How the nonlinear voltage dependence of the amplitude of excitatory postsynaptic potentials induced by cerebral cortical neurons affects cortical rhythmic activity

A nonlinear dependence of the amplitude of excitatory postsynaptic potentials on the membrane potentials was derived. The existence of a region of oscillation stability with an increase in the mean value of nonspecific afferent inflow was demonstrated. A high-frequency oscillation component (40–60 Hz) appears with a pronounced increase in the afferent inflow; this can cause instability in oscillations and abnormal brain activity.     

Oscillatory zones and their role in normal and abnormal sheep purkinje fiber automaticity

The mechanisms by which low [K(+)](o) induces spontaneous activity was studied in sheep Purkinje fibers. Purkinje strands were superfused in vitro and membrane potentials were recorded by means of a microelectrode technique. The results show that low [K(+)](o) increases the slope and amplitude of early diastolic depolarization, sharpens the transition between early and late diastolic depolarizations, induces an after-potential and large pre-potentials through a negative shift of an oscillatory zone. Pre-potentials occur progressively sooner during diastole and merge with the after-potential to induce uninterrupted spontaneous discharge. During recovery, when the rate slows, after- and pre-potentials separate once more, the slower discharge decreasing the after-potentials but not the pre-potentials. Low [K(+)](o) has little effect on the plateau, but markedly slows phase 3 repolarization and may altogether prevent it. At depolarized levels, voltage oscillations, slow responses, sinusoidal fluctuations or quiescence may be present depending on voltage. During the recovery, a train of either sub-threshold oscillations or spontaneous action potentials appear towards the end of phase 3 repolarization. The cessation of the action potentials unmasks large sub-threshold oscillations, that occur in the oscillatory zone. Drive, high [Ca(2+)](o) and norepinephrine increase slope and amplitude of early diastolic depolarization as low [K(+)](o) does. In low [K(+)](o), Cs(+) prevents spontaneous discharge at polarized levels, but not the decrease in resting potential nor the onset of slow responses at depolarized levels. Cs(+) blocks the train of oscillations and of action potentials occurring during recovery. We conclude that low [K(+)](o) steepens early diastolic depolarization and increases its amplitude through an after-potential that results from an increased Ca(2+) load; allows the attainment of the threshold through Cs(+)-sensitive voltage oscillations which develop when the oscillatory zone is entered either by diastolic depolarization or by phase 3 repolarization; and causes voltage oscillations also at depolarized levels, but through a Cs(+)-insensitive different mechanism.     

The physical basis of alpha waves in the electroencephalogram and the origin of the “Berger effect”

Synchronised activity, differing in phase in different populations of neurons, plays an important role in existing theories on the function of brain oscillations (e.g., temporal correlation hypothesis). A prerequisite for this synchronisation is that stimuli are capable of affecting (resetting) the phase of brain oscillations. Such a change in the phase of brain waves is also assumed to underlie the Berger effect: when observers open their eyes, the amplitude of EEG oscillations in the alpha band (8–13 Hz) decreases significantly. This finding is usually thought to involve a desynchronisation of activity in different neurons. For functional interpretations of brain oscillations in the visual system, it therefore seems to be crucial to find out whether or not the phase of brain oscillations can be affected by visual stimuli. To answer this question, we investigated whether alpha waves are generated by a linear or a nonlinear mechanism. If the mechanism is linear – in contrast to nonlinear ones – phases cannot be reset by a stimulus. It is shown that alpha-wave activity in the EEG comprises both linear and nonlinear components. The generation of alpha waves basically is a linear process and flash-evoked potentials are superimposed on ongoing alpha waves without resetting their phase. One nonlinear component is due to light adaptation, which contributes to the Berger effect. The results call into question theories about brain-wave function based on temporal correlation or event-related desynchronisation.Electronic Supplementary Material: Supplementary material is available for this article at     

Age-related dynamics of thalamic-cortical evoked potentials in the rabbit in the early period of life

Data have been obtained on development of evoked potentials in the sensorimotor cortex to electrical stimulation of the thalamic ventroposterolateral nucleus (VPL) in rabbits in early ontogeny. In 3-5 days rabbits, under four times increase of threshold electric stimulation of VPL the thalamocortical response (TCR) is presented by a positive-negative potential with a long latency and minimum amplitude parameters. Second and third TCR positive components to increasing of threshold value of electric stimulation 4 times, are differentiated from 7-8 days age. Age dynamics of TCR amplitude-temporal parameters is characterized by a shortening of latency and an increase of oscillations amplitude, most expressed at 2-3 weeks of postnatal life. TCR of one month rabbit to increased threshold electrical stimulation of VPL is presented by short-latency positive-negative oscillation with a positive phase consisting of three components with successively increasing amplitudes.     

