Physical activity and the brain myelin content in humans.

New imaging sequences and biophysical models allow adopting magnetic resonance imaging (MRI) for in vivo myelin mapping in humans. Understanding myelination and remyelination processes in the brain is fundamental from the perspective of proper design of physical exercise and rehabilitation schemes that aim to slow down demyelination in the aging population and to induce remyelination in patients with neurodegenerative diseases. Therefore, in this review we strive to provide a state-of-the art summary of the existing MRI studies in humans focused on the effects of physical activity on myelination/remyelination. We present and discuss four cross-sectional and four longitudinal studies and one case report. Physical activity and an active lifestyle have a beneficial effect on the myelin content in humans. Myelin expansion can be induced in humans throughout the entire lifespan by intensive aerobic exercise. Additional research is needed to determine (1) what exercise intensity (and cognitive novelty, which is embedded in the exercise scheme) is the most beneficial for patients with neurodegenerative diseases, (2) the relationship between cardiorespiratory fitness and myelination, and (3) how exercise-induced myelination affect cognitive abilities.

Cognitive Functions in Scuba, Technical and Saturation Diving.

Scuba diving as a recreational activity is becoming increasingly popular. However, the safety of this activity, especially in the out-of-comfort zone, has been discussed worldwide. The latest publications bring conclusions regarding negative effects on cognitive functions. We compare the acute and chronic effects of diving on cognitive functioning depending on the type of dive performed, including recreational, technical and saturation diving. However, the results of research show that acute and chronic effects on cognitive functions can be negative. While acute effects are reversible after the ascent, chronic effects include white matter lesions in magnetic resonance imaging scans. We believe that more investigations should be performed to determine the chronic effects that could be observed after a few months of observations in a group of regular, intense divers. In addition, publications referring to technical divers are very limited, which is disquieting, as this particular group of divers seems to be neglected in research concerning the effects of diving on cognitive functions.

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Mild poikilocapnic hypoxia increases very low frequency haemoglobin oxygenation oscillations in prefrontal cortex.

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.

Critical Flicker Fusion Frequency: A Narrative Review.

This review presents the current knowledge of the usage of critical flicker fusion frequency (CFF) in human and animal model studies. CFF has a wide application in different fields, especially as an indicator of cortical arousal and visual processing. In medicine, CFF may be helpful for diagnostic purposes, for example in epilepsy or minimal hepatic encephalopathy. Given the environmental studies and a limited number of other methods, it is applicable in diving and hyperbaric medicine. Current research also shows the relationship between CFF and other electrophysiological methods, such as electroencephalography. The human eye can detect flicker at 50-90 Hz but reports are showing the possibility to distinguish between steady and modulated light up to 500 Hz. Future research with the use of CFF is needed to better understand its utility and application.

Neuroplasticity and Multilevel System of Connections Determine the Integrative Role of Nucleus Accumbens in the Brain Reward System.

A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.

Coupling between Blood Pressure and Subarachnoid Space Width Oscillations during Slow Breathing.

The precise mechanisms connecting the cardiovascular system and the cerebrospinal fluid (CSF) are not well understood in detail. This paper investigates the couplings between the cardiac and respiratory components, as extracted from blood pressure (BP) signals and oscillations of the subarachnoid space width (SAS), collected during slow ventilation and ventilation against inspiration resistance. The experiment was performed on a group of 20 healthy volunteers (12 females and 8 males; BMI=22.1±3.2 kg/m2; age 25.3±7.9 years). We analysed the recorded signals with a wavelet transform. For the first time, a method based on dynamical Bayesian inference was used to detect the effective phase connectivity and the underlying coupling functions between the SAS and BP signals. There are several new findings. Slow breathing with or without resistance increases the strength of the coupling between the respiratory and cardiac components of both measured signals. We also observed increases in the strength of the coupling between the respiratory component of the BP and the cardiac component of the SAS and vice versa. Slow breathing synchronises the SAS oscillations, between the brain hemispheres. It also diminishes the similarity of the coupling between all analysed pairs of oscillators, while inspiratory resistance partially reverses this phenomenon. BP-SAS and SAS-BP interactions may reflect changes in the overall biomechanical characteristics of the brain.

