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Frontal lobe dysfunctions in schizophrenia--II. Impairments of psychological and brain functions.

In Part I of this paper (Levin, 1984), it was proposed that the phenomena of eye movement impairments in schizophrenia are consistent with a dysfunction of frontal eye field mechanisms of ocular-motor control. In Part II, a frontal lobe dysfunction in schizophrenia is also proposed on the basis of clinical, psychological, neurochemical, and neuropathological grounds. There are striking similarities between the clinical frontal syndrome and negative symptom schizophrenia. Parallels between experimental studies of disturbances in attention and information processing, in humans and animals with frontal lobe lesions on the one hand, and in schizophrenics on the other, are noteworthy. The evidence for seemingly disparate dysfunctions in schizophrenia of eye movements, psychomotility, cognition, arousal, motivation and affect, is consistent with a disruption of frontal lobe mechanisms of stimulus-response and drive-response modulation. Studies on the neurochemistry and neuroanatomy of schizophrenia provide further evidence for a frontal lobe dysfunction in a subgroup of schizophrenic patients, particularly those with negative symptoms.

Attention↗

The dopamine systems in the brain, functional classification of different dopamine receptors.

Dopamine (DA) acts as a neurotransmitter in the central nervous system. The main part of the DA cell bodies are localized in the ventral mesencephalon and their axons run together in the medial forebrain bundle before diverging to different terminal areas in the forebrain, like the nucleus caudatus-putamen, nucleus accumbens, septum, amygdala, and several cortical areas like the cingulate, pyriform, entorhinal and prefrontal cortices. The functions of the dopamine systems are discussed in terms of how dopamine can modulate the functions of the area it innervates. Changes in dopaminergic transmission may be found after animals have been exposed to stress. This has implications for the discussion of whether a changed dopaminergic transmission in schizophrenia is a cause to, or a consequence of the disease. Both theories proposing a single localized anatomical site of action for the antipsychotic effect of neuroleptic drugs as well as those implicating a general effect on a number of different regions have been put forward. It is now widely accepted that there exists two classes of DA receptors, the D-1 and D-2 receptors, which have different physiological, and therefore proposed to have different clinical, characteristics. Other research implies however that a subpopulation of D-2 receptors is most important for the antipsychotic effect.

Animals↗

Control of alcohol addiction by SKV therapy--its action on water, food intake, brain function and cell membrane composition.

Alcohol being easily permeable through cell membrane causes toxic damage to many tissues. Rats drinking aqueous ethanol (25% v/v) for 120 days and 240 days showed an initial rise in body weight. The reduced rate in weight gain in chronic alcoholism is associated with a fall in food intake. Ethanol ingesting animals showed slow response to stimuli and increase in blood ethanol and serum GGTP levels. Liver plasma membrane, kidney brush-border membrane and pancreatic plasma membrane from alcoholic rats showed significant alterations in cholesterol/phospholipid molar ratio and membrane ATPases. Water retention with the enlargement of liver and kidney associated with increased fluid consumption are also seen during alcoholism. SKV by breaking alcohol dependence reduces drinking, lowers blood ethanol level and fluid intake without developing withdrawal symptoms. Restriction of ethanol intake by SKV therapy resulted in the reversal of organ enlargement and membrane composition in alcoholics.

Alcoholism↗

Folate and brain function in the elderly.

PURPOSE OF REVIEW: Over the past several decades, folate has emerged as an important nutrient in several key conditions of concern to the elderly. Subclinical levels of folate inadequacy can have significant negative impacts on health in older individuals. RECENT FINDINGS: Serum and red blood cell folate levels are associated with depression in younger individuals, but the relationship is less clear in older people. However, folate status does predict response to antidepressant treatment in older individuals. Cognitive decline and some forms of dementia, including Alzheimer's disease, are associated with lower folate levels. Supplementation with folic acid can provide cognitive benefits in some circumstances. Folic acid supplementation is generally regarded as safe; however, there remains some concern that high levels of folic acid may exacerbate the neurological consequences of a vitamin B12 deficiency. SUMMARY: Evidence for the role of folate in depression and dementia in the aged is increasing, although there remains much about mechanisms to be determined.

Aged↗

The impact of restricted diet on brain function using BOLD-fMRI.

We investigated the effect of a restricted diet model on activity in the human motor cortex using functional magnetic resonance imaging (fMRI). Two series of blood oxygenation level-dependent (BOLD)-fMRI measurements were made in healthy subjects performing simple motor tasks using their right hands. The first series was done 5-10 days prior to the restricted diet schedule (controls), and the second series was performed after 25-28 days of restricted diet, in the form of a religious fast (Ramadan). The size and intensity of the activated area in the motor cortex increased during the time of restricted diet versus the controls. We conclude that restricted diet has a significant effect on cerebral activity, as shown by BOLD-fMRI, although the exact relationship between the images and neuronal activity due to the restricted diet is still to be determined.

