Cerebral vessels have the capacity to transport sodium and potassium.

The activity of Na+, K+-activated adenosinetriphosphatase and the uptake of a potassium analog, rubidium, were found to be similar in cerebral microvessels and choroid plexus when measured in vitro. This similarity suggests that sodium and potassium concentrations in the nascent brain extracellular fluid are determined by the same active process that regulates their concentration in nascent cerebrospinal fluid. The brain microvessels may thereby play on active role in brain potassium homeostasis and brain extracellular fluid formation.

Nicotinic receptor activation in human cerebral cortical interneurons: a mechanism for inhibition and disinhibition of neuronal networks.

Cholinergic control of the activity of human cerebral cortical circuits has long been thought to be accounted for by the interaction of acetylcholine (ACh) with muscarinic receptors. Here we report the discovery of functional nicotinic receptors (nAChRs) in interneurons of the human cerebral cortex and discuss the physiological and clinical implications of these findings. The whole-cell mode of the patch-clamp technique was used to record responses triggered by U-tube application of the nonselective agonist ACh and of the alpha7-nAChR-selective agonist choline to interneurons visualized by means of infrared-assisted videomicroscopy in slices of the human cerebral cortex. Choline induced rapidly desensitizing whole-cell currents that, being sensitive to blockade by methyllycaconitine (MLA; 50 nM), were most likely subserved by an alpha7-like nAChR. In contrast, ACh evoked slowly decaying whole-cell currents that, being sensitive to blockade by dihydro-beta-erythroidine (DHbetaE; 10 microM), were most likely subserved by an alpha4beta2-like nAChR. Application of ACh (but not choline) to the slices also triggered GABAergic postsynaptic currents (PSCs). Evidence is provided that ACh-evoked PSCs are the result of activation of alpha4beta2-like nAChRs present in preterminal axon segments and/or in presynaptic terminals of interneurons. Thus, nAChRs can relay inhibitory and/or disinhibitory signals to pyramidal neurons and thereby modulate the activity of neuronal circuits in the human cerebral cortex. These mechanisms, which appear to be retained across species, can account for the involvement of nAChRs in cognitive functions and in certain neuropathological conditions.

Frontal blood flow changes in recovery from coma.

Two-dimensional studies of cortical blood flow were conducted in 20 closed head injury patients in a comatose state and subsequently in 9 patients as they recovered to an awake and responding state. Comatose patients showed a reduction of frontal flow compared to the resting pattern observed in age matched normal volunteers. In most patients the normal anterior-to-posterior flow gradient was reversed. Increases in global flow, while in coma, tended to exaggerate this reversal. Patients who survived showed a normalization of the regional flow pattern as they regained consciousness. The marked reduction of frontal blood flow in the comatose state was independent of locus of injury as determined by computed tomography (CT) scan data. Combined with previous CBF studies of sensory and cognitive activation, these findings suggest that frontal reduction may be a nonspecific effect of any state or condition involving reduced directed mental activity. This, in turn, raises questions about recent interpretations offered for frontal CBF reduction in psychiatric disease.

Age-related differences in recovery cycle of auditory evoked potentials.

Age-related differences in cerebral responsiveness to stimuli as reflected by the recovery cycle of cortical auditory evoked potentials (EPs) were investigated in healthy young and elderly adults. Pairs of identical tones separated by a fixed 350 msec interval were presented at rates of 1.0/sec, 0.5/sec, and 0.2/sec (inter-pair-intervals of 650, 1650, or 4650 msec). No age difference in the P1-N1 or N1-P2 amplitudes to either tone of the pair was present with the two faster stimulation rates. However, age-specific amplitude effects emerged for the slowest rate. The P1-N1 and especially the N1-P2 amplitude of the EP to the first as compared to that of the second tone was greatly enhanced among the young, but not as much among the elderly adults. Similarly, group differences in baseline to N1 and P2 amplitude measures of EPs to the first tone of the pair were most pronounced at the fastest stimulation rate. These data indicate clear differences in the recovery cycle of EPs between normal young and elderly subjects and demonstrate the applicability of the two-tone stimulation procedure in the assessment of cerebral responsivity in normal and pathologic populations.

