Towards a functional neuroanatomy of conscious perception and its modulation by volition: implications of human auditory neuroimaging studies.

Conscious sensory perception and its modulation by volition are integral to human mental life. Functional neuroimaging techniques provide a direct means of identifying and characterizing in vivo the systems-level patterns of brain activity associated with such mental functions. In a series of positron emission tomography activation experiments, we and our colleagues have examined a range of normal and abnormal auditory states that, when contrasted, provide dissociations relevant to the question of the neural substrates of sensory awareness. These dissociations include sensory awareness in the presence and absence of external sensory stimuli, the transition from sensory unawareness to awareness (or vice versa) in the presence of sensory stimuli, and sensory awareness with and without volition. The auditory states studied include hallucinations, mental imagery, cortical deafness modulated by attention, and hearing modulated by sedation. The results of these studies highlight the distributed nature of the functional neuroanatomy that is sufficient, if not necessary, for sensory awareness. The probable roles of unimodal association (as compared with primary) cortices, heteromodal cortices, limbic/paralimbic regions and subcortical structures (such as the thalamus) are discussed. In addition, interactions between pre- and post-rolandic regions are examined in the context of top-down, volitional modulation of sensory awareness.     

Electroencephalographic correlates of a pathologic inert motor reaction in dogs]

Changes in EEG were examined during setting in of a pathological inert motor reaction in dogs with parts of the tongue brought out and electrodes implanted in the motor cortical area and limbic structures. The reaction was formed when combining stimulation by a salt solution of the part of the tongue with electrical stimulation of the paw. The inert motor reaction is characterized by enhanced synchronization (theta-rhythm) in the hippocampus and increased amplitude of the beta-rhythm in the motor cortical areas. A frequency-amplitude analysis of the summary EEG has shown that the highest correlation was established at the beginning of elaboration of the inert motor reaction only between a small number of limbic structures (the hippocampus, the hypothalamus and the cingulate gyrus), then between all the examined structures of the brain; when the inert reaction became elaborated the number of structures with a high correlation coefficient diminished again and was reduced to the hippocampus, the hypothalamus and the cortical motor area.     

Default network connectivity decodes brain states with simulated microgravity

With great progress of space navigation technology, it becomes possible to travel beyond Earth’s gravity. So far, it remains unclear whether the human brain can function normally within an environment of microgravity and confinement. Particularly, it is a challenge to figure out some neuroimaging-based markers for rapid screening diagnosis of disrupted brain function in microgravity environment. In this study, a 7-day ?6° head down tilt bed rest experiment was used to simulate the microgravity, and twenty healthy male participants underwent resting-state functional magnetic resonance imaging scans at baseline and after the simulated microgravity experiment. We used a multivariate pattern analysis approach to distinguish the brain states with simulated microgravity from normal gravity based on the functional connectivity within the default network, resulting in an accuracy of no less than 85 % via cross-validation. Moreover, most discriminative functional connections were mainly located between the limbic system and cortical areas and were enhanced after simulated microgravity, implying a self-adaption or compensatory enhancement to fulfill the need of complex demand in spatial navigation and motor control functions in microgravity environment. Overall, the findings suggest that the brain states in microgravity are likely different from those in normal gravity and that brain connectome could act as a biomarker to indicate the brain state in microgravity.     

The connectional organization of neural systems in the cat cerebral cortex

BACKGROUND: The mammalian brain consists of the cerebral cortical sheet, which is composed of many distinct areas, the cerebellar cortex, and many non-cortical nuclei. Powerful neuroanatomical techniques have revealed a large number of connections between these structures. The large number of brain structures and the very many connections between them form a strikingly complex network. The complexity of this network has made it difficult to understand how the central nervous system is organized. Recently, however, optimization analysis of an important subset of central nervous connections that occur between the different areas of the cerebral cortex has produced understandable and quantitative representations of the organization of cortical systems of the primate brain. RESULTS: Here we briefly report the extension of this approach to the cortical systems of the cat. There were four connectional clusters of cortical areas in the cat. These clusters of areas corresponded to the visual, auditory, and somato-motor systems, and to the frontal and limbic areas, which we call the fronto-limbic complex. All the major sensory systems were hierarchically organized, and their 'higher' stations were more closely associated with the fronto-limbic complex than were their 'lower' stations. CONCLUSIONS: Features of the organization of the cat brain, together with earlier primate results, suggest that there may be a common cortical plan in mammals. We suggest that this common plan may involve relatively discrete, hierarchically organized, cortical sensory systems and a topologically central fronto-limbic complex. Specific variations on this wiring plan may relate to evolutionary history and selection for particular ecological niches.     

