Posture enhancement with cerebellum transcranial electrical stimulation: a systematic review of current methods and findings.

Recently, transcranial electrical stimulation (tES) has gained increasing popularity among researchers, especially for recovery and improvement, but interpretation of these results is difficult due to variations in study methods and outcome measurements. The main goal of this study was to better understand the postural and balance indicators affected by cerebellar tES, as the cerebellum is the main brain region responsible for controlling balance. For this systematic literature review, three databases were searched for articles where the cerebellum was stimulated by any type of tES in either healthy participants or those with neurologic disorders. Postural, dynamic, and/or static stability measurements were recorded, and risk of bias was assessed on the PEDro scale. A total of 21 studies were included in the analysis. 17 studies reported improvements after application of tES. 14 studies stimulated the cerebellum unilaterally and 15 used this modality for 20 min. Moreover, all studies exclusively used transcranial direct current as the type of stimulation. Evaluation of PEDro results showed that studies included in the analysis utilized good methodology. Although there were some inconsistencies in study results, overall, it was demonstrated that tES can improve balance and postural index under both healthy and neurological conditions. Further research of bilateral cerebellar stimulation or the use of transcranial alternating current stimulation, transcranial random noise stimulation, and transcranial pulsed current stimulation is needed for a more comprehensive assessment of the potential positive effects of cerebellar tES on the balance system.

Brain stimulation methods for pain treatment.

Treatment of pain is one of the most important aims of medicine. Over the past several decades, invasive, semi-invasive and non-invasive brain stimulation methods have been tested and implemented for modulation of the pain. In this review, we bring an overview of those methods including stimulation of both deep brain structures utilizing invasive and semi-invasive techniques and the brain cortex stimulated by non-invasive transcranial magnetic and electrical techniques. Another potentially beneficial method that could modulate pain by stimulating the deep brain with interferential transcranial alternating current is discussed as well.

Possible Mechanisms Underlying Neurological Post-COVID Symptoms and Neurofeedback as a Potential Therapy.

Theoretical considerations related to neurological post-COVID complications have become a serious issue in the COVID pandemic. We propose 3 theoretical hypotheses related to neurological post-COVID complications. First, pathophysiological processes responsible for long-term neurological complications caused by COVID-19 might have 2 phases: (1) Phase of acute Sars-CoV-2 infection linked with the pathogenesis responsible for the onset of COVID-19-related neurological complications and (2) the phase of post-acute Sars-CoV-2 infection linked with the pathogenesis responsible for long-lasting persistence of post-COVID neurological problems and/or exacerbation of another neurological pathologies. Second, post-COVID symptoms can be described and investigated from the perspective of dynamical system theory exploiting its fundamental concepts such as system parameters, attractors and criticality. Thirdly, neurofeedback may represent a promising therapy for neurological post-COVID complications. Based on the current knowledge related to neurofeedback and what is already known about neurological complications linked to acute COVID-19 and post-acute COVID-19 conditions, we propose that neurofeedback modalities, such as functional magnetic resonance-based neurofeedback, quantitative EEG-based neurofeedback, Othmer's method of rewarding individual optimal EEG frequency and heart rate variability-based biofeedback, represent a potential therapy for improvement of post-COVID symptoms.

Effects of vaccination, new SARS-CoV-2 variants and reinfections on post-COVID-19 complications.

Post-COVID-19 complications involve a variety of long-lasting health complications emerging in various body systems. Since the prevalence of post-COVID-19 complications ranges from 8-47% in COVID-19 survivors, it represents a formidable challenge to COVID-19 survivors and the health care system. Post-COVID-19 complications have already been studied in the connection to risk factors linked to their higher probability of occurrence and higher severity, potential mechanisms underlying the pathogenesis of post-COVID-19 complications, and their functional and structural correlates. Vaccination status has been recently revealed to represent efficient prevention from long-term and severe post-COVID-19 complications. However, the exact mechanisms responsible for vaccine-induced protection against severe and long-lasting post-COVID-19 complications remain elusive. Also, to the best of our knowledge, the effects of new SARS-CoV-2 variants and SARS-CoV-2 reinfections on post-COVID-19 complications and their underlying pathogenesis remain to be investigated. This hypothesis article will be dedicated to the potential effects of vaccination status, SARS-CoV-2 reinfections, and new SARS-CoV-2 variants on post-COVID-19 complications and their underlying mechanisms Also, potential prevention strategies against post-COVID complications will be discussed.

