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    Bilingualism Is Associated with Significant Structural and Connectivity Alterations in the Thalamus in Adulthood
    (Mit Press, 2025) Ayyildiz, Behcet; Sayman, Dila; Ayyildiz, Sevilay; Oktem, Ece Ozdemir; Arslan, Ruhat; Colak, Tuncay; Bamac, Belgin
    Language is a sophisticated cognitive skill that relies on the coordinated activity of cerebral cortex. Acquiring a second language creates intricate modifications in brain connectivity. Although considerable studies have evaluated the impact of second language acquisition on brain networks in adulthood, the results regarding the ultimate form of adaptive plasticity remain inconsistent within the adult population. Furthermore, due to the assumption that subcortical regions are not significantly involved in language-related tasks, the thalamus has rarely been analyzed in relation to other language-relevant cortical regions. Given these limitations, we aimed to evaluate the functional connectivity and volume modifications of thalamic subfields using magnetic resonance imaging (MRI) modalities following the acquisition of a second language. Structural MRI and fMRI data from 51 participants were collected from the OpenNeuro database. The participants were divided into three groups: monolingual (ML), early bilingual (EB), and late bilingual (LB). The EB group consisted of individuals proficient in both English and Spanish, with exposure to these languages before the age of 10 years. The LB group consisted of individuals proficient in both English and Spanish, but with exposure to these languages after the age of 14 years. The ML group included participants proficient only in English. Our results revealed that the ML group exhibited increased functional connectivity in all thalamic subfields (anterior, intralaminar-medial, lateral, ventral, and pulvinar) compared with the EB and LB groups. In addition, a significantly decreased volume of the left suprageniculate nucleus was found in the bilingual groups compared with the ML group. This study provides valuable evidence suggesting that acquiring a second language may be protective against dementia, due to its high plasticity potential, which acts synergistically with cognitive functions to slow the degenerative process.
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    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, Lutfu
    Brain 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.
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    Cognitive Function Deficits Associated With Type 2 Diabetes and Retinopathy: Volumetric Brain MR Imaging Study
    (Wiley, 2025) Oktem, Ece Ozdemir; Sayman, Dila; Ayyildiz, Sevilay; Oktem, Caglar; Ipek, Lutfiye; Ayyildiz, Behcet; Aslan, Fatih
    Introduction: Type 2 diabetes mellitus is a ubiquitous chronic inflammatory disease with deleterious effects on various tissues, including the kidney, retina, and peripheral nerves. Studies using histopathology and magnetic resonance imaging have revealed that diabetes-related chronic hyperglycemia may impact the brain's essential functioning by causing microvascular damage. The aim of this study was to examine the cognitive functioning of type 2 diabetic individuals with and without retinopathy by evaluating their morphological, structural, and biochemical differences. Methods: Demographic characteristics, education level, type of diabetes mellitus (DM), disease duration, treatment received, other diabetic complications, such as nephropathy and neuropathy, and detailed medical histories were recorded. All participants underwent an extensive neuropsychological examination with Montreal Cognitive Assessment (MoCA) testing. Brain magnetic resonance imaging was performed to evaluate gray matter volume differences between the groups. Results: Gray matter volume differences between the groups were observed. Differences were observed after multiple corrections (age, education, and total intracranial volume [TIV]). First, the diabetic retinopathy group exhibited a significantly smaller gray matter volume in the right inferior temporal gyrus than the diabetic group (p = 0.032). In addition, the diabetic retinopathy group exhibited a significantly smaller gray matter volume than the control group in the right insula (lateral and central part) (p = 0.011). In addition, MoCA scores exhibited significant correlation with the two regions emerging as statistically significant in our analyses (the right inferior temporal gyrus and right insula) (p = 0.003, p = 0.002, respectively). Conclusion: Our results suggest the presence of a neurodegenerative process associated with cognitive dysfunction that is particularly prominent in the retinopathy stage of DM.
