Browsing by Subject "Brain"
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Item Open Access Accelerated phase-cycled SSFP imaging with compressed sensing(Institute of Electrical and Electronics Engineers Inc., 2015) Çukur, T.Balanced steady-state free precession (SSFP) imaging suffers from irrecoverable signal losses, known as banding artifacts, in regions of large B0 field inhomogeneity. A common solution is to acquire multiple phase-cycled images each with a different frequency sensitivity, such that the location of banding artifacts are shifted in space. These images are then combined to alleviate signal loss across the entire field-of-view. Although high levels of artifact suppression are viable using a large number of images, this is a time costly process that limits clinical utility. Here, we propose to accelerate individual acquisitions such that the overall scan time is equal to that of a single SSFP acquisition. Aliasing artifacts and noise are minimized by using a variable-density random sampling pattern in k-space, and by generating disjoint sampling patterns for separate acquisitions. A sparsity-enforcing method is then used for image reconstruction. Demonstrations on realistic brain phantom images, and in vivo brain and knee images are provided. In all cases, the proposed technique enables robust SSFP imaging in the presence of field inhomogeneities without prolonging scan times. © 2014 IEEE.Item Open Access Age-dependent effects of short-term intermittent fasting and rapamycin treatment in Zebrafish (Danio Rerio) brain(2020-05) Birand, Ergül Dilan ÇelebiWorld populations are rapidly aging, and there is an urgent need to develop interventions that prevent or reverse age-related deterioration of health. To date, several approaches have been developed to extend health span. Among these, non genetic interventions have a higher potential to be utilized in translational studies. Caloric restriction (CR) and its pharmacological mimetic rapamycin, are two applications that have been shown to reliably extend life and health span across species. Despite a growing body of knowledge on how CR and rapamycin show their beneficial effects, their molecular mechanisms in the brain are not completely understood. Furthermore, most studies applied life-long CR, which is not suitable for translational research. To fill this gap, we investigated whether short-term durations of a CR approach intermittent fasting (IF) or rapamycin altered cellular and molecular markers of critical processes in the brain as well as metabolic parameters in the body. To assess how the age of the subjects affect the outcome of the treatments, we included young (6-10 months old) and old (26-31 months) zebrafish, which has recently emerged as a suitable model for gerontological research. Our results demonstrated that IF decreased whole-body glucose and cortisol levels, and increased neural progenitor marker DCAMKL1 in young and old animals. While this proliferation-promoting effect was preceded by suppression of mTOR activity in young, the upregulation of foxm1 and reduced autophagic flux as measured by LC3 II/LC3-I ratio were observed in old animals. Rapamycin, on the other hand, did not alter the metabolic parameters and induced entirely different molecular profiles at young and old ages. The most notable changes in young animals were reduced mTOR activity, LC3-II/LC3-I ratio and expression levels of a global proliferation marker PCNA. In old animals, the marker of activated astrocytes (i.e. GFAP) was decreased, indicating lower neuroinflammation, whereas excitatory-inhibitory balance as measured by PSD-95/Gephyrin ratio was shifted towards a more excitatory state. These results suggested that IF and rapamycin induced distinct metabolic profiles in young and old animals. Furthermore, there was an age dependent reciprocal relationship between proliferation and autophagy, which might be partly due to differential regulation of mTOR activity. Interestingly, rapamycin treatment was more effective in suppressing mTOR activity in young animals, and compared to IF. Nevertheless, these results suggested that rapamycin crosses the blood-brain barrier in zebrafish, and that short-term durations of IF or rapamycin were sufficient to alter the expression levels of key proteins involved in critical mechanisms in the brain.Item Open Access Aging alters the molecular dynamics of synapses in a sexually dimorphic pattern in zebrafish (Danio rerio)(Elsevier, 2017-06) Karoglu, Elif Tugce; Halim, Dilara Ozge; Erkaya, Bahriye; Altaytas, Ferda; Arslan-Ergul, Ayca; Konu, Ozlen; Adams, Michelle M.The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.Item Open Access BRAPH: A graph theory software for the analysis of brain connectivity(Public Library of Science, 2017) Mijalkov, M.; Kakaei, E.; Pereira, J. B.; Westman, E.; Volpe, G.The brain is a large-scale complex network whose workings rely on the interaction between its various regions. In the past few years, the organization