Clinical Neuropsychiatry (2009) 6, 4, 155-165

ADOLESCENT BRAIN DEVELOPMENT AND EXECUTIVE FUNCTIONS:

A PREFRONTAL FRAMEWORK FOR DEVELOPMENTAL PSYCHOPATHOLOGIES

Michele Poletti

Abstract
Objective: the brain undergoes a period of marked development during adolescence, due to the processes of
synaptic pruning and myelination, that improve the efficiency of cortical and cortico-subcortical connectivity. This
brain development has a significant impact on cognitive and emotional processing of adolescents. To describe the
correlates of adolescent brain maturation it’s here proposed a prefrontal framework that highlights anatomical, functional
and developmental differences between executive functions based on the Dorsolateral Prefrontal cortex and executive
functions based on the Orbitofrontal cortex.
Method: a literature review of cognitive and emotional correlates of adolescent brain development in healthy
subjects and in clinical populations was conducted in Electronic databases PubMed and PsycInfo. For the purpose of
this article, Attention Deficit/Hyperactivity Disorder and Major Depression are taken as prototypes of those externalizing
disorders and internalizing disorders, respectively, that may affect adolescents.
Results: executive functions based on the Orbitofrontal cortex mature earlier than executive functions based on
the Dorsolateral Prefrontal cortex. ADHD is characterized by a dysfunction of both types of executive functions, with
differences within clinical subtypes; Major Depression is characterized by a dysfunction of Orbitofrontal Prefrontal
cortex.
Conclusions: a prefrontal framework is useful to describe cognitive and emotional correlates of adolescent brain
development and how this phenomenon may increase the vulnerability of adolescents to psychopathology.

Key Words: adolescence, brain development, prefrontal framework, executive functions, ADHD, major depression

Declaration of interest: None

Michele Poletti
Neurology Unit, Versilia Hospital, Lido Di Camaiore (LU), Italy,
AnSvi, Accademia di Neuropsicologia dello Sviluppo, Parma.

Address for correspondence:

Dr. Michele Poletti
Neurology Unit, Versilia Hospital, via Aurelia 335, Lido di Camaiore, (LU).
+39 0584 6059539, fax: + 39 0584 6059539, michelepoletti79@gmail.com

Introduction portions of the Prefrontal Cortex (PFC) in healthy

Several psychopathologies may have an onset
during adolescence: recent neuroimaging studies
suggest that this phenomenon could be related to the
marked structural development that involves the
cerebral cortex in this temporal window (Paus et al.
2008). In this article is discussed the contribution of
neuropsychology to the assessment of behavioral,
cognitive and affective correlates of this developmental
phenomenon. Empirical findings about correlates of
adolescent brain development are framed within a
prefrontal system that highlights anatomical, functional
and developmental differences between executive
functions (EF), based on the dorsolateral portion of the
Prefrontal cortex (DLPFC), and EF based on the orbital
portion of the Prefrontal cortex (OFC).
This framework is useful not only to explain the
different developmental trends of EF based on different
SUBMITTED JANUARY 2009, ACCEPTED JULY 2009
adolescents, but also to explain why adolescence
represents a temporal window of increased vulnerability
to psychopathology; in order to sustain this hypothesis,
Attention Deficit/Hyperactivity Disorder and Major
Depression are examined as prototypes of externalizing
disorders and internalizing disorders, respectively. A
literature review of studies of healthy and clinical
adolescent populations was conducted to support this
distinction between DLPFC and OFC during
development. Articles published before February 2009
were searched in the electronic databases PubMed and
PsycInfo using the following keywords: adolescence,
brain development, prefrontal cortex, dorsolateral
prefrontal cortex, orbitofrontal cortex, executive
functions, frontal functions, working memory, response
inhibition, reward processing, decision making, delay
aversion, impulsivity, Attention Deficit/Hyperactivity
Disorder, depression, mood disorder.

© 2009 Giovanni Fioriti Editore s.r.l. 155

 Michele Poletti
Adolescent brain development
In recent years, a group of neuroimaging studies
put light on adolescent brain development. This set of
studies (for example Gogtay et al. 2004, Shaw et al.
2008, Sowell et al. 2003, for review see Giedd 2008,
Lenroot and Giedd 2006, Thompson et al. 2005) found
that the adolescent brain has a marked development,
specially in the PFC. Different developmental patterns
of grey matter and white matter have been discovered
by the several longitudinal studies with neuroimaging
methodologies that followed the development of brain
structure from childhood to early adulthood.
White Matter Increase
First, structural Magnetic Resonance Imaging
(MRI), used to measure the size and shape of brain
structure, found that white matter volume increases in
a roughly linear pattern, increasing throughout
development into adulthood (Gogtay et al. 2004). These
changes presumably reflect ongoing myelination of
axons by oligodendrocytes enhancing neuronal
conduction and communication (Casey et al. 2008).
