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c o r t e x x x x ( 2 0 1 4 ) 1e9

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Special issue: Research report

Emotional detachment in psychopathy:Involvement of dorsal default-mode connections

Arjun Sethi a,b,*, Sarah Gregory b, Flavio Dell'Acqua a,Eva Periche Thomas a, Andy Simmons c, Declan G.M. Murphy b,Sheilagh Hodgins d, Nigel J. Blackwood b,1 and Michael C. Craig a,b,1

a NatBrainLab, London, UKb Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, London, UKc NIHR Biomedical Research Centre for Mental Health, Institute of Psychiatry, King's College London, London, UKd Department de Psychiatrie, Universite de Montreal, Canada

a r t i c l e i n f o

Article history:

Received 29 November 2013

Reviewed 31 March 2014

Revised 3 July 2014

Accepted 28 July 2014

Published online xxx

Keywords:

Psychopathy

Emotional detachment

Default-mode network

Cingulum

Diffusion MRI

* Corresponding author. NatBrainLab, Deparpigny Park, London, SE5 8AF, UK.

E-mail address: arjun.sethi@kcl.ac.uk (A.1 Joint last authors.

Please cite this article in press as: Sethi, Aconnections, Cortex (2014), http://dx.doi.

http://dx.doi.org/10.1016/j.cortex.2014.07.0180010-9452/© 2014 Elsevier Ltd. All rights rese

a b s t r a c t

Criminal psychopathy is defined by emotional detachment [Psychopathy Checklist e

Revised (PCL-R) factor 1], and antisocial behaviour (PCL-R factor 2). Previous work has

associated antisocial behaviour in psychopathy with abnormalities in a ventral temporo-

amygdala-orbitofrontal network. However, little is known of the neural correlates of

emotional detachment. Imaging studies have indicated that the ‘default-mode network’

(DMN), and in particular its dorsomedial (medial prefrontal e posterior cingulate)

component, contributes to affective and social processing in healthy individuals.

Furthermore, recent work suggests that this network may be implicated in psychopathy.

However, no research has examined the relationship between psychopathy, emotional

detachment, and the white matter underpinning the DMN. We therefore used diffusion

tensor imaging (DTI) tractography in 13 offenders with psychopathy and 13 non-offenders

to investigate the relationship between emotional detachment and the microstructure of

white matter connections within the DMN. These included the dorsal cingulum (containing

the medial prefrontal e posterior cingulate connections of the DMN), and the ventral

cingulum (containing the posterior cingulate e medial temporal connections of the DMN).

We found that fractional anisotropy (FA) was reduced in the left dorsal cingulum in the

psychopathy group (p ¼ .024). Moreover, within this group, emotional detachment was

negatively correlated with FA in this tract portion bilaterally (left: r ¼ �.61, p ¼ .026; right:

r ¼ �.62, p ¼ .023). These results suggest the importance of the dorsal DMN in the emotional

detachment observed in individuals with psychopathy. We propose a ‘dual-network’

model of white matter abnormalities in the disorder, which incorporates these with pre-

vious findings.

© 2014 Elsevier Ltd. All rights reserved.

tment of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, 16 De Cres-

Sethi).

., et al., Emotional detachment in psychopathy: Involvement of dorsal default-modeorg/10.1016/j.cortex.2014.07.018

rved.

c o r t e x x x x ( 2 0 1 4 ) 1e92

1. Introduction

Criminal psychopathy is characterised by antisocial behav-

iour and a constellation of affective and interpersonal traits

including callousness, shallow affect, and manipulativeness

(R. D. Hare, 1991). These behavioural characteristics have a

significant negative impact on society. For instance, in-

dividuals with psychopathy constitute approximately 15e20%

of the prison population, and commit a disproportionate

number of violent and recidivistic offences (Hart & Hare, 1997;

Hemphill, Hare, & Wong, 1998) that cost the USA over $460

billion a year (Kiehl & Hoffman, 2011). It has been proposed

that psychopathy is a disorder of the ‘paralimbic’ system

(Kiehl, 2006), including structures such as the amygdala and

ventromedial prefrontal cortex (Blair, 2008).