Role of frequency mismatch in neuronal communication through coherence

Neuronal gamma oscillations have been described in local field potentials of different brain regions of multiple species. Gamma oscillations are thought to reflect rhythmic synaptic activity organized by inhibitory interneurons. While several aspects of gamma rhythmogenesis are relatively well understood, we have much less solid evidence about how gamma oscillations contribute to information processing in neuronal circuits. One popular hypothesis states that a flexible routing of information between distant populations occurs via the control of the phase or coherence between their respective oscillations. Here, we investigate how a mismatch between the frequencies of gamma oscillations from two populations affects their interaction. In particular, we explore a biophysical model of the reciprocal interaction between two cortical areas displaying gamma oscillations at different frequencies, and quantify their phase coherence and communication efficiency. We observed that a moderate excitatory coupling between the two areas leads to a decrease in their frequency detuning, up to ～6 Hz, with no frequency locking arising between the gamma peaks. Importantly, for similar gamma peak frequencies a zero phase difference emerges for both LFP and MUA despite small axonal delays. For increasing frequency detunings we found a significant decrease in the phase coherence (at non-zero phase lag) between the MUAs but not the LFPs of the two areas. Such difference between LFPs and MUAs behavior is due to the misalignment between the arrival of afferent synaptic currents and the local excitability windows. To test the efficiency of communication we evaluated the success of transferring rate-modulations between the two areas. Our results indicate that once two populations lock their peak frequencies, an optimal phase relation for communication appears. However, the sensitivity of locking to frequency mismatch suggests that only a precise and active control of gamma frequency could enable the selection of communication channels and their directionality.     

Brain Activity at 70–80 Hz Changes during Olfactory Stimulation Protocols in Drosophila

Oscillatory and synchronized activities in the mammalian brain have been correlated with the execution of complex cognitive tasks. Similar oscillations have been observed in local field potentials (LFPs) in flies, in this case correlated with different attentional states. To further test the significance of these oscillations we recorded LFPs from the brain of Drosophila melanogaster as it responded to the presentation of olfactory stimuli. We find that responses in the 70–80 Hz range increase during olfactory stimulation. Recurrent stimulation specifically decreased the power of LFPs in this frequency range. Delivery of electric shocks before olfactory stimulation modulated LFPs in the 70–80 Hz range by evoking a transient increase. These results suggest that these signals are a simple neuronal correlate of higher-order olfactory processing in flies.     

Sounds reset rhythms of visual cortex and corresponding human visual perception

An event in one sensory modality can phase reset brain oscillations concerning another modality. In principle, this may result in stimulus-locked periodicity in behavioral performance. Here we considered this possible cross-modal impact of a sound for one of the best-characterized rhythms arising from the visual system, namely occipital alpha-oscillations (8-14 Hz). We presented brief sounds and concurrently recorded electroencephalography (EEG) and/or probed visual cortex excitability (phosphene perception) through occipital transcranial magnetic stimulation (TMS). In a first, TMS-only experiment, phosphene perception rate against time postsound showed a periodic pattern cycling at ~10 Hz phase-aligned to the sound. In a second, combined TMS-EEG experiment, TMS-trials reproduced the cyclical phosphene pattern and revealed a ~10 Hz pattern also for EEG-derived measures of occipital cortex reactivity to the TMS pulses. Crucially, EEG-data from intermingled trials without TMS established cross-modal phase-locking of occipitoparietal alpha oscillations. These independently recorded variables, i.e., occipital cortex excitability and reactivity and EEG phase dynamics, were significantly correlated. This shows that cross-modal phase locking of oscillatory visual cortex activity can arise in the human brain to affect perceptual and EEG measures of visual processing in a cyclical manner, consistent with occipital alpha oscillations underlying a rapid cycling of neural excitability in visual areas.     

Human gamma oscillations during slow wave sleep

Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.     