Mild poikilocapnic hypoxia increases very low frequency haemoglobin oxygenation oscillations in prefrontal cortex

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.

Comparison of near infrared spectroscopy (NIRS) and near-infrared transillumination-backscattering sounding (NIR-T/BSS) methods.

The aim of the study was to compare simultaneously recorded a NIR-T/BSS and NIRS signals from healthy volunteers. NIR-T/BSS is a device which give an ability to non-invasively detect and monitor changes in the subarachnoid space width (SAS). Experiments were performed on a group of 30 healthy volunteers (28 males and 2 females, age 30.8 ± 13.4 years, BMI = 24.5 ± 2.3 kg/m2). We analysed recorded signals using analysis methods based on wavelet transform (WT) for the wide frequency range from 0.0095 to 2 Hz. Despite the fact that both devices use a similar radiation source both signals are distinct from each other. We found statistically significant differences for WT amplitude spectra between both signals. Additionally, we showed different relationships of both signals to blood pressure. Collectively, based on the present findings and those of previous studies, we can conclude that the combination of NIR-T/BSS or NIRS signals and time-frequency analysis opens new frontiers in science, and give possibility to understand and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

Inertial Sensors as a Tool for Diagnosing Discopathy Lumbosacral Pathologic Gait: A Preliminary Research.

BACKGROUND: the goal of the study is to ascertain the influence of discopathy in the lumbosacral (L-S) segment on the gait parameters. The inertial sensors are used to determine the pathologic parameters of gait. METHODS: the study involved four patients (44, 46, 42, and 38 years). First, the goal of the survey was to analyze by a noninvasive medical test magnetic resonance imaging (MRI) of each patient. Next, by using inertial sensors, the flexion-extension of joint angles of the left and right knees were calculated. The statistical analysis was performed. The wavelet transform was applied to analyze periodic information in the acceleration data. RESULTS: in the patients with discopathy, the amount of knee flexion attained during stance phase is significantly lower than that of normal (health side), which could indicate poor eccentric control or a pain avoidance mechanism. The biggest differences are observed in the Initial Swing phase. Bending of the lower limb in the knee joint at this stage reaches maximum values during the entire gait cycle. CONCLUSIONS: It has been difficult to quantify the knee angle during gait by visual inspection. The inertial measurement unit (IMU) system can be useful in determining the level of spine damage and its degree. In patients in the first stages of the intervertebral disc disease who may undergo conservative treatment, it may also partially delay or completely exclude the decision to perform a complicated imaging examination which is MRI, often showing a false positive result in this phase of the disease.

Neurovascular Unit as a Source of Ischemic Stroke Biomarkers-Limitations of Experimental Studies and Perspectives for Clinical Application.

Cerebral stroke, which is one of the most frequent causes of mortality and leading cause of disability in developed countries, often leads to devastating and irreversible brain damage. Neurological and neuroradiological diagnosis of stroke, especially in its acute phase, is frequently uncertain or inconclusive. This results in difficulties in identification of patients with poor prognosis or being at high risk for complications. It also makes difficult identification of these stroke patients who could benefit from more aggressive therapies. In contrary to the cardiovascular disease, no single biomarker is available for the ischemic stroke, addressing the abovementioned issues. This justifies the need for identifying of effective diagnostic measures characterized by high specificity and sensitivity. One of the promising avenues in this area is studies on the panels of biomarkers characteristic for processes which occur in different types and phases of ischemic stroke and represent all morphological constituents of the brains' neurovascular unit (NVU). In this review, we present the current state of knowledge concerning already-used or potentially applicable biomarkers of the ischemic stroke. We also discuss the perspectives for identification of biomarkers representative for different types and phases of the ischemic stroke, as well as for different constituents of NVU, which concentration levels correlate with extent of brain damage and patients' neurological status. Finally, a critical analysis of perspectives on further improvement of the ischemic stroke diagnosis is presented.

Coupling of Blood Pressure and Subarachnoid Space Oscillations at Cardiac Frequency Evoked by Handgrip and Cold Tests: A Bispectral Analysis.

