The present study compared adolescents (9 to 17 years old) and adults (21 to 40 years old) on amygdala response to the presentation of fearful faces, focusing on the effects of age and sex. Our current findings suggest that maturation is associated with decreased amygdala and fusiform engagement specifically when passively viewing fearful faces and with increased amygdala–hippocampus connectivity during face processing. This is not only the largest developmentally focused fMRI study on any aspect of face processing, but also the first study to document developmental differences in functional connectivity between the amygdala and activation across the whole brain, as well as developmental differences in fusiform activation to fearful faces.
Our use of a previously studied task within a larger sample adds to the growing literature on the development of the amygdala response to fearful faces (Killgore & Yurgelun-Todd, 2004
; Monk et al., 2003
; Killgore et al., 2001
; Thomas, Drevets, Whalen, et al., 2001
; Baird et al., 1999
) by demonstrating the reproducible nature of developmental differences in amygdala function, an undertaking that is particularly important in order to generate and test new hypotheses based on established findings. We found that passively viewing fearful faces was associated with increased amygdala activation in adolescents relative to adults, suggesting that amygdala involvement in fearful-face processing varies between these two periods of development. This finding is consistent with specific results from Monk et al. (2003)
, using the same rapid event-related design, in our newly acquired sample, in the strictly defined sample culled from Monk et al., and in the large, combined sample including the new group of participants and a subset of participants from Monk et al. In particular, this developmental difference was driven by greater amygdala engagement to fearful, but not neutral, faces when compared to fixations, in adolescents. Adults, on the other hand, showed no differential amygdala response as a function of passively viewing fearful versus neutral faces or versus fixations.
One possible explanation of the present results is that greater amygdala activation in adolescents reflects greater general activation during face processing rather than a specific response to fearful faces. Post hoc fMRI analyses conducted to address this possibility showed no developmental differences in amygdala activation to faces in general or to other facial expressions. We also did not find developmental differences in the amount of time subjects spent looking at different facial regions while passively viewing fearful and neutral faces, indicating that adolescents and adults focus their eyes similarly on distinct aspects of facial stimuli presented during passive viewing and do not focus their gaze differently as a function of development. Thus, the developmental difference in amygdala response was specific to fearful facial expressions viewed passively. Amygdala activation to fearful faces also did not correlate with age within either the adult or the adolescent group, nor did it vary by sex.
Overall, the current study clarifies that, at least with an event-related task design, the previously observed developmental difference in amygdala activation to fearful versus neutral faces is reproducible, thus demonstrating the reliability of our task paradigm. Within the larger sample, we also sought to document the reliability of our past findings in amygdala activation specifically manifest during passive viewing of fearful versus neutral faces, given that this comparison previously yielded the only evidence of developmental differences in amygdala response, albeit in different directions in two studies (Monk et al., 2003
; Thomas, Drevets, Whalen, et al., 2001
). The consistency of the developmental amygdala finding may provide a benchmark from which new hypotheses and theories could be generated about the role of the amygdala in face processing in both typical and atypical development. Of note, however, despite observation of a consistent developmental difference across two independent samples, this study also revealed many instances where adults and adolescents exhibited similarly robust amygdala engagement. As such, adolescent immaturity of amygdala function appears to be relatively subtle: It occurs in an isolated set of attention- and emotion-specific viewing conditions.