Diffusion Tensor Imaging (DTI), used to index
connectivity of white matter fiber tracts, permitted to
look for specific associations between DTI-based
measures of prefrontal white matter development and
cognitive control in children. For example, the
development of working memory was found to be
positively correlated with the fractional anisotropy, an
indicator of myelination and axonal thickness, of
prefrontal-parietal fiber tracts (Nagy et al., 2004). The
same indicator, relative to white matter tracts between
PFC and basal ganglia, was found to be correlated with
the development of inhibitory control, as detected by
performances in go-no go tasks (Liston et al., 2005).
Myelination involves cortico-cortical neural
connections between different prefrontal regions
(including the corpus callosum) and between the
DLPFC and occipital, temporal and parietal association
areas (Gogtay et al. 2004), increasing the efficiency of
conduction and communication by up to a hundred-fold
(Durston et al. 2006).
As evidenced in the proliferation of projections
of white matter tracts across different brain regions,
there is an increase not only in connections among
cortical areas, but between cortical and subcortical areas
(specially between prefrontal regions and limbic and
paralimbic areas, including the amygdala, the nucleus
accumbens and the hippocampus) (Eluvathingal et al.
2007). This anatomical change should be associated
with improved coordination of affect and cognition,
facilitated by the increased connectivity of regions
involved in the processing of emotional information
(the amygdala, ventral striatum, orbitofrontal cortex,
medial prefrontal cortex, and superior temporal sulcus)
and regions involved in cognitive control (DLPFC,
anterior and posterior cingulate, and temporo-parietal
cortices) (Steinberg 2008).
Grey Matter U-Curve Shaped development
The grey matter develops following an inverse U-
156
shaped curve during adolescence. MRI studies found
that different cortical regions reach their peak of grey
matter at different ages. Only occipital lobes follow a
linear increase. Frontal lobes reach their peak at 12 years
of age for males and at 11 years for females. Parietal
lobes reach their peak at 12 years for males, and at 10
for females. Temporal lobes reach their peak at 17 years,
either for males and females (Shaw et al. 2008). Brain
development continues until early adulthood, even if
with weaker intensity. The redefinition of neural
networks, by loss of grey matter, continues, in the PFC
also in the third decade of life (Sowell et al. 2003), and
DLPFC is the last prefrontal cortical area that reaches
its definitive thickness (Lenroot and Giedd 2006).
Studies in nonhuman animals suggest that cortical
dimensions during critical periods for the development
of cognitive functions, may reflect experience-
dependent molding of the architecture of cortical
columns along with dendritic spine and axonal
remodeling (Chklovskii et al. 2004, Mataga et al. 2004,
Hensch 2004, 2005, Sur and Rubinstein 2005). The
cortical thinning that dominates in adolescence might
reflect the use-dependent selective elimination of
synapses (synaptic pruning), a process that enhances
the computational capacity of local circuitry, improving
the ability to modulate activity and implement stop
mechanisms in a prompt manner (Hensch 2004,
Huttenlocher and Dabholkar 1997, Knudsen 2004).
To summarize, the elimination of synaptic
redundant connections support more efficient and
complicated regional neural computations, increasing
firing stability of prefrontal cortical neurons (Rutherford
et al. 1998), more able to fire in concerted and sustained
patterns (Miller and Cohen 2001). At the same time
myelination speeds neural transmissions, allowing
distant brain regions to participate more efficiently in
widely distributed circuitry, that supports top-down
executive control of behavior: communication among
cortical regions can ensure that most refined plans are
generated, while cortico-subcortical communication
enhances top-down modulation of response plan
execution (Luna and Sweeney 2004). This pattern
suggests that adolescent brain development may support
more effective integration of brain functions across
regions, rather than improvements in the computational
capacities of local brain function.
These researches have given new strength to the
fields of developmental psychopathology (Spessot et
al. 2004, Toga et al. 2006) and cognitive development
(Durston and Casey 2006, Kuhn 2006, Paus 2005,
Steinberg 2005). How cognitive and affective correlates
of this prolonged brain development can be framed?
Here is proposed a prefrontal system framework that
distinguishes between EF based on the OFC and EF
based on the DLPFC. The efficacy of this prefrontal
framework is discussed examining different
maturational patterns of EF, either in healthy
adolescents and in adolescents with psychopathologies.
