TY - JOUR A1 - Liebe, Thomas A1 - Dordevic, Milos A1 - Kaufmann, Jörn A1 - Avetisyan, Araks A1 - Skalej, Martin A1 - Müller, Notger Germar T1 - Investigation of the functional pathogenesis of mild cognitive impairment by localisation-based locus coeruleus resting-state fMRI JF - Human Brain Mapping N2 - Dementia as one of the most prevalent diseases urges for a better understanding of the central mechanisms responsible for clinical symptoms, and necessitates improvement of actual diagnostic capabilities. The brainstem nucleus locus coeruleus (LC) is a promising target for early diagnosis because of its early structural alterations and its relationship to the functional disturbances in the patients. In this study, we applied our improved method of localisation-based LC resting-state fMRI to investigate the differences in central sensory signal processing when comparing functional connectivity (fc) of a patient group with mild cognitive impairment (MCI, n = 28) and an age-matched healthy control group (n = 29). MCI and control participants could be differentiated in their Mini-Mental-State-Examination (MMSE) scores (p < .001) and LC intensity ratio (p = .010). In the fMRI, LC fc to anterior cingulate cortex (FDR p < .001) and left anterior insula (FDR p = .012) was elevated, and LC fc to right temporoparietal junction (rTPJ, FDR p = .012) and posterior cingulate cortex (PCC, FDR p = .021) was decreased in the patient group. Importantly, LC to rTPJ connectivity was also positively correlated to MMSE scores in MCI patients (p = .017). Furthermore, we found a hyperactivation of the left-insula salience network in the MCI patients. Our results and our proposed disease model shed new light on the functional pathogenesis of MCI by directing to attentional network disturbances, which could aid new therapeutic strategies and provide a marker for diagnosis and prediction of disease progression. KW - attention KW - locus coeruleus KW - mild cognitive impairment KW - resting-state fMRI Y1 - 2022 U6 - https://doi.org/10.1002/hbm.26039 SN - 1097-0193 VL - 43 SP - 5630 EP - 5642 PB - Wiley CY - New York, NY, USA ET - 18 ER - TY - JOUR A1 - Dordevic, Milos A1 - Hölzer, Sonja A1 - Russo, Augusta A1 - García Alanis, José Carlos A1 - Müller, Notger Germar T1 - The Role of the Precuneus in Human Spatial Updating in a Real Environment Setting—A cTBS Study JF - Life N2 - As we move through an environment, we update positions of our body relative to other objects, even when some objects temporarily or permanently leave our field of view—this ability is termed egocentric spatial updating and plays an important role in everyday life. Still, our knowledge about its representation in the brain is still scarce, with previous studies using virtual movements in virtual environments or patients with brain lesions suggesting that the precuneus might play an important role. However, whether this assumption is also true when healthy humans move in real environments where full body-based cues are available in addition to the visual cues typically used in many VR studies is unclear. Therefore, in this study we investigated the role of the precuneus in egocentric spatial updating in a real environment setting in 20 healthy young participants who underwent two conditions in a cross-over design: (a) stimulation, achieved through applying continuous theta-burst stimulation (cTBS) to inhibit the precuneus and (b) sham condition (activated coil turned upside down). In both conditions, participants had to walk back with blindfolded eyes to objects they had previously memorized while walking with open eyes. Simplified trials (without spatial updating) were used as control condition, to make sure the participants were not affected by factors such as walking blindfolded, vestibular or working memory deficits. A significant interaction was found, with participants performing better in the sham condition compared to real stimulation, showing smaller errors both in distance and angle. The results of our study reveal evidence of an important role of the precuneus in a real-environment egocentric spatial updating; studies on larger samples are necessary to confirm and further investigate this finding. KW - precuneus KW - spatial updating KW - TMS KW - cTBS Y1 - 2022 U6 - https://doi.org/10.3390/life12081239 SN - 2075-1729 VL - 12 SP - 1 EP - 13 PB - MDPI CY - Basel, Schweiz ET - 8 ER - TY - JOUR A1 - Herold, Fabian A1 - Labott, Berit K. A1 - Grässler, Bernhard A1 - Halfpaap, Nicole A1 - Langhans, Corinna A1 - Müller, Patrick A1 - Ammar, Achraf A1 - Dordevic, Milos A1 - Hökelmann, Anita A1 - Müller, Notger Germar T1 - A Link between Handgrip Strength and Executive Functioning: A Cross-Sectional Study in Older Adults with Mild Cognitive Impairment and Healthy Controls JF - Healthcare : open access journal N2 - Older adults with amnestic mild cognitive impairment (aMCI) who in addition to their memory deficits also suffer from frontal-executive dysfunctions have a higher risk of developing dementia later in their lives than older adults with aMCI without executive deficits and older adults with non-amnestic MCI (naMCI). Handgrip strength (HGS) is also correlated with the risk of cognitive decline in the elderly. Hence, the current study aimed to investigate the associations between HGS and executive functioning in individuals with aMCI, naMCI and healthy controls. Older, right-handed adults with amnestic MCI (aMCI), non-amnestic MCI (naMCI), and healthy controls (HC) conducted a handgrip strength measurement via a handheld dynamometer. Executive functions were assessed with the Trail Making Test (TMT A&B). Normalized handgrip strength (nHGS, normalized to Body Mass Index (BMI)) was calculated and its associations with executive functions (operationalized through z-scores of TMT B/A ratio) were investigated through partial correlation analyses (i.e., accounting for age, sex, and severity of depressive symptoms). A positive and low-to-moderate correlation between right nHGS (rp (22) = 0.364; p = 0.063) and left nHGS (rp (22) = 0.420; p = 0.037) and executive functioning in older adults with aMCI but not in naMCI or HC was observed. Our results suggest that higher levels of nHGS are linked to better executive functioning in aMCI but not naMCI and HC. This relationship is perhaps driven by alterations in the integrity of the hippocampal-prefrontal network occurring in older adults with aMCI. Further research is needed to provide empirical evidence for this assumption. KW - MCI KW - hippocampal-prefrontal network KW - handgrip strength KW - exercise cognition KW - aging KW - brain health Y1 - 2022 U6 - https://doi.org/10.3390/healthcare10020230 SN - 2227-9032 VL - 10 SP - 1 EP - 14 PB - MDPI CY - Basel, Schweiz ET - 2 ER -