Two novel developmental findings also emerged from the current study. First, adults had stronger amygdala– hippocampus functional connectivity than did adolescents. Second, adolescents had greater fusiform engagement to fearful versus neutral faces than did adults. With regard to functional connectivity, we found stronger coupling between the amygdala and the hippocampus in adults than in adolescents during the facial emotion viewing task. Functional connectivity, as assessed here, measures the temporal correlation of activity between different brain regions. These new findings suggest that developmental changes in the functional coupling between the amygdala and the hippocampus are likely to occur in the transition from adolescence to adulthood. Signals from the amygdala facilitate identification and detection of emotionally salient stimuli such as facial expressions. In turn, memory storage and retrieval for emotionally salient stimuli may be strengthened between these stages of development through connections to hippocampal regions (Dolcos, LaBar, & Cabeza, 2005
; Richardson, Strange, & Dolan, 2004
; Kilpatrick & Cahill, 2003
). Indeed, evidence suggests that the relationship between cognitive and affective systems continues to develop during adolescence (Ernst et al., 2006
; Nelson et al., 2005
; Casey, Tottenham, & Fossella, 2002
; Casey et al., 2000
), and the degree to which emotion influences face–memory formation may be related to pubertal changes (Nelson et al., 2003
; McGivern, Andersen, Byrd, Mutter, & Reilly, 2002
). Thus, one interpretation of the present connectivity finding is that the greater amygdala– hippocampus coupling in adults is due to maturational changes in the degree to which the amygdala and hippocampus interact in forming memories of emotional faces. Among adults, emotional faces may elicit greater amygdala–hippocampus engagement due to experience and stronger memory formation of such stimuli. Although both the amygdala and the hippocampus have been found to participate in aversive memory, the mnemonic role of the amygdala appears to be confined to simpler functions such as stimulus emotion associations, whereas the hippocampus is involved in more subtle and complex processes such as context conditioning, spatial array relations, and timing-related memory. Overall, the interdependence and breadth of cognitive processes, such as memory and attention, and affective processes, such as emotion perception, may be stronger in the adult brain.
The present study is also the first to document a developmentally based difference in fusiform gyrus response to passively viewed fearful faces. Specifically, activation in the fusiform gyrus was influenced by passively viewing fearful versus neutral faces more in adolescents than in adults. These findings suggest that the neural underpinnings of facial expression perception instantiated in the fusiform face area may continue to develop through adolescence. Our regionally specific developmental findings indicated that adolescents engage the amygdala and the fusiform gyrus when attention is unconstrained during passive viewing of fearful faces more so than adults. Evidence suggests that the amygdala has strong bidirectional connections with the ventral visual processing stream (Amaral & Price, 1984
) and that increased fusiform activation is related to greater input from the amygdala (Vuilleumier, Richardson, Armony, Driver, & Dolan, 2004
; Morris et al., 1998
). Additionally, structural changes in ventral posterior brain regions have been documented across development (Giedd et al., 1999
) and the fusiform gyrus has been implicated in learning-based changes in face processing ability (Gauthier, Tarr, Anderson, Skudlarski, & Gore, 1999
). Evidence of such structural and experience-based changes suggests the presence of strong plasticity in systems that process certain facial emotions (Gauthier et al., 1999
), a possibility consistent with the developmental difference we documented here in fusiform function.
Adolescence is associated with prominent changes in social behavior and emotion regulation that are likely to be related partly to hormonal shifts, and structural and functional maturation in specific neural regions, such as the amygdala, and their interconnections (Nelson et al., 2005
; Spear, 2000
). As such, one explanation for the greater amygdala and fusiform activation in adolescents as compared to adults is that the emotional content of stimuli engages neural systems to a greater degree earlier in development. By adulthood, when control over attention has increased and other higher-level cognitive processes have matured, emotional as compared to neutral stimuli may compete less for emotion processing resources. That is, emotional stimuli may interfere less with the ability of other neural regions to engage in higher-level cognitive tasks later in development. In adolescence, greater priority may be given to resources that process fearful faces. Although the current study focused on the passive-viewing condition to isolate the influence of emotion rather than attention manipulations on neural engagement, other work suggests that changing the context of attention engages neural systems differently across development and that emotional stimuli can interfere with ongoing functions (McClure et al., 2007
; Perez-Edgar et al., 2007
; Monk et al., 2003
; Nelson et al., 2003
Although our primary developmental differences involved amygdala and fusiform response to fearful faces, we did not find age-related differences in amygdala–fusiform coupling during the face processing task. However, positive connectivity between the left amygdala and the fusiform face area [uncorrected p
= .009; corrected p
= .56, t
(59) = 2.44] was found within the whole sample. This latter result is consistent with research suggesting that modulatory interactions occur between the amygdala and the fusiform gyrus (Amaral et al., 2003
; Catani, Jones, Donato, & Ffytche, 2003
; Vuilleumier et al., 2001
), particularly during face–emotion processing. We also did not find any developmental differences in amygdala–prefrontal coupling despite strong connectivity in the entire sample between the amygdala and the ACC or the amygdala and the OFC. Both groups demonstrated similar levels of coupling between the amygdala and these prefrontal regions involved in attention allocation to emotionally salient stimuli (Adolphs, 2001
; Vuilleumier et al., 2001
; Critchley, Elliott, Mathias, & Dolan, 2000
). Thus, across all attention–emotion conditions of the face task, we did not find age-based differences in the functional connectivity between these regions. Overall, our most robust developmental finding emerges for the right amygdala, given that Monk et al. (2003)
found an age-group effect on the right amygdala only and that we did not find similar age-group differences in ACC and OFC activation to passively viewed fearful faces in either the new sample studied here or in the combined, larger sample. Thus, some effects initially noted in Monk et al. occur in only a subset of the participants studied here. As such, they represent less consistent findings than the repeatedly documented between-group differences in amygdala activation.