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    Cognitive impairment in tension-type headache is associated with altered hippocampal functional connectivity
    (Cell Press, 2025) Yulug, Burak; Yalcinkaya, Ali; Safa, Shair Shah; Karakus, Ayse; Sayman, Dila; Cankaya, Seyda; Sayman, Ceyhun
    Tension-type headache (TTH) is a widespread primary headache disorder that causes mild to moderate pain, which may be seen together with cognitive deficits. It is unclear if TTH-linked cognitive impairment is associated with functional alterations. Seventy-five participants were enrolled in the study. Mini Mental State Evaluation (MMSE) and Montreal Cognition Assessment (MoCA) tests were applied to evaluate cognitive impairment. A neuroimaging analysis was applied to determine whether the hippocampus responsible for pain and cognition was affected in TTH patients. Our functional data revealed significant alterations in the connectivity of the subiculum, hippocampal fissure, and left whole hippocampus. Among the significant functional brain alterations observed, the right subiculum consistently interacted with MoCA scores and increased pain intensity. Our findings suggest that TTH patients with cognitive impairment may exhibit unique functional alterations in the hippocampus. This suggests a potential negative association between pain modulation and cognitive processes in the hippocampus that may be responsible for the increased risk of dementia in these patients.
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    Hippocampal connectivity dynamics and volumetric alterations predict cognitive status in migraine: A resting-state fMRI study
    (Academic Press Inc Elsevier Science, 2025) Cankaya, Seyda; Ayyildiz, Behcet; Sayman, Dila; Duran, Umutcan; Ucak, Dogukan; Karaca, Ramazan; Ayyildiz, Sevilay
    The etiology of cognitive decline linked to migraine remains unclear, with a growing recurrence rate and potential increased dementia risk among sufferers. Cognitive dysfunction has recently gained attention as a significant problem among migraine sufferers that can be related to alterations in hippocampal function and structure. This study explores hippocampal subfield connectivity and volume changes in migraine patients. We recruited 90 individuals from Alanya University's Neurology Department, including 49 migraine patients and 41 controls, for functional and anatomical imaging. Using the CONN toolbox and FreeSurfer, we assessed functional connectivity and subfield volumes, respectively. Montreal Cognitive Assessment (MOCA) was used to assess cognition in the entire sample. As a result, migraine patients exhibited significantly lower MOCA scores compared to controls (p<.001). Also, we found significant differences in hippocampal subfields between migraine patients and control groups in terms of functional connectivity after adjusting for years of education; here we showed that the left CA3 showed higher connectivity with right MFG and right occipitolateral cortex. Furthermore, the connectivity of left fimbria with the left temporal lobe and hippocampus and the connectivity of the right hippocampal-tail with right insula, heschl's gyrus, and frontorbital cortex were lower in the migraineurs. Additionally, volumes of specific hippocampal subfields were significantly lower in the migraineurs (whole hippocampus p = 0.004, whole hippocampus head p = 0.003, right CA1 head p = 0.006, and right HATA p = 0.005) compared to controls. In conclusion, these findings indicate that migraine-associated cognitive impairment involves significant functional and structural brain changes, particularly in the hippocampus, which may heighten dementia risk. This pioneering study unveils critical hippocampal alterations linked to cognitive function in migraine sufferers, underscoring the potential for these changes to impact dementia development.
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    Infection with COVID-19 is no longer a public emergency: But what about degenerative dementia?
    (Wiley, 2023) Yulug, Burak; Ayyildiz, Behcet; Ayyildiz, Sevilay; Sayman, Dila; Salar, Ali Behram; Cankaya, Seyda; Ozdemir Oktem, Ece
    Although no longer considered a public health threat, post-COVID cognitive syndrome continues to impact on a considerable proportion of individuals who were infected with COVID-19. Recent studies have also suggested that COVID may be represent a critical risk factor for the development of Alzheimer's disease (AD). We compared 17 COVID patients with 20 controls and evaluated the effects of COVID-19 on general cognitive performance, hippocampal volume, and connections using structural and seed-based connectivity analysis. We showed that COVID patients exhibited considerably worse cognitive functioning and increased hippocampal connectivity supported by the strong correlation between hippocampal connectivity and cognitive scores. Our findings of higher hippocampal connectivity with no observable hippocampal morphological changes even in mild COVID cases may be represent evidence of a prestructural compensatory mechanism for stimulating additional neuronal resources to combat cognitive dysfunction as recently shown for the prodromal stages of degenerative cognitive disorders. Our findings may be also important in light of recent data showing that other viral infections as well as COVID may constitute a critical risk factor for the development of AD. To our knowledge, this is the first study that investigated network differences in COVID patients, with a particular focus on compensatory hippocampal connectivity.
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    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, Burak
    Alzheimer 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.
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    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, Burak
    The 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.
