Correlations between glucose metabolic rates in brain regions of healthy male adults at rest and during language stimulation

This study examines the effect of different behavioral conditions on patterns of correlation between regional cerebral metabolic rates for glucose. Cerebral glucose metabolism was determined with positron emission tomography and (11C)-deoxyglucose in 29 normal subjects between the ages of 23 and 55. Seventeen subjects were studied in an unstimulated (resting) condition and 12 subjects during a phoneme monitoring language stimulation. Partial correlation coefficients, controlling for whole brain glucose metabolism, were calculated for pairs of metabolic rates in 14 cortical and 2 subcortical regions. Both stimulated and unstimulated subjects showed statistically significant correlations between left and right hemisphere homologs. The stimulated subjects also showed significant within-hemisphere correlations between left but not right hemisphere regions. These included left perisylvian regions classically associated with language functions (left inferior frontal, left superior temporal and left transverse temporal cortical regions) as well as other regions. Significant correlations between left regions and a right superior temporal region were also found. In general, these findings show a pattern of cross-hemisphere symmetry at rest and of hemisphere asymmetry during stimulation. Moreover, the asymmetry observed during stimulation appears to be superimposed upon a pattern of cross-hemisphere symmetry similar to that observed in the unstimulated state.     

The effect of auditory input on cerebral laterality

Cerebral laterality was examined for third-, fourth-, and fifth-grade deaf and hearing subjects. The experimental task involved the processing of word and picture stimuli presented singly to the right and left visual hemifields. The analyses indicated the deaf children were faster than the hearing children in overall processing efficiency, and that they performed differently in regard to hemispheric lateralization. The deaf children processed the stimuli more efficiently in the right hemisphere, while the hearing children demonstrated a left-hemisphere proficiency. This finding is discussed in terms of the hypothesis that cerebral lateralization is influenced by auditory processing.     

自由基与蛛网膜下腔出血后脑血管痉挛的关系及防治策略

脑血管痉挛是蛛网膜下腔出血后的严重并发症之一,可引起脑组织严重缺血或迟发性缺血性脑损伤,甚至导致脑梗死,但其病理机制仍未完全清楚,而越来越多的研究表明自由基在脑血管痉挛病理变化过程中发挥着重要作用。通过对自由基与脑血管痉挛之间关系的科学分析,探讨蛛网膜下腔出血后与自由基相关的脑血管痉挛的防治策略。     

Patterns of motor disability in very preterm children

Motor development in very preterm children differs in several important ways from that of children born at full term. Variability is common, although the anatomic and physiologic bases for that variability are often poorly understood. Motor patterns over the first postnatal year may depend on behaviours learned during often long periods of neonatal intensive care. The normal pattern of development may be modified by disturbances of brain function caused both by the interruption of normal brain maturation ex-utero and the superimposition of focal brain injuries following very preterm birth. Abnormal patterns of development over the first year may evolve into clear neuromotor patterns of cerebral palsy or resolve, as "transient dystonias." Cerebral palsy is associated with identified patterns of brain injury secondary to ischaemic or haemorrhagic lesions, perhaps modified by activation of inflammatory cytokines. Cerebral palsy rates have not fallen as might be expected over the past 10 years as survival has improved, perhaps because of increasing survival at low gestations, which is associated with the highest prevalence of cerebral palsy. Children who escape cerebral palsy are also at risk of motor impairments during the school years. The relationship of these impairments to perinatal factors or to neurological progress over the first postnatal year is debated. Neuromotor abnormalities are the most frequent of the "hidden disabilities" among ex-preterm children and are thus frequently associated with poorer cognitive ability and attention deficit disorders. Interventions to prevent cerebral palsy or to reduce these late disabilities in very preterm children are needed.     

Larger brain and white matter volumes in children with developmental language disorder

Developmental language disorder (DLD) is predominantly a language disorder, but children with DLD also manifest non-language impairments, and neuroanatomical abnormalities have been found in multiple areas of the brain, not all language-associated. We therefore performed a whole brain general segmentation analysis of all major brain regions on MRI scans of 24 DLD subjects (16M, 8F) and 30 controls (15M, 15F), ages 5.7 to 11.3 years. Children with DLD showed increased total brain volume, driven predominantly by a substantial increase in the volume of cerebral white matter. Cerebral cortex and caudate were relatively but not absolutely smaller in DLD. These findings are discussed in relation to issues of specificity vs. generality as they arise in debates about (1) modular vs. general processing deficits and connectionist modeling in DLD, (2) language-specific vs. pervasive, non-specific deficits in DLD and (3) specificity of the disorder vs. overlap with other disorders, notably autism.     

