Disgust and happiness recognition correlate with anteroventral insula and amygdala volume respectively in preclinical Huntington's disease

Patients with Huntington's disease (HD) can show disproportionate impairments in recognizing facial signals of disgust, but the neural basis of this deficit remains unclear. Functional imaging studies have implicated the anterior insula in the ability to recognize disgust, but have identified other structures as well, including the basal ganglia. In view of variable insula and basal ganglia volume changes in HD, we used voxel-based morphometry to map regional variations in gray matter (GM) volume in participants carrying the mutation for HD, and correlated this with their performance on a test of facial emotion recognition for six basic emotions (disgust, fear, anger, happiness, sadness, surprise). The volume of the anteroventral insula was strongly correlated with performance on the disgust recognition task. The amygdala volume (bilaterally) correlated with the ability to recognize happy facial expressions. There was marked specificity of the regional correlations for the emotion involved. Recognition of other emotion expressions, or more general cognitive or motor performance as measured by a standardized rating scale, did not correlate with regional brain volume in this group. Control participants showed no effect for any measure. The strong linear correlations for disgust and happiness recognition imply direct involvement of the anterior insula in disgust appreciation, and a similar role for the amygdala in recognizing happy facial expressions. The absence of a significant correlation with the basal ganglia suggests a less critical role for these structures in disgust recognition than has previously been suggested. The findings also highlight the role of neurodegenerative diseases combined with statistical imaging techniques in elucidating the brain basis of behavior and cognition

Progression of structural neuropathology in preclinical Huntington's disease: a tensor based morphometry study

Background and objectives: regional cerebral atrophy occurs in carriers of the Huntington’s disease (HD) gene mutation before clinical diagnosis is possible. The current inability to reliably measure progression of pathology in this preclinical phase impedes development of therapies to delay clinical onset. We hypothesised that longitudinal statistical imaging would detect progression of structural pathology in preclinical carriers of the HD gene mutation, in the absence of measurable clinical change.Methods: thirty subjects (17 preclinical mutation positive, 13 mutation negative) underwent serial clinical and magnetic resonance imaging (MRI) assessments over an interval of 2 years. Statistically significant changes in regional grey and white matter volume on MRI were analysed using tensor based morphometry (TBM). This technique derives a voxel-wise estimation of regional tissue volume change from the deformation field required to warp a subject’s early to late T1 images.Results: over 2 years, there was progressive regional grey matter atrophy in mutation-positive relative to negative subjects, without significant clinical progression of disease. Significant grey matter volume loss was limited to bilateral putamen and globus pallidus externa (GPe), left caudate nucleus, and left ventral midbrain in the region of the substantia nigra.Conclusions: while these results are consistent with previous cross sectional pathologic and morphometric studies, significant progression of atrophy in HD before the onset of significant clinical decline is now demonstrable with longitudinal statistical imaging. Such measures could be used to assess the efficacy of potential disease modifying drugs in slowing the progression of pathology before confirmed clinical onset of HD