المؤلفون: Guodong Weng, Johannes Slotboom, Philippe Schucht, Ekin Ermiş, Roland Wiest, Stefan Klöppel, Jessica Peter, Irena Zubak, Piotr Radojewski

المصدر: NeuroImage, Vol 286, Iss , Pp 120511- (2024)

مصطلحات موضوعية: GABA+, Glx, MRSI, Spectral editing, SLOW, Ultra-high field, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: GABA+ and Glx (glutamate and glutamine) are widely studied metabolites, yet the commonly used magnetic resonance spectroscopy (MRS) techniques have significant limitations, including sensitivity to B0 and B1+-inhomogeneities, limited bandwidth of MEGA-pulses, high SAR which is accentuated at 7T. To address these limitations, we propose SLOW-EPSI method, employing a large 3D MRSI coverage and achieving a high resolution down to 0.26 ml.Simulation results demonstrate the robustness of SLOW-editing for both GABA+ and Glx against B0 and B1+-inhomogeneities within the range of [-0.3, +0.3] ppm and [40 %, 250 %], respectively.Two protocols, both utilizing a 70 mm thick FOV slab, were employed to target distinct brain regions in vivo, differentiated by their orientation: transverse and tilted. Protocol 1 (n = 11) encompassed 5 locations (cortical gray matter, white matter, frontal lobe, parietal lobe, and cingulate gyrus). Protocol 2 (n = 5) involved 9 locations (cortical gray matter, white matter, frontal lobe, occipital lobe, cingulate gyrus, caudate nucleus, hippocampus, putamen, and inferior thalamus).Quantitative analysis of GABA+ and Glx was conducted in a stepwise manner. First, B1+/B1–-inhomogeneities were corrected using water reference data. Next, GABA+ and Glx values were calculated employing spectral fitting. Finally, the GABA+ level for each selected region was compared to the global Glx within the same subject, generating the GABA+/Glx_global ratio.Our findings from two protocols indicate that the GABA+/Glx_global level in cortical gray matter was approximately 16 % higher than in white matter. Elevated GABA+/Glx_global levels acquired with protocol 2 were observed in specific regions such as the caudate nucleus (0.118±0.067), putamen (0.108±0.023), thalamus (0.092±0.036), and occipital cortex (0.091±0.010), when compared to the cortical gray matter (0.079±0.012).Overall, our results highlight the effectiveness of SLOW-EPSI as a robust and efficient technique for accurate measurements of GABA+ and Glx at 7T. In contrast to previous SVS and 2D-MRSI based editing sequences with which only one or a limited number of brain regions can be measured simultaneously, the method presented here measures GABA+ and Glx from any brain area and any arbitrarily shaped volume that can be flexibly selected after the examination. Quantification of GABA+ and Glx across multiple brain regions through spectral fitting is achievable with a 9-minute acquisition. Additionally, acquisition times of 18–27 min (GABA+) and 9–18 min (Glx) are required to generate 3D maps, which are constructed using Gaussian fitting and peak integration.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1053811924000065Test; https://doaj.org/toc/1095-9572Test

الوصول الحر: https://doaj.org/article/1d1b181f04dd4dfcb6241b327b722341Test

المؤلفون: Marta Menéndez-Granda, Nadine Schmidt, Michael Orth, Katharina Klink, Sebastian Horn, Matthias Kliegel, Jessica Peter

المصدر: BMC Psychiatry, Vol 23, Iss 1, Pp 1-10 (2023)

مصطلحات موضوعية: Prospective memory, Event-based, Time-based, Healthy ageing, Incentives, Avoidance of losses, Psychiatry, RC435-571

