Fitzgerald KD, Welsh RC, Gehring WJ, Abelson JL, Himle JA, Liberzon I et al. Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder. Biol Psychiatry 57: 287-294

Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, 48109-0118, USA.
Biological Psychiatry (Impact Factor: 10.26). 03/2005; 57(3):287-94. DOI: 10.1016/j.biopsych.2004.10.038
Source: PubMed


Hyperactivity of the anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been shown to increase with symptom provocation and to normalize with treatment-induced symptom reduction. Although the functional significance of anterior cingulate involvement in OCD remains unknown, electrophysiological evidence has linked this region to error-processing abnormalities in patients with OCD. In this functional magnetic resonance imaging (fMRI) study, we sought to further localize error-processing differences within the ACC of OCD patients compared with healthy subjects.
Event-related fMRI data were collected for eight OCD patients and seven healthy subjects during the performance of a simple cognitive task designed to elicit errors but not OCD symptoms.
Both OCD patients and healthy subjects demonstrated dorsal ACC activation during error commission. The OCD patients exhibited significantly greater error-related activation of the rostral ACC than comparison subjects. Activity in this region was positively correlated with symptom severity in the patients.
Error-processing abnormalities within the rostral anterior cingulate occur in the absence of symptom expression in patients with OCD.

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    • "This dichotomous circuitry contrasts with patterns of fronto-striato-limbic hyperactivation shown in previous OCD studies, which is likely related to differences in task nature and design, leading to distinct functional interpretation . For instance, several studies in OCD show increased activity in frontal areas using different behavioural tasks; however, these studies focus on testing different cognitive processes and tasks rather that symptom generation (Fitzgerald et al., 2005; Maltby et al., 2005; Chamberlain et al., 2008). Moreover, some symptom evocation and provocation studies asked patients to imagine, recognize or recall contexts related to past symptoms using exposure to images or words (Mataix-Cols et al., 2004; Nakao et al., 2005; Schienle et al., 2005; Gilbert et al., 2009; Simon et al., 2010; Baioui et al., 2013) or using real sensory stimulation (physical objects) (McGuire et al., 1994; Rauch et al., 1994; Breiter et al., 1996; Adler et al., 2000; Hendler et al., 2003). "
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    ABSTRACT: Intrusive thoughts and compulsive urges to perform stereotyped behaviours are typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a cognitive bias towards habit formation at the expense of goal-directed performance in obsessive-compulsive disorder. In this study, we test this hypothesis using a novel individualized ecologically valid symptom provocation design: a live provocation functional magnetic resonance imaging paradigm with synchronous video-recording of behavioural avoidance responses. By pairing symptom provocation with online avoidance responses on a trial-by-trial basis, we sought to investigate the neural mechanisms leading to the compulsive avoidance response. In keeping with the model of habit formation in obsessive-compulsive disorder, we hypothesized that this disorder would be associated with lower activity in regions implicated in goal-directed behaviours and higher activity in regions implicated in habitual behaviours. Fifteen patients with obsessive-compulsive disorder and 15 healthy control volunteers participated in this functional magnetic resonance imaging study. Online stimuli were individually tailored to achieve effective symptom provocation at neutral, intermediate and strong intensity levels. During the symptom provocation block, the participant could choose to reject or terminate the provoking stimuli resulting in cessation of the symptom provocation. We thus separately analysed the neural correlates of symptom provocation, the urge to avoid, rejection and relief. Strongly symptom-provoking conditions evoked a dichotomous pattern of deactivation/activation in patients, which was not observed either in control conditions or in healthy subjects: a deactivation of caudate-prefrontal circuits accompanied by hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during patients' symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in obsessive-compulsive disorder. Effective connectivity analysis identified the ventromedial prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry involved in the modulation of compulsivity in obsessive-compulsive disorder. These findings suggest an imbalance in circuitry underlying habitual and goal-directed action control, which may represent a fundamental mechanism underlying compulsivity in obsessive-compulsive disorder. Our results complement current models of symptom generation in obsessive-compulsive disorder and may enable the development of future therapeutic approaches that aim to alleviate this imbalance. URL link:
    Brain 01/2015; DOI:10.1093/brain/awu379 · 9.20 Impact Factor
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    • "The limbic system is a group of interconnected cortical and subcortical structures dedicated to linking visceral states and emotion to cognition and behavior (Mesulam, 2000). The limbic system plays a key role in a variety of psychiatric and neuropsychological disorders including schizophrenia (e.g., Torrey and Peterson, 1974; Reynolds, 1983; White et al., 2008; Leech and Sharp, 2014), major depressive disorder (e.g., Monkul et al., 2007; DeRubeis et al., 2008; Duman and Voleti, 2012), autism (e.g., Amaral et al., 2008), Alzheimer’s disease (e.g., Braak and Braak, 1991), and obsessive-compulsive disorder (e.g., Fitzgerald et al., 2005; Abramowitz et al., 2009). As major white matter tracts underlying connectivity of the limbic system, cingulum bundle (including cingulum cingulate gyrus part or cgc and cingulum hippocampal part or cgh) and fornix (fx) could be affected in the pathological state. "
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    ABSTRACT: The cingulum and fornix play an important role in memory, attention, spatial orientation and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer’s disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc), hippocampal part of the cingulum (cgh) and fornix (fx) were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial and radial diffusivity were measured for traced limbic tracts. Free water elimination (FWE) algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for FWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2-year-old followed by a slow increase to 25-year-old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network (DMN) was confirmed as early as birth. Systematic characterization of length and DTI metrics after FWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with mental disorders.
    Frontiers in Aging Neuroscience 08/2014; 6:228. DOI:10.3389/fnagi.2014.00228 · 4.00 Impact Factor
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    • "Some studies reported hyperactivation of the ACC in adults and children with OCD following errors and interference control (Fitzgerald et al., 2005; Huyser et al., 2011), while others reported hypoactivation of the ACC (Nakao et al., 2005a; Rubia et al., 2011a). Altered inhibition-related brain activation has also been observed in the pre-SMA (Fitzgerald et al., 2005; Rubia et al., 2011a) and insular cortex (Huyser et al., 2011). Increased activation in frontal–striatal regions, including the IFG and putamen, was seen in OCD patients during performance of a Simon task (Marsh et al., 2013). "
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    Frontiers in Human Neuroscience 06/2014; 8:419. DOI:10.3389/fnhum.2014.00419 · 3.63 Impact Factor
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