Menstrual cycle-modulated intrinsic connectivity enhances olfactory performance during periovulatory period.

BACKGROUND: Olfactory capacity increases during the period of ovulation, perhaps as an adjunct to mate selection; however, researchers have yet to elucidate the neural underpinning of menstrual cycle-dependent variations in olfactory performance. METHODOLOGY: A cohort of healthy volunteers (n = 88, grand cohort) underwent testing for gonadal hormone levels and resting-state functional magnetic resonance imaging with a focus on intrinsic functional connectivity (FC) in the olfactory network based on a priori seeds (piriform cortex and orbitofrontal cortex) during the periovulatory (POV) and menstrual (MEN) phases. A subcohort (n = 20, olfaction cohort) returned to the lab to undergo testing of olfactory performance during the POV and MEN phases of a subsequent menstrual cycle. RESULTS: Olfactory performance and FC were both stronger in the periovulatory phase than in the menstrual phase. Enhanced FC was observed in the network targeting the cerebellum in both the grand and olfaction cohorts, while enhanced FC was observed in the middle temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex, and postcentral gyrus in the grand cohort. Periovulatory progesterone levels in the grand cohort were positively correlated with FC in the network targeting the insula and paracentral lobule. CONCLUSIONS: Our analysis revealed that superior olfactory function in the periovulatory period is associated with enhanced intrinsic connectivity in the olfactory network. These findings can be appreciated in the context of evolutionary biology.

Effects of dietary fiber on cecal short-chain fatty acid and cecal microbiota of broiler and laying-hen chicks.

This experiment was conducted to evaluate the effects of feeding dietary fiber on cecal short-chain fatty acid (SCFA) concentration and cecal microbiota of broiler and laying-hen chicks. The lower fiber diet was based on corn-soybean meal (SBM) and the higher fiber diet was formulated using corn-SBM-dried distillers grains with solubles (DDGS) and wheat bran to contain 60.0 g/kg of both DDGS and wheat bran from 1 to 12 d and 80.0 g/kg of both DDGS and wheat bran from 13 to 21 d. Diets were formulated to meet or exceed NRC nutrient requirements. Broiler and laying-hen chicks were randomly assigned to the high and low fiber diets with 11 replicates of 8 chicks for each of the 4 treatments. One cecum from 3 chicks was collected from each replicate: one cecum underwent SCFA concentration analysis, one underwent bacterial DNA isolation for terminal restriction fragment length polymorphism (TRFLP), and the third cecum was used for metagenomics analyses. There were interactions between bird line and dietary fiber for acetic acid (P = 0.04) and total SCFA (P = 0.04) concentration. There was higher concentration of acetic acid (P = 0.02) and propionic acid (P < 0.01) in broiler chicks compared to laying-hen chicks. TRFLP analysis showed that cecal microbiota varied due to diet (P = 0.02) and chicken line (P = 0.03). Metagenomics analyses identified differences in the relative abundance of Helicobacter pullorum and Megamonas hypermegale and the genera Enterobacteriaceae, Campylobacter, Faecalibacterium, and Bacteroides in different treatment groups. These results provide insights into the effect of dietary fiber on SCFA concentration and modulation of cecal microbiota in broiler and laying-hen chicks.

High prevalence of incidental brain findings in primary dysmenorrhoea.

BACKGROUND: Primary dysmenorrhoea (PDM) is inexorably common. PDM women suffer from cramping pain in the lower abdomen that starts with menstruation and lasts for 24-72 h. Up to 90% of adolescent girls and more than 50% of menstruating women worldwide report suffering from it. Ten to 20% of PDM women describe their suffering as severe and distressing. However, nothing is known regarding the association of PDM with possible brain anomalies or abnormalities. METHODS: High-resolution T1-weighted anatomical brain magnetic resonance images (MRI) were acquired for each subject and inspected for incidental findings (normal variants and abnormalities) as a routine procedure in our PDM-related multimodal neuroimaging studies. Altogether, 330 right-handed young women [otherwise healthy PDMs = 163; non-PDM healthy controls (HCs) = 167] were enrolled during the period of 2006-2014. Binomial proportion test was performed for between-group comparisons. RESULTS: PDMs demonstrated significantly higher prevalence of overall incidental brain MRI findings (PDMs: n = 18, 11.0%; HCs: n = 6, 3.6%; p = 0.005) that should be ascribed to a preponderance of normal variants (PDMs: n = 16, 9.8%; HCs: n = 3, 1.8%; p = 0.001), especially cavum septum pellucidum. No significant between-group difference of abnormal findings was found (PDMs: n = 2, 1.2%; HCs: n = 3, 1.8%; p = 0.336). CONCLUSIONS: We report here that otherwise healthy PDMs are associated with high prevalence of normal variants but not brain abnormalities. Our observations invite further epidemiological and neuroscientific studies.

