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Ulrike Grittner

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9 papers

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YNIMG Journal 2026 Journal Article

Harmonizing the stimulation dose of focal transcranial direct current stimulation across target sites

Axel Thielscher
Dayana Hayek
Oula Puonti
Ulrike Grittner
Felix Blankenburg
Rico Fischer
Gesa Hartwigsen
Shu-Chen Li

Focal transcranial direct current stimulation (tDCS) using center-surround electrode montages enables region-specific cortical targeting, and holds promise for both cognitive neuroscience and clinical interventions. However, systematic examinations of dose-response relationships and their regional differences are lacking, hampering informed selections of suited stimulation parameters. In this preparatory methodological study, we present a modeling-based framework to support harmonized empirical dose-response studies of focal tDCS across different target areas. It covers three steps: Determining the approximate electric field strength that had led to behavioral and physiological effects in related prior tDCS studies. In our case, this led to a field strength of 0.2 V/m on average across magnetic resonance images (MRIs) from 43 participants and eight target areas related to different cognitive and motor functions. Second, optimizing the radii of center-surround montages for each target area to - on average across participants - achieve the intended field strength while maximizing focality. An additional test of cross-sample generalization in an independent sample confirms that the intended target field strength is achieved on average for new participants. Third, the pre-determined montage radii and a method for the individualized positioning of the center-surround electrode montages are provided for prospective planning in empirical dose-response studies. By harmonizing the electric field strength between different target regions at the group level, but preserving inter-individual variability, our framework will enable systematic analyses to relate the field strength to behavioral and neuroimaging outcomes, and to assess differences of these relations across regions. The described computational tools are open-source, allowing other researchers to tailor our framework to their specific research questions; and are currently used in a multi-center study involving approximately 1000 datasets.

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YNICL Journal 2025 Journal Article

Lesion Network Mapping of Acute Neurological Deficits and Its Prognostic Value After Ischemic Stroke

Aslı Akdeniz
Ana Sofía Ríos
Uchralt Temuulen
Jochen B. Fiebach
Kersten Villringer
Huma Fatima Ali
Ahmed Khalil
Ulrike Grittner

BACKGROUND: Predicting functional recovery after ischemic stroke is vital for guiding clinical care. This study investigated whether lesion network mapping (LNM), a technique for modeling symptom-specific brain networks, can improve outcome prediction of functional recovery up to one-year post-stroke. METHODS: and AIC. RESULTS: : 0.0468 vs. 0.0159; AIC:1730.598 vs. 1769.222). CONCLUSIONS: LNM-derived scores reflected symptom topography but did not enhance prediction of functional recovery. While promising as a mechanistic tool, the clinical utility of LNM-based damage metrics for prognostication remains limited and requires further validation.

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YNICL Journal 2023 Journal Article

7T amygdala and hippocampus subfields in volumetry-based associations with memory: A 3-year follow-up study of early Alzheimer’s disease

Laura Göschel
Lea Kurz
Andrea Dell'Orco
Theresa Köbe
Peter Körtvélyessy
Ariane Fillmer
Semiha Aydin
Layla Tabea Riemann