Investigation into the neural basis of psychopathy has

been facilitated by the development of in vivo brain imaging

and reliable, well-validated, instruments that permit quanti-

fication of specific traits and behavioural tendencies. Factor

analysis of these traits, using the Psychopathy Checklist e

Revised (PCL-R), suggests that they can be divided into di-

mensions of ‘emotional detachment’ (factor 1) and ‘antisocial

behaviour’ (factor 2) (Hare, 1991, 2003; Hare et al., 1990; Harpur,

Hakstian,&Hare, 1988; Harpur, Hare,&Hakstian, 1989). Factor

2 antisocial scores have been reported to be negatively

correlated with the microstructure of the right uncinate

fasciculus (Craig et al., 2009), a ventral limbic tract connecting

the anterior temporal cortex and amygdala with orbitofrontal

regions (Catani & Thiebault De Schotten, 2012). The relation-

ship between psychopathy/antisocial behaviour and the un-

cinate has since been confirmed (Motzkin, Newman, Kiehl, &

Koenigs, 2011; Sundram et al., 2012). Moreover, the associa-

tion between specific regions within this network and psy-

chopathy and antisocial behaviour is supported by an

increasing number of neuropsychological (Blair, Colledge,

Murray, & Mitchell, 2001; Budhani & Blair, 2005; Budhani,

Richell, & Blair, 2006; Levenston, Patrick, Bradley, & Lang,

2000), lesion (Barrash, Tranel, & Anderson, 2000; Blair &

Cipolotti, 2000; Damasio, Grabowski, Frank, Galaburda, &

Damasio, 1994; Harlow, 1993, 1999; Kluver & Bucy, 1997;

Saver & Damasio, 1991), stimulation (King, 1961) and in vivo

brain imaging studies (Boccardi et al., 2011; Kiehl et al., 2001;

Raine, Buchsbaum, & LaCasse, 1997; Raine, Lencz, Bihrle,

LaCasse, & Colletti, 2000; Veit et al., 2002).

These prior studies have been important first steps in un-

derstanding psychopathy. However, antisocial behaviour is

not specific to psychopathic individuals (Harpur, et al., 1989;

Skeem & Cooke, 2010), and it is emotional detachment (fac-

tor 1) that differentiates psychopathic personality from the

broader diagnosis of Antisocial Personality Disorder. More-

over, emotional detachment in adults with psychopathy is

presumed to reflect a heritable developmental trajectory from

callous-unemotional traits in childhood (Barry et al., 2000;

Forsman, Lichtenstein, Andershed, & Larsson, 2008; Frick,

Kimonis, Dandreaux, & Farell, 2003; Frick & Viding, 2009;

Viding, Blair, Moffitt, & Plomin, 2005; Wootton, Frick,

Shelton, & Silverthorn, 1997). Investigating the neural corre-

lates of factor 1 traits is therefore likely to be of central

importance to understanding the neurodevelopment of

Please cite this article in press as: Sethi, A., et al., Emotional detaconnections, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.201

psychopathic personality. Mounting evidence suggests that

the ‘default-mode’ network (DMN) is linked to psychopathy,

and may be related to emotional detachment in the disorder.

The DMN is a subdivision of the limbic system that has

largely been associated with introspective and self-referent

processing (Gusnard, Akbudak, Shulman, & Raichle, 2001;

Johnson et al., 2006; Kelley et al., 2002). This network con-

sists of a set of regions that are active and functionally

intercorrelated under resting-state conditions (Raichle et al.,

2001). These include the posterior cingulate cortex (PCC), the

medial prefrontal cortex (mPFC), the medial temporal lobe

(MTL), and the angular gyrus (Fox et al., 2005; Fransson, 2005;

Raichle et al., 2001; Shulman et al., 1997). These regions are of

specific interest due to their overlap with areas involved in

affective processing (Kiehl et al., 2001; Maddock, Garrett, &

Buonocore, 2003). This network has also been strongly impli-

cated in social processing (Buckner, Andrews-Hanna, &

Schacter, 2008; Vollm et al., 2006) and moral judgement

(Greene, Sommerville, Nystrom, Darley, & Cohen, 2001;

Harrison et al., 2008). The DMN is therefore well placed to

play an important role in the profound emotional detachment

in psychopathy.

