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Pino Alonso,
Clara López-Solà,
Mónica Gratacós,
Miquel Angel Fullana,
Cinto Segalàs,
Eva Real,
Narcís Cardoner,
Carles Soriano-Mas, Ben J Harrison,
Xavier Estivill,
José M Menchón
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ABSTRACT: Cognitive models emphasize the importance of dysfunctional beliefs as overimportance/need to control thoughts, perfectionism, intolerance of uncertainty, responsibility, and overestimation of threat in obsessive-compulsive disorder (OCD). Twin studies suggest that these beliefs are significantly heritable, but candidate genes associated with them have not been analyzed. We genotyped the Val158Met in the COMT gene and Val66Met variant in the BDNF gene in 141 OCD patients and analyzed their single and interactive effects on the obsessive beliefs questionnaire (OBQ-44). Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype in isolation, but we detected a significant COMT×BDNF interaction effect on responsibility/overestimation of threat and overimportance/need to control thoughts scores. Subjects with the BDNF Met-present and the COMT Met-present genotype showed higher scores on responsibility/overestimation of threat. An interaction between dopaminergic and neurotrophic functional gene variants may influence dysfunctional beliefs hypothesized to contribute to the development of OCD.
Journal of anxiety disorders 03/2013; 27(3):321-327. · 2.68 Impact Factor
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Oren Contreras-Rodríguez,
Jesus Pujol,
Iolanda Batalla, Ben J Harrison,
Javier Bosque,
Immaculada Ibern-Regàs,
Rosa Hernández-Ribas,
Carles Soriano-Mas,
Joan Deus,
Marina López-Solà,
Josep Pifarré,
José M Menchón,
Narcís Cardoner
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ABSTRACT: Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point towards an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face processing network. Twenty-two psychopaths and 22 control subjects were assessed and fMRI maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction (PPI) analysis during an emotional face matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. By contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths' affective-interpersonal disturbances. PPI analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.
Social Cognitive and Affective Neuroscience 02/2013; · 6.13 Impact Factor
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ABSTRACT: In this study, we evaluated insight into different obsessive-compulsive disorder (OCD) symptom dimensions and their impact on clinical and sociodemographic features of patients with OCD.
Sixty OCD patients were assessed with the Brown Assessment of Beliefs Scale (BABS), the Dimensional Yale-Brown Obsessive-Compulsive Scale-Short Version, the Beck Depression Inventory, and the Sheehan Disability Scale. Two methods of using BABS were employed: 1) a traditional approach, which considers a composite of the insight into existing OCD symptoms, and 2) an alternative approach, which includes assessments of insight into each OCD symptom dimension separately.
Composite BABS scores correlated with global severity of OCD and depressive symptoms, and degree of interference on social life/leisure activities and family life/home responsibilities. Dimension-specific correlations between severity of symptoms and insight ranged from very high (P = .87, for hoarding) to moderate (P = .61, for miscellaneous symptoms). Greater severity of depression and concomitant generalized anxiety disorder were independently associated with lower levels of insight into aggressive/checking symptoms. While earlier-onset OCD was associated with lower insight into sexual/religious and symmetry symptoms, later-onset OCD displayed lower insight into hoarding.
Assessing insight into dimension-specific OCD symptoms may challenge the existence of clear-cut OCD with fair or poor insight.
Annals of Clinical Psychiatry 02/2013; 25(1):11-6. · 1.49 Impact Factor
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Albert Batalla,
Carles Soriano-Mas,
Marina López-Solà,
Marta Torrens,
José A Crippa,
Sagnik Bhattacharyya,
Laura Blanco-Hinojo,
Ana B Fagundo, Ben J Harrison,
Santiago Nogué,
Rafael de la Torre,
Magí Farré,
Jesús Pujol,
Rocío Martín-Santos
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ABSTRACT: Neuroimaging studies have shown that chronic consumption of cannabis may result in alterations in brain morphology. Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. We measured the influence of COMT genotype on the volume of four key regions: the prefrontal cortex, neostriatum (caudate-putamen), anterior cingulate cortex and hippocampus-amygdala complex, in chronic early-onset cannabis users and healthy control subjects. We selected 29 chronic cannabis users who began using cannabis before 16 years of age and matched them to 28 healthy volunteers in terms of age, educational level and IQ. Participants were male, Caucasians aged between 18 and 30 years. All were assessed by a structured psychiatric interview (PRISM) to exclude any lifetime Axis-I disorder according to Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition. COMT genotyping was performed and structural magnetic resonance imaging data was analyzed by voxel-based morphometry. The results showed that the COMT polymorphism influenced the volume of the bilateral ventral caudate nucleus in both groups, but in an opposite direction: more copies of val allele led to lesser volume in chronic cannabis users and more volume in controls. The opposite pattern was found in left amygdala. There were no effects of COMT genotype on volumes of the whole brain or the other selected regions. Our findings support recent reports of neuroanatomical changes associated with cannabis use and, for the first time, reveal that these changes may be influenced by the COMT genotype.
Addiction Biology 01/2013; · 4.83 Impact Factor
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Ben J Harrison,
Jesus Pujol,
Narcis Cardoner,
Joan Deus,
Pino Alonso,
Marina López-Solà,
Oren Contreras-Rodríguez,
Eva Real,
Cinto Segalàs,
Laura Blanco-Hinojo,
José M Menchon,
Carles Soriano-Mas
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ABSTRACT: BACKGROUND: Functional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder's prominent clinical heterogeneity. METHODS: To address these concerns, we investigated the influence of major OCD symptom dimensions on brain corticostriatal functional systems in a large sample of OCD patients (n = 74) and control participants (n = 74) examined with resting-state functional magnetic resonance imaging. We employed a valid method for mapping ventral and dorsal striatal functional connectivity, which supported both standard group comparisons and linear regression analyses with patients' scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. RESULTS: Consistent with past findings, patients demonstrated a common connectivity alteration involving the ventral striatum and orbitofrontal cortex that predicted overall illness severity levels. This common alteration was independent of the effect of particular symptom dimensions. Instead, we observed distinct anatomical relationships between the severity of symptom dimensions and striatal functional connectivity. Aggression symptoms modulated connectivity between the ventral striatum, amygdala, and ventromedial frontal cortex, while sexual/religious symptoms had a specific influence on ventral striatal-insular connectivity. Hoarding modulated the strength of ventral and dorsal striatal connectivity with distributed frontal regions. CONCLUSIONS: Taken together, these results suggest that pathophysiological changes among orbitofrontal-striatal regions may be common to all forms of OCD. They suggest that a further examination of certain dimensional relationships will also be relevant for advancing current neurobiological models of the disorder.
Biological psychiatry 11/2012; · 8.93 Impact Factor
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ABSTRACT: Analyses of functional interactions between large-scale brain networks have identified two broad systems that operate in apparent competition or antagonism with each other. One system, termed the default mode network (DMN), is thought to support internally oriented processing. The other system acts as a generic external attention system (EAS) and mediates attention to exogenous stimuli. Reports that the DMN and EAS show anticorrelated activity across a range of experimental paradigms suggest that competition between these systems supports adaptive behavior. Here, we used functional MRI to characterize functional interactions between the DMN and different EAS components during performance of a recollection task known to coactivate regions of both networks. Using methods to isolate task-related, context-dependent changes in functional connectivity between these systems, we show that increased cooperation between the DMN and a specific right-lateralized frontoparietal component of the EAS is associated with more rapid memory recollection. We also show that these cooperative dynamics are facilitated by a dynamic reconfiguration of the functional architecture of the DMN into core and transitional modules, with the latter serving to enhance integration with frontoparietal regions. In particular, the right posterior cingulate cortex may act as a critical information-processing hub that provokes these context-dependent reconfigurations from an intrinsic or default state of antagonism. Our findings highlight the dynamic, context-dependent nature of large-scale brain dynamics and shed light on their contribution to individual differences in behavior.
