Literature Review on Sulcal Tracing: Background Information

Marisa Patti

Significance of the Orbital Frontal Cortex

The orbitofrontal cortex (OFC) found on the ventral side of the
frontal lobe (Kringelbach, 2005; Rolls and Grabenhorst, 2008;
Takayanagi et al. 2010) of the human brain is of unique interest to
those in the neurodevelopmental disorder research community. The
OFC itself is significant for its sensory integration, emotional
processing, evaluation of reinforcers, expectation, motivation, decisionmaking, goal directed behavior, (Ongur and Price, 2000; Kringelbach,
2005; Gottfried et al., 2003; Holland and Gallagher, 2004; Walton et al.,
2004; Nakamura et al. 2007; Chakirova et al. 2010; Haas, 2001;
Kringelbach, 2005; Murray et al., 2007; Rolls and Grabenhorst, 2008;
Takayanagi et al. 2010; Kringelbach, 2005). Specifically for those
interested in its significance in neurodevelopmental disorders, the OFC
has important functions in codifying individual social behaviors,
suggesting individual differences in the OFC may lead to varied and
personalized social behaviors(Nakamura et al. 2007). These
individualized behaviors may be due to the unique differences in
sulcogyral morphology (Chakirova et al. 2010). However, alterations to
the OFC have been linked to illness (Chakirova et al. 2010), specifically
psychiatric disorders including schizophrenia (Jackowski et al., 2012;
Kawasaki et al., 2004; Nakamura et al., 2008; Takayanagi et al., 2010;
Lavoie et al. 2014). Such known alterations include abnormal leftward
sulcal patterns of the anterior cingulate cortex (Ycel et al., 2002; Le
Provost et al., 2003; Fujiwara et al., 2007; Takayanagi et al. 2010). OFC
abnormalities are thought to be the cause of impaired functioning,
increasing the individuals likeliness to exhibit abnormal social
behaviors including withdrawal, depression, instability, and general
socially inappropriate behavior (Chakirova et al. 2010). When
specifically considering the abnormalities in the sulci of the OFC, it
should be considered that the way in which the folding of the sulci
occur can affect long term cognitive domains (Liu et al., 2011; Lavoie
et al. 2014). In order to determine if such abnormalities of the OFC are
related to the development of psychiatric disorders, the variability of
individualized sulcalgyral morphology must be quantified and further
analyzed (Chiavaras et al. 2001).

Architecture of the OFC

Although variations in the OFC exist, there are some
consistencies found throughout human brains. Within the varying
architecture of the OFC, a general trend was found showing that

variability increased when moving medially to laterally (Chiaveras et

al. 2001). Within each hemisphere of the OFC there should be four
sulci, the olfactory, the medial, the lateral, and the transverse
(Chiaveras et al. 2001), dividing the OFC into five major gyri, the gyrus
rectus, the medial orbital gyrus, the anterior and posterior orbital gyri,
and the lateral orbital gyrus (Chiavaras and Petrides, 2000; Chiavaras
et al. 2001). The olfactory sulcus is most medial, followed by the
medial (MOS) and lateral (LOS) sulci found in the center of the OFC
running anteriorly to posteriorly, the transverse sulci is found in
between the MOS and the LOS and runs horizontally (Chiavaras and
Petrides, 2000; Chiaveras et al. 2001). The consistency necessary to
analyze the architecture of individual brains was based off the The
Talairach atlas, which uses a coordinate system to identify
morphological landmarks (Talairach and Tournoux, 1998; Chiaveras et
al. 2001).

Sulci of the OFC

Of the three sulci mentioned, MOS, LOS, and TOS found in both
the left and right hemispheres, noticeable patterns can be consistently
distinguished (Chiavaras and Petrides, 2000; Chiaveras et al. 2001).
Three patterns in particular have been identified and used consistently
in several studies, including a fourth pattern found and used in one
study. The sulcal patterns can be identified individually for each
respective hemisphere, and are based on the continuity of the MOS
and LOS sulci (Nakamura et al. 2007). The pattern types are considered
to be H-shaped based on the morphology of the sulci (Duvernoy,
1999; Chiavaras and Petrides, 2000; Nakamura et al. 2007). Type I is
identified by a break in the continuity of the MOS while the LOS stays
consistent, Type II occurs when both the MOS and LOS remain
continuous, and Type II occurs when both the MOS and LOS have
breaks in their continuity (Nakamura et al. 2007; Chiavaras and
Petrides, 2000; Chiaveras et al. 2001).
Normal V. Abnormal Patterns in the OFC
Differences within the OFC and thus sulci patterns have been
observed between those with neurodevelopmental disorders and those
that are typically developing (Baxter et al., 1987, 1988; Nordahl et al.,
1989; Benkelfat et al., 1990; Insel, 1992; Swedo et al., 1992; Rauch et
al., 1994, 1995; Chiavaras et al. 2001). Broadly, the OFC of individuals
with schizophrenia was found to be smaller in volume than the OFC of
typically developing, healthy individuals (Gur et al., 2000; Convit et al.,
2001; Nakamura et al. 2007). However, MRI studies have found varied
results, suggesting that the OFC volume of those with schizophrenia

may be greater than, equal to, or less than healthy controls. (Gur et al.,
2000; Convit et al., 2001; Chemerinski et al., 2002; Kawasaki et al.,
2004; Suzuki et al., 2005; Kim et al., 2007; Nakamura et al., 2008;
Venkatasubramanian et al., 2008; Baar et al., 1999; Crespo-Facorro et
al., 2000; Yamasue et al., 2004; Shad et al., 2006; Sapara et al., 2007;
Lacerda et al., 2007; Tahakanagi et al. 2010). Although volume of the
OFC using MRI has yielded inconsistent findings, differences in the sulci
patterns of healthy individuals and those with schizophrenia has been
consistent (Kikinis et al., 1994; Nakamura et al. 2007).

Normal V. Abnormal Sulcal Patterns

The distribution of the three commonly used sulcal patterns was
found to be statistically significant when comparing healthy controls to
those with schizophrenia (Takayanagi et al. 2010). The differences
between the sulcal patterns of healthy controls and schizophrenia
patients observed suggest that such patterns can be potentially used
as vulnerability markers for future patients (Brewer et al., 2001, 2003;
Turetsky et al., 2009b; Kamath et al., in press; Takahashi et al. 2014).
Although it is important to consider the sulci patterns in both
hemispheres, it was found that there was more variation in sulcal
patterns in the right hemisphere than the left when comparing normal
controls to individuals with schizophrenia. (Lavoie et al. 2014;
Takayanagi et al. 2010). Although some evidence suggests that
abnormal sulcal patterns may be used as an early diagnostic marker
for schizophrenia, it should be noted that the patterns themselves
might just be related to the vulnerability of an individual developing
schizophrenia, rather than a marker of diagnosis (Yucel et al., 2003;
Lavoie et al 2014). This is based off of the inconsistent attempts to find
significant relationships between sulcal patterns and
neurodevelopmental disorders (Lavoie et al. 2014; Whittle et al. 2013).
Type I, II, and III Sulcal Pattern Significance
The first type of sulcal pattern is associated with significantly higher
IQ scores, higher WAIS-III perceptual organization index, and overall
better cognitive performance than the other types of sulcal patterns
(Nakamura et al. 2007). Healthy controls were more likely to show
expression for Type I than Type II or III (Nakamura et al. 2007;
Takayanagi et al. 2010). The combination of Type I and Type I sulcal
pattern was most commonly found in both hemispheres of healthy
controls, and for those controls who did not , they had at least one
Type I pattern (Lavoie et al 2014). Type I was also found to be common
in those who were at high risk for developing schizophrenia who did

not transition than those who did (Lavoie et al. 2014; Takayanagi et al.
2010). It is important to note that a Type I pattern was found to be
significantly common in healthy controls, and found to specifically be in
the right hemisphere (Lavoie et al. 2014). This is supported by
researching findings showing that those at high risk for developing
schizophrenia who had a Type I pattern in their right hemisphere did
not go on to develop schizophrenia versus those who were at high risk
who did not have a Type I pattern in their right hemisphere (Lavoie et
al. 2014). It is currently unknown weather the absence of a Type I
sulcal pattern, specifically in the right hemisphere, suggests
vulnerability to schizophrenia development, or if the presence of a Type
I pattern suggests a protective quality for future schizophrenia
development (Lavoie et al 2014).
The second type of sucal pattern was found to be associated with
higher levels of perception and working memory, as well as positive
emotionality in healthy controls (Nakamura et al. 2007). Type II was
found to be the next most common sulcal pattern in healthy controls
after Type I (Nakamura et al. 2007;Chakirova et al. 2010).
Of all the patterns, Type III was found to be the most common in
those with schizophrenia (Nakamura et al. 2007). This pattern is
associated with individuals with poor socioeconomic status, poorer
cognitive function, increased impulsivity, and psychotic symptoms
(Nakamura et al. 2007; Chakirova et al 2010; Takayanagi et al. 2010).
Of those with a Type III sulcal pattern, it was found that mostly with a
Type III pattern on their right hemisphere went on to develop
schizophrenic symptoms (Chakirova et al 2010). Some studies suggest
that in schizophrenic patients, Type I was the least common sulcal
pattern to be seen in the right hemisphere and Type III was the most
common (Nakamura et al., 2007, 2008; Lavoie et al 2014). Other
studies found no significant difference between the controls and
patients when evaluating the patterns of the right hemisphere
(Chakirova et al., 2010; Bartholomeusz et al., 2013; Lavoie et al
2014).It is still unclear if it is the presence of Type III or the absence of
Type I which may be related to the schizophrenic phenotype, so the
presence of a Type III pattern may be a risk factor for schizophrenia
(Nakamura et al. 2007; Chakirova et al. 2010; Lavoie et al. 2014).
One study included a fourth sulcal pattern in their research. A Type
IV sulcal pattern was identified in individuals who had a continuous
MOS and a disconnected LOS (Chakirova et al 2010). It was noted that
this pattern was the most rare out of all the other patterns codified
(Chakirova et al 2010).
Differences in Sulcal Characteristics

Although sulcal depth does change with age, differences in sulcal

characteristics were shown to occur between healthy individuals and
schizophrenic patients as well as those with olfactory dysfunction, and
other neurodegenerative diseases (Wang et al., 2011; Mesholam et al.,
1998; Takahashi et al 2014). Changes in sulcal patterns were shown to
occur; however, sulcal patterns will not change after birth (Lavoie et al.
2014). It was also found that there were differences in sulcal length
measurement between healthy populations and those with
schizophrenia (Nakamura at al. 2007). In addition to length, sulcal
depth was also found to differ between healthy populations and those
with schizophrenia (Takahashi et al. 2014). Schizophrenic patients
tended to have more shallow sulci than normal healthy individuals, the
sulci even showed to become shallower as schizophrenic symptoms
progressed (Takahashi et al. 2014). When considering sulcal depth
between hemispheres, it was found that sulci in the right hemisphere
was deeper than the left for both healthy individuals and individuals
with schizophrenia (Takahashi et al 2014). Sulcal depth was found to be
shallower in those with schizophrenia who were not on medications,
suggesting that abnormalities in sulcal depth may be an early marker
for schizophrenic symptoms (Turetsky et al., 2009a; Takahashi et al.,
2013a,b; Brewer et al., 2001, 2003; Turetsky et al., 2009b,
2012;Takahashi et al. 2014).
Developmental Significance
The development of sulcal patterns termed gyrogenesis (Rakic,
1988; Armstrong et al., 1995; Nakamura et al. 2007) occurs during
gestation (Chiaveras et al. 2001). OFC sulci variability occurs during
brain development and progresses mediolaterally, with the olfactory
sulcus developing first, the MOS second, and the LOS developing the
latest (Chiaveras et al. 2001). Considering that sulcal patterns develop
early in life, it is likely that the abnormal sulcal patterns seen in those
with schizophrenia as a marker of the illness before symptoms are
expressed (Chakirova et al. 2010). The folding of the sulci is completed
before birth and shortly after will not change throughout life (Chi et al.,
1977; Worthen et al., 1986; Armstrong et al., 1995; Takayanagi et al.
2010; Chi et al., 1977; Lavoie et al. 2014). It is suggested that if
gyrogenesis or sulcal depth development is disrupted during
development, schizophrenic symptoms may manifest later in life
(Fatemi and Folsom, 2009; Takahashi et al. 2014; Abolmaali et al.,
2002; Hummel et al., 2003; Takahashi et al 2014). Although it is
currently unclear, it is suggested that psychotic phenotypes may be
caused by abnormalities of the sulci in early development and that
such patterns are most likely not due to the progression of illness
(Takahashi et al. 2014).

General Conclusions
The orbital frontal cortex of the human brain is associated with
social behaviors, making this region one of particular interest when
looking for abnormalities in those with neurodevelopmental disorders,
specifically schizophrenia. Abnormalities to consider may be seen in
sulcal patterns or other sulcal characteristics. Sulcal patterns are
identified by the continuity of the MOS, LOS and transverse sulci within
the OFC. Three main patterns were identified, Type I, Type II, and Type
III. Type I was most commonly found in healthy controls whereas Type
III was most commonly seen in patients with schizophrenia. It was
specifically noted that the absence of Type I and the presence of Type
III seen in those with schizophrenia was seen in the right hemisphere
more often than the left. Other variations in sulci seen were variations
in sulci length and depth. These variations were also seen more often
in the right hemisphere of those with schizophrenia. Although it is
currently unclear, these differences in sulci may develop early in life
before the onset of illness. This suggests that abnormalities can be
identified earlier in life and may provide an early marker for
schizophrenia before the onset of illness.

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