INTRODUCTION: The hippocampus is the most prominent single region of interest (ROI) for the diagnosis and prediction of Alzheimer's disease (AD). However, its suitability in the earliest stages of cognitive decline, i.e., subjective cognitive decline (SCD), remains uncertain which warrants the pursuit of alternative or complementary regions. The amygdala might be a promising candidate, given its implication in memory as well as other psychiatric disorders, e.g. depression and anxiety, which are prevalent in SCD. In this 7 tesla (T) magnetic resonance imaging (MRI) study, we aimed to compare the contribution of volumetric measurements of the hippocampus, the amygdala, and their respective subfields, for early diagnosis and prediction in an AD-related study population. METHODS: Participants from a longitudinal study were grouped into SCD (n = 29), mild cognitive impairment (MCI, n = 23), AD (n = 22) and healthy control (HC, n = 31). All participants underwent 7T MRI at baseline and extensive neuropsychological testing at up to three visits (baseline n = 105, 1-year n = 78, 3-year n = 39). Analysis of covariance (ANCOVA) was used to assess group differences of baseline volumes of the amygdala and the hippocampus and their subfields. Linear mixed models were used to estimate the effects of baseline volumes on yearly changes of a z-scaled memory score. All models were adjusted to age, sex and education. RESULTS: Compared to the HC group, individuals with SCD showed smaller amygdala ROI volumes (range across subfields -11% to -1%), but not hippocampus ROI volumes (-2% to 1%) except for the hippocampus-amygdala-transition-area (-7%). However, cross-sectional associations between baseline memory and volumes were smaller for amygdala ROIs (std. ß [95% CI] ranging between 0.16 [0.08; 0.25] and 0.46 [0.31; 0.60]) than hippocampus ROIs (between 0.32 [0.19; 0.44] and 0.53 [0.40; 0.67]). Further, the association of baseline volumes with yearly memory change in the HC and SCD groups was similarly weak for amygdala ROIs and hippocampus ROIs. In the MCI group, volumes of amygdala ROIs were associated with a relevant yearly memory decline [95% CI] ranging between -0.12 [-0.24; 0.00] and -0.26 [-0.42; -0.09] for individuals with 20% smaller volumes than the HC group. However, effects were stronger for hippocampus ROIs with a corresponding yearly memory decline ranging between -0.21 [-0.35; -0.07] and -0.31 [-0.50; -0.13]. CONCLUSION: Volumes of amygdala ROIs, as determined by 7T MRI, might contribute to objectively and non-invasively identify patients with SCD, and thus aid early diagnosis and treatment of individuals at risk to develop dementia due to AD, however associations with other psychiatric disorders should be evaluated in further studies. The amygdala's value in the prediction of longitudinal memory changes in the SCD group remains questionable. Primarily in patients with MCI, memory decline over 3 years appears to be more strongly associated with volumes of hippocampus ROIs than amygdala ROIs.

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YNICL Journal 2023 Journal Article

Comparison of anatomical-based vs. nTMS-based risk stratification model for predicting postoperative motor outcome and extent of resection in brain tumor surgery

Meltem Ivren
Ulrike Grittner
Rutvik Khakhar
Francesco Belotti
Heike Schneider
Paul Pöser
Federico D'Agata
Giannantonio Spena

Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model. We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits. Two hundred and three patients with a median age of 50 years (range: 20–81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72–0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71–0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55–0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65–0.83). The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography.

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YNIMG Journal 2021 Journal Article

Inter-individual and age-dependent variability in simulated electric fields induced by conventional transcranial electrical stimulation

Daria Antonenko
Ulrike Grittner
Guilherme Saturnino
Till Nierhaus
Axel Thielscher
Agnes Flöel

Variations in head and brain anatomy determine the strength and distribution of electrical fields in humans and may account for inconsistent behavioral and neurophysiological results in transcranial electrical stimulation (tES) studies. However, it is insufficiently understood which anatomical features contribute to the variability of the modelled electric fields, and if their impact varies across age groups. In the present study, we tested the associations of global head anatomy, indexed by extra- and intra-cranial volumes, with electric field measures, comparing young and older adults. We modelled six "conventional" electrode montages typically used in tES studies using SimNIBS software in 40 individuals (20 young, 20 older adults; 20-35, 64-79 years). We extracted individual electric field strengths and focality values for each montage to identify tissue volumes that account for variability of the induced electric fields in both groups. Linear mixed models explained most of the inter-individual variability of the overall induced field strength in the brain, but not of field focality. Higher absolute head volume and relative volume of skin, skull and cerebrospinal fluid (CSF) were associated with lower overall electric field strengths. Additionally, we found interactions of age group with head volume and CSF, indicating that this relationship was mitigated in the older group. Our results demonstrate the importance to adjust brain stimulation not only according to brain atrophy, but also to additional parameters of head anatomy. Future studies need to elucidate the mechanisms underlying individual variability of tES effects in young and older adults, and verify the usefulness of the proposed models in terms of neurophysiology and behavior in empirical studies.

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YNICL Journal 2021 Journal Article

Towards a tractography-based risk stratification model for language area associated gliomas

Mehmet Salih Tuncer
Luca Francesco Salvati
Ulrike Grittner
Juliane Hardt
Ralph Schilling
Ina Bährend
Luca Leandro Silva
Lucius S. Fekonja

OBJECTIVES: Injury to major white matter pathways during language-area associated glioma surgery often leads to permanent loss of neurological function. The aim was to establish standardized tractography of language pathways as a predictor of language outcome in clinical neurosurgery. METHODS: We prospectively analyzed 50 surgical cases of patients with left perisylvian, diffuse gliomas. Standardized preoperative Diffusion-Tensor-Imaging (DTI)-based tractography of the 5 main language tracts (Arcuate Fasciculus [AF], Frontal Aslant Tract [FAT], Inferior Fronto-Occipital Fasciculus [IFOF], Inferior Longitudinal Fasciculus [ILF], Uncinate Fasciculus [UF]) and spatial analysis of tumor and tracts was performed. Postoperative imaging and the resulting resection map were analyzed for potential surgical injury of tracts. The language status was assessed preoperatively, postoperatively and after 3 months using the Aachen Aphasia Test and Berlin Aphasia Score. Correlation analyses, two-step cluster analysis and binary logistic regression were used to analyze associations of tractography results with language outcome after surgery. RESULTS: In 14 out of 50 patients (28%), new aphasic symptoms were detected 3 months after surgery. The preoperative infiltration of the AF was associated with functional worsening (cc = 0.314; p = 0.019). Cluster analysis of tract injury profiles revealed two areas particularly related to aphasia: the temporo-parieto-occipital junction (TPO; temporo-parietal AF, middle IFOF, middle ILF) and the temporal stem/peri-insular white matter (middle IFOF, anterior ILF, temporal UF, temporal AF). Injury to these areas (TPO: OR: 23.04; CI: 4.11 - 129.06; temporal stem: OR: 21.96; CI: 2.93 - 164.41) was associated with a higher-risk of persisting aphasia. CONCLUSIONS: Tractography of language pathways can help to determine the individual aphasia risk profile pre-surgically. The TPO and temporal stem/peri-insular white matter were confirmed as functional nodes particularly sensitive to surgical injuries.

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YNIMG Journal 2020 Journal Article

Spermidine intake is associated with cortical thickness and hippocampal volume in older adults

Claudia Schwarz
Nora Horn
Gloria Benson
Isabel Wrachtrup Calzado
Katharina Wurdack
Raimund Pechlaner
Ulrike Grittner
Miranka Wirth

Background The natural polyamine spermidine, known to be important for cellular function, decreases during aging. Previous research has demonstrated beneficial impact of spermidine intake on memory functions in both animal models and humans, suggesting that spermidine may be a preventive approach to delay age-related cognitive decline and possibly even Alzheimer’s disease (AD). However, the association of spermidine intake with brain health in humans is still unknown. In this study, we aimed to determine the association between dietary spermidine intake and structural brain measures in older individuals with subjective cognitive decline (SCD) and healthy controls (HC). Methods Dietary spermidine intake and adherence to Mediterranean Diet (MeDi) were assessed by a self-reported food frequency questionnaire in 90 older adults with SCD and 47 HC. Processing of structural MRI data yielded global brain volumes, hippocampal volume, mean and regional cortical thickness, and cortical thickness in a template encompassing AD-vulnerable regions. In exploratory analyses, the association between spermidine intake and structural brain measures was assessed using adjusted and unadjusted linear regression models. Additionally, we tested for differential associations as a function of group. Mediation analyses were performed to examine whether dietary spermidine intake mediates the associations between adherence to MeDi and structural brain measures. Results Higher spermidine intake was associated with larger hippocampal volume (standardized β = 0. 262, p = 0. 002), greater mean cortical thickness (standardized β = 0. 187, p = 0. 031), and greater cortical thickness in AD-vulnerable brain regions (standardized β = 0. 176, p = 0. 042), the parietal (standardized β = 0. 202, p = 0. 020), and temporal lobes (standardized β = 0. 217, p = 0. 012). No significant differential effect emerged between older adults with SCD and HC. Moreover, a substantial mediating effect of dietary spermidine intake on the associations between adherence to MeDi and structural brain measures was observed. Conclusion Higher dietary spermidine intake was positively associated with several structural brain measures, irrespective of the presence of SCD, and substantially mediated the relationship of adherence to MeDi and structural brain measures. Our data suggest that higher spermidine intake might be a promising dietary approach to preserve brain health in older adults, a hypothesis currently tested in an interventional trial.

