The results of the present study demonstrate that children, adolescents, and adults engage cerebro-cerebellar networks in response to verbal WM challenge. Qualitatively, differences among age groups in WM load-dependency suggest that with increasing age the number of brain regions showing linear load-dependency expands. Specifically, while children display increasing activation in response to increasing WM load in left ventral prefrontal cortex only, adolescents and young adults show this pattern in right prefrontal, left parietal, superior cerebellum bilaterally (VI/Crus I), and right inferior cerebellum (VIIA/VIIB) regions as well. Age group effects for linear load-dependency were found to be statistically significant. Specifically, adolescents and young adults showed increased linear load-dependent activation in the left superior parietal lobule and right superior cerebellum when compared to the children. These data extend findings from adult studies by showing that the neural substrates of linear load-dependency change from childhood to adolescence, and implicate increasing reliance on posterior parietal and cerebellar regions as crucial for this process.
The observation of load-dependent increases in bilateral middle and inferior frontal gyri, the left superior parietal lobule, right inferior cerebellar regions (VIIA/VIIB), and bilateral superior cerebellar hemispheres (VI/Crus I) among the adults studied here replicates previous findings within the prefrontal cortex (Braver et al., 1997
, Rypma et al., 1999
) and cerebellum (Desmond et al., 1997
, Kirschen et al., 2005
). We extend these observations by demonstrating that linear load effects in frontal, parietal, and cerebellar regions, while present on a limited basis among children, are fully present in adolescence. Consistent with Desmond’s model of cerebellar function in verbal WM, we postulate that load-dependent increases in activation in bilateral superior cerebellar hemispheres (VI/Crus I) reflects increased input from ventral frontal regions involved in the articulatory control system of the phonological loop. Further, we speculate that load-dependent increases in right inferior cerebellar regions (VIIA/VIIB) reflect increased input from parietal regions important for phonological storage (Desmond et al., 1997
; Kirschen et al., 2005
; Chen and Desmond, 2005a). This cortical-cerebellar network relies on anatomical connectivity between these regions (Schmahmann, 1991
, Schmahmann, 1996
, Schmahmann and Pandya, 1997
). Thus in our study, parametric increases in activation in cerebellar regions are interpreted to reflect increased WM processing demands.
The increased cerebellar activation among adolescents and adults relative to children during verbal WM reported here is inconsistent with previous studies that have reported decreasing cerebellar activation with age during the performance of object WM (Ciesielski et al., 2006
) and VSWM (Scherf et al., 2006
). It is important to note however, that the cerebellum is thought to play a crucial role in covert speech and phonological storage (Desmond & Fiez, 1998; Chen & Desmond, 2005a; Chen and Desmond, 2005b), processes that are presumably more involved in the maintenance of verbal information than that of the visual information presented in other studies. Thus, our findings provide evidence of developmental changes in cerebellar involvement in verbal WM that are consistent with known developmental improvements in behavioral measures of phonological storage and covert speech (Gathercole, 1999
). These changes may be functionally distinct from developmental changes in cerebellar involvement in other types of WM and suggest a conceptualization of the role of the cerebellum in verbal
WM development. It is also important to note that the previous studies reporting decreasing cerebellar activation with increasing age were examining the main effects of cerebellar activation for object (Ciesielski et al., 2006
) and VSWM (Scherf et al., 2006
). In contrast, the present study examined linear and nonlinear changes in brain activation under conditions of increasing WM load. It is also possible that the differences between the results of the present study and those of previous investigations are related to the use of differences contrasts. Future studies comparing developmental changes in cerebellar involvement in different types of WM within the same subjects will be needed to test these hypotheses.