Neural synchrony during response production and inhibition

Inhibition of irrelevant information (conflict monitoring) and/or of prepotent actions is an essential component of adaptive self-organized behavior. Neural dynamics underlying these functions has been studied in humans using event-related brain potentials (ERPs) elicited in Go/NoGo tasks that require a speeded motor response to the Go stimuli and withholding a prepotent response when a NoGo stimulus is presented. However, averaged ERP waveforms provide only limited information about the neuronal mechanisms underlying stimulus processing, motor preparation, and response production or inhibition. In this study, we examine the cortical representation of conflict monitoring and response inhibition using time-frequency analysis of electroencephalographic (EEG) recordings during continuous performance Go/NoGo task in 50 young adult females. We hypothesized that response inhibition would be associated with a transient boost in both temporal and spatial synchronization of prefrontal cortical activity, consistent with the role of the anterior cingulate and lateral prefrontal cortices in cognitive control. Overall, phase synchronization across trials measured by Phase Locking Index and phase synchronization between electrode sites measured by Phase Coherence were the highest in the Go and NoGo conditions, intermediate in the Warning condition, and the lowest under Neutral condition. The NoGo condition was characterized by significantly higher fronto-central synchronization in the 300-600 ms window, whereas in the Go condition, delta- and theta-band synchronization was higher in centro-parietal regions in the first 300 ms after the stimulus onset. The present findings suggest that response production and inhibition is supported by dynamic functional networks characterized by distinct patterns of temporal and spatial synchronization of brain oscillations.     

Fatty acid metabolism in hepatocytes cultured with hypolipidaemic drugs. Role of carnitine.

The kinetic features of the changes in the cytosolic free Ca2+ concentration, [Ca2+]i, following stimulation by thyrotropin releasing hormone (TRH) were analysed in single cells of a pituitary line (GH3B6) by dual excitation microfluorimetry [Tsien, Rink & Poenie (1985) Cell Calcium 6, 145-157], using fura 2 as intracellular Ca2+ probe. Two phases were observed: initially, [Ca2+]i is raised in a single rapid transient to a maximum averaging 8.0 microM, and in a second phase TRH causes a series of rapid [Ca2+]i oscillations with maxima around 1.0 microM, which are probably due to the enhanced firing of action potentials. TRH triggers both phases independently, i.e. it can elicit either the first or the second phase exclusively. This is also the case in those cells in which [Ca2+]i undergoes rhythmic oscillations due to the firing of spontaneous action potentials [Schlegel, Winiger, Mollard, Vacher, Wuarin, Zahnd, Wolheim & Dufy (1987) Nature (London) 329, 719-721]. The sudden onset of the first phase of TRH action on [Ca2+]i shows that Ca2+ mobilization due to enhanced production of inositol phosphate may occur as rapidly as the firing of action potentials, i.e. in the ms time range. Due to a marked response type heterogeneity and to the randomness of the rapid events, previous monitoring of [Ca2+]i in cell populations had misleadingly suggested small and maintained changes due to TRH. It is concluded that stimulatory regulation of secretion is provided by the generation of rapid [Ca2+]i transients, the frequency of which determines secretory rate. Furthermore, it is demonstrated that the regulation of [Ca2+]i by hormones and neurotransmitters in pituitary and many other cell types will have to be studied at the single cell level in order to appreciate its role in cell activation.     

Phase coding: spikes get a boost from local fields

The brain exhibits coherent, long-range oscillations, and it now appears that these oscillations play a substantial role in neural coding: they can boost the information contained in action potentials by as much as 50%.     

The functional testing of the interhemispheric asymmetry in the spatial organization of rabbit cortical potentials]

Interhemispheric asymmetry was studied of spatial-temporal potentials organization (STPO) of the cortex in non-fixated animals in the states of deep rest, behavioural activity and in the transition period between them. Despite the intrahemispheric differences of the STPO in each of these states, interhemispheric divergences in the character of reconstructions of momentary topograms of the cortical potentials, recorded at 24-channels leading, are limited by 35% of the epoch analysis time. Comparison of the dynamics of intrahemispheric changes of topograms of cortical potentials in the left and right hemispheres in the states of rest and activity revealed a narrowing of temporal period of the absence of resemblance in reconstructions of successive topograms of the left and right hemispheres in comparison with transition processes. In the phase of rest the interhemispheric conjugation of spatial reconstructions in topograms became lowered mainly because of the disturbances of monotony of changes of their reliefs in one of the hemispheres in turn. In the active phase, deviations from STPO of the cortex, characteristic of the state of rest, were met more frequently in the right hemisphere; in that case oscillations of the topograms general mean level connected with the activity of non-specific activating subcortical brain system acquired a significant role in regulation of interhemispheric relations. Presence of interhemispheric resemblance of reconstructions of topograms reliefs in the active phase, despite the tendency to its lowering in comparison with the rest, testifies to the contribution also of the intracortical processes to the interhemispheric spatial synchronization of the cortical potentials in this state.     

