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PubMed2006

Cholinergic modulation of cortical function.

Extensive physiological research has demonstrated a number of common effects of acetylcholine within cortical structures, including the hippocampus, piriform cortex, and neocortex (Hasselmo, 1995, 1999). This article will provide a description of how the different physiological effects of acetylcholine could interact to alter specific functional properties of the cortex. The physiological effects of acetylcholine serve to enhance the influence of feed- forward afferent input to the cortex while decreasing background activity by suppressing excitatory feedback connections within cortical circuits. By enhancing the response to sensory input, high levels of acetylcholine enhance attention to sensory stimuli in the environment and enhance encoding of memory for specific stimuli. Interference from prior memory is reduced by suppressing synapses modified by prior learning (Sevilla et al., 2002; Linster et al., 2003).

Acetylcholine↗

PubMed2005

Electrophysiological studies of myoclonus.

As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification, and about its generator mechanisms. The electroencephalogram-electromyogram polygraph reveals the most important information about the myoclonus of interest. Jerk-locked back-averaging and evoked potential studies combined with recording of the long-latency, long-loop reflexes are useful to investigate the pathophysiology of myoclonus further, especially that of cortical myoclonus. Recent advances in magnetoencephalography and transcranial magnetic stimulation have contributed significantly to the understanding of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in individual patients is important for selecting the most appropriate treatment.

Action Potentials↗

PubMed1989

Regional cerebral blood flow response during and after acute asphyxia in newborn piglets.

The hemodynamic response during and after acute asphyxia was studied in 14 newborn piglets. An apnea-like asphyxial insult was produced in paralyzed mechanically ventilated piglets by discontinuing ventilation until the piglets became bradycardic (heart rate less than 80 beats/min). Seven piglets had organ blood flow measured by microspheres at control, during asphyxia (PO2 = 16 +/- 11 Torr, pH = 7.31 +/- 0.07, PCO2 = 47 +/- 9 Torr), and during recovery from asphyxia. During acute asphyxia, rapid organ blood flow redistribution occurred, producing decreased renal and skeletal muscle blood flow, while coronary blood flow increased. Although total brain blood flow changed little during asphyxia, regional cerebral blood flow (rCBF) analysis revealed significant nonhomogeneous blood flow distribution within the brain during asphyxia, with decreases to the cerebral gray and white matter and the choroid plexus, whereas brain stem structures had increased flow. During recovery with reventilation, total brain blood flow increased 24% above control, with a more uniform distribution and increased flow to all brain regions. The time course of rCBF changes during acute asphyxia was then determined in seven additional piglets with CBF measurements made sequentially at 30-60 s, 60-120 s, and 120-180 s of asphyxia. The vasoconstriction seen in cortical structures, concurrent with the reduction in skeletal and kidney blood flow, known to be sympathetically mediated, suggest a selective reflex effect in this brain region. The more gradual and progressive vasodilation in brain stem regions during asphyxia is consistent with chemical control. These findings demonstrate significant regional heterogeneity in CBF regulation in newborn piglets.

Animals↗

PubMed1975

A normally laminated afferent projection to an abnormally laminated cortex: some olfactory connections in the reeler mouse.

The relative positions of pyramidal and polymorphic cell classes are inverted in the central olfactory cortical structures of the reeler mutant mouse. Each cell class is generated at the normal embryonic time. The polymorphic cells of the mutant, like those of the normal, are generated between E11-E13. The pyramidal cells are formed between E11-E16 in both. Despite the anomalous positions of their somata deep in the cortex the apical dendrites of many pyramidal cells reach and ramify at a superficial cortical level subjacent to the lateral olfactory tract. The main and accessory olfactory bulbs are cytoarchitectonically normal in the mutant and project normally upon the anterior olfactory nucleus, the olfactory tubercle, the hippocampal rudiment, the piriform cortex, the amygdaloid region and the entorhinal cortex. As in the normal animal the axons transverse layer Ialpha, and their terminals are concentrated in the immediately subjacent laminar zone. The rostrally directed cortic-cortical association system of the piriform cortex projects upon the anterior olfactory nucleus in the mutant just as in the normal with a relative concentration of terminals in a lamina subjacent and complementary to the zone of termination afferent systems in the abnormally laminated olfactory cortex of the mutant syggests that, in this system at least, the developmental mechanisms which determine relative position of neuron somata and those which govern axon trajectories and the distribution of axon terminals are largely independent.

