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Murat Yücel

Publications and source records attributed to Murat Yücel.

13 recordsLinked to original sources
PubMed2005

The neurobiological basis of temperament: towards a better understanding of psychopathology.

The ability to characterise psychopathologies on the basis of their underlying neurobiology is critical in improving our understanding of disorder etiology and making more effective diagnostic and treatment decisions. Given the well-documented relationship between temperament (i.e. core personality traits) and psychopathology, research investigating the neurobiological substrates that underlie temperament is potentially key to our understanding of the biological basis of mental disorder. We present evidence that specific areas of the prefrontal cortex (including the dorsolateral prefrontal, anterior cingulate, and orbitofrontal cortices) and limbic structures (including the amygdala, hippocampus and nucleus accumbens) are key regions associated with three fundamental dimensions of temperament: Negative Affect, Positive Affect, and Constraint. Proposed relationships are based on two types of research: (a) research into the neurobiological correlates of affective and cognitive processes underlying these dimensions; and (b) research into the neurobiology of various psychopathologies, which have been correlated with these dimensions. A model is proposed detailing how these structures might comprise neural networks whose functioning underlies the three temperaments. Recommendations are made for future research into the neurobiology of temperament, including the need to focus on neural networks rather than individual structures, and the importance of prospective, longitudinal, multi-modal imaging studies in at-risk youth.

Amygdala↗
PubMed2005

Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia.

The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an "early neurodevelopmental" lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre- or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre- and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness. However, the pathological processes underlying such progressive changes during "late neurodevelopment" remain unclear but may reflect anomalies of synaptic plasticity, abnormal brain maturation, the adverse effects of stress, or other environmental factors. In this context, the features of schizophrenia, including the neuropsychological deficits and behavioral manifestations, can be understood as direct effects of these multiple pathological processes at various neurodevelopmental stages, including genetic and nongenetic etiological factors.

Brain↗
PubMed2005

Hippocampal and anterior cingulate morphology in subjects at ultra-high-risk for psychosis: the role of family history of psychotic illness.

BACKGROUND: While structural brain imaging abnormalities have been identified in schizophrenia and related disorders, it is unclear when they arise. Some appear to predate the illness and may be genetic in origin, while others are associated with the onset of the disorder. METHODS: We examined the hippocampal volumes and anterior cingulate morphology from the MRI scans of 79 male subjects at ultra-high-risk (UHR) for developing psychosis, 35 of whom had a family history of schizophrenia, and compared them with 49 healthy male volunteers. RESULTS: Analysis of covariance demonstrated that left hippocampal volumes were significantly smaller in the UHR group without a family history of schizophrenia, when compared to the UHR group with such history. A similar pattern was found for the left anterior cingulate region, both in terms of reduced paracingulate folding and cingulate sulcus interruptions, although this did not reach significance. CONCLUSIONS: We found that a family history of schizophrenia was not associated with a greater degree of structural brain abnormalities in an ultra-high-risk group, and in fact it was those UHR patients without such history who displayed greater abnormalities, although this only reached significance for the left hippocampus. Thus, it appears that the mechanisms that result in gross morphological anomalies in the hippocampus and anterior cingulate in psychosis are driven more by environmental than genetic factors.

Adult↗
PubMed2005

A manual and automated MRI study of anterior cingulate and orbito-frontal cortices, and caudate nucleus in obsessive-compulsive disorder: comparison with healthy controls and patients with schizophrenia.

Functional imaging and neuropsychological data suggest that interconnected brain structures including the orbito-frontal cortex (OFC), anterior cingulate cortex (ACC) and caudate nucleus (CN) are involved in the pathophysiology of obsessive-compulsive disorder (OCD), but structural imaging studies investigating these regions have yielded inconclusive results. This may be due to inconsistencies in the identification of anatomical boundaries and methodologies utilised (i.e. automated vs. manual tracing). This magnetic resonance imaging study used manual tracing to measure volumes of selected brain regions (OFC, ACC and CN) in OCD patients and compared them with samples of healthy (HC) and psychiatric (schizophrenia; SCZ) controls (n=18 in each group). Concurrently, automated voxel-based analysis was also used to detect subtle differences in cerebral grey and white matter. For the OCD vs. HC comparison, there were no significant volumetric differences detected using the manual or the automated method (although the latter revealed a deficit in the subcortical white matter of the right temporal region). A direct comparison of the two patient groups showed no significant differences using the manual method. However, a moderate effect size was detected for OFC grey matter (reduced in SCZ), which was supported by findings of reduced OFC volume in the automated analysis. Automated analyses also showed reduced volumes in the dorsal (white matter) and ventral ACC (grey and white matter), as well as the left posterior cingulate (grey and white matter) in SCZ. The findings suggest that in contrast to findings in SCZ, there are very few (if any) gross structural anomalies in OCD.

Adult↗
PubMed2005

Functional connectivity during Stroop task performance.

Using covariance-based multivariate analysis, we examined patterns of functional connectivity in rCBF on a practice-extended version of the Stroop color-word paradigm. Color-word congruent and incongruent conditions were presented in six AB trials to healthy subjects during 12 H2(15)O PET scans. Analyses identified two reproducible canonical eigenimages (CE) from the PET data, which were converted to a standard Z score scale after cross-validation resampling and correction for random subject effects. The first CE corresponded to practice-dependent changes in covarying rCBF that occurred over early task repetitions and correlated with improved behavioral performance. This included many regions previously implicated by PET and fMRI studies of this task, which we suggest may represent two "parallel" networks: (i) a cingulo-frontal system that was initially engaged in selecting and mapping a task-relevant response (color naming) when the attentional demands of the task were greatest; and (ii) a ventral visual processing stream whose concurrent decrease in activity represented the task-irrelevant inhibition of word reading. The second CE corresponded to a consistent paradigmatic effect of Stroop interference on covarying rCBF. Coactivations were located in dorsal and ventral prefrontal regions as well as frontopolar cortex. This pattern supports existing evidence that prefrontal regions are involved in maintaining attentional control over conflicting response systems. Taken together, these findings may be more in line with theoretical models that emphasize a role for practice in the emergence of Stroop phenomena. These findings may also provide some additional insight into the nature of anterior cingulate- and prefrontal cortical contributions to implementing cognitive control in the brain.

Arousal↗
PubMed2004

Individual differences in anterior cingulate/paracingulate morphology are related to executive functions in healthy males.

The neuropsychological correlates of inter-individual variations in cortical folding are poorly understood. Anterior cingulate (AC) cortex is one region characterized by considerable variability, particularly with respect to the paracingulate sulcus (PCS), which is present in only 30-60% of individuals and more commonly found in the left cerebral hemisphere. To investigate whether inter-individual differences in this PCS asymmetry are related to cognitive performance, we classified 30 healthy right-handed males as displaying either a leftward, rightward or symmetric pattern of folding based on the incidence and extent of the PCS in each hemisphere, and compared their performance on tasks engaging executive cognitive processes associated with frontal lobe function. We found that the more common leftward PCS asymmetry was associated with better performance across verbal and non-verbal executive tasks, but that PCS variability had no effect on tasks less dependent on executive functions. These results suggest that the leftward pattern of folding is associated with a non-specific performance advantage on cognitively demanding executive function tasks, possibly due to differences in functional interactions between AC/paracingulate cortex and connected frontal regions. It therefore appears that normal variations in brain morphology are associated with individual differences in cognitive abilities.

Adult↗
PubMed2004

Addiction, a condition of compulsive behaviour? Neuroimaging and neuropsychological evidence of inhibitory dysregulation.