The role of cerebral regulatory structures in the formation of human EEG

This article generalizes the results of many years’ studies of the EEG of patients with tumorous lesions in the diencephalic, brainstem, and limbic structures, which fulfill the regulatory function in ensuring integral brain activity. The specific features of the inclusion of individual structures under investigation in the organization of the intra- and interhemispheric relations of cortical biopotentials were demonstrated against the background of diffuse changes in the biopotentials that reflect the systemic character of neurodynamic reorganizations when the regulatory brain structures are involved in the pathological process. This study expands the idea of the predominant functional connection of the diencephalic structures with the right hemisphere and brainstem structures with the left one with determination of the regional specific features of changes in the intrahemispheric EEG coherences. The distinguishing features of intercentral relations when the limbic structures are involved in the pathological process show similarity with the neurodynamic reorganizations in patients with lesions in both diencephalic and (even more so) brainstem structures. Universal elements were detected in the formation of integral adaptive reactions of the brain with lesions in its regulatory structures, which reflects their close functional interaction and makes it possible to consider them the individual links of an integral regulatory system. The study revealed reciprocal changes in various forms of electrical activity, which reflects reciprocation of interaction of individual regulatory structures. This is one of the EEG equivalents of the formation of adaptive-compensatory cerebral reactions. The specificity of influence of the studied regulatory structures are clearly seen in situations of their morphofunctional isolation observed during cerebral coma. In these conditions, when the cortex is functionally inactive, the authors demonstrated the dynamic character of changes in interhemispheric asymmetry, which reflects the dominance of individual links of the regulatory system playing the role of supreme regulator of life support of the body in critical states.     

Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease

Information processing and storing by brain networks requires a highly coordinated operation of multiple neuronal groups. The function of septal neurons is to modulate the activity of archicortical (e.g. hippocampal) and neocortical circuits. This modulation is necessary for the development and normal occurrence of rhythmical cortical activities that control the processing of sensory information and memory functions. Damage or degeneration of septal neurons results in abnormal information processing in cortical circuits and consequent brain dysfunction. Septal neurons not only provide the optimal levels of excitatory background to cortical structures, but they may also inhibit the occurrence of abnormal excitability states.     

Cytoskeletal-associated proteins in the migration of cortical neurons

Neuronal migration is a hallmark of cerebral cortical development as neurons born deep within the brain migrate to the surface in a highly choreographed process. The cytoskeleton extends throughout the cell, mediating the dramatic morphological changes that accompany migration. On a cellular level, proper migration is accompanied by polarization of the cytoskeleton and cellular contents and by dynamic reorganization that generates the force for cell locomotion. Genetic analyses of human brain malformations, as well as genetically engineered mouse mutants, have highlighted a number of cytoskeletal-associated proteins underlying these functions, which are necessary for proper cortical development. While these proteins are involved in diverse molecular mechanisms, disruption during development results in the ectopic placement of neurons in the cortex. We review key cytoskeletal events and the critical cytoskeletal-associated proteins involved in cortical neuronal migration.     

Central neural mechanisms that interrelate sensory and affective dimensions of pain

The perception of pain is highly complex, and requires neural integration from a variety of routes. Spinal pathways to the amygdala, hypothalamus, reticular formation, medial thalamic nuclei, and limbic cortical structures transmit information involved arousal, bodily regulation, and emotional responses. Other, albeit indirect, pathways can carry signals to these same structures, for example, from spinal pathways to somatosensory thalamic and cortical areas, and from these to cortical limbic structures. Indirect cortico-limbic pathways integrate nociception with information about the status of the body and indirect routes must culminate in the prioritization of emotions and responses to pain.     

The agmatine-degrading enzyme agmatinase: a key to agmatine signaling in rat and human brain?

Agmatinase, an ureohydrolase belonging to the arginase family, is widely expressed in mammalian tissues including the brain. Here, it may serve two different functions, the inactivation of the arginine derivative agmatine, a putative neurotransmitter, and the formation of the diamine putrescine. In order to identify the cellular sources of agmatinase expression in the brain, we generated a polyclonal monospecific antibody against recombinant rat agmatinase. With immunocytochemistry, selected areas of rat and human brain were screened. Clearly, in both species agmatinase-like immunoreactivity was predominantly detected in distinct populations of neurons, especially cortical interneurons. Also, principal neurons in limbic regions like the habenula and in the cerebellum robustly expressed agmatinase protein. When comparing the overall agmatinase expression with immunocytochemical data available for agmatine and polyamine biosynthetic enzymes, the observed pattern may argue in favor of an agmatine inactivating function rather than fueling the alternative pathway of polyamine synthesis. The putative neurotransmitter agmatine is seemingly involved with mental disorders. Therefore, agmatinase may be similarly important for pathogenesis. The normal expression profile of the protein as described here may therefore be altered under pathological conditions.     

Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders

Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which primary mood disorders are conceptualized as illnesses that involve abnormalities of brain structure, as well as of brain function. These data suggest specific hypotheses regarding the neural mechanisms underlying pathological emotional processing in mood disorders. They particularly support a role for dysfunction within the prefrontal cortical and striatal systems that normally modulate limbic and brainstem structures involved in mediating emotional behavior in the pathogenesis of depressive symptoms.     

EEG Correlates of Mild Impairments of Higher Cortical Functions

Correlations between the impairments of higher cortical functions (assessed by clinical scores and neuropsychological tests) and multichannel EEG spectra were analyzed in elderly patients with mild dementia and children with cognitive problems. A decrease in the regional cerebral blood flow, an imbalance between neocortical and limbic structures, and a lack of inhibitory influences from the frontal cortex are discussed as probable causes of these brain functional disorders associated with a slow sensorimotor rhythm.     

EEG markers of the disturbed systemic brain activity in hypoxia

Specific rearrangements of the brain bioelectric potential field and the structures where the components (waves) of the main EEG rhythms interact, as well as the stereotactic location and power of the equivalent electrical dipole sources (EEDSs), were studied at various stages of acute experimental hypoxia (breathing for 15–30 min a hypoxic gas mixture containing 8% oxygen in nitrogen). The disrupted intercentral relationships that ensure the formation of the dynamic “morphological equivalent” to support the integrative brain activity, rearrangements of this activity, and the adaptive functions of the whole brain proved to account for partial or complete disintegration of systemic brain activity during acute hypoxia. EEDS tomography showed that EEDSs responsible for the generation of the basic brain rhythmic pattern are normally located in the thalamic structures. At the initial stages of hypoxia, the distribution of the EEDS foci is changed so that the density of EEDSs is increased on the sections that include the hypothalamic region structures, basal nuclei of the forebrain, and the limbic system; the basal, frontal, and medial regions of the temporal lobes of both hemispheres are also involved. With increasing hypoxia, EEDSs appeared in the basal and medial regions of the frontal lobes. At this time, both the surface and deep regions of the frontal lobes of the brain hemispheres are the major targets of the hypoxic effect. At the stages of severe hypoxia, pronounced functional changes in the CNS are observed, including the phenomenon of movement of multiple EEDS foci primarily through the basal and mediobasal regions of the frontal and temporal lobes and in the limbic system structures. Thus, despite the generalized high-amplitude paroxysmal activity that is observed in EEG, a functional disintegration (disruption) of interactions between individual brain regions appears and leads to disturbed regulation of the brain and systemic brain activity. Spatiotemporal EEG markers have been identified that make it possible to assess the individual sensitivity and resistance to hypoxia, as well as the degree of disintegration of his systemic brain activity at different stages of hypoxia.     

Metabolic characteristics of brain structures during conscious and unconscious anxiety

Metabolic processes accompanying conscious and unconscious anxiety states in patients with multiple sclerosis were studied. The correspondence between glucose metabolism rates (evaluated using positron emission tomography images) and indices of conscious and unconscious anxiety (according to the Taylor and Luscher test scores) was estimated. Data on the specific features of brain activity at various levels of conscious and unconscious anxiety were obtained. The elevation of conscious anxiety was accompanied by an increase in the metabolic activity of the left-hemisphere cortical and subcortical structures, as well as by a decrease in the glucose metabolism rate in the majority of right-hemisphere structures (except limbic and thalamic structures). The elevation of unconscious anxiety was accompanied by a decrease in the rate of glucose metabolism in the left frontal structures, whereas in the amygdala, as well as in the other limbic structures (gyrus temporalis inferior), its rate increased.     

Mechanisms of self-regulation and interaction of the central nervous system and of the hypophyseal-sexual system

Literary review on the problem of regulation of the sexual glands functions by the central nervous system and the effect of the sex and tropine hormones on the brain formation activity is given. In experiments on rabbits and rats sexual steroid hormones have been shown to alter the bioelectric activity mainly in the structures of the Nauta septo-hypothalamo-hippocampal circle and the amygdalar circle of the limbic system. The data obtained suggested the steroid hormones participation in the processes of self-regulation of the cerebral reticulo-hypothalamo-limbic complex's functions by means of involving the limbic system circles into the process of reverberation.     

