Visualizing the valence states of europium ions in Eu-doped BaAl2O4 using X-ray nanoprobe mapping.

This study develops and successfully demonstrates visualization methods for the characterization of europium (Eu)-doped BaAl2O4 phosphors using X-ray nanoprobe techniques. X-ray fluorescence (XRF) mapping not only gives information on the elemental distributions but also clearly reveals the valence state distributions of the Eu2+ and Eu3+ ions. The accuracy of the estimated valence state distributions was examined by performing X-ray absorption spectroscopy (XAS) across the Eu L3-edge (6.977 keV). The X-ray excited optical luminescence (XEOL) spectra exhibit different emission lines in the selected local areas. Their corresponding emission distributions can be obtained via XEOL mapping. The emission properties can be understood through correlation analysis. The results demonstrate that the main contribution to the luminescence intensity of the Eu-doped BaAl2O4 comes from the Eu2+ activator and the emission intensity will not be influenced by the concentration of Eu2+ or Eu3+ ions. It is anticipated that X-ray nanoprobes will open new avenues with significant characterization ability for unravelling the emission mechanisms of phosphor materials.

Xenograft of Human Umbilical Mesenchymal Stem Cells Promotes Recovery from Chronic Ischemic Stroke in Rats.

Stroke is a leading cause of adult disability. In our previous study, transplantation of human umbilical mesenchymal stem cells (HUMSCs) in Wharton's jelly in the acute phase of ischemic stroke promotes recovery in rats. Unfortunately, there is no cure for chronic stroke. Patients with chronic stroke can only be treated with rehabilitation or supportive interventions. This study aimed to investigate the potential of xenograft of HUMSCs for treating chronic stroke in rats. Rats were subjected to 90 min middle cerebral artery occlusion and then reperfusion to mimic ischemic cerebral stroke. On day 14 following stroke, HUMSCs were transplanted into the damaged cerebral cortex. The motor function in rats of the Stroke + HUMSCs group exhibited significant improvement compared to that of the Stroke + Saline group, and the trend persisted until day 56 post stroke. The cerebral cortex changes were tracked using magnetic resonance imaging, showing that cerebral atrophy was found starting on day 7 and was reduced significantly in rats receiving HUMSCs compared to that in the Stroke + Saline group from day 21 to day 56. HUMSCs were found to be existed in the rats' cerebral cortex on day 56, with signs of migration. The grafted HUMSCs did not differentiate into neurons or astrocytes and may release cytokines to improve neuroprotection, decrease inflammation and increase angiogenesis. Our results demonstrate that xeno-transplantation of HUMSCs has therapeutic benefits for chronic ischemic stroke. Most importantly, patients do not need to use their own HUMSCs, which is a gospel thing for clinical patients.

Does the Diffuseness of the Nidus Affect the Outcome of Stereotactic Radiosurgery in Patients with Unruptured Cerebral Arteriovenous Malformations?

BACKGROUND: We proposed an algorithm to automate the components within the identification of components within the nidus of cerebral arteriovenous malformations (AVMs) which may be used to analyze the relationship between its diffuseness and treatment outcomes following stereotactic radiosurgery (SRS). OBJECTIVES: to determine the impact of the diffuseness of the AVM nidus on SRS outcomes. METHODS: This study conducted regular follow-ups of 209 patients with unruptured AVMs who underwent SRS. The diffuseness of the AVM nidus was estimated by quantifying the proportions of vascular nidal component, brain parenchyma, and cerebrospinal fluid in T2-weighted MRIs. We used Cox regression analysis to characterize the association between nidal diffuseness and treatment outcomes in terms of obliteration rate and radiation-induced change (RICs) rate following SRS. RESULTS: The median AVM volume was 20.7 cm3. The median duration of imaging follow-up was 51 months after SRS. The overall AVM obliteration rate was 68.4%. RICs were identified in 156 of the 209 patients (74.6%). The median proportions of the nidus of AVM and brain parenchyma components within the prescription isodose range were 30.2 and 52.2%, respectively. Cox regression multivariate analysis revealed that the only factor associated with AVM obliteration rate after SRS was AVM volume. However, a larger AVM volume (>20 mL) and a larger proportion of brain parenchyma (>50%) within the prescription isodose range were both correlated with a higher RIC rate following SRS. CONCLUSIONS: The diffuseness of the nidus indeed appears to affect the RIC rate following SRS in patients with unruptured AVMs.

Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.

Immunosuppression induced by Mycobacterium tuberculosis is important in the pathogenesis of active tuberculosis (TB). However, the impact of depressed TB-specific and non-TB-specific gamma interferon (IFN-γ) response on the treatment outcomes of TB patients remains uncertain. In this prospective cohort study, culture- or pathology-proven active TB patients were enrolled and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays were performed before the initiation of anti-TB treatment. TB-specific IFN-γ responses (TB antigen tube subtracted from the nil tube) and non-TB-specific IFN-γ responses (mitogen tube subtracted from the nil tube) were measured and associated with treatment outcomes, including 2-month culture conversion and on-treatment mortality. A total of 212 active TB patients were included in the analysis. We observed a close correlation between decreased lymphocyte count and lower non-TB-specific IFN-γ responses but not TB-specific IFN-γ responses. Patients with lower non-TB-specific IFN-γ responses had lower 2-month culture conversion rate (71.1% versus 84.7%, respectively; P = 0.033) and higher on-treatment mortality (22.6% versus 5.7%, respectively; P = 0.001) than those with higher non-TB-specific IFN-γ responses. In multivariate analysis, depressed non-TB-specific IFN-γ response was an independent factor associated with 2-month sputum culture nonconversion (odds ratio [OR], 2.49; 95% CI [95% confidence interval], 1.05 to 5.90) and on-treatment mortality (hazard ratio [HR], 2.76; 95% CI, 1.15 to 6.62). In contrast, depressed TB-specific IFN-γ responses were significantly associated with higher on-treatment mortality in univariate analysis but not in multivariate analysis. Our findings suggest that depressed non-TB-specific responses, but not TB-specific IFN-γ responses, as measured by QFT-GIT before the initiation of anti-TB treatment, were significantly associated with worse treatment outcomes in TB patients.

The pathophysiology of episodic cluster headache: Insights from recent neuroimaging research.

Background Cluster headache is a disorder characterized by intermittent, severe unilateral head pain accompanied by cranial autonomic symptoms. Most cases of CH are episodic, manifesting as "in-bout" periods of frequent headache separated by month-to-year-long "out-of-bout" periods of remission. Previous imaging studies have implicated the hypothalamus and pain matrix in the pathogenesis of episodic CH. However, the pathophysiology driving the transition between in- and out-of-bout periods remains unclear. Methods The present study provides a narrative review of previous neuroimaging studies on the pathophysiology of episodic CH, addressing alterations in brain structures, metabolism, and structural and functional connectivity occurring between bout periods. Results Although the precise brain structures responsible for episodic CH are unknown, major roles are indicated for the posterior hypothalamus (especially in acute attacks), the pain neuromatrix with an emphasis on central descending pain modulation, and non-traditional pain processing networks including the occipital, cerebellar, and salience networks. These areas are potentially related to dynamic transitioning between in- and out-of-bout periods. Conclusion Recent progress in magnetic resonance imaging of episodic CH has provided additional insights into dynamic bout-associated structural and functional connectivity changes in the brain, especially in non-traditional pain processing network areas. These areas warrant future investigations as targets for neuromodulation in patients with CH.

White matter hyperintensities in migraine: Clinical significance and central pulsatile hemodynamic correlates.

Background The role of central pulsatile hemodynamics in the pathogenesis of white matter hyperintensities in migraine patients has not been clarified. Methods Sixty patients with migraine (20-50 years old; women, 68%) without overt vascular risk factors and 30 demographically-matched healthy controls were recruited prospectively. Cerebral white matter hyperintensities volume was determined by T1-weighted magnetic resonance imaging with CUBE-fluid-attenuated-inversion-recovery sequences. Central systolic blood pressure, carotid-femoral pulse wave velocity, and carotid augmentation index were measured by applanation tonometry. Carotid pulsatility index was derived from Doppler ultrasound carotid artery flow analysis. Results Compared to the controls, the migraine patients had higher white matter hyperintensities frequency (odds ratio, 2.75; p = 0.04) and greater mean white matter hyperintensities volume (0.174 vs. 0.049, cm3, p = 0.04). Multivariable regression analysis showed that white matter hyperintensities volume in migraine patients was positively associated with central systolic blood pressure ( p = 0.04) and carotid-femoral pulse wave velocity ( p < 0.001), but negatively associated with carotid pulsatility index ( p = 0.04) after controlling for potential confounding factors. The interaction effects observed indicated that the influence of carotid-femoral pulse wave velocity ( p = 0.004) and central systolic blood pressure ( p = 0.03) on white matter hyperintensities formation was greater for the lower-carotid pulsatility index subgroup of migraine patients. White matter hyperintensities volume in migraine patients increased with decreasing carotid pulsatility index and with increasing central systolic blood pressure or carotid-femoral pulse wave velocity. Conclusions White matter hyperintensities are more common in patients with migraine than in healthy controls. Increased aortic stiffness or central systolic blood pressure in the presence of low intracranial artery resistance may predispose patients with migraine to white matter hyperintensities formation.

