Association Between Taurine Level in the Hippocampus and Major Depressive Disorder in Young Women: A Proton Magnetic Resonance Spectroscopy Study at 7T.

BACKGROUND: Major depressive disorder (MDD) is characterized by depressed mood or loss of interest or pleasure. Generally, women are twice as likely as men to have depression. Taurine, a type of amino acid, plays critical roles in neuronal generation, differentiation, arborization, and formation of synaptic connections. Importantly, it enhances proliferation and synaptogenesis in the hippocampus. When injected into animals, taurine has an antidepressant effect. However, there is no in vivo evidence to show an association between taurine concentration in the human brain and the development of MDD. METHODS: Forty-one unmedicated young women with MDD (ages 18-29) and 43 healthy control participants matched for gender and age were recruited in South Korea. Taurine concentration was measured in the hippocampus, anterior cingulate cortex, and occipital cortex of the MDD and healthy control groups using proton magnetic resonance spectroscopy at 7T. Analysis of covariance was used to examine differences in taurine concentration, adjusting for age as a covariate. RESULTS: Taurine concentration in the hippocampus was lower (F1,75 = 5.729, p = .019, Δη2 = 0.073) for the MDD group (mean [SEM] = 0.91 [0.06] mM) than for the healthy control group (1.13 [0.06] mM). There was no significant difference in taurine concentration in the anterior cingulate cortex or occipital cortex between the two groups. CONCLUSIONS: This study demonstrates that a lower level of taurine concentration in the hippocampus may be a novel characteristic of MDD.

Diffusion tensor imaging reveals sex differences in pain sensitivity of rats.

Studies on differences in brain structure and function according to sex are reported to contribute to differences in behavior and cognition. However, few studies have investigated brain structures or used tractography to investigate gender differences in pain sensitivity. The identification of tracts involved in sex-based structural differences that show pain sensitivity has remained elusive to date. Here, we attempted to demonstrate the sex differences in pain sensitivity and to clarify its relationship with brain structural connectivity. In this study, pain behavior test and brain diffusion tensor imaging (DTI) were performed in male and female rats and tractography was performed on the whole brain using fiber tracking software. We selected eight brain regions related to pain and performed a tractography analysis of these regions. Fractional anisotropy (FA) measurements using automated tractography revealed sex differences in the anterior cingulate cortex (ACC)-, prefrontal cortex (PFC)-, and ventral posterior thalamus-related brain connections. In addition, the results of the correlation analysis of pain sensitivity and DTI tractography showed differences in mean, axial, and radial diffusivities, as well as FA. This study revealed the potential of DTI for exploring circuits involved in pain sensitivity. The behavioral and functional relevance's of measures derived from DTI tractography is demonstrated by their relationship with pain sensitivity.

Attenuated facial movement in depressed women is associated with symptom severity, and nucleus accumbens functional connectivity.

It is assumed that mood can be inferred from one's facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage. The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded using webcam. To boost facial movements, the naturalistic audio-visual stimuli were presented. To assess consistent global patterns across facial movements, scores for facial action units were extracted and projected onto principal component using principal component analysis. The associations of component for facial movements with functional brain circuitry was also investigated. Clusters of mouth movements, such as lip press and stretch, identified by principal component analysis, were attenuated in depressive patients compared to those in healthy controls. This component of facial movements was associated with depressive symptoms, and the strengths of resting brain functional connectivity between nucleus accumbens and both posterior insular cortex and thalamus. The evaluation of facial movements may prove to be a promising quantitative marker for assessing depressive symptoms and their underlying brain circuitry.

Structure of AQEE-30 of VGF Neuropeptide in Membrane-Mimicking Environments.

