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Postoperative sleep disorders, particularly the REM sleep disorder, may have a significant deleterious impact on postoperative outcomes and may contribute to the genesis of certain delayed postoperative complications. We have followed the effect of distinct anesthesia regimens (ketamine/diazepam vs. pentobarbital) over 6days following the induction of a stable anesthetized state in adult male Wistar rats, chronically instrumented for sleep recording. In order to compare the effect of both anesthetics in the physiological controls vs. the rats with impaired pedunculopontine tegmental nucleus (PPT) cholinergic innervation, during the operative procedure for the implantation of EEG and EMG electrodes, the bilateral PPT lesion was conducted using ibotenic acid (IBO). We have followed in particular post-anesthesia REM sleep. Our results show the distinct EEG microstructure of the motor cortex during the different stable anesthetized states, and their distinct impact on post-anesthesia REM sleep. In contrast to pentobarbital anesthesia, the ketamine/diazepam anesthesia potentiated the long-lasting post-anesthesia REM statewith higher muscle tone (REM1) vs. REM state with atonia (REM2). Whereas both anesthesias prolonged the post-anesthesia REM sleep duration, the long-term prolongation of the REM1 state was demonstrated only after the ketamine/diazepam anesthesia, first due to the increased number of REM1 episodes, and then due to the prolonged REM1 episodes duration. On the other hand, whereas both anesthetic regimens abolished the prolonged post-anesthesia REM/REM1 sleep and the EEG microstructure disorder during REM sleep, only the pentobarbital abolished the increased NREM/REM/NREM transitions, caused by the PPT lesion. In addition, in the PPT lesioned rats, the ketamine/diazepam anesthesia decreased the Wake/NREM/Wake transitions while the pentobarbital anesthesia decreased the Wake/REM/Wake transitions. Our present study suggests pentobarbital anesthesia as being highly beneficial for post-anesthesia REM sleep in the physiological condition as well as during PPT cholinergic neuropathology.

We studied the impact of aging during sleep in the rat models of Alzheimer's (AD) and Parkinson's (PD) disease cholinergic neuropathology to determine the possible different and earlier onset of age-related sleep disorder during the neurodegenerative diseases vs. healthy aging. We used the bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesioned rats as the in vivo models of functionally distinct cholinergic neuropathology, and we followed the impact of aging on sleep architecture, the electroencephalographic (EEG) microstructure and motor control across sleep/wake states. Our results have shown for the first time that the earliest signs of aging during distinct cholinergic neuropathology were expressed through a different and topographically specific EEG microstructure during rapid eye movement sleep (REM). EEG delta amplitude attenuation within the sensorimotor cortex (SMCx) during REM was the earliest sign of aging in the NB lesion. EEG sigma amplitude augmentation within the motor cortex (MCx) during REM was the earliest sign of aging in the PPT lesion. In addition, aging was differently expressed through the SMCx drive alterations, but it was commonly expressed through the MCx drive alterations during all sleep/wake states. Our study provided evidence of distinct REM sleep disorders and sleep state related cortical drives as the signs of aging onset during functionally distinct cholinergic neuropathologies (NB lesion vs. PPT lesion). (C) 2015 Elsevier B.V. All rights reserved. Serbian Ministry of Education, Science and Technological Development {[}OI 173022]

A number of measures, stemming from nonlinear dynamics, exist to estimate complexity of biomedical objects. In most cases they are appropriate, but sometimes unconventional measures, more suited for specific objects, are needed to perform the task. In our present work, we propose three new complexity measures to quantify complexity of topographic closed loops of alpha carrier frequency phase potentials (CFPP) of healthy humans in wake and drowsy states. EEG of ten adult individuals was recorded in both states, using a 14-channel montage. For each subject and each state, a topographic loop (circular directed graph) was constructed according to CFPP values. Circular complexity measure was obtained by summing angles which directed graph edges (arrows) form with the topographic center. Longitudinal complexity was defined as the sum of all arrow lengths, while intersecting complexity was introduced by counting the number of intersections of graph edges. Wilcoxon's signed-ranks test was used on the sets of these three measures, as well as on fractal dimension values of some loop properties, to test differences between loops obtained in wake vs. drowsy. While fractal dimension values were not significantly different, longitudinal and intersecting complexities, as well as anticlockwise circularity, were significantly increased in drowsy. Graphical abstract An example of closed topographic carrier frequency phase potential (CFPP) loops, recorded in one of the subjects in the wake (A) and drowsy (C) states. Lengths of loop graph edges, r(c