Abnormal early gamma responses to emotional faces differentiate unipolar from bipolar disorder patients.

This study investigates the cortical abnormalities of early emotion perception in patients with major depressive disorder (MDD) and bipolar disorder (BD) using gamma oscillations. Twenty-three MDD patients, twenty-five BD patients, and twenty-four normal controls were enrolled and their event-related magnetoencephalographic responses were recorded during implicit emotional tasks. Our results demonstrated abnormal gamma activity within 100 ms in the emotion-related regions (amygdala, orbitofrontal (OFC) cortex, anterior insula (AI), and superior temporal pole) in the MDD patients, suggesting that these patients may have dysfunctions or negativity biases in perceptual binding of emotional features at very early stage. Decreased left superior medial frontal cortex (smFC) responses to happy faces in the MDD patients were correlated with their serious level of depression symptoms, indicating that decreased smFC activity perhaps underlies irregular positive emotion processing in depressed patients. In the BD patients, we showed abnormal activation in visual regions (inferior/middle occipital and middle temporal cortices) which responded to emotional faces within 100 ms, supporting that the BD patients may hyperactively respond to emotional features in perceptual binding. The discriminant function of gamma activation in the left smFC, right medial OFC, right AI/inferior OFC, and the right precentral cortex accurately classified 89.6% of patients as unipolar/bipolar disorders.

Pain catastrophizing is associated with dental pain in a stressful context.

Pain is associated with anxiety in a dental setting. It has remained unclear how cognitive-affective factors modulate pain and anxiety in a stressful context, such as receiving dental procedures. We hypothesized that both the situational factor (unpredictability about painful stimuli) and the trait factor (pain catastrophizing, i.e., the tendency to interpret pain in negative orientation) account for dental pain. Fifteen healthy participants were recruited to perform an associative learning task. They were asked to learn the pairing between visual cues and the intensity of incoming painful stimuli delivered at the right upper central incisor. Brain activation associated with pain was recorded by functional magnetic resonance imaging (fMRI). The participants reported increased anxiety and pain in the stressful context, where stimuli intensity was not predicted by the preceding cue. The score of the Pain Catastrophizing Scale was positively correlated with the increased pain modulated by unpredictability. Brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual catastrophizing level. Our findings suggest that both the situational factor (unpredictability) and the trait factor (catastrophizing) influence dental pain, highlighting the role of cognitive-affective factors in pain control of dental patients.

Healthy-side dominance of middle- and long-latency neuromagnetic fields in idiopathic sudden sensorineural hearing loss.

Any lesion along the neural axis may induce a subsequent functional reorganization at the level above. The present study used magnetoencephalography to investigate auditory-evoked magnetic fields [a component of the middle-latency auditory evoked fields peaking at approximately 50 ms (P50m) and a component of the long-latency auditory evoked fields peaking at approximately 100 ms (N100m)] on stimulation of both healthy and affected ears in patients with acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL) of moderate degree in order to elucidate the functional plasticity of the auditory system. Sixteen right-handed, previously untreated adult patients with acute unilateral left (n = 8) or right (n = 8) ISSNHL of moderate degree were studied. Sixteen right-handed healthy volunteers with normal hearing served as control. Auditory neuromagnetic responses, measured by a whole-head 306-channel neuromagnetometer, were detected by monaural tone stimulation applied to affected and healthy ears, respectively, in different sessions. Intragroup and intergroup interhemispheric differences of peak dipole strengths and latencies of P50m and N100m, respectively, to monaural tones were evaluated. Healthy-side amplitude dominance of both P50m and N100m was found in ISSNHL, i.e. contralateral dominance was preserved on affected-ear stimulation but ipsilateral dominance was seen on healthy-ear stimulation. The phenomena could be attributed to the combined contralateral attenuation and ipsilateral enhancement of P50m and N100m activity in response to healthy-ear stimulation. Our findings confirmed that functional modulation can occur within the first few tens of milliseconds of evoked response at the auditory cortex in ISSNHL. The mechanisms of healthy-side dominance might be ascribed to a functional retune of auditory pathways, i.e. conjoined contralateral inhibition and ipsilateral excitation of the auditory pathway in response to healthy-ear stimulation. The effect could be registered in cortical responses.

Neural correlates of antisaccade deficits in schizophrenia, an fMRI study.

Schizophrenia patients were known to have oculomotor abnormalities for decades and several studies had found antisaccade impairment to be a biological marker of schizophrenia. In this study, we used functional magnetic resonance imaging (fMRI) to investigate the neural circuits responsible for antisaccade deficits in schizophrenia. Ten normal controls and 10 DSM-IV schizophrenia patients performed antisaccade tasks and control tasks during fMRI. Data were analyzed and task-specific activations were identified using Statistical Parametric Mapping (SPM-2). In normal subjects, antisaccade tasks activated bilateral frontal eye fields, supplementary eye fields, inferior frontal gyrus, superior parietal lobules, inferior parietal lobules, occipital visual cortex, cerebellum, thalamus, and lentiform nuclei (P<0.001). By contrast, schizophrenia patients failed to show activation in bilateral lentiform nucleus, bilateral thalamus, and left inferior frontal gyrus during antisaccade performance. Our findings suggest that schizophrenic antisaccade deficits are associated with dysfunction of fronto-striatal-thalamo-cortical circuits previously demonstrated to be responsible for suppression of the reflexive saccade. Left inferior frontal gyrus, which was known to be responsible for response inhibition on "go/no-go" testing, also plays an important role in schizophrenic antisaccade deficit.

Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI study.

Visceral hypersensitivity in gastric fundus is a possible pathogenesis for functional dyspepsia. The cortical representation of gastric fundus is still unclear. Growing evidence shows that the insula, but not the primary or secondary somatosensory region (SI or SII), may be the cortical target for visceral pain. Animal studies have also demonstrated that amygdala plays an important role in processing visceral pain. We used fMRI to study central projection of stomach pain from fundus balloon distension. We also tested the hypothesis that there will be neither S1 nor S2 activation, but amygdala activation with the fundus distension. A 3T-fMRI was performed on 10 healthy subjects during baseline, fullness (12.7 +/- 0.6 mmHg) and moderate gastric pain (17.0 +/- 0.8 mmHg). fMRI signal was modelled by convolving the predetermined psychophysical response. Statistical comparisons were performed between conditions on a group level. Gastric pain activated a wide range of cortical and subcortical structures, including thalamus and insula, anterior and posterior cingulate cortices, basal ganglia, caudate nuclei, amygdala, brain stem, cerebellum and prefrontal cortex (P < 0.001). A subset of these neuronal substrates was engaged in the central processing of fullness sensation. SI and SII were not activated during the fundus stimulation. In conclusion, the constellation of neuronal structures activated by fundus distension overlaps the pain matrices induced musculocutaneous pain, with the exception of the absence of SI or SII activation. This may account for the vague nature of visceral sensation/pain. Our data also confirms that the insula and amygdala may act as the central role in visceral sensation/pain, as well as in the proposed sensory-limbic model of learning and memory of pain.

MEG localization of rolandic spikes with respect to SI and SII cortices in benign rolandic epilepsy.

The purpose of this study was to study the relationship between interictal spike sources and somatosensory cortices in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We recorded spontaneous magnetoencephalography (MEG) and EEG signals and cortical somatosensory-evoked magnetic fields (SEFs) to electric stimulation of the median nerve in 9 children with BREC. Interictal rolandic discharges (RDs) and SEFs were analyzed by equivalent current dipole (ECD) modeling. Based on the orientation and locations of corresponding ECDs, we compared generators of RDs with primary (SI) and second somatosensory cortices (SII). Our results showed that RDs and SII responses had similar ECD orientation on the magnetic field maps. The ECDs of RDs were localized 15.3 +/- 1.9 and 12.2 +/- 2.8 mm anterior to SI and SII, respectively. The spatial distance on average from the location of RDs to SII (21.9 +/- 1.6 mm) cortex was significantly shorter than to SI cortex (29.7 +/- 1.7 mm) (P<0.01, Wilcoxon signed-rank test). In conclusion, the cortical generators for RDs in patients with BREC are localized in the precentral motor cortex, closer to hand SII than to SI cortex.