AQEE-30 is one of the VGF peptides, which are derived from the VGF polypeptide precursor, and related to various physiological phenomena including neuroprotective effects in Huntington's disease and amyotrophic lateral sclerosis (ALS). Although various functions of AQEE-30 have been reported so far, the structure of this peptide has not been reported yet. In this study, the structure of human AQEE-30 was investigated in hexafluoroisopropanol (HFIP) and dodecyl phosphocholine (DPC) micelle solutions, using circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. CD results showed that AQEE-30 had a partial helical structure in aqueous buffer, and the helical structure was stabilized in the HFIP and DPC micelle solutions. The 3D structures determined by NMR spectroscopy showed that AQEE-30 adopted mainly α-helical structure in both the HFIP and DPC micelle solutions. The surface of AQEE-30 showed that it was predominantly negatively charged. The residues from 601 to 611 in both the HFIP and DPC micelle solutions showed amphiphilicity with four negatively charged residues, glutamate. The C-terminal consecutive arginine residues formed a partial positively charged surface. These results suggest an α-helical active structure of AQEE-30 in the cell-membrane environment.

Functional and Structural Alteration of Default Mode, Executive Control, and Salience Networks in Alcohol Use Disorder.

Alcohol use disorder (AUD) has been related to aberrant functional connectivity (FC) in the salience network (SN), executive control network (ECN), and default mode network (DMN). However, there is a lack of comprehensive and simultaneous examination of these networks in patients with AUD and of their relation to potential anatomical changes. We aimed to comprehensively examine the alteration in FC in the three networks in AUD patients, and the correlation of the alteration with anatomical/structural changes (volume) in the neural areas implicated in these networks, by applying voxel-based morphometry (VBM) and region of interest-to-region of interest connectivity analysis simultaneously. In all, 22 patients with AUD and 22 healthy adults participated in the study and underwent T1 magnetic resonance imaging. Patients with AUD showed increased FCs within the DMN and SN networks, especially in terms of connectivity of the frontal areas and bilateral hippocampi. They also showed decreased FCs in the ECN. In addition, there was significant volume reduction in these areas (frontal areas and hippocampus). The increased FCs within the frontal areas or bilateral hippocampi showed a negative correlation with gray matter volume of these areas in AUD patients. Our findings add to the empirical evidence that the frontal lobe and hippocampi are critical areas that are vulnerable to functional and structural changes due to AUD.

Altered Effective Connectivity within the Fronto-Limbic Circuitry in Response to Negative Emotional Task in Female Patients with Major Depressive Disorder.

Background: Major depressive disorder (MDD) is a mood disorder associated with disruptions in emotional control. Previous studies have investigated abnormal regional activity and connectivity within the fronto-limbic circuit. However, condition-specific connectivity changes and their association with the pathophysiology of MDD remain unexplored. This study investigated effective connectivity in the fronto-limbic circuit induced by negative emotional processing from patients with MDD. Methods: Thirty-four unmedicated female patients with MDD and 28 healthy participants underwent event-related functional magnetic resonance imaging at 7T while viewing emotionally negative and neutral images. Brain regions whose dynamics are driven by experimental conditions were identified by using statistical parametric mapping. Effective connectivity among regions of interest was then estimated by using dynamic causal modeling. Results: Patients with MDD had lower activation of the orbitofrontal cortex (OFC) and higher activation of the parahippocampal gyrus (PHG) than healthy controls (HC). In association with these regional changes, we found that patients with MDD did not have significant modulatory connections from the primary visual cortex (V1) to OFC, whereas those connections of HC were significantly positively modulated during negative emotional processing. Regarding the PHG activity, patients with MDD had greater modulatory connection from the V1, but reduced negative modulatory connection from the OFC, compared with healthy participants. Conclusions: These results imply that disrupted effective connectivity among regions of the OFC, PHG, and V1 may be closely associated with the impaired regulation of negative emotional processing in the female patients with MDD.

Correction to: Functional dissociation of hippocampal subregions corresponding to memory types and stages.

An amendment to this paper has been published and can be accessed via the original article.

Functional dissociation of hippocampal subregions corresponding to memory types and stages.

