Immature Frontal Lobe Contributions to Cognitive Control in Children

“…and John D.E. Gabrieli1,2 1Neurosciences Program Stanford University Stanford, California 94305 Prefrontal lesions in adults and nonhuman primates lead 2 Department of Psychology to impairments in cognitive control (Luria, 1966; Stuss Stanford University and Benson, 1986; Miller and Cohen, 2001).”

“This task combined the Eriksen flanker (Erik- sen and Eriksen, 1974) and go/no-go paradigms (Figure Introduction 1).”

“…University maturation is provided by measures of myelination (YaWashington, D.C. 20057 kovlev and Lecours, 1967; Pfefferbaum et al., 1993; Giedd et al., 1999), gray matter reduction (Jernigan et al., 1991; Pfefferbaum et al., 1993; Sowell et al., 2001), Summary synaptogenesis…”

“The large differences in the present a button box with the index and middle fingers of their right hand.crosssectional study suggests that a major transformaPsyscope (Cohen et al., 1993) was used to generate stimuli and tion occurs between ages 12 and 19, and imaging stud- to collect responses.”

“…1993; Giedd et al., 1999), gray matter reduction (Jernigan et al., 1991; Pfefferbaum et al., 1993; Sowell et al., 2001), Summary synaptogenesis (Huttenlocher, 1979), and resting metabolism (Chugani et al., 1987; for reviews, see Casey Event-related fMRI was employed to characterize dif- et…”

“…that anterior insula may play as important a role in cognitive control as the frontal and cingulate regionshave been observed for studies related to verbal articu- lation (Dronkers, 1996; lesion study) or phonological pro- which have received much attention. cessing (e.g., Paulesu et al., 1993).”

“…(Jernigan et al., 1991; Pfefferbaum et al., 1993; Sowell et al., 2001), Summary synaptogenesis (Huttenlocher, 1979), and resting metabolism (Chugani et al., 1987; for reviews, see Casey Event-related fMRI was employed to characterize dif- et al., 2000a; Gaillard et al., 2001; Diamond,…”

“…and blood flow coding: 13.7 .7; block design: 14.3 .9 [M SEM]).and amount of artifact due to motion, respiration, or Average IQ (estimated from vocabulary and block de-cardiac activity (Gaillard et al., 2001; Casey et al., 2000b; sign tests; see Spreen and Strauss, 1998) was 125 4Diamond, 2002).”

“More anterior foci (adjacent to the inferior frontal gyrus; y 8 to y 30) Response Inhibition Adults exhibited little variability in terms of either perfor-have been observed for studies that required cognitive control (e.g., Garavan et al., 1999; Bunge et al., 2000, mance or regions activated.”

“…(Jernigan et al., 1991; Pfefferbaum et al., 1993; Sowell et al., 2001), Summary synaptogenesis (Huttenlocher, 1979), and resting metabolism (Chugani et al., 1987; for reviews, see Casey Event-related fMRI was employed to characterize dif- et al., 2000a; Gaillard et al., 2001; Diamond, 2002).”

“…that anterior insula may play as important a role in cognitive control as the frontal and cingulate regionshave been observed for studies related to verbal articu- lation (Dronkers, 1996; lesion study) or phonological pro- which have received much attention. cessing (e.g., Paulesu et al., 1993).”

“…robust activation of regions that have been identified in previous studies of response inhibition Unlike the present study, previous go/no-go studies have observed robust lateral prefrontal activation in chil-(Casey et al., 1997; Rubia et al., 2000) but resulted in weak brain-behavior correlations.”

“Insular activa- tion is remarkably ubiquitous in imaging studies but 2001; Dove et al., 2000; Rubia et al., 2001).”

“Evidence from fMRI tion, as measured by tests of reasoning, problem-solving, and IQ (e.g., Dempster, 1992).”

“…of cognitive control are the ability requirement of responding to the central target (Eriksen to filter out irrelevant information in the environment and Eriksen, 1974; Gratton et al., 1988; Botvinick et al., (interference suppression) and the ability to inhibit inap1999; Hazeltine et al., 2000).”