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings.

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Magnetoencephalographic study of rhythmic mid-temporal discharges in non-epileptic and epileptic patients.

To evaluate the source location and clinical significance of rhythmic mid-temporal theta discharges (RMTD) by MEG in non-epileptic and epileptic patients, we conducted simultaneous MEG and EEG recordings with a whole-scalp 306-channel neuromagnetometer in three patients: one with right temporal lobe epilepsy (TLE), one with right frontal lobe epilepsy (FLE), and one with tension headache. We visually detected the RMTD activity and interictal spikes, and then localised their generators by MEG source modelling. We repeated MEG measurement 3 months after right anterior temporal lobectomy (ATL) in the TLE patient; 3 months after anticonvulsant medication in the FLE patient. In epileptic patients, RMTD activities were found during drowsiness over the left temporal channels of both MEG and EEG recordings, and their generators were localised to the left posterior inferior temporal region. In the patient with tension headache, RMTD was localised in the right inferior temporal area. When the epileptic patients became seizure free with disappearance of epileptic spikes, RMTD was still found over the left temporal channels. Besides, some bursts of RMTD appeared also in the right temporal channels in our TLE patient after ATL. Our results indicate that the source of RMTD activity is located in the fissural cortex of the posterior inferior temporal region. As a physiologic rhythm related to dampened vigilance, RMTD has no direct relation to epileptogenic activity.

A left-lateralized network for reading Chinese words: a 3 T fMRI study.

fMRI was used to investigate brain organization for reading in Chinese. Subjects were shown two-character Chinese words. A control task was used to eliminate the non-linguistic visual and motor confounds. Results show that naming of Chinese logographs is characterized by left-lateralized neuronal networks for the processing of orthographic, phonological, and semantic attributes. The orchestration of the middle frontal cortex, superior temporal cortex, superior parietal cortex, basal temporal area and extrastriate cortices of the left hemisphere may manifest the particularity of the central representation of simple word naming in Chinese.

PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.

The ERK 1/2 MAP kinase pathway controls cell growth and survival and modulates integrin function. Here, we report that PEA-15, a protein variably expressed in multiple cell types, blocks ERK-dependent transcription and proliferation by binding ERKs and preventing their localization in the nucleus. PEA-15 contains a nuclear export sequence required for its capacity to anchor ERK in the cytoplasm. Genetic deletion of PEA-15 results in increased ERK nuclear localization with consequent increased cFos transcription and cell proliferation. Thus, PEA-15 can redirect the biological outcome of MAP kinase signaling by regulating the subcellular localization of ERK MAP kinase.

Distinct retinoid X receptor activation function-2 residues mediate transactivation in homodimeric and vitamin D receptor heterodimeric contexts.

The vitamin D receptor (VDR) stimulates transcription as a 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-activated heterodimer with retinoid X receptor (RXR). RXR also forms homodimers to mediate 9-cis retinoic acid (9-cis RA)-induced gene expression. Both receptors possess a C-terminal hormone-dependent activation function-2 (AF-2), a highly conserved region that binds coactivators to transduce the transcriptional signal. By replacing single amino acids within the AF-2 of human RXR alpha (hRXR alpha) or mouse RXR beta (mRXR beta), the contribution of these residues to transactivation by the RXR-VDR heterodimer and the RXR-RXR homodimer was evaluated. In 9-cis RA-responsive homodimers, the second and fourth positions of the AF-2 (leucine and glutamate respectively) are essential. However, in the context of an RXR-VDR heterodimer activated by 1,25(OH)(2)D(3), alteration of these two RXR residues has little effect. Instead, AF-2 residues located towards the C-terminus, such as the penultimate position (L455 in hRXR alpha or L441 in mRXR beta), are crucial for RXR-VDR heterodimers. Indeed, L455A mutant RXR exerts a dominant negative effect on RXR-VDR transcriptional responsiveness to 1,25(OH)(2)D(3). Further experiments with a mutant hRXR alpha (F313A) which elicits 9-cis RA-independent transactivation as a homodimer demonstrate that, when heterodimerized with VDR, this RXR mutant is incapable of activating the RXR-VDR heterocomplex in the absence of the VDR ligand. Taken together, these results indicate that RXR is a subordinate, yet essential transcriptional partner in RXR-VDR-mediated activation of gene expression. Furthermore, a functional switch in RXR AF-2 signaling occurs between RXR residues in the homodimeric versus the heterodimeric states, likely reflecting different interactions between subregions of the AF-2 and coactivator(s).