BACKGROUND: The hippocampus reportedly plays a crucial role in memory. However, examining individual human hippocampal-subfield function remains challenging because of their small sizes and convoluted structures. Here, we identified hippocampal subregions involved in memory types (implicit and explicit memory) and stages (encoding and retrieval). METHODS: We modified the serial reaction time task to examine four memory types, i.e. implicit encoding, explicit encoding, implicit retrieval, and explicit retrieval. During this task, 7-T functional magnetic resonance imaging was used to compare brain activity evoked by these memory types. RESULTS: We found hippocampal activation according to all memory types and stages and identified that the hippocampus subserves both implicit and explicit memory processing. Moreover, we confirmed that cornu ammonis (CA) regions 1-3 were implicated in both memory encoding and retrieval, whereas the subiculum was implicated only in memory retrieval. We also found that CA 1-3 was activated more for explicit than implicit memory. CONCLUSIONS: These results elucidate human hippocampal-subfield functioning underlying memory and may support future investigations into hippocampal-subfield functioning in health and neurodegenerative disease.

Gray Matter Deficits and Dysfunction in the Insula Among Individuals With Intermittent Explosive Disorder.

Although numerous neuroimaging studies have evaluated the characteristics of intermittent explosive disorder (IED), studies on the structural alterations and focal dysfunction in the brain in this condition are limited. This study aimed to identify gray matter deficits and functional alterations in individuals with IED using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) analyses. Fifteen men with IED and 15 age- and sex-matched healthy controls participated in this study. Gray matter volume and brain activation while viewing the anger-inducing films were measured using 7T MRI. VBM results indicated that individuals with IED had significantly reduced gray matter volume in the insula, amygdala, and orbitofrontal area, relative to controls. Gray matter volume in the left insula was negatively correlated with composite aggression scores. fMRI results demonstrated that relative to healthy controls, individuals with IED showed greater activation in the insula, putamen, anterior cingulate cortex, and amygdala during anger processing. Left insular activity was positively correlated with composite aggression scores. Collectively, these findings suggest that structural and functional alterations in the left insula are linked to IED; this provides insight into the neural mechanisms underlying IED.

Structural Characterization of an ACP from Thermotoga maritima: Insights into Hyperthermal Adaptation.

Thermotoga maritima, a deep-branching hyperthermophilic bacterium, expresses an extraordinarily stable Thermotoga maritima acyl carrier protein (Tm-ACP) that functions as a carrier in the fatty acid synthesis system at near-boiling aqueous environments. Here, to understand the hyperthermal adaptation of Tm-ACP, we investigated the structure and dynamics of Tm-ACP by nuclear magnetic resonance (NMR) spectroscopy. The melting temperature of Tm-ACP (101.4 °C) far exceeds that of other ACPs, owing to extensive ionic interactions and tight hydrophobic packing. The D59 residue, which replaces Pro/Ser of other ACPs, mediates ionic clustering between helices III and IV. This creates a wide pocket entrance to facilitate the accommodation of long acyl chains required for hyperthermal adaptation of the T. maritima cell membrane. Tm-ACP is revealed to be the first ACP that harbor an amide proton hyperprotected against hydrogen/deuterium exchange for I15. The hydrophobic interactions mediated by I15 appear to be the key driving forces of the global folding process of Tm-ACP. Our findings provide insights into the structural basis of the hyperthermal adaptation of ACP, which might have allowed T. maritima to survive in hot ancient oceans.

Atrophic Changes and Diffusion Abnormalities of Affected Trigeminal Nerves in Trigeminal Neuralgia Using 7-T MRI.

