Brain networks in Huntington disease
David Eidelberg, D. James Surmeier
David Eidelberg, D. James Surmeier
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Brain networks in Huntington disease

Abstract

Recent studies have focused on understanding the neural mechanisms underlying the emergence of clinical signs and symptoms in early stage Huntington disease (HD). Although cell-based assays have focused on cell autonomous effects of mutant huntingtin, animal HD models have revealed alterations in the function of neuronal networks, particularly those linking the cerebral cortex and striatum. These findings are complemented by metabolic imaging studies of disease progression in premanifest subjects. Quantifying metabolic progression at the systems level may identify network biomarkers to aid in the objective assessment of new disease-modifying therapies and identify new regions that merit mechanistic study in HD models.

Authors

David Eidelberg, D. James Surmeier

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Figure 3

Metabolic activity at key network nodes.

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Metabolic activity at key network nodes. (A) In the putamen, metabolic a...
(A) In the putamen, metabolic activity declined over time in premanifest subjects (P < 0.005). Relatively greater reductions were observed in the subgroup of premanifest gene carriers who subsequently phenoconverted (red) as compared to those who remained asymptomatic (blue). Mean metabolic activity is also displayed for the whole group (black). (B) Regional metabolic activity was also reduced in the cingulate cortex at all 3 time points, without significant longitudinal change. (C) In the thalamus, metabolic activity declined over time (P < 0.01). In the premanifest subjects who did not phenoconvert, thalamic metabolism was elevated at baseline and remained above normal at the subsequent two longitudinal time points. By contrast, baseline thalamic metabolic activity was also elevated in the premanifest subjects who subsequently phenoconverted, but then declined to normal levels as symptoms emerged. (D) Cerebellar metabolism was also elevated at baseline in premanifest subjects, but no subsequent changes were discerned. Mean globally normalized metabolic activity values (± 1 SEM) for the healthy control subjects are represented by horizontal dashed lines. Error bars represent 1 SEM at each time point. Reprinted with permission from Brain (88).