The relevance of the DMN to psychopathy is further sup-

ported by recent functional MRI studies that have reported

abnormal activation and connectivity within this network

among men with psychopathy (Glenn, Raine, & Schug, 2009;

Motzkin, et al., 2011; Pujol et al., 2011). Similarly, structural

imaging studies of both adults with psychopathy (Boccardi

et al., 2011; Ermer, Cope, Nyalakanti, Calhoun, & Kiehl, 2012;

Gregory et al., 2012; de Oliveira-Souza et al., 2008; Yang,

Raine, Colletti, Toga, & Narr, 2009) and boys with conduct

disorder and callous-unemotional traits (De Brito et al., 2009;

Rijsdijsk et al., 2010) have reported abnormal grey matter

volume in DMN regions. Importantly, a preliminary study has

reported that the degree of functional connectivity within a

network containing DMN regions was related to emotional

detachment in individuals with psychopathy (Juarez, Kiehl, &

Calhoun, 2012). These studies collectively point towards the

importance of the DMN in psychopathy, and perhaps

emotional detachment in particular. However, it is unknown

whether (i) previously observed functional differences in

psychopathy are associated with abnormalities in the white

matter anatomy of this network; (ii) whether any such dif-

ferences in this network are related specifically to emotional

detachment.

Direct white matter connections between the medial DMN

regions (Greicius, Supekar, Menon, & Dougherty, 2009) lie

within the cingulum, a long association tract which can be

subdivided into functionally and anatomically distinct por-

tions. For the purposes of this study, we identify two distin-

guishable portions: (i) the dorsal cingulum, connecting the

PCC to the mPFC, which is related to social and emotional

aspects of cognition; and (ii) the ventral cingulum, connecting

PCC to the MTL, which is involved in memory and spatial

orientation (Catani & Thiebault De Schotten, 2012).

In the current study we used DTI tractography to analyse

the dorsal and ventral cingulum in offenders with psychopa-

thy and age- and IQ-matched non-offenders. Based on prior

work, we hypothesised that surrogate indices of

chment in psychopathy: Involvement of dorsal default-mode4.07.018

c o r t e x x x x ( 2 0 1 4 ) 1e9 3

microstructure in these tract portions, and the dorsal segment

in particular, would be reduced in the psychopathy group and

that this would be correlated with factor 1 scores.

2. Methods and materials

2.1. Ethics and consent

This study was approved by the Camberwell St Giles NHS

research ethics committee (formerly the Joint South London

and Maudsley and the Institute of Psychiatry Research Ethics

Committee/South East London REC 4) (reference 06/Q0706/87).

Participants were fully informed of the study requirements

and risks and given the opportunity to ask any questions

before giving informed consent. This consent included

authorising members of the research group to access partici-

pants' official criminal records.

2.2. Participants

All participants were right-handed men who spoke English as

their first language and had a reading age of above 10 years

old. Participants had no history of significant head injury (i.e.,

leading to loss of consciousness for an hour or longer), no

neurological problems, or any significant visual or hearing

impairment. Patients had no history of claustrophobia or

other contraindications to MRI scanning as assessed by self-

report. Participants were also screened for psychiatric disor-

ders using the Structured Clinical Interview for the DSM-IV

(Spitzer, Williams, Gibbon, & First, 1992), and were excluded

if they had any lifetime history of Axis 1 major mental ill-

nesses, or any substance use disorders in the previousmonth.

Participants were also administered the Weschler Adult In-

telligence Scale (Weschler, 1997).

All offenders with psychopathy were recruited via the

National Probation Service, and had committed and been

incarcerated for at least one serious violent crime including

murder, attempted murder, rape, and serious assault.

Forensic psychologists assessed psychiatric, medical and

criminal history by preliminary screening with self-report

measures, probation files and probation officer reports.

Criminal records were retrieved from the Police National

Database.

The PCL-R (Hare, 1991) was conducted by forensic psychi-

atrists and psychologists. Interviews were videotaped, and

25% of these were randomly selected and rerated by a second

trained psychiatrist with a reasonable intraclass correlation

coefficient (ICC) for total PCL-R scores (.81). A PCL-R score of

�25 was used to define offenders as having psychopathy. The

cut-off of 25 has been used in accordance with previous work

(Craig et al., 2009; Gregory et al., 2012), and based on obser-

vations of cross-cultural differences in psychopathy (Cooke &

Michie, 1999). Healthy non-offenders were recruited via

bulletin boards in local unemployment offices and commu-

nity websites. These individuals did not meet the PCL-R �25

criteria for psychopathy, and had never been convicted of a

criminal offence.

Participants were encouraged to abstain from all substance

misuse for a period of twoweeks prior to the scan. Participants

Please cite this article in press as: Sethi, A., et al., Emotional detaconnections, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014

were required to have their saliva tested for alcohol use, and a

urine test to detect illicit drug use before the scanning session.

