时域相干刺激研究进展

脑深部电刺激已成为许多神经和精神疾病的有效治疗方法。然而,侵入性的电极植入会带来手术并发症的风险,并且刺激靶区在植入后很难改变。经颅磁刺激和经颅电刺激等非侵入性刺激方法为调节大脑功能提供了新的途径。但是,尚未证明这些非侵入性脑刺激方法可以直接调节脑深部神经元活动而不影响皮层神经元。因此,这些方法主要用于调节大脑表层脑区的神经活动。时域相干（temporal interference,TI）刺激是通过两个高频电场相互作用,产生低频包络调节神经活动的一种非侵入式脑深部电刺激的新方法,该方法有望解决无创脑深部刺激的需求。本文首先介绍TI刺激的概念以及安全性,然后阐述TI刺激现有研究中的电场分析方法,并讨论电场分析相关的生理模型建模方法和仿真平台以及TI刺激诱发场分布的研究进展与在动物和人体中的应用进展。最后,本文展望了TI刺激技术未来发展方向,以期为无创脑深部刺激研究提供新的研究思路。     

An approach to removing spatially uncorrelated artifacts from EEG recordings

This work deals with elimination artifacts from electroencephalograms (EEGs). Though many methods for solving the problem have been proposed, they either require direct intervention of the researcher, are based on additional measurements (electrooculogram, electrocardiogram, etc.), or cannot remove artifact activity to a sufficient extent. We proposed an automated method that uses of the fact that the electromyogram (EMG) is not correlated and the artifacts of electrode movement at adjacent derivations and is based on the representation of electrical activity in one derivation through activity in other derivations. The analysis of the proposed method using model signals and examples of real EEG recordings has demonstrated its practical effectiveness.     

The dynamics of intracortical interaction during thinking activities

A new method is described of the brain mapping, based on determination of the probability of appearance of isofrequency components in the EEG derivations allowing to evaluate functional interaction of the brain structures in the process of psychic activity. The process of mental construction of visual image from separate elements includes three stages. At the stage of image search the focus of activity is in the occipital cortical area; in the stage of construction it moves to the frontal cortical areas; completion of the task and verbalization of the image are accompanied by joining of the cortical connections in common system. Alongside with the main focus of activity secondary focuses in the temporal cortex are also revealed during the search of the visual image. The topography of interaction at the frequencies of alpha-range in mainly determined by the stage of image construction. In case of prevalence of the image and abstract thinking shift is marked of the activity focuses at the frequencies of theta-range respectively to the right and left hemispheres.     

Correlation of EEG asymmetry and hypnotic susceptibility

Hypnosis research of the last decades confirmed that some cortical regions show characteristic modification of spontaneous brain electrical activity as a function of hypnotic responsiveness. Using FFT spectrum of 16 channel EEG recording, it was demonstrated that in highly susceptible subjects the right parieto-temporal region show more electric power than the left one while the low susceptibles have left side predominance or equilibrated power in all derivations. If a specific (Ericksonian) indirect hypnosis induction was administered, the same right side preponderance could be recorded in low susceptibles, too. On the basis of these results we can confirm the importance of the right parieto-temporal associative area in the alteration of consciousness characterizing hypnotic state.     

Correlation of brain electrical activity and motivation in healthy people

The central mechanisms of regulation of certain types of motivation at different respiration modes were investigated. Brain activity was studied by the safest and sufficiently informative method of electroencephalography. In total, 24 apparently healthy young subjects were examined. The subjects were relatively homogeneous according to the results of the following tests: motivation to success of primarily moderate and high level, moderate readiness to risk, and low motivation to approval. The realization of motivation as the most important component of the functional system of purposeful behavior caused changes in the level of activation of brain structures. A significant increase in the θ-rhythm power in response to forced hyperventilation with room-temperature air and in almost all frequency ranges during forced isocapnic hyperventilation with cold air was detected in virtually all brain regions. Multiple correlations between the studied types of motivation and the electrical activity of the brain at different loading modes were found. An expressed motivation to success is associated with a reduced power of pathological rhythms, whereas a decreased motivation of public approval is associated with the activation of deep structures of the brain at rest and under the influence of cold. At rest and during hyperventilation, an inverse correlation between the readiness to risk and slow brain activity was observed. In the case of cold air inhalation, the lower the individual readiness to take risks, the higher the β-rhythm power in all cortical areas. Regardless of the stable level of certain types of motivation, brain responses to various provocative factors changed the correlation patterns: some correlations became negligible, some were enhanced, and others changed their direction.     

A comparison of the spatial connections of superslow phasic electrical processes recorded from the surface of the head in healthy subjects to the spatial connections of a simultaneously recorded EEG

The EEG and infraslow phasic electrical processes in the band of 0.05-0.5 Hz (ISPP) were simultaneously recorded in 16 derivations (10-20 System without Fz, Cz, and Pz) in 35 women volunteers in the state of quiet wakefulness with closed eyes. Artifacts and non-stationary segments with a sharp amplitude increase were eliminated from the records in preprocessing editing. Spatial correlations were evaluated using maxima of crosscorrelation functions and coherence functions averaged over the whole spectrum. Correlations for both kind of processes appeared to be rather similar, in particular, they were both characterized by the low values if interhemispheric covariations in the temporal areas. The ISSP correlations were significantly lower for the least distance between derivations and had lower spatial gradient than the EEG correlations. There were also some topical differences between the processes. The obtained evidence support the idea of the ISPP as direct manifestations of cortical electrical activity, however, rather specific in relation with the routine EEG correlations.     

Neurophysiological mechanisms of voluntary attention: a review

The review is focused on attention as behavior-controlling process. Neurophysiological, electrophysiological and neuropsychological studies of different brain structures during voluntary attention are analyzed. These data show that selective voluntary attention modulates activity of sensory specific cortical zones involved in relevant signal processing. Fronto-thalamic system consisting of prefrontal cortex and thalamic mediodorsal nuclei is shown to be main source of top-down selective modulation of voluntary attention. The review proposed the hypothetical model of selective cortical activity modulation during voluntary attention based upon the available data and evidence of own electroencephalographic studies.     

Modelling general anaesthesia as a first-order phase transition in the cortex

Since 1997 we have been developing a theoretical foundation for general anaesthesia. We have been able to demonstrate that the abrupt change in brain state brought on by anaesthetic drugs can be characterized as a first-order phase transition in the population-average membrane voltage of the cortical neurons. The theory predicts that, as the critical point of phase change into unconsciousness is approached, the electrical fluctuations in cortical activity will grow strongly in amplitude while slowing in frequency, becoming more correlated both in time and in space. Thus the bio-electrical change of brain-state has deep similarities with thermodynamic phase changes of classical physics. The theory further predicts the existence of a second critical point, hysteretically separated from the first, corresponding to the return path from comatose unconsciousness back to normal responsiveness. There is a steadily accumulating body of clinical evidence in support of all of the phase-transition predictions: low-frequency power surge in EEG activity; increased correlation time and correlation length in EEG fluctuations; hysteresis separation, with respect to drug concentration, between the point of induction and the point of emergence.     

Activity of lactate dehydrogenase in the brain cortex and hippocampus of Mongolian gerbils after global ischemia and reperfusion injuries

Cerebral ischemia results in severe derangements of energy metabolism in the nervous tissue including activation of glycolytic pathway. Activity of cytosolic lactate dehydrogenase (LDH) in the specific brain structures remains unclear. The recent study was aimed at investigation into the LDH activity in the cytoplasm of both hippocampal and cortical neurons in Mongolian gerbils (Meriones unguiculatus) at different durations of reperfusion after global ischemia. Analysis showed that the activity of LDH in pyramidal neurons of various hippocampal areas and neurons of II, III and V cortical layers after 7-minute forebrain ischemia depended on both localization of the neurons and duration ofreperfusion. In general, the changes in postischemic cytosolic LDH activity include significant decrease in the LDH activity 2 days after reperfusion with varying degree of recovery on day 7 of reperfusion.     

Neuronal Localization of Pyroglutamate Aminopeptidase II in Primary Cultures of Fetal Mouse Brain

Pyroglutamate aminopeptidase II is a highly specific membrane-bound ectopeptidase proposed to inactivate thyrotropin releasing hormone (TRH) in brain extracellular space. Its activity was measured in primary cell cultures of fetal brain in an attempt to define its cellular localization. Enzyme activity was detected in hypothalamic or cortical cell membrane fractions from 4- to 12-day-old cultures. When proliferation of nonneuronal cells was abolished by cytosine arabinoside treatment, pyroglutamate aminopeptidase II specific activity was increased as compared to untreated cultures, the opposite was observed for pyroglutamate amino-peptidase I activity. Treatment of cortical cells with the neurotoxic agent glutamate reduced simultaneously pyroglutamate aminopeptidase II and glutamate decarboxylase activities. Glial cell cultures expressed pyroglutamate aminopeptidase I or glutamate synthase activities but not pyroglutamate aminopeptidase II. The data suggest that pyroglutamate aminopeptidase II is predominantly localized in neuronal cells. This is consistent with a role for pyroglutamate aminopeptidase II in TRH-ergic synaptic transmission.     

High-resolution fMRI maps of cortical activation in nonhuman primates: correlation with intrinsic signal optical images

One of the most widely used functional brain mapping tools is blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). This method has contributed to new understandings of the functional roles of different areas in the human brain. However, its ability to map cerebral cortex at high spatial (submillimeter) resolution is still unknown. Other methods such as single- and multiunit electrophysiology and intrinsic signal optical imaging have revealed submillimeter resolution of sensory topography and cortical columnar activations. However, they are limited either by spatial scale (electrophysiology characterizes only local groups of neurons) or by the inability to monitor deep structures in the brain (i.e., cortical regions buried in sulci or subcortical structures). A method that could monitor all regions of the brain at high spatial resolution would be ideal. This capacity would open the doors to investigating, for example, how networks of cerebral cortical columns relate to or produce behavior. In this article we demonstrate that, without benefit of contrast agents, at a magnetic field strength of 9.4 tesla, BOLD fMRI can reveal millimeter-sized topographic maps of digit representation in the somatosensory cortex of the anesthetized squirrel monkey. Furthermore, by mapping the "funneling illusion," it is possible to detect even submillimeter shifts in activation in the cortex. Our data suggest that at high magnetic field strength, the positive BOLD signal can be used to reveal high spatial resolution maps of brain activity, a finding that weakens previous notions about the ultimate spatial specificity of the positive BOLD signal.     

Relations between stimulus-bound eating and intracranial reinforcing strength

Rats with monopolar electrodes implanted in the lateral hypothalamus were trained to self-stimulate, each under 38 different electrical stimulus values. Stimulus-bound drinking and eating (SBB) were elicited by stimulating the rats through the same electrode with the same parameters and the same rate at which they self-administered the stimulation.It was observed that the frequency of SBB depended on the parameters of the electrical stimulus. The Spearman rank order correlation was computed between strength of SBB and the strength of the reinforcing effect elicited by brain stimulation. A factor analysis showed that the reinforcing process elicited by brain stimulation in this area is composed of several factors and that SBB is not loaded in all the factors composing reinforcement.     

The Role of the Genotype in the Development of the Neurophysiological Mechanisms Involved in the Spatial Integration of Neocortex Bioelectric Activity

The contribution of genetic factors into the formation of the neurophysiological mechanisms determining the systemic organization of cortical activity has been estimated in 12 pairs of monozygotic (MZ) and 5 pairs of dizygotic (DZ) twins (18–25 years of age). The similarity of individual patterns of the spatial interaction of cortical bioelectric activity measured for different combinations of EEG statistical relationships from 16 monopolar leads has been estimated in each pair of twins and in each of the 544 pairs of unrelated subjects in both groups. The results of the study suggest a high population invariance and small genetic and phenotypic variations of the morphofunctional systems constituting the main neurophysiological mechanisms of general cerebral integration. Brainstem and subcortical regulatory structures play the leading role in the integration of different brain regions into an organized system. Apparently, the formation of these structures during ontogeny follows the same general pattern in all individuals, because deviation from it is likely to affect the fundamental monomorphic characters of the species. The formation of neocortical interregional connections may be expected to exhibit greater individual variation, with the roles of hereditary and environmental factors in the formation of long and relatively short intercortical interactions being different. Apparently, the individual variation of the long intra- and interhemispheric fiber pathways forming the specific morphological framework of the neocortex is largely determined by the genotype. However, the intercentral interactions mediated by short corticocortical connections that are formed in the course of the vital activity of an individual are likely to be mainly determined by the external and internal environments.     

The spectral correlation characteristics of the brain electrical activity in the rabbit during thirst]

Spectral-correlation analysis of the summate electrical activity of a number of subcortical structures of rabbit brain, having, by literature data, a relation to drinking behaviour showed that the increase of drinking excitability, induced by water deprivation was accompanied by definite reconstruction of biopotentials. In electrical activity of the studied structures, the spectrum power, as a rule, decreased (except in the paraventricular nucleus), and a definite structure of coherent connections between the subcortical and cortical potentials was established. Among the studied subcortical formations, structures (anterior hypothalamic area, lateral preoptic area, medial preoptic area, paraventricular nucleus) could be singled out where reconstructions of spectral characteristics of biopotentials took place most regularity, and the electrical processes in which were characterised by coherence index by an increase of spatial interconnection with the neocortex potentials, what allows to consider them as most significant for organization of drinking excitation.     

Effect of a high-frequency electrical current on the activity of the raphe nuclei and the locus coeruleus

Recovery cycles of primary evoked potentials to light flashes in the visual cortical area of waking rats were studied under conditions of pharmacological and electrical influences on serotonin (5-HT)- and noradren (NA)ergic brain systems. All factors used induced oscillations of the recovery cycles. Periods of oscillations were similar (300-400 ms) during pharmacological suppression of the NA-system and during high-frequency (500 Hz) electrical stimulation or lesion of locus coeruleus. Analogous influences on 5-HT-system were accompanied by oscillations of recovery cycles with a period of 200 ms. Mechanism of inhibitory action of high-frequency electrical stimulation on activity of monoaminergic systems is discussed.     

The human thalamus processes syntactic and semantic language violations

Numerous linguistic operations have been assigned to cortical brain areas, but the contributions of subcortical structures to human language processing are still being discussed. Using simultaneous EEG recordings directly from deep brain structures and the scalp, we show that the human thalamus systematically reacts to syntactic and semantic parameters of auditorily presented language in a temporally interleaved manner in coordination with cortical regions. In contrast, two key structures of the basal ganglia, the globus pallidus internus and the subthalamic nucleus, were not found to be engaged in these processes. We therefore propose that syntactic and semantic language analysis is primarily realized within cortico-thalamic networks, whereas a cohesive basal ganglia network is not involved in these essential operations of language analysis.     

Assessment of Subcortical Source Localization Using Deep Brain Activity Imaging Model with Minimum Norm Operators: A MEG Study

Subcortical structures are involved in many healthy and pathological brain processes. It is crucial for many studies to use magnetoencephalography (MEG) to assess the ability to detect subcortical generators. This study aims to assess the source localization accuracy and to compare the characteristics of three inverse operators in the specific case of subcortical generators. MEG has a low sensitivity to subcortical sources mainly because of their distance from sensors and their complex cyto-architecture. However, we show that using a realistic anatomical and electrophysiological model of deep brain activity (DBA), the sources make measurable contributions to MEG sensors signals. Furthermore, we study the point-spread and cross-talk functions of the wMNE, sLORETA and dSPM inverse operators to characterize distortions in cortical and subcortical regions and to study how noise-normalization methods can improve or bias accuracy. We then run Monte Carlo simulations with neocortical and subcortical activations. In the case of single hippocampus patch activations, the results indicate that MEG can indeed localize the generators in the head and the body of the hippocampus with good accuracy. We then tackle the question of simultaneous cortical and subcortical activations. wMNE can detect hippocampal activations that are embedded in cortical activations that have less than double their amplitude, but it does not completely correct the bias to more superficial sources. dSPM and sLORETA can still detect hippocampal activity above this threshold, but such detection might include the creation of ghost deeper sources. Finally, using the DBA model, we showed that the detection of weak thalamic modulations of ongoing brain activity is possible.     

Studying brain functions with mesoscopic measurements: Advances in electrocorticography for non-human primates

Our brain is organized in a modular structure. Information in different modalities is processed within distinct cortical areas. However, individual cortical areas cannot enable complex cognitive functions without interacting with other cortical areas. Electrocorticography (ECoG) has recently become an important tool for studying global network activity across cortical areas in animal models. With stable recordings of electrical field potentials from multiple cortical areas, ECoG provides an opportunity to systematically study large-scale cortical activity at a mesoscopic spatiotemporal resolution under various experimental conditions. Recent developments in thin, flexible ECoG electrodes permit recording field potentials from not only gyral but intrasulcal cortical surfaces. Our review here focuses on the recent advances of ECoG applications to non-human primates.     

Mapping cortical activity elicited with electrical microstimulation using FMRI in the macaque

Over the last two centuries, electrical microstimulation has been used to demonstrate causal links between neural activity and specific behaviors and cognitive functions. However, to establish these links it is imperative to characterize the cortical activity patterns that are elicited by stimulation locally around the electrode and in other functionally connected areas. We have developed a technique to record brain activity using the blood oxygen level dependent (BOLD) signal while applying electrical microstimulation to the primate brain. We find that the spread of activity around the electrode tip in macaque area V1 was larger than expected from calculations based on passive spread of current and therefore may reflect functional spread by way of horizontal connections. Consistent with this functional transynaptic spread we also obtained activation in expected projection sites in extrastriate visual areas, demonstrating the utility of our technique in uncovering in vivo functional connectivity maps.