We followed the impact of healthy aging on cortical drive during sleep in rats by using the corticomuscular coherence (CMC). We employed the chronic electrodes implantation for sleep recording in adult, male Wistar rats, and followed the aging impact during sleep from 3 to 5.5 months age. We have analyzed the sleep/wake states architecture, and the sleep/wake state related EEG microstructure and CMCs. We evidenced the topographically distinct impact of aging on sleep/wake states architecture within the sensorimotor (SMCx) vs. motor cortex (MCx) from 4.5 to 5.5 months age. Healthy aging consistently altered only the SMCx sleep/wake states architecture, and increased the delta and beta CMCs through both cortical drives during Wake, but only through the MCx drive during REM. According to the delta and beta CMCs values, aging impact through the SMCx drive was opposite, but it was convergent through the MCx drive during Wake vs. REM, and there was a dual and inverse mode for the motor control during REM. (C) 2015 Elsevier Ireland Ltd. All rights reserved. Serbian Ministry of Education, Science and Technological Development Grant {[}OI 173022]

Our aim was to model the dependence of respiratory sinus arrhythmia (RSA) on the respiratory waveform and to elucidate underlying mechanisms of cardiorespiratory coupling. In 30 subjects, RR interval and respiratory signal were recorded during spontaneous and paced (0.1 Hz/0.15 Hz) breathing and their relationship was modeled by a first order linear differential equation. This model has two parameters: a0 (related to the instantaneous degree of abdominal expansion) and a1 (referring to the speed of abdominal expansion). Assuming that a0 represents slowly adapting pulmonary stretch receptors (SARs) and a1 SARs in coordination with other stretch receptors and central integrative coupling; then pulmonary stretch receptors relaying the instantaneous lung volume are the major factor determining cardiovagal output during inspiration. The models results depended on breathing frequency with the least error occurring during slow paced breathing. The role of vagal afferent neurons in cardiorespiratory coupling may relate to neurocardiovascular diseases in which weakened coupling among venous return, arterial pressure, heart rate and respiration produces cardiovagal instability. (C) 2014 Elsevier B.V. All rights reserved.

Background Recently we proposed a new method called generalized Poincare´ plot (gPp) analysis which gave a new insight into the pattern of neurocaridac control. In this study we examined potential of gPp method to reveal changes in cardiac neural control in young athletes during three conditions: supine rest, running and relaxation, with respect to untrained subjects. Methods This method is based on the quantification of Pearson's correlation coefficients r(j, k), between symmetrical (j = k) and asymmetrical summed j previous and k following RR intervals up to the 100th order (j,k.100). Results Differences between groups were obtained at all levels of this analysis. The main result is the significant difference of NAI, normalized index of asymmetry, between groups in running, which was originated in different positions of local maxima of r(j, k). Compared with untrained subjects, these findings indicate modified neural control and altered intrinsic heart rate behavior in athletes which are related to some kind of memory mechanism between RR intervals. Conclusion Obtained results provide great potential of gPp method analysis in the recognition of changes in neurocardiac control in healthy subjects. Further studies are needed for identification of altered cardiac regulatory mechanisms whose background may be useful in the evaluation of genesis of athletes neurocardiovascular pathology. © 2019 Platiša et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

We have investigated the effects of changing the coil-to-skull distance on the motor-evoked responses (MEP) induced with two different magnetic stimulator coils (80 mm round and figure-of-eight coil) at rest and during voluntary muscle contraction. The changes in MEP latency, amplitude and silent period (SP) duration induced by stimulation directly upon the skull, and 1 cm away from the skull were analyzed by computing the probability density distribution (PDD) for the responses obtained from all subjects. This measure corresponds to the finite probability that the event occurs within a given area. Overall, the results were consistent with a distance-induced decrease in magnetic field strength. However, the increase in coil-to-skull distance induced a higher probability of longer latencies in active muscle when stimulating with either coil. Also, stimulating at a distance with the figure-of-eight coil increased the probability of a longer SP duration. The stimulation strength at the two distances was comparable because it was set based on the motor threshold obtained for each distance. Therefore, our results are not entirely compatible with the established exponential drop in magnetic field with increasing distance. Rather, they suggest that a more complex set of interactions occurs in the cortex. The results imply that distinct patterns of cortical network activation may exist related to the distance-induced alterations when the coil is moved away from the skull. Further studies are required to elucidate the precise nature of the distance-related interactions of the magnetic field with the cortex.