Proceedings of the National Academy of Sciences 07/2012; 109(31):12788-93. · 9.68 Impact Factor
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Ben J Harrison,
Jesus Pujol,
Carles Soriano-Mas,
Rosa Hernández-Ribas,
Marina López-Solà,
Hector Ortiz,
Pino Alonso,
Joan Deus,
José M Menchon,
Eva Real,
Cinto Segalàs,
Oren Contreras-Rodríguez,
Laura Blanco-Hinojo,
Narcís Cardoner
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ABSTRACT: Heightened moral sensitivity seems to characterize patients with obsessive-compulsive disorder (OCD). Recent advances in social cognitive neuroscience suggest that a compelling relationship may exist between this disorder-relevant processing bias and the functional activity of brain regions implicated in OCD.
To test the hypothesis that patients with OCD demonstrate an increased response of relevant ventromedial prefrontal and orbitofrontal cortex regions in a functional magnetic resonance imaging study of difficult moral decision making.
Case-control cross-sectional study.
Hospital referral OCD unit and magnetic resonance imaging facility.
Seventy-three patients with OCD (42 men and 31 women) and 73 control participants matched for age, sex, and education level.
Functional magnetic resonance imaging activation maps representing significant changes in blood oxygenation level-dependent signal in response to 24 hypothetical moral dilemma vs nondilemma task vignettes and additional activation maps representing significant linear associations between patients' brain responses and symptom severity ratings.
In both groups, moral dilemma led to robust activation of frontal and temporoparietal brain regions. Supporting predictions, patients with OCD demonstrated significantly increased activation of the ventral frontal cortex, particularly of the medial orbitofrontal cortex. In addition, the left dorsolateral prefrontal cortex and left middle temporal gyrus were more robustly activated in patients with OCD. These results were unexplained by group differences in comorbid affective symptoms. Patients' global illness severity predicted the relative magnitude of orbitofrontal-striatal activation. The severity of "harm/checking" symptoms and "sexual/religious" obsessions predicted the magnitude of posterior temporal and amygdala-paralimbic activation, respectively.
The neural correlates of moral sensitivity in patients with OCD partly coincide with brain regions that are of general interest to pathophysiologic models of this disorder. In particular, these findings suggest that the orbitofrontal cortex together with the left dorsolateral prefrontal cortex may be relevant for understanding the link between neurobiological processes and certain maladaptive cognitions in OCD.
Archives of general psychiatry 07/2012; 69(7):741-9. · 12.26 Impact Factor
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ABSTRACT: The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 04/2012; 37(8):1923-33. · 6.99 Impact Factor
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ABSTRACT: Obsessive-compulsive disorder (OCD) is associated with a range of emotional abnormalities linked to its defining symptoms, comorbid illnesses and cognitive deficits. The aim of this preliminary study was to examine functional changes in the brain that are associated with experimentally induced sad mood in patients with OCD compared with healthy controls in a frontolimbic circuit relevant to both OCD and mood regulation.
Participants underwent a validated sad mood induction procedure during functional magnetic resonance imaging. Analyses focused on mapping changes in the functional connectivity of the subgenual anterior cingulate cortex (ACC) within and between the 2 groups in response to successfully induced sadness.
We enrolled 11 patients with OCD and 10 age-, sex- and IQ-matched controls in our study. Unlike controls, patients with OCD did not demonstrate predicted increases in functional connectivity between the subgenual ACC and other frontal regions during mood induction. Instead, patients demonstrated heightened connectivity between the subgenual ACC and ventral caudate/nucleus accumbens region and the hypothalamus.
Our study included a small, partially medicated patient cohort that precluded our ability to investigate sex or drug effects, evaluate behavioural differences between the groups and perform a whole-brain analysis.
