Cerebral Cortical Structures Research Articles

Cerebral cortex modulation of pain

Pain is a complex experience encompassing sensory-discriminative, affective-motivational and cognitiv e-emotional components mediated by different mechanisms. Contrary to the traditional view that the cerebral cortex is not involved in pain perception, an extensive cortical network associated with pain processing has been revealed using multiple methods over the past decades. This network consistently includes, at least, the anterior cingulate cortex, the agranular insular cortex, the primary (SI) and secondary somatosensory (SII) cortices, the ventrolateral orbital cortex and the motor cortex. These cortical structures constitute the medial and lateral pain systems, the nucleus submedius-ventrolateral orbital cortex-periaqueductal gray system and motor cortex system, respectively. Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine, are involved in the modulation of pain by these cortical structures. In addition, glial cells may also be involved in cortical modulation of pain and serve as one target for pain management research. This review discusses recent studies of pain modulation by these cerebral cortical structures in animals and human.

New insights into central cardiovascular control during exercise in humans: a central command update

The autonomic adjustments to exercise are mediated by central signals from the higher brain (central command) and by a peripheral reflex arising from working skeletal muscle (exercise pressor reflex), with further modulation provided by the arterial baroreflex. Although it is clear that central command, the exercise pressor reflex and the arterial baroreflex are all requisite for eliciting appropriate cardiovascular adjustments to exercise, this review will be limited primarily to discussion of central command. Central modulation of the cardiovascular system via descending signals from higher brain centres has been well recognized for over a century, yet the specific regions of the human brain involved in this exercise-related response have remained speculative. Brain mapping studies during exercise as well as non-exercise conditions have provided information towards establishing the cerebral cortical structures in the human brain specifically involved in cardiovascular control. The purpose of this review is to provide an update of current concepts on central command in humans, with a particular emphasis on the regions of the brain identified to alter autonomic outflow and result in cardiovascular adjustments.

Brain activation by central command during actual and imagined handgrip under hypnosis.

The purpose was to compare patterns of brain activation during imagined handgrip exercise and identify cerebral cortical structures participating in "central" cardiovascular regulation. Subjects screened for hypnotizability, five with higher (HH) and four with lower hypnotizability (LH) scores, were tested under two conditions involving 3 min of 1) static handgrip exercise (HG) at 30% of maximal voluntary contraction (MVC) and 2) imagined HG (I-HG) at 30% MVC. Force (kg), forearm integrated electromyography, rating of perceived exertion, heart rate (HR), mean blood pressure (MBP), and differences in regional cerebral blood flow distributions were compared using an ANOVA. During HG, both groups showed similar increases in HR (+13 +/- 5 beats/min) and MBP (+17 +/- 3 mmHg) after 3 min. However, during I-HG, only the HH group showed increases in HR (+10 +/- 2 beats/min; P < 0.05) and MBP (+12 +/- 2 mmHg; P < 0.05). There were no significant increases or differences in force or integrated electromyographic activity between groups during I-HG. The rating of perceived exertion was significantly increased for the HH group during I-HG, but not for the LH group. In comparison of regional cerebral blood flow, the LH showed significantly lower activity in the anterior cingulate (-6 +/- 2%) and insular cortexes (-9 +/- 4%) during I-HG. These findings suggest that cardiovascular responses elicited during imagined exercise involve central activation of insular and anterior cingulate cortexes, independent of muscle afferent feedback; these structures appear to have key roles in the central modulation of cardiovascular responses.

The Neurobehavioral Nature of Fishes and the Question of Awareness and Pain

This review examines the neurobehavioral nature of fishes and addresses the question of whether fishes are capable of experiencing pain and suffering. The detrimental effects of anthropomorphic thinking and the importance of an evolutionary perspective for understanding the neurobehavioral differences between fishes and humans are discussed. The differences in central nervous system structure that underlie basic neurobehavioral differences between fishes and humans are described. The literature on the neural basis of consciousness and of pain is reviewed, showing that: (1) behavioral responses to noxious stimuli are separate from the psychological experience of pain, (2) awareness of pain in humans depends on functions of specific regions of cerebral cortex, and (3) fishes lack these essential brain regions or any functional equivalent, making it untenable that they can experience pain. Because the experience of fear, similar to pain, depends on cerebral cortical structures that are absent from fish brains, it is concluded that awareness of fear is impossible for fishes. Although it is implausible that fishes can experience pain or emotions, they display robust, nonconscious, neuroendocrine, and physiological stress responses to noxious stimuli. Thus, avoidance of potentially injurious stress responses is an important issue in considerations about the welfare of fishes.

