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Objective The authors investigated a possible relationship between interindividual variability in anterior cingulate gyrus (ACG) morphology and alexithymia. Materials and methods Magnetic resonance images were obtained in 100 healthy university graduates (51 female, 49 male; mean age 25.6 y). Surface area measurements of the ACG were performed on reformatted sagittal views in both hemispheres. The Toronto Alexithymia Scale (TAS-20) and the Temperament and Character Inventory (TCI) were administered. Results Right ACG surface area significantly correlated with TAS-20 total score in men (r = 0.37; p = 0.009) and in women (r = 0.30; p = 0.034). After controlling for three TCI subscales (harm avoidance, self-directedness, and self-transcendency), the correlation between TAS-20 total and right ACG became nonsignificant in women, but was only slightly reduced (r = 0.32; p = 0.032) in men. A linear regression model with right ACG as a dependent variable revealed brain volume, TCI-harm avoidance and TAS 20 total score as significant predictors in the total sample (explained proportion of total variation (EPTV) 37%). In men, beside brain volume, only TAS-20 total score showed a highly significant contribution (EPTV 41%), whereas in women only TCI-harm avoidance was a significant predictor (EPTV 36%). Conclusions The authors' findings indicate that there is a significant positive relation between the size of the right ACG and alexithymia as measured with the TAS in healthy subjects. This applies especially for men whereas in women ACG size is more associated with the subscale harm avoidance of the TCI. Our findings also suggest a partial lateralization of human emotion processing, especially negative emotion.

Background Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. Objective To describe the structural brain alterations detected in the magnetic resonance images of a large series of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of volume changes throughout the brain. Design Case-control study. Setting Referral OCD unit in a tertiary hospital. Participants A consecutive sample of 72 outpatients with OCD and 72 age- and sex-matched control subjects. Interventions Three-dimensional sequences were obtained in all participants. A statistical parametric mapping approach was used to delineate possible anatomical alterations in the entire brain. To preserve volumetric information, voxel values were modulated by the Jacobian determinants (volume change measurement) derived from spatial normalization. Main Outcome Measures Voxelwise brain volumes. Results The brains of patients with OCD showed reduced gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex, and the left insulo-opercular region. A relative increase in gray matter volume was observed bilaterally in the ventral part of the putamen and in the anterior cerebellum. All these brain alterations were abnormally correlated in patients with OCD, and age statistically significantly contributed to the relative enlargement observed in the striatal areas. Disease severity, the nature of symptoms, and comorbidities were not related to the changes described. Nevertheless, patients with prominent aggressive obsessions and checking compulsions showed reduced amygdala volume in the right hemisphere. Conclusions The pattern of anatomical features depicted by this voxelwise approach is consistent with data from functional studies. The reported anatomical maps identified the specific parts of the frontostriatal system that were altered in patients with OCD and detected changes in anatomically connected distant regions. These data further define the structural brain alterations in OCD and may contribute to constraining the prevailing biological models of this psychiatric process.

Delayed acquisition of developmental motor and cognitive milestones is a common clinical expression of many etiological processes. Imaging exams of developmentally delayed children often show no structural brain alterations despite suspicion of brain maturation delay. MRI studies increasingly suggest that white matter myelination finely reflects the progression in functional brain maturation. In this volumetric MRI study, we sought to evaluate whether developmental delay in children with normal conventional MRI exams is associated with reduced myelinated white matter. A total of 100 children (mean age, 4.4 years) with developmental delay and 50 normally developing age-matched control children underwent 3-D MRI to measure the volume of myelinated white matter. Patients showed a significant reduction in the relative content of myelinated white matter (accounting for 19.8% of brain volume in patients and 21.4% in control subjects, P = 0.005). The observed difference was equivalent to a 3.2-year myelination delay. Although the whole hemispheres were invariably symmetrical, the volume of myelinated white matter was asymmetrical in 30% of patients and 10% of control subjects (P = 0.006). We conclude that volumetric assessment of white matter may reveal a reduction in brain myelination beyond early childhood in developmentally delayed children showing normal brain appearance. This finding further emphasizes the view of white matter myelination as an indicator of functional brain maturation.