Evoked potential correlates of right hemisphere involvement in language recovery following stroke.

A probe evoked potentials procedure was used to assess the relative engagement of both cerebral hemispheres during a language task in the following four groups of dextral adults: left hemisphere (LH)-damaged aphasics recovering from stroke, dysarthrics, right hemisphere (RH)-damaged nonaphasic patients, and normal control subjects. In agreement with previous findings using the probe procedure, the present results indicate greater task-specific RH activation in recovering aphasics and, to a lesser degree, dysarthric patients and greater LH activation in both nonaphasic, RH-damaged patients and normal control subjects. On the basis of these data, we suggest that increasing participation of the nondominant hemisphere may subserve restitution of language in adults sustaining LH lesions.

Evidence for right-hemisphere involvement in recovery from aphasia.

Cortical evoked potentials and dichotic listening test scores were used to assess the extent of activation of the two cerebral hemispheres during various language tasks in a group of 21 recovering aphasics, 15 nonaphasic patients with right-hemisphere stroke, and 17 normal volunteers. In agreement with previous findings, both measures suggest greater right-hemisphere activation during language processing in the recovering aphasics than in nonaphasic patients and normal subjects. These data support the view that restitution of language entails reorganization of brain function with increased participation of the nondominant hemisphere.

Magnetic resonance imaging after 'diffuse' nonmissile head injury. A neurobehavioral study.

The diagnosis of diffuse brain injury is considered when computed tomography provides no evidence of an intracranial mass lesion in acute nonmissile head injury. Magnetic resonance imaging (MRI) of a young woman who had sustained severe diffuse brain injury five years earlier disclosed multifocal lesions involving the frontal, temporal, parietal, and occipital lobes. We report the results of serial neurobehavioral assessment for clinical correlation with the brain lesions visualized by MRI. Pending confirmation of our findings in a series of patients studied by MRI during the acute and chronic stages of recovery from head injury, we postulate that the presence and type of neurobehavioral sequelae of diffuse brain injury are related to the intrahemispheric loci of predominantly white matter lesions and degeneration.

Localization of auditory response sources using magnetoencephalography and magnetic resonance imaging.

Magnetoencephalography offers the possibility of localizing accurately and noninvasively the source of intracranial currents associated with normal and abnormal brain activity. The purpose of this study was to assess the validity and across-subject reliability of localization of cortical sources responding to ipsilateral and contralateral auditory stimulation. Magnetic evoked fields to both stimulation conditions were measured in eight consecutive normal subjects, and the cortical sources of these fields were estimated on the basis of these measurements. Subsequent projection of the source location coordinates onto magnetic resonance images showed that in all subjects the sources were accurately estimated to fall in the vicinity of the auditory cortex and that two separate sources may account for the response to ipsilateral and contralateral stimulation.

Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report.

To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state.

Cognition in relation to magnetic resonance imaging in head-injured children and adolescents.

To investigate the relationship between cognitive sequelae and magnetic resonance imaging (MRI) findings following closed head injury of varying severity in the pediatric age range, 76 head-injured children and adolescents were studied at least 3 months after trauma and compared with 57 normal controls. Problem solving, planning, verbal and design fluency, memory, and response modulation were assessed. Significant effects of injury were obtained on all of the cognitive measures. Cognitive impairment was more consistently present on the various outcome measures in children who were 6 to 10 years old at the time of the study than in the older children and adolescents. Magnetic resonance imaging disclosed areas of abnormal signal in the frontal lobes of 42 patients, whereas focal lesions restricted to the extrafrontal region were found in 15 children. Regression analyses disclosed that taking into account the size of frontal lobe lesion enhanced the relationship between cognitive performance and the severity of injury.

Mutism after closed head injury.