Somatosensory gating is altered and associated with migraine chronification: A magnetoencephalographic study.

Background Brain excitability is changed in migraine but not fully characterized yet. This study explored if somatosensory gating is altered in migraine and linked to migraine chronification. Methods Paired electrical stimuli were delivered to the left index fingers of 21 patients with migraine without aura (MO), 22 patients with chronic migraine (CM), and 36 controls. The first and second responses to the paired stimuli were obtained from the contralateral primary (cSI), contralateral secondary (cSII) and ipsilateral secondary (iSII) somatosensory cortices to compute the gating ratios (second vs. first response strengths). Results The first and second cSI responses and gating ratios differed in all groups ( p < 0.05); the responses were typically smaller in the MO and CM groups. The cSI gating ratio increased as a continuum across controls (0.73 ± 0.04, p < 0.001), MO (0.83 ± 0.04) to CM (0.97 ± 0.06) and was higher in CM vs. controls ( p < 0.001). When MO and CM were combined, cSI gating ratio was associated with headache frequency (r = 0.418, p = 0.005). Paired responses and gating ratios of cSII and iSII did not differ among the groups. Conclusions Somatosensory gating is altered in migraine and associated with headache chronification. Further studies must clarify if this abnormal sensory modulation is a true gating deficit independent of low preexcitation level.

Bout-associated intrinsic functional network changes in cluster headache: A longitudinal resting-state functional MRI study.

Background Previous imaging studies on the pathogenesis of cluster headache (CH) have implicated the hypothalamus and multiple brain networks. However, very little is known regarding dynamic bout-associated, large-scale resting state functional network changes related to CH. Methods Resting-state functional magnetic resonance imaging data were obtained from CH patients and matched controls. Data were analyzed using independent component analysis for exploratory assessment of the changes in intrinsic brain networks and their relationship between in-bout and out-of-bout periods, as well as correlations with clinical observations. Results Compared to healthy controls, CH patients had functional connectivity (FC) changes in the temporal, frontal, salience, default mode, somatosensory, dorsal attention, and visual networks, independent of bout period. Compared to out-of-bout scans, in-bout scans showed altered FC in the frontal and dorsal attention networks. Lower frontal network FC correlated with longer duration of CH. Conclusions The present findings suggest that episodic CH with dynamic bout period shifts may involve bout-associated FC changes in multiple discrete cortical areas within networks outside traditional pain processing areas. Dynamic changes in FC in frontal and dorsal attention networks between bout periods could be important for understanding episodic CH pathophysiology.

Hippocampus and amygdala volume in relation to migraine frequency and prognosis.

Objectives To investigate the structural changes of hippocampus and amygdala and their relationships with migraine frequency and prognosis. Methods Hippocampus and amygdala volumes were measured by 3-T brain magnetic resonance imaging (MRI) in 31 controls and 122 migraine patients who were categorized into eight groups by headache frequency: group 1 (1-2 headache days/month), 2 (3-4), 3 (5-7), 4 (8-10), 5 (11-14), 6 (15-19), 7 (20-24), and 8 (25-30). Headache frequency was reassessed 2 years later and a frequency reduction ≥50% was regarded a good outcome. Results Hippocampus and amygdala volumes fluctuated in patient groups but did not differ from the controls. In migraine patients, the bilateral hippocampus volumes peaked in group 3. The volumes and headache frequencies correlated positively in groups 2-3 on bilateral sides (L: r = 0.44, p = 0.007; R: r = 0.35, p = 0.037), and negatively in groups 3-7 on the left side (5-24 days/month; L: r = -0.31, p = 0.004) and groups 3-8 on the right side ( r = -0.31, p = 0.002). The left amygdala volume also peaked in group 3, and correlated with headache frequency in groups 1-3 ( r = 0.34, p = 0.020) and groups 3-6 ( r = -0.30, p = 0.012). The volumetric changes of the right amygdala with headache frequency did not reach statistical significance. At 2-year follow-up, the right hippocampus volume was positively associated with a good migraine outcome after adjustment of headache frequency (OR 4.72, p = 0.024). Conclusions Hippocampus and amygdala display a structural plasticity linked to both headache frequency and clinical outcome of migraine.