Involvement of cerebral cortical structures in the classical conditioning of eyelid responses in rabbits

The classical conditioning of the eyelid motor system in alert behaving rabbits has been used to study the expression of Fos in the hippocampus, and in the occipital, parietal, piriform and temporal cortices. Animals were classically conditioned with both delay and trace conditioning paradigms. As conditioned stimulus, both short and long (20 and 100 ms) tones (600 Hz, 90 dB) or short, weak (20 ms, 1 kg/cm 2) air puffs were used. The unconditioned stimulus was always a long, strong (100 ms, 3 kg/cm 2) air puff that started 250–270 ms after the onset of the conditioned stimulus. The expression of Fos was significantly increased after both delayed and trace conditioning in the hippocampus, and in the parietal and piriform cortices contralateral to the unconditioned stimulus presentation side, compared with equivalent ipsilateral structures in conditioned animals, or with Fos production in the same contralateral structures in pseudo-conditioned and control animals. Fos expression in some cortical sites was specific to tone versus air puff stimuli when used as conditioned stimulus. Thus, Fos expression was significantly increased in the contralateral temporal lobe when tones were used as conditioned stimulus, for both delayed and trace conditioning paradigms, but not when animals were conditioned to short, weak air puffs. The present results indicate a specific Fos activation in several cerebral cortical structures during associative eyelid conditioning.

Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction

Background & Aims: Manganese (Mn) deposition could be responsible for the T 1-weighted magnetic resonance signal hyperintensities observed in cirrhotic patients. These experiments were designed to assess the regional specificity of the Mn increases as well as their relationship to portal-systemic shunting or hepatobiliary dysfunction. Methods: Mn concentrations were measured in (1) brain samples from basal ganglia structures (pallidum, putamen, caudate nucleus) and cerebral cortical structures (frontal, occipital cortex) obtained at autopsy from 12 cirrhotic patients who died in hepatic coma and from 12 matched controls; and from (2) brain samples (caudate/putamen, globus pallidus, frontal cortex) from groups (n = 8) of rats either with end-to-side portacaval anastomosis, with biliary cirrhosis, or with fulminant hepatic failure as well as from sham-operated and normal rats. Results: Mn content was significantly increased in frontal cortex (by 38%), occipital cortex (by 55%), pallidum (by 186%), putamen (by 66%), and caudate (by 54%) of cirrhotic patients compared with controls. Brain Mn content did not correlate with patient age, etiology of cirrhosis, or history of chronic hepatic encephalopathy. In cirrhotic and portacaval-shunted rats, Mn content was increased in pallidum (by 27% and 57%, respectively) and in caudate/putamen (by 57% and 67%, respectively) compared with control groups. Mn concentration in pallidum was significantly higher in portacaval-shunted rats than in cirrhotic rats. No significant changes in brain Mn concentrations were observed in rats with acute liver failure. Conclusions: These findings suggest that brain Mn deposition results both from portal-systemic shunting and from liver dysfunction. GASTROENTEROLOGY 1999;117:640-644

NEURAL CONTROL OF THE CARDIORESPIRATORY SYSTEM: CEREBRAL CORTICAL ACTIVATION DURING EXERCISE

1015 While advances towards a complete understanding of cardiorespiratory regulation are ongoing, the primary mechanisms responsible for controlling cardiovascular and respiratory systems during exercise are still subject to debate. The purpose of this symposium is to provide the latest information concerning the activation of cerebral cortical structures during exercise and their potential influence on the neural control of the cardiorespiratory system in humans. Towards this purpose, specific objectives will include: i) a presentation of the basic technology and methodology employed to detect neural activation, as well as their current and future applications (Friberg); ii) a review of previous investigations assessing cerebral blood flow during exercise and future questions to be addressed (Mitchell); iii) a discussion of discrete cortical sites related to respiratory regulation during exercise(Guz); iv) a discussion of cortical regions related to cardiovascular regulation during exercise and future studies (Williamson). It is a goal of this symposium to integrate information from radiological, neurophysiological, behavioral, and exercise sciences. At the end of this symposium, attendees should have a greater understanding of the role played by the cerebral cortex during exercise, methods used to assess brain activation, and specific regions of the brain that may be involved in cardiorespiratory regulation during exercise.

Altered expression of microtubule-associated protein 1B in cerebral cortical structures of pentylenetetrazole-treated rats.

Using Northern blot, immunoblotting, immunocytochemistry, and in situ hybridization, we show that a single administration of the convulsant pentylenetetrazole leads to robust, long-term changes in microtubule-associated protein 1B and its mRNA, in the adult rat brain. The first increases in MAP1B mRNA were detected at 15 hr following pentylenetetrazole administration in the temporal (Te2) and perirhinal cortex followed by increases in microtubule-associated protein 1B immunoreactivity at 72 hr postseizure. In contrast, the levels of microtubule-associated protein 1B mRNA and protein in layers I-II of the retrosplenial and parietal cortex (Par2) declined visibly by 24 hr and 72 h, respectively, post-seizure. The changes included loss of staining in layers I-II and development of structures resembling "strings-of-beads" along the fibers of projection neurons of layer V. The levels of microtubule-associated protein 1B mRNA in the entorhinal cortex peaked at later times (72 h), especially in layers II-III, and returned to control levels by 10 days. Whereas the levels of microtubule-associated protein 1B immunoreactivity in the retrosplenial and parietal cortex recovered by 5-10 days, it persisted at high levels through day 35 in layer V of the temporal cortex (Te2), layers II-III of the perirhinal cortex and layers I-II of the lateral entorhinal cortex. These results indicate that seizure activity leads to long-term upregulation of genes coding for structural elements that are characteristic of the immature brain such as microtubule-associated protein 1B.

Selective loss of binding sites for the glutamate receptor ligands [3H]kainate and (S)-[3H]5-fluorowillardiine in the brains of rats with acute liver failure.

There is increasing evidence that alterations of glutamatergic function are implicated in the pathogenesis of central nervous system consequences of acute liver failure. The aim of the study was to assess the integrity of glutamate receptors in the brain in experimental ischemic liver failure using quantitative receptor autoradiography and the selective ligands [3H]MK801 (for N-methyl-D-aspartate [NMDA] sites), [3H]5-fluorowillardiine (for non-NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] subclass sites), and [3H]kainate (for non-NMDA, kainate subclass sites). At coma stages of encephalopathy, a selective loss of up to 60% of binding sites for the kainate- and AMPA-receptor ligands was observed in cerebral cortical and hippocampal structures as well as in the hypothalamus and cerebellum. The finding of a selective loss of AMPA sites at coma stages of encephalopathy in this model of acute liver failure is consistent with previous electrophysiological reports of inhibition of AMPA-mediated neuronal depolarization resulting from exposure of hippocampal neurons to millimolar concentrations of ammonia. On the other hand, the present study showed that binding sites for the NMDA-receptor ligand [3H]MK801 at coma stages of encephalopathy in acute liver failure were within normal limits in all brain structures examined. NMDA sites are uniquely neuronal, whereas kainate and AMPA sites are localized on both neurons and astrocytes. Therefore, the selective loss of non-NMDA sites in acute liver failure may also reflect astrocytic changes in this condition. Because astrocytic glutamate receptors are implicated in K+ and neurotransmitter reuptake, alterations in their density could result in altered neuronal excitability and thus be responsible for the neurological dysfunction characteristic of hepatic encephalopathy in acute liver failure.

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.

Magnetic Resonance Imaging Morphometric Analysis of Cerebral Volume Loss in Human Immunodeficiency Virus Infection

Magnetic resonance imaging was used to compare male subjects seropositive for antibody to human immunodeficiency virus type 1 (HIV positive), with and without medical symptoms, with two groups of men who were seronegative (HIV negative). The control subjects included men at high risk for exposure to HIV-1 and those at low risk. None of the HIV-positive subjects met criteria for HIV-associated dementia or had detectable opportunistic brain disease. Quantitative image-analytic techniques were used to estimate volumes of ventricular and cortical cerebrospinal fluid, cerebral white matter, and cortical and subcortical gray matter structures. Relative to low-risk group control subjects and asymptomatic HIV-positive subjects, nondemented but medically symptomatic HIV-positive subjects showed significant increases in cerebrospinal fluid, reduced volume of cerebral white matter, and reduced cerebral gray matter volumes. Unexpectedly, however, some cerebrospinal fluid increases and gray matter volume decreases were present in the seronegative high-risk control subjects as well.

Expression of c-fos mRNA in rat brain after intracerebroventricular administration of corticotropin-releasing hormone

Expression of the proto-oncogene c-fos is known to increase in rat brain following various types of seizures. Measuring c-fos mRNA or protein levels was shown to be a good cellular marker for neurons activated during central nervous system (CNS) excitation. In this study, we used in situ hybridization analysis of c-fos mRNA to determine brain regions activated by a peptide that has been closely linked to stress responsivity and kindling-like seizure activity. Corticotropin-releasing hormone (CRH) was injected into the left lateral ventricle of rats and produced the late onset of seizures between 1.5-5 h after its administration. Rats were sacrificed at various time points after the administration of CRH or sterile water, and c-fos mRNA levels were determined. In the preseizure state, CRH increased c-fos unilaterally in several cerebral cortical structures (most prominently in the dorsal endopiriform nucleus and in the piriform and insular cortices). CRH-induced seizures increased c-fos bilaterally in the same cortical regions, and in addition, in the hippocampus and olfactory bulb. The data are congruous with the hypothesis that intracerebroventricularly (i.c.v.) administered CRH elicits a rapid kindling-like response.

Local cerebral blood flow is increased in rapid-eye-movement sleep in fetal sheep

Behavioral state-induced changes in fetal cerebral blood flow were continuously monitored with a simple thermal dilution method. Thermojunctions were heated 1.5 degrees C above reference thermojunctions implanted contralaterally in various cerebral cortical and subcortical structures of four near-term fetal sheep. Temperature difference in rapid-eye-movement sleep was lower than in non-rapid-eye-movement sleep (p = 0.014), reflecting convective heat loss from increased blood flow. Temperature difference also varied significantly with the locus of placement in the brain (p = 0.003), reflecting, in part, regional differences in cerebral blood flow. The thermocouple method gives qualitative, continuous information on local cerebral blood flow that could be useful in monitoring the vascular response to changing functional activity during prenatal brain development.

Cerebral hypometabolism in progressive supranuclear palsy studied with positron emission tomography.

Progressive supranuclear palsy (PSP) is characterized by supranuclear palsy of gaze, axial dystonia, bradykinesia, rigidity, and a progressive dementia. Pathological changes in this disorder are generally restricted to subcortical structures, yet the type and range of cognitive deficits suggest the involvement of many cerebral regions. We examined the extent of functional impairment to cerebral cortical and subcortical structures as measured by the level of glucose metabolic activity at rest. Fourteen patients with PSP were compared to 21 normal volunteers of similar age using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose metabolism was reduced in the caudate nucleus, putamen, thalamus, pons, and cerebral cortex, but not in the cerebellum in the patients with PSP as compared to the normal subjects. Analysis of individual brain regions revealed significant declines in cerebral glucose utilization in most regions throughout the cerebral cortex, particularly those in the superior half of the frontal lobe. Declines in the most affected regions of cerebral cortex were greater than those in any single subcortical structure. Although using conventional neuropathological techniques the cerebral cortex appears to be unaffected in PSP, significant and pervasive functional impairments in both cortical and subcortical structures are present. These observations help to account for the constellation of cognitive symptoms in individual patients with PSP and the difficulty encountered in identifying a characteristic psychometric profile for this group of patients.

Positron emission tomography study of human brain functional development.

From over 100 children studied with 2-deoxy-2[18F]fluoro-D-glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 mumol/min/100 gm), and rapidly rose to reach adult values (19 to 33 mumol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 mumol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to decline, and reached adult rates again by the latter part of the second decade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.

Effect of delta-sleep-inducing peptide on the interaction of symmetric cerebral cortical structures after transection of the corpus callosum

Effect of delta-sleep-inducing peptide on the interaction of symmetric cerebral cortical structures after transection of the corpus callosum

Myoclonus in Alzheimer's disease.

Myoclonus was studied electrophysiologically in seven patients with clinically diagnosed Alzheimer's disease. There seem to be at least two physiological types of myoclonus in Alzheimer's disease. Cerebral cortical structures might participate in the generation of myoclonus in one type, while the other type is probably generated by subcortical structures.

1711 ENERGY STATE OF THE BRAIN IN EXPERIMENTAL NEONATAL STATUS EPILEPTICUS

Cerebral metabolic responses to status epilepticus (SE) were investigated for the first time in neonatal primates. Ten 14-day old Marmoset monkeys were anesthetized with ketamine & monitored for systemic BP, blood gases & glucose. An IM injection of bicuculline produced tonic-clonic convulsions without hypoxemia, hypoglycemia or hypotension for 30 min,; thereafter, brains were quick frozen & prepared for regional NADH reflectance fluorometry & ATP bioluminescence. Micro-samples of forebrain were analyzed for ATP (C-2.66, SE-2.04), P-creatine (C-3.45, SE-0.92), Glucose (C-3.57, SE-0.20) and Lactate (C-1.23, SE-10.05)mmol/kg. Similar alterations in metabolite levels were noted in diencephalon and in deep cerebral cortical structures. NADH fluorometry produced patchy relatively symmetrical areas of enhanced fluorescence in boundary zones between anterior & middle cerebral arteries of cerebral cortex, in cingulate gyri & diencephalon. Regional ATP was decreased globally in SE animals. Furthermore, ATP levels were not statistically different in brain regions with high or low NADH fluorescence. Thus, glycolytic intermediates & high energy reserves are disrupted in brains of neonatal Marmosets sustaining SE. The insult follows in part a vascular distribution. Whether or not the altered energy state is severe enough to be associated with brain damage is under investigation. (Supported by Research Service of the Veterans Administration and by NIH #PNS-13515 and #HD-15738.

Distribution of immunoreactive dynorphin B in discrete areas of the rat brain and spinal cord

The distribution of immunoreactive (ir)-dynorphin B in 101 microdissected rat brain and spinal cord regions was determined using a specific radioimmunoassay. The highest concentration of dynorphin B in brain was found in the substantia nigra (1106.2 fmol/mg protein). Very high concentrations of ir-dynorphin B (> 400 fmol/mg protein) were also found in the lateral preoptic area, parabrachial nuclei and globus pallidus. Relatively high concentrations of ir-dynorphin B (250–400 fmol/mg protein) were found in 19 nuclei, including the periaqueductal gray matter, anterior hypothalamic nucleus, median eminence, nucleus accumbens and hippocampus. Moderate levels of the peptide (between 100 and 250 fmol/mg protein) were found in 42 brain nuclei such as the perifornical nucleus, nucleus of the diagonal band, medial forebrain bundle, and dorsal premamillary nucleus. Low concentrations of ir-dynorphin B (< 100 fmol/mg protein) were found in 28 brain areas, e.g. cerebral cortical structures (parietal, cingulate, frontal), claustrum, olfactory bulb, lateral and periventricular thalamic nuclei. The cerebellar cortex has the lowest dynorphin B concentration (53.7 fmol/mg protein). Spinal cord segments exhibit low or moderate (cervical segment) levels of the peptide. The neurointermediate lobe of the pituitary gland is extremely rich in ir-dynorphin B (11,047.1 fmol/mg protein).

Nitrous Oxide Markedly Increases Cerebral Cortical Metabolic Rate and Blood Flow in the Goat

Studies to date on the influence of N2O on cerebral blood flow (CBF) and metabolism in dogs, rodents, and humans have produced conflicting results. In the present study the authors have employed techniques in the awake, freely breathing nonstressed goat that allowed the authors to 1) serially obtain rapidly frozen cerebral cortical biopsy specimens (for labile metabolite assay) and 2) measure changes in cerebral O2 metabolism (CMRO2) and total and regional CBF (rCBF). Thus, with each animal utilized as its own control, the authors studied N2O effects on the above variables. Two determinations of the effects of 1 h of N2O (70% via a mask) on these variables were performed on each animal. Following introduction of N2O, PaCO2 and arterial blood pressure did not change, but arterial epinephrine levels declined over the 60-min period. Total CBF increased in the first 5 min of N2O exposure, reached a maximum of 165% control at 15 min, and then decreased to 143% control at 60 min. rCBF evaluations showed that much of this CBF increase was confined to cerebral cortical structures (188-246% control at 60 min). Over the same period cortical CMRO2 increased to 170% of control. No appreciable changes in the levels of high-energy phosphates or glycolytic intermediates were found at 60 min of N2O. The authors attribute the described changes solely to the presence of N2O and not to sympathoadrenal influences, altered ventilation, or anything related to the experimental preparation, and they conclude that N2O (at least in goats) is associated with a marked cerebral cortical "activation".