Milos Dordevic

Background: Stroke is the leading cause of disability worldwide. Upper extremity paresis is the most common functional consequence, affecting more than half of all stroke survivors. Research has shown that an adequate therapy should begin in the sub-acute stage, but also that an enhanced intensity and frequency of therapy can positively affect patients’ recovery curve. Therefore, here we assessed whether an additional VR-based training can be beneficial for recovery of stroke patients, with particular emphasis on upper extremity functions. Methods: The study was organized as prospective and single-blinded (analysis). Two groups of pairwise-matched subacute stroke patients with arm paresis were recruited at our rehabilitation clinic while controlling for gender, age, sidedness and modified Rankin scale (mRS). Both groups – conventional therapy (CT) and conventional therapy plus virtual reality (CT + VR) – received 30–45 min of conventional therapy on 3 to 4 days/week over 4 weeks; in addition to that, the CT + VR group received 3 times per week a specially designed VR-based training for upper extremity. Data acquisition was performed within 24 h before the baseline and after the training has ended. Main outcomes were patients’ performance on Fugl-Meyer test for upper extremity (FME), Box-and-Block test, hand dynamometry and Functional independence test (FIM). Results: Twenty-two subjects aged 57–85 were pairwise-matched and assigned to the conventional therapy (CT) group ( n = 11, 67.82 ± 8.69 years; three females) and the conventional therapy plus virtual reality (CT + VR) group ( n = 11, 70.45 ± 6.79 years; three females). No difference in gender, age, sidedness, mRS and mini-mental status examination (MMSE) existed between the two groups. The CT + VR group showed significantly better improvements over time on FME (44.3 ± 7.8 to 58.7 ± 11.2 vs. 42.1 ± 6.2 to 49.5 ± 10.9; p = 0.009) and FIM (90.1 ± 18.0 to 118.1 ± 6.9 vs. 105.0 ± 12.4 to 110.6 ± 12.6; p < 0.001), compared to the CT group. Other tests revealed no significant differences. Discussion: As hypothesized, an additional immersive VR-based training can be beneficial for stroke patients suffering from upper extremity deficiency. Nevertheless, the principle of specificity could be observed, with only trained functions being associated with improvements on FME and FIM. Future studies with larger sample of participants are required to confirm these findings.

Background: Stroke is the leading cause of disability worldwide. Upper extremity paresis is the most common functional consequence, affecting more than half of all stroke survivors. Research has shown that an adequate therapy should begin in the sub-acute stage, but also that an enhanced intensity and frequency of therapy can positively affect patients’ recovery curve. Therefore, here we assessed whether an additional VR-based training can be beneficial for recovery of stroke patients, with particular emphasis on upper extremity functions. Methods: The study was organized as prospective and single-blinded (analysis). Two groups of pairwise-matched subacute stroke patients with arm paresis were recruited at our rehabilitation clinic while controlling for gender, age, sidedness and modified Rankin scale (mRS). Both groups – conventional therapy (CT) and conventional therapy plus virtual reality (CT + VR) – received 30–45 min of conventional therapy on 3 to 4 days/week over 4 weeks; in addition to that, the CT + VR group received 3 times per week a specially designed VR-based training for upper extremity. Data acquisition was performed within 24 h before the baseline and after the training has ended. Main outcomes were patients’ performance on Fugl-Meyer test for upper extremity (FME), Box-and-Block test, hand dynamometry and Functional independence test (FIM). Results: Twenty-two subjects aged 57–85 were pairwise-matched and assigned to the conventional therapy (CT) group ( n = 11, 67.82 ± 8.69 years; three females) and the conventional therapy plus virtual reality (CT + VR) group ( n = 11, 70.45 ± 6.79 years; three females). No difference in gender, age, sidedness, mRS and mini-mental status examination (MMSE) existed between the two groups. The CT + VR group showed significantly better improvements over time on FME (44.3 ± 7.8 to 58.7 ± 11.2 vs. 42.1 ± 6.2 to 49.5 ± 10.9; p = 0.009) and FIM (90.1 ± 18.0 to 118.1 ± 6.9 vs. 105.0 ± 12.4 to 110.6 ± 12.6; p < 0.001), compared to the CT group. Other tests revealed no significant differences. Discussion: As hypothesized, an additional immersive VR-based training can be beneficial for stroke patients suffering from upper extremity deficiency. Nevertheless, the principle of specificity could be observed, with only trained functions being associated with improvements on FME and FIM. Future studies with larger sample of participants are required to confirm these findings.

Background: Temporal lobe epilepsy is the most common pharmaco-resistant type of epilepsy. The chance of obtaining seizure freedom after resective surgery in pharmaco-resistant mesial temporal lobe patients (mTLE) is significantly higher compared to pharmaceutical treatment (at least 50–60% compared to less than 15%). However, some factors (e.g., craniotomy) may prevent epilepsy patients undergoing surgery. A recent advancement in epilepsy surgery, i.e., magnetic resonance guided laser interstitial thermal therapy (MRgLITT), has become an attractive alternative for performance of selective amygdala-hippo-campectomy, especially because of its minimal invasiveness. Among other medial temporal lobe structures, the hippocampus is particularly important for successful processing of vestibular inputs. Nevertheless, it is still unclear whether mTLE patients who underwent MRgLITT perform worse on vestibular-dependent tests, including balancing, spatial orientation and rotational memory. Methods: Nine patients (Age 40.1 ± 14.5; 2 females) underwent vestibular-dependent assessments before and after MRgLITT using the following test battery: (I) clinical balancing test (CBT), (II) triangle completion test (TCT) and (III) rotational memory test (RM). Results: We found significant improvement from pre- to post-surgery in the vestibular-dependent spatial orientation test, namely in the wheelchair condition of the triangle completion test. Additionally, the obtained effect sizes were medium to large in favor of post-surgery assessment for the majority of conditions in the three tests applied in this study, indicating that the assessment of a larger number of patients could also, potentially, lead to significant results in these cases. Conclusions: This plausibility study is the first to assess vestibular-dependent balancing, spatial orientation and rotational memory functions before and after MRgLITT in mTLE patients. Even with a small sample of nine patients, significant changes and medium to high effect sizes in favor of surgery were observed. Nevertheless, prospective studies with larger sample sizes are necessary for appropriate estimation of MRgLITT effectiveness in these functional domains.

Background: About 65 million people worldwide are affected by epilepsy, with temporal lobe epilepsy being the most common type resistant to drugs and often requiring surgical treatment. Although open surgical approaches, such as temporal lobectomy, have been the method of choice for decades, minimally invasive MRgLITT has demonstrated promising results. However, it remains unknown whether patients who underwent one of these two approaches would show better performance on vestibulo-spatial tasks. Methods: Twenty-seven patients were included in three different groups: (1) MRgLITT (37.0 ± 15.1 years, two females), (2) R-OP (44 ± 15.7 years, five females) and (3) No-OP (43 ± 11.2 years, three females)—with no significant differences in age, disease duration and number of medications. Groups were compared on their performance in three vestibular-dependent tests: (1) clinical balance test (CBT), (2) triangle completion test (TCT) and (3) rotational memory (RM) test. Results: Significantly better performance of MRgLITT patients, in comparison to the other two groups (R-OP and No-OP), was found for the TCT. The other tests revealed no significant differences between the groups. Conclusions: Patients who underwent MRgLITT performed significantly better on the vestibular-dependent spatial orientation task (TCT) compared to those who underwent temporal lobectomy (R-OP) and non-operated patients. Speculations about reasons for such an effect—including minimal invasiveness with less “collateral damage”, influence of operated side, timing of surgery, sample heterogeneity and others—need to be assessed in detail in larger-scale, prospective longitudinal studies.

Functional near-infrared spectroscopy (fNIRS) allows for a reliable assessment of oxygenated blood flow in relevant brain regions. Recent advancements in immersive virtual reality (VR)-based technology have generated many new possibilities for its application, such as in stroke rehabilitation. In this study, we asked whether there is a difference in oxygenated hemoglobin (HbO₂) within brain motor areas during hand/arm movements between immersive and non-immersive VR settings. Ten healthy young participants (24.3 ± 3.7, three females) were tested using a specially developed VR paradigm, called “bus riding”, whereby participants used their hand to steer a moving bus. Both immersive and non-immersive conditions stimulated brain regions controlling hand movements, namely motor cortex, but no significant differences in HbO₂ could be found between the two conditions in any of the relevant brain regions. These results are to be interpreted with caution, as only ten participants were included in the study.

Background Given that, up to date, there is no effective strategy to treat dementia, a timely start of interventions in a prodromal stage such as mild cognitive impairment (MCI) is considered an important option to lower the overall societal burden. Although autonomic functions have been related to cognitive performance, both aspects have rarely been studied simultaneously in MCI. Objective The aim of the present study was to investigate cardiac autonomic control in older adults with and without MCI. Methods Cardiac autonomic control was assessed by means of heart rate variability (HRV) at resting state and during cognitive tasks in 22 older adults with MCI and 29 healthy controls (HCs). Resting HRV measurement was performed for 5 minutes during a sitting position. Afterwards, participants performed three PC-based tasks to probe performance in executive functions and language abilities (i.e., Stroop, N-back, and a verbal fluency task). Results Participants with MCI showed a significant reduction of HRV in the frequency-domain (high frequency power) and nonlinear indices (SD2, D2, and DFA1) during resting state compared to HCs. Older individuals with MCI exhibited decreases in RMSSD and increases in DFA1 from resting state to Stroop and N-back tasks, reflecting strong vagal withdrawal, while this parameter remained stable in HCs. Conclusion The results support the presence of autonomic dysfunction at the early stage of cognitive impairment. Heart rate variability could help in the prediction of cognitive decline as a noninvasive biomarker or as a tool to monitor the effectiveness of therapy and prevention of neurodegenerative diseases.

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.

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.

Sleep problems can be caused by psychological stress but are also related to cardiovascular and neurodegenerative diseases. Improving lifestyle behaviors, such as good sleep hygiene, can help to counteract the negative effects of neurodegenerative diseases and to improve quality of life. The purpose of this cross-sectional study was to investigate the relationship between subjectively reported measures of sleep quality (via Pittsburgh Sleep Quality Index (PSQI)) and objective measures of cardiac autonomic control (via resting state heart rate variability (HRV)) among individuals with mild cognitive impairment (MCI). The PSQI and resting state HRV data of 42 MCI participants (69.0 ± 5.5; 56–80 years) were analyzed. Nineteen of the participants reported poor sleep quality (PSQI score > 5). Good sleepers showed higher resting heart rate than bad sleepers (p = 0.037; ES = 0.670). Correlation analysis showed a significant correlation between the parameter HF nu and sleep efficiency, contrasting the expected positive association between reduced HRV and poor sleep quality in healthy and individuals with specific diseases. Otherwise, there were no significances, indicating that measures of subjective sleep quality and resting HRV were not related in the present sample of MCI participants. Further research is needed to better understand the complex relationship between HRV and lifestyle factors (e.g., sleep) in MCI.

Objectives: In this study, based on the known vestibulo-hippocampal connections, we asked whether mild chronic vestibulopathy leads only to vestibular-related deficits or whether there are effects on hippocampal function, structure, and cognition in general. In more detail, we assessed whether chronic vestibulopathy leads to (a) deficits in vestibular tasks without cognitive demand (balancing), (b) deficits in spatial cognitive tasks that require vestibular input (path integration, rotational memory), (c) deficits in spatial cognitive tasks that do not rely on vestibular input, (d) deficits in general cognitive function, and (e) atrophy in the brain. Methods: A total of 15 patients with chronic uni- or bilateral vestibulopathy (56.8 ± 10.1 years; 4 females) were included in this study and were age- and gender-matched by the control participants (57.6 ± 10.5) in a pairwise manner. Given their clinical symptoms and their deficits of the vestibulo-ocular reflex (VOR) the patients could be classified as being mildly affected. All participants of the underwent the following tests: clinical balance (CBT), triangle completion (TCT) for path integration, rotational memory (RM), the visuo-spatial subset of the Berlin intelligence structure test (BIS-4) and d2-R for attention and concentration, and a structural MRI for gray matter analysis using voxel-based morphometry (VBM). Results: Compared to the healthy controls, the vestibulopathy patients performed significantly worse in terms of CBT, TCT, and RM but showed no differences in terms of the BIS-4 and d2-R. There were also no significant volumetric gray matter differences between the two groups. Conclusions: This study provides evidence that both non-cognitive and cognitive functions that rely on vestibular input (balancing, path integration, rotational memory) are impaired, even in mild chronic vestibulopathy, while other cognitive functions, which rely on visual input (visuo-spatial memory, attention), are unimpaired in this condition, together with an overall intact brain structure. These findings may reflect a segregation between vestibular- and visual-dependent processes in the medial temporal lobe on the one hand and a structure–function dissociation on the other.