Greater periventricular white matter hyperintensity severity in basilar artery branch atheromatous disease.

BACKGROUND: Basilar artery branch atheromatous disease (BABAD), in which basilar artery atheroma occludes penetrating arteries at their origin, is a common etiology of posterior circulation stroke (PCS). It is currently unknown whether white matter hyperintensity(WMH), a marker of small vessel disease(SVD), is associated with BABAD. METHODS: The present study analyzed data from patients with PCS who were enrolled in the Taipei Veterans General Hospital Stroke Registry between January 1, 2010 and February 28, 2014. WMH severity was rated using the Scheltens scale. We used multivariate analyses to: (1) compare the severity of WMH between patients with BABAD, patients with large-artery > 50% atherosclerotic stenosis-related PCS(LAA), and non-stroke subjects(NS); and (2) evaluate the relationship between WMH severity and the 3-month prognosis of patients with BABAD. RESULTS: The study pool included 151 BABAD, 97 LAA, and 78 non-stroke patients. Multivariate analyses adjusting for age, sex, and vascular risk factors showed that compared to patients with LAA [Odds ratio(OR) = 0.51, p = 0.037] and NS (OR = 0.40, p = 0.004), patients with BABAD (OR = 1) had greater WMH severity (score ≥ 50th percentile) in periventricular, but not subcortical, regions. Moreover, greater periventricular WMH severity predicted poor 3-month functional outcomes (modified Rankin Scale > 3) with an OR of 3.21 (p = 0.028) in BABAD patients. CONCLUSIONS: We are the first to show a significant association between WMH and BABAD that is independent of vascular risk factors and atherosclerotic large-artery disease. Our results suggest that small vessel abnormalities other than lipohyalinosis may be involved in BABAD pathophysiology. A future management strategy should include both large and small vessel protection.

Altered insula-default mode network connectivity in fibromyalgia: a resting-state magnetoencephalographic study.

BACKGROUND: Fibromyalgia (FM) is a disabling chronic pain syndrome with unknown pathophysiology. Functional magnetic resonance imaging studies on FM have suggested altered brain connectivity between the insula and the default mode network (DMN). However, this connectivity change has not been characterized through direct neural signals for exploring the embedded spectrotemporal features and the pertinent clinical relevance. METHODS: We recorded the resting-state magnetoencephalographic activities of 28 patients with FM and 28 age- and sex-matched controls, and analyzed the source-based functional connectivity between the insula and the DMN at 1-40 Hz by using the minimum norm estimates and imaginary coherence methods. We also measured the connectivity between the DMN and the primary visual (V1) and somatosensory (S1) cortices as intrapatient negative controls. Connectivity measurement was further correlated with the clinical parameters of FM. RESULTS: Compared with the controls, patients with FM reported more tender points (15.2±2.0 vs. 5.9±3.7) and higher total tenderness score (TTS; 29.1±7.0 vs. 7.7±5.5; both p < 0.001); they also had decreased insula-DMN connectivity at the theta band (4-8 Hz; left, p = 0.007; right, p = 0.035), but displayed unchanged V1-DMN and S1-DMN connectivity (p > 0.05). When patients with FM and the controls were combined together, the insula-DMN theta connectivity was negatively correlated with the number of tender points (left insula, r = -0.428, p = 0.001; right insula, r = -0.4, p = 0.002) and TTS score (left insula, r = -0.429, p = 0.001; right insula, r = -0.389, p = 0.003). Furthermore, in patients with FM, the right insula-DMN connectivity at the beta band (13-25 Hz) was negatively correlated with the number of tender points (r = -0.532, p = 0.004) and TTS (r = -0.428, p = 0.023), and the bilateral insula-DMN connectivity at the delta band (1-4 Hz) was negatively correlated with FM Symptom Severity (left: r = -0.423, p = 0.025; right: r = -0.437, p = 0.020) and functional disability (Fibromyalgia Impact Questionnaire; left: r = -0.415, p = 0.028; right: r = -0.374, p = 0.050). CONCLUSIONS: We confirmed the frequency-specific reorganization of the insula-DMN connectivity in FM. The clinical relevance of this connectivity change may warrant future studies to elucidate its causal relationship and potential as a neurological signature for FM.