The aim of the study was to assess blood pressure-subarachnoid space (BP-SAS) width coupling properties using time-frequency bispectral analysis based on wavelet transforms during handgrip and cold tests. The experiments were performed on a group of 16 healthy subjects (F/M; 7/9) of the mean age 27.2 ± 6.8 years and body mass index of 23.8 ± 4.1 kg/m2. The sequence of challenges was first handgrip and then cold test. The handgrip challenge consisted of a 2-min strain, indicated by oral communication from the investigator, at 30% of maximum strength. The cold test consisted of 2 min of hand immersion to approximately wrist level in cold water of 4 °C, verified by a digital thermometer. Each test was preceded by 10 min at baseline and was followed by 10-min recovery recordings. BP and SAS were recorded simultaneously. Three 2-min stages of the procedure, baseline, test, and recovery, were analyzed. We found that BP-SAS coupling was present only at cardiac frequency, while at respiratory frequency both oscillators were uncoupled. Handgrip and cold test failed to affect BP-SAS cardiac-respiratory coupling. We showed similar handgrip and cold test cardiac bispectral coupling for individual subjects. Further studies are required to establish whether the observed intersubject variability concerning the BP-SAS coupling at cardiac frequency has any potential clinical predictive value.

Oscillations of Subarachnoid Space Width as a Potential Marker of Cerebrospinal Fluid Pulsatility.

In the cerebrospinal fluid (CSF) circulation, two components can be distinguished: bulk flow (circulation) and pulsatile flow (back and forth motion). CSF pulsatile flow is generated by both cardiac and respiratory cycles. Recent years have seen increased interest in cardiac- and respiratory-driven CSF pulsatility as an important component of cerebral homeostasis. CSF pulsatility is affected by cerebral arterial inflow and jugular outflow and potentially linked to white matter abnormalities in various diseases, such as multiple sclerosis or hypertension. In this review, we discuss the physiological mechanisms associated with CSF pulsation and its clinical significance. Finally, we explain the concept of using the oscillations of subarachnoid space width as a surrogate for CSF pulsatility.

Nicotine-induced CREB and DeltaFosB activity is modified by caffeine in the brain reward system of the rat.

Coffee and nicotine consumption are frequently combined, indicating possible intensifying effect of caffeine on smoking behavior, although neurobiological background of this phenomenon remains unknown. We aimed at determining the effect of caffeine and nicotine, applied separately or simultaneously, on activation of six structures of the brain reward system: nucleus accumbens (NAc), ventral tegmental area (VTA), amygdala (Amg), hippocampus (Hip), medial prefrontal cortex (mPfr) and dorsal striatum (CdP) in the adult male Wistar rats. Activation of two transcription factors, the phosphorylated form of cyclic AMP-response element binding protein (pCREB) and DeltaFosB (ΔFosB) was assessed by immunohistochemistry after multiple-dose five-days psychostimulants administration followed by 20min and 24h survival, respectively. Nicotine evoked the highest increase of pCREB-immunoreactivity (-ir) in NAc, while caffeine exerted the weakest effect in mPfr and CdP. Nicotine/caffeine co-administration resulted in decrease of pCREB-ir in NAc and increase in Amg, compared with the effect of each psychostimulant used separately. Nicotine was the strongest psychostimulant activating ΔFosB-ir in Amg, whereas caffeine - in Hip. Nicotine/caffeine-exerted effect upon ΔFosB-ir in Amg was weaker, whereas in mPfr stronger, than nicotine-evoked effect in these structures. In summary, pCREB and ΔFosB activation is dependent on the type of stimulus, brain structure and functional context. Activation of both transcription factors is responsible for caffeine's modifying effect upon nicotine-related behaviors and must be taken into account while quitting cigarette smoking.

BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity.