Working Memory and Transcranial-Alternating Current Stimulation-State of the Art: Findings, Missing, and Challenges.

Working memory (WM) is a cognitive process that involves maintaining and manipulating information for a short period of time. WM is central to many cognitive processes and declines rapidly with age. Deficits in WM are seen in older adults and in patients with dementia, schizophrenia, major depression, mild cognitive impairment, Alzheimer's disease, etc. The frontal, parietal, and occipital cortices are significantly involved in WM processing and all brain oscillations are implicated in tackling WM tasks, particularly theta and gamma bands. The theta/gamma neural code hypothesis assumes that retained memory items are recorded via theta-nested gamma cycles. Neuronal oscillations can be manipulated by sensory, invasive- and non-invasive brain stimulations. Transcranial alternating-current stimulation (tACS) and repetitive transcranial magnetic stimulation (rTMS) are frequency-tuned non-invasive brain stimulation (NIBS) techniques that have been used to entrain endogenous oscillations in a frequency-specific manner. Compared to rTMS, tACS demonstrates superior cost, tolerability, portability, and safety profile, making it an attractive potential tool for improving cognitive performance. Although cognitive research with tACS is still in its infancy compared to rTMS, a number of studies have shown a promising WM enhancement effect, especially in the elderly and patients with cognitive deficits. This review focuses on the various methods and outcomes of tACS on WM in healthy and unhealthy human adults and highlights the established findings, unknowns, challenges, and perspectives important for translating laboratory tACS into realistic clinical settings. This will allow researchers to identify gaps in the literature and develop frequency-tuned tACS protocols with promising safety and efficacy outcomes. Therefore, research efforts in this direction should help to consider frequency-tuned tACS as a non-pharmacological tool of cognitive rehabilitation in physiological aging and patients with cognitive deficits.

Effect of neurofeedback therapy on neurological post-COVID-19 complications (A pilot study).

OBJECTIVE: Anxiety, fatigue and depression are common neurological manifestations after COVID-19. So far, post-COVID complications were treated by rehabilitation, oxygen therapy and immunotherapy. Effects of neurofeedback on post-COVID complications and their potential interrelatedness have not been studied yet. In this pilot study, we investigated the effectiveness of neurofeedback (Othmer method) for treatment of fatigue, anxiety, and depression after COVID-19. METHODS: 10 participants met inclusion criteria for having positive anamnesis of at least one of the following complications following COVID-19: fatigue, anxiety, and depression which were measured by questionnaires. ANOVA was used for calculating differences in questionnaire score before and after neurofeedback. Pearson's correlation coefficient was used to calculate correlations between anxiety, depression and fatigue. RESULTS: After five neurofeedback sessions, there came to significant reduction of severity of post-COVID anxiety and depression persisting for at least one month. Effect of neurofeedback on fatigue was insignificant. Severity of anxiety, fatigue and depression as well as reductions in depression and fatigue were positively correlated with each other. CONCLUSION: These findings showed effectiveness neurofeedback for reducing anxiety and depression after COVID-19 and for studying correlations between neurological complications after COVID-19. However, since our pilot clinical trial was open-label, it is hard to differentiate between neurofeedback-specific and unspecific effects on our participants. Future randomized controlled trials with more robust sample are necessary to investigate feasibility of neurofeedback for post-COVID neurological complications. The study has identification number trial ID ISRCTN49037874 in ISRCTN register of clinical trials (Retrospectively registered).

10 Minutes Frontal 40 Hz tACS-Effects on Working Memory Tested by Luck-Vogel Task.

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.

Effects of Transcranial Alternating Current Stimulation and Neurofeedback on Alpha (EEG) Dynamics: A Review.