A framework for Executive Functions
PFC is one of the latest cortical region to mature
and to reach its definitive thickness during adolescence
(Lenroot and Giedd 2006). PFC is involved in several
Clinical Neuropsychiatry (2009) 6, 4
 Developmental psychopathologies and prefrontal cortex
cognitive functions, like language, movement and high
level perception, but plays also a fundamental role in
functions usually defined as EF (Stuss 1992). EF are
usually considered a variety of high level cognitive
processes as attention, set-shifting, planning, working
memory, cognitive flexibility, decision-making,
feedback use, error detection, response inhibition and
self regulation, that are necessary for an appropriate
affective and contextual goal-directed behavior
(Alvarez and Emory 2006, Miyake et al. 2000).
Anatomical distinction
In order to describe the different cognitive and
behavioural deficits after injuries to its different portions
(Stuss and Levine 2002), neuroscience actually
distinguishes between DLPFC-related EF (DLPFC-EF)
and OFC-related EF (OFC-EF) (Ardila 2008). DLPFC
comprises the lateral portions of Brodmann’s areas 9,
10, 11, and 12; areas 45 and 46 and the superior part of
area 47 (Damasio 1996, Gazzaniga et al. 1998). In
addition to its connections with OFC, DLPFC is
connected to a variety of brain areas that allow it to
play an important role in the integration of sensory and
mnemonic information and in the regulation of
intellectual function and action. These areas include
thalamus, basal ganglia (the dorsal caudate nucleus),
hippocampus, and primary and secondary associative
areas of neocortex, including posterior temporal,
parietal, and occipital areas (Fuster 1989). OFC consists
of both orbital (ventral) and medial regions of PFC,
including the medial portions of Brodmann’s areas 9,
10, 11, and 12; areas 13 and 25; and the inferior portion
of area 47 (Damasio 1996, Gazzaniga et al. 1998). OFC
is part of a frontostriatal circuit that has strong
connections to the amygdala and other parts of the
limbic system (Chudasama and Robbins 2006). Hence,
OFC is well suited for the integration of affective and
cognitive information, and for the regulation of
motivated and goal-oriented behavior (Rolls 2004).
Functional distinction
DLPFC-EF have been differently labelled; some
authors label them as “Cool EF”, being based on a
cognitive and controlled elaboration of information
(Zelazo and Mueller 2002); other authors label them
as “Metacognitive EF” (Ardila 2008). DLPFC EF
permit an attentional control on behavior and include
working memory, planning, task or set-switching,
problem solving, strategy development: they are
assessed by classic executive tasks like the Trail Making
Test (Reitan 1958), the Wisconsin Card Sorting Test
(Grant and Berg 1948), the Tower of London (Shallice
1982) and the Stroop Test (Stroop 1935).
Also OFC-EF have been differently labelled: some
authors label them as “Hot EF”, being based on an
emotional and automatic processing of information
(Zelazo and Mueller 2002); other authors label them
as “Emotional/Motivational EF” (Ardila 2008). OFC-
EF guide a reward-based control of behavior and the
management of risk; they include reward processing,
reversal learning and decision making: they are assessed
Clinical Neuropsychiatry (2009) 6, 4
by gambling tasks or decision tasks (Hongwanishkul
et al. 2005), like the Iowa Gambling Task (Bechara et
al. 1994). Overall, it’s important to underline that a clear
distinction between DLPFC-EF and OFC-EF is possible
only distinguishing respective neural correlates; at a
behavioral level of analysis, considering performance
in experimental tasks or in real-life situations, it’s
possible to think only in terms of a prevalence of a
typology of EF, never in terms of presence/absence
(Ardila 2008, Galotti 2007). Does this prefrontal system
framework fit to describe cognitive and affective
correlates of adolescent brain development? Recent
experimental results supporting the usefulness of this
approach in healthy and clinical adolescent populations
are reported and discussed in the next sections.
Maturation of DLPFC vs. OFC Executive
Functions during adolescence
DLPFC Executive Functions
An increasing number of researches, using a
standard neuropsychological approach, revealed that
DLPFC-EF develop from childhood to adolescence
(Davies and Rose 1999, Korkman et al. 2001, Levin et
al. 1991, Stuss 1992, Welsh and Pennington 1988, Welsh
et al. 1991) following different developmental trends,
reaching adult-like levels of performance at different
ages. A comparison from different studies is difficult
because many tasks are used to assess the same function
and few studies assess many EF simultaneously,
impeding to look for latent common variables (Huizinga
et al. 2006, Miyake et al. 2000). Recent studies
reassessed the topic of DLPFC-EF maturation,
combining neuropsychological tasks (Brocki and
Bohlin 2004, Conklin et al. 2007, Gathercole et al. 2004,
Huizinga et al. 2006, Luciana et al. 2005), behavioral
tasks (Luna et al. 2004) and neuroimaging (Crone et
al. 2006, Durston et al. 2002, O’Hare et al. 2008).
