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Neurodegeneration

Does Huntington's disease disrupt the amygdala before symptoms?

Mason SL, Zhang J, Begeti F, et al. · Neuropsychologia · 2015

Open access · cc by · source: Europe PMC

People carrying the Huntington's gene showed weaker coupling between the amygdala and the face-processing area of the brain while seeing angry faces, and this weakening was greater the closer they were to predicted disease onset.

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Study at a glance

Design
Case-control — Two cross-sectional group comparisons: fMRI with amygdala PPI connectivity (gene carriers vs controls) and an eyes-based social cognition test across disease stages.
N
Study 1 (fMRI): 20 pre-manifest gene carriers and 23 controls. Study 2 (RMET): 29 pre-manifest carriers, 50 manifest patients and 26 separate controls; 11 people took part in both.
Population
Adults carrying the Huntington's disease gene (pre-manifest and manifest at all stages) and healthy controls from a UK clinic
Outcome
Amygdala functional connectivity during implicit angry-face processing; Reading the Mind in the Eyes Test score

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Key findings

Carriers and controls did the scanner task equally fast and accurately, but carriers showed weaker amygdala-to-right-fusiform connectivity, and weaker connectivity went with being closer to estimated onset (r = 0.45). Eyes-test scores fell steadily with disease stage; pre-manifest carriers as a group did not differ from controls, but their scores dropped as predicted onset approached. In a small subgroup tested on both tasks within a year, connectivity and eyes-test performance were strongly correlated (r = 0.77).

Methodology

In the first study, 20 pre-manifest gene carriers and 23 controls did a simple face-or-house button task in an MRI scanner while angry and neutral faces appeared without them being told about the emotions; the researchers measured how activity in the left amygdala co-varied with the rest of the brain for angry versus neutral faces. In the second study, 29 pre-manifest carriers, 50 patients at early, moderate or late stage, and 26 controls did the Reading the Mind in the Eyes Test, which asks people to judge mental states from photographs of eyes.

Limitations

The samples were small and the connectivity difference only survived a more lenient statistical threshold than the whole-brain analysis, as the authors admit. Both studies are cross-sectional, so they show stage-related differences rather than tracking decline within the same people. The link between connectivity and the eyes test rests on only a handful of people, after two were removed, and emotion recognition itself was never tested in the carriers; mood, executive function and age effects were not fully controlled.

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