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    Subjective cognitive decline in major depressive patients is associated with altered entropy and connectivity changes of temporal and insular region
    (Springernature, 2025) Yulug, Burak; Yalcinkaya, Ali; Safa, Shair Shah; Sayman, Dila; Cankaya, Seyda; Karakus, Ayse; Sayman, Ceyhun
    Depressive cognitive impairment is seen in a significant number of patients with depression. However, it remains challenging to differentiate between patients with amnestic (those with subjective cognitive impairment complaints) and non-amnestic major depressive disorder, highlighting the urgent need for additional objective tools to help classify these patients more accurately. We analyzed cognitive state, alterations in regional entropy and functional connectivity measures of the brain between patients with major depression and healthy controls. The depressed cohort was categorized as either amnestic or non-amnestic, depending on self-reported experiences of forgetfulness. The superior temporal region and insula exhibited altered entropy and connectivity measures in individuals with depression and subjective cognitive impairment, which was correlated with impaired executive functions, a pattern not being evident in the control group. Our findings support the notion that insular and superior temporal entropic alterations are linked to subjective cognitive changes in the pathology of depression. These regions also hold potential as biomarkers for determining the underlying objective cognitive deficits in subjective cognitive complaints in patients with major depressive disorder (MDD). This underscores the need for improved diagnostic approaches and the implementation of practical dynamic neuroimaging modalities capable of addressing the current challenges in diagnosing subjective cognitive impairment in MDD, offering promise for the future management of patients with depression.
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    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 Aziz
    Introduction: 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.
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    The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder
    (Wiley, 2024) Yulug, Burak; Ayyildiz, Sevilay; Sayman, Dila; Karaca, Ramazan; Ipek, Lutfiye; Cankaya, Seyda; Salar, Ali Behram
    INTRODUCTIONEmotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms.METHODSWe compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as amnestic or nonamnestic, based on the members' subjective reports concerning their forgetfulness. We then sought to determine whether these patients would differ in terms of objective neuroimaging and cognitive findings.RESULTSThe right pulvinar exhibited altered connectivity in individuals with depression with objective cognitive impairment, a finding which was not apparent in depressive patients with subjective cognitive impairment.DISCUSSIONThe pulvinar may play a role in depression-related cognitive impairments. Connectivity network changes may differ between objective and subjective cognitive impairment in depression and may play a role in the increased risk of dementia in patients with depression.
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    The Role of Willpower in Major Depressive Disorder: An fMRI Study
    (Wiley, 2025) Yulug, Burak; Uygur, Burak; Sayman, Dila; Cankaya, Seyda; Ayyildiz, Behcet; Ayyildiz, Sevilay; Oktem, Ece Ozdemir
    Introduction The brain network correlates of personality traits in major depressive disorder (MDD) have not yet been investigated. Furthermore, it is still unclear whether personality traits relate to the depressive episode.Methods This study assessed network properties, depression severity, and personality traits in patients with MDD (n = 25) compared with age- and sex-matched healthy controls (n = 22). We performed TCI questionnaire which assesses novelty seeking (NS, an urge to explore new experiences with heightened emotional responses), harm avoidance (HA, the tendency to hold back when faced with unpleasant situations), reward dependence (RD, a tendency to seek and value rewards rooted in social recognition), persistence (P, an individual's ability to remain focused and driven toward goals despite encountering challenges), self-directness (SD, an expression of willpower that enables individuals to adapt their behavior to situational demands while remaining focused on their personal goals and values), cooperativeness (C, a behavioral trait reflecting a person's general approach to others; ranging from friendly and cooperative to hostile), and self-transcendence (ST, lessening of self-centeredness, allowing for expanded empathy) traits of participants.Results MDD patients with distinctive character traits exhibited significant differences in terms of depression diagnosis and severity of Hamilton Depression Rating Scale scores compared to the controls. The MDD patients also exhibited reduced resting-state network activity between the posterior default mode network, right putamen, and right frontal pole, while SD was significantly less frequently diagnosed in MDD patients. In evaluating the network correlates, differences in the SD traits were significantly associated with critical brain network alterations that were not evident in other traits.Discussion To the best of our knowledge, this is the first study to provide preliminary evidence of an abnormal connectome in the SD trait in MDD, thus providing convincing evidence for personalized antidepressant treatment strategies in MDD. A small sample size and our depression group being not drug-naive were our limitation for this research.