الوصف: Abstract Background Prospective memory is important for our health and independence but declines with age. Hence, interventions to enhance prospective memory, for example by providing an incentive, may promote healthy ageing. The neuroanatomical correlates of prospective memory and the processing of incentive-related prospective memory changes in older adults are not fully understood. In an fMRI study, we will therefore test whether incentives improve prospective memory in older adults and how prospective memory is processed in the brain in general, and when incentives are provided. Since goals and interests change across adulthood, avoiding losses is becoming more important for older adults than achieving gains. We therefore posit that loss-related incentives will enhance prospective memory, which will be subserved by increased prefrontal and midbrain activity. Methods We will include n = 60 healthy older adults (60–75 years of age) in a randomized, single-blind, and parallel-group study. We will acquire 7T fMRI data in an incentive group and a control group (n = 30 each, stratified by education, age, and sex). Before and after fMRI, all participants will complete questionnaires and cognitive tests to assess possible confounders (e.g., income, personality traits, sensitivity to reward or punishment). Discussion The results of this study will clarify whether loss-related incentives can enhance prospective memory and how any enhancement is processed in the brain. In addition, we will determine how prospective memory is processed in the brain in general. The results of our study will be an important step towards a better understanding of how prospective memory changes when we get older and for developing interventions to counteract cognitive decline.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-244XTest

الوصول الحر: https://doaj.org/article/7cc6851370c247359073f9df3bae956bTest

المؤلفون: Christine Krebs, Jessica Peter, Esther Brill, Stefan Klöppel, Anna-Katharine Brem

المصدر: Frontiers in Psychology, Vol 14 (2023)

مصطلحات موضوعية: older adults, tDCS, tACS, cognitive training, education, age, Psychology, BF1-990

الوصف: Computerized cognitive training (CCT) has been shown to improve cognition in older adults via targeted exercises for single or multiple cognitive domains. Combining CCT with non-invasive brain stimulation is thought to be even more effective due to synergistic effects in the targeted brain areas and networks. However, little is known about the moderating effects of sex, age, and education on cognitive outcomes. Here, we investigated these factors in a randomized, double-blind study in which we administered CCT either combined with transcranial direct (tDCS), alternating (tACS) current stimulation or sham stimulation. 59 healthy older participants (mean age 71.7 ± 6.1) received either tDCS (2 mA), tACS (5 Hz), or sham stimulation over the left dorsolateral prefrontal cortex during the first 20 min of a CCT (10 sessions, 50 min, twice weekly). Before and after the complete cognitive intervention, a neuropsychological assessment was performed, and the test scores were summarized in a composite score. Our results showed a significant three-way interaction between age, years of education, and stimulation technique (F(6,52) = 5.53, p = 0.007), indicating that the oldest participants with more years of education particularly benefitted from tDCS compared to the sham group, while in the tACS group the youngest participants with less years of education benefit more from the stimulation. These results emphasize the importance of further investigating and taking into account sex, age, and education as moderating factors in the development of individualized stimulation protocols.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03475446.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1243099/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/f9a657c985994fc39f7c887521855871Test

المؤلفون: Alexandra König, Johannes Tröger, Elisa Mallick, Mario Mina, Nicklas Linz, Carole Wagnon, Julia Karbach, Caroline Kuhn, Jessica Peter

المصدر: BMC Psychiatry, Vol 22, Iss 1, Pp 1-8 (2022)

مصطلحات موضوعية: Depressive symptoms, Automated speech analysis, Acoustic features, Textual features, Machine learning, Psychiatry, RC435-571

الوصف: Abstract Background Automated speech analysis has gained increasing attention to help diagnosing depression. Most previous studies, however, focused on comparing speech in patients with major depressive disorder to that in healthy volunteers. An alternative may be to associate speech with depressive symptoms in a non-clinical sample as this may help to find early and sensitive markers in those at risk of depression. Methods We included n = 118 healthy young adults (mean age: 23.5 ± 3.7 years; 77% women) and asked them to talk about a positive and a negative event in their life. Then, we assessed the level of depressive symptoms with a self-report questionnaire, with scores ranging from 0–60. We transcribed speech data and extracted acoustic as well as linguistic features. Then, we tested whether individuals below or above the cut-off of clinically relevant depressive symptoms differed in speech features. Next, we predicted whether someone would be below or above that cut-off as well as the individual scores on the depression questionnaire. Since depression is associated with cognitive slowing or attentional deficits, we finally correlated depression scores with performance in the Trail Making Test. Results In our sample, n = 93 individuals scored below and n = 25 scored above cut-off for clinically relevant depressive symptoms. Most speech features did not differ significantly between both groups, but individuals above cut-off spoke more than those below that cut-off in the positive and the negative story. In addition, higher depression scores in that group were associated with slower completion time of the Trail Making Test. We were able to predict with 93% accuracy who would be below or above cut-off. In addition, we were able to predict the individual depression scores with low mean absolute error (3.90), with best performance achieved by a support vector machine. Conclusions Our results indicate that even in a sample without a clinical diagnosis of depression, changes in speech relate to higher depression scores. This should be investigated in more detail in the future. In a longitudinal study, it may be tested whether speech features found in our study represent early and sensitive markers for subsequent depression in individuals at risk.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-244XTest

