Why do humans born without the corpus callosum, the major interhemispheric commissure, lack the disconnection syndrome classically described in callosotomized patients? This paradox was discovered by Nobel laureate Roger Sperry in 1968, and has remained unsolved since then. To tackle the hypothesis that alternative neural pathways could explain this puzzle, we investigated patients with callosal dysgenesis using structural and functional neuroimaging, as well as neuropsychological assessments. We identified two anomalous white-matter tracts by deterministic and probabilistic tractography, and provide supporting resting-state functional neuroimaging and neuropsychological evidence for their functional role in preserved interhemispheric transfer of complex tactile information, such as object recognition. These compensatory pathways connect the homotopic posterior parietal cortical areas (Brodmann areas 39 and surroundings) via the posterior and anterior commissures. We propose that anomalous brain circuitry of callosal dysgenesis is determined by long-distance plasticity, a set of hardware changes occurring in the developing brain after pathological interference. So far unknown, these pathological changes somehow divert growing axons away from the dorsal midline, creating alternative tracts through the ventral forebrain and the dorsal midbrain midline, with partial compensatory effects to the interhemispheric transfer of cortical function.callosal agenesis | callosal plasticity | human connectome

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In this integrative review, we discuss findings supporting the use neuroimaging biomarkers in the diagnosis and treatment of obsessive-compulsive disorder (OCD). To do so, we have selected the most recent studies that attempted to identify the underlying pathogenic process associated with OCD and whether they provide useful information to predict clinical features, natural history or treatment responses. Studies using functional magnetic resonance (fMRI), voxel-based morphometry (VBM), diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy (1H MRS) in OCD patients are generally supportive of an expanded version of the earlier cortico-striatal-thalamus-cortical (CSTC) model of OCD. Although it is still unclear whether this information will be incorporated into the daily clinical practice (due to current conceptual approaches to mental illness), statistical techniques, such as pattern recognition methods, appear promising in identifying OCD patients and predicting their outcomes.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric illness characterized by obsessions and/or compulsions. Its pathophysiology is still not well understood but it is known that the cortico-striatal-thalamic-cortical (CSTC) circuitry plays an important role. Here, we used a multi-method MRI approach combining proton magnetic resonance spectroscopy (H1-MRS) and diffusion tensor imaging (DTI) techniques to investigate both the metabolic and the microstructural white matter (WM) changes of the anterior cingulate cortex (ACC) in OCD patients as compared to healthy controls. Twenty-three OCD patients and 21 age-, sex-, and education-matched healthy volunteers participated in the study. Our 1H-MRS findings show increased levels of Glx in ACC in OCD. Further, significantly lower fractional anisotropy (FA) values were observed in OCD patients’ left cingulate bundle (CB) as compared to healthy controls. Finally, there was a negative correlation between FA in the left CB and level of obsessions, as well as the duration of the illness. Our findings reinforce the involvement of CSTC bundles in pathophysiology of OCD, pointing to a specific role of glutamate (glutamine) and WM integrity.

Pharmacological data and animal models support the hypothesis that the dopaminergic (DA) system is implicated in obsessive-compulsive disorder (OCD). Therefore, this case-control study assessed whether genetics variations in catechol-O-methyltransferase gene (COMT) could influence susceptibility to OCD and OCD features in a Brazilian sample. A sample of 199 patients with OCD and 200 healthy individuals was genotyped for -287A > G (rs2075507) and Val158Met (rs4680) single nucleotide polymorphisms (SNPs) by TaqMan(®) or restriction mapping. We observed a statistically significant predominance of the Met low-activity allele in the male patient group as compared to the male healthy control group. The -287A > G polymorphism's genotypes and alleles were significantly overrepresented among male individuals with ordering and female subjects with washing symptoms. We also found female hoarders to exhibit a significant higher frequency of the low activity Met/Met genotype of Val158Met polymorphism compared to female patients who did not express this dimension. Our data suggest an influence of COMT polymorphisms on OCD and OCD patients' features, such as gender, and ordering, washing, and hoarding symptom dimensions. Further studies to confirm the clinical importance of COMT SNPs in OCD are warranted.

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