We applied a novel approach to respiratory waveform analysis-Monotone Signal Segments Analysis (MSSA) on 6-h recordings of respiratory signals in rats. To validate MSSA as a respiratory signal analysis tool we tested it by detecting: breaths and breath-to-breath intervals; respiratory timing and volume modes; and changes in respiratory pattern caused by lesions of monoaminergic systems in rats. MSSA differentiated three respiratory timing (tachypneic, eupneic, bradypneic-apneic), and three volume (artifacts, normovolemic, hypervolemic-sighs) modes. Lesion-induced respiratory pattern modulation was visible as shifts in the distributions of monotone signal segment amplitudes, and of breath-to-breath intervals. Specifically, noradrenergic lesion induced an increase in mean volume (p ≤ 0.03), with no change of the mean breath-to-breath interval duration (p ≥ 0.06). MSSA of timing modes detected noradrenergic lesion-induced interdependent changes in the balance of eupneic (decrease; p ≤ 0.02), and tachypneic (an increase; p ≤ 0.02) breath intervals with respect to control. In terms of breath durations within each timing mode, there was a tendency toward prolongation of the eupneic (p ≤ 0.08) and bradypneic-apneic (p ≤ 0.06) intervals. These results demonstrate that MSSA is sensitive to subtle shifts in respiratory rhythmogenesis not detectable by simple respiratory pattern descriptive statistics. MSSA represents a potentially valuable new tool for investigations of respiratory pattern control. © 2008 Elsevier B.V. All rights reserved. This is accepted peer-reviewed version of the article: Bojic, T., Saponjic, J., Radulovacki, M., Carley, D. W., & Kalauzi, A. (2008). Monotone Signal Segments Analysis as a novel method of breath detection and breath-to-breath interval analysis in rat. Respiratory physiology & neurobiology, 161(3), 273-280. [http://dx.doi.org/10.1016/j.resp.2008.03.001] Published version: [https://vinar.vin.bg.ac.rs/handle/123456789/8871]

Objectives: We hypothesized that the impact of distinct anesthetic regimens could be differently expressed during anesthesia and on post-anesthesia sleep in the neurodegenerative diseases. Therefore, we followed the impact of ketamine/diazepam and pentobarbital anesthesia in a rat model of the severe Parkinson's disease cholinergic neuropathology on the electroencephalographic (EEG) microstructure and respiratory pattern during anesthesia, and on the post-anesthesia sleep. Methods: We performed the experiments on adult, male, spontaneously breathing Wistar rats chronically instrumented for sleep recording. The bilateral pedunculopontine tegmental nucleus (PPT) lesion was done by ibotenic acid microinfusion. Following postoperative recovery, we recorded sleep for 6 h, induced anesthesia 24 h later using ketamine/diazepam or pentobarbital, and repeated sleep recordings sessions 48 h and 6 days later. During 20 min of each anesthesia we recorded both the EEG and respiratory movements. For sleep and EEG analysis, Fourier analysis was applied on 6-h recordings, and each 10-s epoch was differentiated as a state of wakefulness (Wake), non-rapid eye movement (NREM) or rapid eye movement (REM). Additionally, the group probability density distributions of all EEG frequency band relative amplitudes were calculated for each state, with particular attention during anesthesia. For respiratory pattern analysis we used Monotone Signal Segments Analysis. The PPT lesion was identified through nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry. Results and conclusions: Our data show that the ketamine/diazepam anesthetic regimen in the PPT-lesioned rats induces more alterations in the EEG microstructure and respiratory pattern than does the pentobarbital anesthesia. In addition, the equal time required to establish an anesthetized state, and the long-term effect on postanesthesia sleep in the PPT-lesioned vs. control rats suggest this anesthetic regimen as potentially more beneficial both for anesthesia induction and for post-anesthesia sleep in the surgical procedures of the elderly, and Parkinson's, and Alzheimer's patients. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. Serbian Ministry of Education, Science and Technological Development Grant {[}OI 173022]