Animals↗

PubMed1994

Patterns of cerebral glucose metabolism detected with positron emission tomography differ in multiple system atrophy and olivopontocerebellar atrophy.

We used positron emission tomography with [18F]fluorodeoxyglucose to study local cerebral metabolic rates for glucose (ICMRglc) in patients with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA) in comparison with normal control subjects. IN MSA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In sOPCA, absolute lCMRglc was significantly decreased in the brainstem, cerebellum, putamen, thalamus, and cerebral cortex. In dOPCA, absolute lCMRglc was significantly decreased in the brainstem and cerebellum but not in the other structures. Examination of lCMRglc normalized to the cerebral cortex in comparison with normal controls revealed in MSA significant decreases in the brainstem, cerebellum, and putamen but, in both sOPCA and dOPCA, significant decreases only in the brainstem and cerebellum. The findings indicate that these three disorders all show a marked decrease of lCMRglc in the brainstem and cerebellum but differ in the degree of hypometabolism in forebrain and cerebral cortical structures. The results are consistent with the possibility that, in many cases, sOPCA will evolve into MSA. Moreover, positron emission tomography may provide helpful diagnostic information in these neurodegenerative diseases.

Adult↗

PubMed1976

Differential cortical degradation in the two members of early conjugant pairs of Oxytricha fallax.

A differential resorption of the anterior ventral cortical structures is shown to occur in early conjugating pairs of Oxytricha. The member on the pair's left resorbs the collar membranelles and the frontal and right marginal cirri; the member on the pair's right resorbs the central and posterior membranelles (lapel) of the adoral zone of membranelles. The lapel of the left member then aligns with the collar of the right member to form a composite structure which appears with light and scanning electron microscopy to be completely integrated. Consequently, a 4-5-hour-old pair contains slightly more than one complete set of anterior ventral organelles (viz., one extra set of undulating membranes) and two complete sets of ventral and anal cirri. Analysis of conjugant pairs in which the two members are joined in abnormal positions suggests that neither the proximity of certain cortical organelles to the region of cytoplasmic bridge formation, the specific pairing position, nor the relocation of certain cortical organelles into a different cortical region is directly responsible for determining which resorption pattern occurs. Furthermore, analysis of the cortical events in conjugating doublets suggests that neither nuclear determination nor differential gene expression can account for the phenomena observed in Oxytricha.

Animals↗

PubMed1993

Spreading depression can be restricted to distinct depths of the rat cerebral cortex.

In cerebral cortex of rats recurrent and single spreading depressions (SDs) were elicited by KCl application and by needle prick, respectively. SDs were monitored by recording changes of DC (direct current) potentials and of K+ concentration ([K+]o) in the extracellular space using K(+)-selective microelectrodes. Profiles of DC potential and of [K+]o were obtained by stepwise lowering a microelectrode array consisting of up to four electrodes into the brain cortex. Recurrent SDs propagating from the site of KCl application had lower frequencies and longer duration in superficial compared to deeper cortical structures. Single SD elicited by needle prick 3 mm away from the recording sites usually invaded the whole grey matter and showed DC potential shifts that differed in shape from the recurrent SDs. At a depth restricted to 1000 microns SD-related DC potential shifts and rises in [K+]o were drastically diminished. In 2 of 8 experiments prick-elicited SD was absent either above or below cortical depths of 800-1000 microns. The results suggest a barrier for vertical SD propagation in cortical depth between 800 and 1200 microns. The observations are relevant for application of noninvasive techniques (DC electroencephalography, magnetoencephalography) to detect SD in the brain.

Animals↗

PubMed2005

Polarity of the ascidian egg cortex and relocalization of cER and mRNAs in the early embryo.

The mature ascidian oocyte is a large cell containing cytoplasmic and cortical domains polarized along a primary animal-vegetal (a-v) axis. The oocyte cortex is characterized by a gradient distribution of a submembrane monolayer of cortical rough endoplasmic reticulum (cER) and associated maternal postplasmic/PEM mRNAs (cER-mRNA domain). Between fertilization and first cleavage, this cER-mRNA domain is first concentrated vegetally and then relocated towards the posterior pole via microfilament-driven cortical contractions and spermaster-microtubule-driven translocations. The cER-mRNA domain further concentrates in a macroscopic cortical structure called the centrosome attracting body (CAB), which mediates a series of asymmetric divisions starting at the eight-cell stage. This results in the segregation of determinant mRNAs and their products in posterior cells of the embryo precursors of the muscle and germ line. Using two species of ascidians (Ciona intestinalis and Phallusia mammillata), we have pursued and amplified the work initiated in Halocynthia roretzi. We have analysed the cortical reorganizations in whole cells and in cortical fragments isolated from oocytes and from synchronously developing zygotes and embryos. After fertilization, we observe that a cortical patch rich in microfilaments encircles the cER-mRNA domain, concentrated into a cortical cap at the vegetal/contraction pole (indicating the future dorsal pole). Isolated cortices also retain microtubule asters rich in cER (indicating the future posterior pole). Before mitosis, parts of the cER-mRNA domain are detected, together with short microtubules, in isolated posterior (but not anterior) cortices. At the eight-cell stage, the posteriorly located cER-mRNA domain undergoes a cell-cycle-dependant compaction into the CAB. The CAB with embedded centrosomal microtubules can be isolated with cortical fragments from eight-cell-stage embryos. These and previous observations indicate that cytoskeleton-driven repositioning and compaction of a polarized cortical domain made of rough ER is a conserved mechanism used for polarization and segregation of cortical maternal mRNAs in embryos of evolutionarily distant species of ascidians.

Animals↗

PubMed2004

Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 organizes ERM proteins at the apical membrane of polarized epithelia.

Ezrin-radixin-moesin (ERM) proteins regulate the organization and function of specific cortical structures in polarized epithelial cells by connecting filamentous (F)-actin to plasma membrane proteins. The contribution of ERM proteins to these structures depends on a conformational change to an active state in which the C-terminal region interacts with F-actin and the N-terminal domain interacts with membrane ligands. The specific ligands necessary for stabilizing ERM proteins at the membrane are not known. By generating mice deficient for ERM-binding phosphoprotein 50/Na(+)/H(+) exchanger regulatory factor 1 (EBP50/NHERF1), which binds the N-terminal domain of ERM proteins, we found that EBP50 is required for the maintenance of active ERM proteins at the cortical brush border membranes (BBM) of polarized epithelia. In EBP50(-/-) mice, ERM proteins were significantly decreased specifically in BBM from kidney and small intestine epithelial cells, whereas they remained unchanged in the cytoplasm. In wild-type animals, EBP50 was localized to the BBM compartment where it was processed by cleavage of the ERM-binding motif. In BBM, active ERM proteins formed distinct complexes with full-length EBP50 and with F-actin, suggesting a switch mechanism in which proteolytically processed EBP50 would release ERM proteins to complex with F-actin. The structural defects found in the EBP50(-/-) intestinal microvilli were reminiscent of those described in ezrin(-/-) mice, suggesting a role for EBP50 in organizing apical epithelial membranes.

Actins↗

PubMed1982

[Correlative aspects between function and structure in hippocampal processes (Ammon's formation)].

In post-mortem material with pronounced primary epilepsy-independent pathomorphic findings of Ammon's formation, the correlation with symptomatic epilepsy and the typical psychic disturbance phenomena was studied. While a connection between the lesion and the epileptic disease could be confirmed with a certain probability, this remains problematic with respect to impairments of memory, orientation capacity, working-up of experiences and drive and reaction capacity. Although in all examined subjects clinical deficiency phenomena of one type or the other were present, additional lesions, especially of nuclear regions which are associated with AF and cortical structures will certainly also be responsible.

Adolescent↗

PubMed1989

Acute ultrastructural response of hypoxic hypoxia with relative ischemia in the isolated brain.

The acute cortical response to surgical brain isolation and subsequent extracorporal normoxic or 30 min hypoxic (PaO2 = 20 mm Hg) perfusions (hypoxic hypoxia with relative ischemia) was evaluated. Cerebral blood flow, arterial pH and CO2 were maintained constant during both perfusions; only the arterial oxygen content was changed. The isolated brain model used in this and previous investigations produces no qualitative ultrastructural changes in the neocortex following brain isolation and normoxic perfusion. However, the acute cortical structural response to 30 min of hypoxic hypoxia with relative ischemia demonstrated a number of important observations. Hypoxic hypoxia produced ultrastructural responses common to cerebral ischemia such as nuclear chromatin clumping, nucleolar condensation and cytoskeletal breakdown. Although neuronal abnormalities seen after 30 min of hypoxic hypoxia were similar to those acute neuronal changes observed following complete cerebral ischemia without recirculation, they differed three ways: (a) mitochondrial swelling and microvacuolation were observed in many cortical pyramidal neurons. (b) Glycogen particles within astroglial processes were observed even after a 30-min period of hypoxic hypoxia. (c) Perivascular astroglial swelling was minimal despite considerable perineuronal swelling. In contrast, incomplete cerebral ischemia produces mitochondrial changes similar to those in hypoxic hypoxia but also causes the depletion of tissue glycogen and perivascular glial swelling. Thus, hypoxic hypoxia with relative ischemia produces a unique acute ultrastructural response compared to either complete or incomplete cerebral ischemia.

Animals↗

PubMed1999

Using partial directed coherence to describe neuronal ensemble interactions.

This paper illustrates the use of the recently introduced method of partial directed coherence in approaching how interactions among neural structures change over short time spans that characterize well defined behavioral states. Central to the method is its use of multivariate time series modelling in conjunction with the concept of Granger causality. Simulated neural network models were used to illustrate the technique's power and limitations when dealing with neural spiking data. This was followed by the analysis of multi-unit activity data illustrating dynamical change in the interaction of thalamo-cortical structures in a behaving rat.

Action Potentials↗

PubMed1999

Carbachol induces fast oscillations in the medial but not in the lateral entorhinal cortex of the isolated guinea pig brain.

Fast oscillations at 25-80 Hz (gamma activity) have been proposed to play a role in attention-related mechanisms and synaptic plasticity in cortical structures. Recently, it has been demonstrated that the preservation of the entorhinal cortex is necessary to maintain gamma oscillations in the hippocampus. Because gamma activity can be reproduced in vitro by cholinergic activation, this study examined the characteristics of gamma oscillations induced by arterial perfusion or local intracortical injections of carbachol in the entorhinal cortex of the in vitro isolated guinea pig brain preparation. Shortly after carbachol administration, fast oscillatory activity at 25.2-28.2 Hz was observed in the medial but not in the lateral entorhinal cortex. Such activity was transiently associated with oscillations in the theta range that showed a variable pattern of distribution in the entorhinal cortex. No oscillatory activity was observed when carbachol was injected in the lateral entorhinal cortex. Gamma activity in the medial entorhinal cortex showed a phase reversal at 200-400 microm, had maximal amplitude at 400-500 microm depth, and was abolished by arterial perfusion of atropine (5 microM). Local carbachol application in the medial entorhinal cortex induced gamma oscillations in the hippocampus, whereas no oscillations were observed in the amygdala and in the piriform, periamygdaloid, and perirhinal cortices ipsilateral and contralateral to the carbachol injection. Hippocampal oscillations had higher frequency than the gamma activity recorded in the entorhinal cortex, suggesting the presence of independent generators in the two structures. The selective ability of the medial but not the lateral entorhinal cortex to generate gamma activity in response to cholinergic activation suggests a differential mode of signal processing in entorhinal cortex subregions.

Animals↗

PubMed1995

Sensory cortical processing and the biological basis of personality.

Action-oriented personality traits such as sensation seeking, extraversion, and impulsivity have been related to a pronounced amplitude increase of auditory evoked scalp potentials with increasing stimulus intensity. Dipole source analysis represents a crucial methodological progress in this context, because overlapping subcomponents of the scalp potentials can be separated and can be related to their generating cortical structures. In a study on 40 healthy subjects, it was found that sensation seeking is clearly related to the auditory evoked response pattern (N1/P2-component, stimulus intensities: 60, 70, 80, 90, 100 dB SPL) of the superior temporal plane including primary auditory cortex, but not to that of secondary auditory areas in the lateral temporal cortex. These results support the concept that the serotonergic brain system, which is supposed to modulate sensory processing in primary auditory cortices, is an important factor underlying individual differences in sensation seeking.

Adult↗

PubMed1984

In situ PCO2 in the renal cortex, liver, muscle, and brain of the New Zealand white rabbit.

Recent studies have shown that in situ PCO2 in rat renal cortical structures far exceeds systemic arterial PCO2. These results were opposite to previous assumptions that renal proximal tubule fluid PCO2 approximated arterial PCO2. The present studies examined the species and organ specificity of the elevated PCO2 in 39 New Zealand White rabbits studied under normal acid-base conditions. In situ PCO2 was measured in renal cortex, superficial hepatic parenchyma, skeletal muscle, superficial cerebral cortex, and femoral nerve, artery, and vein. The results showed rabbit renal cortical PCO2 (57.2 +/- 1.2 mmHg) to be higher than both systemic arterial (39.1 +/- 2.0 mmHg) and venous PCO2 (45.4 +/- 2.1 mmHg). Similarly, liver PCO2 (64.1 +/- 3.5 mmHg) was found to be significantly higher than systemic arterial and venous PCO2 and also higher than portal and hepatic vein PCO2. Skeletal muscle, cerebral cortex, and femoral nerve PCO2 levels were usually greater than systemic arterial PCO2 but less than systemic venous PCO2. These observations show that in situ PCO2 is significantly elevated above afferent and efferent blood PCO2 in the kidney and liver but not in muscle or brain. A possible explanation for these findings in the former two organs may be high CO2 production and/or trapping of CO2 by their vascular systems.

Animals↗

PubMed2003

Brain processing of meter and rhythm in music. Electrophysiological evidence of a common network.

To determine cortical structures involved in "global" meter and "local" rhythm processing, slow brain potentials (DC potentials) were recorded from the scalp of 18 musically trained subjects while listening to pairs of monophonic sequences with both metric structure and rhythmic variations. The second sequence could be either identical to or different from the first one. Differences were either of a metric or a rhythmic nature. The subjects' task was to judge whether the sequences were identical or not. During processing of the auditory tasks, brain activation patterns along with the subjects' performance were assessed using 32-channel DC electroencephalography. Data were statistically analyzed using MANOVA. Processing of both meter and rhythm produced sustained cortical activation over bilateral frontal and temporal brain regions. A shift towards right hemispheric activation was pronounced during presentation of the second stimulus. Processing of rhythmic differences yielded a more centroparietal activation compared to metric processing. These results do not support Lerdhal and Jackendoff's two-component model, predicting a dissociation of left hemispheric rhythm and right hemispheric meter processing. We suggest that the uniform right temporofrontal predominance reflects auditory working memory and a pattern recognition module, which participates in both rhythm and meter processing. More pronounced parietal activation during rhythm processing may be related to switching of task-solving strategies towards mental imagination of the score.

Adult↗

PubMed2004

Neurocognitive aging and cardiovascular fitness: recent findings and future directions.

In the first century, ce, the Roman satirist Juneval famously observed Orandum est, ut sit mens sana in corpore sano, or "A sound mind in a sound body is something to be prayed for." This implicit link between mental and physical health, also paralleled by Eastern philosophies and practices such as tai chi, has survived the millennia since Juneval and his contemporaries. More recently, controlled examinations of the effects of physical fitness on cognitive performance have shown that improving cardiovascular fitness (CVF) can help to reduce the deleterious effects of age on cognition and brain structure. Thus, as we age, it may well be the case that a sound mind is a natural concomitant of a sound body. Numerous cross-sectional and longitudinal studies have examined the effects of aerobic exercise on cognitive performance in aging humans since earlier studies, which found that physically fit older adults performed better on simple cognitive tasks than their less-fit counterparts. This base of knowledge recently has been furthered through examinations of cortical structure (Colcombe et al., 2003) and neurocognitive function in aging humans via functional and structural magnetic resonance imaging techniques. In this manuscript, we will briefly review some of our recent research on the effects of CVF on brain function, structure, and behavior in older adults. We will then outline some of our current and future directions in this area.

Aging↗

PubMed1988

Morphometric analysis of the human corpus callosum and anterior commissure.

The cross-sectional areas of the corpus callosum (CC) and anterior commissure (AC) were determined by computer-assisted morphometry in normal human brains obtained at autopsy. In addition, the shape of each CC was examined qualitatively by three "blind" observers. A two-fold variation was observed in the cross-sectional area of the CC. Surprisingly, callosal cross-sectional area was not significantly related to brain weight. Moreover, contrary to recent reports, neither simple inspection nor morphometry revealed structural variation related to sex. A striking, seven-fold, variation was observed in the cross-sectional area of the AC. However, AC cross-sectional area was not related either to brain weight or CC cross-sectional area. A trend toward sexual dimorphism in AC cross-sectional area was observed, with males having the larger AC's. Since the interhemispheric commissures are composed, to a large extent, of fibers that link the various cortical areas of the two hemispheres, these observations suggest that variation in the cross-sectional area of the interhemispheric commissures is not simply related to brain weight or sex but, rather, reflects a similar degree of variation in some aspect of cortical structure.

Brain↗