“…require1997) and inhibit prepotent response tendencies or an active response (go), participants must inhibit a pre-strategies (Costantini and Hoving, 1973; Casey et al., potent tendency to respond on all trials on the minority1997; Williams et al., 1999; Diamond, 1988; Luna et al., of no-go trials.”

“In contrast, there was dren (Casey et al., 1997; Vaidya et al., 1998).”

“Using thestimuli or stimulus dimensions (Hazeltine et al., 2000), index and middle fingers of their right hand, subjects pressed a left or shift cognitive sets (Konishi et al., 1999).”

“Insular activa- tion is remarkably ubiquitous in imaging studies but 2001; Dove et al., 2000; Rubia et al., 2001).”

“Bjorkland, 1993) include tasks in which subjects must In the go/no-go paradigm, subjects must withhold re-ignore irrelevant stimuli (Tipper et al., 1989; Ridderinkhof sponding to an inappropriate stimulus, while respondinget al., 1997; Comalli et al., 1962; Lorsbach and Reimer, to all other stimuli.”

“…robust activation of regions that have been identified in previous studies of response inhibition Unlike the present study, previous go/no-go studies have observed robust lateral prefrontal activation in chil-(Casey et al., 1997; Rubia et al., 2000) but resulted in weak brain-behavior correlations.”

“Functional images were acquired formaturation of the mind. the same set of slices using a T2*-sensitive gradient echo spiral References pulse sequence (Glover and Lai, 1998) (1000 ms TR, 30 ms TE, 60 flip angle, 24 cm field of view, 64 64 data acquisition matrix).”

“…and blood flow coding: 13.7 .7; block design: 14.3 .9 [M SEM]).and amount of artifact due to motion, respiration, or Average IQ (estimated from vocabulary and block de-cardiac activity (Gaillard et al., 2001; Casey et al., 2000b; sign tests; see Spreen and Strauss, 1998) was 125 4Diamond, 2002).”

“…by measures of myelination (YaWashington, D.C. 20057 kovlev and Lecours, 1967; Pfefferbaum et al., 1993; Giedd et al., 1999), gray matter reduction (Jernigan et al., 1991; Pfefferbaum et al., 1993; Sowell et al., 2001), Summary synaptogenesis (Huttenlocher, 1979), and resting metabolism (Chugani…”

“…kovlev and Lecours, 1967; Pfefferbaum et al., 1993; Giedd et al., 1999), gray matter reduction (Jernigan et al., 1991; Pfefferbaum et al., 1993; Sowell et al., 2001), Summary synaptogenesis (Huttenlocher, 1979), and resting metabolism (Chugani et al., 1987; for reviews, see Casey Event-related…”

“On eachresponding (Casey et al., 1997; Konishi et al., 1998; trial, they viewed an array of five stimuli, including a central arrowRubia et al., 2001), suppress interference from irrelevant and two stimuli on either side of it (flankers) (Figure 1).”

“…frontal gyrus displayed a weaker, but also positive, correlation between activation and performance liams et al., 1999) and were more susceptible to interfer- ence from the environment (Tipper et al., 1989; Ridde-(identified at p .01; BA 9; [44, 14, 32]; z 3.00; 144 mm3). rinkhof et al., 1997).”

“More anterior foci (adjacent to the inferior frontal gyrus; y 8 to y 30) Response Inhibition Adults exhibited little variability in terms of either perfor-have been observed for studies that required cognitive control (e.g., Garavan et al., 1999; Bunge et al., 2000, mance or regions activated.”

“Neuron, Vol. 33, 301–311, January 17, 2002, Copyright 2002 by Cell Press”

“…of cognitive control are the ability requirement of responding to the central target (Eriksen to filter out irrelevant information in the environment and Eriksen, 1974; Gratton et al., 1988; Botvinick et al., (interference suppression) and the ability to inhibit inap1999; Hazeltine et al., 2000).”

“…and blood flow coding: 13.7 .7; block design: 14.3 .9 [M SEM]).and amount of artifact due to motion, respiration, or Average IQ (estimated from vocabulary and block de-cardiac activity (Gaillard et al., 2001; Casey et al., 2000b; sign tests; see Spreen and Strauss, 1998) was 125 4Diamond, 2002).”