This new set of combined studies (Blakemore and
Choudhury 2006 for review) confirmed that different
DLPFC-EF develop from childhood through
adolescence to young adulthood at different rates,
reaching mature functional levels at different ages. This
is also confirmed by neuroimaging studies, whose
results suggest there may be a dissociation within neural
correlates of performances between working memory
tasks and response inhibition tasks. Working memory
tasks increasingly activate, with age, lateral PFC regions
(Klingberg et al. 2002, Kwon et al. 2002) and in-
creasingly recruit complex neural networks (Crone et
al. 2006); for example, while in children working
memory tasks (verbal and spatial) activate only the left
ventral PFC, since adolescence the same tasks activate
a complex prefrontal-parietal-cerebellar neural network
(Crone et al. 2006, O’Hare et al. 2008). On the other
side, response inhibition tasks decreasingly recruit, with
age, complex neural networks, showing increasingly
focal activation in specific regions (inferior PFC: Aron
et al., 2004) thought to play a critical role in response
inhibition (Durston et al. 2002, Tamm et al. 2002).
A recent meta-analysis of studies published
between 1984 and 2004 on the development of DLPFC-
EF, is useful to provide a general representation of their
157
 Michele Poletti
maturation from childhood to adolescence (Romine and
Reynolds 2005). General trends included medium to
large age-related increases in performance between 5
and 8 years of age. Similarly, medium to large effects
were found between the span of 8 to 11 years of age.
Small to medium age-related increases were evident
between the range of 11 to 14 years. Changes in per-
formance between 14 and 17 years of age, across the
prefrontal abilities reviewed, ranged from no age-
related change to medium-size change. Variability in
age-related increase between the 17 years to adulthood
emerges, with some prefrontal functions displaying no
age-related increase and others demonstrating a large
increase in mean performance. This meta-analysis
found that across the areas of planning, verbal fluency
and response inhibition the greatest period of
development was between the ages of 5 and 8 years.
During the 8 to 11 age span, significant increases were
evident across all prefrontal functions. A small increase
in performance in response inhibition was found
between 11 and 14 years of age; however, no age-related
increase in performance was evident after this age
period. A continued development of planning and verbal
fluency was noted throughout adolescence, with
improvement in performance even in the 17 years of
age to early adulthood period.
OFC Executive Functions
With regard to OFC-EF, they are generally
assessed by decision tasks. As a matter of fact, when a
choice has to be made, information about expected
outcomes have to be maintained in memory in order to
be compared and integrated with information about
internal states and current subjective goals. This inte-
grative process generates outcome expectancies, that
are internal representations of possible consequences
of own actions: OFC plays a crucial role in the
generation of these outcome expectancies (Wallis
2007).
While the assessment of decision making in adults
has generated an extensive amount of researches, few
studies approached the study of this function in
adolescence. Recent results from developmental studies
reported that performances in decision tasks are worse
than those of adults until 11-12 years of age, because
of a bias for immediate wins, despite possible greater
future gains (Crone et al. 2005). Using a developmental
version of this task in a sample of subjects from 7 to 15
years of age and varying the frequency and the temporal
discount of wins and punishments, this study found an
age-related increase of the sensitivity toward possible
future punishments, also in uncertain situations. Up to
12 years of age, only when the punishment was very
probable and heavy it received attention by subjects,
while it was ignored in other cases.
Few studies directly examined the maturation of
decision making during adolescence with the same tasks
used with adults, as the Iowa Gambling Task (Bechara
et al. 1994). In one study (Crone and van der Molen
2004) with four age groups (6-9, 10-12, 13-15, 18-25
year-olds), the youngest subjects drew equally from the
good and bad decks. The two middle groups showed
modest improvement over time; by the final trial block,
158
they were drawing from the good decks about 55% and
60% of the time, respectively. By the final block,
however, the young adults were drawing from the good
deck nearly 75% of the time, and they began shifting
towards the good decks much earlier than the younger
groups. Another study, of 9 to 17-year-olds, also found
significant improvement in performance on this task
with age (Hooper et al. 2004). 14-17 year-olds drew
from the good decks more often than 9-10 year-olds
(although not as often than 11-13 year olds) and began
shifting to the good decks earlier than either of the
younger groups.
Successful performances on the decision tasks
require participants to pay attention to the outcomes of
their choices, using this feedback in their future choices.
Thus, poor performances in decision tasks may result
from an insensitivity to loss or from an inability to use
feedbacks in anticipation of future risk. A recent
physiological study demonstrated that the ability to
anticipate future outcomes of decisions continues to
develop until late adolescence (Crone and van der
Molen 2007), supporting the hypothesis that 8-10-year-
old and 12-14-year-old children perform like OFC-
damaged adult patients (Damasio 1994), because they
fail to anticipate outcomes prior to making a decision.
