Amygdala habituation: A reliable fMRI phenotype

Abstract

Amygdala function is of high interest for cognitive, social and psychiatric neuroscience, emphasizing the need for reliable assessments in humans. Previous work has indicated unsatisfactorily low within-subject reliability of amygdala activation fMRI measures. Based on basic science evidence for strong habituation of amygdala response to repeated stimuli, we investigated whether a quantification of habituation provides additional information beyond the usual estimate of the overall mean activity. We assessed the within-subject reliability of amygdala habituation measures during a facial emotion matching paradigm in 25 healthy subjects. We extracted the amygdala signal decrement across the course of the fMRI run for the two test-retest measurement sessions and compared reliability estimates with previous findings based on mean response amplitude. Retest-reliability of the session-wise amygdala habituation was significantly higher than the evoked amygdala mean amplitude (intraclass correlation coefficients (ICC)=0.53 vs. 0.16). To test the task-specificity of this finding, we compared the retest-reliability of amygdala habituation across two different tasks. Significant amygdala response decrement was also seen in a cognitive task (n-back working memory) that did not per se activate the amygdala, but was totally unreliable in that context (ICC~0.0), arguing for task-specificity. Together the results show that emotion-dependent amygdala habituation is a robust and considerably more reliable index than the mean amplitude, and provides a robust potential endpoint for within-subject designs including pharmaco-fMRI studies.

Reliability of an fMRI paradigm for emotional processing in a multisite longitudinal study

“…Based on these prior single-site studies [Johnstone et al, 2005; Lipp et al, 2014; Plichta et al, 2012; Sauder et al, 2013; Van den Bulk et al, 2013], the reliability coefficients for amygdala activation in this study fall within the expected range. Activation was more stable in the right amygdala than the left amygdala, consistent with prior work using the same task (Manuck et al, 2007; Plichta et al, 2014), which may be due to high visuospatial demands of emotion matching rather than underlying neural properties. It has also been suggested that amygdala activation is more reliable to fearful faces than other facial expressions (Sauder et al, 2013; Stark et al, 2004); however, the current block design precluded comparisons by emotional expression.…”

“…Emotion labeling and emotion matching were also compared with implicit baseline (consisting of unmodeled fixation events during the intertrial intervals). We selected these contrasts based on prior work with this task [Fakra et al, 2008; Hariri et al, 2000; Lieberman et al, 2007; Plichta et al, 2014]. …”

“…The motion-corrected, smoothed, and filtered data were probed for mean and maximum percent signal change for each contrast of interest. Amygdala habituation was calculated based on the amplitude difference between the first and second run of the task for each condition (Blackford et al, 2013; Plichta et al, 2014). …”

“…We predicted that variance in activation due to person-related factors would be greater than variance due to site-related factors and that the person effect would be reliable across sites for the amygdala and IFG. Given recent evidence that habituation has more stable test-retest reliability than amplitude of activation for the amygdala (Plichta et al, 2014), we also examined amygdala habituation. In the second study sample, fMRI data for all healthy individuals who had been recruited as control participants in the NAPLS study (for comparison to the CHR sample) were aggregated across sites using two statistical methods.…”

Using Functional Neuroimaging to Refine the Diagnostic Construct of Borderline Personality Disorder

“…Other potential sources of these inconsistent findings have been suggested, including differences in habituation to emotional stimuli, which have been noted in individuals with BPD [125,126]. Differences in amygdala habituation to fearful stimuli may be a more reliable neural marker than amygdala activation, which may be more variable across an entire task [127,128]. van Zutphen additionally argues that differences in levels of dissociation in individuals with BPD, which is often not assessed in fMRI studies using emotion processing tasks, may account for differences in amygdala activation -that is, dissociation may disrupt emotion processing and amygdala activation [129].…”