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YNICL Journal 2018 Journal Article

Combining viscoelasticity, diffusivity and volume of the hippocampus for the diagnosis of Alzheimer's disease based on magnetic resonance imaging

Lea M. Gerischer
Andreas Fehlner
Theresa Köbe
Kristin Prehn
Daria Antonenko
Ulrike Grittner
Jürgen Braun
Ingolf Sack

Dementia due to Alzheimer's Disease (AD) is a neurodegenerative disease for which treatment strategies at an early stage are of great clinical importance. So far, there is still a lack of non-invasive diagnostic tools to sensitively detect AD in early stages and to predict individual disease progression. Magnetic resonance elastography (MRE) of the brain may be a promising novel tool. In this proof-of-concept study, we investigated whether multifrequency-MRE (MMRE) can detect differences in hippocampal stiffness between patients with clinical diagnosis of dementia due to AD and healthy controls (HC). Further, we analyzed if the combination of three MRI-derived parameters, i. e. , hippocampal stiffness, hippocampal volume and mean diffusivity (MD), improves diagnostic accuracy. Diagnostic criteria for probable dementia due to AD were in line with the NINCDS-ADRDA criteria and were verified through history-taking (patient and informant), neuropsychological testing, routine blood results and routine MRI to exclude other medical causes of a cognitive decline. 21 AD patients and 21 HC (median age 75years) underwent MMRE and structural MRI, from which hippocampal volume and MD were calculated. From the MMRE-images maps of the magnitude |G*| and phase angle φ of the complex shear modulus were reconstructed using multifrequency inversion. Median values of |G*| and φ were extracted within three regions of interest (hippocampus, thalamus and whole brain white matter). To test the predictive value of the main outcome parameters, we performed receiver operating characteristic (ROC) curve analyses. Hippocampal stiffness (|G*|) and viscosity (φ) were significantly lower in the patient group (both p <0. 001). ROC curve analyses showed an area under the curve (AUC) for | G*| of 0. 81 [95%CI 0. 68–0. 94]; with sensitivity 86%, specificity 67% for cutoff at |G*|=980Pa) and for φ an AUC of 0. 79 [95%CI 0. 66–0. 93]. In comparison, the AUC of MD and hippocampal volume were 0. 83 [95%CI 0. 71–0. 95] and 0. 86 [95%CI 0. 74–0. 97], respectively. A combined ROC curve of |G*|, MD and hippocampal volume yielded a significantly improved AUC of 0. 90 [95%CI 0. 81–0. 99]. In conclusion, we demonstrated reduced hippocampal stiffness and reduced hippocampal viscosity, as determined by MMRE, in patients with clinical diagnosis of dementia of the AD type. Diagnostic sensitivity was further improved by the combination with two other MRI-based hippocampal parameters. These findings motivate further investigation whether MMRE can detect decreased brain stiffness already in pre-dementia stages, and whether these changes predict cognitive decline.

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YNIMG Journal 2016 Journal Article

Brain stimulation during an afternoon nap boosts slow oscillatory activity and memory consolidation in older adults

Julia Ladenbauer
Nadine Külzow
Sven Passmann
Daria Antonenko
Ulrike Grittner
Sascha Tamm
Agnes Flöel

Sleep-related consolidation of declarative memories, as well as associated neurophysiological events such as slow oscillatory and spindle activity, deteriorate in the course of aging. This process is accelerated in neurodegenerative disease. Transcranial slow oscillatory stimulation (so-tDCS) during sleep has been shown to enhance slow oscillatory brain activity and thereby improve memory consolidation in young subjects. Here, we investigated whether so-tDCS applied to older adults during an afternoon nap exerts similar effects. Eighteen older human subjects were assessed using visuo-spatial (picture memory, primary, and location memory) and verbal memory tasks before and after a 90-min nap either comprising weak so-tDCS at 0. 75Hz over fronto-central location or sham (no) stimulation in a within-subject design. Electroencephalographic activity was recorded throughout the naps and immediate effects of stimulation on brain activity were evaluated. Here, spectral power within three frequency bands of interest were computed, i. e. , slow oscillatory activity, slow spindle and fast spindle activity; in 1-min stimulation-free intervals following 5 stimulation blocks. So-tDCS significantly increased frontal slow oscillatory activity as well as fast spindle activity, and significantly improved picture memory retention after sleep. Retention in the location memory subtask and in the verbal memory task was not affected. These findings may indicate a novel strategy to counteract cognitive decline in aging in a convenient manner during brief daytime naps.

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