of the human brain network has been studied extensively using concepts from graph theory, where the brain is represented as a set of nodes connected by edges. This representation of the brain as a connectome can be used to assess important measures that reflect its topological architecture. We have developed a freeware MatLab-based software (BRAPH–BRain Analysis using graPH theory) for connectivity analysis of brain networks derived from structural magnetic resonance imaging (MRI), functional MRI (fMRI), positron emission tomography (PET) and electroencephalogram (EEG) data. BRAPH allows building connectivity matrices, calculating global and local network measures, performing non-parametric permutations for group comparisons, assessing the modules in the network, and comparing the results to random networks. By contrast to other toolboxes, it allows performing longitudinal comparisons of the same patients across different points in time. Furthermore, even though a user-friendly interface is provided, the architecture of the program is modular (object-oriented) so that it can be easily expanded and customized. To demonstrate the abilities of BRAPH, we performed structural and functional graph theory analyses in two separate studies. In the first study, using MRI data, we assessed the differences in global and nodal network topology in healthy controls, patients with amnestic mild cognitive impairment, and patients with Alzheimer’s disease. In the second study, using resting-state fMRI data, we compared healthy controls and Parkinson’s patients with mild cognitive impairment. © 2017 Mijalkov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Item Open Access Caloric restriction reinforces the stem cell pool in the aged brain without affecting overall proliferation status(Elsevier BV, 2022-11-01) Erbaba, Begün; Macaroğlu, Duygu; Avcı, N. İlgim Ardıç; Ergül , Ayça Arslan; Adams, Michelle M.Overfeeding (OF) and obesity increase the risk for brain aging and neurodegenerative diseases due to increased oxidative stress and neuroinflammation, which likely contribute to cellular dysfunction. In contrast, caloric restriction (CR) is an intervention known for its effects on extending both life- and health-span. In the current study, the effects on the aging brain of two short-term feeding regimens, OF and CR, were investigated. We applied these diets for 12 weeks to both young and aged zebrafish. We performed protein and mRNA level analysis to examine diet-mediated effects on any potential age-related alterations in the brain. Markers implicated in the regulation of brain aging, cell cycle, proliferation, inflammation, and cytoskeleton were analyzed. The most prominent result observed was a downregulation in the expression levels of the stem cell marker, Sox2, in CR-fed animals as compared to OF-fed fish. Furthermore, our data highlighted significant age-related downregulations in Tp53, Myca, and L-plastin levels. The multivariate analyses of all datasets suggested that as opposed to OF, the adaptive mechanisms increasing lifespan via CR are likely exerting their effects by reinforcing the stem cell pool and downregulating inflammation. The data reveal important therapeutic targets with respect to the state of nutrient uptake for the slowing down of the detrimental effects of aging, resulting in a healthy and extended lifespan, as well as lowering the risk for neurodegenerative disease.Item Open Access Convection-reaction equation based magnetic resonance electrical properties tomography (cr-MREPT)(Institute of Electrical and Electronics Engineers Inc., 2014) Hafalir, F. S.; Oran, O. F.; Gurler, N.; Ider, Y. Z.Images of electrical conductivity and permittivity of tissues may be used for diagnostic purposes as well as for estimating local specific absorption rate distributions. Magnetic resonance electrical properties tomography (MREPT) aims at noninvasively obtaining conductivity and permittivity images at radio-frequency frequencies of magnetic resonance imaging systems. MREPT algorithms are based on measuring the B1 field which is perturbed by the electrical properties of the imaged object. In this study, the relation between the electrical properties and the measured B1 field is formulated for the first time as a well-known convection-reaction equation. The suggested novel algorithm, called 'cr-MREPT,' is based on the solution of this equation on a triangular mesh, and in contrast to previously proposed algorithms, it is applicable in practice not only for regions where electrical properties are relatively constant but also for regions where they vary. The convective field of the convection-reaction equation depends on the spatial derivatives of the B1 field, and in the regions where its magnitude is low, a spot-like artifact is observed in the reconstructed electrical properties images. For eliminating this artifact, two different methods are developed, namely 'constrained cr-MREPT' and 'double-excitation cr-MREPT.' Successful reconstructions are obtained using noisy and noise-free simulated data, and experimental data from phantoms.Item Open Access Development of a thulium (Tm:YAP) laser system for brain tissue ablation(2011) Bilici, T.; Mutlu, S.; Kalaycioglu H.; Kurt, A.; Sennaroglu, A.; Gulsoy, M.In this study, a thulium (Tm:YAP) laser system was developed for brain surgery applications. As the Tm:YAP laser is a continuous-wave laser delivered via silica fibers, it would have great potential for stereotaxic neurosurgery with highest local absorption in the IR region. The laser system developed in this study allowed the user to set the power level, exposure time, and modulation parameters (pulse width and on-off cycles). The Tm:YAP laser beam (200-600 mW, 69-208 W/cm 2) was delivered from a distance of 2 mm to cortical and subcortical regions of ex-vivo Wistar rat brain tissue samples via a 200-μm-core optical fiber. The system performance, dosimetry study, and ablation characteristics of the Tm:YAP laser were tested at different power levels by maximizing the therapeutic effects and minimizing unwanted thermal side-effects. The coagulation and ablation diameters were measured under microscope. The maximum ablation efficiency (100 × ablation diameter/coagulation diameter) was obtained when the Tm:YAP laser system was operated at 200 mW for 10 s. At this laser dose, the ablation efficiency was found to be 71.4% and 58.7% for cortical and subcortical regions, respectively. The fiber-coupled Tm:YAP laser system in hence proposed for the delivery of photothermal therapies in medical applications. © 2011 Springer-Verlag London Ltd.Item Open Access Dietary and pharmacological interventions that inhibit mammalian target of rapamycin activity alter the brain expression levels of neurogenic and glial markers in an age-and treatment-dependent manner(Mary Ann Liebert, 2020) Çelebi-Birand, Dilan; Ardıç, Narin İlgim; Karoğlu-Eravşar, Elif Tuğçe; Şengül, Göksemin Fatma; Kafalıgönül, Hulusi; Adams, Michelle M.Intermittent fasting (IF) and its mimetic, rapamycin extend lifespan and healthspan through mechanisms that are not fully understood. We investigated different short-term durations of IF and rapamycin on cellular and molecular changes in the brains of young (6–10 months) and old (26–31 months) zebrafish. Interestingly, our results showed that IF significantly lowered glucose levels while increasing DCAMKL1 in both young and old animals. This proliferative effect of IF was supported by the upregulation of foxm1 transcript in old animals. Rapamycin did not change glucose levels in young and old animals but had differential effects depending on age. In young zebrafish, proliferating cell nuclear antigen and the LC3-II/LC3-I ratio was decreased, whereas glial fibrillary acidic protein and gephyrin were decreased in old animals. The changes in proliferative markers and a marker of autophagic flux suggest an age-dependent interplay between autophagy and cell proliferation. Additionally, changes in glia and inhibitory tone suggest a suppressive effect on neuroinflammation but may push the brain toward a more excitable state. Mammalian target of rapamycin (mTOR) activity in the brain following the IF and rapamycin treatment was differentially regulated by age. Interestingly, rapamycin inhibited mTOR more potently in young animals than IF. Principal component analysis supported our conclusion that the regulatory effects of IF and rapamycin were age-specific, since we observed different patterns in the expression levels and clustering of young and old animals. Taken together, our results suggest that even a short-term duration of IF and rapamycin have significant effects in the brain at young and old ages, and that these are age and treatment dependent.Item Restricted Dinsel cemaat ve evrensel özne II(2001) Tura, Saffet MuratItem Open Access Disrupted network topology in patients with stable and progressive mild cognitive impairment and alzheimer's disease(Oxford University Press, 2016) Pereira, J. B.; Mijalkov, M.; Kakaei, E.; Mecocci, P.; Vellas, B.; Tsolaki, M.; Kłoszewska, I.; Soininen, H.; Spenger, C.; Lovestone, S.; Simmons, A.; Wahlund, L.-O.; Volpe, G.; Westman, E.Recent findings suggest that Alzheimer's disease (AD) is a disconnection syndrome characterized by abnormalities in large-scale networks. However, the alterations that occur in network topology during the prodromal stages of AD, particularly in patients with stable mild cognitive impairment (MCI) and those that show a slow or faster progression to dementia, are still poorly understood. In this study, we used graph theory to assess the organization of structural MRI networks in stable MCI (sMCI) subjects, late MCI converters (lMCIc), early MCI converters (eMCIc), and AD patients from 2 large multicenter cohorts: ADNI and AddNeuroMed. Our findings showed an abnormal global network organization in all patient groups, as reflected by an increased path length, reduced transitivity, and increased modularity