Neuronal correlates and serotonergic modulation of behavioural inhibition and reward in healthy and antisocial individuals
Introduction
Antisocial personality disorder (ASPD) is characterised by a disregard for and violation of rights of others (APA, 1994) and is associated with increased rates of aggressive and criminal behaviour. There is increasing evidence for a neurobiological basis of ASPD, including genetic liability, aberrant serotonergic function, neuropsychological deficits and structural and functional brain abnormalities (reviewed in Pridmore et al. (2005)). Individuals with ASPD display behavioural symptoms, such as impulsivity, as well as affective impairment. Previous neuroimaging research has mainly focused on the affective component of the disorder; little work has been conducted investigating the neuronal correlates of impulsive responding in this group.
In healthy individuals neuronal correlates of behavioural inhibition, one aspect of impulsivity, include anterior cingulate (ACC), dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) (reviewed in Elliott (2005)). In antisocial groups abnormal brain activations during tasks requiring restraint of motor responding (Go/No-Go tasks) have been described (Völlm et al., 2004). Functional neuroimaging studies using reward tasks in healthy control groups (reviewed in O’Doherty (2004)) have implicated a number of brain regions mediating the behavioural and motivational effects of reward, including ventral striatum, dopaminergic midbrain, amygdala and orbitofrontal cortex. Amygdala, striatum and midbrain appear to be involved in the experience of reward while OFC is thought to mediate the integration of reward and punishment stimuli to inform future behaviour. Behavioural (Dolan and Park, 2002) and imaging (Völlm et al., 2007) studies in personality disordered groups have led to the proposal that deficits observed in behavioural choice involving reward and punishment may be related to prefrontal cortex dysfunction in Cluster B personality disordered patients.
An inverse relationship between impulsivity and 5-HT function has been demonstrated across a broad range of population samples (Dolan et al., 2001). 5-HT modulation has also been associated with alterations in behavioural choice following reward and punishment (Cools et al., 2005). Recently, neuroimaging research has investigated how 5-HT might exert its effect on these neuropsychological processes. In healthy individuals several studies have shown enhanced brain activations in prefrontal, particularly orbitofrontal, cortex during behavioural inhibition after administration of a range of different serontonergic drugs (Anderson et al., 2002, Del Ben et al., 2005, Völlm et al., 2006). Enhanced parietal cortex activations were identified during reward processing (Völlm et al., 2006).
In this study we used functional magnetic resonance imaging (fMRI) to identify brain areas associated with behavioural inhibition and reward in healthy and ASPD individuals and differences in activations between the two groups. We further investigated the effect of a serontonergic manipulation with the 5-HT2C-agonist m-chlorophenylpiperazine (mCPP) on these activations. Due to the deficient baseline 5-HT function in ASPD individuals, we hypothesised that a drug enhancing postsynaptic 5-HT function would have a larger effect on task related signal change in the ASPD group compared to the healthy control group.
Section snippets
Participants
Male ASPD participants were recruited from a variety of sources including a high security and a private sector medium security forensic psychiatric hospital and an open prison, all located in the North-West of England. Additional individuals were recruited via probation and from the general public using newspaper advertisements. Male healthy control participants were recruited from university staff (particularly non-academic staff) and the student population as well as from the general public.
Sociodemographic and behavioural data
Control participants were significantly younger than those with ASPD (mean controls 30.5, range 18–55; mean ASPD 42.1, range 29–56; P < 0.001). Individuals with ASPD and healthy control participants differed in years of education (12.3 vs. 16.4: P < 0.001). However, IQ scores were not significantly different between the two groups (mean controls 103.9, range 89–130; mean ASPD 99.4, range 89–113; P = 0.077).
ASPD participants had higher total BIS scores compared to control individuals which just missed
Discussion
In this study we examined two neuropsychological processes proposed to be impaired in antisocial individuals: impulsivity and reward processing. We investigated task performance on a Go/No-Go and a reward task and used fMRI to identify brain activations associated with performing these tasks in antisocial personality disordered individuals and in a healthy control group. We further explored whether a serontonergic drug challenge (mCPP) modulated task related neuronal activations. Our results
Conclusions
In conclusion, in this study we demonstrated reduced task related brain activations in prefrontal and parietal regions during performance of a behavioural inhibition task as well as increased engagement of parts of the reward circuit during a reward task in a group of individuals with ASPD. This may reflect deficits in executive function and a possible attentional component to impulsivity in ASPD. We also found evidence that the restraint condition engaged pre/subgenual cortex and other emotion
Role of funding source
Funding for this study was provided by the Medical Research Council; the MRC had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Contributors
B.V., P.R., R.E., I.A., S.W., M.D. and B.D. were involved in the design of the study; B.V., P.R., R.E., I.A., S.W., M.D. and B.D. wrote the protocol. B.V. and P.R. collected the data; B.V. and P.R. managed data collection and databases; B.V., P.R., S.M. and R.R. analysed the data; B.V. wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest statement
None declared.
Acknowledgements
We acknowledge the support of the Manchester Clinical Research Facility.
References (33)
- et al.
Cognitive and emotional influences in anterior cingulate cortex
Trends in Cognitive Sciences
(2000) - et al.
Role of 5-HT(2C) receptors in the control of central dopamine function
Trends in Pharmacological Science
(2001) - et al.
Neurocognitive function in antisocial personality disorder
Psychiatry Research
(2000) - et al.
Role of the orbitofrontal cortex in reinforcement processing and inhibitory control: evidence from functional magnetic resonance imaging studies in healthy human subjects
International Review of Neurobiology
(2005) - et al.
Response inhibition and impulsivity: an fMRI study
Neuropsychologia
(2003) - et al.
An event-related potential investigation of response inhibition in schizophrenia and psychopathy
Biological Psychiatry
(2000) - et al.
Ventral frontal deficits in psychopathy: neuropsychological test findings
Neuropsychologia
(1995) Reward representations and reward-related learning in the human brain: insights from neuroimaging
Current Opinion in Neurobiology
(2004)- et al.
Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain
Neuroscience
(1999) - et al.
Neuronal correlates of reward and loss in Cluster B personality disorder: a functional magnetic resonance imaging study
Psychiatry Research: Neuroimaging
(2007)