Consistent with the role of the ventral prefrontal cortex in WM maintenance processes (D'Esposito et al., 1999
, D'Esposito et al., 2000
, Veltman et al., 2003
), we observed increasing activation with increasing WM load in ventral prefrontal cortex within all age groups studied here, suggesting that WM maintenance systems are mature by age 7. In contrast, parietal and cerebellar involvement in linear load-dependency was observed only in the adolescent and young adult age groups, suggesting continued development of those WM processes supported by parietal and cerebellar regions between childhood and adolescence. Although there is some disagreement about its precise location (Becker et al., 1999), recent neuropsychological (for a review see (Muller and Knight, 2006
) and neuroimaging (Ravizza et al., 2004) work has implicated the parietal cortex as the site of the phonological storage component of verbal WM and suggests that the dorsal parietal cortex is particularly sensitive to manipulations of verbal WM load. As noted above, several studies have described a role for the cerebellum in the phonological loop component of verbal WM (Desmond et al., 1997
; Chen et al., 2005
; Kirschen et al., 2005
). Thus, our findings suggest that developmental differences in verbal WM may relate specifically to changes in the phonological storage component of verbal WM maintenance. Additional investigations using event related designs will be needed to isolate the maintenance stage of verbal WM within a given trial to further address this hypothesis. Future studies will also need to directly manipulate phonological storage processes by varying both the length of the maintenance period or the quality of encoding.
Nonlinear responses to increasing WM load were observed in adolescents, but not children or young adults. Among adolescents, inverted U-shaped responses were observed in medial parietal and prefrontal regions, consistent with previous observations in adults (Rypma et al., 1999
; Kirschen et al., 2005
; Caseras et al., 2006). Nonlinear load-dependent activation was significantly increased in right ventral prefrontal cortex among young adults, relative to children, although this region was not observed in the young adult mean activation map, perhaps to due to differences in the sample sizes between age groups. Nonetheless, young adult subjects displayed statistically significant increases in nonlinear load-dependent activation, relative to children, in right ventral prefrontal cortex. Nonlinear load-dependency may indicate recruitment of different working memory mechanisms at different WM loads (Braver et al., 1997
, Gould et al., 2003
). Regions showing nonlinear responses to increasing WM load showed increased activation to medium load trials and similar levels of activation to low and high load trials. This pattern is consistent with the notion of a brain region being recruited as task demands increase (from low to medium WM loads), but then “dropping out” as task demands become overly difficult (from medium to high WM loads).
Dissociating developmental changes in brain activation from changes that may be due to performance differences among different age groups is an important and complex issue (Durston and Casey, 2006
). In the present study, adolescents and adults recruited several brain regions not recruited by children, with no apparent benefit to accuracy, given that accuracy did not vary with age. Response time differences may contribute to observed differences in brain activation between young adults and children, but it is important to note that although adults were significantly faster than children there were no accuracy differences between these groups. Furthermore, there were no significant differences in RT between adolescents and children, and adolescents displayed increased linear-load dependent activation relative to children in the same location as young adults subjects. Perhaps group differences in RT stem from adults performing low and medium trials at ceiling, and the more diffuse pattern of activation among older participants would facilitate performance only if the task were more demanding. Three WM load levels may not be sufficient to characterize the full spectrum of parametric changes in both behavior and BOLD signal that occur in response to WM challenge.
The present study extends knowledge of WM development in several important ways. First, although linear load effects have been shown in adults, the present findings are the first, to our knowledge, to investigate load effects in verbal WM across childhood, adolescence, and adulthood. Developmental changes in the network of regions recruited in response to increasing WM load suggest that changes in phonological processing may be most prominent, as evidenced by increasing activation with age in parietal and cerebellar regions crucial for this cognitive process. Second, cerebellar support of verbal WM develops between childhood and adolescence, and our results suggest that the role of the cerebellum in the cognitive development of verbal WM may differ from its role in visual-spatial WM. These results demonstrate that, while children, adolescents, and young adults activate similar cerebro-cerebellar verbal working memory networks, the extent to which they reply on parietal and cerebellar regions in response to increasing task difficulty changes significantly between childhood and adolescence.