The ventral striatum and ventral frontal cortex were distinctly and differentially modulated in their connectivity with the subgenual ACC during the experience of sad mood in patients with OCD. These results suggest that, in patients with OCD, induced sadness appears to have provoked a primary subcortical component of the hypothesized "OCD circuit," which may offer insights into why OCD symptoms tend to develop and worsen during disturbed emotional states.
Journal of psychiatry & neuroscience: JPN 03/2012; 37(4):231-40. · 5.34 Impact Factor
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Leonardo F Fontenelle,
Luca Cocchi, Ben J Harrison,
Roseli G Shavitt,
Maria Conceição do Rosário,
Ygor A Ferrão,
Maria Alice de Mathis,
Aristides V Cordioli,
Murat Yücel,
Christos Pantelis,
Jair de Jesus Mari,
Euripedes C Miguel,
Albina R Torres
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ABSTRACT: We evaluated whether traumatic events are associated with a distinctive pattern of socio-demographic and clinical features of obsessive-compulsive disorder (OCD). We compared socio-demographic and clinical features of 106 patients developing OCD after post-traumatic stress disorder (PTSD; termed post-traumatic OCD), 41 patients developing OCD before PTSD (pre-traumatic OCD), and 810 OCD patients without any history of PTSD (non-traumatic OCD) using multinomial logistic regression analysis. A later age at onset of OCD, self-mutilation disorder, history of suicide plans, panic disorder with agoraphobia, and compulsive buying disorder were independently related to post-traumatic OCD. In contrast, earlier age at OCD onset, alcohol-related disorders, contamination-washing symptoms, and self-mutilation disorder were all independently associated with pre-traumatic OCD. In addition, patients with post-traumatic OCD without a previous history of obsessive-compulsive symptoms (OCS) showed lower educational levels, greater rates of contamination-washing symptoms, and more severe miscellaneous symptoms as compared to post-traumatic OCD patients with a history of OCS.
Journal of anxiety disorders 03/2012; 26(2):377-83. · 2.68 Impact Factor
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ABSTRACT: Background: Major depressive disorder is associated with functional alterations in activity and resting-state connectivity of the extended medial frontal network. In this study we aimed to examine how task-related medial network activity and connectivity were affected in depression. Methods: 18 patients with major depressive disorder, aged 15- to 24-years-old, were matched with 19 healthy control participants. We characterized task-related activations and deactivations while participants engaged with an executive-control task (the multi-source interference task, MSIT). We used a psycho-physiological interactions approach to examine functional connectivity changes with subgenual anterior cingulate cortex. Voxel-wise statistical maps for each analysis were compared between the patient and control groups. Results: There were no differences between groups in their behavioral performances on the MSIT task, and nor in patterns of activation and deactivation. Assessment of functional connectivity with the subgenual cingulate showed that depressed patients did not demonstrate the same reduction in functional connectivity with the ventral striatum during task performance, but that they showed greater reduction in functional connectivity with adjacent ventromedial frontal cortex. The magnitude of this latter connectivity change predicted the relative activation of task-relevant executive-control regions in depressed patients. Conclusion: The study reinforces the importance of the subgenual cingulate cortex for depression, and demonstrates how dysfunctional connectivity with ventral brain regions might influence executive-attentional processes.
Frontiers in psychiatry / Frontiers Research Foundation. 01/2012; 3:14.
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Frontiers in psychiatry / Frontiers Research Foundation. 01/2012; 3:72.