Prospective study of patients admitted to a hospital for closed head injury showed that nine patients (nearly 3%) became mute for varying periods despite recovery of consciousness and communication through a nonspeech channel. Computed tomography (CT) showed subcortical lesions situated primarily in the putamen and internal capsule of four patients, whereas four of the five patients without subcortical lesions had left-hemisphere cortical injury. The patients without subcortical injury visualized by CT exhibited a longer duration of impaired consciousness consistent with severe diffuse brain injury and they showed more long-term linguistic deficits. We related our findings to recent studies of atypical aphasia after occlusive vascular lesions of the basal ganglia.

Visuospatial tasks compared via activation of regional cerebral blood flow.

Regional cerebral blood flow was measured in 19 subjects during the performance of three tasks thought to primarily involve right hemisphere processing: judgement of line orientation, mental rotation of three-dimensional cube arrays, and a fragment puzzle task. Asymmetries in hemispheric flow (right side greater) were only observed in the line orientation and rotation conditions and were present in both sexes. The magnitude of the asymmetry was greater in the rotation task which also showed an asymmetry in parietal flow. Thus mental rotation placed the most asymmetric demand on cerebral resources. This provides a task that more reliably activates the right hemisphere than those previously reported and suggests a truly "mental manipulative" aspect to right hemisphere advantage in visuospatial performance.

Evoked potential indices of selective hemispheric engagement in affective and phonetic tasks.

Evoked potentials (EPs) to a probe click stimulus were recorded from left and right temporal areas of dextral adults engaged in phonetic and prosodic processing of an emotionally charged tape recorded conversation. Attenuation of the probe EP amplitudes was significantly greater in the left and right hemispheres during the phonetic and prosodic tasks, respectively, indicating lateral dominance shifts depending on selective processing of linguistic vs affective cues conveyed by the same speech signals.

CBF gradient changes elicited by visual stimulation and visual memory tasks.

Normal volunteers underwent three successive scans of regional cerebral blood flow (rCBF) using the 133Xe inhalation technique during visual stimulation, a recognition memory task and a resting state defined by high EEG alpha content. Since the stimulation was virtually identical in both non-rest conditions, we were able to separate the CBF pattern resulting from simple stimulation and that resulting from the cognitive (recognition memory) component alone. These turned out to have very nearly opposite effects on the normal anterior-to-posterior resting state gradient: the sensory component diminished the gradient, while the cognitive component exaggerated it. It is suggested that these normative data can be of clinical value in the study of cerebral recovery/reorganization following post-traumatic amnesia.

Cerebral metabolic and vasopressin and oxytocin responses during osmotic stimulation in conscious rats.

Intravenous infusion of hypertonic saline increased plasma [Na (+) ] and osmolality and induced a short-latency drinking response. These changes were associated with increased glucose utilization in the supraoptic and paraventricular nuclei and neural lobe, and decreases in the medial septum and nucleus ambiguus. The increases in glucose utilization were more accentuated in the supraoptic nuclei than in paraventricular nuclei, indicating that they are more sensitive to osmotic stimulation than the paraventricular nuclei. In association with enhanced activity in the hypothalamo-neurohypophysial system, plasma vasopressin and oxytocin concentrations increased, with a preferential increase of oxytocin over vasopressin. The hormonal contents in the neural lobe were not depleted by the osmotic stimulus despite the large increases of their concentrations in the plasma.

Infantile right hemisphere injury: a case report with MRI and 13 year follow-up.

Serial neuropsychological findings were obtained in a case of infantile right parietal injury who was studied over a 13 year follow-up period. Magnetic resonance imaging at age 13 years documented extensive injury to the right hemisphere, particularly the parietal region. Serial examinations at age 7 and 13 years showed intact visual attention, normal expression and processing of affect and variable visuospatial abilities. However, intellectual development was generally depressed. Implications of these findings for recovery from early brain injury are discussed.

Effects of sinoaortic denervation on glucose utilization in the subfornical organ and pituitary neural lobe during administration of angiotensin II.

Angiotensin II infused intravenously into sinoaortic-denervated rats induced drinking and increased glucose utilization in the subfornical organ and pituitary neural lobe in amounts not different from those observed in sham-operated animals. We suggest that inputs from baroreceptors have a negligible influence on glucose metabolism in the subfornical organ during infusion of angiotensin II.