“Within PFC, a region in right to withhold inappropriate responses than were adults (Costantini and Hoving, 1973; Casey et al., 1997; Wil-middle frontal gyrus displayed a weaker, but also positive, correlation between activation and performance liams et al., 1999) and were more susceptible to…”

“Yet evidence indicates that diverse types of inhibitory control of attention and action appear to share substantially similar neural bases (Bunge et al. 2002, Cohen et al. 2012).”

“Further support for this claim is provided by two recent fMRI studies in which involvement of the right lateral prefrontal cortex was detected when participants inhibited a prepotent response in a sensory motor task (Bunge et al., 2002) and also in a deductive-reasoning task (Goel & Dolan, 2003).”

“…over a period of time results in both refinement within brain regions as well as fine tuning of projections from these regions (Brown et al. 2005; Bunge et al. 2002; Casey et al. 1997; Casey et al. 2002; Luna et al. 2001; Moses et al. 2002; Schlaggar et al. 2002; Tamm et al. 2002; Thomas et al.…”

“…Bunge, Dudukovic, Thomason, Vaidya, & Gabrieli, 2002; Casey, Trainor et al., 1997; Casey et al., 2002a; Crone, Donohue, Honomichl, Wendelken, & Bunge, 2006; Luna et al., 2001; Moses et al., 2002; Schlaggar et al., 2002; Tamm et al., 2002; Thomas et al., 2004; Turkeltaub, Gareau, Flowers,…”

“…developental improvements in EF component processes and recent ndings emerging from brain imaging studies of cognitive develpment (e.g., Bunge et al., 2002; Casey et al., 1997; Crone, onohue, Wendelken, Honomichl, & Bunge, in preparation; urston et al., 2002; Klingberg et al., 2002;…”

“Crucially, response selection in tasks recruits the parietal cortex, as well as the prefrontal lobe (Bunge 2004; Bunge et al. 2002b; Cohen Kadosh et al. 2007; Göbel et al. 2004; Jiang & Kanwisher 2003; Rosenthal et al. 2006).”

“Developmental fMRI studies support these findings ( Bunge, Dudukovic, Thomason, Vaidya, & Gabrieli, 2002; Casey et al., 1995; Luna et al., 2001; Rubia et al., 2000; Tamm, Menon, & Reiss, 2002).”

“These changes appear to show activation shifts of prefrontal regions from diffuse to more focal recruitment over time (Casey et al., 1997; Bunge et al., 2002; Moses et al., 2002; Durston et al., 2006).”

“Bunge et al. (2002) concluded that immature prefrontal activation accounted for poor performance on inhibition tasks; development brings both improved performance and a shift in the brain areas associated with these functions.”

“…cingulate, and dorsal premotor cortex (Halsband and Passingham, 1985; Schluter et al., 1998; Praamstra et al., 1999; Hazeltine et al., 2000; Rubia et al., 2001; Bunge et al., 2002b; Rushworth et al., 2002; Hazeltine et al., 2003; Schumacher et al., 2003; Koski et al., 2005; Wager et al., 2005).”

“This type of executive control was described by Bunge, Dudukovic, Thomason, Vaidya, and Gabrieli (2002) as “interference suppression.” In contrast, the SART uses simple stimuli that are presented with a rule to either respond or refrain from responding.”

“Early in development, inhibitory control appears to be associated with LIFG regions, and the prominence of right IFG emerges only later in life [23].”

“Although task-based studies generally interpret greater bilaterality as reflecting cortical immaturity (Bunge et al., 2002; Wood et al., 2004; Smyser et al., 2010), reasons for the re-emergence of bilaterality in aging are debated.”

“In terms of the functional consequences of this maturational delay, many researchers have suggested that specific cortical underdevelopment in prefrontal systems may be responsible for the slow progression of cognitive control abilities on tasks such as the Stroop task, the go/ no-go task (e.g., Bunge, Dudukovic, Thom…”

“The shift from diffuse activation may represent attenuation of activation in other, less critical, cortical areas, either in the number of regions activated or in the extent of activated tissue (Brown et al. , 2005; Bunge et al. , 2002).”

“This is consistent with evidence from many other studies that have demonstrated that these regions are involved in response inhibition (Bunge et al., 2002; Casey et al., 1997, 2001; Durston et al., 2002; Garavan, Ross & Stein, 1999; Konishi, Nakajima, Uchida, Sekihara & Miyashita, 1998; Konishi,…”

“Developmentally, cortical association areas including the prefrontal and parietal cortex thought to subserve age-related improvement in cognitive control [26–30] undergo delayed maturation [31–33].”

“Although some previous evidence exists for maturation of parietal brain regions during motor response inhibition [Rubia et al., 2000; Bunge et al., 2002], interference inhibition in stimulus-response incompatibility tasks [Adleman et al., 2002], and task switching [Casey et al., 2004], to our…”

“Further, the findings suggest that these neuroanatomical changes occur over a protracted period of time (Brown et al., 2005; Bunge et al., 2002; Casey, Thomas, et al., 2002; Casey, Trainor, et al., 1997; Crone, Donohue, Honomichl, Wendelken, & Bunge, 2006; Luna et al., 2001; Moses et al., 2002; Schlaggar et al., 2002;…”

“Bunge et al. (2002) have demonstrated that each of these kinds of inhibition shows a different developmental trajectory and engages different areas of the prefrontal cortex.”

“…studies have shown that, relative to adults, young children typically activate larger and more diffuse regions of prefrontal cortex when performing tasks that require attentional control, such as Go/NoGo or Flanker tasks (Casey et al. 1997; Bunge et al. 2002; Tamm et al. 2002; Durston et al. 2006).”

“However, mature performance is accompanied by differences in brain function underlying performance at younger ages (Thomas et al. 1999; Rubia et al. 2000, 2005, 2007; Luna et al. 2001; Bunge et al. 2002).”

“…2001; Peterson et al., 2002; Schumacher and D'Esposito, 2002), GNG tasks (Casey et al., 1997; Klingberg and Roland, 1997; Konishi et al., 1999; Liddle et al., 2001; Menon et al., 2001; Rubia et al., 2001), and flanker tasks (Bunge et al., 2002a,b; Casey et al., 2000; Hazeltine et al., 2000).”

“A number of studies have underscored differences between these age groups on similar tasks of executive function, with children failing to utilize the same prefrontal brain areas as adult subjects (Thomas et al., 1999; Rubia et al., 2000; Bunge et al., 2002; Schlaggar et al., 2002).”

“Many paradigms have been used, together with fMRI, to assess the neurobiological basis of these abilities, including go/nogo, flanker, stop signal, and anti saccade tasks (Bunge et al 2002; Casey et al., 1997b; Casey, Giedd, & Thomas, 2000a; Durston et al., 2003; Luna et al., 2001).”

“Children recruit distinct and often larger, more diffuse frontostriatal regions when performing cognitive control tasks (Casey et al., 1997a,b, 2002a; Luna et al., 2001; Bunge et al., 2002).”

“Parietal activation has been observed previously for incongruent relative to congruent or neutral flanker trials (e.g., Carter et al., 2000; Casey et al., 2000; Bunge et al., 2002).”

“One such approach is to use performance matching to equate behavioral performance [28,31 ,33,35].”

“, 2003), executive functions (Bunge et al., 2002; Dumontheil and Klingberg, 2011; Somerville et al., 2010; Wendelken et al., 2011b), and even social, moral, and emotional cognition (Decety et al.”

“During late childhood and adolescence, the development of the frontal lobes is associated with better performance on executive control tasks (Bunge, Dudukovic, Thomason, Vaidya, & Gabrieli, 2002; Travis, 1998).”

“Across studies there have been findings indicating that aspects of the inferior frontal gyrus (Brodmann’s areas 45 and 46 or BA 45/46) and premotor regions (BA46) increase activation with age (Bunge et al., 2002; Rubia et al., 2000).”

“Although the right IFG is activated by a large number of conditions (Duncan & Owen (2000) for a meta-analysis), there is a preponderance of studies that have specifically focused upon response inhibition (Garavan et al. 1999; De Zubicaray et al. 2000; Menon et al. 2001; Bunge et al. 2002; Garavan et al. 2002; Rubia et…”

“, 1999, 2001) and with reports of functional changes in PFC activation during performance of behavioral inhibition and working memory tasks (Bunge et al., 2002; Casey et al., 2000; Kwon et al., 2002).”

“…developmental trajectory of executive control through the first decades of life, reflecting the late development of prefrontal brain structures (Bunge et al. 2002; Casey et al. 1995; Durston et al. 2002; Lenroot et al. 2007; for review see Mesulam 2002), complicates assessment techniques.”

“Cerebral Cortex July 2010;20:1613--1629 doi:10.1093/cercor/bhp225 Advance Access publication October 29, 2009”

“, 2005) Orbitofrontal cortex is linked to simple rule representation, whereas ventrolateral prefrontal cortex and dorsolateral prefrontal cortex are linked to representation of sets of conditional rules and rule switching (Bunge & Zelazo, 2006; Crone, Wendelken, Donohue, & Bunge, 2006) Orbitofrontal cortex is theorize…”

“…belief that frontal maturation is involved (Casey et al., 1995, 1997, 2002; Thomas et al., 1999; Gaillard et al., 2000, 2003; Holland et al., 2001; Luna et al., 2001; Bunge et al., 2002; Klingberg et al., 2002; Kwon et al., 2002; Schlaggar et al., 2002b; Tamm et al., 2002; Booth et al., 2003).”

“Additionally, adults engaged the inferior parietal cortex more strongly than youths on the Simon and set-shifting tasks [32 ], and a similar finding has previously been reported for the Go–No-Go task [24].”

“…al. 1999; Carter et al. 1998, 2000; Petrides et al. 1993) that include the prefrontal, parietal, and anterior cingulate cortex (Braver et al. 2001; Bunge et al. 2002; de Zubicaray et al. 2000) but also the basal ganglia (Graybiel 1997; Middleton and Strick 2000) thanks to its connections with the…”

“…regions that can extend into adulthood together delineate a vast age-range during which amygdala–cortical functional connections may develop (Bunge et al., 2002; Casey et al., 1997, 2000; Giedd et al., 1996; Gogtay et al., 2004; NeuroImage 95 (2014) 193–207 ⁎ Corresponding author at:…”

“The relationship between the efficiency of executive function and related brain activity was often discussed in earlier studies (Bunge et al., 2002; Wager et al., 2005; Li et al., 2006a; MFG, Middle frontal gyrus; SFG, superior frontal gyrus; OFC, orbitofrontal cortex; PCC, posterior cingulate…”

“…prepotent responses or to resolve response competition (e.g. Casey et al., 1997; Garavan et al., 1999; MacDonald et al., 2000; Liddle et al., 2001; Bunge et al., 2002a,b), with right DLPFC in particular appearing to play a general role in response selection across different stimulus materials…”

“The prefrontal cortex develops more slowly than other brain areas, reaching maturation only late in adolescence ( Bunge, Dudukovic, Thomasson, Vaidya & Gabrieli, 2002 ).”

“Due to the immaturity of the PFC in the very young, children appear to differentially recruit these regions in inhibitory control tasks when compared to adults (Bunge et al., 2002; Durston et al., 2002).”

“Children show significantly higher intensity of activation than adults in frontal lobe regions (Bunge et al., 2002) including bilateral medial frontal gyrus and medial aspects of bilateral superior frontal gyrus (Booth et al., 2003).”

“For example, during tasks that require the inhibition of a prepotent response (the performance of which improves with age), adolescents have increased PFC activity in some subregions and decreased activity in others (Bunge et al., 2002; Rubia et al., 2000; Tamm et al., 2002).”

“…children with adults) have focused on aspects of executive control and found evidence for a higher susceptibility to interference in children that was paralleled by maturational differences in underlying frontostriatal circuitry (Bunge et al., 2002; Durston et al., 2002, Casey et al., 2002).”