BACKGROUND: Magnetic resonance imaging (MRI) has been widely used for visualizing trigeminal nerves in trigeminal neuralgia. OBJECTIVE: To assess atrophy and diffusion abnormalities of affected trigeminal nerves in trigeminal neuralgia with 7-T MRI. METHODS: In this prospective study, 14 patients (mean age 49 years; range 31-64 years) with trigeminal neuralgia underwent 7-T MRI. We measured trigeminal nerve volumes along their course through the pontocerebellar cistern. We also evaluated fractional anisotropy (FA) and quantitative anisotropy (QA) values within cisternal segment and pontine nuclei of the affected-side and unaffected-side trigeminal nerves, using diffusion tensor imaging (DTI). Associations between DTI metrics and Barrow Neurological Institute (BNI) pain scores were examined. RESULTS: The volumes were significantly smaller for the affected trigeminal nerves (33.83 ± 23.12 mm3) than for the unaffected ones (47.76 ± 32.48 mm3; p = 0.008). Cisternal segment FA and QA values were significantly lower in affected trigeminal nerves than in unaffected ones. However, DTI measurements in the pontine nuclei revealed no significant differences between affected-side and unaffected-side trigeminal nerves. No DTI metrics significantly correlated with BNI pain scores. CONCLUSION: Our results suggest that 7-T MRI allows identifications of atrophy and diffusion abnormalities of trigeminal nerves in trigeminal neuralgia.

Dynamic Causal Modeling of Effective Connectivity During Anger Experience in Healthy Young Men: 7T Magnetic Resonance Imaging Study.

Little is known about how anger-associated brain regions integrate and modulate external input. Therefore, we investigated the neural connectivity architecture of anger processing using a dynamic causal modeling (DCM) approach. Thirteen subjects underwent functional magnetic resonance imaging (fMRI) while viewing anger-inducing film clips. Conventional fMRI and DCM analyses were conducted to identify a dominant connectivity model. Viewing anger-inducing film clips led to activation in the left superior temporal gyrus, left insula, and left orbitofrontal cortex (OFC). The results of a group-level comparison of eight connectivity models based on conventional fMRI findings showed superiority of the model including reciprocal effective connectivities between the left insula, left superior temporal gyrus, and left orbitofrontal gyrus and bottom-up connectivity from the left superior temporal gyrus to the left orbitofrontal gyrus. Positive coupling effects were identified for connectivities between the left superior temporal gyrus and left insula and the left superior temporal gyrus and left OFC. A negative coupling effect was identified for connectivity between the left OFC and left insula. In conclusion, we propose a model of effective connectivity associated with the anger experience based on dynamic causal modeling. The findings have implications for various psychiatric disorders related to abnormalities in anger processing.

Tyr51: Key Determinant of the Low Thermostability of the Colwellia psychrerythraea Cold-Shock Protein.

Cold-shock proteins (Csps) are expressed at lower-than-optimum temperatures, and they function as RNA chaperones; however, no structural studies on psychrophilic Csps have been reported. Here, we aimed to investigate the structure and dynamics of the Csp of psychrophile Colwellia psychrerythraea 34H, ( Cp-Csp). Although Cp-Csp shares sequence homology, common folding patterns, and motifs, including a five ß-stranded barrel, with its thermophilic counterparts, its thermostability (37 °C) was markedly lower than those of other Csps. Cp-Csp binds heptathymidine with an affinity of 10-7 M, thereby increasing its thermostability to 50 °C. Nuclear magnetic resonance spectroscopic analysis of the Cp-Csp structure and backbone dynamics revealed a flexible structure with only one salt bridge and 10 residues in the hydrophobic cavity. Notably, Cp-Csp contains Tyr51 instead of the conserved Phe in the hydrophobic core, and its phenolic hydroxyl group projects toward the surface. The Y51F mutation increased the stability of hydrophobic packing and may have allowed for the formation of a K3-E21 salt bridge, thereby increasing its thermostability to 43 °C. Cp-Csp exhibited conformational exchanges in its ribonucleoprotein motifs 1 and 2 (754 and 642 s-1), and heptathymidine binding markedly decreased these motions. Cp-Csp lacks salt bridges and has longer flexible loops and a less compact hydrophobic cavity resulting from Tyr51 compared to mesophilic and thermophilic Csps. These might explain the low thermostability of Cp-Csp. The conformational flexibility of Cp-Csp facilitates its accommodation of nucleic acids at low temperatures in polar oceans and its function as an RNA chaperone for cold adaptation.