These data rejected the hypothesis that 8-10-year-old
children and 12-14-year-old children perform
disadvantageously because they would have failed to
process the outcomes of their decisions.
Functional neuroimaging has recently been used
to investigate developmental differences in neural
correlates of decision making. In a fMRI study, 18
adolescents (9-17 year-old) and 20 adults (20-40 year-
old) underwent brain scan during an economic decision
task, that directly assessed risk-taking behaviors during
choice selection (Eishel et al. 2007). OFC and dorsal
Anterior Cingulate Cortex (ACC) were examined
selectively since both have been implicated in reward-
related processes and resolution of conflicting
decisions, respectively (Fleck et al. 2006). Group
comparisons revealed greater activation in the OFC and
dorsal ACC, in adults than in adolescents, when making
risky selections. Furthermore, reduced activity in these
areas correlated with greater risk-taking performances
in adolescents and in the combined group. These data
show that adolescents engage prefrontal regulatory
structures to a lesser extent than adults when making
risky economic choices.
Another study (Galvan et al. 2006) examined the
development of neural correlates of reward-seeking
behaviors. 37 participants (7-29 years of age) underwent
fMRI while performing a task that manipulated reward
values. The results show exaggerated nucleus
accumbens activity relative to PFC activity, in
adolescents compared to children and adults. Nucleus
accumbens activity in adolescents was similar to adults
in both extent of activity and sensitivity to reward
values, although the magnitude of activity was
exaggerated. In contrast, the extent of OFC activity in
adolescents looked more like children’s extent than the
adults’ extent, with less focal patterns of activity.
All these empirical results, at behavioral and
functional levels, confirm what suggested by
neuroanatomical studies, that is the OFC-limbic system
matures earlier than the cognitive-regulatory system,
Clinical Neuropsychiatry (2009) 6, 4
 Developmental psychopathologies and prefrontal cortex
becoming disproportionately activated relative to later
maturing top-down control system, and biasing the
adolescent’s action toward immediate over future gains.
Only when a cognitive-regulatory activity is well
functioning, the prefrontal activity is adequately
balanced between reward evaluation and cognitive
regulation. This maturational mismatch between
different portions of the PFC is deemed to be one of
the causes of affect dysregulation in adolescence, a
phenomenon that may be considered as an increased
vulnerability to mood disorders, in particular
depression. In the next paragraph are reviewed
neurocognitive studies on adolescent depression.
Executive Functions in Adolescent Major
Depression
While DLPFC-EF are reported within the average
range in adolescents with Major Depression (MD)
(Fravre et al. 2009), some recent studies, assessing
OFC-EF in internalizing developmental psycho-
pathologies, reported altered neural responses in choice
tasks with rewards varying in magnitude and
probability. For example, adolescents with MD exhibit
weaker neural response than control participants in OFC
during both anticipation/decision and reward-
processing phases of the task (Forbes et al. 2006).
Another study investigated reward-related decision
making within a longitudinal study of 221 11-year-old
boys, 25 of whom suffered of MD at age 10 or 11
(Forbes et al. 2007). Participants completed a behavioral
decision-making task varying probability and
magnitude of rewards. Under conditions involving a
high probability of winning, adolescents with MD failed
to distinguish between options involving small or large
possible rewards, while subjects with anxiety or
externalizing disorders at age 10 or 11 did not differ
from others in their reward-related decisions. Low
frequency of choosing the high-probability-large reward
option at age 11 predicted depressive disorders, anxiety
disorders, and depressive symptoms 1 year later.
Furthermore, reward-related decisions predicted later
depressive or anxiety disorders even when adjusting
for the continuity of such disorders and the presence of
concurrent externalizing disorders.
As reported in studies with adults with MD
(Epstein et al. 2006, Keedwell et al. 2005, Knutson et
al. 2008), the dysfunction of OFC-EF in adolescents
with MD is also suggested by the weak activation of
the striatum during reward anticipation and reward
outcome. As a matter of fact, striatum and OFC are
strictly connected in a subcortical- prefrontal network
and involved in reward processing (O’Doherty 2004).
In a recent study (Forbes et al. 2009) 15 adolescents
with MD disorder and 28 adolescents with no history
of psychiatric disorder, ages 8-17 years, underwent
fMRI while performing a guessing task involving
monetary reward. Participants also reported their
subjective positive affect in natural environments during
a 4-day cell-phone-based ecological momentary
assessment. Adolescents with major depressive disorder
exhibited less striatal response than healthy comparison
adolescents during reward anticipation and reward
outcome, but more response in dorsolateral and medial
Clinical Neuropsychiatry (2009) 6, 4
prefrontal cortex. Diminished activation in a caudate
region was correlated with lower subjective positive
affect in natural environments, particularly within the
depressed group.
