The role of the amygdala during emotional processing in Huntington's disease: From pre-manifest to late stage disease

Abstract

BackgroundDeficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis.MethodsWe investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: “the Reading the Mind in the Eyes Test” which has been previously been shown to be amygdala dependent.ResultsPsychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p<0.05). Furthermore, performance on the “Reading the Mind in the Eyes Test” correlated negatively with proximity to disease onset and became progressively worse with each stage of disease.ConclusionAbnormalities in the neural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis. Furthermore, the “Reading the Mind in the Eyes Test” is a surrogate measure of amygdala function that is clinically useful across the entire cross-section of disease stages in HD.

Through your eyes or mine? The neural correlates of mental state recognition in Huntington's disease

“…Furthermore, the grey matter volume of left temporo‐parietal junction in healthy participants is positively related to RMET scores (Sato et al, ). Interestingly, we did not identify specific differences in amygdala activity between patients and controls during the RMET as has previously been hypothesized (Mason et al, ), although other findings such as differential activity in the insula and anterior cingulate are in line with previous studies using other facial expression tasks (Dogan et al, ; Labuschagne et al, 2013). The selective deficit on the standard (emotion) version of the RMET provides further support for the likelihood that patients with HD (including premanifest patients) can exhibit a deficit in social cognition per se , rather than their impairments on tasks involving theory of mind being incidental to motor, sensory, or general cognitive impairment.…”

“…Most early studies of social cognition in HD explored emotion recognition, and many highlighted a disproportionate deficit in the recognition of disgusted facial expressions (Gray, Young, Barker, Curtis, & Gibson, ; Montagne et al, ; Sprengelmeyer et al, ), although later studies revealed that deficits are common with other negative emotions such as anger (Henley et al, ; Mason et al, ). Interestingly, correlations between emotion expression and recognition have been highlighted in this patient population (Trinkler, Cleret de Langavant, & Bachoud‐Lévi, ).…”

Increased irritability, anxiety, and immune reactivity in transgenic Huntington’s disease monkeys

“…It is possible that the pattern of hostility exhibited by HD monkeys is due to alterations in amygdala activity. Recent studies in HD patients have shown decreased amygdala activity during emotional tasks lending support for this hypothesis (Mason et al, 2015; Van den Stock, et al, 2015). Additionally, HD patients have also been shown to exhibit lower fear and higher anger ratings of fearful pictures as compared to healthy controls (Eddy, et al, 2011).…”

An image‐based model of brain volume biomarker changes in Huntington's disease

“…The optic chiasm is not expected to be pathologically involved in the disease progression, but may undergo changes in volume due to the atrophy of surrounding tissues. Measurements of the volume of the third ventricle by transcranial sonography have shown that it is significantly larger in HD patients than HCs 38. Finally, the EBM predicts the posterior insula and basal forebrain as late‐stage biomarkers.…”