The human amygdala: a systematic review and meta-analysis of volumetric magnetic resonance imaging

The structure and function of the human amygdala is attracting increasing attention in the scientific literature, particularly since the advent of high resolution magnetic resonance imaging (MRI). We carried out a systematic review of the published literature reporting left and right amygdala volumes from MRI in non-clinical subjects. Our aim was to estimate the normal range of the volume of the amygdala and to account for heterogeneity of the measures. The factors we considered included the detail given regarding various subject factors, the plane of scan acquisition, slice thickness and contiguity, magnet strength, positional and volume correction, and the reliability of measurement. Thirty-nine studies with 51 data sets fulfilled selection criteria. The mean +/- 95% confidence interval for the left amygdala volume was 1726.7 mm(3) +/- 35.1, and right was 1691.7 mm(3) +/- 37.2. The left-right difference did not reach statistical significance. The overall range of reported volumes was 1050 mm(3) to 3880 mm(3). The amygdala is significantly larger in men and shows an inverse correlation with age. The main methodological factor found to influence amygdala measurement was anatomical definition. Studies using 'Watson's criteria' (Neurology 42 (1992) 1743) produced significantly larger volumes than the remainder. An index of study quality revealed an inverse relationship with volume-the higher the quality the smaller the volume. This reflected such factors as slice thickness, correction for brain volume, positional correction and number of subjects. We conclude by putting forward a detailed operationalised anatomical delineation of the amygdala, based on Watson's criteria. This work should guide future research in obtaining accurate and reliable amygdala volume measures which in turn will aid comparisons with clinical groups and the specification of structural-functional relationships. (C) 2002 Published by Elsevier Science B.V.