This revealed some offenders tested positive for substances,

despite being requested to refrain from substance use prior to

the scan. A forensic psychologist, and a member of the

research team (S.G.), assessed the participants to ascertain

their suitability to enter the scanning environment and

adhere to the safety protocol. Participants were reimbursed

for their time at the National Minimum Wage rate.

2.3. Scanning

Scanning was performed using a GE 1.5T Sigma Excite MRI

Scanner (actively shieldedmagnetic field gradients: max amp.

40 mTm�1) using a multi-slice doubly refocused spin echo EPI

sequence acquisition based on (Jones et al., 2002) using body

coil RF transmission and 8 channel head coil NMR reception.

60 contiguous near axial slices were acquired with

2.5 � 2.5 � 2.5 mm voxels. Acquisition had an echo time of

101.3 msec, with an effective repetition time of 12e20 RR in-

tervals (using cardiac gating). Amaximumdiffusionweighting

of 1300 sec mm�1 was used, and 64 diffusion-weighted brain

volumes with diffusion gradients uniformly distributed in

space were collected at each slice location, as well as 7 vol-

umes without diffusion weighting applied.

2.4. Analysis

Data was corrected for eddy currents and motion distortion,

and the diffusion tensor was estimated. Whole brain trac-

tography (step size: .5 mm; FA threshold: .2; angle threshold:

30�) was then performed using Euler integration (Basser,

Pajevic, Pierpaoli, Duda, & Aldroubi, 2000). Data was pro-

cessed using ExploreDTI. The dorsal and ventral cingulum

were identified and dissected on the axial plane (Fig. 1) and

tract-specific measures were extracted using TrackVis. The

cingulum was initially defined by one region of interest (ROI)

on the sagittal plane and dissected bilaterally, with an ROI at

the midline to exclude callosal fibres. The division between

the dorsal and ventral portions of the cingulum was defined

anatomically as the point above the splenium of the corpus

callosum on the midline slice. An exclusion ROI was used at

this slice, to exclude fibres of the ventral cingulum that

continued into the region defined as the dorsal cingulum.

Dissections were performed blind to diagnosis by amember of

the research team (AS), and then repeated by a second blinded

member independently (EPT).

Tract measures of fractional anisotropy (FA; an indirect

measure of fibre myelination and axonal integrity and orga-

nisation) and radial diffusivity (an ostensibly more specific

marker of fibre myelination) were examined for between

group differences using one-way ANOVA, and correlations

with PCL-R measures were assessed using Pearson's product-

moment (two-tailed) correlation in SPSS. To control for vari-

ables of no interest, we performed an ANCOVA analysis to

assess difference between the psychopathy and control group.

Dissection reliability was assessed using ICC analyses (two

way mixed absolute agreement model model) for FA mea-

surements in our tracts of interest.

chment in psychopathy: Involvement of dorsal default-mode.07.018

Fig. 1 e (a) Fractional anisotropy colour maps with overlaid ROI for the dorsal (green) and ventral (blue) cingulum. (b) DTI

tractography reconstruction of the dorsal (green) and ventral (blue) cingulum.

c o r t e x x x x ( 2 0 1 4 ) 1e94

3. Results

We compared 13 offenders with psychopathy (PCL-R ¼ 28 ± 2),

aged 40 ± 10 years, with full scale IQ 90 ± 12, to 13 non-

offenders (PCL-R ¼ 4 ± 3), aged 34 ± 9 years, with full scale

IQ 98 ± 13. The two groups did not significantly differ in age or

IQ.

One-way ANOVAs revealed that the psychopathy group

had significantly lower FA in the left dorsal cingulum [F (1,

24) ¼ 5.83, p ¼ .024] and ventral cingulum bilaterally [left: F (1,

24) ¼ 7.60, p ¼ .011; right: F (1, 24) ¼ 4.81, p ¼ .038] (Fig. 2). The

observed FA differences in the left dorsal cingulum FA

remained significant even after controlling for alcohol,

cocaine and cannabis dependency (as determined by the SCID;

Table 1) [F (1, 15) ¼ 5.78, p ¼ .030]. FA differences in the ventral

cingulum were no longer significant at p ¼ .05 [left: F (1,

15) ¼ 3.00, p ¼ .104; right: F (1, 15) ¼ 1.46, p ¼ .245]. Radial

diffusivity did not differ significantly between the groups in

either tract portion.

