Murat Yucel | Monash University (original) (raw)

Papers by Murat Yucel

Research paper thumbnail of Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control

A principal feature of drug addiction is a reduced ability to regulate control over the desire to... more A principal feature of drug addiction is a reduced ability to regulate control over the desire to procure drugs regardless of the risks involved. Traditional models implicated the neural 'reward' system in providing a neurobiological model of addiction. Newer models however, have expanded on this circuitry to include two separate, but interconnecting systems, the limbic system in the incentive sensitization of drugs, and the prefrontal cortex (PFC) in regulating inhibitory control over drug use. Until the recent developments in neuroimaging and brain stimulation techniques, it has been extremely difficult to assess the involvement of the PFC in addiction. In the current review, we explore the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggest how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use. Following this, we investigate the recent neuropsychological, neuroimaging and brain stimulation studies that explore the presence of these inhibitory deficits, and frontostriatal dysfunctions, across various different substance groups. Further insight into these deficits could contribute to the development of treatment strategies which target these cognitive impairments, and frontostriatal dysfunction, in reducing drug-seeking behaviors.

Research paper thumbnail of Neurobiological Markers of Illness Onset in Psychosis and Schizophrenia: The Search for a Moving Target

Neuropsychology Review, 2009

In this review, we describe neuropsychological and brain imaging findings in the early stages of ... more In this review, we describe neuropsychological and brain imaging findings in the early stages of psychosis and schizophrenia. We focus on recent clinical high-risk studies and consider whether the evidence supports these as 'endo-

Research paper thumbnail of Evidence for neuronal dysfunction in the anterior cingulate of patients with schizophrenia: A proton magnetic resonance spectroscopy study at 3 T

Schizophrenia Research, 2007

The anterior cingulate region is thought to be dysfunctional in schizophrenia, but whether this i... more The anterior cingulate region is thought to be dysfunctional in schizophrenia, but whether this is the result of reduced neuronal integrity or changes in neurotransmitter systems remains an issue of debate. Fifteen male patients with schizophrenia and 14 male controls were assessed using proton magnetic resonance spectroscopy, with regions of interest placed in the right and left dorsal and rostral cingulate. The metabolites of interest were N-acetylaspartate (NAA), a putative neuronal marker, and glutamate + glutamine (Glx), which may index synapse number. Schizophrenia patients had lower NAA concentrations throughout the dorsal and rostral portions of the anterior cingulate and in both hemispheres, but showed no changes in Glx. Anterior cingulate involvement in schizophrenia is likely to be a result of neuronal loss or dysfunction.

Research paper thumbnail of Neuronal, physiological and brain–behavioural abnormalities in opiate-addicted individuals

Molecular Psychiatry, 2007

Illustrated are the group level dorsal anterior cingulate cortex (dACC) BOLD activation maps and ... more Illustrated are the group level dorsal anterior cingulate cortex (dACC) BOLD activation maps and the spatial location of the volume localized proton-MRS (superimposed in blue) on a sagittaly oriented structural MR image (MNI, Talairach brain) for healthy controls (panel a) and opiate-dependent subject (panel b). While both groups activated the dACC to comparable levels, the opiate-using group (i) failed to show the expected correlations between dACC physiological activity and behavioural measures of control (that is, response errors) shown by the control group, (ii) had significantly increased task-related activation of fronto-parietal and cerebellar regions to achieve a comparable level of behavioural control as healthy controls and (iii) exhibited significantly reduced concentrations of N-acetylaspartate (NAA) and glutamate/glutamine (Glx) within the dACC (panel c; horizontal bars represent mean values). Taken together, these findings suggest that neuronal abnormalities and a breakdown of normal brain-behaviour relationships within the dACC of opiate addicted individuals may result in the recruitment of a compensatory network of brain regions in situations requiring behavioural control. For more information on this topic, please see the article by Yü cel et al. on pp 691-702. 4

Research paper thumbnail of Functional and Biochemical Alterations of the Medial Frontal Cortex in Obsessive-Compulsive Disorder

Archives of General Psychiatry, 2007

The medial frontal cortex (MFC), including the dorsal anterior cingulate and the supplementary mo... more The medial frontal cortex (MFC), including the dorsal anterior cingulate and the supplementary motor area, is critical for adaptive and inhibitory control of behavior. Abnormally high MFC activity has been a consistent finding in functional neuroimaging studies of obsessive-compulsive disorder (OCD). However, the precise regions and the neural alterations associated with this abnormality remain unclear.

