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The investigation of the brain connectome with functional magnetic resonance imaging (fMRI) and graph theory analyses has recently gained much popularity, but little is known about the robustness of these properties, in particular those derived from active fMRI tasks. Here, we studied the test-retest reliability of brain graphs calculated from 26 healthy participants with three established fMRI experiments (n-back working memory, emotional face-matching, resting state) and two parcellation schemes for node definition (AAL atlas, functional atlas proposed by Power et al.). We compared the intra-class correlation coefficients (ICCs) of five different data processing strategies and demonstrated a superior reliability of task-regression methods with condition-specific regressors. The between-task comparison revealed significantly higher ICCs for resting state relative to the active tasks, and a superiority of the n-back task relative to the face-matching task for global and local network properties. While the mean ICCs were typically lower for the active tasks, overall fair to good reliabilities were detected for global and local connectivity properties, and for the n-back task with both atlases, smallworldness. For all three tasks and atlases, low mean ICCs were seen for the local network properties. However, node-specific good reliabilities were detected for node degree in regions known to be critical for the challenged functions (resting-state: default-mode network nodes, n-back: fronto-parietal nodes, face-matching: limbic nodes). Between-atlas comparison demonstrated significantly higher reliabilities for the functional parcellations for global and local network properties. Our findings can inform the choice of processing strategies, brain atlases and outcome properties for fMRI studies using active tasks, graph theory methods, and within-subject designs, in particular future pharmaco-fMRI studies., (© 2013 Elsevier Inc. All rights reserved.)

Even more than in cognitive research applications, moving fMRI to the clinic and the drug development process requires the generation of stable and reliable signal changes. The performance characteristics of the fMRI paradigm constrain experimental power and may require different study designs (e.g., crossover vs. parallel groups), yet fMRI reliability characteristics can be strongly dependent on the nature of the fMRI task. The present study investigated both within-subject and group-level reliability of a combined three-task fMRI battery targeting three systems of wide applicability in clinical and cognitive neuroscience: an emotional (face matching), a motivational (monetary reward anticipation) and a cognitive (n-back working memory) task. A group of 25 young, healthy volunteers were scanned twice on a 3T MRI scanner with a mean test-retest interval of 14.6 days. FMRI reliability was quantified using the intraclass correlation coefficient (ICC) applied at three different levels ranging from a global to a localized and fine spatial scale: (1) reliability of group-level activation maps over the whole brain and within targeted regions of interest (ROIs); (2) within-subject reliability of ROI-mean amplitudes and (3) within-subject reliability of individual voxels in the target ROIs. Results showed robust evoked activation of all three tasks in their respective target regions (emotional task=amygdala; motivational task=ventral striatum; cognitive task=right dorsolateral prefrontal cortex and parietal cortices) with high effect sizes (ES) of ROI-mean summary values (ES=1.11-1.44 for the faces task, 0.96-1.43 for the reward task, 0.83-2.58 for the n-back task). Reliability of group level activation was excellent for all three tasks with ICCs of 0.89-0.98 at the whole brain level and 0.66-0.97 within target ROIs. Within-subject reliability of ROI-mean amplitudes across sessions was fair to good for the reward task (ICCs=0.56-0.62) and, dependent on the particular ROI, also fair-to-good for the n-back task (ICCs=0.44-0.57) but lower for the faces task (ICC=-0.02-0.16). In conclusion, all three tasks are well suited to between-subject designs, including imaging genetics. When specific recommendations are followed, the n-back and reward task are also suited for within-subject designs, including pharmaco-fMRI. The present study provides task-specific fMRI reliability performance measures that will inform the optimal use, powering and design of fMRI studies using comparable tasks., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Williams syndrome (WS) is a rare genetic disorder caused by the deletion of approximately 25 genes on chromosome 7q11.23 and is characterized by both hypersociability and increases in specific phobia and anticipatory anxiety regarding non-social entities or circumstances. Alterations in amygdala reactivity and prefrontal regulation consistent with the observed behavioral pattern of social versus non-social abnormalities have been previously demonstrated in individuals with WS (Meyer-Lindenberg et al., 2005). However, in that study, the social stimulus (faces) matching task was more difficult than the non-social scene (IAPS stimuli) matching task, making it impossible to disambiguate the relative contributions of task difficulty and stimulus type (social versus non-social). In the present study, we examined the performance of the same group of participants with WS and normal IQs during a more cognitively demanding task using the same scene stimuli as in the prior study. Confirming previous findings, the results indicated (a) a differential response of prefrontal regions as a function of task difficulty and (b) a persistently increased activation of the amygdala to non-social scenes by individuals with WS regardless of cognitive load. These data provide further evidence of disruption in amygdala-prefrontal circuitry in individuals with WS., (Copyright (c) 2009. Published by Elsevier Inc.)

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. [ABSTRACT FROM AUTHOR]

Abstract: In the social neuroscience of face processing, multiple roles are attributed to amygdala: signalling of fear/threat-stimuli, of emotional expression, and general salience. The current study aimed at a direct comparison of amygdala activation attributable to these conditions by contrasting amygdala responses to matched emotional (threatening and non-threatening) and of non-emotional salient faces in a visual search paradigm using cartoon faces. Participants (21 healthy volunteers) had to detect a target face (angry, happy, blue, red, differing in the exact same features) in an array of closely matched non-target faces. Behavioural results revealed a pop-out effect for all targets compared to non-targets, indicating that they were all salient, independently of being emotional or non-emotional. While significant amygdala activation was obtained for all trials with salient faces (compared to those containing only non-target faces), no significant differences in activation emerged between emotional threatening, emotional non-threatening, and non-emotional targets. Moreover, right and left amygdala activation for target trials was found correlated to the behavioural measure of target detection. These findings provide evidence for a general role of the amygdala in signalling salience in a visual search independent of modality. Given the critical involvement of the amygdala in several neuropsychiatric disorders, the current findings may contribute to further our understanding on dysfunctional neural circuits in these disorders. [ABSTRACT FROM AUTHOR]