Of note, the developmental amygdala differences reported here contrast with those of Thomas, Drevets, Whalen, et al. (2001)
, who found greater amygdala response to passively viewed neutral versus fearful faces in children relative to adults. Clearly, several factors may explain these opposing findings. Nevertheless, our primary hypothesis is that the use of different fMRI task paradigms across studies remains the most influential factor, given growing evidence documenting the strong effects of task parameters on amygdala engagement. Specifically, Thomas, Drevets, Whalen, et al. used a block design, whereas Monk et al. (2003)
used an event-related design. In a block design, each experimental condition is presented continuously for an extended time period and the different conditions are alternated over time (e.g., a block of fear faces, followed by a block of neutral faces). This approach yields a measure of sustained neural activation within the block. In an event-related design, stimuli are presented in multiple, independent-event types (e.g., event trials of different face emotion stimuli randomly distributed throughout the task). The event-related design measures phasic neural activation in response to stimuli for specific events. Past fMRI block-design studies in adults demonstrated increased amygdala activation to the presentation of fearful faces (Whalen et al., 2001
; Breiter et al., 1996
; Morris et al., 1996
), but also found that the amygdala response can habituate to repeated exposure to fearful faces (Whalen et al., 1998
; Breiter et al., 1996
). Moreover, the stimulus duration also differs dramatically across studies. Whereas the current study presented faces for 4000 msec, requiring subjects to respond to each face in the attention conditions, Thomas, Drevets, Whalen, et al., Whalen et al. (1998)
, and Breiter et al. (1996)
all presented faces in rapid succession (each for 500 msec), providing limited time for participants to process individual faces. The repeated, rapid contiguous presentation of fearful faces as in and Thomas, Drevets, Whalen, et al. may have influenced amygdala habituation differently than did the alternated, slow presentation of fearful faces as in Monk et al., which may account for the contradictory findings. Thus, although the findings from these two studies are opposite, they are based on different approaches to measuring functional neural activity, and this difference is likely to be the most influential factor on outcome. To better understand how amygdala activation differs based on task design, future work is needed that directly compares amygdala response to fearful faces using a block design and an event-related design.
The present study has some methodological limitations. We selected the passive-viewing context to be consistent with past studies of amygdala response to fearful faces. However, the passive-viewing condition does not allow for experimental control over subjects’ attention, possibly leading to individually generated cognitive activity during face processing. Indeed, past fMRI work suggests that cognitive processes can attenuate amygdala response (Hariri, Mattay, Tessitore, Fera, & Weinberger, 2003
; Hariri, Bookheimer, & Mazziotta, 2000
). The eye movement data we collected out of the scanner do not support this possibility because they indicate no differences between adolescents and adults in the amounts of time spent looking at different facial regions (i.e., eyes, nose, mouth) or facial expressions (i.e., fearful vs. neutral). Despite inherent limitations of passive viewing, using conditions implemented previously in multiple studies in adults is advantageous given the relative scarcity of data on adolescents. Further, because passive-viewing tasks have consistently been effective at evoking amygdala responses to fearful faces, they offer an established method for examining the questions of interest in the present study.
A second limitation concerns the relatively indirect implications that our between-group ROI-focused findings carry for our findings from the functional connectivity analysis. Although the former analysis focused on a subset of data, generated in two face–emotions passively viewed, the latter analysis focuses on activity across the entire task. As noted above, we focused on specific events for our ROI analysis, based on prior findings in Monk et al. (2003)
. For our functional connectivity analysis, we relied on methods that have been most consistently implemented in previous work (McClure et al., 2007
; Pezawas et al., 2005
). However, recent advances in functional connectivity analysis approaches also delineate methods for examining changes in connectivity during one or another event class.
Future studies, using alternative task designs and statistical approaches, may allow for tighter integration between ROI-based and functional connectivity-based analytic approaches, with each approach focusing on the same specific event classes. Certainly, the current task has proved useful in generating insights into the manner in which face–emotions and attention states interact. Nevertheless, as discussed below, when considering novel functional connectivity approaches, efforts to extend current insights on amygdala development might best be devoted to future studies using novel tasks that address limitations in the current task. For example, because the current study demonstrates the importance of passive viewing, future functional connectivity studies might implement designs that only collect data in this one attention state while focusing on changes in connectivity during specific face–emotion events. Exclusive focus on this one attention state would allow a novel task of similar length to the task used here to yield far more data in the most relevant classes of events than was possible in the current study.
A third limitation of the present study relates to the age range of our sample. There was a gap in study participants between the ages of 17 and 21 years, making it difficult to interpret potential changes in amygdala function that may occur across the very early ages of adulthood. In particular, the present findings do not allow for a clear demarcation of a specific age at which changes in amygdala activation to fearful faces may initiate. It is possible that, with increased age, and thus, experience, the hippocampus and associated memory functions may play a modulatory role over the amygdala; some support for this may stem from our finding of greater amygdala–hippocampus connectivity later in development. Another age-related limitation involves classifying the adolescent group solely based on age in years. It may be fruitful in future research to also define human adolescence based on pubertal status. The wide range of pubertal stages requires a study to examine a large number of adolescents who fall within each stage; unfortunately, the current study did not have enough data available regarding pubertal status to make meaningful comparisons across puberty stages. We also found that within-group variability in age did not relate to amygdala activation to fearful faces linearly or curvili-nearly. Although our result is consistent with work examining age effects on amygdala function in adolescence (Yurgelun-Todd & Killgore, 2006
), other research has documented nonlinear relationships between age and the size of certain brain structures, such as the prefrontal cortex, that undergo protracted development from ages 4 through 22 years (Lenroot & Giedd, 2006
). Samples with a sufficiently large number of individuals to be divided into bins of narrowly defined age groups, across specified periods of development, are needed to understand more fully how age is associated with changes in amygdala function across development.
Finally, the present study failed to detect amygdala activation in adults while they passively viewed fearful versus neutral faces. This result runs counter to the observation from adult fMRI block-design studies that consistently demonstrated amygdala activation to fearful faces (Breiter et al., 1996
; Morris et al., 1996
), although not all previous block-design studies of facial fear perception in adults have found amygdala activation (Sprengelmeyer, Rausch, Eysel, & Przuntek, 1998
). Of note, amygdala engagement in passive-viewing, event-related fearful-face presentation paradigms, such as the one used in the current study, occurs less consistently than in block-design paradigms, as exemplified by a recent event-related fMRI study in adults that failed to detect amygdala activation to fearful faces (Deeley et al., 2007
). It is possible that a failure to detect amygdala activation to fearful versus neutral faces in adults may reflect the small number of event-replicates in each attention condition, each of which included only eight trials of fearful faces. As noted above in the discussion of functional connectivity approaches, future studies should consider the advantages and disadvantages of implementing studies with novel task parameters. Specifically, the inclusion of a greater number of fearful face trials might engage the adult amygdala response on this condition; likewise, more trials could alter the adolescent response. Although alternative designs or contrasts may be more sensitive to adult amygdala response to fearful faces, one must also consider the possibility that these different approaches could potentially yield reduced sensitivity to developmental differences in amygdala activation through distinct, task-related effects on temporal processes such as fatigue, learning, or habituation.
