Spectroscopic abnormalities in the pregenual anterior cingulate cortex in obsessive-compulsive disorder using proton magnetic resonance spectroscopy: a controlled study.

BACKGROUND: The main aim of the present study is to determine the role of metabolites observed using proton magnetic resonance spectroscopy (1H-MRS) in obsessive-compulsive disorder (OCD). As the literature describing biochemical changes in OCD yields conflicting results, we focused on accurate metabolite quantification of total N-acetyl aspartate (tNAA), total creatine (tCr), total choline-containing compounds (tCh), and myo-inositol (mI) in the anterior cingulate cortex (ACC) to capture the small metabolic changes between OCD patients and controls and between OCD patients with and without medication. METHODS: In total 46 patients with OCD and 46 healthy controls (HC) matched for age and sex were included in the study. The severity of symptoms in the OCD was evaluated on the day of magnetic resonance imaging (MRI) using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Subjects underwent 1H-MRS from the pregenual ACC (pgACC) region to calculate concentrations of tNAA, tCr, tCho, and mI. Twenty-eight OCD and 28 HC subjects were included in the statistical analysis. We compared differences between groups for all selected metabolites and in OCD patients we analyzed the relationship between metabolite levels and symptom severity, medication status, age, and the duration of illness. RESULTS: Significant decreases in tCr (U = 253.00, p = 0.022) and mI (U = 197.00, p = 0.001) in the pgACC were observed in the OCD group. No statistically significant differences were found in tNAA and tCho levels; however, tCho revealed a trend towards lower concentrations in OCD patients (U = 278.00, p = 0.062). Metabolic concentrations showed no significant correlations with the age and duration of illness. The correlation statistics found a significant negative correlation between tCr levels and YBOCS compulsions subscale (cor = -0.380, p = 0.046). tCho and YBOCS compulsions subscale showed a trend towards a negative correlation (cor = -0.351, p = 0.067). Analysis of subgroups with or without medication showed no differences. CONCLUSIONS: Patients with OCD present metabolic disruption in the pgACC. The decrease in tCr shows an important relationship with OCD symptomatology. tCr as a marker of cerebral bioenergetics may also be considered as a biomarker of the severity of compulsions. The study failed to prove that metabolic changes correlate with the medication status or the duration of illness. It seems that a disruption in the balance between these metabolites and their transmission may play a role in the pathophysiology of OCD.

Glutamatergic abnormalities in the pregenual anterior cingulate cortex in obsessive-compulsive disorder using magnetic resonance spectroscopy: A controlled study.

In this study, we utilized proton magnetic resonance spectroscopy (MRS) to understand the role of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) of OCD patients in the pregenual anterior cingulate cortex (pgACC). In total, 54 patients with OCD and 54 healthy controls (HC) matched for age and sex were included in the study. They underwent MRS in the pgACC region to calculate the concentrations of Glu, Gln, GABA, and Glu + Gln (Glx). After quality control of the MRS data, 21 OCD and 21 HC were statistically analyzed. The severity of symptoms were evaluated using the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the statistical analysis, we compared differences between groups for the metabolites; in the OCD we analyzed the correlations with symptom severity, medication status, age, and duration of illness. A significant decrease in Glx, in Glu, and in Gln in the pgACC were observed in the OCD compared to HC. The correlation statistics showed a significant positive correlation between Glu levels and the YBOCS compulsions subscale. The results indicate that patients with OCD present a disturbance in glutamatergic metabolism in the pgACC. The results also demonstrate that these changes correlate with the severity of compulsions.

Evidence for the Association between the Intronic Haplotypes of Ionotropic Glutamate Receptors and First-Episode Schizophrenia.

The heritable component of schizophrenia (SCH) as a polygenic trait is represented by numerous variants from a heterogeneous group of genes each contributing a relatively small effect. Various SNPs have already been found and analyzed in genes encoding the NMDAR subunits. However, less is known about genetic variations of genes encoding the AMPA and kainate receptor subunits. We analyzed sixteen iGluR genes in full length to determine the sequence variability of iGluR genes. Our aim was to describe the rate of genetic variability, its distribution, and the co-occurrence of variants and to identify new candidate risk variants or haplotypes. The cumulative effect of genetic risk was then estimated using a simple scoring model. GRIN2A-B, GRIN3A-B, and GRIK4 genes showed significantly increased genetic variation in SCH patients. The fixation index statistic revealed eight intronic haplotypes and an additional four intronic SNPs within the sequences of iGluR genes associated with SCH (p < 0.05). The haplotypes were used in the proposed simple scoring model and moreover as a test for genetic predisposition to schizophrenia. The positive likelihood ratio for the scoring model test reached 7.11. We also observed 41 protein-altering variants (38 missense variants, four frameshifts, and one nonsense variant) that were not significantly associated with SCH. Our data suggest that some intronic regulatory regions of iGluR genes and their common variability are among the components from which the genetic predisposition to SCH is composed.

Functional Connectivity Changes in Obsessive-Compulsive Disorder Correspond to Interference Control and Obsessions Severity.

Introduction: Deficits in neurocognitive mechanisms such as inhibition control and cognitive flexibility have been suggested to mediate the symptoms in obsessive-compulsive disorder (OCD). These mechanisms are proposedly controlled by the "affective" and "executive" orbitofronto-striato-thalamo-cortical (CSTC) circuits with well-documented morphological and functional alterations in OCD that are associated with OCD symptoms. The precuneus region has been suggested in OCD as another key structure associated with the mechanism of "thought-action fusion." Our study aimed to elucidate the association of the altered functional coupling of the CSTC nodes (and precuneus), the OCD symptoms, and interference control/cognitive flexibility. Methods: In a group of 36 (17 medicated and 19 drug-free) OCD patients and matched healthy volunteers, we tested functional connectivity (FC) within the constituents of the dorsolateral prefrontal cortex "executive" CSTC, the orbitofrontal cortex/anterior cingulate "affective" CSTC, and precuneus. The functional connections showing the strongest effects were subsequently entered as explanatory variables to multiple regression analyses to identify possible associations between observed alterations of functional coupling and cognitive (Stroop test) and clinical measures (obsessions, compulsions, and anxiety level). Results: We observed increased FC (FWE p < 0.05 corr.) between CSTC seeds and regions of the parieto-occipital cortex, and between the precuneus and the angular gyrus and dorsolateral prefrontal cortex. Decreased FC was observed within the CSTC loop (caudate nucleus and thalamus) and between the anterior cingulate cortex and the limbic lobe. Linear regression identified a relationship between the altered functional coupling of thalamus with the right somatomotor parietal cortex and the Stroop color-word score. Similar association of thalamus FC has been identified also for obsessions severity. No association was observed for compulsions and anxiety. Conclusions: Our findings demonstrate altered FC in OCD patients with a prevailing increase in FC originating in CSTC regions toward other cortical areas, and a decrease in FC within the constituents of CSTC loops. Moreover, our results support the role of precuneus in OCD. The association of the cognitive and clinical symptoms with the FC between the thalamus and somatomotor cortex indicates that cognitive flexibility and inhibitory control are strongly linked and both mechanisms might contribute to the symptomatology of OCD.

Fusiform Activity Distinguishes Between Subjects With Low and High Xenophobic Attitudes Toward Refugees.

This study analyzes how people's attitudes to the European refugee crisis (ERC) correspond to selected psychological state and trait measures and impact the neural processing of media images of refugees. From a large pool of respondents, who filled in an online xenophobia questionnaire, we selected two groups (total N = 38) with the same socio-demographic background, but with opposite attitudes toward refugees. We found that a negative attitude toward refugees (high xenophobia - HX) was associated with a significantly higher conscientiousness score and with a higher trait aggression and hostility, but there was no group effect connected with empathy, fear, and anxiety measures. At the neural level we found that brain activity during the presentation of ERC stimuli is affected by xenophobic attitudes-with more xenophobic subjects exhibiting a higher BOLD response in the left fusiform gyrus. However, while the fMRI results demonstrate increased attention and vigilance toward ERC-related stimuli in the HX group, they do not show differentiated patterns of brain activity associated with perception of dehumanized outgroup.

Brain volumes and their ratios in Alzheimer´s disease on magnetic resonance imaging segmented using Freesurfer 6.0.

Ratios between opposing volumes from brain magnetic resonance imaging (MRI) can provide additional information to volumes in Alzheimer's disease (AD). Brain three-dimensional MPRAGE MRI at 3T were segmented into 44 regions using FreeSurfer v6 in 75 participants. The region's size in absolute volumes and relative proportions to the whole brain volume were compared between 39 AD patients and 36 age-, education- and sex-matched normal controls (NC). Volumes of the most atrophied parts were related to the opposing volumes of the most enlarged parts as ratios. The most atrophic structures in AD were both hippocampi. By contrast, the greatest enlargements in AD were inferior parts of both lateral ventricles. The best ratio for each side was the hippocampo-horn proportion calculated as ratio: the hippocampus / (the hippocampus + inferior lateral ventricle). Its optimal cut-off of 74% yielded sensitivity of 74% and specificity of 78% on the left and sensitivity of 74% and specificity of 78% on the right. The hippocampo-horn proportion is another measure to evaluate the degree of hippocampal atrophy on brain MRI in percentages. It has a potential to be simplified into a comparison of two-dimensional corresponding areas or a visual assessment.

Could Prolonged Usage of GPS Navigation Implemented in Augmented Reality Smart Glasses Affect Hippocampal Functional Connectivity?

BACKGROUND: Augmented reality (AR) glasses with GPS navigation represent the rapidly evolving technology which spares (and externalizes) navigational capacities. Regarding the expected everyday usage of this device, its impact on neuroplastic brain changes and navigation abilities should be evaluated. AIMS: This study aimed to assess possible changes in functional connectivity (FC) of hippocampus and other brain regions involved in spatial navigation. METHODS: Thirty-three healthy participants completed two resting state functional magnetic resonance imaging (rsfMRI) measurements at the baseline and after 3 months. For this period, the experimental group (n = 17) has had used AR device (Vuzix M100) with incorporated GPS guidance system during navigation in real world. Participants from the control group (n = 16) have not used any GPS device while navigating during walking. The rsfMRI FC of right and left hippocampi was analyzed using a seed-driven approach. Virtual city task was used to test navigational abilities both before and after the usage of AR device. RESULTS: We identified strong functional coupling of right and left hippocampi at the baseline (p < 0.05, FDR corrected). Mild changes in bilateral hippocampal FC (p < 0.05, FDR uncorrected) were observed in both assessed groups mainly between the bilateral hippocampi and between each hippocampus and temporal regions and cerebellum. However, the experimental group showed FC decrease after three months of using GPS navigation implemented in AR glasses in contrast to FC increase in the control group without such intervention. Importantly, no effect of intervention on navigational abilities was observed. DISCUSSION: Our observation supports the assumption that externalization of spatial navigation to technological device (GPS in AR glasses) can decrease the functional coupling between hippocampus and associated brain regions. Considering some limitations of the present study, further studies should elucidate the mechanism of the observed changes and their impact on cognitive abilities.