compared with controls. In addition, lMCIc, eMCIc, and AD patients showed a decreased path length and mean clustering compared with the sMCI group. At the local level, there were nodal clustering decreases mostly in AD patients, while the nodal closeness centrality detected abnormalities across all patient groups, showing overlapping changes in the hippocampi and amygdala and nonoverlapping changes in parietal, entorhinal, and orbitofrontal regions. These findings suggest that the prodromal and clinical stages of AD are associated with an abnormal network topology.Item Open Access EEG işareti üzerinde sara ataklarının ve sara belirtisi işaretlerin bulunması(2008-04) Yücel, Zeynep; Özgüler, A. BülentSymptoms of epilepsy, which is characterized by abnormal brain electrical activity, can be observed on electroencephalography (EEG) signal. This paper employs models of chaotic measures of EEG and aims to help detection of epilepsy seizures and diagnosis of epileptic indicators in seizure-free signals. ©2008 IEEE.Item Open Access Effect of speech intelligibility on visual short-term memory performance(2007) Kitapci, K.; Yılmazer, Semiha; Erkip F.The aim of this study is to find out effects of speech intelligibility on visual short-term memory performance by testing 34 interior architecture students in three different sound environments. Those sound environments were composed of real office sounds and a speech sample that are mixed to achieve varying STI levels of 'continuous noise', 'masked speech' and 'speech' sound environments [2]. Test procedure had three steps: first questionnaire, computer based short-term memory test and second questionnaire. Results show that there is no significant difference of visual short-term memory performance between varying sound environments, however subjective results derived from questionnaires show that students were distracted most by 'speech' sound environment.Item Open Access Effects of aging and short-term dietary restriction on neurogenesis and cellular senescence in the zebrafish (Danio Reio) brain(2016-09) Erbaba, BegünCurrently we know from rodent and fish studies that adult neuron generation is reduced but still continues in old animals with a dynamic change throughout aging. This process occurs mainly in hippocampal region, which is thought to be analogous to a region in telencephalon of the zebrafish brain. Changes in this neuron turnover are thought to be one contributing factor to cognitive change occuring with advanced age. Since we know that external factors can affect the process of neurogenesis, and as previous studies showed, dietary restriction (DR) extends life span; here, we hypothesized that DR should also alleviate several age associated alterations. In order to test this, we applied a 10-week feeding regimen to young (8-9 months) and old (26-32.5 months) male and female fish. We had two dietary regimen groups, one fed Ad libitum and one fed with a DR that was a pattern of every-other-day feeding, which is a widely accepted method of DR. A total of 124 animals were used in this study. As a result, a significant loss of body weight in both young and old DR groups was observed without an effect on body lengths. To be able to label actively dividing cells we used Bromodeoxyuridine (BrdU), which is a thymidine analog. It is injected into the fish intraperitoneally prior to euthanasia. Four hours later the brains were dissected and fixed for sectioning. We obtained cross-sectional slices of 50 m thickness with a vibratome, performed immunostaining with antibodies against BrdU, NeuN (neuronal marker), HuC (neuronal marker); and visualized the brain sections with confocal microscopy forming 3D reconstructed pictures. We counted the BrdU positive cells in all brain slices, forming a regional map of the telencephalic region of zebrafish brain, in which we documented the specific regions where the adult neurogenesis dominates the most and least. Our results confirmed that there are more BrdU positive cells in young animals than olds, and that age is correlated with an increased senescence associated fi-galactosidase (SA-fi-gal) activity, along with shortened telomere lengths. The 10-week diet was not found to be creating a significant change in cell proliferation rates, cellular senescence, or the differentiation pattern of glial cells. However, it was demonstrated to have a shortening effect on telomere lengths. Our data suggest that the potential effects of DR could be related to telomere regulation. Therefore, in order to detect differentially expressed genes that could be related to this mechanism between the groups, we performed microarray analysis with differing DR regimens. Initial data indicated no significant effects of a 4-week diet on gene expression differences among aged fish. Further analysis of the different periods of DR will be performed. Taken together, the effects of age are more robust than a short-term DR.Item Open Access Effects of aging, diet and potential genetic interventions on the levels of Smurf2 and its interacting partners in Zebrafish (Danio Rerio) brain(2020-09) Şaşik, Melek Umay TüzAging is a natural process that is ultimate combination of numerous intrinsic and extrinsic changes in an organism. Contrary the common belief, brain aging is not a loss of neurons while it has been shown that subtle cellular and synaptic alterations have contribution to brain aging. Therefore, the molecular and cellular alterations may give more insight into the brain aging process. There are some hallmarks of aging that are common features in different organisms including genomic instability, telomere attrition, cellular senescence. There are some common factors with the ability to regulate more than one of the hallmarks of aging such as Smurf2. HECTdomain E3 ubiquitin ligase Smurf2 has several roles in the cellular processes for example, telomere attrition and cellular senescence. Moreover, its gene expression is higher in the aged brain. Although there are several publications about Smurf2, most of them focused on its role in cancer. We believed that Smurf2 levels should be examined in terms of brain aging. The first aim of the study was to examine the levels of Smurf2 and its interacting partners across lifespan. Although the Smurf2 protein level was not increased significantly in the whole zebrafish brain, its protein level was upregulated significantly in telencephalon and cerebellum. Also, subcellular protein fractionation demonstrated an enriched Smurf2 level in the cytosolic part. In the case of gene expression levels, smurf2 level was significantly higher in aged whole brain although its expression was downregulated during aging in telencephalon and cerebellum. In addition, the levels of mdm2, ep300a and sirt1 were lower in the aged telencephalon. According to multivariate analysis there is a potential balance between Smurf2-mediated ubiquitination, ep300a-mediated acetylation and Sirt1- mediated deacetylation but with advancing age, this balance may disrupt and other regulatory genes should also take a role to sustain cellular stability. The second aim was to investigate the roles of Smurf2 on brain aging with the help of genetic interventions including inducible knockin, stable knockout or transient knockdown. Since stable knockin and knockout models should be genotyped before further investigations, the genotyping and phenotyping methods were employed to find an efficient and reliable way. Also, transient knockdown via Vivo-morpholino was applied to adult brain and efficient post injection times of two different morpholinos were identified in order to examine the effects of Smurf2 knockdown in both young and old zebrafish. Lastly, it was aimed to examine the effects of non-genetic interventions including dietary regimens and pharmacological compounds on the gene expression of smurf2 and its interacting partners and the levels of the neuronal proteins and proliferation/senescence proteins. The opposing short-term dietary regimens, overfeeding and caloric restriction, were altered the levels of neuronal proteins, HuC and DCAMKL1, and their relation with proliferation and senescence proteins during aging. Also, the gene expression levels of smurf2 and interacting partners except tp53 was not influenced by dietary regimens and aging in terms of whole brain. Also, multivariate analysis indicated that the correlations among smurf2, mdm2, ep300a and sirt1 were conserved in both young and old ages independent to dietary regimen which may imply that the balance between ubiquitination, acetylation and deacetylation is maintained in order to provide cellular stability during aging. Heclin, an inhibitor of HECT E3 ligases, were employed to inhibit Smurf2 activity. Before using in adult zebrafish, heclin was applied to embryos to see its effects. The higher dose of heclin decreased the survival ratio and altered the gene expression levels of downstream gene drastically. So, moderate dose of heclin should be applied to the adult brain and neuronal markers should be examined to observe target effects rather than off-target, unspecific impacts. Taken together, Smurf2 has potential roles during aging and it could be a promising target to delay the brain aging process and probably the onset of age-related cognitive decline.Item Open Access Effects of caloric restriction on the antagonistic and integrative hallmarks of aging(Elsevier, 2021) Erbaba, Begün; Arslan-Ergül, Ayça; Adams, Michelle M.Aging is a significant risk factor for cognitive decline associated with neurodegenerative diseases, which makes understanding what promotes ‘healthy brain aging’ very important. Studies suggest that caloric restriction (CR) is a non-genetic intervention that reliably extends life- and healthspan. Here, we review the CR literature related to both the subject of aging and alterations in cell cycle machinery, especially surrounding the regulation of the E2F/DP1 complex, to elucidate the cellular protection mechanisms in the brain induced via dietary applications. The alterations extending lifespan via CR appear to exert their effects by promoting survival of individual cells, downregulating cell proliferation, and inducing stem cell quiescence, which results in keeping the stem cell reserve for extreme needs. This survival instinct of cells is believed to cause some molecular adaptations for their maintenance of the system. Avoiding energy waste of proliferation machinery promotes the long term survival of the individual cells and this is due to adaptations to the limited nutrient supply in the environment. Such a protective mechanism induced by diet could be promoted via the downregulation of crucial cell cycle-related transcription activators. This review article aims to bring attention to the importance of molecular adaptations induced by diet that promote healthy brain aging. It will provide insights into alternative targets for new treatments or neuroprotective approaches against neurodegenerative pathophysiologies.Item Open Access Experimental and model based investigation of period doubling phenomenon in human steady state visual evoked potential responses(2018-07) Tuncel, YiğitObjective. Previous human Steady State Visual Evoked Potential (SSVEP) experiments have yielded different results regarding the range of stimulus frequencies in which Period Doubling (PD) behavior is observed. There also is lacking information about the consistency and repeatability of the occurences of subharmonic oscillations. The neural mechanism of such oscillations have also not been explored. To elaborate these rather unknown aspects of the PD behavior in SSVEP responses, an experimental and model based approach has been taken. Approach. The experimental side of the study aims at obtaining experimental and statistical data regarding the frequency range of PD generation and also investigates other characteristics of PD. In two sets of experiments, seven subjects were presented a sinusoidal flickering light stimulus with frequencies varying from 15 Hz to 42 Hz. To observe the short term repeatability in PD generation, another set of 5 successive experiments performed on five subjects with 10-minute breaks in between. To obtain the SSVEP responses, filtering, signal averaging and Power Spectral Density (PSD) estimation were applied to the recorded EEG. From the PSD estimates, Subharmonic Occurrence Rates (SORs) were calculated for each experiment and were used along with ANOVA for interpreting the outcomes of the short term repeatability experiments. The model based side of the study aims at explaining the observed phenomena in mathematical terms. For this purpose, Robinson’s Corticothalamic Model was implemented in both C and Simulink. The experimental procedure was reanimated on the model and the subharmonic generation in the model depending on different values for parameters was observed. The feedback loop that is responsible for the generation of subharmonic components was identified in the model, and this loop was isolated from the rest of the model and further analyzed with a describing function approach. Main Results. The experimental results showed that although fundamental (excitation frequency) and second harmonic components appear in almost all SSVEP spectra, there is considerable inter-subject and intra-subject variability regarding PD occurrence. PD occurs for all stimulus frequencies from 15 Hz to 42 Hz when all subjects are considered together. Furthermore, the statistical analyses of short term repeatability experiments suggest that in the short term, PD generation is consistent when all frequencies are considered together but for a single frequency significant short term differences occur. There also is considerable variation in the ratio of subharmonic amplitude to fundamental amplitude across different frequencies for a given subject. The modelling results showed that the subharmonic oscillations in the model are of resonance nature and that they can be obtained virtually in any frequency interval depending on the values of the parameters in the system. The intra-thalamic feedback loop in the model is identified to be the potential source of subharmonic oscillations in the system output. When isolated from the rest of the model and examined by itself, it has been found that this feedback loop can show a resonance phenomenon at the subharmonic frequency. By deriving a set of equations containing the necessary conditions for this resonance phenomenon, a semi-analytical method by which one can find the existence of these oscillations has been developed. Significance. From the experimental studies, important results and statistical data are obtained regarding PD generation. Our results indicate that modelling studies should attempt to generate PD for a broader range of stimulus frequencies by adjusting the parameter values. It is argued that SSVEP based BCI applications would likely benefit from the utilization of subharmonics in classification. Our