Brain-derived neurotrophic factor (BDNF) is one of the most widely distributed and extensively studied neurotrophins in the mammalian brain. Among its prominent functions, one can mention control of neuronal and glial development, neuroprotection, and modulation of both short- and long-lasting synaptic interactions, which are critical for cognition and memory. A wide spectrum of processes are controlled by BDNF, and the sometimes contradictory effects of its action can be explained based on its specific pattern of synthesis, comprising several intermediate biologically active isoforms that bind to different types of receptor, triggering several signaling pathways. The functions of BDNF must be discussed in close relation to the stage of brain development, the different cellular components of nervous tissue, as well as the molecular mechanisms of signal transduction activated under physiological and pathological conditions. In this review, we briefly summarize the current state of knowledge regarding the impact of BDNF on regulation of neurophysiological processes. The importance of BDNF for future studies aimed at disclosing mechanisms of activation of signaling pathways, neuro- and gliogenesis, as well as synaptic plasticity is highlighted.

Transcription factor Pax6 is expressed by astroglia after transient brain ischemia in the rat model.

Reactive astrogliosis is regarded as an universal astrocytic response to different kinds of lesions, concerned with glial fibrillary acidic protein (GFAP) up-regulation, cellular hypertrophy and proliferation. The origin of reactive and proliferating cells in the adult brain is still disputable. Persistent progenitors as well as de-differentiating adult cells of various glial lineages are regarded as possible candidates. Pax6 transcription factor is one of the characteristic markers of astroglial de-differentiation, also important for regulation of neural and glial proliferation. Various kinds of pathological stimuli evoke reactive response, differentiated in its morphological, biochemical and immunological character. The aim of this study was to assess the dynamics of astroglial morphological and proliferative response to ischemic injury. One-hour transient focal cerebral ischemia was applied to evoke the reactive astrogliosis in twenty five adult male Wistar rats. The astrocytic morphological and proliferative reactions to ischemia were studied in the period of 6 weeks by means of GFAP and Pax6 immunofluorescent staining. A strong reactive astroglial response was observed in the cerebral cortex and striatum, manifested by GFAP and Pax6 up-regulation and astrocytic hypertrophy. Apparent morphological changes appeared within 24 hrs after ischemia. The GFAP/Pax6 colocalization was numerous and observed 24 hrs after ischemia. A characteristic spatial distribution of GFAP/Pax6 double-labelled astrocytes and Pax6 single-labelled nuclei was revealed, with the latter situated more distantly from the ischemic core. The maximal intensity of astrocytic reaction was present from the first post-ischemic week. Astroglial hypertrophic changes and proliferative reaction were more intense in the striatum than in the cerebral cortex. Our observations reveal intensive astroglial de-differentiation and proliferative response, reflected by dynamic Pax6 up-regulation within GFAP-immunoreactive astrocytes. Transient cerebral ischemia evokes strong reactive astrogliosis, which is apparently differentiated in respect to the post-ischemic period and particular brain structure.

The astrocytic contribution to neurovascular coupling--still more questions than answers?

Cerebral blood flow adequate for brain activity and metabolic demand is maintained through the processes of autoregulation and neurovascular coupling. Astrocytes undoubtedly make an important contribution to these processes. The critical factors that determine the polarity of astrocytic response include: metabolites (e.g., arachidonic acid and its derivatives, lactate and oxygen concentrations), ions (H(+), Ca(2+) and K(+)), gliotransmitters (glutamate, Glu; gamma-aminobutyric acid, GABA; d-serine; adenosine 5'-triphosphate, ATP and brain derived neurotrophic factor, BDNF), neuronal activity and vascular tone. Although the astrocytic contribution to neurovascular coupling has been intensively studied, a few important questions still remain, such as: (1) the modulatory function of astrocytes in tripartite synapses, including effects related to the strength of synaptic stimulation and the particular signaling pathway (astrocytic or neuronal) that becomes activated, (2) the significance of the vasoconstrictive reaction evoked by arachidonic acid metabolites (e.g., 20-hydroxyeicosatetraenoic acid, 20-HETE) under both physiological and pathological conditions, (3) the relationship between brain activity level and metabolic processes occurring in astrocytes, which is studied using neuroradiological techniques and (4) the astrocytic contribution to the neurovascular response under pathological conditions. Hence, the function of astrocytes in neurovascular coupling remains ambiguous. The function of astrocytes is beneficial and integrative in physiological conditions, but under definitive pathological conditions may become detrimental and involved in the development of diseases like ischemic stroke, arterial hypertension and Alzheimer's disease.