Research paper thumbnail of Anterior cingulate glutamate–glutamine levels predict symptom severity in women with obsessive–compulsive disorder

Australian and New Zealand Journal of Psychiatry, 2008

Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-co... more Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-compulsive disorder.

Research paper thumbnail of State, trait and biochemical influences on human anterior cingulate function

NeuroImage, 2007

The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations... more The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations requiring cognitive control, especially during states of conflict. However, little is known about how individual differences in the neural characteristics of the dACC and major dimensions of behavior, affect this brain response. We recruited 28 healthy adults and employed a multi-modal neuroimaging approach combined with a task designed to specifically activate the human dACC and statistical path analysis to demonstrate clear roles for intelligence, personality and concentrations of neuronal N-acetylaspartate in determining dACC activation. These influences were comparable in magnitude to those associated with the experience of conflict. Our findings extend current understandings of the neural substrates of cognitive control by modeling the effect of neuronal viability, intelligence, and personality, on dACC activation. They also highlight the importance of considering enduring personal characteristics when mapping human brain-behavior relationships.

Research paper thumbnail of Anatomic Abnormalities of the Anterior Cingulate Cortex Before Psychosis Onset: An MRI Study of Ultra-High-Risk Individuals

Biological Psychiatry, 2008

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the... more Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis.

Research paper thumbnail of Aetiological overlap between obsessive-compulsive related and anxiety disorder symptoms: multivariate twin study

The British journal of psychiatry : the journal of mental science, Jan 22, 2015

BackgroundThe aetiological boundary between obsessive-compulsive related disorders (OCRDs) includ... more BackgroundThe aetiological boundary between obsessive-compulsive related disorders (OCRDs) including obsessive-compulsive disorder (OCD) and anxiety disorders is unclear and continues to generate debate.AimsTo determine the genetic overlap and the pattern of causal relationships among OCRDs and anxiety disorders.MethodMultivariate twin modelling methods and a new regression analysis to infer causation were used, involving 2495 male and female twins.ResultsThe amount of common genetic liability observed for OCD symptoms was higher when considering anxiety disorders and OCRDs in the model v. modelling OCRD symptoms alone. OCD symptoms emerged as risk factors for the presence of generalised anxiety, panic and hoarding symptoms, whereas social phobia appeared as a risk factor for OCD symptoms.ConclusionsOCD represents a complex phenotype that includes important shared features with anxiety disorders and OCRDs. The novel patterns of risk identified between OCD and anxiety disorder may he...

Research paper thumbnail of Reduced concentration of N-acetyl-aspartate associated with volume reduction of the hippocampus in heavy cannabis users

Research paper thumbnail of The Association between Regular Cannabis Exposure and Alterations of Human Brain Morphology: An Updated Review of the Literature

Current Pharmaceutical Design, 2014

Research paper thumbnail of Volumetric differences in the anterior cingulate cortex prospectively predict alcohol-related problems in adolescence

Psychopharmacology, 2014

Rationale Individual differences in brain structure and function are suggested to exist prior to ... more Rationale Individual differences in brain structure and function are suggested to exist prior to the onset of alcohol abuse. Cross-sectional studies have demonstrated abnormalities in brain regions underlying affective processes that may form a pathway to the emergence of later alcohol abuse and dependence in vulnerable individuals. However, no prospective studies have examined whether these abnormalities predict later problems with alcohol. Objective This study aims to examine whether individual differences in affect and brain volume prospectively predict alcohol-related problems in adolescence. Method Adolescent drinkers (n=98) were recruited from an ongoing prospective, longitudinal study examining adolescent emotional development. At age 12, participants underwent structural magnetic resonance imaging to obtain volumetric data on the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex (ACC), and completed a self-report measure of affective temperament. At age 16, participants completed a questionnaire measuring alcohol use, with 39 % reporting alcohol-related problems in the past year. Results Pre-existing differences in the left ACC predicted problem drinking. Alcohol-related problems were associated with higher levels of temperamental negative affectivity; however, these were not correlated with anterior cingulate volumes.

Research paper thumbnail of Effect of long-term cannabis use on axonal fibre connectivity

Brain, 2012

Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid r... more Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment.

