Quinton Deeley

Altered connections on the road to psychopathy

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of ⩾25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala–OFC network, we also studied two ‘non-limbic’ control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala–OFC limbic network underpin the neurobiological basis of psychopathy.

The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study

It has been suggested that people with autistic spectrum disorder (ASD) have altered development (and connectivity) of limbic circuits. However, direct evidence of anatomical differences specific to white matter pathways underlying social behaviour and emotions in ASD is lacking. We used Diffusion Tensor Imaging Tractography to compare, in vivo, the microstructural integrity and age-related differences in the extended limbic pathways between subjects with Asperger syndrome and healthy controls. Twenty-four males with Asperger syndrome (mean age 23+/-12 years, age range: 9-54 years) and 42 age-matched male controls (mean age 25+/-10 years, age range: 9-54 years) were studied. We quantified tract-specific diffusivity measurements as indirect indexes of microstructural integrity (e.g. fractional anisotropy, FA; mean diffusivity, MD) and tract volume (e.g. number of streamlines) of the main limbic tracts. The dissected limbic pathways included the inferior longitudinal fasciculus, inferior frontal occipital fasciculus, uncinate, cingulum and fornix. There were no significant between-group differences in FA and MD. However, compared to healthy controls, individuals with Asperger syndrome had a significantly higher number of streamlines in the right (p=.003) and left (p=.03) cingulum, and in the right (p=.03) and left (p=.04) inferior longitudinal fasciculus. In contrast, people with Asperger syndrome had a significantly lower number of streamlines in the right uncinate (p=.02). Within each group there were significant age-related differences in MD and number of streamlines, but not FA. However, the only significant age-related between-group difference was in mean diffusivity of the left uncinate fasciculus (Z(obs)=2.05) (p=.02). Our preliminary findings suggest that people with Asperger syndrome have significant differences in the anatomy, and maturation, of some (but not all) limbic tracts.

In vivo 1H-magnetic resonance spectroscopy study of amygdala-hippocampal and parietal regions in autism.

OBJECTIVE The neural basis for autistic spectrum disorders is unclear, but abnormalities in the development of limbic areas and of glutamate have been suggested. Proton magnetic resonance spectroscopy ((1)H-MRS) can be used to measure the concentration of brain metabolites. However, the concentration of glutamate/glutamine in brain regions implicated in autistic spectrum disorders has not yet been examined in vivo. METHOD The authors used (1)H-MRS to investigate the neuronal integrity of the amygdala-hippocampal complex and a parietal control region in adults with autistic spectrum disorders and healthy subjects. RESULTS People with autistic spectrum disorders had a significantly higher concentration of glutamate/glutamine and creatine/phosphocreatine in the amygdala-hippocampal region but not in the parietal region. CONCLUSIONS Abnormalities in glutamate/glutamine may partially underpin the pathophysiology of autistic spectrum disorders, and the authors confirm earlier reports that limbic areas are metabolically aberrant in these disorders.

Dissociation in hysteria and hypnosis: evidence from cognitive neuroscience

Jean-Martin Charcot proposed the radical hypothesis that similar brain processes were responsible for the unexplained neurological symptoms of ‘hysteria’, now typically diagnosed as ‘conversion disorder’ or ‘dissociative (conversion) disorder’, and the temporary effects of hypnosis. While this idea has been largely ignored, recent cognitive neuroscience studies indicate that (i) hypnotisability traits are associated with a tendency to develop dissociative symptoms in the sensorimotor domain; (ii) dissociative symptoms can be modelled with suggestions in highly hypnotisable subjects; and (iii) hypnotic phenomena engage brain processes similar to those seen in patients with symptoms of hysteria. One clear theme to emerge from the findings is that ‘symptom’ presentation, whether clinically diagnosed or simulated using hypnosis, is associated with increases in prefrontal cortex activity suggesting that intervention by the executive system in both automatic and voluntary cognitive processing is common to both hysteria and hypnosis. Nevertheless, while the recent literature provides some compelling leads into the understanding of these phenomena, the field still lacks well controlled systematically designed studies to give a clear insight into the neurocognitive processes underlying dissociation in both hysteria and hypnosis. The aim of this review is to provide an agenda for future research.