Event-related potentials in neuropsychological studies of language

Experiments are described in which event-related potentials (ERPs) are employed to study the specialization of functions between and within the cerebral hemispheres during the performance of language and nonlanguage tasks by normal adults. Similar studies of deaf subjects suggest that the functional organization of the brain may be altered after different early language and sensory experiences. Studies of patients with alexia without agraphia suggest that the ERP may be a valuable tool with which to study cerebral reorganization after brain damage.     

Changes in plasma corticosterone and cerebral biogenic amines and their catabolites during training and testing of mice in passive avoidance behavior

Concentrations of cerebral biogenic amines and their catabolites, and of plasma corticosterone were determined 10 min after training and testing of passive avoidance behavior in mice. Training and testing of mice that had acquired the task well resulted in statistically significant increases of plasma corticosterone, of the DOPAC:DA ratio [an index of dopamine (DA) metabolism] in prefrontal cortex, and of MHPG:NE ratios [an index of norepinephrine (NE) metabolism] in hypothalamus and brain stem. There were also decreases of NE in hypothalamus and brain stem, and an increase of 5-HIAA:5-HT [an index of serotonin (5-HT) metabolism] and of tryptophan in brain stem. Some of these changes also occurred in mice merely exposed to the apparatus but not trained. Plasma corticosterone concentrations were significantly higher in mice that performed the task well compared to those that did not, and there were significant correlations between this measure and the avoidance performance. Although there was only one statistically significant correlation between a cerebral metabolite and the avoidance performance (a decrease in hypothalamic NE), there were indications of relationships between cerebral biogenic amine metabolism and the performance. The patterns of neurochemical and endocrine changes closely resemble those previously observed in response to various stressors. Thus, the changes could reflect stress responses, which may or may not be related directly to the performance of the avoidance task.     

Induced lateral orientation and persuasibility

It was hypothesized from three different lines of evidence that relative activation of the left cerebral hemisphere of right-handers would increase resistance to a persuasive message as compared to relative activation of the right hemisphere. An experiment was performed using 22 subjects who heard the counterattitudinal message in only one ear and filled in response measures while their body was turned toward that same side. Subjects who listened and turned toward the left agreed more with the views of the message (p less than .05) and produced more thought favorable to the message (p less than .05) than those induced to orient rightward. It was concluded that these results may be due to asymmetries in selective attention, counterarguing, consistency, self-awareness, and perseveration between the cerebral hemispheres of the normal human brain.     

Cerebral lateralization for speech in deaf and normal children

The cerebral lateralization pattern for speech production in normal hearing and congenitally deaf children was studied using the dual-task paradigm. Performance under the verbal task conditions showed predicted left hemispheric dominance for speech production in the normal hearing children. No developmental trends in asymmetry were found, suggesting that speech lateralization is present in normal 3-year-old children. These data support the developmental invariance hypothesis of cerebral organization. Deaf children showed more symmetrical patterns of cerebral control for speech production. No developmental trends in functional brain organization were observed among prepubescent deaf children.     

Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor

Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.     

Correlating brain metabolism with stereotypic and locomotor behavior

Many studies have shown that developmental cocaine exposure alters brain function and behavior; the present study examined the relationship between brain metabolism and behavioral responses to drug challenge. SKF 82958, a selective D1 dopamine agonist, was administered to preweaning cocaine-exposed (50 mg/kg/day) rats and controls at 60 days of age. Deoxyglucose was administered 30 min later, during the peak behavioral response, to measure brain functional activity Pearson product-moment correlations of behavior (locomotor activity and Stereotypic behavior) with rates of glucose metabolism in components of the nigrostriatal and mesolimbic circuits were analyzed. The analysis revealed that under saline-challenge conditions in control animals, rates of metabolism in mesolimbic regions are positively correlated to rates of locomotor activity, whereas in cocaine-treated rats, these correlations were absent. Following SKF challenge, a different pattern was seen; locomotor activity or Stereotypic behavior was not correlated with mesolimbic or nigrostriatal metabolism, respectively,in controls but was positively correlatedin cocaine-treatedrats. Therefore, cocaine exposure during development enhances the coupling of metabolism in components of the mesolimbic and nigrostriatal dopamine systems with the behavioral output associated with these systems under drug-challenge conditions. This may be due to loss of inhibitory influences within the mesolimbic and nigrostriatal systems. Thus, the correlation of behavior and cerebral glucose metabolism provides a unique way of examining the effect of developmental cocaine exposure.     

