The role of vestibular afferent input in systemic interactions of cortical areas in the human brain

To investigate the role of vestibular afferent input in systemic interactions between cortical areas of the human brain, the dynamics of interregional cortical interactions has been studied in patients with cervical dystonia during their therapy by the removal of the transtympanic chemical vestibular receptor. It has been found that even unilateral vestibular dereception leads to a profound reorganization of systemic interactions between remote cortical areas, particularly, the anterior and posterior associative areas in both hemispheres. Relationships indicating the role of vestibular input in the organization of integrative brain activity have been found, which confirms its systemic role.     

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: A Neuroendocrine Approach to Patients With Traumatic Brain Injury

Objective: Traumatic brain injury (TBI) is now recognized as a major public health concern in the United States and is associated with substantial morbidity and mortality in both children and adults. Several lines of evidence indicate that TBI-induced hypopituitarism is not infrequent in TBI survivors and may contribute to the burden of illness in this population. The goal of this article is to review the published data and propose an approach for the neuroendocrine evaluation and management of these patients.Methods: To identify pertinent articles, electronic literature searches were conducted using the following keywords: “traumatic brain injury,” “pituitary,” “hypopituitarism,” “growth hormone deficiency,” “hypogonadism,” “hypoadrenalism,” and “hypothyroidism.” Relevant articles were identified and considered for inclusion in the present article.Results: TBI-induced hypopituitarism appears to be more common in patients with severe TBI. However, patients with mild TBI or those with repeated, sports-, or blast-related TBI are also at risk for hypopituitarism. Deficiencies of growth hormone and gonadotropins appear to be most common and have been associated with increased morbidity in this population. A systematic approach is advised in order to establish the presence of pituitary hormone deficiencies and implement appropriate replacement therapies.Conclusion: The presence of traumatic hypopituitarism should be considered during the acute phase as well as during the rehabilitation phase of patients with TBI. All patients with moderate to severe TBI require evaluation of pituitary function. In addition, symptomatic patients with mild TBI and impaired quality of life are at risk for hypopituitarism and should be offered neuroendocrine testing.Abbreviations: CBG = corticosteroid-binding globulin DI = diabetes insipidus GH = growth hormone IGF-1 = insulin-like growth factor 1 SIADH = syndrome of inappropriate antidiuretic hormone T₄ = thyroxine TBI = traumatic brain injury TSH = thyroid-stimulating hormone     

Stabilization of motor asymmetry in the goldfish under the influence of optokinetic stimulation

Adaptation as a memory model appears, at the cellular level, as an increase in the resistivity of neurons to fatigue under the influence of repetitive natural training stimulation. Selective induction of adaptational changes in separate compartments of one and the same neuron can also serve as an important instrument for identification of the roles of these compartments in the integrative function of the individual neuron. Mauthner neurons (MNs) of fishes (the goldfish in particular) possess a clearly differentiated soma and two dendrites, lateral and ventral ones. The soma and lateral dendrite of each MN receive afferentation from the ipsilateral vestibular apparatus; at present, the functional and morphological aspects of selective adaptational modifications induced in these compartments by adequate vestibular stimulation have been examined in detail. As to the ventral MN dendrite receiving visual afferentation from the contralateral eye via the ipsilateral tectum, it remained impossible until now to realize the respective approach. We found that training sessions of visual optokinetic stimulation performed in certain modes provide selective activation of one MN through its ventral dendrite and increase the resistivity of this cell to fatiguing stimulation. Therefore, we first demonstrated the possibility of adaptational changes in an individual ventral dendrite of the MN. If fishes were preliminarily adapted with respect to vestibular stimulation, and the resistivity of the soma and lateral dendrite was selectively increased, the resistivity to fatiguing visual test stimulation also increased. On the other hand, if fishes were preliminarily adapted with respect to visual stimulation, the resistivity to fatiguing vestibular stimulation also increased. The observed increase in the resistivity of MNs of fishes adapted due to sensory stimulation of one afferent input with respect to sensory stimulation of other sensory input, as well as an increase in the resistivity to sensory stimulation of one modality, probably show that the mechanism of increase in the resistivity is the same in both cases. Neirofiziologiya/Neurophysiology, Vol. 40, No. 3, pp. 211–220, May–June, 2008.     