AIMS: Addiction has been conceptualized as a shift from controlled experimentation to uncontrolled, compulsive patterns of use. Current neurobiological models of addiction emphasize changes within the brain's reward system, such that drugs of abuse 'hijack' this system and bias behaviour towards further drug use. While this model explains the involuntary nature of craving and the motivational drive to continue drug use, it does not explain fully why some addicted individuals are unable to control their drug use when faced with potentially disastrous consequences. In this review, we argue that such maladaptive and uncontrolled behaviour is underpinned by a failure of the brain's inhibitory control mechanisms. DESIGN: Relevant neuroimaging, neuropsychological and clinical studies are reviewed, along with data from our own research. FINDINGS: The current literature suggests that in addition to the brain's reward system, two frontal cortical regions (anterior cingulate and orbitofrontal cortices), critical in inhibitory control over reward-related behaviour, are dysfunctional in addicted individuals. These same regions have been implicated in other compulsive conditions characterized by deficits in inhibitory control over maladaptive behaviours, such as obsessive-compulsive disorder. CONCLUSIONS: We propose that in chronically addicted individuals, maladaptive behaviours and high relapse rates may be better conceptualized as being 'compulsive' in nature as a result of dysfunction within inhibitory brain circuitry, particularly during symptomatic states. This model may help to explain why some addicts lose control over their drug use, and engage in repetitive self-destructive patterns of drug-seeking and drug-taking that takes place at the expense of other important activities. This model may also have clinical utility, as it allows for the adoption of treatments effective in other disorders of inhibitory dysregulation.

Behavior, Addictive↗
PubMed2003

Early and late neurodevelopmental disturbances in schizophrenia and their functional consequences.

OBJECTIVE: The evidence from structural imaging studies supports the notion that schizophrenia arises from an early abnormality in brain development. In this paper we review the timing of structural changes in schizophrenia and argue that schizophrenia is a neuro-developmental disorder with limited progressive brain changes occurring during the evolution and early phase of psychosis. METHOD: The available cross-sectional and longitudinal studies are reviewed, along with data from our own research. RESULTS: The current literature, including our own data, suggests that structural brain changes are apparent premorbidly, consistent with a neurodevelopmental lesion. These are prominent in frontal and cingulate regions, and appear related to premorbid neuropsychological deficits in executive function. However, there appear to be additional brain changes over the transition to illness and beyond. CONCLUSIONS: We propose first, that an early neurodevelopmental insult interacts with either normal or abnormal postpubertal brain maturation to produce further (late neurodevelopmental) brain structural and functional changes; and second, that the effect of such neurodevelopmental lesions will have different consequences for functions that normally develop early in life, such as memory, compared with functions developing later, such as executive functions. A model is presented suggesting that the structural and functional abnormalities in schizophrenia can be understood as a consequence of the neurodevelopmental stage at which brain changes occur.

Brain↗
PubMed2003

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

BACKGROUND: 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. AIMS: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed2002

Paracingulate morphologic differences in males with established schizophrenia: a magnetic resonance imaging morphometric study.

BACKGROUND: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia. METHODS: Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex. RESULTS: Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere. CONCLUSIONS: These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.

Adult↗
PubMed2002

Anterior cingulate activation during Stroop task performance: a PET to MRI coregistration study of individual patients with schizophrenia.

OBJECTIVE: The authors used single-subject functional imaging analyses to 1) corroborate the findings of anterior cingulate hypoperfusion during an attentional task in schizophrenia and 2) examine whether anterior cingulate activation is associated with underlying morphology. METHOD: Five healthy subjects and six patients with schizophrenia underwent positron emission tomography scanning while they performed the Stroop task. The medial-frontal lobes were masked out for analysis, and activation peaks were individually coregistered to each subject's magnetic resonance imaging scan. RESULTS: Healthy subjects showed activations in both limbic and paralimbic anterior cingulate regions. Patients with schizophrenia showed only paralimbic activations, and these were apparent only in patients having a paracingulate sulcus. CONCLUSIONS: These findings suggest that 1) patients with schizophrenia have limbic-anterior cingulate hypoperfusion during attentional tasks and 2) paralimbic activation is associated with underlying morphology.

Adult↗