These preliminary studies on OFC-EF in
adolescents with MD demonstrated the usefulness of a
neurocognitive approach to the study of psycho-
pathologies with adolescent onset: they gave prelimi-
nary experimental evidence that 1) adolescents with an
internalizing disorder like MD may often present a
dysfunction in reward processing; 2) the reduction of
the striatal reward system is directly related to the
reduction of positive affectivity (Diekhof et al. 2008,
Poletti 2008 for review). The link between an altered
reward processing and MD is of particular interest,
because of the high rate of mood disorders with an onset
during adolescence (Pine et al. 1998, Pine et al. 2002,
Salujia et al. 2004). Recently, some theoretical models
have been proposed to explain adolescent vulnerability
to depression. The “Social information processing
network” (SIPN: Nelson et al. 2004) proposed that
changes in social behaviors during adolescence are
related with the development of different neural
networks involved in the processing of social
information. These three neural networks develop along
different trajectories: in particular the affective node
(almost overlapping the subcortical limbic system and
the OFC), develops earlier than the cognitive regulatory
node, principally based on the PFC (Eluvatinghal et al.
2006, Lenroot and Giedd 2006). This maturational
mismatch implies that during adolescence there is a
temporal window of increased vulnerability to affective
dysregulation as the activation of the affective node is
not adequately counterbalanced by and controlled by
the PFC (Rubia et al. 2000), resulting in having
difficulty to modulate emotional reactions to social
stimuli (Yurgelun-Todd 2007). However, the SIPN
model of affect dysregulation does not provide an
explanation for the specific vulnerability of adolescents
to depression, considering that affective dysregulation
is an important clinical feature also of anxiety disorders
(Ladoucer et al. 2005) and somatoform disorders
(Waller and Scheidt 2006).
The dysregulated positive affect model (Forbes
and Dahl 2005) examined the relationship between
adolescent depression and the development of the
reward processing systems, framing depression as a
reduction in positive affectivity: the remodelling of
neural systems at the basis of reward processing could
result in an higher vulnerability to the dysregulation of
affect and could predispose to depression. An
advancement of these models on the relationship
between depression and representation of reward in
adolescence has been recently proposed (Davey et al.
2008). Brain development and the consequent cognitive
maturation allow adolescents to represent abstract and
complex rewards, for example found in complex
relationships: as a matter of fact the susceptibility to
peer pressure follows an inverted U-shaped curve, that
has its peak during adolescence, around age 14, and
declines thereafter (Gardner and Steinberg 2005,
Steinberg and Monahan 2007). The brain becomes able
to encode more complex rewards, while social changes
see adolescents become more sociable and engaged in
more complex social situations and relationships, that
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 Michele Poletti
are more instable and need to be more actively pursued.
All these changes lead to psychological changes
including an increased sensitivity to social relationships,
and the ability to see both themselves and the
relationships in a more extended temporal context
(Davey et al. 2008). How do these psychological
changes impact on reward system? Recent researches
have highlighted features of reward system that are
relevant to understand its role in depression: first,
dopaminergic reward system is activated by the
anticipation of rewards rather then their consummation
and by stimuli that predict rewards rather then rewards
themselves (Knutson et al. 2000, Schultz 1998);
secondly, the dopaminergic reward system responds to
novel, intermittent and unexpected rewards rather than
expected rewards where learning has already occurred
(O’Doherty et al. 2002), and transiently suppressed
when an expected reward is omitted (Hollerman and
Schultz 1998). Then the onset of depression during
adolescence may result from the frustration, or
omission, of highly anticipated social rewards involving
love, belonging to social groups and social agency
(Davey et al. 2008). The omission of expected rewards
may cause a prolonged suppression of the reward
system, resulting in a reduced positive affectivity: this
phenomenon, combined with other vulnerability factors
(environmental, cognitive and genetic: Yap et al. 2007)
may cause depression (Yap et al. 2008).
These theoretical models can be summarized and
integrated underlining that adolescents received an
increased stimulation by their environment and because
their cognitive abilities allow a widen temporal
perspective. This increased stimulation activates the
affective node, in particular the reward system, whose
activity is not counterbalanced by an adequate activity
of the regulatory node for a prolonged temporal
window. Adolescence represents a period of increased
potentialities but also increased vulnerabilities: if
complex social and future rewards become available,
this may increase the motivation to action; at the same
time, when adolescents fail to achieve these rewards
(generating frustration and disappointment, and a
prolonged suppression of reward system) or when
rewards overwhelm the affective node, they may
develop internalizing psychopathologies like MD.
Executive Functions in Attention Deficit/
Hyperactivity Disorder
Attention Deficit/Hyperactivity Disorder (ADHD)
is here taken as a paradigmatic example of externalizing
developmental psychopathology. ADHD is considered
to have a strong biological aetiology (Swanson et al.