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Jesus Pujol,
Iolanda Batalla,
Oren Contreras-Rodríguez, Ben J Harrison,
Vanessa Pera,
Rosa Hernández-Ribas,
Eva Real,
Laura Bosa,
Carles Soriano-Mas,
Joan Deus,
Marina López-Solà,
Josep Pifarré,
José M Menchón,
Narcís Cardoner
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ABSTRACT: Neuroimaging research has demonstrated the involvement of a well-defined brain network in the mediation of moral judgment in normal population, and has suggested the inappropriate network use in criminal psychopathy. We used functional magnetic resonance imaging (fMRI) to prove that alterations in the brain network subserving moral judgment in criminal psychopaths are not limited to the inadequate network use during moral judgment, but that a primary network breakdown would exist with dysfunctional alterations outside moral dilemma situations. A total of 22 criminal psychopathic men and 22 control subjects were assessed and fMRI maps were generated to identify (i) brain response to moral dilemmas, (ii) task-induced deactivation of the network during a conventional cognitive task and (iii) the strength of functional connectivity within the network during resting-state. The obtained functional brain maps indeed confirmed that the network subserving moral judgment is underactive in psychopathic individuals during moral dilemma situations, but the data also provided evidence of a baseline network alteration outside moral contexts with a functional disconnection between emotional and cognitive elements that jointly construct moral judgment. The finding may have significant social implications if considering psychopathic behavior to be a result of a primary breakdown in basic brain systems.
Social Cognitive and Affective Neuroscience 10/2011; · 6.13 Impact Factor
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Narcís Cardoner, Ben J Harrison,
Jesús Pujol,
Carles Soriano-Mas,
Rosa Hernández-Ribas,
Marina López-Solá,
Eva Real,
Joan Deus,
Hector Ortiz,
Pino Alonso,
José M Menchón
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ABSTRACT: OBJECTIVES. The abnormal processing of emotional stimuli is common to a variety of psychiatric disorders. Specifically, patients with prominent anxiety symptoms generally overreact to emotional cues, which has been linked to increased amygdala activation. However, in OCD, enhanced responses are predominantly obtained using disease-specific stimuli and preferentially involve frontostriatal systems. METHODS. We assessed 21 OCD patients and 21 healthy controls with fMRI during an emotional face-processing paradigm involving active response generation to test for alterations in both brain activation and task-induced functional connectivity of the frontal cortex, the amygdala and the fusiform face area. RESULTS. OCD patients showed significantly greater activation of "face-processing" regions including the amygdala, fusiform gyrus and dorsolateral prefrontal cortex. The reciprocal connectivity between face-processing regions was enhanced in OCD. Importantly, we detected significant correlations between patients' clinical symptom severity and both task-related region activation and network functional connectivity. CONCLUSIONS. The results suggest that OCD patients may show enhanced brain responsiveness during emotional face-processing when tasks involve active response generation. Our findings diverge from previously described alterations in anxiety disorders, as patients showed enhanced amygdala-prefrontal connectivity as opposed to negative reciprocal interaction. This pattern would appear to be disorder-specific and was significantly related to obsessive-compulsive symptom severity.
The World Journal of Biological Psychiatry 08/2011; 12(5):349-63. · 2.38 Impact Factor
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Jesus Pujol,
Carles Soriano-Mas,
Juan D Gispert,
Matías Bossa,
Santiago Reig,
Hector Ortiz,
Pino Alonso,
Narcís Cardoner,
Marina López-Solà, Ben J Harrison,
Joan Deus,
José M Menchón,
Manuel Desco,
Salvador Olmos
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ABSTRACT: Obsessive-compulsive disorder (OCD) emerges during childhood through young adulthood coinciding with the late phases of postnatal brain development when fine remodeling of brain anatomy takes place. Previous research has suggested the existence of subtle anatomical alterations in OCD involving focal volume variations in different brain regions including the frontal lobes and basal ganglia. We investigated whether anatomical changes might also involve variations in the shape of the frontobasal region. A total of 101 OCD patients and 101 control subjects were examined using magnetic resonance imaging. A cross-sectional image highly representative of frontal-basal ganglia anatomy was selected in each individual and 25 reliable anatomical landmarks were identified to assess shape changes. A pixel-wise morphing approach was also used to dynamically illustrate the findings. We found significant group differences for overall landmark position and for most individual landmarks delimiting the defined frontobasal region. OCD patients showed a deformation pattern involving shortening of the anterior-posterior dimension of the frontal lobes and basal ganglia, and enlargement of cerebrospinal fluid spaces around the frontal opercula. In addition, we observed significant correlation of brain tissue shape variation with frontal sinus size. Identification of a global change in the shape of the frontobasal region may further contribute to characterizing the nature of brain alterations in OCD. The coincidence of brain shape variations with morphological changes in the frontal sinus indicates a potential association of OCD to late development disturbances, as the frontal sinus macroscopically emerges during the transition between childhood and adulthood.
