OBJECTIVE: The aim of this work was to study the differences at the whole-brain level between self-paced and cued movement processing in Parkinson's disease (PD). METHODS: High density electroencephalogram (HD-EEG) was recorded during the performance of self-paced movements (Bereitschaftspotential - BP) and visually cued movements (VMT) in PD patients (n = 38) and in a group of healthy controls (HC, n = 23). Oscillatory changes in the alpha, beta, and gamma frequencies were evaluated and correlated to the clinical scales- MDS-UPDRS and Freezing of Gait Questionnaire (FOGQ). RESULTS: The main difference in the alpha range was an activation in the basal ganglia area during VMT performance as compared to BP performance; this activation was present only in HC. The most important finding was observed in the high beta range: a higher activation of the right postcentral area during BP performance in PD subjects as compared to HC, correlating to the severity of FOG. Moreover, PD patients had lower gamma activation of the right frontal areas. CONCLUSION: A simplification of motor circuits and a hyperactivation of the right somatosensory cortex were observed in PD subjects. SIGNIFICANCE: Future studies should be focused on this area to confirm or disprove its role in FOG.

• MeSH
• elektroencefalografie * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc * patofyziologie   MeSH
• podněty MeSH
• pohyb fyziologie   MeSH
• senioři MeSH
• somatosenzorické korové centrum * patofyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Working memory (WM) is essential for the temporary storage and processing of information required for complex cognitive tasks and relies on neuronal theta and gamma oscillations. Given the limited capacity of WM, researchers have investigated various methods to improve it, including transcranial alternating current stimulation (tACS), which modulates brain activity at specific frequencies. One particularly promising approach is theta-gamma peak-coupled-tACS (TGCp-tACS), which simulates the natural interaction between theta and gamma oscillations that occurs during cognitive control in the brain. The aim of this study was to improve WM in healthy young adults with TGCp-tACS, focusing on both behavioral and neurophysiological outcomes. Thirty-one participants completed five WM tasks under both sham and verum stimulation conditions. Electroencephalography (EEG) recordings before and after stimulation showed that TGCp-tACS increased power spectral density (PSD) in the high-gamma region at the stimulation site, while PSD decreased in the theta and delta regions throughout the cortex. From a behavioral perspective, although no significant changes were observed in most tasks, there was a significant improvement in accuracy in the 14-item Sternberg task, indicating an improvement in phonological WM. In conclusion, TGCp-tACS has the potential to promote and improve the phonological component of WM. To fully realize the cognitive benefits, further research is needed to refine the stimulation parameters and account for individual differences, such as baseline cognitive status and hormonal factors.

• MeSH
• chování fyziologie   MeSH
• dospělí MeSH
• elektrická stimulace MeSH
• elektroencefalografie MeSH
• gama rytmus EEG fyziologie   MeSH
• krátkodobá paměť * fyziologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• přímá transkraniální stimulace mozku * metody   MeSH
• theta rytmus EEG fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Despite advances in understanding the cellular and molecular processes underlying memory and cognition, and recent successful modulation of cognitive performance in brain disorders, the neurophysiological mechanisms remain underexplored. High frequency oscillations beyond the classic electroencephalogram spectrum have emerged as a potential neural correlate of fundamental cognitive processes. High frequency oscillations are detected in the human mesial temporal lobe and neocortical intracranial recordings spanning gamma/epsilon (60-150 Hz), ripple (80-250 Hz) and higher frequency ranges. Separate from other non-oscillatory activities, these brief electrophysiological oscillations of distinct duration, frequency and amplitude are thought to be generated by coordinated spiking of neuronal ensembles within volumes as small as a single cortical column. Although the exact origins, mechanisms and physiological roles in health and disease remain elusive, they have been associated with human memory consolidation and cognitive processing. Recent studies suggest their involvement in encoding and recall of episodic memory with a possible role in the formation and reactivation of memory traces. High frequency oscillations are detected during encoding, throughout maintenance, and right before recall of remembered items, meeting a basic definition for an engram activity. The temporal coordination of high frequency oscillations reactivated across cortical and subcortical neural networks is ideally suited for integrating multimodal memory representations, which can be replayed and consolidated during states of wakefulness and sleep. High frequency oscillations have been shown to reflect coordinated bursts of neuronal assembly firing and offer a promising substrate for tracking and modulation of the hypothetical electrophysiological engram.

• MeSH
• elektroencefalografie MeSH
• kognice * fyziologie   MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• mozkové vlny fyziologie   MeSH
• paměť fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Although electrical muscle stimulation (EMS) of skeletal muscle effectively prevents muscle atrophy, its effect on the breakdown of muscle component proteins is unknown. In this study, we investigated the biological mechanisms by which EMS-induced muscle contraction inhibits disuse muscle atrophy progression. Experimental animals were divided into a control group and three experimental groups: immobilized (Im; immobilization treatment), low-frequency (LF; immobilization treatment and low-frequency muscle contraction exercise), and high-frequency (HF; immobilization treatment and high-frequency muscle contraction exercise). Following the experimental period, bilateral soleus muscles were collected and analyzed. Atrogin-1 and Muscle RING finger 1 (MuRF-1) mRNA expression levels were significantly higher for the experimental groups than for the control group but were significantly lower for the HF group than for the Im group. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) mRNA and protein expression levels in the HF group were significantly higher than those in the Im group, with no significant differences compared to the Con group. Both the Forkhead box O (FoxO)/phosphorylated FoxO and protein kinase B (AKT)/phosphorylated AKT ratios were significantly lower for the Im group than for the control group and significantly higher for the HF group than for the Im group. These results, the suppression of atrogin-1 and MuRF-1 expression for the HF group may be due to decreased nuclear expression of FoxO by AKT phosphorylation and suppression of FoxO transcriptional activity by PGC-1alpha. Furthermore, the number of muscle contractions might be important for effective EMS.

• MeSH
• kosterní svaly metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• PPAR gama metabolismus   MeSH
• PPARGC1A metabolismus   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• svalová atrofie prevence a kontrola   genetika   metabolismus   MeSH
• svalové proteiny metabolismus   MeSH
• transkripční faktory * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

High-frequency oscillations (HFOs) represent an electrographic biomarker of endogenous epileptogenicity and seizure-generating tissue that proved clinically useful in presurgical planning and delineating the resection area. In the neocortex, the clinical observations on HFOs are not sufficiently supported by experimental studies stemming from a lack of realistic neocortical epilepsy models that could provide an explanation of the pathophysiological substrates of neocortical HFOs. In this study, we explored pathological epileptiform network phenomena, particularly HFOs, in a highly realistic murine model of neocortical epilepsy due to focal cortical dysplasia (FCD) type II. FCD was induced in mice by the expression of the human pathogenic mTOR gene mutation during embryonic stages of brain development. Electrographic recordings from multiple cortical regions in freely moving animals with FCD and epilepsy demonstrated that the FCD lesion generates HFOs from all frequency ranges, i.e., gamma, ripples, and fast ripples up to 800 Hz. Gamma-ripples were recorded almost exclusively in FCD animals, while fast ripples occurred in controls as well, although at a lower rate. Gamma-ripple activity is particularly valuable for localizing the FCD lesion, surpassing the utility of fast ripples that were also observed in control animals, although at significantly lower rates. Propagating HFOs occurred outside the FCD, and the contralateral cortex also generated HFOs independently of the FCD, pointing to a wider FCD network dysfunction. Optogenetic activation of neurons carrying mTOR mutation and expressing Channelrhodopsin-2 evoked fast ripple oscillations that displayed spectral and morphological profiles analogous to spontaneous oscillations. This study brings experimental evidence that FCD type II generates pathological HFOs across all frequency bands and provides information about the spatiotemporal properties of each HFO subtype in FCD. The study shows that mutated neurons represent a functionally interconnected and active component of the FCD network, as they can induce interictal epileptiform phenomena and HFOs.

• MeSH
• elektroencefalografie MeSH
• epilepsie * MeSH
• fokální kortikální dysplazie * MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• TOR serin-threoninkinasy MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

• MeSH
• bezvědomí MeSH
• elektroencefalografie metody   MeSH
• epilepsie parciální * MeSH
• lidé MeSH
• mozek MeSH
• záchvaty * diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Working memory is a cognitive process that involves short-term active maintenance, flexible updating, and processing of goal- or task-relevant information. All frequency bands are involved in working memory. The activities of the theta and gamma frequency bands in the frontoparietal network are highly involved in working memory processes; theta oscillations play a role in the temporal organization of working memory items, and gamma oscillations influence the maintenance of information in working memory. Transcranial alternating current stimulation (tACS) results in frequency-specific modulation of endogenous oscillations and has shown promising results in cognitive neuroscience. The electrophysiological and behavioral changes induced by the modulation of endogenous gamma frequency in the prefrontal cortex using tACS have not been extensively studied in the context of working memory. Therefore, we aimed to investigate the effects of frontal gamma-tACS on working memory outcomes. We hypothesized that a 10-min gamma tACS administered over the frontal cortex would significantly improve working memory outcomes. Young healthy participants performed Luck-Vogel cognitive behavioral tasks with simultaneous pre- and post-intervention EEG recording (Sham versus 40 Hz tACS). Data from forty-one participants: sham (15 participants) and tACS (26 participants), were used for the statistical and behavioral analysis. The relative changes in behavioral outcomes and EEG due to the intervention were analyzed. The results show that tACS caused an increase in the power spectral density in the high beta and low gamma EEG bands and a decrease in left-right coherence. On the other hand, tACS had no significant effect on success rates and response times. Conclusion: 10 min of frontal 40 Hz tACS was not sufficient to produce detectable behavioral effects on working memory, whereas electrophysiological changes were evident. The limitations of the current stimulation protocol and future directions are discussed in detail in the following sections.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Prostate adenocarcinoma (CaP) is one of the most common malignancies in men in Slovakia and in the world. The disease accounts for more than 22% of all tumors in the male population. Screening studies show an increase in the diagnosis of CaP without improvement in overall or CaP-specific mortality. The main goal of the work is to evaluate the incidence of CaP in the group of patients examined and treated during the period from 2014 to 2019 at the urological outpatient clinic of the Railway Hospital (RH) in Košice, and to evaluate the risks and treatment options. METHODS: Men aged 40 to 75 years underwent a preventive examination in 2014-2019 at the urology outpatient clinic, RH Košice. The number of screened patients was 3,943. Epidemiological parameter, diagnosis-related examinations (prostate specific antigen - PSA examination, digital rectal examination, and ultrasonography examination) as well as the frequency of examinations were monitored during the specified period on the basis of documentation. The number of prostate biopsies, incidence of prostate cancer and relation to PSA values were also monitored, as well as the classification of prostate cancers according to the degree of risk. Initial treatment in individual patients was also evaluated. RESULTS: PSA values in patients who underwent biopsy ranged from 3.6 ng/mL to 2,000 ng/mL. We observed positive digital rectal examination in 52 patients. Of the number of patients examined, 231 (61.28%) were positive biopsies. There were negative biopsies with the finding of benign prostatic hyperplasia in 92 patients or chronic prostatitis in 54 patients, i.e., 146 (38.72%). According to the criteria for risk assessment based on the PSA value and the result of the histological examination, we diagnosed 109 low-risk patients, 57 medium-risk patients and 24 high-risk patients. CONCLUSION: CaP is detected by prevention about 10 years before it develops clinically. The main aim of preventive examinations should be to detect, in particular, high-risk forms of early-stage prostate cancer and to improve the quality of life of men. Due to the results of extensive studies, it is necessary to continue the active search for prostate cancer. This reduces the risk of metastatic forms of CaP.

