Owledge (http://www.webofknowledge.com) for fMRI studies of inhibited temperament available through April 2014. Search terms were: (“inhibited temperament” or “behavioral inhibition” or “behaviorally inhibited”) AND (MRI OR neuroimaging OR “brain activation” OR “brain activity”). We also included studies found by searching reference lists and manuscripts in press. Studies were eligible for inclusion if they included a comparison between individuals with an inhibited temperament and individuals with an average or uninhibited temperament. Studies had to include coordinates of their findings in either Montreal Neurological Institute (MNI) or Talairach space. Two hundred and eighty-nine (289) articles were identified. Of the articles, 98 were excluded for not being an empirical study, 19 were excluded for non-human data, 85 were excluded for not including functional imaging data, 71 were excluded for not including a measure of inhibited temperament, two were excluded for containing only correlations within an inhibited group, and one study was excluded for reporting no group differences in functional activation. Data from 13 studies were included (Bar-Haim et al., 2009; Blackford et al., 2013, 2011, 2009; Clauss et al., 2014a, 2011; Guyer et al., 2006; Helfinstein et al., 2011; Jarcho et al., 2014, 2013; P ez-Edgar et al., 2007; Schwartz et al., 2012, 2003a). Coordinates were included for the contrast of inhibited temperament group versus controlAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptProg Neurobiol. Author manuscript; available in PMC 2016 April 01.Clauss et al.Avermectin B1a molecular weight Pagegroup or the interaction (e.g. temperament ?emotion) if reported. Meta-analyses were conducted using GingerALE software (version 2.3.2; http://www.brainmap.org/ale), which uses an activation likelihood estimation (ALE) to test for overlap between foci across studies (Eickhoff et al., 2009). A random-effects model was used. All data were transformed to MNI space using the tal2icbm function within the GingerALE software and peak coordinates were modeled with a 3D Gaussian kernel with a FWHM of 8.5?.5 (larger FWHM for studies with fewer subjects). Convergence across all studies was calculated as the union of each individual study, with a voxel p-value of .01 and a cluster size of 25 voxels (200 mm3). There were four clusters where the inhibited temperament group had significantly greater activation than the uninhibited temperament group. The inhibited group had greater activation in the amygdala, three regions of the basal ganglia (globus pallidus, putamen, and caudate), and the middle frontal gyrus (see Table 1 and Figure 3). There were no regions where the uninhibited group had greater activation. Thus, inhibited temperament was associated with heightened activation in brain regions involved in both novelty/threat processing and Fruquintinib clinical trials reward processing/inhibitory control. Of note, these three regions–the amygdala, basal ganglia, and PFC–have been proposed to form an interconnected circuit responsible for governing motivated behaviors in healthy adults (Ernst et al., 2006; see: Ernst and Fudge, 2009). In this Triadic Model, approach behaviors are governed by the basal ganglia (reward) while avoidance is governed by the amygdala (fear); approach/avoidance behavior is regulated through complex PFC feedback loops with both of these regions. Balanced regulation of the basal ganglia and amygdala is hypothesized to be important to adaptive behavior in a variet.Owledge (http://www.webofknowledge.com) for fMRI studies of inhibited temperament available through April 2014. Search terms were: (“inhibited temperament” or “behavioral inhibition” or “behaviorally inhibited”) AND (MRI OR neuroimaging OR “brain activation” OR “brain activity”). We also included studies found by searching reference lists and manuscripts in press. Studies were eligible for inclusion if they included a comparison between individuals with an inhibited temperament and individuals with an average or uninhibited temperament. Studies had to include coordinates of their findings in either Montreal Neurological Institute (MNI) or Talairach space. Two hundred and eighty-nine (289) articles were identified. Of the articles, 98 were excluded for not being an empirical study, 19 were excluded for non-human data, 85 were excluded for not including functional imaging data, 71 were excluded for not including a measure of inhibited temperament, two were excluded for containing only correlations within an inhibited group, and one study was excluded for reporting no group differences in functional activation. Data from 13 studies were included (Bar-Haim et al., 2009; Blackford et al., 2013, 2011, 2009; Clauss et al., 2014a, 2011; Guyer et al., 2006; Helfinstein et al., 2011; Jarcho et al., 2014, 2013; P ez-Edgar et al., 2007; Schwartz et al., 2012, 2003a). Coordinates were included for the contrast of inhibited temperament group versus controlAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptProg Neurobiol. Author manuscript; available in PMC 2016 April 01.Clauss et al.Pagegroup or the interaction (e.g. temperament ?emotion) if reported. Meta-analyses were conducted using GingerALE software (version 2.3.2; http://www.brainmap.org/ale), which uses an activation likelihood estimation (ALE) to test for overlap between foci across studies (Eickhoff et al., 2009). A random-effects model was used. All data were transformed to MNI space using the tal2icbm function within the GingerALE software and peak coordinates were modeled with a 3D Gaussian kernel with a FWHM of 8.5?.5 (larger FWHM for studies with fewer subjects). Convergence across all studies was calculated as the union of each individual study, with a voxel p-value of .01 and a cluster size of 25 voxels (200 mm3). There were four clusters where the inhibited temperament group had significantly greater activation than the uninhibited temperament group. The inhibited group had greater activation in the amygdala, three regions of the basal ganglia (globus pallidus, putamen, and caudate), and the middle frontal gyrus (see Table 1 and Figure 3). There were no regions where the uninhibited group had greater activation. Thus, inhibited temperament was associated with heightened activation in brain regions involved in both novelty/threat processing and reward processing/inhibitory control. Of note, these three regions–the amygdala, basal ganglia, and PFC–have been proposed to form an interconnected circuit responsible for governing motivated behaviors in healthy adults (Ernst et al., 2006; see: Ernst and Fudge, 2009). In this Triadic Model, approach behaviors are governed by the basal ganglia (reward) while avoidance is governed by the amygdala (fear); approach/avoidance behavior is regulated through complex PFC feedback loops with both of these regions. Balanced regulation of the basal ganglia and amygdala is hypothesized to be important to adaptive behavior in a variet.