Discovery of the sources of some descending forebrain systems by the retrograde axonal transport of horseradish peroxidase method

The location of neurons forming fiber systems descending into the brain-stem reticular formation, red nucleus, and relay nuclei of the dorsal columns was studied in cats by the retrograde axonal transport of horseradish peroxidase method. The cortical projection regions, structures of the limbic system, and the hypothalamus were shown to form fiber systems that descend to the brain stem, whereas the orbito-frontal cortex is the chief source of cortico-reticular projections. The possible functional role of these descending systems in the central control of somatic and visceral functions is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 11, No. 3, pp. 218–226, May–June, 1979.     

Transient structures of the human fetal brain: subplate, thalamic reticular complex, ganglionic eminence

Morphological features of the subplate, the thalamic reticular complex and the ganglionic eminence, which represent three major transient structures of the human fetal forebrain, are summarized with special reference to their functional roles. The subplate harboring various neuronal types is an outstandingly wide zone subjacent to the cortical plate in the human fetal brain. Within the subplate various cortical afferents establish synaptic contacts for a prolonged period before entering the cortical plate. Therefore, the subplate is regarded as a "waiting compartment" which is required for the formation of mature cortical connections. Next to the thalamic reticular nucleus, within the fibers of internal capsule, the perireticular nucleus is located which has been established as a distinct entity during development. Its various neuronal types express a number of different neuroactive substances. Perinatally, the perireticular nucleus is drastically reduced in size. It is involved in the guidance of corticofugal and thalamocortical fibers. The ganglionic eminence is a conspicuous proliferative area that persists throughout nearly the entire fetal period. In the human fetal brain it extends medially upon the dorsal thalamic nuclei which receive precursor cells from the ganglionic eminence. Postmitotic cells in the marginal zone of the ganglionic eminence serve as an intermediate target for growing axons. On the whole, all three structures establish transient neural circuitries that may be essential for the formation of adult projections. The characteristics of the three transient structures are particularly relevant for developmental neuropathology as these structures may be damaged in disorders that preferentially occur in preterm infants.     

Possible mechanisms of the anterior limbic cortex influence on the neuron activity of the vago-solitary complex

In ananesthetized cats, neurons of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DMNV) revealed phasic excitatory responses to separate single vagal and cortical stimuli. Stimulation of the anterior limbic cortex combined with vagal stimulation resulted in inhibitory or excitatory modification of the vagal induced responses of the NTS and DMNV neurons. The data obtained suggest that complete inhibitory effects are related to general cortical mechanisms of control of the functional state of the brain stem visceral neurons. Selective inhibition of the vagal induced responses by limbic cortex stimulation is due to particular cortical mechanisms of the visceral sensory transmission control via the NTS neurons.     

Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study

The presence of central cannabinoid receptor (CB1), involving the N-terminal 14 amino acid peptide, was demonstrated in the rat brain by immunohistochemistry. Intensely stained neurons were observed in the principal neurons of the hippocampus, striatum, substantia nigra, cerebellar cortex, including the Purkinje cells. Moderate CB1-IR cell bodies and fibers were present in the olfactory bulb, cingulate, entorhinal and piriform cortical areas, amygdala and nucleus accumbens. The perivascular glial fibers have shown moderate to high density CB1-IR in olfactory and limbic structures. Low density was detected in the thalamus and hypothalamus and area postrema. The CB1 receptor was widely distributed in the forebrain and sparsely in the hindbrain. These new data support the view that the endogenous cannabinoids play an important role in different neuronal functions as neuromodulators or neurotransmitters.     

Interrelationship between the neocortex and limbic system in emotional stress and epileptiform syndromes

The paper describes bioelectrical correlates of negative emotional states on three models: 1) states caused by local, chronic electric stimulation of negative emotiogenic zones (in cats, rabbits); 2) by a neurogenic stress in rats resulting from a conflict of afferent excitations; 3) by an experimental syndrome--"expectation stress". The data attest that hypersynchronization of bioelectrical activity in limbic and cortical structures is a sufficiently significant correlate of an emotional stress. It is assumed that hypersynchronization reflects one of the general mechanisms of involvement of brain structures in a state of neurogenic stress and its manifestation.