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Öğe A structural and resting-state functional connectivity investigation of the pulvinar in elderly individuals and Alzheimer's disease patients(Wiley, 2023) Velioglu, Halil Aziz; Ayyildiz, Behcet; Ayyildiz, Sevilay; Sutcubasi, Bernis; Hanoglu, Lutfu; Bayraktaroglu, Zubeyir; Yulug, BurakIn Alzheimer's disease (AD), structural and functional changes in the brain may give rise to disruption of specific cognitive functions. The aim of this study is to investigate the functional connectivity alterations in the pulvinar's subdivisions and total pulvinar voxel-based morphometry (VBM) changes in individuals with AD and healthy controls. A seed-based functional connectivity analysis was applied to the anterior, inferior, lateral, and medial pulvinar in each hemisphere. Furthermore, VBM analysis was carried out to compare gray matter (GM) volume differences in the pulvinar and thalamus between the two groups. Connectivity analysis revealed that the pulvinar subdivisions had decreased connectivity in individuals with AD. In addition, the pulvinar and thalamus in each hemisphere were significantly smaller in the AD group. The pulvinar may have a role in AD-related cognitive impairments and the intrinsic connectivity network changes and GM loss in pulvinar subdivisions suggest the cognitive deterioration occurring in those with AD. HighlightsThe pulvinar may play a role in pathophysiology of cognitive impairments in those with Alzheimer's disease (AD).Decreased structural volume and functional connectivity were found in patients with AD.The inferior pulvinar is functionally the most affected subdivision by AD compared to the others.Öğe Brain temperature in healthy and diseased conditions: A review on the special implications of MRS for monitoring brain temperature(Elsevier France-Editions Scientifiques Medicales Elsevier, 2023) Yulug, Burak; Velioglu, Halil Aziz; Sayman, Dila; Cankaya, Seyda; Hanoglu, LutfuBrain temperature determines not only an individual's cognitive functionality but also the prognosis and mor-tality rates of many brain diseases. More specifically, brain temperature not only changes in response to different physiological events like yawning and stretching, but also plays a significant pathophysiological role in a number of neurological and neuropsychiatric illnesses. Here, we have outlined the function of brain hyperthermia in both diseased and healthy states, focusing particularly on the amyloid beta aggregation in Alzheimer's disease.Öğe Decreased frontal and orbital volumes and increased cerebellar volumes in patients with anosmia Of Unknown origin: A subtle connection?(Pergamon-Elsevier Science Ltd, 2023) Avnioglu, Seda; Sahin, Caner; Cankaya, Seyda; Ozen, Ozkan; Dikici, Rumeysa; Yilmaz, Halil; Velioglu, Halil AzizPurpose: Neuroimaging studies have shown that anosmia is accompanied by a decreased olfactory bulb volume, yet little is known about alterations in cerebral and cerebellar lobule volumes. The purpose of this study was to investigate structural brain alterations in anosmic patients.Methods: Sixteen anosmic patients (mean age 42.62 +/- 16.57 years; 6 women and 10 men) and 16 healthy controls (mean age 43.37 +/- 18.98 years; 9 women and 7 men) were included in this retrospective study. All subjects who underwent magnetic resonance imaging scans were analyzed using VolBrain and voxel-based morphometry after olfactory testing.Results: Despite being statistically insignificant, analysis using VBM revealed greater gray matter (GM) and white matter in the anosmia group compared to the healthy subjects. However, decreased GM (p < 0.001) and increased cerebellar (p = 0.046) volumes were observed in the anosmic patients.Conclusions: The study revealed structural brain alterations in specific areas beyond the olfactory bulb. Our re-sults indicate that the cerebellum may play an exceptional role in the olfactory process and that this will be worth evaluating with further dynamic neuroimaging studies.Öğe EGb 761 reduces Ca2+ influx and apoptosis after pentylenetetrazole treatment in a neuroblastoma cell line(Frontiers Media Sa, 2023) Ovey, Ishak Suat; Ozsimsek, Ahmet; Velioglu, Halil Aziz; Altay, Ozlem; Mardinoglu, Adil; Yulug, BurakBackground: Transient receptor potential (TRP) channels have been found to have significant implications in neuronal outgrowth, survival, inflammatory neurogenic pain, and various epileptogenic processes. Moreover, there is a growing body of evidence indicating that transient receptor potential (TRP) channels have a significant impact on epilepsy and its drug-resistant subtypes.Objective: We postulated that EGb 761 would modulate TRPA1 channels, thereby exhibiting anti-inflammatory and neuroprotective effects