الوصول الحر: https://doaj.org/article/44177b145fef4cf18722e82b51e0e781Test

المؤلفون: Esther Brill, Christine Krebs, Michael Falkner, Jessica Peter, Katharina Henke, Marc Züst, Lora Minkova, Anna-Katharine Brem, Stefan Klöppel

المصدر: BMC Psychiatry, Vol 22, Iss 1, Pp 1-11 (2022)

مصطلحات موضوعية: Computerized cognitive training, Alzheimer’s disease, Mild cognitive impairment, Subjective cognitive decline, Serious games, Cognitive training, Psychiatry, RC435-571

الوصف: Abstract Background Alzheimer’s disease (AD) is a major public health issue. Cognitive interventions such as computerized cognitive trainings (CCT) are effective in attenuating cognitive decline in AD. However, in those at risk of dementia related to AD, results are heterogeneous. Efficacy and feasibility of CCT needs to be explored in depth. Moreover, underlying mechanisms of CCT effects on the three cognitive domains typically affected by AD (episodic memory, semantic memory and spatial abilities) remain poorly understood. Methods In this bi-centric, randomized controlled trial (RCT) with parallel groups, participants (planned N = 162, aged 60–85 years) at risk for AD and with at least subjective cognitive decline will be randomized to one of three groups. We will compare serious game-based CCT against a passive wait list control condition and an active control condition (watching documentaries). Training will consist of daily at-home sessions for 10 weeks (50 sessions) and weekly on-site group meetings. Subsequently, the CCT group will continue at-home training for an additional twenty-weeks including monthly on-site booster sessions. Investigators conducting the cognitive assessments will be blinded. Group leaders will be aware of participants’ group allocations. Primarily, we will evaluate change using a compound value derived from the comprehensive cognitive assessment for each of three cognitive domains. Secondary, longitudinal functional and structural magnetic resonance imaging (MRI) and evaluation of blood-based biomarkers will serve to investigate neuronal underpinnings of expected training benefits. Discussion The present study will address several shortcomings of previous CCT studies. This entails a comparison of serious game-based CCT with both a passive and an active control condition while including social elements crucial for training success and adherence, the combination of at-home and on-site training, inclusion of booster sessions and assessment of physiological markers. Study outcomes will provide information on feasibility and efficacy of serious game-based CCT in older adults at risk for AD and will potentially generalize to treatment guidelines. Moreover, we set out to investigate physiological underpinnings of CCT induced neuronal changes to form the grounds for future individually tailored interventions and neuro-biologically informed trainings. Trial registration This RCT was registered 1st of July 2020 at clinicaltrials.gov (Identifier NCT04452864).