Effective connectivity during working memory and resting states: A DCM study.

Although the relationship between resting-state functional connectivity and task-related activity has been addressed, the relationship between task and resting-state directed or effective connectivity - and its behavioral concomitants - remains elusive. We evaluated effective connectivity under an N-back working memory task in 24 participants using stochastic dynamic causal modelling (DCM) of 7 T fMRI data. We repeated the analysis using resting-state data, from the same subjects, to model connectivity among the same brain regions engaged by the N-back task. This allowed us to: (i) examine the relationship between intrinsic (task-independent) effective connectivity during resting (Arest) and task states (Atask), (ii) cluster phenotypes of task-related changes in effective connectivity (Btask) across participants, (iii) identify edges (Btask) showing high inter-individual effective connectivity differences and (iv) associate reaction times with the similarity between Btask and Arest in these edges. We found a strong correlation between Arest and Atask over subjects but a marked difference between Btask and Arest. We further observed a strong clustering of individuals in terms of Btask, which was not apparent in Arest. The task-related effective connectivity Btask varied highly in the edges from the parietal to the frontal lobes across individuals, so the three groups were clustered mainly by the effective connectivity within these networks. The similarity between Btask and Arest at the edges from the parietal to the frontal lobes was positively correlated with 2-back reaction times. This result implies that a greater change in context-sensitive coupling - from resting-state connectivity - is associated with faster reaction times. In summary, task-dependent connectivity endows resting-state connectivity with a context sensitivity, which predicts the speed of information processing during the N-back task.

Investigation of cationicity and structure of pseudin-2 analogues for enhanced bacterial selectivity and anti-inflammatory activity.

Pseudin-2 (Ps), isolated from the frog Pseudis paradoxa, exhibits potent antibacterial activity and cytotoxicity. To develop antimicrobial peptides with anti-inflammatory activity and low cytotoxicity, we designed Ps analogues with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. We further substituted Gly11 with Pro (Ps-P analogues) to increase bacterial cell selectivity. Ps analogues retained antimicrobial activity and exhibited reduced cytotoxicity, whereas Ps-P analogues exhibited lower cytotoxicity and antimicrobial activity. Tertiary structures revealed that Ps has a linear α-helix from Leu2 to Glu24, whereas Ps-P has a bend at Pro11 between two short α-helixes. Using various biophysical experiments, we found that Ps analogues produced much higher membrane depolarization than Ps-P analogues, whereas Ps-P analogues may penetrate bacterial cell membranes. Ps and its analogue Ps-K18 exhibited potent anti-inflammatory activity in LPS-stimulated RAW264.7 and mouse dendritic cells via a mechanism involving the Toll-like receptor 4 (TLR4) pathway. These activities may arise from their direct inhibition of the formation of TLR4-MD-2_LPS complex, implying that amphipathic α-helical structure with an optimum balance between enhanced cationicity and hydrophobicity may be essential for their anti-inflammatory activity. The bent structure provided by Pro substitution plays an important role in enhancing bacterial cell selectivity and cell penetration.

Crystal structure of the EnvZ periplasmic domain with CHAPS.

Bacteria sense and respond to osmolarity through the EnvZ-OmpR two-component system. The structure of the periplasmic sensor domain of EnvZ (EnvZ-PD) is not available yet. Here, we present the crystal structure of EnvZ-PD in the presence of CHAPS detergent. The structure of EnvZ-PD shows similar folding topology to the PDC domains of PhoQ, DcuS, and CitA, but distinct orientations of helices and ß-hairpin structures. The CD and NMR spectra of EnvZ-PD in the presence of cholate, a major component of bile salts, are similar to those with CHAPS. Chemical cross-linking shows that the dimerization of EnvZ-PD is significantly inhibited by the CHAPS and cholate. Together with ß-galactosidase assay, these results suggest that bile salts may affect the EnvZ structure and function in Escherichia coli.

