Abstract
Introduction Psychopathy is a personality disorder characterised by disturbance in affective, interpersonal, and behavioural domains. Typically, it is the behavioural disturbances, including impulsivity, poor behavioural controls, and persistent contravention of societal norms, that brings the psychopath to the attention of society. The psychopaths’ behavioural disturbance has been conceptualized as arising from impaired response inhibition. Event-related potential research (Kiehl et al., 2000, Biological Psychiatry, 48) suggests that psychopathy is associated with abnormal neural activity during suppression of inappropriate responses. We used event-related fMRI to elucidate the neurobiological correlates of response inhibition during performance of a Go/NoGo task. Using this task in healthy controls Liddle et al. (2001, Human Brain Mapping, 12) demonstrated the importance of lateral frontal cortex in response inhibition. We hypothesised that psychopaths would show less activation in lateral frontal cortex during processing of NoGo stimuli than would healthy controls. Methods Fourteen psychopaths were recruited from a maximum-security prison and compared with fourteen healthy control participants selected from the general population. Psychopathy was assessed using the Hare Psychopathy Checklist-Revised (PCL-R) (Hare, 1991). Groups were matched for age, parental socioeconomic status, and IQ. All participants were right-handed, native English speakers, without history of head injury or psychotic illness. Task procedures are as described in Liddle et al. (2001). The visual stimuli for the Go and NoGo trials were the letters ‘X’ and ‘A’ respectively, presented for a period of 250 msecs each. Each trial commenced with a descending count of asterisks in order to increase motor response preparation. Twenty-four Go and 24 NoGo trials were randomly presented in a single scanning session. Imaging was performed using a General Electric 1.5 T whole body system fitted with a Horizon echo-speed upgrade. Functional image volumes were collected with a gradient-echo sequence (TR/IE 2500/50 ms, flip angle 90”, FOV 24x24 cm, 64x64 matrix, 62.5 kHz bandwidth, 3.75x3.75 mm in plane resolution, 4 mm slice thickness, 29 slices). Functional images were realigned, normalised, and smoothed using Statistical Parametric Mapping (SPM99). Event-related responses to the Go and NoGo stimuli were modeled with a synthetic haemodynamic response function composed of two gamma functions and their temporal derivatives. To test the hypothesis of reduced activation in lateral frontal cortex in psychopaths, we tested for significant group differences in activation during NoGo trials within I0mm diameter spherical regions centred on the loci of activation in lateral frontal cortex reported by Liddle et al. (2001). Results No significant differences between groups in accuracy of performance were observed. In accordance with the hypothesis, psychopaths exhibited significantly less activation in lateral frontal cortex, bilaterally, than healthy controls during NoGo trials: xyz = -48 -4 52, Z=3.78; xyz = 36 0 36, Z=3.66. Discussion We have demonstrated that inhibiting a behavioural response is associated with less lateral frontal activation in psychopaths compared to healthy control subjects. This is consistent with previous electrophysiological findings. Kiehl et al. (2000) reported that psychopaths exhibited a reduced amplitude of the frontal negative potential (N275) during NoGo trials. Taken together, these findings indicate that the cerebral mechanism for response inhibition is impaired in psychopathy.
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