Xenograft of human umbilical mesenchymal stem cells from Wharton's jelly as a potential therapy for rat pilocarpine-induced epilepsy.

We evaluated the effects of intra-hippocampal transplantation of human umbilical mesenchymal stem cells (HUMSCs) on pilocarpine-treated rats. Sprague-Dawley rats were divided into the following three groups: (1) a normal group of rats receiving only PBS, (2) a status epilepticus (SE) group of rats with pilocarpine-induced SE and PBS injected into the hippocampi, and (3) a SE+HUMSC group of SE rats with HUMSC transplantation. Spontaneous recurrent motor seizures (SRMS) were monitored using simultaneous video and electroencephalographic recordings at two to four weeks after SE induction. The results showed that the number of SRMS within two to four weeks after SE was significantly decreased in SE+HUMSCs rats compared with SE rats. All of the rats were sacrificed on Day 29 after SE. Hippocampal morphology and volume were evaluated using Nissl staining and magnetic resonance imaging. The results showed that the volume of the dorsal hippocampus was smaller in SE rats compared with normal and SE+HUMSCs rats. The pyramidal neuron loss in CA1 and CA3 regions was more severe in the SE rats than in normal and SE+HUMSCs rats. No significant differences were found in the hippocampal neuronal loss or in the number of dentate GABAergic neurons between normal and SE+HUMSCs rats. Compared with the SE rats, the SE+HUMSCs rats exhibited a suppression of astrocyte activity and aberrant mossy fiber sprouting. Implanted HUMSCs survived in the hippocampus and released cytokines, including FGF-6, amphiregulin, glucocorticoid-induced tumor necrosis factors receptor (GITR), MIP-3ß, and osteoprotegerin. In an in vitro study, exposure of cortical neurons to glutamate showed a significant decrease in cell viability, which was preventable by co-culturing with HUMSCs. Above all, the expression of human osteoprotegerin and amphiregulin were significantly increased in the media of the co-culture of neurons and HUMSCs. Our results demonstrate the therapeutic benefits of HUMSC transplantation for the development of epilepsy, which are likely due to the ability of the cells to produce neuroprotective and anti-inflammatory cytokines. Thus, HUMSC transplantation may be an effective therapy in the future.

Impacts of Cigarette Smoking and Basilar Artery Flow on 1-year Recovery in 3-Month survivors of Intracranial Vertebrobasilar Artery Dissection-related Ischemic Stroke.

OBJECTIVE: Intracranial vertebrobasilar artery dissection (iVBD) is an important etiology for posterior circulation ischemic stroke (PCS); however, its long-term functional outcome has been seldom reported. The present study aimed to elucidate the functional outcomes and the predictors of poor functional recovery at 1-year after iVBD-caused PCS. METHODS: Patients with iVBD-caused PCS who had been recruited in the Stroke Registry of Taipei Veterans General Hospital between January 1, 2012 to February 28, 2014 were included. Multivariate analysis was used to detect predictors for poor 1-year functional recovery [modified Rankin Scale (mRS) ≥ 4]. RESULTS: Sixty patients [age: 66.3±15.1 years; 45(75%) men] were included. At 1-year after stroke, 61.7% of patients had good functional status (mRS 0-1); however, 21.6% of patients were disabled (mRS≥4). Multivariate analyses showed that older age, cigarette-smoking history and low basilar-artery (BA) flow velocity were significantly associated with poor functional recovery independent of stroke severity at admission. The results also revealed a synergistic effect of cigarette-smoking and low BA flow on poor 1-year functional recovery: patients with both, a history of cigarette-smoking and low BA flow (≤24cm/s) had an odds ratio of 276.1 (p=0.007) leading to poor 1-year functional recovery, versus patients with neither cigarette-smoking history nor low BA flow. CONCLUSIONS: Our results suggest that adequate blood flow may be key to functional recovery after iVBDcaused PCS. Methods to improve blood flow and tissue perfusion after iVBD-caused PCS should be considered in the future clinical studies with the purpose to improve functional recovery in these patients.

Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study.

