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Background: Reduced expression or impaired signalling of tropomyosin receptor kinases (Trk receptors) are found in a vast spectrum of CNS disorders. [18F]TRACK is the first PET radioligand for TrkB/C with proven in vivo brain penetration and on-target specific signal. Here we report dosimetry data for [18F]TRACK in healthy humans. 6 healthy participants (age 22–61 y, 3 female) were scanned on a General Electric Discovery PET/CT 690 scanner. [18F]TRACK was synthesized with high molar activities (Am = 250 ± 75 GBq/µmol), and a dynamic series of 12 whole-body scans were acquired after injection of 129 to 147 MBq of the tracer. Images were reconstructed with standard corrections using the manufacturer's OSEM algorithm. Tracer concentration time-activity curves (TACs) were obtained using CT-derived volumes-of-interest. Organ-specific doses and the total effective dose were estimated using the Committee on Medical Internal Radiation Dose equation for adults and tabulated Source tissue values (S values). Results: Average organ absorbed dose was highest for liver and gall bladder with 6.1E−2 (± 1.06E−2) mGy/MBq and 4.6 (± 1.18E−2) mGy/MBq, respectively. Total detriment weighted effective dose EDW was 1.63E−2 ± 1.68E−3 mSv/MBq. Organ-specific TACs indicated predominantly hepatic tracer elimination. Conclusion: Total and organ-specific effective doses for [18F]TRACK are low and the dosimetry profile is similar to other 18F-labelled radio tracers currently used in clinical settings. [ABSTRACT FROM AUTHOR]

Neuroimaging assessment of motor neuron disease has turned into a cornerstone of its clinical workup. Amyotrophic lateral sclerosis (ALS), as a paradigmatic motor neuron disease, has been extensively studied by advanced neuroimaging methods, including molecular imaging by MRI and PET, furthering finer and more specific details of the cascade of ALS neurodegeneration and symptoms, facilitated by multicentric studies implementing novel methodologies. With an increase in multimodal neuroimaging data on ALS and an exponential improvement in neuroimaging technology, the need for harmonization of protocols and integration of their respective findings into a consistent model becomes mandatory. Integration of multimodal data into a model of a continuing cascade of functional loss also calls for the best attempt to correlate the different molecular imaging measurements as performed at the shortest inter-modality time intervals possible. As outlined in this perspective article, simultaneous PET/MRI, nowadays available at many neuroimaging research sites, offers the perspective of a one-stop shop for reproducible imaging biomarkers on neuronal damage and has the potential to become the new gold standard for characterizing motor neuron disease from the clinico-radiological and neuroscientific perspectives. [ABSTRACT FROM AUTHOR]

Rationale: Cardiovascular exercise is an effective method to improve cardiovascular health outcomes, but also promote neuroplasticity during stroke recovery. Moderate-intensity continuous cardiovascular training (MICT) is an integral part of stroke rehabilitation, yet it may remain a challenge to exercise at sufficiently high intensities to produce beneficial adaptations to neuroplasticity. High-intensity interval training (HIIT) could provide a viable alternative to achieve higher intensities of exercise by using shorter bouts of intense exercise interspersed with periods of recovery.Methods and Design: This is a two-arm, parallel-group multi-site RCT conducted at the Jewish Rehabilitation Hospital (Laval, Québec, Canada) and McMaster University (Hamilton, Ontario, Canada). Eighty participants with chronic stroke will be recruited at both sites and will be randomly allocated into a HIIT or MICT individualized exercise program on a recumbent stepper, 3 days per week for 12 weeks. Outcomes will be assessed at baseline, at 12 weeks post-intervention, and at an 8-week follow-up.Outcomes: The primary outcome is corticospinal excitability, a neuroplasticity marker in brain motor networks, assessed with transcranial magnetic stimulation (TMS). We will also examine additional markers of neuroplasticity, measures of cardiovascular health, motor function, and psychosocial responses to training.Discussion: This trial will contribute novel insights into the effectiveness of HIIT to promote neuroplasticity in individuals with chronic stroke.Trial Registration: ClinicalTrials.gov NCT03614585 . Registered on 3 August 2018. [ABSTRACT FROM AUTHOR]