Organization of resting state cortical networks is of fundamental importance for the phenomenon of awareness, which is altered in the first part of hypnagogic period (Hori stages 1-4). Our aim was to investigate the change in brain topography pattern of EEG alpha attractor correlation dimension (CD) in the period of transition from Hori stage 1 to 4. EEG of ten healthy adult individuals was recorded in the wake and drowsy states, using a 14 channel average reference montage, from which 91 bipolar channels were derived and filtered in the wider alpha (6-14 Hz) range. Sixty 1 s long epochs of each state and individual were subjected to CD calculation according to the Grassberger-Procaccia method. For such a collection of signals, two embedding dimensions, d = {5,10}, and 22 time delays 7 = 2-23 samples were explored. Optimal values were d = 10 and 7 = 18, where both saturation and second zero crossing of the autocorrelation function occurred. Bipolar channel CD underwent a significant decrease during the transition and showed a positive linear correlation with electrode distance, stronger in the wake individuals. Topographic distribution of bipolar channels with above median CD changed from longitudinal anterior-posterior pattern (awake) to a more diagonal pattern, with localization in posterior regions (drowsiness). Our data are in line with the literature reporting functional segregation of neuronal assemblies in anterior and posterior regions during this transition. Our results should contribute to understanding of complex reorganization of the cortical part of alpha generators during the wake/drowsy transition. (C) 2014 Elsevier B.V. All rights reserved.

We examined the effects of gender and age in young and middle-aged subjects on the level of cardiorespiratory interaction by analyzing properties of cardiac, respiratory and cardiac-respiratory regulatory mechanisms under paced breathing. In 56 healthy subjects, ECG (RR interval) and respiratory signal were simultaneously acquired in supine position at paced (0.1-0.45 Hz, steps of 0.05 Hz) and spontaneous breathing. The participants were divided into gender matched group of young adults (19-25 years old) and middle-aged adults (35-44 years old). Power spectral analysis was applied on RR interval time series and spectral components in very low frequency (VLF), low frequency (LF) and high frequency (HF) ranges were computed. We also calculated Sample entropy of RR interval series (SampEnRR), respiratory series (SampEnResp), and their cross-sample entropy (cross-SampEn). Under paced breathing, reduction of all spectral powers with age (p LT 0.05) is not gender dependent but reduction of some entropy measures is; SampEnRR and SampEnResp were lower only in men (p LT 0.05). In the middle-aged subjects, effect of gender on spectral measures is significant; males had lower HF (p LT 0.05). Pattern of dependencies of SampEn and cross-SampEn on paced breathing frequency were significantly different in men (young vs. middle-aged, p = 0.001 and p = 0.037) and in middle-aged subjects (females vs. males, p = 0.011 and p = 0.008). In middle-aged males, lower entropy measures indicated reduced and less complex partial cardiac and respiratory control, and central cardio-respiratory control. In conclusion, in healthy middle-aged subjects changes in cardio-respiratory coupling are detectable only in males. (C) 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

A non-invasive bioimpedance spectroscopy (BIS) and Cole-Cole impedance model parameters (R0, R∞, τ and α) were used to analyze electrical properties of intact and stripped human skin for both gender subjects divided into younger and older age groups. R0, R∞ and τ significantly increased while α significantly decreased with age in stripped skin for both genders (p

In order to identify the differences for the onset and progression of functionally distinct cholinergic innervation disorders, we investigated the effect of bilateral nucleus basalis (NB) and pedunculopontine tegmental nucleus (PPT) lesions on sleep/wake states and electroencephalographic (EEG) microstructure in rats, chronically implanted for sleep recording. Bilateral NB lesion transiently altered Wake/NREM duration within the sensorimotor cortex, and Wake/REM duration within the motor cortex, while there was no change in the sleep/wake states distributions following the bilateral PPT lesion. Bilateral PPT lesion sustainably increased the Wake/REM and REM/Wake transitions followed by inconsistent dysregulation of the NREM/REM and REM/NREM transitions in sensorimotor cortex, but oppositely by their increment throughout four weeks in motor cortex. Bilateral NB lesion sustainably decreased the NREM/REM and REM/NREM transitions during four weeks in the sensorimotor cortex, but oppositely increased them in the motor cortex. We have shown that the sustained beta and gamma augmentation within the sensorimotor and motor cortex, and across all sleep/wake states, simultaneously with Wake delta amplitude attenuation only within the sensorimotor cortex, were the underlying EEG microstructure for the sleep/wake states-transitions structure disturbance following bilateral PPT lesion. In contrast, the bilateral NB lesion only augmented REM theta in sensorimotor cortex during three weeks. We have shown that the NB and PPT lesions induced differing, structure-related EEG microstructure and transition structure disturbances particularly expressed in motor cortex during NREM and REM sleep. We evidenced for the first time the different topographical expression of the functionally distinct cholinergic neuronal innervation impairment in rat. (C) 2013 Elsevier B.V. All rights reserved. Serbian Ministry of Education, Science and Technological Development [OI 173022]

The pedunculopontine tegmental nucleus (PPT) represents a major aggregation of cholinergic neurons in the mammalian brainstem, which is important in the generation and maintenance of REM sleep. We investigated the effects of unilateral and bilateral PPT lesions on sleep and all the conventional sleep-state related EEG frequency bands amplitudes, in an attempt to find the EEG markers for the onset and progression of PPT cholinergic neuronal degeneration. The experiments were performed on 35 adult male Wistar rats, chronically implanted for sleep recording. During the surgical procedure for EEG and EMG electrodes implantation, the unilateral or bilateral PPT lesion was produced under ketamine/diazepam anesthesia, by the stereotaxically guided microinfusion of 100 nl 0.1M ibotenic acid (IBO) into PPT. We applied Fourier analysis to signals acquired throughout 6h of recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We also calculated the group probability density estimates (PDE) of all Wake, NREM and REM conventional EEG frequency amplitudes, and the number of all the transition states using MATLAB 6.5. Our results show that the unilateral or bilateral PPT lesions did not change the sleep/wake architecture, but did change the sleep/wake state transitions structure and the sleep/state related "EEG microstructure". Unilateral or bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions from 14 to 35 days after lesions. This was followed by decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion. The unilateral PPT lesion augmented both Wake theta and REM beta while it also attenuated the relative amplitude of the Wake delta frequency, with a delay of one week. Following a bilateral PPT lesion there was augmentation of the relative amplitude of the Wake, NREM, and REM beta and REM gamma frequency which occurred simultaneously to NREM and Wake delta attenuation. We have shown that the PPT cholinergic neuronal loss sustainably increased the number of the Wake/REM and REM/Wake transitions and augmented sleep-states related cortical activation that was simultaneously expressed by the high frequency amplitude augmentation, as well as Wake and NREM delta frequency attenuation.

University of Belgrade, Department of Neurobiology, Institute for Biological Research-Sinisa Stankovic, 11060, Belgrade, Serbia Abstract. Thisstudywasaimedtoexplorethesleep/wakestatesrelatedcortico-pontinethetacarrierfrequency phase shiftfollowingasystemicallyinducedchemicalaxotomyofthemonoaminergicafferentswithinabrainofthefreelymovingrats.Ourexperimentswereperformedin14adult,male Sprague Dawley rats, chronically implanted for sleep recording. We recorded sleep during baseline condition, following sham injection (saline i.p. 1 ml/kg), and every week for 5 weeks fol-lowing injection of the systemic neurotoxins (DSP-4 or PCA; 1 ml/kg, i.p.) for chemical axotomy of the locus coeruleus (LC) and dorsal raphe (DR) axon terminals. Aftersleep/wakestatesiden-tification, FFT analysis was performed on 5s epochs. Theta carrier frequency phase shift (∆Φ)was calculated for each epoch by averaging theta Fourier component phase shifts, and the ∆Φvalues were plotted for each rat in control condition and 28 days following the monoaminergic lesions, as a time for permanently established DR or LC chemical axotomy. Calculated group averages have shown that ∆Φ increased between pons and cortex significantlyinallsleep/wakestates (Wake, NREM and REM) following the monoaminergic lesions, with respect to controls. Monoaminergic lesions established the pontine leading role in the brain theta oscillations during all sleep/wake states.Key words: Monoaminergic lesion — Sleep/wake states — Theta carrier frequency phase shift— Locus coeruleus — Nucleus dorsalis raphe IntroductionNeuronal network oscillations in the brain functions, and neuronal synchrony within the same network or between interrelated networks, have been extensively investigated on different oscillation bands (Singer 1993). However, theexact mechanisms of brain oscillations and synchroniza-tion of neuronal activity within single or between differentbrain structures are not well understood (Penttonen and Buzsaki 2003). The hippocampal theta rhythm is the most studiedrhythm in rat. Theta oscillations occur across many brain

Phases of alpha oscillations recorded by EEG were typically studied in the context of event or task related experiments, rarely during spontaneous alpha activity and in different brain states. During wake-to-drowsy transition they change unevenly, depending on the brain region. To explore their dynamics, we recorded ten adult healthy individuals in these two states. Alpha waves were treated as stable frequency and variable amplitude signals with one carrier frequency (CF). A method for calculating their CF phase shifts (CFPS) and CF phase potentials (CFPP) was developed and verified on surrogate signals as more accurate than phase shifts of Fourier components. Probability density estimate (PDE) of CFPS, CFPP and CF phase locking showed that frontal and fronto-temporal areas of the cortex underwent more extensive changes than posterior regions. The greatest differences were found between pairs of channels involving F7, F8, F3 and F4 (PDE of CFPS); F7, F8. T3 and 14 (CFPP); F7, F8, F3, F4, C3, C4 and T3 (decrease in CF phase locking). A topographic distribution of channels with above the average phase locking in the wake state revealed two separate regions occupying anterior and posterior brain areas (with intra regional and inter hemispheric connections). These regions merged and became mutually phase locked longitudinally in the drowsy state. Changes occurring primarily in the frontal and fronto-temporal regions correlated with an early decrease of alertness. Areas of increased phase locking might be correlated with topography of synchronous neuronal assemblies conceptualized within neural correlates of consciousness. (C) 2012 Elsevier B.V. All rights reserved.

Sigma and theta frequency electroencephalogram (EEG) oscillations exhibit substantial and well-recognized shifts with transitions across sleep and wake states. We aimed in this study to test the changes in coupling between these characteristic oscillations of non-rapid-eye-movement (NREM)/rapid-eye-movement (REM) sleep within and between cortical and pontine EEGs following monoaminergic lesion, by using the Pearson's product-moment correlation coefficients. Experiments were performed in 14 adult, male Sprague Dawley rats chronically instrumented for sleep recording. We lesioned the dorsal raphe nucleus axon terminals in four rats using PCA neurotoxin (p-chloroamphetamine; Sigma-Aldrich, MO) administered as two intraperitoneal (IP) injections (6 mg/kg) 24 h apart. Lesioning of locus coeruleus axon terminals was performed in five rats using DSP-4 neurotoxin (N-2-chloroethyl-N-ethyl-2-bromobenzilamine; Sigma-Aldrich, MO) in a single IP dose of 50 mg/kg. Our previous study [Saponjic et al., Physiol Behav 90:1-10, 2007] demonstrated that these systemically induced monoaminergic lesions failed to produce significant changes in sleep/wake distribution from control conditions. The present study, by using spectral analysis and by examining the Pearson's correlation coefficients and their approximate probability density (APD) distribution profiles in control and lesion condition, demonstrates significant augmentation of the sigma/theta coupling strength, an inversion of cortical sigma/theta coupling direction and emergence of an additional sigma/theta coupling "mode" specific to the post-lesion state only within the cortex. By using the Pearson's correlation coefficients and their APD profiles, instead of classical sleep/wake distribution analysis, as a measure of direction and strength of sigma/theta coupling within and between cortex and pons, we were able to uncover the impact of a tonically decreased level of brain monoamines as altered strength and mode of coupling between sigma and theta oscillations. Specifically, a new mode of sigma/theta coupling emerged following lesion, which was specific to NREM sleep, suggests that loss of monoaminergic signaling interferes with NREM sleep consolidation. Our results also indicate an importance of monoamines in control of the sleep spindle and theta rhythm generators. Serbian Ministry of Science and Technological Development [143005, 143027]; NIH [AG01630]

Aim of this preliminary study was to examine and compare topographic distribution of Higuchi's fractal dimension (FD, measure of signal complexity) of EEG signals between states of relaxed wakefulness and drowsiness, as well as their FD differences. The experiments were performed on 10 healthy individuals using a fourteen-channel montage. An explanation is offered on the causes of the detected FD changes. FD values of 60 s records belonging to wake (Hori's stage 1) and drowsy (Hori's stages 2-4) states were calculated for each channel and each subject. In 136 out of 140 epochs an increase in FD was obtained. Relationship between signal FD and its relative alpha amplitude was mathematically modeled and we quantitatively demonstrated that the increase in FD was predominantly due to a reduction in alpha activity. The model was generalized to include other EEG oscillations. By averaging FD values for each channel across 10 subjects, four clusters (O2O1; T6P4T5P3; C3F3F4C4F8F7; T4T3) for the wake and two clusters (O2O1P3T6P4T5; C3C4F4F3F8T4T3F7) for the drowsy state were statistically verified. Topographic distribution of FD values in wakefulness showed a lateral symmetry and a partial fronto-occipital gradient. In drowsiness, a reduction in the number of clusters was detected, due to regrouping of channels T3, T4, O1 and O2. Topographic distribution of absolute FD differences revealed largest values at F7, O1 and F3. Reorganization of channel clusters showed that regionalized brain activity, specific for wakefulness, became more global by entering into drowsiness. Since the global increase in FD during wake-to-drowsy transition correlated with the decrease of alpha power, we inferred that increase of EEG complexity may not necessarily be an index of brain activation. © 2009 Elsevier Ltd. All rights reserved.

The experiments were performed in 14 adult, male Sprague Dawley rats chronically instrumented for sleep recording and recorded during baseline condition, following sham injection (saline i.p. 1 ml/kg), and every week for 5 weeks following injection of the systemic neurotoxins (DSP-4 or PCA; 1 ml/kg, i.p.) for chemical axotomy of the locus coeruleus (LC) and dorsal raphe (DR) axon terminals. In our former study we demonstrated that the systemically induced lesion of the noradrenergic or serotonergic axon terminals did not affect the sleep-wake distribution from control condition. In this Study, by using spectral analysis and phase shift spectra of the cortical and pontine EEG we analyzed cortico-pontine theta oscillation synchronization phase shift on 6-hour recordings in control condition and 28 days following the monoaminergic lesions, as a time for permanently established DR or LC chemical axotomy. Our results demonstrated for the first time that chronically decreased brain monoamines in freely moving rats changed cortico-pontine theta synchronization phase shift. Pons became a leading theta oscillator. We assume that deficit of monoamines induced predominance of the NREM/REM transitions, characterized with phasic theta oscillations (the increased density of clustered P waves which intrinsic frequency corresponds to theta frequency oscillations), and may produced preceding phasic theta versus tonic theta oscillation drive. Serbian Ministry of Science and Technological Development [143005, 143027]; NIH [AG016303]

With application of the Higuchi algorithm, fractal dimension (FD) values of the electrocortical activity of the rat parietal cerebral and paravermal cerebellar cortex were calculated, before and after unilateral discrete injury of the left parietal cortex. Immediately following the first acute injury, in a group of six rats, a reversible increase in mean FD was found at the left (ipsilateral side to the injury) cerebral cortex, from 1.38 to 1.59, and at the left cerebellar cortex from 1.51 to 1.73. In addition, an indication of plastic changes after repeated (third) injury was found as an irreversible increase in mean FD: 1.54 on the left and 1.48 on the right side of parietal cortex.

We investigated cerebellar electrocortical activity before and after unilateral brain injury in anesthetized rats. Spectral analysis of cerebellar activity was obtained by Fast Fourier Transformation. There was a dominance of delta frequency range, while the wide gamma range presented no more than 5% of the total mean power spectra of cerebellar activity before brain injury. A few minutes after brain injury and within the first 90 minutes, there was a decrease of total mean power spectra and a relative decrease of delta range power to about 30%, some increase of beta range, and an increase of gamma range to 20-25%. Relative increase of gamma range in the cerebellar mean power spectra was still present 120 min after the brain injury, while other changes started to diminish. We suggest that spectral changes within slow and fast (gamma) frequency ranges of cerebellar activity may be indicators of the brain state after acute injury.