Adult↗

Regional brain function in schizophrenia. I. A positron emission tomography study.

Local cerebral glucose metabolism was determined with 18-F-fluorodeoxyglucose using positron emission tomography in a sample of 12 unmedicated schizophrenics and 12 matched normal controls. The data were analyzed for absolute metabolic rates and region/whole-brain ratios using the cortical-subcortical, antero-posterior, and laterality dimensions. Lobar areas within cortical regions were also compared. Across groups, subcortical metabolism was higher than cortical metabolism. Patients had lower metabolism, cortically and subcortically, and a steeper subcortical to cortical gradient. Patients with higher scores on the Brief Psychiatric Rating Scale had higher absolute metabolism and higher left relative to right hemispheric metabolism than did patients with lesser severity. The results did not show "hypofrontality" in schizophrenia. These findings provide some support for cerebral dysfunction in schizophrenia and indicate the need for further examination of the cortical-subcortical dimension.

Brain↗

[Significance of pregnancy and labor complications for the genesis of brain function disorders. Results of an epidemiologic study of 8-year-old children].

An epidemiological and a clinical study were conducted to examine the importance of pregnancy and delivery complications in the genesis of cerebral dysfunction, the studies comprising a total of 495 children of 8 years of age. In the case definition of cerebral dysfunction, methodic improvements were used that had been demanded by those who had been critical of the clinical procedure. The results showed that clinical dysfunction is a risk factor for diseases in child psychiatry. There were no signs pointing to uniform psychopathological patterns (on the lines of a hyperkinetic syndrome) in children with cerebral dysfunction. There was no enhanced incidence of other diseases in the anamnesis of children with cerebral dysfunction. On the whole, the concept of cerebral dysfunction cannot be upheld at least to the extent presumed so far. A comparison between field study random samples and clinical study random samples showed that the classical postulates of the concept apply at most to a negligible minority only.

Brain Damage, Chronic↗

Effects of elevated ICP on brain function: can the multiparametric monitoring system detect the 'Cushing Response'?

The 'Cushing Response' is a significant phenomenon associated with elevated ICP. The purpose of our study was to examine the effects of the intracranial hypertension level and duration on the cerebral tissue physiology, using a Multiprobe assembly (MPA). The parameters monitored simultaneously included ICP, CBF, mitochondrial NADH redox state, extracellular K+ and H+ levels, DC potential and ECoG, calculated CPP and blood pressure. Two groups of rats were used. In one group, ICP was elevated to 50-60 mmHg for 13-15 min and, in the second group, ICP was elevated to 20 mmHg for 30 min. The results show that ICP of 50-60 mmHg led to CPP reduction below the lower limits of autoregulation. However, ICP of 20 mmHg, even for a prolonged period of time is completely tolerated. Additionally, we found that the 'Cushing Response', developed in the moderate treatment (ICP = 20 mmHg) is beneficial, assuring high CBF levels under intracranial hypertension. Furthermore, CBF and CPP monitoring, apparently, are not sufficient for autoregulation assessment; more parameters are needed.

Animals↗

Association between brain functional failure and dementia severity in Alzheimer's disease: resting versus stimulation PET study.

OBJECTIVE: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. METHOD: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. RESULTS: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. CONCLUSIONS: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest.

Acoustic Stimulation↗

Molecular regulators of brain function: a new view.

A working hypothesis is proposed based on two mutually dependent concepts: neurons may be functionally regulated not only by presently known neurotransmitters but by many kinds of informational substances. Known informational substances are considered in categories corresponding to major regulators of the central nervous system, including transmitters, peptides, hormones, "factors" and various proteins. Many new informational substances are being discovered by the application of DNA technology. Alongside neuronal circuitry that forms the basis for conventional neuroanatomy and neurophysiology, and that operates through conventional synaptic junctions, is a system here called parasynaptic, i.e. in "parallel with" synapse-linked circuitry. In the parasynaptic system, informational substances reach specific target cell receptors by diffusion from release points through extracellular fluids. The parasynaptic system has the same degree of selectivity as synaptic circuitry but possesses, in addition, a domain of versatility and plasticity lacking in "hardwired" circuitry; the latter is, however, also influenced by highly potent informational substances in the ambient extracellular fluid.

Animals↗

Long-term alterations in brain function following cocaine administration during the preweanling period.