A functional magnetic resonance imaging study of inhibitory control in obsessive-compulsive disorder

People with obsessive-compulsive disorder (OCD) have abnormalities in cognitive and motor inhibition, and it has been proposed that these are related to dysfunction of fronto-striatal circuits. However, nobody has investigated neuro-functional abnormalities during a range of inhibition tasks in adults with OCD. The aims of the study were to compare brain activation of people with OCD and controls during three tasks of inhibitory control. Ten unmedicated adults with OCD and 11 healthy controls performed three different tasks of motor and cognitive inhibitory control during event-related functional magnetic resonance imaging: a Go/No-go task (motor inhibition), a motor Stroop task (interference inhibition) and a Switch task (cognitive flexibility). People with OCD displayed significantly different patterns of brain activation compared to controls during all three tasks. During the Go/No-go and Switch experiments, people with OCD had underactivation in task-relevant orbitofrontal/dorsolateral prefrontal, striatal and thalamic regions. During the motor Stroop and Switch tasks, people with OCD also displayed underactivation in temporo-parietal areas. In the Go/No-go and motor Stroop tasks the OCD group showed increased activation compared to controls in cerebellum and predominantly posterior brain regions. OCD is associated with task-relevant fronto-striatal dysfunction during motor inhibition and cognitive switching. In addition, parieto-temporal dysfunction was observed during tasks with a higher attentional load.

Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study

BACKGROUND Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype. METHOD We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender. RESULTS VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome. CONCLUSIONS Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

White matter integrity in Asperger syndrome: a preliminary diffusion tensor magnetic resonance imaging study in adults.

Background: Autistic Spectrum Disorder (ASD), including Asperger syndrome and autism, is a highly genetic neurodevelopmental disorder. There is a consensus that ASD has a biological basis, and it has been proposed that it is a “connectivity” disorder. Diffusion Tensor Magnetic Resonance Imaging (DT‐MRI) allows measurement of the microstructural integrity of white matter (a proxy measure of “connectivity”). However, nobody has investigated the microstructural integrity of whole brain white matter in people with Asperger syndrome. Methods: We measured the fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD) of white matter, using DT‐MRI, in 13 adults with Asperger syndrome and 13 controls. The groups did not differ significantly in overall intelligence and age. FA, MD and RD were assessed using whole brain voxel‐based techniques. Results: Adults with Asperger syndrome had a significantly lower FA than controls in 13 clusters. These were largely bilateral and included white matter in the internal capsule, frontal, temporal, parietal and occipital lobes, cingulum and corpus callosum. Conclusions: Adults with Asperger syndrome have widespread significant differences from controls in white matter microstructural integrity.

An fMRI study of facial emotion processing in children and adolescents with 22q11.2 deletion syndrome.

Background22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood.MethodsWe used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9–17 years) and healthy controls (aged 8–17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls.ResultsWithin groups, contrasts showed that individuals significantly activated ‘face responsive’ areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment—social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum.ConclusionsRegions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.

Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces.

A distributed, serotonergically innervated neural system comprising extrastriate cortex, amygdala and ventral prefrontal cortex is critical for identification of socially relevant emotive stimuli. The extent to which a genetic variation of serotonin transporter gene 5‐HTTLPR impacts functional connectivity between the amygdala and the other components of this neural system remains little examined. In our study, neural activity was measured using event‐related functional magnetic resonance imaging in 29 right‐handed, white Caucasian healthy subjects as they viewed mild or prototypical fearful and neutral facial expressions. 5‐HTTLPR genotype was classified as homozygous for the short allele (S/S), homozygous for the long allele (L/L) or heterozygous (S/L). S/S showed greater activity than L/L within right fusiform gyrus (FG) to prototypically fearful faces. To these fearful faces, S/S more than other genotype subgroups showed significantly greater positive functional connectivity between right amygdala and FG and between right FG and right ventrolateral prefrontal cortex (VLPFC). There was a positive association between measure of psychoticism and degree of functional connectivity between right FG and right VLPFC in response to prototypically fearful faces. Our data are the first to show that genotypic variation in 5‐HTTLPR modulates both the amplitude within and the functional connectivity between different components of the visual object‐processing neural system to emotionally salient stimuli. These effects may underlie the vulnerability to mood and anxiety disorders potentially triggered by socially salient, emotional cues in individuals with the S allele of 5‐HTTLPR.

Modulating the Default Mode Network Using Hypnosis

Abstract Debate regarding the neural basis of the hypnotic state continues, but a recent hypothesis suggests that it may produce alterations in the default mode network (DMN). DMN describes a network of brain regions more active during low-demand compared to high-demand task conditions and has been linked to processes such as task-independent thinking, episodic memory, semantic processing, and self-awareness. However, the experiential and cognitive correlates of DMN remain difficult to investigate directly. Using hypnosis as a means of altering the resting (“default”) state in conjunction with subjective measures and brain imaging, the authors found that the state of attentional absorption following a hypnotic induction was associated with reduced activity in DMN and increased activity in prefrontal attentional systems, under invariant conditions of passive visual stimulation. The findings that hypnosis and spontaneous conceptual thought at rest were subjectively and neurally distinctive are also relevant to understanding hypnosis itself.