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-244XTest

الوصول الحر: https://doaj.org/article/fd3421266f314e28be692b4208c09715Test

المؤلفون: Xiang Zhou, Andrej Besse, Jessica Peter, Maximilian Johannes Steinhardt, Cornelia Vogt, Silvia Nerreter, Eva Teufel, Emilia Stanojkovska, Xianghui Xiao, Hannah Hornburger, Larissa Haertle, Max Mendez Lopez, Umair Munawar, Angela Riedel, Seungbin Han, Elmer Maurits, Herman S. Overkleeft, Bogdan Florea, Hermann Einsele, K. Martin Kortüm, Christoph Driessen, Lenka Besse, Leo Rasche

المصدر: Haematologica, Vol 108, Iss 6 (2023)

مصطلحات موضوعية: Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: Optimal carfilzomib dosing is a matter of debate. We analyzed the inhibition profiles of proteolytic proteasome subunits β5, β2 and β1 after low-dose (20/27 mg/m2) versus high-dose (≥36 mg/m2) carfilzomib in 103 pairs of peripheral blood mononuclear cells from patients with relapsed/refractory (RR) multiple myeloma (MM). β5 activity was inhibited (median inhibition >50%) in vivo by 20 mg/m2, whereas β2 and β1 were co-inhibited only by 36 and 56 mg/m2, respectively. Coinhibition of β2 (P=0.0001) and β1 activity (P=0.0005) differed significantly between high-dose and low-dose carfilzomib. Subsequently, high-dose carfilzomib showed significantly more effective proteasome inhibition than low-dose carfilzomib in vivo (P=0.0003). We investigated the clinical data of 114 patients treated with carfilzomib combinations. High-dose carfilzomib demonstrated a higher overall response rate (P=0.03) and longer progression-free survival (PFS) (P=0.007) than low-dose carfilzomib. Therefore, we escalated the carfilzomib dose to ≥36 mg/m2 in 16 patients who progressed during low-dose carfilzomib-containing therapies. High-dose carfilzomib recaptured response (≥ partial remission) in nine (56%) patients with a median PFS of 4.4 months. Altogether, we provide the first in vivo evidence in RRMM patients that the molecular activity of high-dose carfilzomib differs from that of low-dose carfilzomib by coinhibition of β2 and β1 proteasome subunits and, consequently, high-dose carfilzomib achieves a superior anti-MM effect than low-dose carfilzomib and recaptures the response in RRMM resistant to low-dose carfilzomib. The optimal carfilzomib dose should be ≥36 mg/m2 to reach a sufficient anti-tumor activity, while the balance between efficacy and tolerability should be considered in each patient.

وصف الملف: electronic resource

العلاقة: https://haematologica.org/article/view/10969Test; https://doaj.org/toc/0390-6078Test; https://doaj.org/toc/1592-8721Test

الوصول الحر: https://doaj.org/article/145781d6796c4523aa127a2cf8216c97Test

المؤلفون: Nadine Schmidt, Matthias Kliegel, Jessica Peter

المصدر: Brain Stimulation, Vol 16, Iss 1, Pp 212- (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X23002930Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/4d13dc08ff1c4e9c8fb20304a60f3a06Test

المؤلفون: Christine Krebs, Jessica Peter, Esther Brill, Stefan Klöppel, Anna-Katharine Brem

المصدر: Brain Stimulation, Vol 16, Iss 1, Pp 314- (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X23005818Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/57dc2e439fc64f4585734d89712102c7Test

المؤلفون: Jessica Peter, Isabella Mayer, Thomas Kammer, Lora Minkova, Jacob Lahr, Stefan Klöppel, Michel J. Grothe, Michael Orth

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract We assessed the structure–function relationship of the human cholinergic system and hypothesized that structural measures are associated with short-latency sensory afferent inhibition (SAI), an electrophysiological measure of central cholinergic signal transmission. Healthy volunteers (n = 36) and patients with mild cognitive impairment (MCI, n = 20) underwent median nerve SAI and 3T structural MRI to determine the volume of the basal forebrain and the thalamus. Patients with MCI had smaller basal forebrain (p 10% SAI) had more basal forebrain volume than non-responders (p = 0.004) or patients with MCI (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/14a640e78bd34437a2d0eb958651d24eTest

المؤلفون: Nadine Schmidt, Matthias Kliegel, Jessica Peter

المصدر: Brain Stimulation, Vol 16, Iss 1, Pp 204-205 (2023)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1935861X23002711Test; https://doaj.org/toc/1935-861XTest

الوصول الحر: https://doaj.org/article/36729398acfc4df39c360e5fdde733feTest