Commentary by Annemieke M. Apergis-Schoute and Elizabeth A. Phelps

The paper by Ball et al. (2007) reports a technically sound imaging study, in which the authors address an important issue regarding the contribution of different subregions to amygdala function. The authors’ approach is to combine standard fMRI with probabilistic anatomical maps to show intrinsic functional differentiation within the amygdala. With this approach they make a valuable initial attempt at subdivision-level investigation of the human amygdala.

Using probabilistic maps is an effective tool to anatomically differentiate the different amygdala subregions (Amunts et al., 2005). However, in order to correctly assign functional attributes to the different amygdala nuclei, a better approach would be to use high resolution functional images. In their study, the authors use conventional 3mm isotropic voxels to acquire functional images of the amygdala. One has to take in to consideration, though, that the centers of the different amygdala nuclei are at most 1 cm apart, and the borders much closer (Mai et al., 1997). Although the authors restricted the region of interest (ROI) analysis to the core of the amygdala subregions with >=90% assignment probability, this does not necessarily represent the likelihood that the functional data belongs to this specific subregion of the amygdala. In order to effectively dissociate the functional aspects of the amygdala subregions, higher spatial resolution of the functional images is required, e.g. 1mm isotropic voxels.

The study by Ball et al. (2007) confirms that the amygdala is involved in processing of auditory stimuli. However, by choosing to look at music-related amygdala responses, the authors do not take advantage of the vast animal literature on functional differences between the various amygdala subnuclei. Moreover, the authors’ differentiation of the laterobasal (LB) and centromedial (CM), as respectively having the most positive and negative signal changes, is not persuasive, considering that the centers of these nuclei are less than 1 cm apart (Mai et al., 1997), and that the authors have to rely on changes in 3mm isotropic voxels.

As there is no precedent for investigating functional differences of amygdala subnuclei related to emotional music, the authors have to rely on other human fMRI studies using conventional 3mm isotropic voxels. Therefore, the authors essentially do not make the translational link between the animal literature, in which the functions of specific amygdala subregions have been identified, and the human amygdala. A more suitable approach would be to use the highly studied fear conditioning paradigm where clear differences between amygdala subregions have been established (Amorapanth et al., 2000; Anglada-Figueroa and Quirk, 2005; Repa et al., 2001).

The authors address another interesting point about lateralization of emotional functions in the context of subregional differences within the amygdala. They discuss the possibility that activation of specific amygdala subregions may account for lateralized amygdala activation as seen in previous imaging studies. To investigate this possibility, one should use high resolution fMRI to elucidate lateralization of amygdala activation.

As the authors state in their concluding paragraph, using probabilistic maps for subdivision-level investigation of the human amygdala, is a good first step. Indeed, to pursue amygdala subdivision investigation further, it is crucial to employ high resolution fMRI combined with a well-developed paradigm taken from the animal literature.

In summary, using a well-developed animal model, combined with high resolution fMRI, in addition to employing probabilistic maps, can shed new light on the functioning of the human amygdala by revealing the roles of the subnuclei that compromise the human amgydala.





Amorapanth, P, LeDoux, JE, Nader, K (2000) Different lateral amygdala outputs mediate reactions and actions elicited by a fear-arousing stimulus. Nat Neurosci. 3(1):74-9.

Amunts K, Kedo, O, Kindler M, Pieperhoff, P, Mohlberg, H, Shah, NJ, Habel, U, Schneider, F, Zilles, K (2005) Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anat Embryol 210(5-6):447-53.

Anglada-Figueroa, D, Quirk, GJ (2005) Lesions of the basal amygdala block expression of conditioned fear but not extinction. J Neurosci. 2005 25(42):9680-5.

Ball, T, Rahm, B, Eickhoff, SB, Schulze-Bonhage, A, Speck, O, Mutschler, I (2007) Response properties of human amygdala subregions: evidence based on functional MRI combined with probabilistic anatomical maps. PLoS ONE. 2:e307

Mai, JK, Paxinos, G, Assheuer, J (1997) Atlas of the Human Brain Academic Pr

Repa, JC, Muller, J, Apergis, J, Desrochers, TM, Zhou, Y, LeDoux, JE (2001) Two different lateral amygdala cell populations contribute to the initiation and storage of memory. Nat Neurosci. 4(7):724-31.