 8. The Neurobiology of Personality  199
The primary cortical component of the 
reward system is the medial OFC (mOFC), 
a region involved in monitoring the reward 
value of stimuli through integration of he -
donic and sensory information (Berridge 
& Kringelbach, 2008). Several structural 
MRI studies have detected positive associa -
tions of extraversion with volume of mOFC 
(Cremers et al., 2011; De  Young et al., 2010; 
Omura, Constable, & Canli, 2005), though 
other large studies have failed to replicate 
this result (Bjørnebekk et al., 2013; Liu et 
al., 2013; Riccelli et al., 2017), and one 
found the effect in women but an opposite 
effect in men (Li et al., 2014). Two addi -
tional studies that successfully replicated 
the effect are notable because, unlike the 
other studies cited, they tested associations 
with the mOFC as an a priori region of in -
terest, thus increasing power dramatically 
by avoiding testing the whole brain (Grodin 
& White, 2015; Uro Šević, Collins, Muetzel, 
Lim, & Luciana, 2012). (Tests across the 
whole brain require correcting significance 
levels for a great many individual statistical 
tests.) Additionally, Uro Šević et al. found 
that baseline mOFC volume predicted in -
creases in extraversion over a 2-year period 
in adolescence. Some evidence from func -
tional imaging also implicates the mOFC 
in extraversion, with one study finding that 
extraversion predicted greater functional 
connectivity between mOFC and other 
brain regions when making decisions about 
rewards, and another showing a correlation 
between extraversion and glucose metabo -
lism in mOFC while at rest (Civai, Hawes, 
De Young, & Rustichini, 2016; Volkow et 
al., 2011).
A few structural and functional studies 
suggest that the amygdala might be impli -
cated in extraversion, presumably because 
of its involvement in the salience of reward -
ing stimuli. Two studies indicated associa -
tions between amygdalar volume and ex -
traversion, though one of these was in the 
left amygdala and the other was in the right 
(Cremers et al., 2011; Lewis et al., 2014), 
whereas another found no association 
(Cherbuin et al., 2008). A study of function -
al connectivity found that extraversion was 
correlated with connectivity between the 
amygdala and other regions of the reward 
network (Aghajani et al., 2013).Neuroticism
Neuroticism  describes the tendency to ex -
perience all forms of negative emotion— 
anxiety, stress, depression, anger, irritability, 
insecurity, panic, and so forth. Widespread 
agreement exists that neuroticism reflects 
variation in the biological systems governing 
defensive responses to threat, punishment, 
and uncertainty (Allen & De  Young, 2017; 
Shackman et al., 2016). In Gray’s reinforce -
ment sensitivity theory, neuroticism was hy -
pothesized to reflect the joint sensitivity of 
the two major defensive systems, the behav -
ioral inhibition system (BIS) and the fight– 
flight–  freeze system (FFFS; Gray & Mc -
Naughton, 2000). The BIS controls response 
to threats in the form of conflicts between 
goals, most often approach–  avoidance con -
flicts (e.g., wanting to approach a potential 
mate, but also wanting to avoid rejection). 
When conflict or uncertainty is detected, 
the BIS increases passive avoidance, involv -
ing heightened anxiety, increased vigilance 
and rumination, and inhibition of approach 
behavior. The FFFS, in contrast, is sensitive 
to situations in which one’s only motivation 
is to escape or eliminate a threat, and it trig -
gers active defensive responses, such as pan -
icked flight or defensive anger. At the core of 
the BIS, neuroanatomically, are medial tem -
poral lobe structures, including the hippo -
campus and amygdala, whereas at the core 
of the FFFS are structures in the midbrain 
and brainstem, including the hypothalamus 
and periaqueductal grey (though the amyg -
dala is involved in the FFFS as well, and the 
two systems interact closely). Research on 
the neural correlates of neuroticism largely 
confirms these associations, while also im -
plicating several cortical regions that regu -
late the subcortical structures associated 
with the BIS and FFFS.
Neuroticism is the largest risk factor for 
most mental disorders and hence has re -
ceived more neuroscientific attention than 
other Big Five traits (Lahey, 2009). The 
brain structure most frequently linked to 
neuroticism is the amygdala, an almond- 
shaped cluster of nuclei located subcorti -
cally. The amygdala orchestrates vigilance 
in response to relevant information, includ -
ing reallocation of attention and arousal of 
the sympathetic nervous system. (We use 