Exploring the brain with drugs

The nature and distribution of drag-induced or dragmodified responses, in health and in disease or experimental approximations of similarly disturbed function, have been investigated. From the results it appears that: 1. A sensitive substrate of drag action is the neurohumorally-determined synaptic equilibrium, which is transiently disturbed by transmission and distorted by drugs. These act through their ability to mimic or alter the duration of action of the cholinergic, excitatory, or adrenergic and serotoninergic inhibitory neurohumors. 2. Cerebral synaptic responsiveness to drugs isqualitatively identical at various cerebral sites sampled, including the cortex, subcortex and brainstem. This, therefore, is a general characteristic which, however, exhibits markedquantitative differences. 3. Because of such differential thresholds, drugs can cause disruption of normal relations or equilibrium between parts of the brain, as with LSD, or, if appropriately used, can act to promote restoration of equilibrium, as with tranquilizers and antidepressants. 4. A concept of cerebral homeostasis can be equated with mental health and its disturbance with psychosis, which is then regarded as a failure of cerebral integration. Clinical yardsticks for measuring degrees of functional integration are proposed, which make use of subclinical doses of drugs to challenge cerebral homeostasis in quantified lever-pressing and perceptual aberration-tracking situations. Exploration of the brain with drugs allows also exploration of the mind, for which it is the substrate. Drugs may be used to increase understanding of cerebral function in health and disease and to assess functional disintegration, as in brain damage, aging, mental retardation and mental disturbance. Proposed clinical yardsticks based on this could be used for diagnosis, evaluation of therapy, screening populations for individuals in need of preventive or prophylactic care, and in evaluation of new drugs.     

Hemispheric differences in temporal resolution

A review of the relevant clinical and experimental literature gives the conclusion that the cerebral hemispheres differ in temporal resolution of input, with the language-dominant hemisphere showing finer acuity. This conclusion is supported by evidence from performance of patients with unilateral brain damage on tests of temporal resolution, performance of developmental dyslexics on similar tasks, and left-right sensory field differences in temporal acuity in normal human subjects. While it is unlikely that a hemispheric difference in temporal resolution is sufficient to give a complete account of lateralized functions, such attempts to show more primitive physiological differences between the hemispheres are more likely to be fruitful than attempts which differentiate the hemispheres in terms of higher-order psychological functions.     

Transverse diffusivity of cerebral parenchyma predicts visual tracking performance in relapsing–remitting multiple sclerosis

This study investigated the relation between cerebral damage related to multiple sclerosis (MS) and cognitive decline as determined by two classical mental tracking tests. Cerebral damage in 15 relapsing–remitting MS patients was measured by diffusion tensor imaging (DTI). Fractional anisotropy, longitudinal and transverse diffusivity were defined in the cerebral parenchyma. Cognitive performance of the MS patients was assessed with the oral response format of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). A significant correlation was found between performance on the SDMT and the fractional anisotropy in the brain. This correlation was predominantly induced by transverse diffusivity. Transverse diffusivity refers to the diffusion across fibers rather than along the fibers and is believed to be a specific marker for axonal loss and demyelination associated with MS. No significant association between DTI-measures and PASAT performance was found and this negative finding was mainly attributed to psychometric qualities. These results indicate that diffusivity along the non-principal diffusion direction, a possible signature of MS-related white matter pathology, contributes to information processing speed as measured with the SDMT, a task that requires close visual tracking and a widely used clinical marker for cognitive decline in MS.     

The statistical interaction of cerebral specialization and integration in the interpretation of dynamic brain images

Two constructs of brain function, namely cerebral specialization and integration, have been examined in the analysis of blood flow and metabolic function resulting from dynamic imaging procedures. The purpose of the current paper is to illustrate the interaction of these two constructs at the statistical level. Because of the statistical interaction, it is argued that the currently accepted statistical evidence for cerebral specialization is, in fact, partially a function of the degree of regional cerebral integration. Therefore, found asymmetries of flow or rate may be solely a function of cerebral integration. These points are discussed with respect to developing a better understanding of stimulus/brain/behavior relations.     

MRI findings in boys with specific language impairment

Magnetic resonance imaging scans of specifically language-impaired (SLI) boys were examined to determine whether atypical cerebral findings could be documented in children whose primary deficits were in language skills. Clinical examination of the scans failed to reveal any visually obvious lesions or abnormalities. In contrast, measurement of the scans revealed atypical perisylvian asymmetries in most of these subjects. The distribution of perisylvian asymmetries in SLI subjects was significantly different from the distribution in controls (p less than .01). Measurement of other brain regions revealed that extraperisylvian areas were occasionally deviant in individual SLI subjects; but no one region was consistently deviant across the SLI group. Thus, only atypical perisylvian asymmetries were linked to the language disorder. These neuroanatomical findings suggest that a prenatal alteration of brain development underlies specific language impairment.     

Neuroimaging studies in eating disorders

The understanding of the eating disorders (EDs) anorexia (AN) and bulimia nervosa (BN) has undergone remarkable advancements in the past decade. Most studies that have been done in AN show brain gray and white matter volume loss during the ill state that, at least in part, remit with recovery. Similar patterns occur for brain phospholipids assessed using magnet resonance spectroscopy (MRS). Imaging studies have been used to provide functional information regarding serotonin neuroreceptor dynamics, regional cerebral blood flow, or cerebral glucose metabolism. Such studies have implicated cingulate, frontal, temporal, and parietal regions in AN. Investigators have found that challenges such as food and body image distortions may activate some of these regions, raising the possibility that such studies may shed light on puzzling AN symptoms, such as body image distortions or extremes of appetitive behaviors. Emerging data suggest these disturbances persist after recovery from AN, suggesting the possibility that these are traits that may create a vulnerability to develop an ED. While fewer studies have been done in BN or binge eating disorder, there may be disturbances of serotonin metabolism in similar brain regions. Taken together, these findings give promise for future investigations with the hope of delineating brain pathways that contribute to the etiology of EDs     

Electroencephalographic intercentral interaction as a reflection of normal and pathological human brain activity

The authors summarized EEG findings and defined the nature of the intercentral EEG relationships in different functional states in healthy subjects and patients with organic cerebral pathology, based on a coherence analysis. Similar EEG characteristics in healthy individuals were identified: an anterior-posterior gradient of average coherence levels, the type of cortical-subcortical relationships in anterior cerebral structures. Right- and left-handed individuals showed frequent and regional differences in EEG coherence, which mainly reflected specificity of intracortical relationships. Development and regression of pathology in right-and left-handed individuals with organic brain lesions were thought to be caused by these differences. Lesions of regulatory structures (diencephalic, brain stem and limbic structures) provoked a more diffused kind of changes of intercentral relationships, in contrast to cortical pathology. These changes tended to reciprocate. The dynamic nature of intercentral relationships and their interhemispheric differences was revealed when changing functional states of the brain (increase and decrease of functional level) in healthy individuals and patients with organic cerebral pathology in the process of conscious and psychic activity restoration. Changing activity predominance of certain regulatory structures was considered one of the most important factors determining the dynamic nature of EEG coherence.     

Functional neuroimaging of autistic disorders

Functional neuroimaging methods hold promise for elucidating the neurobiology of autistic disorders, yet they present difficult practical and scientific challenges when applied to these complex and heterogeneous syndromes. Single-state studies of brain metabolism and blood flow thus far have failed to yield consistent findings, but suggest considerable variability in regional patterns of cerebral synaptic activity. Patients with idiopathic autism are less likely to show abnormalities than are patients with comorbid illness or epilepsy. Activation studies have begun to suggest alterations in brain organization for language and cognition. Neurotransmitter studies using positron emission tomography (PET) suggest abnormalities of serotonergic and dopaminergic function. Studies using magnetic resonance spectroscopy (MRS) have begun to document metabolic deficits in the frontal cortex and cerebellum. A single study using magnetoencephalography suggests a high incidence of epileptiform activity in children with autistic regression. Research needs include well-controlled developmental studies, particularly of young subjects and relatively homogeneous subgroups, which balance scientific rigor with ethical constraints. Investigations of the serotonergic and dopaminergic systems, limbic-based memory and emotional systems, and the role of epileptiform activity in autism represent priorities for future research.     

Language lateralization and handedness: Estimates based on clinical data

The suggestion that the cerebral representation of language is bilateral in at least some left handers relies on using the proportion of aphasics found in available clinical samples of sufferers of unilateral brain damage as a valid estimate of the probability that aphasia will occur following unilateral brain damage. This results in an overestimate of this probability since the clinical sample includes only cases with both unilateral brain damage and clinical symptoms and excludes cases with unilateral brain damage without clinical symptoms. With adjustment for this overestimate the clinical data are consistent with unilateral cerebral representation of language in left handers.