This report examines the long-term effects of cocaine exposure during postnatal days (P) 11-20 on the metabolic function of major central neuronal systems. Cocaine (50mg/kg) or vehicle was administered subcutaneously to rat pups during P 11-20. At 60-64 days of age, the rats were examined for cerebral glucose metabolic patterns. In cocaine-treated females 18 of the 46 structures evaluated showed increased metabolic rates including 5 of 6 structures within the motor system and 7 of 17 limbic structures. No decreased rates were seen. In males, cocaine had no effects in the motor structures or hypothalamus while 2 of 17 structures within the limbic system showed decreased rates of glucose utilization and 2 of 11 structures within the sensory systems showed increased rates. These results indicate that female rats show greater long-term metabolic effects than males and that cocaine exposure during P 11-20 produces different metabolic effects than cocaine exposure during P 1-10 which we previously reported.

Animals↗

Real time human brain function: observations and inferences from single trial analysis of magnetoencephalographic signals.

This paper brings together results obtained by applying Magnetic Field Tomography (MFT) to the analysis of Magnetoencephalography (MEG) data over the last decade. It emphasizes the most recent developments where the availability of helmet-like MEG probes with well over 100 sensing coils provide a full coverage of the head. The paper shows that it is possible to extract tomographic information from single trial, millisecond by millisecond MEG signal, and demonstrates two ways that this capability can be exploited. First, the single trial reconstructions are used to obtain robust statistical measures of changes of activity over small latency windows. Second, the interaction between areas is studied by computing the mutual information between short, time-lagged sections of the single trial time-courses. The usefulness of the computationally demanding approach is demonstrated by analyzing experiments using two widely used protocols, one for face and affect recognition and the other for Contingent Magnetic Variation (CMV). The results show foci of significant changes of activity, which are consistent with what is reported in the literature and provide a deeper understanding of their significance. Some new, but not all that unexpected, findings also emerge from the analysis.

Brain↗

Post-ingestion interference with brain function prevents attenuation of neophobia in rats.

Attenuation of the neophobic rejection of novel flavours is mediated by a memorial process the properties of which were examined by testing its resistance to functional disruption. Rats maintained on a 24-h water deprivation schedule consumed only 3 ml of the novel apple juice but doubled its intake during the second presentation 2 days later. This attenuation of neophobia (AN) was prevented by pentobarbital anaesthesia (40 mg/kg) induced 0 and 1 h, but not 4 and 7 h, after the first apple juice presentation. AN was also disrupted by ether anaesthesia (5 min), hypothermia (20 degrees C body temperature), bilateral cortical spreading depression and electroconvulsive shock (50 mA, 1.5 sec) applied 0-1 h, but not 2 or more hours, after the first apple juice presentation. The results are consonant with the 'learned safety' hypothesis and indicate that a 2-4 h long continuous absence of noxious consequences of food ingestion is required to classify a gustatory stimulus as safe or neutral. Since interventions interfering with AN do not disrupt formation of conditioned taste aversion, the two forms of adaptive control of food selection are obviously mediated by fundamentally different neural mechanisms.

Anesthesia↗

Dynamic sculpting of brain functional connectivity is correlated with performance.

In this study, we examined the relationship between cortical coupling, reflected in event related partial coherence (ERPC) and cognitive processing speed while subjects performed a set of Raven's Progressive Matrices (RPM), a task used to measure IQ. Fifty-five participants (29 males) performed a computerized version of the RPM where they were required to identify the shape (probe) that is consistent with a matrix of displayed shapes. Participants indicated a match or non-match by pressing a micro-switch with either the right or left hand. The steady state visually evoked potential (SSVEP) was elicited by a 13 Hz uniform visual flicker superimposed over the visual fields and the SSVEP event-related coherence (SSVEP-ERPC) calculated for all 2016 unique electrode pairs. The linear correlation between SSVEP-ERPC and processing speed (the inverse of reaction time) was calculated for all electrode pairs for all time points during the 3 sec interval that the probes were on the screen. Using correlation coeffident thresholds corresponding to p=0.001 we identified those electrode pairs where SSVEP-ERPC or neural synchronization was significantly correlated with processing speed. At a point 0.8 sec before the appearance of the probe we observed that the synchronization between specific prefrontal, frontal and central sites was correlated with processing speed. We suggest that this relationship may reflect the efficiency of working memory processes and speed of information processing.

Adolescent↗

[Somatosensory evoked potentials/fields--exploration of brain function].

We have summarized the history of electroencephalography(EEG) since 1875, when a paper by Richard Caton was published describing the first EEG recordings in animals. Somatosensory evoked potentials (SEPs) were recorded by George Dawson in 1951. Thereafter, SEPs were developed for clinical use with other evoked potentials such as auditory evoked potentials(VEPs). To understand evoked potentials, related mechanism of induction of far-fields-potentials(FFP) following stimulation of the median nerve has been discussed. SEPs consisted of P9, N9, N10, P11, N11, N13, P13, P14, N18, N20 and P20/P22. Scalp recorded P9 FFP arises from the distal portion of the branchial plexus as reflected by N9 stationary negative potential recorded over the stimulated arm. Cervical N11 and N13 arise from the root entry zone and dorsal horn, respectively. Scalp recorded P13, P14 and N18 FFP originate from the brainstem. In this communication, magnetoencephalography(MEG) and results of one of our recent studies on somatosensory evoked fields(SEFs) are also discussed. One of the important features of MEG is that magnetic signals detected outside the head arise mainly from cortical currents tangential to the skull. Since the net postsynaptic current follows the orientation of cortical pyramidal cells, the MEG signals mainly reflect activity of the fissural cortex, whereas radial current may remain undetected. In our study, we demonstrated SEFs elicited by compression and decompression of a subject's glabrous skin by a human operator. Their dipoles were tangentially oriented from the frontal lobe to parietal lobe.

Animals↗

Monitoring of brain function by means of evoked potentials in cerebral aneurysm surgery.

Deliberate arterial hypotension is currently used to operate upon cerebral aneurysms. However, it is not ascertained whether this practice is really safe for all patients, especially those presenting with preoperative vasospasm. 50 patients, requiring surgical treatment for cerebral aneurysm, have been submitted, during surgery, to the recording of Somatosensory Evoked Potentials (SEPs) on median nerve stimulation. This technique allows the functional evaluation of neural pathways mediating the somatosensory stimuli and of primary somatosensory cortex; it is known that a decrease of cerebral perfusion may affect the SEP waveforms in terms of reduced subcortical conduction velocity (i.e., increased central conduction time, CCT) and of reduced cortical response amplitude. These changes may be apparent before a permanent neurological damage is produced. Preoperative SEP recording demonstrated a prolonged CCT, possibly related to vasospasm, in 9 patients, a normal clinical evaluation notwithstanding (grade I and II). During intraoperative deliberate hypotension, a SEP change has always been produced. No postoperative damage has been observed, however, as long as the CCT did not exceed 9 msec for 10 minutes (maximum normal CCT value is 6.7 msec) and as the cortical response had been visible throughout the whole surgical procedure. The critical value of CCT has been reached at a mean arterial pressure (MAP) lower than 60 Torr in patients with a normal preoperative SEP recording; at the opposite, in patients presenting with a prolonged preoperative CCT, the value of 9 msec was arrived at with a MAP value that is generally accepted as safe for all patients (75 Torr).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Age-related dynamics of cognitive brain functions in humans: an electrophysiological approach.

Event-related P300 potentials closely reflect cognitive functions such as stimulus discrimination (N250) and processing time (P300 latencies) as well as attention capabilities (P300 amplitudes). To delineate the age-related dynamics of P300 potentials, we investigated 250 healthy subjects between 18 and 98 years of age in a cross-sectional study. A total of 330 visual P300 tests was performed in two different paradigms (PI, passive condition, n = 80; PII, active condition, n = 250). In both P300 paradigms, the N250 and P300 latencies were markedly prolonged (p < .0001) in older age, whereas the N250 and P300 latency differences between PII and PI did not change (p > .05). The P300 amplitudes in paradigm I and II revealed only a slight age-related reduction. In fact, the P300 amplitude ratios between PII and PI remained constant. Third-order polynomial regressions provided the best fit of the aging-P300 interactions in paradigms I and II for both males and females. Interestingly, females showed a greater and possibly earlier P300 latency increase during aging than males. These age-related changes of P300 potentials indicate a rather mild cognitive decline that does not accelerate before old age and may be different between both sexes.

Adolescent↗

Brain function and cognition in a community sample of elderly Latinos.

BACKGROUND: Previous studies using PET to measure cerebral glucose metabolism in AD have found metabolic reductions in the temporoparietal and posterior cingulate cortices in individuals with dementia and those at risk of developing it. This study was designed to extend this finding to individuals selected from a population-based cohort of Mexican Americans with a wide spectrum of cognitive ability. METHODS: A group of 93 individuals was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired, cognitively impaired but not demented (CIND), and demented. PET was performed with the tracer [(18)F]-fluorodeoxyglucose, and data were analyzed with both statistical parametric mapping and an atrophy-corrected volume of interest approach. RESULTS: Individuals with dementia had metabolic reductions that were most robust in the posterior cingulate cortex, whereas CIND subjects had less statistically robust reductions in the posterior cingulate cortex. Cingulate hypometabolism increased the risk of dementia and was a significant risk factor for dementia in logistic regression models that also incorporated MR measures of hippocampal volume and white matter hyperintensities. CONCLUSION: Posterior cingulate cortical hypometabolism is clearly detected in individuals with dementia who are selected from a population with lower education and a high prevalence of cerebrovascular risk factors, supporting the generalizability of this finding. These metabolic reductions occur prior to the onset of dementia but only in those persons with relatively advanced symptoms.

Aged↗