Independent activation of subfornical organ and hypothalamo-neurohypophysial system during administration of angiotensin II.

The autoradiographic deoxyglucose method was employed to investigate: 1) whether the increased glucose utilization in the subfornical organ (SFO) during administration of angiotensin II (AII) depends on the neural inputs to the SFO; and 2) to investigate whether the activation of the hypothalamo-neurohypophysial system during administration of AII depends on inputs from the SFO. The ventral stalk of the SFO, which contains the majority of efferent and afferent projections of this circumventricular structure, was interrupted with knife cuts three days before the deoxyglucose experiments. Intravenous infusion of AII (2.5 micrograms/min) for 45 min increased glucose utilization in the SFO and neural lobe in the lesioned animals to the same extent as in the sham-operated animals. Drinking, however, was significantly reduced in lesioned animals. These experiments disclose independent parallel mechanisms responsible for activation of the SFO and the hypothalamo-neurohypophysial system by AII.

Desmopressin, but not vasopressin, decreases activity of the hypothalamo-neurohypophysial system in Brattleboro rats.

The pituitary neural lobe of homozygous Brattleboro rats has high rates of glucose utilization not affected by chronic treatment with exogenous vasopressin, despite attenuation of polydipsia and polyuria. We evaluated whether this effect may result from the inability of vasopressin to affect the hypothalamo-neurohypophysial metabolism or from the development of resistance to chronic vasopressin treatment. We used the [14C]deoxyglucose method to compare 28-h effects of vasopressin treatment (5 U/kg, i.m., twice a day) with that of desmopressin (100 micrograms/kg, i.p., once a day), a long-lasting antidiuretic hormone, on glucose utilization of the hypothalamo-neurohypophysial system and related structures in conscious homozygous Brattleboro rats. Vasopressin and desmopressin reduced water intake, plasma osmolality and plasma Na+ concentration similarly. Vasopressin decreased glucose utilization in the supraoptic nucleus, subfornical organ and median preoptic nucleus, but did not alter activity in the paraventricular nucleus and neural lobe. Desmopressin decreased glucose utilization in all these structures. The results indicate that desmopressin has a more potent inhibitory action on the hypothalamo-neurohypophysial system than vasopressin over this short duration of treatment. The lack of response in the neural lobe from chronic treatment with vasopressin seems to be due to its inability to affect the paraventricular nucleus metabolism. The maintenance of metabolic activity in the paraventricular nucleus of vasopressin-treated Brattleboro rats suggests that this structure contributes importantly to the metabolism of neural lobe.

Neuronal nicotinic receptors in synaptic functions in humans and rats: physiological and clinical relevance.

The present report describes the participation of nicotinic receptors (nAChRs) in controlling the excitability of local neuronal circuitries in the rat hippocampus and in the human cerebral cortex. The patch-clamp technique was used to record responses triggered by the non-selective agonist ACh and the alpha7-nAChR-selective agonist choline in interneurons of human cerebral cortical and rat hippocampal slices. Evidence is provided that functional alpha7- and alpha4beta2-like nAChRs are present on somatodendritic and/or preterminal/terminal regions of interneurons in the CA1 field of the rat hippocampus and in the human cerebral cortex and that activation of the different nAChR subtypes present in the preterminal/terminal areas of the interneurons triggers the tetrodotoxin-sensitive release of GABA. Modulation by nAChRs of GABAergic transmission, which can result either in inhibition or disinhibition of pyramidal neurons, depends both on the receptor subtype present in the interneurons and on the agonist acting upon these receptors. Not only do alpha7 nAChRs desensitize faster than alpha4beta2 nAChRs, but also alpha7 nAChR desensitization induced by ACh lasts longer than that induced by choline. These mechanisms, which appear to be retained across species, might explain the involvement of nAChRs in cognitive functions and in such neurological disorders as Alzheimer's disease and schizophrenia.