Background: During recovery from stroke, the contralesional motor cortex (M1) may undergo maladaptive changes that contribute to impaired interhemispheric inhibition (IHI). Transcranial direct current stimulation (tDCS) with the cathode over contralesional M1 may inhibit this maladaptive plasticity, normalize IHI, and enhance motor recovery. Objective: The objective of this systematic review and meta-analysis was to evaluate available evidence to determine whether cathodal tDCS on contralesional M1 enhances motor re-learning or recovery post-stroke more than sham tDCS. Methods: We searched OVID Medline, Embase, and the Cochrane Central Register of Controlled Trials for participants with stroke (>1 week post-onset) with motor impairment and who received cathodal or sham tDCS to contralesional M1 for one or more sessions. The outcomes included a change in any clinically validated assessment of physical function, activity, or participation, or a change in a movement performance variable (e.g., time, accuracy). A meta-analysis was performed by pooling five randomized controlled trials (RCTs) and comparing the change in Fugl–Meyer upper extremity scores between cathodal and sham tDCS groups. Results: Eleven studies met the inclusion criteria. Qualitatively, four out of five cross-over design studies and three out of six RCTs reported a significant effect of cathodal vs. sham tDCS. In the quantitative synthesis, cathodal tDCS (n = 65) did not significantly reduce motor impairment compared to sham tDCS (n = 67; standardized mean difference = 0.33, z = 1.79, p = 0.07) with a little observed heterogeneity (I 2 = 5%). Conclusions: The effects of cathodal tDCS to contralesional M1 on motor recovery are small and consistent. There may be sub-populations that may respond to this approach; however, further research with larger cohorts is required. [ABSTRACT FROM AUTHOR]

We report on a new implementation and first numerical tests of the fourth-order algebraicdiagramatic construction [ADC(4)] propagator method for K-shell ionization in molecules. The theory, which has been presented in a preceding paper (paper I) [J. Chem. Phys. 115, 10621 (2001)], is based on an intermediate state representation (ISR) or non-Dyson reformulation of the general ADC approach and uses the core-valence separation approximation to specialize the method to the case of core-level ionization. The ISR form offers the possibility to go beyond the finite perturbation-theoretical expressions of the previous (strict) ADC(4) scheme, and several such modifications are considered. The general aim of the present development is to establish a practical "frozen" orbital method that can be applied equally well to systems with and without equivalent core levels. A set of small model calculations has been carried out on the 1s ionization in CO and N[sub 2] allowing us to compare the ADC results with those of large-scale configuration interaction treatments and analyze the performance of several ADC(4) modifications in describing the 1s ionization energies as a function of the bond lengths. These studies clearly demonstrate the need for improving the previous (strict) ADC(4) scheme. In the theoretical description of the C1s and N1s ionization, the proposed modifications lead to a substantial improvement, whereas in the case of the O1s ionization further developments appear to be necessary. In another set of calculations using reasonably large basis sets, the improved ADC(4) method is applied to the vibrational structure in the CO C1s and N[sub 2] N1s ionization spectra. The results are in very good agreement with the findings of recent high-resolution measurements. An interesting feature is the different behavior of the g and u components of the N1s ionization energy curves of N[sub 2] leading to different vibrational line intensity distributions. [ABSTRACT FROM AUTHOR]