Transcranial alternating current stimulation (tACS) and neurofeedback (NFB) are two different types of non-invasive neuromodulation techniques, which can modulate brain activity and improve brain functioning. In this review, we compared the current state of knowledge related to the mechanisms of tACS and NFB and their effects on electroencephalogram (EEG) activity (online period/stimulation period) and on aftereffects (offline period/post/stimulation period), including the duration of their persistence and potential behavioral benefits. Since alpha bandwidth has been broadly studied in NFB and in tACS research, the studies of NFB and tACS in modulating alpha bandwidth were selected for comparing the online and offline effects of these two neuromodulation techniques. The factors responsible for variability in the responsiveness of the modulated EEG activity by tACS and NFB were analyzed and compared too. Based on the current literature related to tACS and NFB, it can be concluded that tACS and NFB differ a lot in the mechanisms responsible for their effects on an online EEG activity but they possibly share the common universal mechanisms responsible for the induction of aftereffects in the targeted stimulated EEG band, namely Hebbian and homeostatic plasticity. Many studies of both neuromodulation techniques report the aftereffects connected to the behavioral benefits. The duration of persistence of aftereffects for NFB and tACS is comparable. In relation to the factors influencing responsiveness to tACS and NFB, significantly more types of factors were analyzed in the NFB studies compared to the tACS studies. Several common factors for both tACS and NFB have been already investigated. Based on these outcomes, we propose several new research directions regarding tACS and NFB.

Working Memory and Cross-Frequency Coupling of Neuronal Oscillations.

Working memory (WM) is the active retention and processing of information over a few seconds and is considered an essential component of cognitive function. The reduced WM capacity is a common feature in many diseases, such as schizophrenia, attention deficit hyperactivity disorder (ADHD), mild cognitive impairment (MCI), and Alzheimer's disease (AD). The theta-gamma neural code is an essential component of memory representations in the multi-item WM. A large body of studies have examined the association between cross-frequency coupling (CFC) across the cerebral cortices and WM performance; electrophysiological data together with the behavioral results showed the associations between CFC and WM performance. The oscillatory entrainment (sensory, non-invasive electrical/magnetic, and invasive electrical) remains the key method to investigate the causal relationship between CFC and WM. The frequency-tuned non-invasive brain stimulation is a promising way to improve WM performance in healthy and non-healthy patients with cognitive impairment. The WM performance is sensitive to the phase and rhythm of externally applied stimulations. CFC-transcranial-alternating current stimulation (CFC-tACS) is a recent approach in neuroscience that could alter cognitive outcomes. The studies that investigated (1) the association between CFC and WM and (2) the brain stimulation protocols that enhanced WM through modulating CFC by the means of the non-invasive brain stimulation techniques have been included in this review. In principle, this review can guide the researchers to identify the most prominent form of CFC associated with WM processing (e.g., theta/gamma phase-amplitude coupling), and to define the previously published studies that manipulate endogenous CFC externally to improve WM. This in turn will pave the path for future studies aimed at investigating the CFC-tACS effect on WM. The CFC-tACS protocols need to be thoroughly studied before they can be considered as therapeutic tools in patients with WM deficits.

Naturalistic experience transforms sensory maps in the adult cortex of caged animals.

Much of what is known about the functional organization and plasticity of adult sensory cortex is derived from animals housed in standard laboratory cages. Here we report that the transfer of adult rats reared in standard laboratory cages to a naturalistic habitat modifies the functional and morphological organization of the facial whisker representation in the somatosensory 'barrel' cortex. Cortical whisker representations, visualized with repeated intrinsic signal optical imaging in the same animals, contracted by 46% after four to six weeks of exposure to the naturalistic habitat. Acute, multi-site extracellular recordings demonstrated suppressed evoked neuronal responses and smaller, sharper constituent receptive fields in the upper cortical layers (II/III), but not in the thalamic recipient layer (IV), of rats with naturalistic experience. Morphological plasticity of the layer IV barrel field was observed, but on a substantially smaller scale than the functional plasticity. Thus, transferring animals to an environment that promotes the expression of natural, innate behaviours induces a large-scale functional refinement of cortical sensory maps.

Large-scale organization of rat sensorimotor cortex based on a motif of large activation spreads.