Research paper thumbnail of Reduced orbitofrontal cortical thickness in male adolescents with internet addiction

Behavioral and Brain Functions, 2013

The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and... more The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and behavioral addictions. However, no study to date has examined OFC thickness in internet addiction. In the current study, we investigated the existence of differences in cortical thickness of the OFC in adolescents with internet addiction. On the basis of recently proposed theoretical models of addiction, we predicted a reduction of thickness in the OFC of internet addicted individuals. Participants were 15 male adolescents diagnosed as having internet addiction and 15 male healthy comparison subjects. Brain magnetic resonance images were acquired on a 3T MRI and group differences in cortical thickness were analyzed using FreeSurfer. Our results confirmed that male adolescents with internet addiction have significantly decreased cortical thickness in the right lateral OFC (p<0.05). This finding supports the view that the OFC alterations in adolescents with internet addiction reflect a shared neurobiological marker of addiction-related disorders in general.

Research paper thumbnail of Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness

The British Journal of Psychiatry, 2003

The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizoph... more The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder. To examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness. Magnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features. Compared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did (n=21) and did not (n=42) subsequently develop a psychotic illness. Although ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify individuals who subsequently make the transition to psychosis.

Research paper thumbnail of A disturbed sense of self in the psychosis prodrome: Linking phenomenology and neurobiology

Neuroscience & Biobehavioral Reviews, 2009

Research paper thumbnail of Hippocampal pathology in individuals at ultra-high risk for psychosis: a multi-modal magnetic resonance study

Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unc... more Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24 months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippocampal volume, hippocampal T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippocampal volume in the at-risk group compared to comparison subjects regardless of later transition status; on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippocampal head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippocampus prior to the development of psychosis, but that they are limited to the left hippocampal head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder.

Research paper thumbnail of Anatomic Abnormalities of the Anterior Cingulate Cortex Before Psychosis Onset: An MRI Study of Ultra-High-Risk Individuals

Biological Psychiatry, 2008

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the... more Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis.

Research paper thumbnail of Morphology of the anterior cingulate cortex Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing in young men at ultra-high risk of developing a psychotic illness a psychotic illness

Research paper thumbnail of Developmental Changes in Brain Network Hub Connectivity in Late Adolescence

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 17, 2015

The human brain undergoes substantial development throughout adolescence and into early adulthood... more The human brain undergoes substantial development throughout adolescence and into early adulthood. This maturational process is thought to include the refinement of connectivity between putative connectivity hub regions of the brain, which collectively form a dense core that enhances the functional integration of anatomically distributed, and functionally specialized, neural systems. Here, we used longitudinal diffusion magnetic resonance imaging to characterize changes in connectivity between 80 cortical and subcortical anatomical regions over a 2 year period in 31 adolescents between the ages of 15 and 19 years. Connectome-wide analysis indicated that only a small subset of connections showed evidence of statistically significant developmental change over the study period, with 8% and 6% of connections demonstrating decreased and increased structural connectivity, respectively. Nonetheless, these connections linked 93% and 90% of the 80 regions, respectively, pointing to a selecti...

Research paper thumbnail of Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control

A principal feature of drug addiction is a reduced ability to regulate control over the desire to... more A principal feature of drug addiction is a reduced ability to regulate control over the desire to procure drugs regardless of the risks involved. Traditional models implicated the neural 'reward' system in providing a neurobiological model of addiction. Newer models however, have expanded on this circuitry to include two separate, but interconnecting systems, the limbic system in the incentive sensitization of drugs, and the prefrontal cortex (PFC) in regulating inhibitory control over drug use. Until the recent developments in neuroimaging and brain stimulation techniques, it has been extremely difficult to assess the involvement of the PFC in addiction. In the current review, we explore the involvement of the frontostriatal circuitry in regulating inhibitory control, and suggest how dysregulation of these circuits could be involved in an increased difficulty in ceasing drug use. Following this, we investigate the recent neuropsychological, neuroimaging and brain stimulation studies that explore the presence of these inhibitory deficits, and frontostriatal dysfunctions, across various different substance groups. Further insight into these deficits could contribute to the development of treatment strategies which target these cognitive impairments, and frontostriatal dysfunction, in reducing drug-seeking behaviors.

Research paper thumbnail of Neurobiological Markers of Illness Onset in Psychosis and Schizophrenia: The Search for a Moving Target

Neuropsychology Review, 2009

In this review, we describe neuropsychological and brain imaging findings in the early stages of ... more In this review, we describe neuropsychological and brain imaging findings in the early stages of psychosis and schizophrenia. We focus on recent clinical high-risk studies and consider whether the evidence supports these as 'endo-

Research paper thumbnail of Evidence for neuronal dysfunction in the anterior cingulate of patients with schizophrenia: A proton magnetic resonance spectroscopy study at 3 T

Schizophrenia Research, 2007

The anterior cingulate region is thought to be dysfunctional in schizophrenia, but whether this i... more The anterior cingulate region is thought to be dysfunctional in schizophrenia, but whether this is the result of reduced neuronal integrity or changes in neurotransmitter systems remains an issue of debate. Fifteen male patients with schizophrenia and 14 male controls were assessed using proton magnetic resonance spectroscopy, with regions of interest placed in the right and left dorsal and rostral cingulate. The metabolites of interest were N-acetylaspartate (NAA), a putative neuronal marker, and glutamate + glutamine (Glx), which may index synapse number. Schizophrenia patients had lower NAA concentrations throughout the dorsal and rostral portions of the anterior cingulate and in both hemispheres, but showed no changes in Glx. Anterior cingulate involvement in schizophrenia is likely to be a result of neuronal loss or dysfunction.

Research paper thumbnail of Neuronal, physiological and brain–behavioural abnormalities in opiate-addicted individuals

Molecular Psychiatry, 2007

Illustrated are the group level dorsal anterior cingulate cortex (dACC) BOLD activation maps and ... more Illustrated are the group level dorsal anterior cingulate cortex (dACC) BOLD activation maps and the spatial location of the volume localized proton-MRS (superimposed in blue) on a sagittaly oriented structural MR image (MNI, Talairach brain) for healthy controls (panel a) and opiate-dependent subject (panel b). While both groups activated the dACC to comparable levels, the opiate-using group (i) failed to show the expected correlations between dACC physiological activity and behavioural measures of control (that is, response errors) shown by the control group, (ii) had significantly increased task-related activation of fronto-parietal and cerebellar regions to achieve a comparable level of behavioural control as healthy controls and (iii) exhibited significantly reduced concentrations of N-acetylaspartate (NAA) and glutamate/glutamine (Glx) within the dACC (panel c; horizontal bars represent mean values). Taken together, these findings suggest that neuronal abnormalities and a breakdown of normal brain-behaviour relationships within the dACC of opiate addicted individuals may result in the recruitment of a compensatory network of brain regions in situations requiring behavioural control. For more information on this topic, please see the article by Yü cel et al. on pp 691-702. 4

Research paper thumbnail of Functional and Biochemical Alterations of the Medial Frontal Cortex in Obsessive-Compulsive Disorder

Archives of General Psychiatry, 2007

The medial frontal cortex (MFC), including the dorsal anterior cingulate and the supplementary mo... more The medial frontal cortex (MFC), including the dorsal anterior cingulate and the supplementary motor area, is critical for adaptive and inhibitory control of behavior. Abnormally high MFC activity has been a consistent finding in functional neuroimaging studies of obsessive-compulsive disorder (OCD). However, the precise regions and the neural alterations associated with this abnormality remain unclear.

Research paper thumbnail of Anterior cingulate glutamate–glutamine levels predict symptom severity in women with obsessive–compulsive disorder

Australian and New Zealand Journal of Psychiatry, 2008

Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-co... more Anterior cingulate glutamate-glutamine levels predict symptom severity in women with obsessive-compulsive disorder.

Research paper thumbnail of State, trait and biochemical influences on human anterior cingulate function

NeuroImage, 2007

The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations... more The dorsal part of the human anterior cingulate cortex (dACC) is reliably activated in situations requiring cognitive control, especially during states of conflict. However, little is known about how individual differences in the neural characteristics of the dACC and major dimensions of behavior, affect this brain response. We recruited 28 healthy adults and employed a multi-modal neuroimaging approach combined with a task designed to specifically activate the human dACC and statistical path analysis to demonstrate clear roles for intelligence, personality and concentrations of neuronal N-acetylaspartate in determining dACC activation. These influences were comparable in magnitude to those associated with the experience of conflict. Our findings extend current understandings of the neural substrates of cognitive control by modeling the effect of neuronal viability, intelligence, and personality, on dACC activation. They also highlight the importance of considering enduring personal characteristics when mapping human brain-behavior relationships.