Rhythmic bioelectrical activity of the cerebral cortex analyzed with allowance for the nonlinear voltage dependence of excitatory postsynaptic potentials induced by neocortical neurons

A nonlinear voltage dependence between the membrane and excitatory postsynaptic potentials coming via corticocortical connections was derived based on literature data. The existence of a region of stability of oscillations with increasing mean value of nonspecific afferent input was shown. As the afferent input strongly increases, a high-frequency component of oscillations (40-60 Hz), appeas which may result in the instability of oscillations and initiation of abnormal brain activity.     

Average beta burst duration profiles provide a signature of dynamical changes between the ON and OFF medication states in Parkinson’s disease

Parkinson’s disease motor symptoms are associated with an increase in subthalamic nucleus beta band oscillatory power. However, these oscillations are phasic, and there is a growing body of evidence suggesting that beta burst duration may be of critical importance to motor symptoms. This makes insights into the dynamics of beta bursting generation valuable, in particular to refine closed-loop deep brain stimulation in Parkinson’s disease. In this study, we ask the question “Can average burst duration reveal how dynamics change between the ON and OFF medication states?”. Our analysis of local field potentials from the subthalamic nucleus demonstrates using linear surrogates that the system generating beta oscillations is more likely to act in a non-linear regime OFF medication and that the change in a non-linearity measure is correlated with motor impairment. In addition, we pinpoint the simplest dynamical changes that could be responsible for changes in the temporal patterning of beta oscillations between medication states by fitting to data biologically inspired models, and simpler beta envelope models. Finally, we show that the non-linearity can be directly extracted from average burst duration profiles under the assumption of constant noise in envelope models. This reveals that average burst duration profiles provide a window into burst dynamics, which may underlie the success of burst duration as a biomarker. In summary, we demonstrate a relationship between average burst duration profiles, dynamics of the system generating beta oscillations, and motor impairment, which puts us in a better position to understand the pathology and improve therapies such as deep brain stimulation.     

Stimulus Phase Locking of Cortical Oscillation for Auditory Stream Segregation in Rats

The phase of cortical oscillations contains rich information and is valuable for encoding sound stimuli. Here we hypothesized that oscillatory phase modulation, instead of amplitude modulation, is a neural correlate of auditory streaming. Our behavioral evaluation provided compelling evidences for the first time that rats are able to organize auditory stream. Local field potentials (LFPs) were investigated in the cortical layer IV or deeper in the primary auditory cortex of anesthetized rats. In response to ABA- sequences with different inter-tone intervals and frequency differences, neurometric functions were characterized with phase locking as well as the band-specific amplitude evoked by test tones. Our results demonstrated that under large frequency differences and short inter-tone intervals, the neurometric function based on stimulus phase locking in higher frequency bands, particularly the gamma band, could better describe van Noorden’s perceptual boundary than the LFP amplitude. Furthermore, the gamma-band neurometric function showed a build-up-like effect within around 3 seconds from sequence onset. These findings suggest that phase locking and amplitude have different roles in neural computation, and support our hypothesis that temporal modulation of cortical oscillations should be considered to be neurophysiological mechanisms of auditory streaming, in addition to forward suppression, tonotopic separation, and multi-second adaptation.     

Human motor unit recruitment and derecruitment during long lasting intermittent contractions.

Seven healthy subjects were investigated in cyclic ramp-and-hold long lasting isometric contractions. Wire branched electrodes were used for selective recording of single motor unit (MU) potentials from m. biceps brachii. MU behaviour was defined in terms of recruitment/derecruitment thresholds (RT and DT) and the duration of interspike intervals (ISI). A total of 63 MUs was investigated: 40 units were active from the beginning of the task performance and another 23 were recruited later. There were no changes in the recruitment pattern of MUs with fatigue development - a short first ISI followed by a very long second one and an almost constant firing rate after this transient phase. The tendency of RT to gradually decrease dominates the results. Thus, the required constant rate of force increase with fatigue development was maintained mostly by the mechanisms of space coding (i.e., decrease of RT and recruitment of additional MUs). Oppositely, the time behaviour of the DT changes was not uniform and rate coding was an essential mechanism in the adaptation of MU activity to muscle fatigue during relaxation phases. The recruitment pattern and fatigue related behaviour of the additionally recruited MUs were similar to those of MUs active from the first cycle of the motor task performance.     