modelling study is the first to investigate the source of subharmonic oscillations on a mathematical brain model. An experimental verification of the potential origin of such oscillations, which was identified to be the intra-thalamic loop, would be an important work. The proposed semi-analytical method could potentially be used to speed up a future parameter sweep study. We observed that in the current model alpha oscillation and subharmonic oscillations are in some way interrelated and they can not be generated together for any stimulation frequency. This is referred to as alpha entrainment, and is visible only for some stimulation frequencies in experimental results. Thus, we claim that the model is insufficient in explaining the PD phenomenon in SSVEP responses.Item Open Access Full‐brain coverage and high‐resolution imaging capabilities of passband b‐SSFP fMRI at 3T(Wiley‐Liss, Inc., 2008) Lee, J. H.; Dumoulin, S.; Sarıtaş, Emine Ülkü; Glover, G.; Wandell, B.; Nishimura, D.; Pauly, J.Passband balanced-steady-state free precession (b-SSFP)fMRI is a recently developed method that utilizes the passband(flat portion) of the b-SSFP off-resonance response to measureMR signal changes elicited by changes in tissue oxygenationfollowing increases in neuronal activity. Rapid refocusing andshort readout durations of b-SSFP, combined with the relativelylarge flat portion of the b-SSFP off-resonance spectrum allowsdistortion-free full-brain coverage with only two acquisitions.This allows for high-resolution functional imaging, without thespatial distortion frequently encountered in conventional high-resolution functional images. Finally, the 3D imaging compati-bility of the b-SSFP acquisitions permits isotropic-voxel-sizehigh-resolution acquisitions. In this study we address some ofthe major technical issues involved in obtaining passband b-SSFP-based functional brain images with practical imaging pa-rameters and demonstrate the advantages through breath-holding and visual field mapping experiments. Magn ResonMed 59:1099 –1110, 2008.Item Open Access Gadolinium leakage into subarachnoid space and cystic metastases(2013) Elçin Yildiz, A.; Atli, E.; Karli Oǧuz, K.Subarachnoid space (SAS) and cystic metastatic lesions of brain parenchyma appear hypointense on fluid-attenuated inversion-recovery (FLAIR) and T1-weighted magnetic resonance imaging (MRI) unless there is a hemorrhage or elevated protein content. Otherwise, delayed enhancement and accumulation of contrast media in SAS or cyst of metastases should be considered. We present hyperintense SAS and cystic brain metastases of lung cancer on FLAIR and T1-weighted MRI, respectively, in a patient who had been previously given contrast media for imaging of spinal metastases and had mildly impaired renal functions, and discuss the relevant literature. © Turkish Society of Radiology 2013.Item Open Access Gene expression changes in aging zebrafish (Danio rerio) brains are sexually dimorphic(BioMed Central, 2014) Arslan-Ergül, Ayça; Adams, Michelle M.Background: Brain aging is a multi-factorial process due to both genetic and environmental factors. The zebrafish has recently become a popular model organism for examining aging and age-related diseases because as in humans they age gradually and exhibit cognitive decline. Few studies have examined the biological changes in the aging brain that may contribute to these declines and none have examined them within individuals with respect to gender. Our aim was to identify the main genetic pathways associated with zebrafish brain aging across gender. We chose males and females from specific age groups (young, 7.5-8.5 months and old, 31-36 months) based on the progression of cognitive decline in zebrafish. RNA was isolated from individual brains and subjected to microarray and qPCR analysis. Statistical analyses were performed using a two-way ANOVA and the relevant post-hoc tests. Results: Our results demonstrated that in the brains of young and old male and female zebrafish there were over 500 differentially expressed genes associated with multiple pathways but most notably were those related to neurogenesis and cell differentiation, as well as brain and nervous system development. Conclusions: The gene expression of multiple pathways is altered with age and differentially expressed in males and females. Future studies will be aimed at determining the causal relationships of age-related changes in gene expression in individual male and female brains, as well as possible interventions that counteract these alterations.Item Open Access High-speed, thermal damage-free ablation of brain tissue with femtosecond pulse bursts(IEEE, 2016) Kerse, Can; Yavaş, Seydi; Kalaycıoğlu, Hamit; Asik M.D.; Akçaalan, Önder; İlday, F. ÖmerWe report a novel ultrafast burst mode fiber laser system and results on ablation of rat brain tissue at rates approaching an order of magnitude improvement over previous reports, with no discernible thermal damage. © 2015 IEEE.