title: The Role of the Amygdala in Facial Trustworthiness Processing: A Systematic Review and Meta-Analyses of fMRI Studies.
abstract: BACKGROUND
  Faces play a key role in signaling social cues such as signals of trustworthiness. Although several studies identify the amygdala as a core brain region in social cognition, quantitative approaches evaluating its role are scarce.
  
  
  OBJECTIVE
  This review aimed to assess the role of the amygdala in the processing of facial trustworthiness, by analyzing its amplitude BOLD response polarity to untrustworthy versus trustworthy facial signals under fMRI tasks through a Meta-analysis of effect sizes (MA). Activation Likelihood Estimation (ALE) analyses were also conducted.
  
  
  METHODS
  Articles were retrieved from MEDLINE, ScienceDirect and Web-of-Science in January 2016. Following the PRISMA statement guidelines, a systematic review of original research articles in English language using the search string "(face OR facial) AND (trustworthiness OR trustworthy OR untrustworthy OR trustee) AND fMRI" was conducted.
  
  
  METHODS
  The MA concerned amygdala responses to facial trustworthiness for the contrast Untrustworthy vs. trustworthy faces, and included whole-brain and ROI studies. To prevent potential bias, results were considered even when at the single study level they did not survive correction for multiple comparisons or provided non-significant results. ALE considered whole-brain studies, using the same methodology to prevent bias. A summary of the methodological options (design and analysis) described in the articles was finally used to get further insight into the characteristics of the studies and to perform a subgroup analysis. Data were extracted by two authors and checked independently.
  
  
  RESULTS
  Twenty fMRI studies were considered for systematic review. An MA of effect sizes with 11 articles (12 studies) showed high heterogeneity between studies [Q(11) = 265.68, p < .0001; I2 = 95.86%, 94.20% to 97.05%, with 95% confidence interval, CI]. Random effects analysis [RE(183) = 0.851, .422 to .969, 95% CI] supported the evidence that the (right) amygdala responds preferentially to untrustworthy faces. Moreover, two ALE analyses performed with 6 articles (7 studies) identified the amygdala, insula and medial dorsal nuclei of thalamus as structures with negative correlation with trustworthiness. Six articles/studies showed that posterior cingulate and medial frontal gyrus present positive correlations with increasing facial trustworthiness levels. Significant effects considering subgroup analysis based on methodological criteria were found for experiments using spatial smoothing, categorization of trustworthiness in 2 or 3 categories and paradigms which involve both explicit and implicit tasks.
  
  
  CONCLUSIONS
  Significant heterogeneity between studies was found in MA, which might have arisen from inclusion of studies with smaller sample sizes and differences in methodological options. Studies using ROI analysis / small volume correction methods were more often devoted specifically to the amygdala region, with some results reporting uncorrected p-values based on mainly clinical a priori evidence of amygdala involvement in these processes. Nevertheless, we did not find significant evidence for publication bias.
  
  
  CONCLUSIONS
  Our results support the role of amygdala in facial trustworthiness judgment, emphasizing its predominant role during processing of negative social signals in (untrustworthy) faces. This systematic review suggests that little consistency exists among studies' methodology, and that larger sample sizes should be preferred.
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra (UC), Coimbra, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Santos
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra (UC), Coimbra, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Almeida
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra (UC), Coimbra, Portugal.|Laboratory of Biostatistics and Medical Informatics, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra (UC), Coimbra, Portugal.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Oliveiros
authors.affiliation: Visual Neuroscience Laboratory, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra (UC), Coimbra, Portugal.|Laboratory of Biostatistics and Medical Informatics, Institute for Biomedical Imaging and Life Sciences (CNC.IBILI), Faculty of Medicine, University of Coimbra (UC), Coimbra, Portugal.|Institute for Nuclear Sciences Applied to Health (ICNAS), Brain Imaging Network of Portugal, Coimbra, Portugal.
authors.forename: Miguel
authors.identifier: http://orcid.org/0000-0003-4364-6373
authors.initials: M
authors.lastname: Castelo-Branco
mesh_terms: D000679:Amygdala / Q000000981:diagnostic imaging / Q000502:physiology*; D001921:Brain / Q000000981:diagnostic imaging; D016208:Databases, Factual; D005145:Face / Q000502:physiology*; D006801:Humans; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging; D010364:Pattern Recognition, Visual