Gait impairment during complex walking in older adults is thought to result from a progressive failure to compensate for deteriorating peripheral inputs by central neural processes. It is the primary hypothesis of this article that failure of higher cerebral adaptations may already be present in middle-aged adults who do not present observable gait impairments. We, therefore, compared metabolic brain activity during steering of gait (ie, complex locomotion) and straight walking (ie, simple locomotion) in young and middle-aged individuals. Cerebral distribution of [18F]-fluorodeoxyglucose, a marker of brain synaptic activity, was assessed during over ground straight walking and steering of gait using positron emission tomography in seven young adults (aged 24 ± 3) and seven middle-aged adults (aged 59 ± 3). Brain regions involved in steering of gait (posterior parietal cortex, superior frontal gyrus, and cerebellum) are retained in middle age. However, despite similar walking performance, there are age-related differences in the distribution of [18F]-fluorodeoxyglucose during steering: middle-aged adults have (i) increased activation of precentral and fusiform gyri, (ii) reduced deactivation of multisensory cortices (inferior frontal, postcentral, and fusiform gyri), and (iii) reduced activation of the middle frontal gyrus and cuneus. Our results suggest that preclinical decline in central sensorimotor processing in middle age is observable during complex walking. [ABSTRACT FROM AUTHOR]

We evaluated whether transcranial direct current stimulation (tDCS) in two different montages could improve picture naming abilities in participants with anomic Alzheimer Disease or Frontotemporal dementia. Methods: Utilizing a double-blind cross-over design, twelve participants were trained on picture naming over a series of 10 sessions with 30 min of anodal (2 mA) tDCS stimulation to either the left inferior parietotemporal region (P3), the left dorsolateral prefrontal cortex (F3), or sham stimulation. We evaluated performance on a trained picture naming list, an equivalent novel untrained list, and additional neuropsychological tasks. Results: For trained item picture naming, significantly larger improvement was seen for real stimulation vs. sham stimulation for both the DLPFC and left inferior parieto-temporal stimulation montages at the end of the stimulation sessions. The parieto-temporal montage remained superior to sham 2 weeks poststimulation. Significant improvement vs. sham was also seen for novel "untrained" item picture naming 2 weeks post-stimulation when the parieto-temporal montage was given, whereas no change was observed when the DLPFC montage was given. Finally, comparing groups when they received the parieto-temporal montage, participants with semantic variant Primary Progressive Aphasia (PPA) showed the least improvement for untrained items after their sessions. Scores on the additional neuropsychological tasks were unchanged. Conclusion: tDCS stimulation has promise as a treatment for individuals with anomia arising from neurodegenerative disease, but its effectiveness can vary depending on the training given, the montage location used, as well as a participants' diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline.Methods: We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function.Results: A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = -0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex.Interpretation: The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576-587. [ABSTRACT FROM AUTHOR]

APPIAN is an automated pipeline for user-friendly and reproducible analysis of positron emission tomography (PET) images with the aim of automating all processing steps up to the statistical analysis of measures derived from the final output images. The three primary processing steps are coregistration of PET images to T1-weighted magnetic resonance (MR) images, partial-volume correction (PVC), and quantification with tracer kinetic modeling. While there are alternate open-source PET pipelines, none offers all of the features necessary for making automated PET analysis as reliably, flexibly and easily extendible as possible. To this end, a novel method for automated quality control (QC) has been designed to facilitate reliable, reproducible research by helping users verify that each processing stage has been performed as expected. Additionally, a web browser-based GUI has been implemented to allow both the 3D visualization of the output images, as well as plots describing the quantitative results of the analyses performed by the pipeline. APPIAN also uses flexible region of interest (ROI) definition—with both volumetric and, optionally, surface-based ROI—to allow users to analyze data from a wide variety of experimental paradigms, e.g., longitudinal lesion studies, large cross-sectional population studies, multi-factorial experimental designs, etc. Finally, APPIAN is designed to be modular so that users can easily test new algorithms for PVC or quantification or add entirely new analyses to the basic pipeline. We validate the accuracy of APPIAN against the Monte-Carlo simulated SORTEO database and show that, after PVC, APPIAN recovers radiotracer concentrations within 93–100% accuracy. [ABSTRACT FROM AUTHOR]

Chronic pain patients present with cortical gray matter alterations, observed with anatomical magnetic resonance (MR) imaging. Reduced regional gray matter volumes are often interpreted to reflect neurodegeneration, but studies investigating the cellular origin of gray matter changes are lacking. We used multimodal imaging to compare 26 postmenopausal women with fibromyalgia with 25 healthy controls (age range: 50-75 years) to test whether regional gray matter volume decreases in chronic pain are associated with compromised neuronal integrity. Regional gray matter decreases were largely explained by T1 relaxation times in gray matter, a surrogate measure of water content, and not to any substantial degree by GABAA receptor concentration, an indirect marker of neuronal integrity measured with [18F] flumazenil PET. In addition, the MR spectroscopy marker of neuronal viability, N-acetylaspartate, did not differ between patients and controls. These findings suggest that decreased gray matter volumes are not explained by compromised neuronal integrity. Alternatively, a decrease in neuronal matter could be compensated for by an up regulation of GABAA receptors. The relation between regional gray matter and T1 relaxation times suggests decreased tissue water content underlying regional gray matter decreases. In contrast, regional gray matter increases were explained by GABAA receptor concentration in addition to T1 relaxation times, indicating perhaps increased neuronal matter or GABAA receptor up regulation and inflammatory edema. By providing information on the histological origins of cerebral gray matter alterations in fibromyalgia, this study advances the understanding of the neurobiology of chronic widespread pain. [ABSTRACT FROM AUTHOR]

Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, with few PSD-specific instruments. Choice will depend on purpose of assessment, with differing instruments needed for brief screening (e.g., Montreal Cognitive Assessment) or diagnostic formulation (e.g., NINDS VCI battery). A comprehensive evaluation should include assessment of pre-stroke cognition (e.g., using Informant Questionnaire for Cognitive Decline in the Elderly), mood (e.g., using Hospital Anxiety and Depression Scale), and functional consequences of cognitive impairments (e.g., using modified Rankin Scale). A large number of biomarkers for PSD, including indicators for genetic polymorphisms, biomarkers in the cerebrospinal fluid and in the serum, inflammatory mediators, and peripheral microRNA profiles have been proposed. Currently, no specific biomarkers have been proven to robustly discriminate vulnerable patients ('at risk brains') from those with better prognosis or to discriminate Alzheimer's disease dementia from PSD. Further, neuroimaging is an important diagnostic tool in PSD. The role of computerized tomography is limited to demonstrating type and location of the underlying primary lesion and indicating atrophy and severe white matter changes. Magnetic resonance imaging is the key neuroimaging modality and has high sensitivity and specificity for detecting pathological changes, including small vessel disease. Advanced multi-modal imaging includes diffusion tensor imaging for fiber tracking, by which changes in networks can be detected. Quantitative imaging of cerebral blood flow and metabolism by positron emission tomography can differentiate between vascular dementia and degenerative dementia and show the interaction between vascular and metabolic changes. Additionally, inflammatory changes after ischemia in the brain can be detected, which may play a role together with amyloid deposition in the development of PSD. Prevention of PSD can be achieved by prevention of stroke. As treatment strategies to inhibit the development and mitigate the course of PSD, lowering of blood pressure, statins, neuroprotective drugs, and anti-inflammatory agents have all been studied without convincing evidence of efficacy. Lifestyle interventions, physical activity, and cognitive training have been recently tested, but large controlled trials are still missing. [ABSTRACT FROM AUTHOR]

The peri-infarct cortex (PIC) is the site of long-term physiologic changes after ischemic stroke. Traditional methods for delineating the peri-infarct gray matter (GM) have used a volumetric Euclidean distance metric to define its extent around the infarct. This metric has limitations in the case of cortical stroke, i.e., those where ischemia leads to infarction in the cortical GM, because the vascularization of the cerebral cortex follows the complex, folded topology of the cortical surface. Instead, we used a geodesic distance metric along the cortical surface to subdivide the PIC into equidistant rings emanating from the infarct border and compared this new approach to a Euclidean distance metric definition. This was done in 11 patients with [F-18]-Flumazenil ([18-F]-FMZ) positron emission tomography (PET) scans at 2 weeks post-stroke and at 6 month follow-up. FMZ is a PET radiotracer with specific binding to the alpha subunits of the type A γ-aminobutyric acid (GABAA) receptor. Additionally, we used partial-volume correction (PVC) of the PET images to compensate for potential cortical thinning and long-term neuronal loss in follow-up images. The difference in non-displaceable binding potential (BPND) between the stroke unaffected and affected hemispheres was 35% larger in the geodesic versus the Euclidean peri-infarct models in initial PET images and 48% larger in follow-up PET images. The inter-hemispheric BPND difference was approximately 17-20% larger after PVC when compared to uncorrected PET images. PET studies of peri-infarct GM in cortical strokes should use a geodesic model and include PVC as a preprocessing step. Hum Brain Mapp 38:326-338, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile - T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds. Diffusion MRI adds another dimension by showing graded damage to white matter, making it more sensitive to white matter injury than FLAIR. Regions of neuroinflammatory disruption of the blood-brain barrier with increased permeability can be quantified and visualized with dynamic contrast-enhanced MRI. PET shows metabolism of glucose and accumulation of amyloid and tau, which is useful in showing abnormal metabolism in Alzheimer's disease. Combining MRI and PET allows identification of patients with mixed dementia, with MRI showing white matter injury and PET demonstrating regional impairment of glucose metabolism and deposition of amyloid. Excellent anatomical detail can be observed with 7.0-Tesla MRI. Imaging is the optimal method to follow the effect of treatments since changes in MRI scans are seen prior to those in cognition. This review describes the role of various imaging modalities in the diagnosis and treatment of vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Post-stroke aphasia syndromes as a clinical entity arise from the disruption of brain networks specialized in language production and comprehension due to permanent focal ischemia. This approach to post-stroke aphasia is based on two pathophysiological concepts: 1) Understanding language processing in terms of distributed networks rather than language centers and 2) understanding the molecular pathophysiology of ischemic brain injury as a dynamic process beyond the direct destruction of network centers and their connections. While considerable progress has been made in the past 10 years to develop such models on a systems as well as a molecular level, the influence of these approaches on understanding and treating clinical aphasia syndromes has been limited. Objective & Methods: In this article, we review current pathophysiological concepts of ischemic brain injury, their relationship to altered information processing in language networks after ischemic stroke and how these mechanisms may be influenced therapeutically to improve treatment of post-stroke aphasia. Conclusion: Understanding the pathophysiological mechanism of post-stroke aphasia on a neurophysiological systems level as well as on the molecular level becomes more and more important for aphasia treatment, as the field moves from standardized therapies towards more targeted individualized treatment strategies comprising behavioural therapies as well as non-invasive brain stimulation (NIBS). [ABSTRACT FROM AUTHOR]