in a neuroblastoma cell line. Our rationale was to investigate the impact of EGb 761 in a controlled model of pentylenetetrazole-induced generalized epilepsy.Methodology: We evaluated the neuroprotective, antioxidant and anti-apoptotic effects of EGb 761 both before and after the pentylenetetrazole application in a neuroblastoma cell line. Specifically, we focused on the effects of EGB 761 on the activity of Transient receptor potential (TRP) channels.Results: EGb 761 applications both before and after the pentylenetetrazole incubation period reduced Ca release and restored apoptosis, ROS changes, mitochondrial depolarization and caspase levels, suggesting a prominent prophylactic and therapeutic effect of EGb 761 in the pentylenetetrazole-induced epileptogenesis process.Conclusion: Our basic mechanistic framework for elucidating the pathophysiological significance of fundamental ion mechanisms in a pentylenetetrazole treated neuroblastoma cell line provided compelling evidence for the favorable efficacy and safety profile of Egb 761 in human-relevant in vitro model of epilepsy. To the best of our knowledge, this is the first study to investigate the combined effects of EGb 761 and pentylenetetrazole on TRP channels and measure their activation level in a relevant model of human epileptic diseases.Öğe Exosomes: A missing link between chronic systemic inflammation and Alzheimer's disease?(Elsevier France-Editions Scientifiques Medicales Elsevier, 2023) Ozansoy, Mehmet; Mikati, Houda; Velioglu, Halil Aziz; Yulug, BurakExosomes are potent mediators of physiological and pathological processes. In Alzheimer's disease and in-flammatory disorders, due to exosomes' distinctive ability to cross the blood-brain barrier, a bidirectional communication between the periphery and the central nervous system exists. Since exosomes can carry various biochemical molecules, this review investigates the role of exosomes as possible mediators between chronic systemic inflammatory diseases and Alzheimer's disease. Exosomes carry pro-inflammatory molecules generated in the periphery, travel to the central nervous system, and target glial and neuronal cells. Microglia and astro-cytes then become activated, initiating chronic neuroinflammation. As the aging brain is more susceptible to such changes, this state of neuroinflammation can stimulate neuropathologies, impair amyloid-beta clearance capa-bilities, and generate dysregulated microRNAs that alter the expression of genes critical in Alzheimer's disease pathology. These processes, individually and collectively, become significant risk factors for the development of Alzheimer's disease.Öğe Left lateral parietal rTMS improves cognition and modulates resting brain connectivity in patients with Alzheimer?s disease: Possible role of BDNF and oxidative stress(Academic Press Inc Elsevier Science, 2021) Velioglu, Halil Aziz; Hanoglu, Lutfu; Bayraktaroglu, Zubeyir; Toprak, Guven; Guler, Eray Metin; Bektay, Muhammed Yunus; Mutlu-Burnaz, OzlemRepetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuromodulation technique which is increasingly used for cognitive impairment in Alzheimer?s Disease (AD). Although rTMS has been shown to modify Brain-Derived Neurotrophic Factor (BDNF) and oxidative stress levels in many neurological and psychiatric diseases, there is still no study evaluating the relationship between memory performance, BDNF, oxidative stress, and resting brain connectivity following rTMS in Alzheimer?s patients. Furthermore, there are increasing clinical data showing that the stimulation of strategic brain regions may lead to more robust improvements in memory functions compared to conventional rTMS. In this study, we aimed to evaluate the possible disease-modifying effects of rTMS on the lateral parietal cortex in AD patients who have the highest connectivity with the hippocampus. To fill the mentioned research gaps, we have evaluated the relationships between resting-state Functional Magnetic Resonance Imaging (fMRI), cognitive scores, blood BDNF levels, and total oxidative/antioxidant status to explain the therapeutic and potential disease-modifying effects of rTMS which has been applied at 20 Hz frequencies for two weeks. Our results showed significantly increased visual recognition memory functions and clock drawing test scores which were associated with elevated peripheral BDNF levels, and decreased oxidant status after two weeks of left lateral parietal TMS stimulation. Clinically our findings suggest that the left parietal region targeted rTMS application leads to significant improvement in familiarity-based cognition associated with the network connections between the left parietal region and the hippocampus.