Human Brain Mapping 07/2011; 32(7):1100-8. · 5.88 Impact Factor
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ABSTRACT: Neuroimaging studies have consistently implicated alterations of the basal ganglia and orbitofrontal cortex in the pathophysiology of OCD, however, recent work also emphasizes more diffuse patterns of brain alteration as occurring in this disorder. The goal of this study was to extend such observations by investigating large-scale brain functional network correlates of cognitive-control performance in OCD patients.
We combined fMRI with a validated task of cognitive control and a multivariate statistical method to assess multiple functional networks encompassing broad task-relevant cortical regions in OCD patients and matched controls. Functional networks of interest were targeted a priori and the groups were compared in terms of the spatiotemporal profile of network responses (functional connectivity) during the task performance in a data-driven manner.
Task performance was equivalent in both groups and each distinct network demonstrated strong overlap in its general response during task. However, significant differences in functional connectivity were also observed between groups that appeared driven by specific phases of task performance. Such differences were most pronounced during rest-task transitions and mainly involved dorsal anterior cingulate and insular cortices within the paralimbic network. Relative heightened functional connectivity of insula in patients during task correlated with a measure of patients' state anxiety.
Our findings provide a novel functional imaging characterization of brain network alterations associated with cognitive-control in OCD. Additionally, these findings raise questions about the role of patients' arousal states on the performance of cognitive imaging tasks that are otherwise assumed to be emotionally neutral.
Human Brain Mapping 05/2011; 33(5):1089-106. · 5.88 Impact Factor
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ABSTRACT: The basic concepts underlying compulsive, impulsive and addictive behaviours overlap, which may help explain why laymen use these expressions interchangeably. Although there has been a large research effort to better characterize and disentangle these behaviours, clinicians and scientists are still unable to clearly differentiate them. Accordingly, obsessive-compulsive disorder (OCD), impulse control disorders (ICD) and substance-related disorders (SUD) overlap on different levels, including phenomenology, co-morbidity, neurocircuitry, neurocognition, neurochemistry and family history. In this review we summarize these issues with particular emphasis on the role of the opioid system in the pathophysiology and treatment of OCD, ICD and SUD. We postulate that with progression and chronicity of OCD, the proportion of the OCD-related behaviours (e.g. checking, washing, ordering and hoarding, among others) that are driven by impulsive 'rash' processes increase as involvement of more ventral striatal circuits becomes prominent. In contrast, as SUD and ICD progress, the proportion of the SUD- and ICD-related behaviours that are driven by compulsive 'habitual' processes increase as involvement of more dorsal striatal circuits become prominent. We are not arguing that, with time, ICD becomes OCD or vice versa. Instead, we are proposing that these disorders may acquire qualities of the other with time. In other words, while patients with ICD/SUD may develop 'compulsive impulsions', patients with OCD may exhibit 'impulsive compulsions'. There are many potential implications of our model. Theoretically, OCD patients exhibiting impulsive or addictive features could be managed with drugs that address the quality of the underlying drives and the involvement of neural systems. For example, agents for the reduction or prevention of relapse of addiction (e.g. heavy drinking), which modulate the cortico-mesolimbic dopamine system through the opioid (e.g. buprenorphine and naltrexone), glutamate (e.g. topiramate), serotonin (e.g. ondansetron) or γ-aminobutyric acid (e.g. baclofen and topiramate) systems, may prove to show some benefit in certain forms of OCD. Based on the available evidence, we suggest that the treatment of patients with these disorders must account for alterations in the underlying motivations and neurobiology of the condition. We provide an initial guide to the specific treatments that future clinical trials might consider in patients with OCD. For example, it might be wise to test naltrexone in patients with co-morbid SUD and ICD, topiramate in patients with co-morbid ICD and eating disorders, and baclofen in patients with co-morbid Tourette's syndrome. These trials could also include scales aimed at assessing underlying impulsivity (e.g. Barratt Impulsiveness Scale) to check whether this construct might predict response to drugs acting on the reward system.