Background: Cortical injections of the vasoconstrictor endothelin-1 (ET1) have widely been used to induce focal circumscribed ischemic lesions in the motor cortex of rodents in the context of stroke recovery studies. In order to apply this model correctly, it is essential to understand the time course of regional flow changes and of the development of penumbra and infarction. Methods: Multitracer micro-PET of ET1 focal ischemia in rats was performed using [11C]-flumazenil ([11C]FMZ) as a flow- and viability tracer and [18F]-fluoromisonidazole ([18F]FMISO) as hypoxia marker in order to characterize the physiological time-course of this model. Nine adult Sprague-Dawley rats received stereotaxic injections of ET1 into the right primary motor cortex, 3 served as controls. PET imaging was started 2, 3 and 20 h after the last ET1 injection. Histology was obtained at the end of the scans. Standardized uptake value ratios reflecting cerebral blood flow (CBF), [11C]FMZ-binding and [18F]FMISO-retention were calculated for the region of hypoperfusion and the normoperfused cortex. Results: CBF in the hypoperfused cortex was significantly reduced (p < 0.01) at 5 h (0.58 ± 0.025), 6 h (0.54 ± 0.043) and 23 h (0.66 ± 0.024) compared to controls (1.00 ± 0.011) and moderately reduced (p < 0.05) in the remainder of the affected hemisphere at 5 h (0.93 ± 0.036). [11C]FMZ-binding was within the control range at all time points. Significant [18F]FMISO-retention (1.16 ± 0.091, p < 0.05) was observed only after 6 h in the ischemic core that later turned into infarct. Conclusion: ET1 injections yield reproducible, slowly developing ischemic lesions with constant levels of hypoperfusion. This multitracer micro-PET study suggests that the ET1 model is appropriate for inducing chronic circumscribed ischemic lesions but seems to be less suited for studying acute stroke pathophysiology. [ABSTRACT FROM AUTHOR]

BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2% and 40.1%, respectively. The steps were then combined in two different ways: (a) a 'sequential process' using the zeolite and A200 in batch processes; and (b) a 'parallel process' using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

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Objectives: To review the literature on the specific role of the right cerebral hemisphere during recovery from aphasia in order to address the lack of consensus among authors. To derive a theoretical model reconciling the controversial findings in the literature. Methods: Initial PubMed, MEDLINE (1946 to 5 May 2012) and PsycINFO (1806 to first week June 2012) searches on recovery mechanisms from aphasia, whether treatment-related or not, retrieved a total of 35 English language articles. Articles, cross-referenced in this initial set were also reviewed if they met the inclusion criteria, thus resulting in a total of 42 articles included in this review. Main outcomes: Recruitment of the right hemisphere during recovery from aphasia can be effective if it occurs during a critical time window post-stroke. The recruitment's effectiveness will depend on the lesion's location, extent and permanence. Preservation of core language processing areas will generate minimal right hemisphere recruitment and vice versa. Some experimental studies seem to suggest that the improvement linked to a particular hemisphere can be modulated by specific therapy methods. Conclusion: The specific conditions in which effective right recruitment takes place may have important implications for rehabilitation treatment. These findings could lead to improved recovery in people suffering from aphasia. However, more research with non-invasive brain stimulation is needed. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence from single case studies, small case series and randomized controlled trials seems to suggest that inhibitory noninvasive brain stimulation (NIBS) over the contralesional inferior frontal gyrus (IFG) of right-handers in conjunction with speech and language therapy (SLT) improves recovery from poststroke aphasia. Application of inhibitory NIBS to improve recovery in left-handed patients has not yet been reported. Methods: A total of 29 right-handed subacute poststroke aphasics were randomized to receive either 10 sessions of SLT following 20 min of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the contralesional IFG or 10 sessions of SLT following sham stimulation; 2 left-handers were treated according to the same protocol with real rTMS. Language activation patterns were assessed with positron emission tomography prior to and after the treatment; 95% confidence intervals for changes in language performance scores and the activated brain volumes in both hemispheres were derived from TMS- and sham-treated right-handed patients and compared to the same parameters in left-handers. Results: Right-handed patients treated with rTMS showed better recovery of language function in global aphasia test scores (t test, p < 0.002) as well as in picture-naming performance (ANOVA, p = 0.03) than sham-treated right-handers. In treated right-handers, a shift of activation to the ipsilesional hemisphere was observed, while sham-treated patients consolidated network activity in the contralesional hemisphere (repeated-measures ANOVA, p = 0.009). Both left-handed patients also improved, with 1 patient within the confidence limits of TMS-treated right-handers (23 points, 15.9-28.9) and the other patient within the limits of sham-treated subjects (8 points, 2.8-14.5). Both patients exhibited only a very small interhemispheric shift, much less than expected in TMS-treated right-handers, and more or less consolidated initially active networks in both hemispheres. Conclusion: Inhibitory rTMS over the nondominant IFG appears to be a safe and effective treatment for right-handed poststroke aphasics. In the 2 cases of left-handed aphasics no deterioration of language performance was observed with this protocol. However, therapeutic efficiency is less obvious and seems to be more related to the dominance pattern prior to the stroke than to the TMS intervention. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites ( XAD7 HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta-zeolite-based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta-zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources. [ABSTRACT FROM AUTHOR]