The number of task trials cannot entirely account for the lack of adult amygdala engagement to fear-faces viewed passively. Indeed, in analyses of the nose-rating attention state, we did detect amygdala activation in adults in a similarly constructed contrast using eight fearful faces. Regardless, as noted above, future studies would benefit from a paradigm with more event replicates across fewer attention states. We used a relatively low number of task trials in the current study in order to employ the identical task paradigm from our prior study. This paradigm was designed originally with relatively few within-condition stimulus replications, in part, so that it would be tolerable to younger participants and would generate data across four attention conditions. This approach has been effective in prior research for eliciting amygdala activation in adolescents recruited from different sources and who are either healthy or at risk for or currently affected with a mental disorder (Monk et al., 2003
; McClure et al., 2007
; Perez-Edgar et al., 2007
; Roberson-Nay et al., 2006
; Nelson et al., 2003
) and in two past developmental studies (Monk et al., 2003
; Nelson et al., 2003
). Although we have achieved within-lab reliability with this face-viewing task design, it remains important for other research groups to use the same task design to increase the comparability and generalizability of findings across studies and laboratories.
Despite these limitations, the present findings inform our understanding of fundamental changes in neuro-physiological function across development. Overall, the main results suggest that there are different balances of neural input at different periods across human development. In adolescence, there may be a greater tendency toward using neural resources for facial identification and perception, whereas in adulthood, there may be a greater bias toward using resources for memory of emotional information. For example, the greater amygdala and fusiform activation in adolescents than in adults suggests that these regions utilize neurophysiological input to a greater degree during the perception of fearful faces earlier in development. The amygdala and the fusiform gyrus are important for quick detection and recognition of emotionally salient stimuli (LeDoux, 2000
; Whalen et al., 1998
), and the amygdala additionally is implicated in learning and generating responses to such stimuli (LeDoux, 2000
; Bechara, Damasio, Damasio, & Lee, 1999
) and in modulating their consolidation into memory (Hamann, Ely, Grafton, & Kilts, 1999
; Cahill & McGaugh, 1998
). Activations of these regions may reflect a perception of fearful faces as more novel in adolescence than in adulthood, possibly leading to greater input via these neural regions when processing fearful faces than during adulthood. Perhaps through enhanced cognitive control and memory function that comes with age, adults by comparison use less input from the amygdala and the fusiform gyrus to perceive fearful faces.
The connectivity findings indicate that the neural circuitry underlying memory of facial emotion changes between adolescence and adulthood, suggesting that maturation of adult-level memory of emotional faces involves the functional integration of both the amygdala and the hippocampus, and perhaps a greater tightening of the communication between these two regions by adulthood. As this is the first developmental study to measure the functional connectivity of neural responses to emotional faces, these findings provide a foundation from which other studies of connectivity may build and underscore the need for more research on patterns of functional connectivity during face processing across development to increase our understanding of the brain–behavior intersection.
There are several possible extensions of the present study. First, the influence of task design remains an important methodological question, and more work is needed to tease apart how event-related and block task designs may influence amygdala response to fearful faces in different ways. Although it is beyond the scope of the present study, future studies could compare the time course of amygdala response between event-related and block task designs to understand possible task-related differences in the amygdala habituation process found to occur while viewing fearful faces. Second, further developmental investigations will be needed to monitor location of gaze during performance of this task in the scanner. Simultaneously tracking eye movements and measuring functional brain changes during face viewing may clarify neural mechanisms underlying developmental differences in processing facial emotion. A recent study indicates that a deficit in fear recognition in a patient with bilateral amygdala damage stems from an inability to use information from the eye region in faces (Adolphs et al., 2005
) and other work has found amygdala response to direct eye contact to be an important social signal (Kawashima et al., 1999
). Third, one direction for the functional connectivity work presented here would be to use other analytical approaches to infer directionality of influence between functionally connected regions during facial expression processing (Ramnani, Behrens, Penny, & Matthews, 2004
). Finally, it will be important to use findings from typical samples such as those presented here to understand adolescence as a vulnerable time for emerging psychopathology based on developmental trajectories of emotion processing and associated changes in neural function that place adolescents at risk for affective disorders.