Epilepsy investigated non-invasively using Elecroencephalography (EEG) and Magnetoencephalography (MEG)

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Volume conductor modeling of the human head for electroencephalography (EEG) used in epilepsy

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Prefrontal and posterior parietal contributions to the perceptual awareness of touch

Which brain regions contribute to the perceptual awareness of touch remains largely unclear. We collected structural magnetic resonance imaging scans and neurological examination reports of 70 patients with brain injuries or stroke in S1 extending into adjacent parietal, temporal or pre-/frontal regions. We applied voxel-based lesion-symptom mapping to identify brain areas that overlap with an impaired touch perception (i.e., hypoesthesia). As expected, patients with hypoesthesia (n = 43) presented lesions in all Brodmann areas in S1 on postcentral gyrus (BA 1, 2, 3a, 3b). At the anterior border to BA 3b, we additionally identified motor area BA 4p in association with hypoesthesia, as well as further ventrally the ventral premotor cortex (BA 6, BA 44), assumed to be involved in whole-body perception. At the posterior border to S1, we found hypoesthesia associated effects in attention-related areas such as the inferior parietal lobe and intraparietal sulcus. Downstream to S1, we replicated previously reported lesion-hypoesthesia associations in the parietal operculum and insular cortex (i.e., ventral pathway of somatosensory processing). The present findings extend this pathway from S1 to the insular cortex by prefrontal and posterior parietal areas involved in multisensory integration and attention processes

Fat perception in the human frontal operculum, insular and somatosensory cortex

Here, we combined magnetic resonance imaging with lesion-symptom mapping in patients with chronic brain lesions to investigate brain representations of sugar and fat perception. Patients and healthy controls rated chocolate milkshakes that only differed in sugar or fat content. As compared to controls, patients showed an impaired fat, but not sugar perception. Impairments in fat perception overlapped with the anterior insula and frontal operculum, together assumed to underpin gustatory processing. We also identified the mid-dorsal insula as well as the primary and secondary somatosensory cortex - regions previously assumed to integrate oral-sensory inputs. These findings suggest that fat perception involves a specific set of brain regions that were previously reported to underpin gustatory processing and oral-sensory integration processes

Adiposity related brain plasticity induced by bariatric surgery

Previous magnetic resonance imaging (MRI) studies revealed structural-functional brain reorganization 12 months after gastric-bypass surgery, encompassing cortical and subcortical regions of all brain lobes as well as the cerebellum. Changes in the mean of cluster-wise gray/white matter density (GMD/WMD) were correlated with the individual loss of body mass index (BMI), rendering the BMI a potential marker of widespread surgery-induced brain plasticity. Here, we investigated voxel-by-voxel associations between surgery-induced changes in adiposity, metabolism and inflammation and markers of functional and structural neural plasticity. We re-visited the data of patients who underwent functional and structural MRI, 6 months (n = 27) and 12 months after surgery (n = 22), and computed voxel-wise regression analyses. Only the surgery-induced weight loss was significantly associated with brain plasticity, and this only for GMD changes. After 6 months, weight loss overlapped with altered GMD in the hypothalamus, the brain’s homeostatic control site, the lateral orbitofrontal cortex, assumed to host reward and gustatory processes, as well as abdominal representations in somatosensory cortex. After 12 months, weight loss scaled with GMD changes in right cerebellar lobule VII, involved in language-related/cognitive processes, and, by trend, with the striatum, assumed to underpin (food) reward. These findings suggest time-dependent and weight-loss related gray matter plasticity in brain regions involved in the control of eating, sensory processing and cognitive functioning