Changes in the somatosensory evoked potentials in the night sleep of healthy subjects under conditions of preceding emotional stress

Somatosensory evoked potentials (SEP) were studied in eight healthy subjects in a state of alertness, in different stages of night sleep and also in night sleep after previous emotional stress. Characteristic changes of SEP were revealed in the second stage of sleep in delta-sleep and in the phase of rapid sleep. In conditions of emotional stress changes in SEP characteristics in periods of alertness and of night sleep were observed, expressed in the amplitude increase of a number of components. Asymmetry was revealed with predominance of the amplitude increase in the right hemisphere in the phase of the rapid sleep testifying to different roles of the cerebral hemispheres in processing of emotionally significant information. SEP changes in different functional states after the influence of emotional stress were considered as the reflection of non-specific activation increase possibly due to activation of the limbic structures in response to stress-producing stimulus.     

Operant control of EEG and event-related and slow brain potentials

Research on operant control of brain potentials is reviewed. From single-unit firing and spontaneous EEG activity to event-related potentials such as sensory and pain evoked potentials, and slow potential shifts, most of the aspects of electrical brain activity have been investigated. Results produced by conditioning of spontaneous EEG oscillations (alpha and theta) dampened the early enthusiasm: e.g., no increase above baseline levels could be achieved and no reliable behavioral effects became manifest. Evidence accumulates, however, that operant conditioning of the sensorimotor rhythm (12–15 Hz) may lead to successful self-regulation and that epileptic patients may profit from the training. First steps in the conditioning of brainstem, as well as pain evoked potentials suggest that self-regulation of EPs can be achieved by adequate biofeedback procedures. If some of the observed behavioral effects prove to be stable, the therapeutic usefulness seems to be within reach. A comparable progress has been achieved for the operant control of slow potentials (DC-shifts across seconds). Biofeedback procedures have been used successfully as a scientific tool to achieve systematic variations on a psychological level and to record psychological covariations. This method may provide insights into the behavioral meaning of electrical brain activity.     

Phase synchronization of skin blood flow oscillations in humans under asymmetric local heating

The hypothesis is proposed that an external local stimulus may cause a change in the phase relationships of oscillations in the peripheral skin blood flow of contralateral extremities. To test this assumption, the wavelet phase coherence of skin blood flow oscillations of the left and right forearms of 18 healthy volunteers of both sexes at rest and in response to unilateral local heating was investigated. An area of the skin of the left forearm was exposed to heat and the native blood perfusion in an area of the skin of the right forearm was recorded simultaneously. It was shown that an asymmetric local change of skin perfusion led to a significant change in the phase relationships of the blood flow oscillations in all the analyzed frequency ranges. A significant reduction of phase synchronization of oscillations of skin blood flow in the range of endothelial, neurogenic, and myogenic activity, as well as in the range of respiratory rhythm was revealed. In contrast, in the range of the cardiac rhythm, a significant increase in phase synchronization of the oscillations of the blood flow of contralateral skin areas of the forearm was detected.     

The phase response of the cortical slow oscillation

Cortical slow oscillations occur in the mammalian brain during deep sleep and have been shown to contribute to memory consolidation, an effect that can be enhanced by electrical stimulation. As the precise underlying working mechanisms are not known it is desired to develop and analyze computational models of slow oscillations and to study the response to electrical stimuli. In this paper we employ the conductance based model of Compte et al. (J Neurophysiol 89:2707–2725, 2003) to study the effect of electrical stimulation. The population response to electrical stimulation depends on the timing of the stimulus with respect to the state of the slow oscillation. First, we reproduce the experimental results of electrical stimulation in ferret brain slices by Shu et al. (Nature 423:288–293, 2003) from the conductance based model. We then numerically obtain the phase response curve for the conductance based network model to quantify the network’s response to weak stimuli. Our results agree with experiments in vivo and in vitro that show that sensitivity to stimulation is weaker in the up than in the down state. However, we also find that within the up state stimulation leads to a shortening of the up state, or phase advance, whereas during the up–down transition a prolongation of up states is possible, resulting in a phase delay. Finally, we compute the phase response curve for the simple mean-field model by Ngo et al. (EPL Europhys Lett 89:68002, 2010) and find that the qualitative shape of the PRC is preserved, despite its different mechanism for the generation of slow oscillations.