We also report a negative correlation between PCL-R factor

1 scores and FA in the left [r (11) ¼ �.61, p ¼ .026] and right [r

(11) ¼ �.62, p ¼ .023] dorsal cingulum within the psychopathy

group. Importantly, there was no relationship between factor

2 scores and dorsal cingulum FA, or between either factor and

ventral cingulum FA (Table 2).

Table 1 e Prevalence of substance use disorders within psychop

Drug % Dependency

Offenders with psychopathy N

Alcohol 40%

Cannabis 30%

Cocaine 30%

Stimulants 0%

Sedatives 0%

Opioids 10%

Hallucinogens 0%

Other 0%

N.B. Data incomplete for three participants from each group.

Please cite this article in press as: Sethi, A., et al., Emotional detaconnections, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.201

Finally, to assess reliability of these dissections we

employed ICC analyses (two way mixed absolute agreement

model), which showed high agreement between raters (AS &

EPT) in all tracts (Left dorsal cingulum FA: ICC ¼ .99, p < .001;

Left ventral cingulum FA: ICC ¼ .96, p < .001; Right dorsal

cingulum FA: ICC ¼ .99, p < .001; Right ventral cingulum FA:

ICC ¼ .93, p < .001).

4. Discussion

The results from this study extend our understanding of the

role of the paralimbic system in psychopathy. We suggest a

model of the disorder where the main diagnostic features are

at least partly dissociable at the network level. We previously

reported that antisocial behaviour (factor 2) in psychopathy is

associated with abnormalities in the microstructure of a

ventral ‘temporo-amygala-orbitofrontal’ network (connected

by the uncinate fasciculus) (Craig et al., 2009). The current

study extends that work, and suggests that emotional

detachment (factor 1) in psychopathy is associated with ab-

normalities in a different neural circuit e the dorsal ‘default-

mode’ network (Fig. 3). Such a relationship is also supported

by previous functional imaging studies in individuals with

psychopathy (Glenn et al., 2009; Juarez et al., 2012).

athy and non-offender groups.

Fischer's exact test p-value

on-offenders

0% 5.00 .087

10% 1.25 .582

0% 3.53 .211

0% e e

0% e e

0% 1.05 1.000

0% e e

0% e e

chment in psychopathy: Involvement of dorsal default-mode4.07.018

Fig. 2 e Differences in Fractional Anisotropy (FA) between individuals with psychopathy and non-offenders *p < .05.

c o r t e x x x x ( 2 0 1 4 ) 1e9 5

Our findings suggest that this relationship is specific to the

dorsal component of the DMN. This is consistent with func-

tions associated with this subdivision of the DMN. The mPFC

is involved in introspection and social function, including

emotional reflection (Gusnard et al., 2001), and evaluating self-

and other-emotional states (Ochsner et al., 2004). The PCC has

been observed to be responsive to emotional stimuli (Maddock

et al., 2003), and is also activated by evaluation of emotional

states (Ochsner et al., 2004). Collectively, these regions are

active during moral judgement (Greene et al., 2001; Harrison

et al., 2008), where they are understood to reflect ‘emotional

engagement’ with moral dilemmas (Greene & Haidt, 2002;

Greene et al., 2001). Similarly, both have also been observed

to be active during socio-affective processing [i.e., empathy

(Vollm et al., 2006)]. Abnormalities in such functions could

plausibly mediate emotional detachment in psychopaths.

Indeed, this is not only consistent with the nature of the traits

described by emotional detachment (e.g., lack of guilt, shallow

affect), but also with specific socio-affective (Blair, 2005;

Shamay-Tsoory, Harari, Aharon-Peretz, & Levkovitz, 2010)

and moral-affective (Koenigs, Kruepke, Zeier, & Newman,

2012) behavioural abnormalities observed in individuals with

psychopathy.

The selective relationship between emotional detachment

and the dorsal DMN also partially distinguishes the DMN

Table 2 e Psychopathy checklist revised correlations withfractional anisotropy in the dorsal and ventral cingulum.

Measure Pearon's r DF p

Factor 1

Left

Dorsal cingulum �.61 11 .026*

Ventral cingulum .08 11 .794

Right

Dorsal cingulum �.62 11 .023*

Ventral cingulum �.01 11 .979

Factor 2

Left

Dorsal cingulum �.01 11 .988

Ventral cingulum �.30 11 .322

Right

Dorsal cingulum �.14 11 .646

Ventral cingulum �.43 11 .146

*p < .05.

Please cite this article in press as: Sethi, A., et al., Emotional detaconnections, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.2014

abnormalities observed in psychopathy from those observed

in other psychiatric populations. DMN differences have, for

example, been observed in depression (Sheline et al., 2009),

attention deficit hyperactivity disorder (ADHD) (Castellanos &

Proal, 2012; Sonuga-Barke& Castellanos, 2007), dementias (Bai

et al., 2012; Filippi et al., 2013; Greicius, Srivastava, Reiss, &

Menon, 2004), schizophrenia (Koch et al., 2013), and autism

(Assaf et al., 2010). However, the contribution of the DMN has

been conceptualised differently in each of these disorders. For

example, in ADHD, it has been suggested that they reflect a

difficulty ‘switching’ between default-mode and fronto-

parietal control networks (Castellanos & Proal, 2012; Sonuga-

Barke & Castellanos, 2007). In Alzheimer's disease, dysfunc-

tion has been reported to be associated with the more ventral

PCC-MTL component of this network (Greicius et al., 2004),

thus disconnecting themedial temporalmemory system from

other regions.

In psychopathy, abnormalities in a dorsal subdivision of

the DMN associated with introspection and social, moral and

affective processing appear to contribute to emotional

detachment. This is consistent with autistic spectrum condi-

tions which exhibit a similar relationship to the DMN, with

social deficits related to dorsal mPFC and PCC subnetworks

(Assaf et al., 2010). Further work is however required to

Fig. 3 e The default mode network, connecting the mPFC

and PCC. The temporo-amygdala-orbitofrontal network

connecting the orbitofrontal cortex (OFC) and amygdala.

chment in psychopathy: Involvement of dorsal default-mode.07.018

c o r t e x x x x ( 2 0 1 4 ) 1e96

determine the exact contribution of overlapping functional

anatomical networks to these disorders and others, and how

differences in distinct sub networks and networkenetwork

interactions lead to the array of psychiatric manifestations

associated with the DMN. Such work is essential for refining

future neuroanatomical models of these disorders.

The proposed ‘dual network’ model of psychopathy sup-

ports a shift in the prevailing conceptualisation of psychopa-

thy, which has focused on differences within, and between,

the amygdala and orbitofrontal cortex (Blair, 2008). One of the

main limitations of this earlier model was that similar dif-

ferences had been reported in other, non-psychopathic, anti-

social populations (Hoptman et al., 2010; Sarkar et al., 2013;

Sundram et al., 2012). The current model can accommodate

these findings, and provide a putative explanation of the two

core features of criminal psychopathy. Although it is probable

that other regions/networks are relevant to psychopathy

(Juarez et al., 2012), findings from this study and others

strongly suggest the importance of the identified dorsal

(Ermer et al., 2012; Glenn et al., 2009; Gregory et al., 2012;

Juarez et al., 2012; Motzkin et al., 2011; de Oliveira-Souza

et al., 2008; Pujol et al., 2011; Yang et al., 2009) and ventral

(Blair, 2008; Craig et al., 2009; Motzkin et al., 2011) networks. In

summary, this dual network model suggests a differential

contribution of ventral and dorsal paralimbic sub-networks to

the discrete features of psychopathy.

The biological mechanism(s) underpinning these network

abnormalities are not yet clear, though they may reflect a

primary deficit in white matter maturation. FA increases with

age during the first two decades of life, and in some tracts

(including the cingulum and uncinate fasciculus) this process

is protracted over a longer period (Lebel, Walker, Leemans,

Phillips, & Beaulieu, 2008). Therefore, reduced FA in psychop-

athy could be related to an aberrantmaturational trajectory of

these limbic pathways. This is consistent with findings that

boys with conduct disorder and callous-unemotional traits

exhibit a divergent pattern of white matter development from

typically developing controls (De Brito et al., 2009). However,

white matter differences could also be secondary to develop-

mental changes within ventral and/or dorsal brain regions.

Furtherwork is needed to investigate these hypotheses, and to

characterise the aetiology of any such changes.

