Riffkin J, Yucel M, Maruff P, Wood SJ, Soulsby B, Olver J et al. 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. Psychiatry Res 138: 99-113

Melbourne Neuropsychiatry Centre, University of Melbourne and Sunshine Hospital, Melbourne, Victoria, Australia.
Psychiatry Research (Impact Factor: 2.47). 03/2005; 138(2):99-113. DOI: 10.1016/j.pscychresns.2004.11.007
Source: PubMed


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.

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    • "Data for this analysis were obtained from all ten WMV datasets including 333 patients with OCD and 344 healthy controls (Carmona et al, 2007; Duran et al, 2009; Koprivova et al, 2009; Lazaro et al, 2011; Matsumoto et al, 2010; Pujol et al, 2004; Riffkin et al, 2005; Togao et al, 2010; van den Heuvel et al, 2009; Yoo et al, 2008). Patients showed significantly increased WMV in anterior midline WM structures, approximately corresponding to the corpus callosum (CC) and the cingulum bundle, as well as the right anterior thalamic radiation and the left arcuate fasciculus. "
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    ABSTRACT: White matter abnormalities have long been suspected in obsessive-compulsive disorder (OCD) but the available evidence has been inconsistent. We conducted the first multimodal meta-analysis of white matter volume (WMV) and fractional anisotropy (FA) studies in OCD. All voxel-wise studies comparing WMV or FA between patients with OCD and healthy controls in the PubMed, ScienceDirect, Google Scholar, Web of Knowledge and Scopus databases were retrieved. Manual searches were also conducted and authors were contacted soliciting additional data. Thirty-four datasets were identified, of which 22 met inclusion criteria (five of them unpublished; comprising 537 adult and pediatric patients with OCD and 575 matched healthy controls). Whenever possible, raw statistical parametric maps were also obtained from the authors. Peak and raw WMV and FA data were combined using novel multimodal meta-analytic methods implemented in effect-size signed differential mapping (ES-SDM). Patients with OCD showed widespread white matter abnormalities, but findings were particularly robust in the anterior midline tracts (crossing between anterior parts of cingulum bundle and body of corpus callosum), which showed both increased WMV and decreased FA, possibly suggesting an increase of fiber crossing in these regions. This finding was also observed when the analysis was limited to adult participants, and especially pronounced in samples with a higher proportion of medicated patients. Therefore, patients with OCD may have widespread white matter abnormalities, particularly evident in anterior midline tracts, though these changes might be, at least in part, attributable to the effects of therapeutic drugs.Neuropsychopharmacology accepted article preview online, 10 January 2014. doi:10.1038/npp.2014.5.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2014; 39(7). DOI:10.1038/npp.2014.5 · 7.05 Impact Factor
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    • "Out of a total of 56 reviewed publications reporting cingulate boundaries, 13 do not mention the PCG (Ballmaier et al. 2004; van Elst et al. 2003; Flashman et al. 2001; Raz et al. 1995; Salat et al. 2001; Sowell et al. 2002; Woodward et al. 2006). Three treated the PCG as part of the cingulate region (Convit et al. 2001; Ranta et al. 2009; Wible et al. 1995), 10 included it as part of the superior frontal gyrus on the medial aspect (Bremner et al. 1998; John et al. 2006; Lindberg et al. 2009; MacLullich et al. 2006; Suzuki et al. 2005; Szeszko et al. 1999a, b; Yamasue et al. 2004), though 27 treat it as a separate entity altogether (Bremner et al. 2002; Crespo-Facorro et al. 1999; Fornito et al. 2006; McCormick et al. 2006; Monkul et al. 2007; Noga et al. 1995; Paus et al. 1996; Rademacher et al. 1992; Riffkin et al. 2005; Takahashi et al. 2002). "
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    ABSTRACT: Manual volumetric measurement of the brain's frontal lobe and its subregions from magnetic resonance images (MRIs) is an established method for researching neural correlates of clinical disorders or cognitive functions. However, there is no consensus between methods used to identify relevant boundaries of a given region of interest (ROI) on MRIs, and those used may bear little relation to each other or the underlying structural, functional and connective architecture. This presents challenges for the analysis and synthesis of such results. We therefore performed a systematic literature review to highlight variations in the anatomical boundaries used to measure frontal regions, contextualised by up-to-date evidence from histology, hodology and neuropsychology. We searched EMBASE and MEDLINE for studies in English reporting three-dimensional boundaries for manually delineating the brain's frontal lobe or sub-regional ROIs from MRIs. Exclusion criteria were: exclusive use of co-ordinate grid systems; insufficient detail to allow method replication; publication in grey literature only. Papers were assessed on quality criteria relating to bias, reproducibility and protocol rationale. There was a large degree of variability in the three-dimensional boundaries of all regions used by the 208 eligible papers. Half of the reports did not justify their rationale for boundary selection, and each paper met on average only three quarters of quality criteria. For the frontal lobe and each subregion (frontal pole, anterior cingulate, dorsolateral, inferior-lateral, and orbitofrontal) we identified reproducible methods for a biologically plausible target ROI. It is hoped that this synthesis will guide the design of future volumetric studies of cerebral structure.
    Brain Structure and Function 03/2013; 219(1). DOI:10.1007/s00429-013-0527-5 · 5.62 Impact Factor
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    • "The boundaries of the OFC were based on a previously published method (Riffkin et al., 2005). A line through the AC-PC was used to define the superior boundary of the OFC. "
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    ABSTRACT: The devastating social, emotional, and economic consequences of human aggression are laid bare nightly on newscasts around the world. Aggression is principally mediated by neural circuitry comprising multiple areas of the prefrontal cortex and limbic system, including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), amygdala, and hippocampus. A striking characteristic of these regions is their structural asymmetry about the midline (i.e., left vs. right hemisphere). Variations in these asymmetries have been linked to clinical disorders characterized by aggression and the rate of aggressive behavior in psychiatric patients. Here we show for the first time that structural asymmetries in prefrontal cortical areas are also linked to aggression in a normal population of early adolescents. Our findings indicate a relationship between parent reports of aggressive behavior in adolescents and structural asymmetries in the limbic and paralimbic ACC and OFC, and moreover, that this relationship varies by sex. Furthermore, while there was no relationship between aggression and structural asymmetries in the amygdala or hippocampus, hippocampal volumes did predict aggression in females. Taken together, the results suggest that structural asymmetries in the prefrontal cortex may influence human aggression, and that the anatomical basis of aggression varies substantially by sex.
    Social Cognitive and Affective Neuroscience 02/2013; 9(4). DOI:10.1093/scan/nst013 · 7.37 Impact Factor
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