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    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, Burak
    In 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.
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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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    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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    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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    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 Association of Vertebrobasilar System Morphology and Geometry with the Posterior and Anterior Ischemic Stroke
    (Pera Yayincilik Hizmetleri, 2025) Demirtas, Ismet; Ayran, Aysegul; Kus, Koral Caglar; Leblebici, Asim; Ayyildiz, Behcet; Aliyev, Shamil; Ayyildiz, Sevilay
    Objective: Morphometric and geometric variations in the vertebrobasilar system (VBS) may influence cerebral hemodynamics, potentially contributing to ischemic strokes in both anterior and posterior circulatory territories. This study aimed to investigate the association between VBS morphology and ischemic stroke localization. Methods: This retrospective observational study analyzed multidetector computed tomography angiography images from 431 patients (187 females, 244 males, mean age: 65.3 +/- 14.6 years). Patients were categorized into three groups: anterior circulation ischemic stroke (ACIS, n=184), posterior circulation ischemic stroke (PCIS, n=88), and control subjects (n=159). Morphometric parameters were assessed using 3D Slicer software. Results: Significant differences in basilar artery (BA) length were observed between stroke groups and controls, with ACIS and PCIS groups exhibiting longer BA lengths (p<0.05). Males had significantly longer vertebral artery (VA) lengths than females in the control and ACIS groups (p value < 0.05). The vertebrobasilar junction angle was significantly wider in females than in males (p value = 0.046). BA bending was predominantly directed to the right across all groups, with no significant differences between the stroke and control groups. VA dominance was more frequent on the left in ACIS and the right in PCIS, while VA hypoplasia was less common in stroke patients compared to controls, contrary to previous reports. Conclusion: While certain morphometric and geometric variations in the VBS were observed, the evidence for a direct association between these characteristics and the localization of ischemic stroke was limited and inconclusive. These findings suggest that vertebrobasilar morphology may not independently determine stroke localization.
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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.