BACKGROUND: Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH. It is unknown whether the hypothalamus interacts significantly with these areas, and whether any such interactions vary between the 'in-bout' and 'out-of-bout' periods in CH. This study aimed to investigate the resting-state functional connectivity (FC) of the hypothalamus of patients with CH. METHODS: Using 3-T functional MRI, we conducted a seed-based resting-state intrinsic FC analysis of the hypothalamus in 18 episodic CH patients during in-bout and out-of-bout periods, and in 19 healthy controls. Correlations between hypothalamic FC and clinical variables were also assessed. RESULTS: Compared to controls, CH patients showed hypothalamic FC changes with the medial frontal gyrus and occipital cuneus during in-bout and out-of-bout periods. Compared to out-of-bout scans, in-bout scans revealed decreased hypothalamic FC with the medial frontal gyrus, precuneus, and cerebellar areas (tonsil, declive and culmen). Additionally, the annual bout frequency correlated significantly with the hypothalamic FC in the cerebellar culmen (r=-0.576, p=0.02) and cerebellar declive (r=-0.522, p=0.038). CONCLUSIONS: Our findings suggest that in CH, FC differences between the hypothalamus and its regional distribution extends beyond traditional pain processing areas, primarily to the cerebellar, frontal and occipital areas. These changes may be important and associated with CH pathophysiology.

Soluble epoxide hydrolase activity regulates inflammatory responses and seizure generation in two mouse models of temporal lobe epilepsy.

Neuroinflammation is known to be involved in epileptogenesis with unclear mechanisms. Inhibition of soluble epoxide hydrolase (sEH) seems to offer anti-inflammatory protection to ischemic brain injury in rodents. Thus, it is hypothesized that sEH inhibition might also affect the neuroinflammatory responses caused by epileptic seizures. In the present study, we investigated the involvement of sEH in neuroinflammation, seizure generation and subsequent epileptogenesis using two mouse models of temporal lobe epilepsy. Experimental epileptic seizures were induced by either pilocarpine or electrical amygdala kindling in both wild-type (WT) C57BL/6 mice and sEH knockout (sEH KO) mice. The sEH expression in the hippocampus was detected by immunohistochemistry and Western blot analysis. The effects of the sEH hydrolase inhibitors, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) and N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy) phenyl)-urea (TPPU), and of the genetic deletion of sEH on seizure-induced neuroinflammatory responses and the development of epilepsy were evaluated. In the hippocampus of WT mice, sEH was mainly expressed in astrocytes (GFAP(+)), neurons (NeuN(+)) and scattered microglia (Iba-1(+)) in the regions of CA1, CA3 and dentate gyrus. Expression of sEH was significantly increased on day 7, 14, 21 and 28 after pilocarpine-induced status epilepticus (SE). Administration with sEH inhibitors attenuated the SE-induced up-regulation of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), the degradation of EETs, as well as IκB phosphorylation. Following treatment with AUDA, the frequency and duration of spontaneous motor seizures in the pilocarpine-SE mice were decreased and the seizure-induction threshold of the fully kindled mice was increased. Up-regulation of hippocampal IL-1ß and IL-6 was found in both WT and sEH KO mice after successful induction of SE. Notably, sEH KO mice were more susceptible to seizures than WT mice. Seizure related neuroinflammation and ictogenesis were attenuated by pharmacological inhibition of sEH enzymatic activity but not by sEH genetic deletion. Therefore, sEH may play an important role in the generation of epilepsy. Furthermore, the effectiveness of AUDA in terms of anti-inflammatory and anti-ictogenesis properties suggests that it may have clinical therapeutic implication for epilepsy in the future, particularly when treating temporal lobe epilepsy.

Theory of mind and social functioning in patients with temporal lobe epilepsy.

OBJECTIVE: This study aimed to explore the effects of theory of mind (ToM) and related potential risk factors, including cognitive functions, psychiatric status, and seizure-related clinical variables, on social functioning in patients with temporal lobe epilepsy (TLE). METHODS: Sixty-seven patients with intractable TLE who were potential candidates for epilepsy surgery and 30 matched controls were included. All participants completed four tasks measuring different levels of ToM (False Belief, Faux Pas Recognition, Implication Stories, and Visual Cartoon), the Symptom Checklist-90-Revised (SCL-90-R), the Social and Occupational Functioning Scale for Epilepsy (SOFSE), and neuropsychological tests. RESULTS: The patients exhibited impairments in both basic and advanced ToM. Multiple regression analyses revealed the following: (1) the SOFSE total score was significantly predicted by the Faux Pas Recognition (FPR), Global Severity Index (GSI) score of the SCL-90-R, and Full-Scale intelligence quotient (IQ) of the Wechsler Adult Intelligence Scale (WAIS), which accounted for 38%, 11%, and 8% of the variance, respectively; and (2) the FPR was a significant predictor of all SOFSE subscales, whereas the GSI score contributed substantially to the Interpersonal Relationships, Communication, and Occupation subscales of the SOFSE. SIGNIFICANCE: Advanced ToM, measured by impaired faux pas recognition, is a relatively strong predictor of poor social functioning in surgical candidates for intractable TLE. Identifying ToM impairment may help plan nonpharmacologic treatment for improving social functions in patients with intractable TLE.

Region-specific reduction of auditory sensory gating in older adults.

Aging has been associated with declines in sensory-perceptual processes. Sensory gating (SG), or repetition suppression, refers to the attenuation of neural activity in response to a second stimulus and is considered to be an automatic process to inhibit redundant sensory inputs. It is controversial whether SG deficits, as tested with an auditory paired-stimulus protocol, accompany normal aging in humans. To reconcile the debates arising from event-related potential studies, we recorded auditory neuromagnetic reactivity in 20 young and 19 elderly adult men and determined the neural activation by using minimum-norm estimate (MNE) source modeling. SG of M100 was calculated by the ratio of the response to the second stimulus over that to the first stimulus. MNE results revealed that fronto-temporo-parietal networks were implicated in the M100 SG. Compared to the younger participants, the elderly showed selectively increased SG ratios in the anterior superior temporal gyrus, anterior middle temporal gyrus, temporal pole and orbitofrontal cortex, suggesting an insufficient age-related gating to repetitive auditory stimulation. These findings also highlight the loss of frontal inhibition of the auditory cortex in normal aging.

Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization.

Sensory gating (SG), referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII). However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1-) induced event-related desynchronization (ERD) contributes to a less-suppressed stimulus 2- (S2-) evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc). Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity.

Temporo-frontal functional connectivity during auditory change detection is altered in Alzheimer's disease.

Cortico-cortical connections might be disturbed in patients with Alzheimer's disease (AD). This study aimed to investigate the alterations of functional connectivity in AD during auditory change detection processing by measuring the local neuronal activation and functional connectivity between cortical regions. Magnetoencephalographic responses to deviant and standard sounds were recorded in 16 AD patients, 18 young controls and 16 elderly controls. Larger source amplitudes and shorter peak latencies were found in the right temporal magnetic mismatch responses of young controls compared with elderly controls and AD patients. During deviant stimuli, the right theta temporal-frontal phase synchrony was significantly smaller in AD than in young controls and elderly controls. Moreover, the left temporal-frontal synchronization at theta and alpha bands was reduced in AD and elderly controls compared with young controls. In conclusion, the loss in temporo-frontal theta synchronization might be an electrophysiological hallmark of AD.

Altered white matter microstructural connectivity in cluster headaches: a longitudinal diffusion tensor imaging study.

BACKGROUND: Functional and structural disruptions to the pain matrix, which may involve changes in white matter (WM) pathways connecting the pain-processing system and hypothalamus, have been implicated in the pathophysiology of cluster headache (CH). However, previous studies have obtained inconclusive results regarding WM changes in CH, and WM variations between "in-bout" and "out-of-bout" periods of CH remain to be determined. METHODS: Multiple diffusivity indices obtained by diffusion tensor imaging (DTI) and post-hoc probabilistic tractography were used to elucidate CH pathophysiology. RESULTS: Compared to healthy participants, in-bout CH patients showed regionally higher absolute (radial and mean) diffusivities in the left medial frontal gyrus and frontal sub-gyrus and lower absolute (axial, radial and mean) diffusivities in the right parahippocampal gyrus of the limbic lobe. These changes during the in-bout period generally persisted in the out-of-bout period, except for the left cerebellar tonsil. Post-hoc probabilistic tractography showed highly consistent anatomical connections between these altered areas and the hypothalamus across participants. CONCLUSIONS: Distinct WM changes were observed in episodic CH. Connections between the pain-modulation areas and hypothalamus may be involved in CH pathophysiology.