Drugs 05/2011; 71(7):827-40. · 4.23 Impact Factor
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ABSTRACT: Previous diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD) have reported inconsistent findings, and it is not known whether observed findings are related to abnormalities in axonal structure or myelination.
In this DTI study, we investigated fractional anisotropy, as well as axial and radial diffusivity, in 21 patients with OCD and 29 healthy controls.
We found decreased fractional anisotropy in the body of the corpus callosum in the OCD group, which was underpinned by increased radial diffusivity. Limitations: The cross-sectional design was the main limitation.
Our findings of increased radial diffusivity provide preliminary evidence for abnormal myelination in patients with OCD.
Journal of psychiatry & neuroscience: JPN 01/2011; 36(1):42-6. · 5.34 Impact Factor
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ABSTRACT: Studies of depressed patients have demonstrated increased amygdala activation to negative affective stimuli. In this study, we used a paradigm that employed personally relevant social stimuli, which are known to strongly activate the amygdala, to test whether the amygdala demonstrated aberrant activity in depressed participants as they responded to stimuli with positive valence.
Nineteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. They completed a novel functional magnetic resonance imaging task in which they received social feedback from people who they believed had evaluated them. Voxelwise statistical parametric maps of brain response to positive social feedback and to a control feedback condition were compared to test the hypothesis that differences in neural response between depressed and control participants would arise in the amygdala.
Depressed participants showed increased neural response to the positive- versus control-feedback condition in the amygdala (p < .05, corrected). An exploratory analysis showed that depressed participants responded to faces from both feedback conditions with increased activity in regions subserving social appraisal (ventrolateral prefrontal cortex and inferior parietal cortex) and affective processing (pregenual anterior cingulate cortex and anterior insular cortex; p < .001, uncorrected).
Depressed patients responded to positive social feedback with increased amygdala activation, demonstrating that amygdala hyperresponsivity in depression is not restricted to negatively-valenced stimuli. The heightened sensitivity of depressed participants to social evaluation may help explain symptoms of depression such as social withdrawal.
Biological psychiatry 01/2011; 69(8):734-41. · 8.93 Impact Factor
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Ben J Harrison,
Jesus Pujol,
Oren Contreras-Rodríguez,
Carles Soriano-Mas,
Marina López-Solà,
Joan Deus,
Hector Ortiz,
Laura Blanco-Hinojo,
Pino Alonso,
Rosa Hernández-Ribas,
Narcís Cardoner,
José M Menchón
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ABSTRACT: Activity decreases, or deactivations, of midline and parietal cortical brain regions are routinely observed in human functional neuroimaging studies that compare periods of task-based cognitive performance with passive states, such as rest. It is now widely held that such task-induced deactivations index a highly organized 'default-mode network' (DMN): a large-scale brain system whose discovery has had broad implications in the study of human brain function and behavior. In this work, we show that common task-induced deactivations from rest also occur outside of the DMN as a function of increased task demand. Fifty healthy adult subjects performed two distinct functional magnetic resonance imaging tasks that were designed to reliably map deactivations from a resting baseline. As primary findings, increases in task demand consistently modulated the regional anatomy of DMN deactivation. At high levels of task demand, robust deactivation was observed in non-DMN regions, most notably, the posterior insular cortex. Deactivation of this region was directly implicated in a performance-based analysis of experienced task difficulty. Together, these findings suggest that task-induced deactivations from rest are not limited to the DMN and extend to brain regions typically associated with integrative sensory and interoceptive processes.
PLoS ONE 01/2011; 6(7):e22964. · 4.09 Impact Factor