The characteristics of the opioid regulation of the afferent reactions of the stomach and duodenum to the early stages of their acute damage]

Acute cat experiments were conducted to study the effect of naloxone, moradol and dalargin on the formation of afferent reactions of gastroduodenal complex components by registration of cortical and subcortical evoked potentials during electrostimulation of the stomach and duodenum at an early stage of their acute lesion. It is found that agonists and antagonists of opiate receptors prevent the depression of afferentation of gastroduodenal complex components early after acute lesion. It is suggested that the main mechanism underlying the depression of gastric and duodenal afferent reactions at early post-alteration period may be related to activation of intraorganic opioid systems.     

Afferentation of the heart in pathological states of the myocardium

The state of afferent connections between sinoatrial node zone (SNZ) in the normal and affected myocardium (reversible ischemia, necrosis) and rostral parts of the brain cortex (RPC) was studied with the help of evoked potentials in acute experiments on cats. Interruption of afferent connections (SNZ-RPC) during reversible ischemia and experimental myocardial necrosis of the right ventricle was revealed. Ultramicroscopic data of SNZ studies as well as electrophysiologic changes registered in RCP during irritation of the peripheral part of the right vagus nerve and local application of GABA on SNZ suggest possible interruption of cardiac afferentation at the level of SNZ due to the mechanism of presynaptic inhibition.     

Features of corticofugal effects of the motor area of the cortex on processing of heterogeneous afferentation in the parafascicular complex of the thalamus in the cat

Evoked potentials to somatic and visual stimuli were recorded in the parafascicular complex (parafascicular nuclei--centrum medianum--Pf--CM) of the thalamus of cats anaesthetized by nembutal. Cooling of the motor cortex was also used. The influence of the motor cortex on processing of the visual and somatic afferent signals at the thalamic level was found to be direct but different by its character. The motor cortex exerted unidirectional facilitatory modulatory action of a tonic type on the processing of visual afferentation and general facilitatory influence against the background of which particular excitatory and inhibitory effects were seen which it exerted on the processing of somatic signals. Episodically the motor cortex completely controlled the afferent inputs activated by somatic impulses. The motor cortical area non-equally influenced afferentation of the same modality forming the different components of the evoked potentials in Pf--CM. On the base of our present and earlier obtained data an idea has been formed of existence of a general principle of differentiated influences of polysensory areas on heterogeneous afferentation on nonspecific and association thalamic nuclei, and of realization of these influences through separation of functionally isolated subsystems in descending pathways. Each of the subsystems by closing separate thalamo-cortical circuits might transmit signals of a single modality.     

Polyfunctionality of neurons: The blocking of extreme pathological afferentation leads to an improvement of the higher functions of the brain

In this paper, a possible mechanism for improving the functional state of the brain regions maintaining locomotor, visual, auditory, and higher functions of the brain during the correction of the generalized spastic syndrome (botulinotherapy with Xeomin) in patients in the vegetative state (VS) is discussed. If the vegetative state is considered as a stable pathological condition (SPC) of the brain, then, in terms of the theory of the structural-functional organization of brain systems with rigid and flexible elements (N.P. Bechtereva), the therapy led to an unbalance of SPC, functional liberation of neurons, redistribution of their functions to ensure other activities, and the formation of new interneuronal connections. Taking into account the functional variability of neurons (S.V. Medvedev), the blocking of the neuromuscular transmission in spastic muscles reduces the abnormal afferent and efferent hyperactivity of motor and sensory neuronal circuits, which liberates the brain for other activities. Clinically, this allows considering botulinotherapy of drug-resistant muscle spasticity in patients in VS and minimal consciousness not only as a symptomatic treatment but also as indirect neuroprotection.     

Electrographic Correlates of Brain Reactions to Afferent Stimuli in Postcomatose Unconscious States after Severe Brain Injury

Analysis of the character and systemic organization of cerebral reactions to external effects aids in adequate evaluation of functional and adaptive human capabilities in norm and pathology. Changes in the spatiotemporal organization of the EEG (according to visual and spectral coherence analyses, as well as localization of equivalent dipole sources of pathological EEG phenomena) and the electrooculogram in response to afferent stimuli at different stages of postcomatose recovery of mental activity were studied in 84 patients with severe brain injury in a prolonged postcomatose unconscious state. Both standard indifferent (a rhythmically flashing light and an acoustic tone) and functionally significant (a moving contrasting black-and-white strip, a red spot, the mother’s voice, music, etc.) afferent stimuli were used. Functionally different reactive changes in the EEG were detected even in deep inhibition of consciousness (a vegetative state). EEG reactions including a strengthening of pathological foci in the CNS with dominant features suggested a poor prognosis. In the absence of such foci, a positive activating effect on mental recovery was found for afferent stimulation, in particular, functionally significant stimulation. Selective sensitivity of the CNS to certain external stimuli was observed for certain unconscious states.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 5–15.Original Russian Text Copyright © 2005 by Sharova.     

Effects of Near-Threshold Stimulation of the Vestibular Apparatus on Postural Responses Evoked by Displacements of the Visualized Surrounding

In healthy subjects in the relaxed upward stance and perceiving a virtual visual environment (VVE), we recorded postural reactions to isolated visual and vestibular stimulations or their combinations. Lateral displacements of the visualized virtual scene were used as visual stimuli. The vestibular apparatus was stimulated by application of near-threshold galvanic current pulses to the proc. mastoidei of the temporal bones. Isolated VVE shifts evoked mild, nonetheless clear, body tilts readily distinguished in separate trials; at the same time, postural effects of isolated vestibular stimulation could be detected only after averaging of several trials synchronized with respect to the beginning of stimulation. Under conditions of simultaneous combined presentation of visual and vestibular stimuli, the direction of the resulting postural responses always corresponded to the direction of responses induced by VVE shifts. The contribution of an afferent volley from the vestibular organ depended on the coincidence/mismatch of the direction of motor response evoked by such a volley with the direction of response to visual stimulation. When both types of stimulations evoked unidirectional body tilts, postural responses were facilitated, and the resulting effect was greater than that of simple summation of the reactions to isolated actions of the above stimuli. In the case where isolated galvanic stimulation evoked a response opposite with respect to that induced by visual stimulation, the combined action of these stimuli of different modalities evoked postural responses identical in their magnitude, direction, and shape to those evoked by isolated visual stimulation. The above findings allow us to conclude that the effects of visual afferent input on the vertical posture under conditions of our experiments clearly dominate. In general, these results confirm the statement that neuronal structures involved in integrative processing of different afferent volleys preferably select certain type of afferentation carrying more significant or more detailed information on displacements (including oscillations) of the body in space.     

Genesis of different components of evoked response in the associative parietal cortex of the cat's brain

The responses evoked in the associative parietal region of the brain by different peripheral stimuli constitute a complex reaction. An early short-latent component of the associative response (ECAR) is formed as the result of specific afferentation, whereas the long-latent late component that follows it is evoked by pulsations from nonspecific, reticular, and associative nuclei in the thalamus or by pulsations arriving from specific nuclei by indirect routes. The cortical mechanisms whereby ECAR arise may be provided by the structural-organization characteristics of interneuronal connections, in particular by the presence in all cortical layers of the terminals of afferent fibers, which establish contact that are mainly axodendritic.Institute of Normal and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 4, pp. 399–405, July–August, 1970.     

Suppressor of Cytokine Signaling-2 (SOCS2) Regulates the Microglial Response and Improves Functional Outcome after Traumatic Brain Injury in Mice

Traumatic brain injury (TBI) is frequently characterized by neuronal, axonal and myelin loss, reactive gliosis and neuroinflammation, often associated with functional deficits. Endogenous repair mechanisms include production of new neurons from precursor cells, but usually the new neurons fail to integrate and survive more than a few weeks. This is in part mediated by the toxic and inflammatory environment present in the injured brain which activates precursor cells to proliferate and differentiate but limits survival of the newborn progeny. Therefore, an understanding of mechanisms that regulate production and survival of newborn neurons and the neuroinflammatory response after brain injury may lead to therapeutic options to improve outcomes. Suppressor of Cytokine Signaling 2 (SOCS2) promotes hippocampal neurogenesis and survival of newborn neurons in the adult brain and regulates anti-inflammatory responses in the periphery, suggesting it may be a useful candidate to improve outcomes of TBI. In this study the functional and cellular responses of SOCS2 over-expressing transgenic (SOCS2Tg) mice were compared to wildtype littermates following mild or moderately severe TBI. Unlike wildtype controls, SOCS2Tg mice showed functional improvement on a ladder test, with a smaller lesion volume at 7d post injury and increased numbers of proliferative CD11b⁺ microglia/macrophages at 35d post-injury in the mild injury paradigm. At 7d post-moderately severe injury there was an increase in the area covered by cells expressing an anti-inflammatory M2 phenotype marker (CD206⁺) but no difference in cells with a pro-inflammatory M1 phenotype marker (CD16/32⁺). No effect of SOCS2 overexpression was observed in production or survival of newborn neurons, even in the presence of the neuroprotective agent erythropoietin (EPO). Therefore, SOCS2 may improve outcome of TBI in mice by regulating aspects of the neuroinflammatory response, promoting a more anti-inflammatory environment, although this was not sufficient to enhance survival of newborn cortical neurons.     

The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury

Traumatic brain injury (TBI) provokes primary and secondary damage on endothelium and brain parenchyma, leading neurons die rapidly by necrosis. The mammalian target of rapamycin signalling pathway (mTOR) manages numerous aspects of cellular growth, and it is up-regulated after moderate to severe traumatic brain injury (TBI). Currently, the significance of this increased signalling event for the recovery of brain function is unclear; therefore, we used two different selective inhibitors of mTOR activity to discover the functional role of mTOR inhibition in a mouse model of TBI performed by a controlled cortical impact injury (CCI). Treatment with KU0063794, a dual mTORC1 and mTORC2 inhibitor, and with rapamycin as well-known inhibitor of mTOR, was performed 1 and 4 hours subsequent to TBI. Results proved that mTOR inhibitors, especially KU0063794, significantly improved cognitive and motor recovery after TBI, reducing lesion volumes. Also, treatment with mTOR inhibitors ameliorated the neuroinflammation associated with TBI, showing a diminished neuronal death and astrogliosis after trauma. Our findings propose that the involvement of selective mTORC1/2 inhibitor may represent a therapeutic strategy to improve recovery after brain trauma.     

Hematopoietic thymocyte precursors. III. A population of thymocytes with the capacity to return ("home") to the thymus.

A subpopulation of thymocytes with the capacity to return (“home”) to and repopulate the thymus of an irradiated mouse has been identified. These cells differ from the majority of cortical thymocytes in that they are of a lower buoyant density and have higher cortisone and X-ray resistance. They also bear an antigen common to mouse brain but not found on the majority of cortical thymocytes. This subpopulation is derived from a hematopoietic thymocyte progenitor and provides an intrathymic reserve of thymocyte precursors. It appears to be a non self-sustaining “transit” population in the pathway of T-cell development.     

Purkinje cells in posterior cerebellar vermis encode motion in an inertial reference frame

The ability to orient and navigate through the terrestrial environment represents a computational challenge common to all vertebrates. It arises because motion sensors in the inner ear, the otolith organs, and the semicircular canals transduce self-motion in an egocentric reference frame. As a result, vestibular afferent information reaching the brain is inappropriate for coding our own motion and orientation relative to the outside world. Here we show that cerebellar cortical neuron activity in vermal lobules 9 and 10 reflects the critical computations of transforming head-centered vestibular afferent information into earth-referenced self-motion and spatial orientation signals. Unlike vestibular and deep cerebellar nuclei neurons, where a mixture of responses was observed, Purkinje cells represent a homogeneous population that encodes inertial motion. They carry the earth-horizontal component of a spatially transformed and temporally integrated rotation signal from the semicircular canals, which is critical for computing head attitude, thus isolating inertial linear accelerations during navigation.     

Neuronal activity controls the development of interneurons in the somatosensory cortex

BACKGROUND

Neuronal activity in cortical areas regulates neurodevelopment by interacting with defined genetic programs to shape the mature central nervous system. Electrical activity is conveyed to sensory cortical areas via intracortical and thalamocortical neurons, and includes oscillatory patterns that have been measured across cortical regions.

OBJECTIVE

In this work, we review the most recent findings about how electrical activity shapes the developmental assembly of functional circuitry in the somatosensory cortex, with an emphasis on interneuron maturation and integration. We include studies on the effect of various neurotransmitters and on the influence of thalamocortical afferent activity on circuit development. We additionally reviewed studies describing network activity patterns.

METHODS

We conducted an extensive literature search using both the PubMed and Google Scholar search engines. The following keywords were used in various iterations: “interneuron”, “somatosensory”, “development”, “activity”, “network patterns”, “thalamocortical”, “NMDA receptor”, “plasticity”. We additionally selected papers known to us from past reading, and those recommended to us by reviewers and members of our lab.

RESULTS

We reviewed a total of 132 articles that focused on the role of activity in interneuronal migration, maturation, and circuit development, as well as the source of electrical inputs and patterns of cortical activity in the somatosensory cortex. 79 of these papers included in this timely review were written between 2007 and 2016.

CONCLUSION

Neuronal activity shapes the developmental assembly of functional circuitry in the somatosensory cortical interneurons. This activity impacts nearly every aspect of development and acquisition of mature neuronal characteristics, and may contribute to changing phenotypes, altered transmitter expression, and plasticity in the adult. Progressively changing oscillatory network patterns contribute to this activity in the early postnatal period, although a direct requirement for specific patterns and origins of activity remains to be demonstrated.

     

Immediate, but not delayed, microsurgical skull reconstruction exacerbates brain damage in experimental traumatic brain injury model

Moderate to severe traumatic brain injury (TBI) often results in malformations to the skull. Aesthetic surgical maneuvers may offer normalized skull structure, but inconsistent surgical closure of the skull area accompanies TBI. We examined whether wound closure by replacement of skull flap and bone wax would allow aesthetic reconstruction of the TBI-induced skull damage without causing any detrimental effects to the cortical tissue. Adult male Sprague-Dawley rats were subjected to TBI using the controlled cortical impact (CCI) injury model. Immediately after the TBI surgery, animals were randomly assigned to skull flap replacement with or without bone wax or no bone reconstruction, then were euthanized at five days post-TBI for pathological analyses. The skull reconstruction provided normalized gross bone architecture, but 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining results revealed larger cortical damage in these animals compared to those that underwent no surgical maneuver at all. Brain swelling accompanied TBI, especially the severe model, that could have relieved the intracranial pressure in those animals with no skull reconstruction. In contrast, the immediate skull reconstruction produced an upregulation of the edema marker aquaporin-4 staining, which likely prevented the therapeutic benefits of brain swelling and resulted in larger cortical infarcts. Interestingly, TBI animals introduced to a delay in skull reconstruction (i.e., 2 days post-TBI) showed significantly reduced edema and infarcts compared to those exposed to immediate skull reconstruction. That immediate, but not delayed, skull reconstruction may exacerbate TBI-induced cortical tissue damage warrants a careful consideration of aesthetic repair of the skull in TBI.     

The role of the thalamic ventrolateral nucleus in the cortical effect on the activity of vestibular neurons

Electrocoagulation of lateral vestibular nucleus (NVL) reduces inhibitory effect of the motor and somatosensory areas and enhances the inhibitory effect of limbic, vestibular, and orbital cortical areas. Facilitating effect was enhanced by electrostimulation of the motor area and reduced by the stimulation of other cortical areas. Following the coagulation of the NVL, the ascending afferent flow to the cortex seems to be reduced. This results in diminishing of the cortical neurones tone and readjusts the descending influences upon the NVL neurones activity.     

The principle of the minimal support of a functional system. The neuronal mechanisms]

Developing nervous cells are characterized by an important trait: a capability for functioning long before the full maturity. During this period, the excitable membrane of a neuron has specific characteristics, the dendritic apparatus is not fully developed, and the level of afferent input is low. All this complicates the initiation of synaptic and impulse potentials. It is suggested that the functioning of neurons at the early developmental stages is underlain by a system of adaptation including: 1) the phenomenon of redundancy (increased number of neurons, spines, and synapses, increased branching); 2) factors increasing the probability to receive the expected afferentation (orientation and growth of dendrites towards the afferent input, structure and localization of branching foci); 3) factors facilitating the initiation of neuronal discharge (juvenile channels generating ion currents, electric interaction between cells, additional triggering zones). The common goal of this whole group of factors is to facilitate the response of a cell to a single or weak signal. This is the principal condition ensuring the realization of neuronal interaction at early stages of brain development. Thus, the essence of the principle of the minimal provision of the early functional systems in Anokhin's theory of systemogenesis that the early functional system involves receptor cells and neurons of hierarchical brain structures that have been the first to mature heterochronously and are at the earliest maturation stage. Achieving the result analogous to that achieved by an adult organism is subserved by additional mechanisms characteristic exclusively for the early maturation stages of neurons and functional systems, which enable the nervous cells to function efficiently even at the early stages of maturity.     

Role of the pulmonary mechanoreceptor apparatus in molding the natural respiration of the frog Rana temporaria

In acute experiments on the frog Rana temporaria, studies have been made of the effect of afferent impulsation in pulmonary mechanoreceptors on respiration pattern. Simultaneous recordings were made of total afferent activity in the pulmonary branch of the vagal nerve and of the activity of motor respiratory nerves as an index of respiration pattern. It was shown that to the end of ventilation period, the level of afferentation decreases up to a threshold value which favours the onset of inspiration. Artificial decrease of afferentation level by the increase in CO2 content in the lung or by novocain application to the latter always resulted in extra-inspiration. On vagotomized frogs, it was found that maximum level of afferent influences is necessary for the onset of expiration.     

The Rich Get Richer: Brain Injury Elicits Hyperconnectivity in Core Subnetworks

There remains much unknown about how large-scale neural networks accommodate neurological disruption, such as moderate and severe traumatic brain injury (TBI). A primary goal in this study was to examine the alterations in network topology occurring during the first year of recovery following TBI. To do so we examined 21 individuals with moderate and severe TBI at 3 and 6 months after resolution of posttraumatic amnesia and 15 age- and education-matched healthy adults using functional MRI and graph theoretical analyses. There were two central hypotheses in this study: 1) physical disruption results in increased functional connectivity, or hyperconnectivity, and 2) hyperconnectivity occurs in regions typically observed to be the most highly connected cortical hubs, or the “rich club”. The current findings generally support the hyperconnectivity hypothesis showing that during the first year of recovery after TBI, neural networks show increased connectivity, and this change is disproportionately represented in brain regions belonging to the brain''s core subnetworks. The selective increases in connectivity observed here are consistent with the preferential attachment model underlying scale-free network development. This study is the largest of its kind and provides the unique opportunity to examine how neural systems adapt to significant neurological disruption during the first year after injury.