Research paper thumbnail of Anatomic Abnormalities of the Anterior Cingulate Cortex Before Psychosis Onset: An MRI Study of Ultra-High-Risk Individuals

Biological Psychiatry, 2008

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the... more Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis.

Research paper thumbnail of Aetiological overlap between obsessive-compulsive related and anxiety disorder symptoms: multivariate twin study

The British journal of psychiatry : the journal of mental science, Jan 22, 2015

BackgroundThe aetiological boundary between obsessive-compulsive related disorders (OCRDs) includ... more BackgroundThe aetiological boundary between obsessive-compulsive related disorders (OCRDs) including obsessive-compulsive disorder (OCD) and anxiety disorders is unclear and continues to generate debate.AimsTo determine the genetic overlap and the pattern of causal relationships among OCRDs and anxiety disorders.MethodMultivariate twin modelling methods and a new regression analysis to infer causation were used, involving 2495 male and female twins.ResultsThe amount of common genetic liability observed for OCD symptoms was higher when considering anxiety disorders and OCRDs in the model v. modelling OCRD symptoms alone. OCD symptoms emerged as risk factors for the presence of generalised anxiety, panic and hoarding symptoms, whereas social phobia appeared as a risk factor for OCD symptoms.ConclusionsOCD represents a complex phenotype that includes important shared features with anxiety disorders and OCRDs. The novel patterns of risk identified between OCD and anxiety disorder may he...

Research paper thumbnail of Reduced concentration of N-acetyl-aspartate associated with volume reduction of the hippocampus in heavy cannabis users

Research paper thumbnail of The Association between Regular Cannabis Exposure and Alterations of Human Brain Morphology: An Updated Review of the Literature

Current Pharmaceutical Design, 2014

Research paper thumbnail of Volumetric differences in the anterior cingulate cortex prospectively predict alcohol-related problems in adolescence

Psychopharmacology, 2014

Rationale Individual differences in brain structure and function are suggested to exist prior to ... more Rationale Individual differences in brain structure and function are suggested to exist prior to the onset of alcohol abuse. Cross-sectional studies have demonstrated abnormalities in brain regions underlying affective processes that may form a pathway to the emergence of later alcohol abuse and dependence in vulnerable individuals. However, no prospective studies have examined whether these abnormalities predict later problems with alcohol. Objective This study aims to examine whether individual differences in affect and brain volume prospectively predict alcohol-related problems in adolescence. Method Adolescent drinkers (n=98) were recruited from an ongoing prospective, longitudinal study examining adolescent emotional development. At age 12, participants underwent structural magnetic resonance imaging to obtain volumetric data on the amygdala, hippocampus, orbitofrontal cortex, and anterior cingulate cortex (ACC), and completed a self-report measure of affective temperament. At age 16, participants completed a questionnaire measuring alcohol use, with 39 % reporting alcohol-related problems in the past year. Results Pre-existing differences in the left ACC predicted problem drinking. Alcohol-related problems were associated with higher levels of temperamental negative affectivity; however, these were not correlated with anterior cingulate volumes.

Research paper thumbnail of Effect of long-term cannabis use on axonal fibre connectivity

Brain, 2012

Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid r... more Cannabis use typically begins during adolescence and early adulthood, a period when cannabinoid receptors are still abundant in white matter pathways across the brain. However, few studies to date have explored the impact of regular cannabis use on white matter structure, with no previous studies examining its impact on axonal connectivity. The aim of this study was to examine axonal fibre pathways across the brain for evidence of microstructural alterations associated with long-term cannabis use and to test whether age of regular cannabis use is associated with severity of any microstructural change. To this end, diffusion-weighted magnetic resonance imaging and brain connectivity mapping techniques were performed in 59 cannabis users with longstanding histories of heavy use and 33 matched controls. Axonal connectivity was found to be impaired in the right fimbria of the hippocampus (fornix), splenium of the corpus callosum and commissural fibres. Radial and axial diffusivity in these pathways were associated with the age at which regular cannabis use commenced. Our findings indicate long-term cannabis use is hazardous to the white matter of the developing brain. Delaying the age at which regular use begins may minimize the severity of microstructural impairment.

Research paper thumbnail of Reduced orbitofrontal cortical thickness in male adolescents with internet addiction

Behavioral and Brain Functions, 2013

The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and... more The orbitofrontal cortex (OFC) has consistently been implicated in the pathology of both drug and behavioral addictions. However, no study to date has examined OFC thickness in internet addiction. In the current study, we investigated the existence of differences in cortical thickness of the OFC in adolescents with internet addiction. On the basis of recently proposed theoretical models of addiction, we predicted a reduction of thickness in the OFC of internet addicted individuals. Participants were 15 male adolescents diagnosed as having internet addiction and 15 male healthy comparison subjects. Brain magnetic resonance images were acquired on a 3T MRI and group differences in cortical thickness were analyzed using FreeSurfer. Our results confirmed that male adolescents with internet addiction have significantly decreased cortical thickness in the right lateral OFC (p<0.05). This finding supports the view that the OFC alterations in adolescents with internet addiction reflect a shared neurobiological marker of addiction-related disorders in general.

Research paper thumbnail of Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness

The British Journal of Psychiatry, 2003

The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizoph... more The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder. To examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness. Magnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features. Compared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did (n=21) and did not (n=42) subsequently develop a psychotic illness. Although ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify individuals who subsequently make the transition to psychosis.

Research paper thumbnail of A disturbed sense of self in the psychosis prodrome: Linking phenomenology and neurobiology

Neuroscience & Biobehavioral Reviews, 2009

Research paper thumbnail of Hippocampal pathology in individuals at ultra-high risk for psychosis: a multi-modal magnetic resonance study

Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unc... more Although the hippocampus is a key brain region in the pathophysiology of schizophrenia, it is unclear whether structural or biochemical abnormalities predate illness onset. In this study, we used magnetic resonance imaging and spectroscopy data acquired prior to both the onset of psychosis and treatment with antipsychotics to determine this. Sixty-six young people clinically at ultra high-risk of development of psychosis were recruited, 59 of whom did not later develop a psychotic disorder and 7 who had done so after at least 24 months follow-up. These participants were compared with 29 healthy comparison subjects on multiple independent magnetic resonance measures: hippocampal volume, hippocampal T2 relaxation time, and medial temporal lobe metabolite concentrations (including N-acetylaspartate). We found similar reductions in left hippocampal volume in the at-risk group compared to comparison subjects regardless of later transition status; on the right this only reached significance for the at-risk group who did not transition to psychosis. T2 relaxation time in the left hippocampal head was significantly elevated in the later-psychotic group, and this elevation positively correlated with total positive symptoms in the UHR group as a whole. Medial temporal lobe metabolite concentrations did not differ. These findings suggest that there are subtle pathological changes in the hippocampus prior to the development of psychosis, but that they are limited to the left hippocampal head. However, standard measures of neuroanatomical disturbance do not appear to be predictive of later transition, and instead are likely to be non-specific and common in cases that later develop a non-psychotic disorder.

Research paper thumbnail of Anatomic Abnormalities of the Anterior Cingulate Cortex Before Psychosis Onset: An MRI Study of Ultra-High-Risk Individuals

Biological Psychiatry, 2008

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the... more Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis.

Research paper thumbnail of Morphology of the anterior cingulate cortex Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing in young men at ultra-high risk of developing a psychotic illness a psychotic illness

Research paper thumbnail of Developmental Changes in Brain Network Hub Connectivity in Late Adolescence

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 17, 2015

The human brain undergoes substantial development throughout adolescence and into early adulthood... more The human brain undergoes substantial development throughout adolescence and into early adulthood. This maturational process is thought to include the refinement of connectivity between putative connectivity hub regions of the brain, which collectively form a dense core that enhances the functional integration of anatomically distributed, and functionally specialized, neural systems. Here, we used longitudinal diffusion magnetic resonance imaging to characterize changes in connectivity between 80 cortical and subcortical anatomical regions over a 2 year period in 31 adolescents between the ages of 15 and 19 years. Connectome-wide analysis indicated that only a small subset of connections showed evidence of statistically significant developmental change over the study period, with 8% and 6% of connections demonstrating decreased and increased structural connectivity, respectively. Nonetheless, these connections linked 93% and 90% of the 80 regions, respectively, pointing to a selecti...