Lung abscess in congenital cystic adenomatoid malformation: report of one case.

Congenital cystic adenomatoid malformation (CCAM) of the lung is an uncommon anomaly of fetal development of terminal respiratory structures. Patients with CCAM may present either in the newborn with progressive respiratory distress, or in older children with recurrent pulmonary infections. Lung abscess is an extremely rare presentation. Herein we report an 8-year-old girl with type 1 CCAM who presented as lung abscess.

Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains.

Members of the Frizzled family of seven-pass transmembrane proteins serve as receptors for Wnt signalling proteins. Wnt proteins have important roles in the differentiation and patterning of diverse tissues during animal development, and inappropriate activation of Wnt signalling pathways is a key feature of many cancers. An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling. Recently, an LDL-receptor-related protein has been shown to function as a co-receptor for Wnt proteins and to bind to a Frizzled CRD in a Wnt-dependent manner. To investigate the molecular nature of the Wnt signalling complex, we determined the crystal structures of the CRDs from mouse Frizzled 8 and secreted Frizzled-related protein 3. Here we show a previously unknown protein fold, and the design and interpretation of CRD mutations that identify a Wnt-binding site. CRDs exhibit a conserved dimer interface that may be a feature of Wnt signalling. This work provides a framework for studies of homologous CRDs in proteins including muscle-specific kinase and Smoothened, a component of the Hedgehog signalling pathway.

Activation of the hypothalamus characterizes the acupuncture stimulation at the analgesic point in human: a positron emission tomography study.

We performed a positron emission tomography study, using regional cerebral blood flow as the index of brain activity, to address the specificity of brain activation pattern by acupuncture stimulation of short duration at the classical analgesic point. Needling manipulation at 2 Hz was performed at a classical point of prominent analgesic efficacy (Li 4, Heku) and a near-by non-classical/non-analgesic point, respectively, in normal subjects. Regions activated by acupuncture stimulation at Li 4 included the hypothalamus with an extension to midbrain, the insula, the anterior cingulate cortex, and the cerebellum. Of note, it was only the stimulation at Li 4 that activated the hypothalamus under the similar psychophysical ratings of acupuncture sensation (deqi) as elicited by the stimulation at the two points, respectively. The data suggested that the hypothalamus might characterize the central expression of acupuncture stimulation at the classical analgesic point and serve as one key element in mediating analgesic efficacy of acupuncture stimulation.

Electroacupuncture-induced neural activation detected by use of manganese-enhanced functional magnetic resonance imaging in rabbits.

OBJECTIVE: To investigate the effects of acupuncture on neural activity detected by use of manganese-enhanced functional magnetic resonance imaging (fMRI) and elucidate the relationship between somatic acupoint stimulation and brain activation. ANIMALS: 40 New Zealand White rabbits. PROCEDURE: Manganese-enhanced fMRI was performed in anesthetized rabbits manipulated with electroacupuncture (EA) on Zusanli (ST-36) and Yanglingquan (GB-34) acupoints. Image acquisition was performed on a 1.5T superconductive clinical scanner with a circular polarized extremity coil. T1-weighted images were acquired sequentially as follows: baseline, after mannitol injection, after manganese infusion, and 5 and 20 minutes after initiation of EA. RESULTS: Changes in focal neural activity were detected by use of manganese-enhanced fMRI. Stimulation on Zusanli (ST-36) for 5 minutes resulted in activation of the hippocampus, whereas stimulation on Yanglingquan (GB-34) resulted in activation of the hypothalamus, insula, and motor cortex. Activation became less specific after 20 minutes of EA. Furthermore, stimulation on ipsilateral acupoints led to bilateral brain activation. CONCLUSIONS AND CLINICAL RELEVANCE: Each acupoint has a corresponding cerebral linkage, and stimulation on these points resulted in time-dependent neural activation. Understanding the linkage between peripheral acupoint stimulation and central neural pathways may provide a useful guide for clinical applications of acupuncture.