carriers compared to healthy controls, implementing seed‐based connectivity, independent component analysis, regional property, and graph analysis approaches. Visual network showed reduced connectivity in manifest HD, while network/areas underpinning motor functions were consistently altered in both manifest HD and pre‐HD, showing disease stage‐dependent changes. Cognitive networks underlying executive and attentional functions showed divergent anterior–posterior alterations, possibly reflecting compensatory mechanisms. The involvement of these networks in pre‐HD is still unclear. In conclusion, aberrant connectivity of the sensory‐motor network is observed in the early stage of HD while, as pathology spreads, other networks might be affected, such as the visual and executive/attentional networks. Moreover, sensory‐motor and executive networks exhibit hyper‐ and hypo‐connectivity patterns following different spatiotemporal trajectories. These findings could potentially help to implement future huntingtin‐lowering interventions.

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“…Significantly reduced synchronization in the sensory-motor network, particularly in the medial primary motor area (M1) posterior to the supplementary motor area, was detected by another study23. Others have reported no difference to controls2425. Some studies have also shown correlations between disease burden and functional connectivity25.…”

Section: Discussionmentioning

confidence: 99%

Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

Gorges

Müller

Mayer

et al. 2017

Sci Rep

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Structural and functional changes attributable to the neurodegenerative process in Huntington’s disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.

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Longitudinal resting state fMRI analysis in healthy controls and premanifest Huntington's disease gene carriers: A three-year follow-up study

Abstract: Based on the results found in this study, the provisional conclusion is that RS-fMRI lacks sensitivity in detecting changes in functional connectivity in HD gene carriers prior to disease manifestation over a 3-year follow-up period.

Cited by 36 publications

References 47 publications

Connectomic imaging reveals Huntington‐related pathological and pharmaceutical effects in a mouse model

Connectomic imaging reveals Huntington‐related pathological and pharmaceutical effects in a mouse model

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

Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease

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