Background A number of recent neuroimaging findings in depression have provided new insight into the biological substratum of depressive illness. The question now is what particular relevance the structural brain alteration described may have within the clinical context of depressive patients. We investigated a possible relationship between brain cerebrospinal fluid (CSF) space changes and patient prognosis in melancholic depression. Method Fifty-five patients who met DSM-IV criteria for major depressive disorder with melancholic features were examined with 3-dimensional magnetic resonance imaging, and CSF volumes were measured for global brain CSF and for lateral ventricles and left and right sylvian fissure regions. Clinical outcome was prospectively assessed during a 6-month standardized antidepressive treatment period (Phase I) and in a 2-year follow-up (Phase II) of recovered patients. The outcome measurements were total days to symptom remission (Phase I) and to eventual symptom relapse or recurrence (Phase II). The study took place from July 1998 to Dec. 2001. Results Phase I: Enlargement of CSF spaces in the left sylvian fissure region predicted poor treatment response. Volume measurements from this region accounted for 35% of remission time variance. Median time to full clinical remission was 82 days in patients with severe changes, 51 days in the case of mild-to-moderate CSF enlargement, and 35 days in patients with no left sylvian fissure region alterations. Phase II: Severe enlargement of global cortical CSF spaces was associated with increased risk of depression relapse or recurrence. Patients with severe cortical CSF changes showed a 7.8-fold excess risk of depression relapse/recurrence compared with patients with no cortical CSF space alteration. Conclusion Our data suggest that MRI-detected CSF space enlargement may be an important neuroimaging marker for poor prognosis in melancholic depression.

BackgroundSocial anxiety often involves a combination of hypervigilance and avoidance to potentially warning signals including the facial expression of emotions. Functional imaging has demonstrated an increase in amygdala response to emotional faces in subjects with social anxiety. Nevertheless, it is unclear to what extent visual areas processing faces influence amygdala reactivity in different socially anxious individuals. We assessed the influence of the fusiform gyrus activation on amygdala response to emotional faces in the non-clinical range of social anxiety.MethodTwenty-two normal subjects showing a wide range in social anxiety scores were examined using functional magnetic resonance imaging (fMRI) during the processing of happy and fearful faces. A dimensional analysis approach was used involving voxel-wise mapping of the correlation between subjects' social anxiety scores and amygdala activation, before and after controlling for fusiform gyrus activation.ResultsWe observed that only after controlling for subjects' level of activation of the fusiform gyrus was there an association between social anxiety ratings and amygdala response to both happy and fearful faces. The fusiform gyrus influence was more robust during the fear condition. Of note, fusiform gyrus response to fearful faces showed a negative correlation with additional behavioral assessments related to avoidance, including social anxiety scores, harm avoidance and sensitivity to punishment.ConclusionsRelevant interactions among the emotional face-processing stages exist in the non-clinical range of social anxiety that may ultimately attenuate amygdala responses. Future research will help to establish the role of this effect in a clinical context.

The notion of a “default mode of brain function” has taken on certain relevance in human neuroimaging studies and in relation to a network of lateral parietal and midline cortical regions that show prominent activity fluctuations during passive imaging states, such as rest. In this study, we perform three fMRI experiments that demonstrate consistency and specialization in the default mode network. Correlated activity fluctuations of default mode network regions are identified during ( i ) eyes-closed spontaneous rest, ( ii ) activation by moral dilemma, and ( iii ) deactivation by Stroop task performance. Across these imaging states, striking uniformity is shown in the basic anatomy of the default mode network, but with both tasks clearly and differentially modulating this activity compared with spontaneous fluctuations of the network at rest. Against rest, moral dilemma is further shown to evoke regionally specific activity increases of hypothesized functional relevance. Mapping spontaneous and task-related brain activity will help to constrain the meaning of the default mode network. These findings are discussed in relation to recent debate on the topic of default modes of brain function.

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action.

The substantial individual heterogeneity that characterizes mental illness is often ignored by classical case-control designs that rely on group mean comparisons. Here, we present a comprehensive, multiscale characterization of individual heterogeneity of brain changes in 1294 cases diagnosed with one of six conditions and 1465 matched healthy controls. Normative models identified that person-specific deviations from population expectations for regional grey matter volume were highly heterogeneous, affecting the same area in

Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders.

Background: Deep brain stimulation (DBS) is emerging as a promising tool in the treatment of refractory obsessive-compulsive disorder (OCD) but the search for the best target still continues. This issue is especially relevant when particularly resistant profiles are observed in some patients, which have been ascribed to individual responses to DBS according to differential patterns of connectivity. As patients have been implanted, new dilemmas have emerged, such as what to do when the patient does not respond to surgery. Case presentation: Here we describe a 22-year-old male with extremely severe OCD who did not respond to treatment with DBS in the nucleus accumbens, but who did respond after explanting and reimplanting leads targeting the ventral capsule-ventral striatum region. Information regarding the position of the electrodes for both surgeries is provided and possible brain structures affected during stimulation are reviewed. To our knowledge this case is the first in the literature reporting the removal and reimplantation of DBS leads for therapeutical benefits in a patient affected by a mental disorder. Conclusion: The capability for explantation and reimplantation of leads should be considered as part of the DBS therapy reversibility profile in resistant mental disorders, as it allows application in cases of non-response to the first surgery.

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30) and reactive (n = 65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.