Parcellation according to function (e.g., visual, somatosensory, auditory, motor) is considered a fundamental property of sensorimotor cortical organization, traditionally defined from cytoarchitectonics and mapping studies relying on peak evoked neuronal activity. In the adult rat, stimulation of single whiskers evokes peak activity at topographically appropriate locations within somatosensory cortex and provides an example of cortical functional specificity. Here, we show that single whisker stimulation also evokes symmetrical areas of suprathreshold and subthreshold neuronal activation that spread extensively away from peak activity, effectively ignoring cortical borders by spilling deeply into multiple cortical territories of different modalities (auditory, visual and motor), where they were blocked by localized neuronal activity blocker injections and thus ruled out as possibly caused by "volume conductance." These symmetrical activity spreads were supported by underlying border-crossing, long-range horizontal connections as confirmed with transection experiments and injections of anterograde neuronal tracer experiments. We found such large evoked activation spreads and their underlying connections regardless of whisker identity, cortical layer, or axis of recorded responses, thereby revealing a large scale nonspecific organization of sensorimotor cortex based on a motif of large symmetrical activation spreads. Because the large activation spreads and their underlying horizontal connections ignore anatomical borders between cortical modalities, sensorimotor cortex could therefore be viewed as a continuous entity rather than a collection of discrete, delineated unimodal regions, an organization that could coexist with established specificity of cortical organization and that could serve as a substrate for associative learning, direct multimodal integration and recovery of function after injury.

Czech Republic 20 years after Chernobyl accident.

The territory of the Czech Republic was contaminated as a result of the breakdown in the Chernobyl nuclear power plant in 1986. The Czech population received low doses of ionising radiation which, though it could not cause a deterministic impact, could have had stochastic effects expressed in the years following the accident. Twenty years after the accident is a long enough time to assess its stochastic effects, primarily tumours and genetic impairment. The moderate amount of radioactive fallout received by the Czech population in 1986 increased thyroid cancer in the following years; on the other hand, no obvious genetic impact was found.

Representation of species-specific vocalizations in the medial geniculate body of the guinea pig.

Individual nuclei of the auditory pathway contribute in a specific way to the processing of complex acoustical signals. We investigated the responses of single neurons to typical guinea pig vocalizations (purr, chutter, chirp and whistle) in the ventral part of the medial geniculate body (MGB) of anesthetized guinea pigs. The neuronal and population peristimulus time histograms (PSTHs) reflected the repetition frequency of individual phrases in the calls. The patterns of PSTHs correlated well with the sound temporal envelope in calls with short phrases (purr, chirp). The dominant onset character of the neuronal responses resulted in a lower correlation between the sound envelope and the PSTH pattern in the case of longer calls (chutter and whistle). A time-reversed version of whistle elicited on average a 13% weaker response than did the natural whistle. The rate-characteristic frequency (CF) profile provided only a coarse representation of the sound frequency spectrum without detailed information about the individual spectral peaks and their relative magnitudes. In comparison with the inferior colliculus (Suta et al. in J Neurophysiol 90:3794-3808, 2003), the processing of species-specific vocalizations in the MGB differs in: (1) a less precise representation of the temporal envelope in the case of longer calls, but not in the case of calls consisting of one or more short phrases; (2) a less precise rate-CF representation of the spectral envelope in the case of low-frequency calls, but not in the case of broad-band calls; (3) a smaller difference between the responses to natural and time-reversed whistle.

Representation of species-specific vocalizations in the inferior colliculus of the guinea pig.

The responses of individual neurons to 4 typical guinea pig vocalization calls (purr, chutter, chirp, and whistle) were recorded in the inferior colliculus (IC) of anesthetized guinea pigs. All calls elicited a response in about 80% of units. Unit selectivity for individual calls was low, given that a majority of neurons (55% of 124 units) responded to all vocalizations and only a small portion of neurons (3%) responded to only one call or did not respond to any of the calls (3%). In 15% of units, the response to one call was > or =25% stronger than the response to any other sound (tone, noise, and other calls); these neurons were selective for chirp or whistle, and no unit preferred chutter or purr. Neuronal activity provided information about the spectrotemporal patterns of the calls. Peristimulus time histograms (PSTHs) reflected the energy of the near-characteristic frequency band, and the population PSTH reliably matched the sound envelope for calls characterized by one or more short impulses (chirp, purr, and chutter) but did not exactly fit the envelope for whistle--a slow-modulated and relatively long call. Calculations based on firing rates indicated the approximate positions of the main spectral peaks but did not always reflect their relative magnitude. The time-reversed version of whistle elicited on average a weaker response than did the natural whistle (by 24%), but there were neurons with a significantly stronger response to the natural ("forward-selective," 30%) as well as to the time-reversed whistle ("reverse-selective," 15%). This study does not prove the existence of units selectively responding to animal calls, but it provides evidence for the encoding of the spectrotemporal acoustic patterns of vocalizations by IC units.