Availability of central α4β2* nicotinic acetylcholine receptors in human obesity

Purpose: Obesity is thought to arise, in part, from deficits in the inhibitory control over appetitive behavior. Such motivational processes are regulated by neuromodulators, specifically acetylcholine (ACh), via α4β2* nicotinic ACh receptors (nAChR). These nAChR are highly enriched in the thalamus and contribute to the thalamic gating of cortico-striatal signaling, but also act on the mesoaccumbal reward system. The changes in α4β2* nAChR availability, however, have not been demonstrated in human obesity thus far. The aim of our study was, thus, to investigate whether there is altered brain α4β2* nAChR availability in individuals with obesity compared to normal-weight healthy controls. Methods: We studied 15 non-smoking individuals with obesity (body mass index, BMI: 37.8 ± 3.1 kg/m2; age: 39 ± 14 years, 9 females) and 16 normal-weight controls (non-smokers, BMI: 21.9 ± 1.7 kg/m2; age: 28 ± 7 years, 13 females) by using PET and the α4β2* nAChR selective (−)-[18F]flubatine, which was applied within a bolus-infusion protocol (294 ± 16 MBq). Volume-of-interest (VOI) analysis was performed in order to calculate the regional total distribution volume (VT). Results: No overall significant difference in VT between the individuals with obesity and the normal-weight volunteers was found, while the VT in the nucleus basalis of Meynert tended to be lower in the individuals with obesity (10.1 ± 2.1 versus 11.9 ± 2.2; p = 0.10), and the VT in the thalamus showed a tendency towards higher values in the individuals with obesity (26.5 ± 2.5 versus 25.9 ± 4.2; p = 0.09). Conclusion: While these first data do not show greater brain α4β2* nAChR availability in human obesity overall, the findings of potentially aberrant α4β2* nAChR availability in the key brain regions that regulate feeding behavior merit further exploration

Roux-en-Y gastric bypass surgery progressively alters radiologic measures of hypothalamic inflammation in obese patients

There is increased interest in whether bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) achieve their profound weight-lowering effects in morbidly obese individuals through the brain. Hypothalamic inflammation is a well-recognized etiologic factor in obesity pathogenesis and so represents a potential target of RYGB, but clinical evidence in support of this is limited. We therefore assessed hypothalamic T2-weighted signal intensities (T2W SI) and fractional anisotropy (FA) values, 2 validated radiologic measures of brain inflammation, in relation to BMI and fat mass, as well as circulating inflammatory (C-reactive protein; CrP) and metabolic markers in a cohort of 27 RYGB patients at baseline and 6 and 12 months after surgery. We found that RYGB progressively increased hypothalamic T2W SI values, while it progressively decreased hypothalamic FA values. Regression analyses further revealed that this could be most strongly linked to plasma CrP levels, which independently predicted hypothalamic FA values when adjusting for age, sex, fat mass, and diabetes diagnosis. These findings suggest that RYGB has a major time-dependent impact on hypothalamic inflammation status, possibly by attenuating peripheral inflammation. They also suggest that hypothalamic FA values may provide a more specific radiologic measure of hypothalamic inflammation than more commonly used T2W SI values

Epileptiform Activity in Alcohol Dependent Patients and Possibilities of Its Indirect Measurement

Background: Alcohol dependence during withdrawal and also in abstinent period in many cases is related to reduced inhibitory functions and kindling that may appear in the form of psychosensory symptoms similar to temporal lobe epilepsy frequently in conditions of normal EEG and without seizures. Because temporal lobe epileptic activity tend to spread between hemispheres, it is possible to suppose that measures reflecting interhemispheric information transfer such as electrodermal activity (EDA) might be related to the psychosensory symptoms. Methods and Findings: We have performed measurement of bilateral EDA, psychosensory symptoms (LSCL-33) and alcohol craving (ACQ) in 34 alcohol dependent patients and 32 healthy controls. The results in alcohol dependent patients show that during rest conditions the psychosensory symptoms (LSCL-33) are related to EDA transinformation (PTI) between left and right EDA records (Spearman r = 0.44, p,0.01). Conclusions: The result may present potentially useful clinical finding suggesting a possibility to indirectly assess epileptiform changes in alcohol dependent patients

Variable Anisotropic Brain Electrical Conductivities in Epileptogenic Foci

Source localization models assume brain electrical conductivities are isotropic at about 0.33 S/m. These assumptions have not been confirmed ex vivo in humans. This study determined bidirectional electrical conductivities from pediatric epilepsy surgery patients. Electrical conductivities perpendicular and parallel to the pial surface of neocortex and subcortical white matter (n = 15) were measured using the 4-electrode technique and compared with clinical variables. Mean (±SD) electrical conductivities were 0.10 ± 0.01 S/m, and varied by 243% from patient to patient. Perpendicular and parallel conductivities differed by 45%, and the larger values were perpendicular to the pial surface in 47% and parallel in 40% of patients. A perpendicular principal axis was associated with normal, while isotropy and parallel principal axes were linked with epileptogenic lesions by MRI. Electrical conductivities were decreased in patients with cortical dysplasia compared with non-dysplasia etiologies. The electrical conductivity values of freshly excised human brain tissues were approximately 30% of assumed values, varied by over 200% from patient to patient, and had erratic anisotropic and isotropic shapes if the MRI showed a lesion. Understanding brain electrical conductivity and ways to non-invasively measure them are probably necessary to enhance the ability to localize EEG sources from epilepsy surgery patients

Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs