Ascending Brain Stem Research Articles

Spinal ascendant necrosis with endotoxin shock associated to staphylococcus Aureus - case report

Bacterial meningitis is rarely complicated by spinal cord involvement in adults. We report a We report a case of Staphylococcus aureus septicemia complicated by meningitis and extensive spinal cord injury, 21-year-old man with tattoos all over the body. The patient's neurological condition worsened within two days, leading to ascending brain stem necrosis and death. The magnetic resonance imaging (MRI) demonstrated intramedullary hyperintensity on T2-weighted image. Postmortem microscopic examination confirmed that the extensive spinal cord injury was of ischemic origin, caused by diffuse leptomeningitis and endarteritis and multiple pulmonary micro-abscess and intravascular disseminated disease and neurotoxic shock associated to Staphylococcus Aureus was diagnosed.

Circadian and wakefulness-sleep modulation of cognition in humans

Cognitive and affective processes vary over the course of the 24 h day. Time of day dependent changes in human cognition are modulated by an internal circadian timekeeping system with a near-24 h period. The human circadian timekeeping system interacts with sleep-wakefulness regulatory processes to modulate brain arousal, neurocognitive and affective function. Brain arousal is regulated by ascending brain stem, basal forebrain (BF) and hypothalamic arousal systems and inhibition or disruption of these systems reduces brain arousal, impairs cognition, and promotes sleep. The internal circadian timekeeping system modulates cognition and affective function by projections from the master circadian clock, located in the hypothalamic suprachiasmatic nuclei (SCN), to arousal and sleep systems and via clock gene oscillations in brain tissues. Understanding the basic principles of circadian and wakefulness-sleep physiology can help to recognize how the circadian system modulates human cognition and influences learning, memory and emotion. Developmental changes in sleep and circadian processes and circadian misalignment in circadian rhythm sleep disorders have important implications for learning, memory and emotion. Overall, when wakefulness occurs at appropriate internal biological times, circadian clockwork benefits human cognitive and emotion function throughout the lifespan. Yet, when wakefulness occurs at inappropriate biological times because of environmental pressures (e.g., early school start times, long work hours that include work at night, shift work, jet lag) or because of circadian rhythm sleep disorders, the resulting misalignment between circadian and wakefulness-sleep physiology leads to impaired cognitive performance, learning, emotion, and safety.

Cholinergic Regulation of the Posterior Medial Thalamic Nucleus

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep-wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.

Theta Rhythm of the Hippocampus: Subcortical Control and Functional Significance

The theta rhythm is the largest extracellular synchronous signal that can be recorded from the mammalian brain and has been strongly implicated in mnemonic processes of the hippocampus. We describe (a) ascending brain stem-forebrain systems involved in controlling theta and nontheta (desynchronization) states of the hippocampal electroencephalogram; (b) theta rhythmically discharging cells in several structures of Papez's circuit and their possible functional significance, specifically with respect to head direction cells in this same circuit; and (c) the role of nucleus reuniens of the thalamus as a major interface between the medial prefrontal cortex and hippocampus and as a prominent source of afferent limbic information to the hippocampus. We suggest that the hippocampus receives two main types of input: theta rhythm from ascending brain stem- diencephaloseptal systems and information bearing mainly from thalamocortical/cortical systems. The temporal convergence of activity of these two systems results in the encoding of information in the hippocampus, primarily reaching it from the entorhinal cortex and nucleus reuniens.

Chapter 28 The modular organization of brain systems. Basal forebrain: the last frontier

Computational anatomical studies suggest that specific clusters of projection neurons in the basal forebrain together with specific prefrontal and posterior cortical associational regions constitute distributed parts of functional parallel circuits. The predictable sequence of cell clusters consisting of various types of noncholinergic cell populations in the basal forebrain suggests further subdivisions within these circuits. It is possible that similar to the parallel basal ganglia circuits (Alexander and Crutcher, 1990), large number of specialized channels and sub-channels exist within this triangular circuitry that permit parallel, multilevel processing concurrently. The location and size of the active modules may temporarily vary according to the prevalence of state-related diffuse ascending brain stem and specific telencephalic inputs. From this latter group of afferents, the prefrontal input may function as an external threshold control which allocates attentional resources via the basal forebrain to distributed cortical processes in a selective, self-regulatory fashion.

A model of theta rhythm production in the septal-hippocampal system and its modulation by ascending brain stem pathways.

Recent experimental observations have disclosed the existence of a septal-hippocampal feedback circuit, composed of medial septum diagonal band of Broca (ms-dbB) GABAergic projections to the inhibitory interneurons of the hippocampus, and hippocampal GABAergic projections to the ms-dbB, the major targets of which are the GABAergic septo-hippocampal projection cells. We propose that this feedback circuit provides the mechanism for the rhythmic suppression of interneuronal activity in the hippocampus, which is observed as low-level GABAergic-mediated theta activity. We also propose that this circuit may be the mechanism by which ascending brain stem pathways to the ms-dbB, in particular from the reticular formation, can influence hippocampal information processing in response to particular behavioral states, by exercising control over the level and frequency of theta activity in the hippocampus. In support of these proposals, we describe a minimal computational model of the feedback circuit which uses a set of four coupled differential equations describing the average dynamic activity of the populations of excitatory and inhibitory cells involved in the circuit. We demonstrate through simulations the inherently robust 4-6-Hz oscillatory dynamics of the circuit, and show that manipulation of internal connection strengths and external modulatory influences on this circuit changes the dynamics in a way which closely mimics corresponding manipulations in recent neurophysiological experiments investigating theta activity.

Epilepsy and sleep

This review discusses several aspects of epilepsy and sleep. The level of wakefulness is controlled by transmitters such as acetylcholine, norepinephrine, serotonin, and histamine. These neurotransmitters are involved in modulatory neurotransmission of the ascending brain stem systems, which play an important role in controlling the sleep-wake cycle. Experimental evidence suggests that rapid eye movement sleep atonia is induced by increased endogenous acetylcholine release. Regarding sleep factors, recent data suggest that prolactin may stimulate rapid eye movement sleep and that growth hormone-releasing factor is involved in non-rapid eye movement sleep regulation. The neuropharmacologic features of several animal models of epilepsy have been investigated. Epileptiform discharges of genetic absence seizures in rats have been found to be suppressed by cholinergic drugs. The beta-carboline abecarnil has a strong antiepileptic effect on spike-wave discharges in rats that generate spontaneous spike-wave discharges, and it may be useful as an antiepileptic drug. Sleep epilepsy has been studied in a model of amygdala-kindled kittens. During the postkindling development, multifocal epilepsy with convulsions occurred that were distributed throughout the sleep-wake cycle; this finding agrees with the clinical literature. A typical feature of juvenile myoclonic epilepsy is the occurrence of seizures in a strict relationship to the sleep-wake cycle. There is now some neurophysiologic evidence that this syndrome also causes disturbance of sleep stability with increased arousal reactions. Nocturnal paroxysmal dystonia is not a homogeneous entity. Several clinical reports indicate that the short-lasting variant is most likely a form of frontal lobe epilepsy, but the nature of the longer-lasting variants is still obscure.

Neuronal activity of the hippocampus deprived of ascending brain stem influences.

1. After basal undercutting of the septum the hippocampus is deprived of ascending direct influences of the brain stem structures and those redirected to the septum, and in a third of the neurons of fields CA1 and CA3 low-frequency (3.3–4.5 Hz) rhythmic bursts can be observed. Theta-like vibrations with a similar low frequency are recorded on the EEG of the hippocampus. Intravenous introduction of eserine leads to a limited increase in the frequency of the rhythmic component (within a range of 1 Hz). 2. The neurons are characterized by a low (46–47%) reactivity to sensory stimuli. 3. The nature of the specific and phasic reactions, typical under normal conditions for field CA1, does not change but they can be observed in both fields. There appear unusual prolonged effects expressed in a stable shift of the level of the activity of the neurons during the period of application of a series of sensory stimuli, and also slowly developing diffuse activation reactions that increase indefinitely in duration. The normal extinction of the reactions is impaired, in the majority of cases the dynamics being incremental in nature. 4. One can observe a sudden fall in the number of tonic inhibiting effects.

Monoamine distribution in primate brain V. Monoaminergic nuclei: Anatomy, pathways and local organization

Monoamine distribution in primate brain V. Monoaminergic nuclei: Anatomy, pathways and local organization

Monoamine distribution in primate brain. V. Monoaminergic nuclei: Anatomy, pathways, and local organization

Monoamine distribution in primate brain. V. Monoaminergic nuclei: Anatomy, pathways, and local organization

Projections of the Inferior Colliculus in Insectivores and Primates; pp. 301–313

The inferior colliculus is a nucleus of obligatory synapse in the ascending brain stem auditory pathways. Projections from the inferior colliculus in primates and insectivores are similar to that demonstrated in other mammals, with short direct projections to the external nucleus of the colliculus and adjacent regions of the central gray and superior colliculus ipsilaterally, and fibers crossing in the commissure of the colliculus to innervate the contralateral central and external nuclei. Long projection fibers enter the brachium of the inferior colliculus bilaterally, but the projection is markedly heavier on the side ipsilateral to the lesion. Brachial fibers supply terminals to two regions of the rostral midbrain tegmentum, the parabrachial area and the interstitial nucleus of the inferior brachium. On reaching the thalamus, brachial fibers bypass the caudal tip of the medial geniculate, but arborize to form a dense plexus of axons and terminals throughout the remainder of the principal nucleus of the geniculate and the entire internal division on the ipsilateral side. A lighter and more restricted projection to the opposite medial geniculate is seen in all primates, and particularly in the hedgehog. The small size of the contralateral tectothalamic pathway in the hedgehog is the only significant species difference noted in this study.

Projections of the Inferior Colliculus in Insectivores and Primates; pp. 314–327

The inferior colliculus is a nucleus of obligatory synapse in the ascending brain stem auditory pathways. Projections from the inferior colliculus in primates and insectivores are similar to that demonstrated in other mammals, with short direct projections to the external nucleus of the colliculus and adjacent regions of the central gray and superior colliculus ipsilaterally, and fibers crossing in the commissure of the colliculus to innervate the contralateral central and external nuclei. Long projection fibers enter the brachium of the inferior colliculus bilaterally, but the projection is markedly heavier on the side ipsilateral to the lesion. Brachial fibers supply terminals to two regions of the rostral midbrain tegmentum, the parabrachial area and the interstitial nucleus of the inferior brachium. On reaching the thalamus, brachial fibers bypass the caudal tip of the medial geniculate, but arborize to form a dense plexus of axons and terminals throughout the remainder of the principal nucleus of the geniculate and the entire internal division on the ipsilateral side. A lighter and more restricted projection to the opposite medial geniculate is seen in all primates, and particularly in the hedgehog. The small size of the contralateral tectothalamic pathway in the hedgehog is the only significant species difference noted in this study.

Ascending brain stem projections of the anteroventral cochlear nucleus in the rhesus monkey.

AbstractIn a series of seventeen rhesus monkeys attempts were made to produce discrete stereotaxic lesions in the anteroventral cochlear nucleus (Av). Anterograde degeneration was described in detail in four cases with lesions confined within the cochlear complex to Av. Fibers decussating at pontine levels coursed exclusively in the trapezoid body. Degenerated fibers projected: ipsi‐laterally to the lateral superior olivary nucleus; bilaterally to the preolivary nuclei; to the lateral side of the ipsilateral medial superior olive and the medial side of the contralateral medial superior olive; and to the contralateral medial trapezoid nucleus. A topographic projection upon the medial superior olive was demonstrated. Projections were bilateral but mainly crossed to the nuclei of the lateral lemniscus and central nucleus of the inferior colliculus; the posterior end of the ipsilateral ventral nucleus of the lateral lemniscus contained an island of profuse degeneration. A few fibers crossed in the commissure of the inferior colliculus. Few if any fibers from Av projected to the contralateral magnocellular medial geniculate.

Effect of interrupting the hypothalamic nervous connections on the norepinephrine and serotonin content of the hypothalamus

The effect of bilateral lesions interrupting the different incoming and outgoing fibers to and from the hypothalmus on the concentration of norepinephrine and serotonin in the hypothalamus was studied in six experimental groups of cats. In some groups the concentration of dopamine and of serotonin was also determined in the corpus striatum. Lesions interrupting brain stem ascending fibers travelling along the base of the midbrain produce a significant decrease of the hypothalamic serotonin and of the striatal serotonin and dopamine. Lesions lateral to the hypathalamus are associated with a significant decrease of dopamine in the corpus striatum. Lesions located rostrally, caudally, laterally and dorsally to the hypothalamus and interrupting a great number of the interconnections of the hypothalamus do not modify the concentration of the hypothalamic norepinephrine. In contrast to the synthesis of serotonin and dopamine which depend on the integrity of ascending brain stem pathways, the elaboration of the hypothalamic norepinephrine apparently takes place independently of the central nervous pathways related to the hypothalamus.

Modulation of brain stem electrical activity by visceral (urinary bladder) distension

In 32 acute experiments in the cat a correlation between sudden changes in the bladder pressure and the electrical activity of the brain was observed. In the waking state an increasing intravesical pressure served as an alerting stimulus to the nonspecific ascending brain stem mechanisms resulting in further desynchronization of the EEG record. In contrast, hypersynchrony in the form of spindle-like activity occurred at the peak pressure or more commonly during the fall of bladder pressure. When spindle activity was present in the background record an increased intravesical pressure often triggered a spindle before arousal of the electrical pattern took place. In these instances the hypersynchrony induced during the fall of intravesical pressure was considerably enhanced. Less consistent results were obtained from distension of other hollow viscera.

Effect upon the EEG of acute injury to the brain stem activating system

The effect upon the EEG in the unanesthetized “encéphale isolé” of acute brain stem lesions in a position to involve the ascending reticular activating system has been studied. Elimination of the bulbar segment was without marked effect. Some synchronization followed elimination of the pons, but the most pronounced and prolonged changes occurred as a result of mesencephalic transection, or of discrete injury to the midbrain tegmentum or basal diencephalon, following which the EEG activation pattern of low voltage fast activity was reduced or abolished and the cortical record became dominated by recurring bursts or spindles of high voltage slow waves, like those of normal sleep or barbiturate anesthesia. Bursts could be recorded from the intralaminar and other nuclei of the thalamus and these thalamic bursts were abolished by acute decortication. Conversely, cortical bursts were abolished by acute thalamic lesions. Possible interrelations of these regions in this activity is discussed. These results offer an explanation for the clinical observation of somnolence following basal injury to the brain, and suggest that a maintained influence of the ascending brain stem activating system underlies wakefulness, while absence of this influence precipitates sleep.

Brain stem reticular formation and activation of the EEG

1. 1. Stimulation of the reticular formation of the brain stem evokes changes in the EEG, consisting of abolition of synchronized discharge and introduction of low voltage fast activity in its place, which are not mediated by any of the known ascending or descending paths that traverse the brain stem. The alteration is a generalized one but is most pronounced in the ipsilateral hemisphere and, sometimes, in its anterior part. 2. 2. This response can be elicited by stimulating the medial bulbar reticular formation, pontile and midbrain tegmentum, and dorsal hypothalamus and subthalamus. The bulbar effect is due to ascending impulses relayed through these more cephalic structures. The excitable substrate possesses a low threshold and responds best to high frequencies of stimulation. 3. 3. Some background synchrony of electrocortical activity is requisite for manifestation of the response. In the “encephale isole”, reticular stimulation has no additional effect upon the fully activated EEG. With synchrony, in spontaneous drowsiness or light chloralosane anesthesia, the effect of reticular stimulation is strikingly like Berger's alpha wave blockade, or any arousal reaction. In full chloralosane anesthesia, high voltage slow waves are blocked but no increase in lower amplitude, fast activity occurs. With barbiturate anesthesia, the reticular response is difficult to elicit or is abolished. 4. 4. In the chloralosane preparation, the secondary cortical response evoked by a sensory volley is generally unaffected by reticular stimulation. Consequent sensory after-discharge is abolished, however, as is pyramidal tract discharge and jerky movements referable to it. Outside the sensory receiving area, secondary responses themselves may be reduced or prevented. 5. 5. The convulsive spikes produced by local strychnine and those of a fit following supramaximal cortical excitation, are not decreased by stimulating the reticular formation. 6. 6. The cortical recruiting response induced by low frequency stimulation of the diffuse thalamic projection system is reduced or abolished by reticular stimulation. 7. 7. There is some indication that the cortical effect of reticular stimulation may be mediated by this diffuse thalamic projection system, for synchronized activity within it is similarly prevented by reticular excitation, and direct high frequency stimulation of this system, within the thalamus, reproduces the reticular response. It is possible, however, that other mechanisms may be involved in its mediation. 8. 8. The reticular response and the arousal reaction to natural stimuli have been compared in the “encéphale isolé”, in which EEG synchrony was present during spontaneous relaxation or was produced by recruiting mechanisms, and the two appear identical. 9. 9. The possibility that the cortical arousal reaction to natural stimuli is mediated by collaterals of afferent pathways to the brain stem reticular formation, and thence through the ascending reticular activating system, rather than by intra-cortical spread following the arrival of afferent impulses at the sensory receiving areas of the cortex, is under investigation. 10. 10. The possibility is considered that a background of maintained activity within this ascending brain stem activating system may account for wakefulness, while reduction of its activity either naturally, by barbiturates, or by experimental injury and disease, may respectively precipitate normal sleep, contribute to anesthesia or produce pathological somnolence.

Brain stem reticular formation and activation of the EEG

1. 1. Stimulation of the reticular formation of the brain stem evokes changes in the EEG, consisting of abolition of synchronized discharge and introduction of low voltage fast activity in its place, which are not mediated by any of the known ascending or descending paths that traverse the brain stem. The alteration is a generalized one but is most pronounced in the ipsilateral hemisphere and, sometimes, in its anterior part. 2. 2. This response can be elicited by stimulating the medial bulbar reticular formation, pontile and midbrain tegmentum, and dorsal hypothalamus and subthalamus. The bulbar effect is due to ascending impulses relayed through these more cephalic structures. The excitable substrate possesses a low threshold and responds best to high frequencies of stimulation. 3. 3. Some background synchrony of electrocortical activity is requisite for manifestation of the response. In the “encephale isole”, reticular stimulation has no additional effect upon the fully activated EEG. With synchrony, in spontaneous drowsiness or light chloralosane anesthesia, the effect of reticular stimulation is strikingly like Berger's alpha wave blockade, or any arousal reaction. In full chloralosane anesthesia, high voltage slow waves are blocked but no increase in lower amplitude, fast activity occurs. With barbiturate anesthesia, the reticular response is difficult to elicit or is abolished. 4. 4. In the chloralosane preparation, the secondary cortical response evoked by a sensory volley is generally unaffected by reticular stimulation. Consequent sensory after-discharge is abolished, however, as is pyramidal tract discharge and jerky movements referable to it. Outside the sensory receiving area, secondary responses themselves may be reduced or prevented. 5. 5. The convulsive spikes produced by local strychnine and those of a fit following supramaximal cortical excitation, are not decreased by stimulating the reticular formation. 6. 6. The cortical recruiting response induced by low frequency stimulation of the diffuse thalamic projection system is reduced or abolished by reticular stimulation. 7. 7. There is some indication that the cortical effect of reticular stimulation may be mediated by this diffuse thalamic projection system, for synchronized activity within it is similarly prevented by reticular excitation, and direct high frequency stimulation of this system, within the thalamus, reproduces the reticular response. It is possible, however, that other mechanisms may be involved in its mediation. 8. 8. The reticular response and the arousal reaction to natural stimuli have been compared in the “encéphale isolé”, in which EEG synchrony was present during spontaneous relaxation or was produced by recruiting mechanisms, and the two appear identical. 9. 9. The possibility that the cortical arousal reaction to natural stimuli is mediated by collaterals of afferent pathways to the brain stem reticular formation, and thence through the ascending reticular activating system, rather than by intra-cortical spread following the arrival of afferent impulses at the sensory receiving areas of the cortex, is under investigation. 10. 10. The possibility is considered that a background of maintained activity within this ascending brain stem activating system may account for wakefulness, while reduction of its activity either naturally, by barbiturates, or by experimental injury and disease, may respectively precipitate normal sleep, contribute to anesthesia or produce pathological somnolence.