Twin studies provide a unique method for studying

development, and may provide clues as to the aetiology of

neurobiological differences in psychopathy. For example,

using this approach, boys with callous-unemotional traits

have been reported to exhibit heritable greymatter anomalies

within the DMN (Rijsdijsk et al., 2010). This suggests that at

least some differences within the DMN appear to be heritable

in psychopathy. However, it is also possible that the reported

differences in white matter microstructure could be influ-

enced by environmental factors. In particular, drug de-

pendency is known to exert a significant effect on FA (Ashtari

et al., 2009; Harris et al., 2008; Lim, Choi, Pomara, Wolkin, &

Rotrosen, 2002; Pfefferbaum, Rosenbloom, Rohlfing, &

Sullivan, 2009; Pfefferbaum & Sullivan, 2005). This potential

confound does not appear to have influenced our results,

however, as the observed reductions in FA remained signifi-

cant after controlling for group differences in life-time di-

agnoses of alcohol, cocaine, and cannabis dependence

Please cite this article in press as: Sethi, A., et al., Emotional detaconnections, Cortex (2014), http://dx.doi.org/10.1016/j.cortex.201

between groups. This suggests that the reported association

between emotional detachment and FA in the dorsal

cingulum cannot simply be explained by these environmental

factors. Nevertheless, future studies would benefit from a

control group matched for substance misuse and include

twin, and longitudinal, designs to tease apart putative envi-

ronmental and genetic influences more clearly.

Further studies are also required to overcome other limi-

tations of the current study. This includes the relatively small

sample size, and the need to replicate our findings in a larger

sample. The current study may have also benefited from

assessing the connectivity profile of the angular gyrus, which

contributes to the DMN. Reconstruction of the angular gyrus'connections with other DMN regions is limited by the inability

of the tensor model to resolve crossing fibres (Greicius et al.,

2009). However, this could potentially be addressed in future

studies, as high angular resolution diffusion imaging (HARDI)

techniques (Tuch et al., 2002), such as spherical deconvolution

(Dell'Acqua et al., 2010; Tournier, Calamante, Gadian, &

Connelly, 2004), continue to develop. Lastly, the proposed

model should be interpreted within the context of its predic-

tive limitations. For example, it is probable that there are other

regions/networks which also contribute to factor 1 and 2 in

psychopaths. In addition, other neurobiological differences

may contribute to functional abnormalities that are not

encapsulated by the PCL-R. For example, we also observed

differences in the ventral cingulum that did not relate to

either PCL-R factor. This is consistent with our understanding

that this tract is more associated with memory and spatial

orientation, than emotional and social processing (Catani &

Thiebault De Schotten, 2012).

5. Conclusions

The current study, combined with previous work, suggests

that it may be possible to fractionate the behavioural pheno-

type of psychopathy [that is, emotional detachment (PCL-R

factor 1) and antisocial behaviour (factor 2)] on the network

level. Whilst differences in a ventral ‘temporo-amygdala-

orbitofrontal’ network are related to antisocial behaviour in

psychopathy, we report that emotional detachment is related

to abnormalities in a dorsal ‘default-mode’ network. Further

work is required to determine the cause of these differences,

and if they predict outcome. Due to the apparent heritability

and early-emergence of affective and interpersonal traits, the

DMN may represent a more specific target for future studies

aimed at understanding the neurodevelopmental trajectory of

psychopathy and potential treatments.

Funding

This research was funded by research grants from: The

Department of Health (the National Forensic Mental Health

R&D programme; MRD 12/102); TheMinistry of Justice (a DSPD

programme grant); The Psychiatry Research Trust; The NIHR

Biomedical Research Centre, South London and Maudsley

NHS Foundation Trust, and Institute of Psychiatry (King'sCollege London).

chment in psychopathy: Involvement of dorsal default-mode4.07.018

c o r t e x x x x ( 2 0 1 4 ) 1e9 7

Conflict of interest

None.

Human and animal rights

The authors assert that all procedures contributing to this

work comply with the ethical standards of the relevant na-

tional and institutional committees on human experimenta-

tion and with the Helsinki Declaration of 1975, as revised in

2008. Informed consent was obtained for all human subjects.

Acknowledgements

We gratefully acknowledge the work of Ms. Sam Prior, Ms.

Clare Goodwin, Mr. William Wainwright, Mr. Ruben Azevedo,

Mr. Francis Vergunst, Ms. Lucy Butler, Ms. Leila Niknejad, Dr.

Anna Plodowski, Dr. Philip Baker, Dr. Timothy Rogers, Dr.

Preethi Chabbra, Dr. Stephen Attard, Dr. Seema Sukhwal, Dr.

Nathan Kolla, Dr. Paul Wallang, and Dr. Clare Conway in

participant recruitment and assessment.

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