Öğe Neuroimaging-Guided Transcranial Magnetic and Direct Current Stimulation in MCI: Toward an Individual, Effective and Disease-Modifying Treatment(Sage Publications Inc, 2023) Hanoglu, Lutfu; Velioglu, Halil Aziz; Hanoglu, Taha; Yulug, BurakThe therapeutic approaches currently applied in Alzheimer's disease (AD) and similar neurodegenerative diseases are essentially based on pharmacological strategies. However, despite intensive research, the effectiveness of these treatments is limited to transient symptomatic effects, and they are still far from exhibiting a true therapeutic effect capable of altering prognosis. The lack of success of such pharmacotherapy-based protocols may be derived from the cases in the majority of trials being too advanced to benefit significantly in therapeutic terms at the clinical level. For neurodegenerative diseases, mild cognitive impairment (MCI) may be an early stage of the disease continuum, including Alzheimer's. Noninvasive brain stimulation (NIBS) techniques have been developed to modulate plasticity in the human cortex in the last few decades. NIBS techniques have made it possible to obtain unique findings concerning brain functions, and design novel approaches to treat various neurological and psychiatric conditions. In addition, its synaptic and cellular neurobiological effects, NIBS is an attractive treatment option in the early phases of neurodegenerative diseases, such as MCI, with its beneficial modifying effects on cellular neuroplasticity. However, there is still insufficient evidence about the potential positive clinical effects of NIBS on MCI. Furthermore, the huge variability of the clinical effects of NIBS limits its use. In this article, we reviewed the combinatory approach of NIBS with various neuroimaging and electrophysiological methods. Such methodologies may provide a new horizon to the path for personalized treatment, including a more individualized pathophysiology approach which might even define new specific targets for specific symptoms of neurodegenerations.Öğe Parietal memory network and memory encoding versus retrieval impairments in PD-MCI patients: A hippocampal volume and cortical thickness study(Wiley, 2024) Sahin, Serhat; Velioglu, Halil Aziz; Yulug, Burak; Bayraktaroglu, Zubeyir; Yildirim, Suleyman; Hanoglu, LutfuObjective: The pathophysiology behind memory impairment in Parkinson's Disease Mild Cognitive Impairment (PD-MCI) is unclear. This study aims to investigate the hippocampal and cortical atrophy patterns in PD-MCI patients with different types of memory impairments, categorized as Retrieval Failure (RF) and Encoding Failure (EF). Methods: The study included 16 healthy controls (HC) and 34 PD-MCI patients, divided into RF (N = 18) and EF (N = 16) groups based on their Verbal Memory Processes Test (VMPT) scores, including spontaneous recall, recognition, and Index of Sensitivity to Cueing (ISC). Hippocampal subfields and cortical thicknesses were measured using the FreeSurfer software for automatic segmentation. Results: Compared to the HC group, the EF group exhibited significant atrophy in the left lateral occipital region and the right caudal middle frontal, superior temporal, and inferior temporal regions (p < 0.05). The RF group displayed significant atrophy in the left lateral occipital, middle temporal, and precentral regions, as well as the right pars orbitalis and superior frontal regions (p < 0.05). Hippocampal subfield analysis revealed distinct volume differences between HC-EF and RF-EF groups, with significant reductions in the CA1, CA3, and CA4 subregions in the EF group, but no differences between HC and RF groups (p > 0.05). Conclusion: Gray matter atrophy patterns differ in PD-MCI patients with encoding and retrieval memory impairments. The significant hippocampal atrophy in the EF group, particularly in the CA subregions, highlights its potential role in disease progression and memory decline. Additionally, the convergence of atrophy in the lateral occipital cortex across both RF and EF groups suggests the involvement of the Parietal Memory Network (PMN) in PD-related memory impairment.Öğe Quantitative evaluation of brain volumes in drug-free major depressive disorder using MRI-Cloud method(Lippincott Williams & Wilkins, 2021) Avnioglu, Seda; Velioglu, Halil Aziz; Cankaya, Seyda; Yulug, BurakBackground Quantitative analysis of the high-resolution T1-weighted images provides useful markers to measure anatomical changes during brain degeneration related to major depressive disorder (MDD). However, there are controversial findings regarding these volume alterations in MDD indicating even to increased volumes in some specific regions in MDD patients. Methods This study is a case-controlled study including 23 depression patients and 15 healthy subject person and 20-38 years of age, who have been treated at the Neurology and Psychiatry Department here. We compared specific anatomic regions between drug-free MDD patients and control group through MRI-Cloud, which is a novel brain imaging method that enables to analyze multiple brain regions simultaneously. Results We have found that frontal, temporal, and parietal hemispheric volumes and middle frontal gyrus, inferior frontal gyrus, superior parietal gyrus, cingulum-hippocampus, lateral fronto-orbital gyrus, superior temporal gyrus, superior temporal white matter, middle temporal gyrus subanatomic regions were significantly reduced bilaterally in MDD patients compared to the control group, while striatum, amygdala, putamen, and nucleus accumbens bilaterally increased in MDD group compared to the control group suggesting that besides the heterogeneity among studies, also comorbid factors such as anxiety and different personal traits could be responsible for these discrepant results. Conclusion Our study gives a strong message that depression is associated with altered structural brain volumes, especially, in drug-free and first-episode MDD patients who present with similar duration and severity of depression while the role of demographic and comorbid risk factors should not be neglected.Öğe Repetitif Transkraniyal Manyetik Stimülasyon ile Alzheimer Hastalığında Hipokampal N-Asetilaspartat Düzeyinin ve Görsel Hafıza Skorlarının İyileştirilmesi(2024) Velioglu, Halil Aziz; Sayman, Dila; Hanoğlu, Lütfü; Ertan, Gulhan; Cankaya, Seyda; Yuluğ, BurakAlzheimer hastalığının (AH) patofizyolojisine yönelik yapılan son çalışmalar, hipokampal işlevsellikle ilgili çeşitli kognitif bozuklukları içermektedir. Bununla birlikte, mevcut klinik araştırmalar, AH’nin heterojen bilişsel spektrumunun tam kapsamını göz önünde bulunduramamakta ve kesin tanısal ve terapötik sonuçlar çıkarmak için gereken spesifik yöntemlerin eksikliğine neden olmaktadır. Bu, aynı zamanda AH’li insanlarda tanı ve tedavi rejimlerini uyarlamak için in-vivo metabolik ölçümlerini de içermektedir. Manyetik rezonans spektroskopisi ve tekrarlayan transkraniyal manyetik stimülasyon (rTMS), AH tedavisinde modifiye edilmesi gereken iki yeni tanı ve tedavi yaklaşımıdır. Bu çalışmada, rTMS tedavisi öncesi ve sonrası in-vivo hipokampal metabolitleri değerlendirerek AH’li kişilerde rTMS’nin altta yatan terapötik rolünü araştırmayı amaçladık. Önceki çalışmamızda fMRI verileri kullanılarak elde edilen verilere ve literatürde bildirilen referanslara dayanarak, bu çalışmada rTMS stimülasyonundan sonra hipokampal NAA verilerini kullanmaya karar verdik ve NAA seviyelerinin anlamlı derecede yükseldiğini gördük. Bildiğimiz kadarıyla, başka hiçbir çalışma, rTMS’nin AH’li insanlarda hipokampal metabolitler üzerindeki etkisini değerlendirmemiştir.Öğe Repetitive Transcranial Magnetic Stimulation Improves Hippocampal N-Acetlaspartate Levels and Visual Memory Scores in Alzheimer's Disease(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2024) Velioglu, Halil Aziz; Sayman, Dila; Hanoglu, Lutfu; Akan, Gulhan Ertan; Cankaya, Seyda; Yulug, BurakThe latest research into the pathophysiology of Alzheimer's Disease (AD) has included several cognitive deficits related to hippocampal functioning. However, current clinical research fails to consider the full extent of the heterogeneous cognitive spectrum of AD, resulting in a lack of the specific methods required to draw definitive diagnostic and therapeutic conclusions. This also includes in-vivo metabolic measurements for tailoring the diagnostic and therapeutic regimens in humans with AD. Magnetic resonance spectroscopy and repetitive transcranial magnetic stimulation (rTMS) are two novel diagnostic and therapeutic approaches that must be modified to treat AD. In the present study, we aimed to investigate the underlying therapeutic role of rTMS in humans with AD by evaluating the in -vivo hippocampal metabolites before and after rTMS treatment. Based on the data obtained using the fMRI data in our previous study and on the references reported in the literature, in the present study, we decided to use hippocampal NAA data after rTMS stimulation and found a significant increase in NAA levels. To the best of our knowledge, no other study has evaluated the effect of rTMS on hippocampal metabolites in humans with AD.Öğe rTMS reduces delta and increases theta oscillations in Alzheimer's disease: A visual-evoked and event-related potentials study(Wiley, 2024) Velioglu, Halil Aziz; Dudukcu, Esra Zeynep; Hanoglu, Lutfu; Guntekin, Bahar; Akturk, Tuba; Yulug, BurakBackground: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative therapy for Alzheimer's disease (AD) due to its ability to modulate neural networks and enhance cognitive function. This treatment offers the unique advantage of enabling real-time monitoring of immediate cognitive effects and dynamic brain changes through electroencephalography (EEG).Objective: This study focused on exploring the effects of left parietal rTMS stimulation on visual-evoked potentials (VEP) and visual event-related potentials (VERP) in AD patients.Methods: Sixteen AD patients were recruited for this longitudinal study. EEG data were collected within a Faraday cage both pre- and post-rTMS to evaluate its impact on potentials.Results: Significant alterations were found in both VEP and VERP oscillations. Specifically, delta power in VEP decreased, while theta power in VERP increased post-rTMS, indicating a modulation of brain activities.Discussion: These findings confirm the positive modulatory impact of rTMS on brain activities in AD, evidenced by improved cognitive scores. They align with previous studies highlighting the potential of rTMS in managing hyperexcitability and oscillatory disturbances in the AD cortex.Conclusion: Cognitive improvements post-rTMS endorse its potential as a promising neuromodulatory treatment for cognitive enhancement in AD, thereby providing critical insights into the neurophysiological anomalies in AD and possible therapeutic avenues.Öğe Smoking affects global and regional brain entropy in depression patients regardless of depression: Preliminary findings(Pergamon-Elsevier Science Ltd, 2024) Velioglu, Halil Aziz; Yildiz, Sultan; Ozdemir-Oktem, Ece; Cankaya, Seyda; Lundmark, Anton Kjell; Ozsimsek, Ahmet; Hanoglu, LutfuObjective: This study examines the effect of smoking on global and regional brain entropy in patients with Major Depressive Disorder (MDD), aiming to elucidate the relationship between smoking habits and brain network complexity in depression. Methods: The study enrolled 24 MDD patients, divided into smokers and non-smokers, from Alanya Alaaddin Keykubat University and Istanbul Medipol University. Resting-state fMRI data were acquired and processed. The complexity of neuronal activity was assessed using dispersion entropy, with statistical significance determined by a suite of tests including Kolmogorov -Smirnov, Student 's t-test, and Mann -Whitney U test. Results: The smoking cohort exhibited higher global brain entropy compared to the non-smoking group (p = 0.033), with significant differences in various brain networks, indicating that smoking may alter global brain activity and network dynamics in individuals with MDD. Conclusion: The study provides evidence that smoking is associated with increased brain entropy in MDD patients, suggesting that chronic smoking may influence cognitive and emotional networks. This underscores the importance of considering smoking history in the treatment and prognosis of MDD. The findings call for further research to understand the mechanistic links between smoking, brain entropy, and depression.Öğe The Adaptive Role of Entorhinal Cortical Thickness in Post-COVID 19 Cognitive Impairment(Turkish Neuropsychiatry Assoc-Turk Noropsikiyatri Dernegi, 2025) Cankaya, Seyda; Ipek, Lutfiye; Ayyildiz, Sevilay; Sayman, Dila; Karaca, Ramazan; Ayyildiz, Behcet; Velioglu, Halil AzizIntroduction: Only limited information is still available concerning cognitive dysfunctions and cortical thickness in individuals who recovered from mild COVID-19 infections and did not require hospitalization. Our aim was to evaluate if the highly adaptive potential of cortical thickness might play a critical role in COVID-19-related cognitive disorder in a compensatory manner. Methods: Fifteen individuals with no history of medical, neurological, or psychiatric disease and with positive COVID-19 test results, and sixteen healthy age and education-matched healthy controls identified from the official hospital health system were evaluated in terms of cognitive scores using Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog) and brain MRI cortical thickness measurements using FreeSurfer Version 7.40. Results: An increased cortical thickness in the right entorhinal cortex (EC) and impaired cognition (increased ADAS score) were observed in the post-COVID 19 group as compared to the controls confirmed by the student's t test (respectively, p-0.006, p<0.001). The apparent correlation observed between cognitive impairment and increased entorhinal cortical thickness in our COVID-19 patients might suggest a continuum pathophysiology between healthy and COVID-19 affected brains that was not evident in previous COVID-19 cases with cognitive impairment. Conclusion: Our findings of increased entorhinal cortical thickness, together with impaired cognitive scores, may indicate a flexible role of EC thickness in compensatory mechanisms of cognition.