In the healthy brain, there are close correlations between task-related activation of the primary motor cortex (M1), the magnitude of interhemispheric inhibition, and microstructural properties of transcallosal fiber tracts. After subcortical stroke affecting the pyramidal tract (PT), an abnormal pattern of bilateral activity develops in M1. With this prospective longitudinal study, we aimed to determine whether a morphological correlate of poststroke disinhibition could be measured within 20 days and 6 months of PT stroke. Using diffusion tensor imaging with tractography, we delineated transcallosal motor fibers (CMF) in nine PT stroke patients, six patients with subcortical infarct not affecting the PT (NonPT) and six transient ischemic attack patients. We compared changes in CMF fractional anisotropy ratios (rFA) with rFA in a distinct bundle of callosal occipital fibers (COF). At the initial time point, there were no significant differences in rFA between groups and fiber bundles. At follow-up, PT-group rFACMF was significantly lower than PT-group rFACOF and NonPT-group rFACMF. PT-group rFACMF decreased over time and correlated with rFA of the PT (rFAPT) retrograde to the infarct at 6 months. Our data suggest a progressive degenerative transsynaptic effect of PT stroke on CMF, which could be a morphological correlate of transcallosal disinhibition. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that induces changes in cortical excitability: anodal stimulation increases while cathodal stimulation reduces excitability. Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity. The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow (ΔrCBF) using positron emission tomography (PET) during bilateral tDCS. Nine healthy subjects underwent repeated rCBF measurements with 15O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex (M1). Motor evoked potentials (MEPs) were also assessed before and after real and sham stimulation. During tDCS with active movement, ΔrCBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation. This decrease in ΔrCBF was accompanied by a decrease in MEP amplitude on the cathodal side. No effect was observed on resting or activated rCBF relative to sham stimulation. We thus conclude that it is the interaction of cathodal tDCS with activation-induced ΔrCBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS. [ABSTRACT FROM AUTHOR]

Objective Case series with 11C-PK11195 and positron emission tomography (PET) in stroke patients suggest that activated microglia may be detected in remote brain regions with fiber tract connections to the lesion site as an indicator of poststroke neuroinflammation. However, the specificity of these imaging findings remains to be demonstrated. Methods In a prospective controlled study, we measured microglia activity using 11C-PK11195-PET along the pyramidal tract, as defined by diffusion tensor imaging, in 21 patients with first-time acute subcortical ischemia within 2 weeks of stroke. Uptake ratios (affected vs unaffected side) were determined for a set of standardized volumes of interest along the pyramidal tracts (PT). Uptake ratios from patients in whom the PT was affected were compared with those in whom the PT was not affected. Uptake ratios were related to motor deficit and lesion size according to correlation analyses. Results Increased uptake ratios were only found in patients in whom the PT was affected by stroke. In the affected hemisphere, uptake was increased at the level of pons, midbrain, and internal capsule, but not in the oval center. The extent of remote microglia activation was independent of infarct size or clinical measures of stroke severity. Interpretation A specific activation of microglia was only found in patients in whom the PT was affected by the stroke and only caudal (anterograde) to the lesion; no activation was found in the retrograde direction or in those patients in whom the PT was not affected. These findings were independent of infarct size and may represent changes secondary to early Wallerian degeneration. Ann Neurol 2009;66:825-832 [ABSTRACT FROM AUTHOR]