2007): for example, neuroimaging studies reported a
reduced volume of PFC (Yeo et al. 2003), whose
morphology is related to behavioral phenotypes of
subjects affected by this psychopathology (Dickstein
et al. 2006). Neurocognitive approaches to ADHD
focused on the presence of executive deficits: a poor
inhibitory control on internal and external interferences
has been proposed as primary deficit, leading to
secondary difficulties of working memory, motivation
and affect regulation, those abilities that enable goal-
directed behaviors (Barkley 1997, 2004; Dobler et al.
160
2005; Halperin and Schulz 2006; Sergeant 2000).
Globally, these studies identified in the poor inhibitory
control, specially at a motor level, the core deficit of
ADHD. Inhibitory control is a EF based on the right
inferior PFC (Aron et al. 2004) and several studies
reported that the developmental curve of this function
ends around 14-15 years of age, when performance in
inhibitory tasks become similar to those of adult
subjects (Romine and Reynolds 2005). A recent meta-
analysis put many doubts on the efficacy of the
inhibitory control deficit to describe cognitive deficits
of all ADHD subjects, highlighting the phenotypical
heterogeneity of this clinical population (Lijffjt et al.
2005): as a matter of fact, an inhibitory deficit is
reported in many studies but it could be explained also
by impairments of other functions active during the task
(Martinussen et al. 2005). Another meta-analysis
(Wilcutt et al. 2005), examining results from 83 studies
on EF in ADHD, for a total amount of 6700 subjects,
reported that the only robust finding across studies is a
spatial working memory deficit: the hypothesis of a
common inhibitory deficit in ADHD is not confirmed
(Bitaskou et al. 2008).
To better describe the heterogeneity of per-
formances of ADHD subjects, it has been recently
proposed that executive dysfunction is related to the
attention deficit but not to the hyperactivity/impulsivity
trait (Diamond 2005, Nigg 2005, Stefanatos and Baron
2007). A better description of different ADHD
phenotypes involves an inhibitory control deficit and a
delay aversion (Johansen 2009, Solanto et al. 2001).
Delay aversion indicates the preference for immediate
over delayed rewards and is measured by decision tasks
in which subjects choose between small immediate and
large delayed rewards (Bitsakou et al. 2006, Muller et
al. 2006). Choices of the small immediate reward (that
is delay aversion) are uncorrelated with inhibitory
difficulties, suggesting that inhibitory deficits and delay
aversion in ADHD are dissociable processes: so
performances on either tasks are only moderately
associated with ADHD but together correctly classify
nearly 90% of children and adolescents with ADHD
(Sonuga-Barke et al. 2003).
In order to explain the presence of these dissociable
behavioral characteristics in ADHD subjects, it has been
recently proposed that inattention reflects a deficit of
DLPFC-EF (inhibitory control and spatial working
memory) (Martel et al. 2007), while hyperactivity/
impulsivity symptoms reflect a deficit of OFC-EF
(delay aversion): this approach gives rise to the
possibility that some subjects with ADHD manifest
primarily a DLPFC-EF dysfunction, some subjects
manifest mainly a OFC-EF deficit, whereas others
manifest both types (Castellanos et al. 2006). For
example, it has been reported that a risky decision-
making style in the IGT, taken as an index of OFC-EF,
is associated with hyperactivity/impulsivity symptoms
but not with inattentive symptoms in adolescents with
ADHD (Toplak et al. 2005).
In summary, whereas studies on cognitive
dysfunction in ADHD have mostly focused on DLPFC-
EF, the presence of impairments in incentive,
motivational and reward-related processing based on
the OFC suggested that both these types of EF may
present deficits and deserve attention during the
Clinical Neuropsychiatry (2009) 6, 4
 Developmental psychopathologies and prefrontal cortex
assessment (Sonuga-Barke et al. 2008). As a matter of
fact, these dissociable deficits continue to differently
influence behavioural performance of ADHD subjects
also during young adulthood, for example making
distinct contributions to academic skill difficulties
(Thorell 2007).
Discussion
Longitudinal MRI studies have shown that, during
adolescence, the human cerebral cortex undergoes a
period of marked maturation. This phenomenon is
particularly evident in the PFC, one of the latest cortical
areas to mature and to reach its definitive shape, at the
beginning of adulthood. Brain development supports
cognitive and affective maturation of adolescents, leading
them towards an adult way of thinking and behaving.
These cognitive and affective correlates of brain
development are framed within a prefrontal system-
approach, that distinguishes DLPFC-EF and OFC-EF.
DLPFC sustains a cognitive elaboration of information,
while OFC, due to its strong connections with limbic
structures, sustains an interaction between cognition and
emotion, motivating goal-directed behaviors.
The applicability of this framework is demon-
strated by studies on healthy adolescents. OFC-EF and
DLPFC-EF mature at different rates: there is some
evidence that the maturation of these regions may take
place along somewhat different timetables (Lenroot and
Giedd 2006), with performance on exclusively OFC
tasks reaching adult levels earlier than performance on
exclusively DLPFC tasks (Hooper et al. 2004, Romine
and Reynolds 2005).
Also studies on developmental psychopathologies
highlighted the usefulness of this theoretical framework.
Studies on ADHD adolescents demonstrated that
different symptoms are related to different executive
deficits: the dysfunction of OFC-EF, evidenced by a
delay aversion, is related to hyperactivity/impulsivity
symptoms, while the dysfunction of DLPFC-EF,
evidenced by deficits in inhibitory control and in spatial
working memory, is related to inattentive symptoms.
Studies on adolescents with MD revealed a dysfunction
of OFC-EF, in particular reward processing. Recent
models attempted to explain the specific relationship
between an altered reward processing and the increased
vulnerability to depression in adolescents, highlighting
that adolescence involves the management of more
complex and social rewards than in infancy: if on the
one hand this phenomenon raises motivation to action,
on the other side it may temporarily suppress the reward
system if rewards are not reached or overwhelms reward
system, leading to an affect dysregulation.
This review provided evidence that a framework
that distinguishes DLPFC-EF and OFC-EF fits to
describe cognitive and affective correlates of adolescent
brain development, and to characterize cognitive and
emotional processing dysfunctions at the basis of some
developmental psychopathologies.
Clinical implications
The evidence about a dysfunctional executive
Clinical Neuropsychiatry (2009) 6, 4
processing related to different developmental
psychopathologies like MD and ADHD offers a new
perspective to clinical assessment. First, in clinical
practice the measurement of EF may indirectly suggest
the level of functional impairment due to a
developmental psychopathology. This information,
matched with other information available to clinicians,
may help in the diagnostic phase and in the planning of
a therapy or of a rehabilitation program. Second, the
assessment of EF could be used to evaluate the effects
of therapeutic/rehabilitative interventions at the end of
treatments and in follow-up phases. Referring in
particular to psychopathologies examined in this paper,
interventions for MD may be usually pharmacological
(Tsapakis et al. 2008), psychotherapeutic (Watanabe et
al. 2007, Weisz et al. 2006) or either. It’s possible to
hypothesize that an improvement of mood due to the
therapy may go with an improvement of performances
in tasks sensitive to EF and this finding could be
considered as an indirect index of the beneficial effects
of the treatment. For what concerns ADHD, the finding
that this psychopathology is related to specific EF
dysfunction not only offers a way to assess possible
beneficial effects of treatments, but also suggests the
possibility to plan interventions alternative or integrated
to the pharmacological one. As a matter of fact,
preliminary attempts to rehabilitate subjects with
ADHD have been focused on possible beneficial effects
of a cognitive training of those EF that have been shown
as impaired in this clinical population, in particular
working memory (Klingberg et al. 2002, 2005). For
example these studies found that a brief, intensive trai-
ning of working memory not only improved working
memory performances, but also improved performances
of other non-trained EF (planning, inhibition) and had
beneficial effects at a behavioral level (reduction of
number of head movements).
Future directions
Future studies have to investigate the different
functioning of these two types of EF in other
developmental psychopathologies, specially those that
in adulthood are characterized by an executive deficit
and an affect dysregulation, for example Obsessive
Compulsive Disorder (Chamberlain et al. 2008) and
Borderline Personality Disorder (Kunert et al. 2003).
Considering that adolescents with internalizing
disorders present a dysfunction of OFC-EF, it could be
interesting to investigate if, conversely, subjects with
externalizing disorders like Conduct Disorder and
Oppositional Defiant Disorder present a dysfunction
of DLPFC-EF. Preliminary studies suggested that a
deficit of inhibitory control, specially of motor
responses, is more frequent in adolescents with Conduct
Disorder (Herba et al. 2006) and substance abuse (Nigg
et al. 2006) than in healthy age-matched controls.
It could then be hypothesized that a dysfunction
of OFC-EF is involved in internalizing disorders and a
dysfunction of DLPFC-EF is involved in externalizing
disorders. Interestingly ADHD could be considered a
disorder at the intersection of these different clinical
conditions (Swanson et al. 2007), whose subtypes
present different executive deficits within this DLPFC-
161
 Michele Poletti
OFC framework. By this perspective, there is a need of
further attention to the assessment of executive
functioning in those adolescents that present co-
occurrence disorders (Boylan et al. 2007, Wolff and
Ollendick 2006), for example Conduct Disorder and
Major Depression.
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