Activation of the thalamic parafascicular nucleus by electrical stimulation of the peripheral vestibular nerve in rats.

The parafascicular nucleus (PFN) of the thalamus is a primary structure in the feedback circuit of the basal ganglia-thalamo-cortical system, as well as in the neural circuit of the vestibulo-thalamo-striatal pathway. We investigated the characteristics of the functional connectivity between the peripheral vestibular system and the PFN in rats. A single electrical stimulation was applied to the horizontal semicircular canal nerve in the peripheral vestibular end-organs. This resulted in polysynaptic local field potentials (LFPs) in the PFN, which were composed of long-lasting multiple waves. The LFPs were prominently seen contralateral to the stimulation site. The PFN LFPs were suppressed by transient chemical de-afferentation of peripheral vestibular activity using a 5% lidocaine injection into the middle ear. The spontaneous firing rate of the single units increased after electrical stimulation to the horizontal canal nerve in a frequency-dependent manner. The induction of cFos protein was more prominent in the contralateral PFN than in the ipsilateral PFN following horizontal semicircular canal nerve stimulation. The functional vestibulo-parafascicular connection is a neural substrate for the transmission of vestibular sensory information to the basal ganglia.

Neural substrates of sexual arousal in heterosexual males: event-related fMRI investigation.

BACKGROUND: Sexual behavior is an important role for the survival of species. The advancement of brain imaging methods has enabled the understanding of the brain mechanism related to sexual arousal. The previous studies on the brain mechanism related to sexual arousal have mostly conducted on block design paradigm. METHODS: Despite its requirement for stricter experimental control, the event-related paradigm is known to be more efficient in detecting instant emotional and cognitive responses. The paradigm also enables the observation of hemodynamic responses through time. Therefore, this study used the event-related fMRI to examine the brain activation in various areas associated with sexual arousal as well as changes in hemodynamic responses with time. RESULTS: Strong activations were observed in the various areas associated with sexual arousal comprised of various factors: (1) activation areas related to cognitive factors: the occipital lobe and parietal lobe; (2) activation areas related to emotional factors: the thalamus and amygdala; (3) activation areas related to motivational factors: the anterior cingulate gyrus, orbitofrontal cortex, and insula; and (4) activation areas related to physiological factors: the precentral gyrus, putamen, and globus pallidus. We also identified the activation of the putamen and globus pallidus that were not well observed in previous block design studies. In the result of the hemodynamic response, the neural activity in those areas showed more transient aspects of the hemodynamic responses relative to the neural activity of other areas. CONCLUSIONS: These results suggested that the event-related paradigm is better at detecting the neural activity of the brain regions, which tend to appear suddenly, but disappear soon.

Manganese-enhanced MR imaging of brain activation evoked by noxious peripheral electrical stimulation.

As imaging technology develops, magnetic resonance imaging (MRI) has furthered our understanding of brain function by clarifying the anatomical structure and generating functional imaging data related to information processing in pain conditions. Recent studies have reported that manganese (Mn(2+))-enhanced MRI (MEMRI) provides valuable information about the functions of the central nervous system. The aim of this study was to identify specific brain regions activated during noxious electric stimulation using high-resolution MEMRI. Male Sprague Dawley rats were divided into three groups: naïve, sham electrical stimulation, and noxious electric stimulation. Under urethane with α-chloralose mixture anesthesia, a catheter was placed in the external carotid artery to administrate 20% mannitol and manganese chloride (25mM MnCl2). Noxious electric stimulation (2Hz, 10V) was applied to the hind paw with a needle electrode. Stimulation-induced neuronal activation was detected using 4.7-T MRI. In response to noxious electrical stimulation, remarkable Mn(2+)-enhanced signals were observed in the agranular insular cortex, auditory cortex, primary somatosensory cortex of the hind limb, and granular and dysgranular insular cortex, which correspond to sensory tactile electric stimulus to the hindpaws. These results indicate that the combination of MEMRI with activity-induced Mn(2+)-dependent contrast can delineate functional areas in the rat brain.