• MeSH
• časná detekce nádoru MeSH
• kvalita života MeSH
• lidé MeSH
• nádory prostaty * diagnóza   epidemiologie   MeSH
• prostata patologie   MeSH
• prostatický specifický antigen * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: Patients with decompensated cirrhosis suffer from recurrent infections and inadequate responses to prophylactic vaccinations. However, many patients present with hypergammaglobulinemia (HGG), indicating a sustained ability to generate antibody responses. As follicular T helper (Tfh) cells are central facilitators of humoral immunity, we hypothesized that Tfh cell responses may be altered in advanced liver disease and we aimed to identify the mechanisms underlying any such alterations. METHODS: Tfh, regulatory T (Treg) cells, B cells, circulating cytokines and immunoglobulins were analyzed in cohorts of patients with compensated (n = 37) and decompensated cirrhosis (n = 82) and in non-cirrhotic controls (n = 45). Intrahepatic T cells were analyzed in 8 decompensated patients. The influence of IL-2 on Tfh cell function was evaluated in vitro, including Tfh cell cloning and T cell-B cell co-cultures with clones and primary tonsil-derived Tfh cells. RESULTS: Tfh cell frequencies were reduced in patients with decompensated cirrhosis, with phenotypic signatures indicative of increased IL-2 signaling. Soluble IL-2 receptor (sCD25) was elevated in these patients and CD4 T cells were more responsive to IL-2 signaling, as characterized by STAT5 phosphorylation. IL-2 exposure in vitro diminished the Tfh phenotype and resulted in impaired Tfh helper function in co-culture experiments with naïve B cells. Tfh cells were barely detectable in cirrhotic livers. IL-2 signatures on Tfh cells in decompensated patients correlated with immunoglobulin levels, which were found to be associated with improved survival. CONCLUSIONS: Tfh cell impairment represents a previously underestimated feature of cirrhosis-associated immune dysfunction that is driven by IL-2. The presence of HGG in decompensated patients predicts an intact Tfh cell compartment and is associated with a favorable outcome. LAY SUMMARY: Patients with advanced cirrhosis often fail to generate protective immunity after prophylactic vaccinations and suffer from recurring infections that are associated with high mortality. Follicular T helper (Tfh) cells are specialized CD4 T cells that enable the emergence of antibody responses against microbial pathogens. This report demonstrates that Tfh cells are impaired in patients with advanced cirrhosis due to interleukin-2 signaling, a cytokine that is known to impair the generation of Tfh cells.

• MeSH
• B-lymfocyty imunologie   MeSH
• dospělí MeSH
• folikulární pomocné T-buňky imunologie   MeSH
• hypergamaglobulinemie komplikace   MeSH
• imunoglobulin G krev   MeSH
• interleukin-2 krev   MeSH
• jaterní cirhóza krev   komplikace   imunologie   MeSH
• kohortové studie MeSH
• kokultivační techniky MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové supresorové proteiny metabolismus   MeSH
• prognóza MeSH
• průřezové studie MeSH
• regulační T-lymfocyty imunologie   MeSH
• senioři MeSH
• signální transdukce imunologie   MeSH
• transkripční faktor STAT5 metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various frequency ranges are coordinated across the space of the human cortex and time of memory processing is inconclusive. They can either be coordinated together across the frequency spectrum at the same cortical site and time or induced independently in particular bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated low frequency theta, intermediate frequency alpha and beta, and high frequency gamma power in a mosaic pattern of discrete cortical sites. A majority of the cortical sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and high frequency activities propagated in independent sequences across the visual, temporal and prefrontal cortical areas throughout subsequent phases of memory encoding. Our results provide a holistic, simplified model of the spectral activities engaged in the formation of human memory, suggesting an anatomically and temporally distributed mosaic of coordinated brain rhythms.

• MeSH
• datové soubory jako téma MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• epilepsie diagnostické zobrazování   chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• paměť fyziologie   MeSH
• počítačová rentgenová tomografie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH