A NWB-based dataset and processing pipeline of human single-neuron activity during a declarative memory task.

A challenge for data sharing in systems neuroscience is the multitude of different data formats used. Neurodata Without Borders: Neurophysiology 2.0 (NWB:N) has emerged as a standardized data format for the storage of cellular-level data together with meta-data, stimulus information, and behavior. A key next step to facilitate NWB:N adoption is to provide easy to use processing pipelines to import/export data from/to NWB:N. Here, we present a NWB-formatted dataset of 1863 single neurons recorded from the medial temporal lobes of 59 human subjects undergoing intracranial monitoring while they performed a recognition memory task. We provide code to analyze and export/import stimuli, behavior, and electrophysiological recordings to/from NWB in both MATLAB and Python. The data files are NWB:N compliant, which affords interoperability between programming languages and operating systems. This combined data and code release is a case study for how to utilize NWB:N for human single-neuron recordings and enables easy re-use of this hard-to-obtain data for both teaching and research on the mechanisms of human memory.

Mapping neuronal inputs to REM sleep induction sites with carbachol-fluorescent microspheres.

The cholinergic agonist carbachol was conjugated to latex microspheres that were fluorescently labeled with rhodamine and used as neuroanatomical probes that show little diffusion from their injection site and retrogradely label neurons projecting to the injection site. Microinjection of this pharmacologically active probe into the gigantocellular field of the cat pontine brain stem caused the awake cats to fall into rapid movement (REM) sleep indistinguishable from that produced by free carbachol. Three-dimensional computer reconstruction of the retrogradely labeled neurons revealed a widely distributed neuronal network in the pontine tegmentum. These pharmacologically active microspheres permit a new precision in the characterization and mapping of neurons associated with the control of behavioral state and of other cholinergic networks.

Long-range temporal correlations in the spontaneous spiking of neurons in the hippocampal-amygdala complex of humans.

The spontaneous or background discharge patterns of in vivo single neuron is mostly considered as neuronal noise, which is assumed to be devoid of any correlation between successive inter-spike-intervals (ISI). Such random fluctuations are modeled only statistically by stochastic point process, lacking any temporal correlation. In this study, we have investigated the nature of spontaneous irregular fluctuations of single neurons from human hippocampus-amygdala complex by three different methods: (i) detrended fluctuation analysis (DFA), (ii) multiscale entropy (MSE), (iii) rate estimate convergence. Both the DFA and MSE analysis showed the presence of long-range power-law correlation over time in the ISI sequences. Moreover, we observed that the individual spike trains presented non-random structure on longer time-scales and showed slow convergence of rate estimates with increasing counting time. This power-law correlation and the slow convergence of statistical moments were eliminated by randomly shuffling the ISIs even though the distributions of ISIs were preserved. Thus the power-law relationship arose from long-term correlations among ISIs that were destroyed by shuffling the data. Further, we found that neurons which showed long-range correlations also showed statistically significant correlated firing as measured by correlation coefficient or mutual information function. The presence of long-range correlations indicates the history-effect or memory in the firing pattern by the associative formation of a neuronal assembly.

Venous angiography is needed to interpret inferior petrosal sinus and cavernous sinus sampling data for lateralizing adrenocorticotropin-secreting adenomas.

Bilateral simultaneous venous sampling of ACTH from the inferior petrosal sinus is a reliable test for diagnosing Cushing's disease, but is not reliable for lateralizing ACTH-secreting pituitary adenomas. We reviewed 23 consecutive patients with Cushing's disease who underwent venous angiography of the cavernous and inferior petrosal sinuses followed by bilateral simultaneous venous sampling of ACTH in the inferior petrosal and cavernous sinuses. Venous drainage was bilaterally symmetric in 14 patients (61%) and asymmetric in 9 (39%). The most common asymmetric pattern (6 patients) was for blood from both cavernous sinuses to drain into the right inferior petrosal sinus, with no significant drainage into the left. Cavernous sinus sampling in 21 patients correctly lateralized the tumor in 12 cases of symmetric venous drainage, but in only 3 cases of asymmetric drainage. Inferior petrosal sinus sampling in all 23 patients correctly lateralized the tumor in 12 cases of symmetric drainage, but in only four cases of asymmetric drainage. Overall, venous sampling correctly lateralized 70% of the tumors. Incorrect lateralization in cases of asymmetric venous drainage is probably attributable to shunting of blood toward the side of dominant venous drainage. Our findings illustrate the need for venography in all patients undergoing venous sampling of ACTH because an understanding of the venous drainage patterns is essential to correctly interpret venous sampling data and warn physicians that the lateralization data may be incorrect or unreliable.

Dose-related suppression of REM sleep and PGO waves by the serotonin-1 agonist eltoprazine.

Parental administration of the serotonin-1 agonist eltoprazine (0.0625 to 4.0 mg/kg [0.0002 to 0.016 mmol/kg]) in freely moving cats produced significant suppression of electrophysiologic rapid eye movement (REM) sleep signs, ponto-geniculo-occipital (PGO) activity, and REM sleep behavior. The virtual total suppression of REM sleep (0.4%, 4.0 mg/kg) and PGO wave activity (2 to 4 mg/kg) in exchange for increasing amounts of non-REM (NREM) slow-wave sleep was a dose-dependent function of the amount of eltoprazine administered. Wakefulness was unaffected by eltoprazine regardless of dose. Concurrent with this dose-dependent suppression of REM was a dose-dependent increase in electroencephalographic synchrony and mean electromyographic amplitude. Since eltoprazine was found to shift the balance between REM and NREM sleep but did not change the balance between sleep and waking, it is a potentially useful tool for the investigation of serotonergic-cholinergic interaction.

The aspirin metabolite sodium salicylate causes focal cerebral hemorrhage and cell death in rats with kainic acid-induced seizures.

Aspirin (acetylsalicylic acid), and its main metabolite sodium salicylate, have been shown to protect neurons from excitotoxic cell death in vitro. The objective of our study was to investigate the possible neuroprotective effects of sodium salicylate in vivo in rats with kainic acid-induced seizures, a model for temporal lobe epilepsy in human patients. Male Sprague-Dawley rats received intraperitoneal injections of kainic acid either alone, or with sodium salicylate given before and for 40h after kainic acid injections. The control group received either phosphate-buffered saline or sodium salicylate without co-administration of kainic acid. Animals developed status epilepticus, which was aborted 1.5-2h later with diazepam. On day 3 following kainic acid-induced seizures, animals received bromodeoxyuridine to measure cellular proliferation, and were killed under anesthesia 24h later. Brains were removed, sectioned, and analysed for gross histological changes, evidence of hemorrhage, DNA fragmentation, cellular proliferation, and microglial immunohistochemistry. We report that sodium salicylate did not protect neurons from seizure-induced cell death, and to the contrary, it caused focal hemorrhage and cell death in the hippocampal formation and the entorhinal/piriform cortex of rats with kainic acid-induced seizures. Hemorrhage was never observed in animals that received vehicle, kainic acid or sodium salicylate only, which indicated that sodium salicylate exerted its effect only in animals with seizures, and was confined to select regions of the brain that undergo seizure activity. Large numbers of cells displaying DNA fragmentation were detected in the hippocampal formation, entorhinal/piriform cortex and the dorsomedial thalamic nucleus of rats that received kainic acid or kainic acid in combination with sodium salicylate. Bromodeoxyuridine immunohistochemistry revealed large numbers of proliferating cells in and around the areas with most severe neural injury induced by kainic acid or kainic acid co-administered with sodium salicylate. These same brain regions displayed intense staining with a microglia-specific marker, an indication of microglial activation in response to brain damage. In all cases, the degree of cell death, cell proliferation and microglia staining was more severe in animals that received the combination of kainic acid and sodium salicylate when compared to animals that received kainic acid alone. We hypothesize that our findings are attributable to sodium salicylate-induced blockade of cellular mechanisms that protect cells from calcium-mediated injury. These initial observations may have important clinical implications for patients with epilepsy who take aspirin while affected by these conditions, and should promote further investigation of this relationship.

A cholinoceptive desynchronized sleep induction zone in the anterodorsal pontine tegmentum: locus of the sensitive region.

Carbachol, a long-acting cholinergic agonist, was microinjected (4 micrograms/250 nl per 90 s) into 90 sites within the anterodorsal pontine tegmentum of four cats and the time to onset and percentage of time spent in a desynchronized sleep-like state during 40 min postinjection were calculated. Compared with more posteroventral pontine sites, the shorter latencies and higher percentages observed confirmed earlier predictions of a sensitive cholinoceptive zone in the anterodorsal pons. In 27 trials a desynchronized sleep-like state was observed within 5 min; in 31 trials the latency was 5-10 min and in the remaining 32 trials, greater than 10 min. Plotting the desynchronized sleep-like state latency and the desynchronized sleep-like state percentage as a function of the three-dimensional coordinates revealed that injection sites with short latency (less than 5 min) and high percentage (greater than 80%) were concentrated between the coordinates of P 1.0 to 3.5 and V -3.5 to -5.5, at the lateral coordinate L 2.0. On the frontal plane, the short desynchronized sleep-like state latency and high desynchronized sleep-like state percentage sites begin in the pontine tegmental region just lateral to the ventral tegmental nucleus and extend 3 mm ventrocaudally. A regression plot of the data in sagittal plane 2.0 revealed a short latency axis, around which the short latency sites cluster, running in a slightly dorsoventral direction from about P 1.0 to V -4.0 to P 4.0 to V -5.5. This observation suggests that the sensitive zone might approximate a cylinder in shape, a hypothesis supported by the correlation of longer latencies and lower percentages at increasing radial distance from the axis. The non-linear relationship between cholinergic potency and distance from the short latency axis suggests that the desynchronized sleep-like state latency is a function of two factors; a variable diffusion-based delay of carbachol to distant neuronal populations involved in the desynchronized sleep-like state production, and a fixed recruitment-based delay following activation of neurons in the sensitive zone. Interpretation of these findings in light of earlier studies involving microstimulation of the pontine tegmentum argue in favor of a distributed network of discrete neuronal populations as the source of desynchronized sleep generation.

A cholinoceptive desynchronized sleep induction zone in the anterodorsal pontine tegmentum: spontaneous and drug-induced neuronal activity.

The effect of carbachol microapplication (4 micrograms/250 nl per 90 s) on the discharge of neurons in the anterodorsal pons of four cats was studied using a newly devised microinjector-microelectrode assembly. Neurons were classified according to the magnitude of their discharge rate increases (or decreases) in physiological desynchronized sleep as desynchronized-on (or desynchronized-off) before injecting carbachol. When carbachol produced a desynchronized sleep-like state only half (15 out of 30) of the desynchronized-on cells were activated (desynchronized-on/desynchronized sleep-like state-on) while the other half were not (desynchronized-on/desynchronized sleep-like state-not on). Compared with the non-activated cells, the desynchronized-on/desynchronized sleep-like state-on cells had three features consistent with playing an active role in desynchronized sleep generation: these cells had a higher mean discharge frequency in desynchronized sleep and higher ratio of discharge frequency in desynchronized sleep compared with wakefulness; they did not fire in phase with electromyogram excitation of neck muscles; and they were concentrated in the short latency desynchronized sleep-like state induction zone described in the companion paper. The three-way correlation between the optimal anatomical site for short latency desynchronized sleep-like state induction, the selective neuronal discharge pattern in desynchronized sleep and the cholinergic activation pattern in the desynchronized sleep-like state suggest that we may have identified a neuronal population that is cholinoceptively activated as part of the physiological mechanism of desynchronized sleep generation.

Nocardial brain abscess: treatment strategies and factors influencing outcome.

The successful management of nocardial brain abscess remains problematic. The authors report 11 cases of nocardial brain abscess treated between 1971 and 1993 and review 120 cases reported since 1950. The clinical findings included focal deficits in 55 patients (42%), nonfocal findings in 36 (27%), and seizures in 39 (30%). Extraneural nocardiae were present in 66% of the cases; pulmonary (38%) and cutaneous/subcutaneous (20%) locations were the most frequent. The abscesses were single in 54% of the patients, multiple in 38%, and of unknown number in 8%. Forty-four of 131 patients (34%) were immunocompromised; since 1975, 18 of 40 immunocompromised patients (45%) were transplant recipients and six (15%) had human immunodeficiency virus. The mortality rate was 24% after initial craniotomy and excision (11/45), 50% after aspiration/drainage (17/34), and 30% after nonoperative therapy (7/23); 29 cases (22%) were diagnosed at autopsy. The mortality rate was 33% in patients with single abscesses and 66% in those with multiple abscesses (P < 0.0003). There was no difference in the mortality rates of immunocompromised and nonimmunocompromised patients treated before computed tomography (CT) was available; since the advent of CT, however, the mortality rate has been significantly higher in immunocompromised patients (55% vs. 20%, P < 0.05). Although the mortality rate for nocardial brain abscesses has dropped almost 50% since the advent of CT, it has remained virtually unchanged in immunocompromised patients and is three times higher than that of other bacterial brain abscesses (30% vs. 10%). The authors recommend image-directed stereotactic aspiration for diagnosis; however, craniotomy and total excision are necessary in most cases, because nocardial abscesses are usually multiloculated. Patients with minimal neurological deficits or small abscesses may be treated initially with antibiotics alone. Sulfonamides, alone or in combination with trimethoprim, are most effective and should be continued for at least 1 year. Minocycline, imipenem, or aminoglycoside in combination with a third-generation cephalosporin may be used with reasonably good success as second-line agents in cases of allergy or nonresponsiveness to sulfa agents.

Improved management of multiple brain abscesses: a combined surgical and medical approach.

Bacterial brain abscesses occur in approximately 1500 to 2500 patients each year in the United States. Multiple abscesses have been noted in 10 to 50% of these patients. The goal of this study was to better define the roles of surgery and medical management in patients harboring multiple brain abscesses and to develop an algorithmic approach to the treatment of these complex patients. Between 1976 and 1992, 16 patients with multiple brain abscesses were treated by a single physician (M.L.R.). The ages of the patients ranged from 1.5 to 73 years (median, 47 yr). In all patients, a diagnosis of multiple abscesses was made by computed tomography (15 patients) or magnetic resonance imaging (1 patient) brain scans. The number of abscesses per patient ranged from 2 to 30, and the abscesses were located in all regions of the brain. Thirteen received a combination of antibiotics and surgical drainage, and three received antibiotics only. Surgery was performed on abscesses larger than 2.5 cm or on those situated in critical areas of the brain or causing significant mass effect. Excision and open aspiration via craniotomy and stereotactic aspiration were analyzed on the basis of the location of the lesion and infecting organism. Any abscess that enlarged after 2 weeks of antibiotics or that failed to shrink after 3 to 4 weeks of antibiotics was again aspirated or excised. Forty-three surgical procedures were performed in 13 patients, and 8 (62%) of the patients operated on required more than one surgical procedure. No significant morbidity was observed in any of the surgical procedures. Antibiotics were administered intravenously for an average of 6 to 8 weeks and were adjusted according to organism type and sensitivity to antibiotics. One patient (6%) died, and the remaining 15 patients had resolution of all abscesses and good neurological recovery within 6 months. On the basis of these results, we propose a combined surgical and medical approach to the treatment of patients with multiple brain abscesses. We recommend the aggressive surgical drainage of all abscesses larger than 2.5 cm in diameter, combined with 6 to 8 weeks of intravenous antibiotics. Biweekly computed tomography or magnetic resonance imaging is necessary to closely monitor patients for evidence of abscess growth or failure to resolve despite antibiotics, prompting another operation. The application of this combined approach should yield cure rates of more than 90% in patients with multiple brain abscesses, a result similar to that expected when treating patients with solitary lesions.

The "filum intermedium" sign: focal in utero spinal cord infarct and extraspinal thecal sac. Case report.

This report describes the unique case of a child born with paraplegia and a neurogenic bladder who was found to have a dysplastic, nonossified T-12 vertebral body, midline fusion of the T-12 neural arches, obliteration of the spinal canal at T-12, and an extraspinal thecal sac in the T11-L1 region. Neural tissue was focally absent from T9-12, but neural structures above and below were preserved. Narrowing of the thecal sac on myelograms and sagittal magnetic resonance images signifies in utero focal infarction of the spinal cord after neurulation but before formation of the posterior half of the spinal canal. The infarction resulted in severe focal narrowing of the thecal sac from T10-L1, resembling a premature and duplicated filum terminale; to denote the radiographic appearance of these anomalies, the authors have coined the term "filum intermedium" sign. The extremely unusual radiographic findings in this child illustrate the important interactions between neural tube, neural crest, and somite in the development of the spinal cord and spinal column. Correlation of the radiographic findings with the embryological differentiation and migration of these structures suggests that the spinal anomalies were caused by a focal insult, probably vascular in origin, occurring between the sixth and eighth weeks of gestation. The identification of a focally narrowed thecal sac and spinal cord (the "filum intermedium" sign) localizes the time of the insult to between the first and third month of gestation, and therefore is a useful marker in understanding developmental malformation of the spinal cord.

Treatment options and prognosis for multicentric juvenile pilocytic astrocytoma.

Little is known about the risk of developing multicentric disease in patients with juvenile pilocytic astrocytoma (JPA), and even less about its prognosis. Only five cases have been reported. Between 1986 and 1992, the authors treated 90 patients with either primary or recurrent JPA, 11 of whom developed multicentric spread. Ten patients had primary tumors in the hypothalamic region, eight were under 4 years of age at initial diagnosis, all had initially undergone a subtotal resection or biopsy, and 10 received postoperative multiagent chemotherapy or irradiation for residual disease. Multicentric spread was discovered immediately to 108 months after initial diagnosis; nine patients were asymptomatic at the time. Most patients received chemotherapy for the multicentric disease, which was found throughout the craniospinal axis. During 21 to 148 months of follow-up monitoring, seven patients had stabilization or regression of multicentric disease and four died. Patients with hypothalamic region tumors were 23 times more likely to develop multicentric spread than were those with primary tumors located elsewhere (p < 0.001). Based on this review, it is concluded that multicentric spread of JPA occurs more frequently than was previously recognized. In patients with subtotally resected JPA and several years of follow-up review via magnetic resonance imaging, the incidence of recurrence in a site different from the original was 12%. Patients with subtotally resected JPA in the hypothalamic region should be considered to be at high risk for developing multicentric spread. Chemotherapy appears useful in stabilizing multicentric disease. Earlier detection and intervention may result in longer disease-free survival in patients with multicentric spread of JPA.

Corpus callosotomy: a quantitative study of the extent of resection, seizure control, and neuropsychological outcome.

Corpus callosotomy is valuable for controlling medically intractable generalized seizures in appropriate patients, but postoperative development of language disorders, neuropsychological impairment, and motor dysfunction have all been noted. The extent of callosum resection has been implicated as a possible determinant of outcome, but this hypothesis has not been formally tested. Analysis of the records of all patients who underwent corpus callosotomy at the University of California, San Francisco, from 1986 to 1991 showed that, of 15 patients who underwent anterior or complete callosotomy, seven were entirely or nearly seizure-free, four had at least a 50% reduction in seizure frequency, and four had no change. To determine callosal size and extent of callosotomy, preoperative and postoperative magnetic resonance images were measured with computer-based planimetry. Seizure outcome was not significantly associated with preoperative callosal size or extent of callosotomy. Intelligence quotient scores did not change significantly after callosotomy. No severe neuropsychological deficits developed after anterior or complete callosotomy, even in patients with mixed cerebral dominance or bilateral language representation. These results indicate that division of the anterior one-half to two-thirds of the corpus callosum is nearly as effective as more extensive anterior sectioning or complete callosotomy in reducing drop-attack and generalized tonic-clonic seizures in appropriate patients, and that the extent of callosotomy is not an important factor on outcome when at least 50% to 65% of the callosum is divided. Mixed cerebral dominance and other unusual patterns of language and memory organization do not appear to increase the postoperative risk for neuropsychological deficits, regardless of the extent of anterior section.

Idiopathic hypertrophic cranial pachymeningitis. Report of three cases.

Hypertrophic cranial pachymeningitis is a rare, idiopathic form of granulomatous pachymeningitis. This report describes three cases of hypertrophic cranial pachymeningitis and discusses the clinical, radiographic, and pathological findings in these and other reported cases. These lesions typically cause progressive cranial nerve palsies, headaches, and cerebellar dysfunction. They occur in patients of all age groups; the peak incidence is in the sixth decade. Hypertrophic cranial pachymeningitis is best identified by magnetic resonance imaging. The diagnosis is established by excluding all other granulomatous and infectious diseases. A dural biopsy is essential to confirm the diagnosis. Hypertrophic cranial pachymeningitis is initially responsive to steroid therapy, but in most cases it recurs or progresses despite treatment. Surgical excision of granulomas is occasionally necessary to alleviate a mass effect. The long-term outcome remains uncertain for most patients, but progressive disease is usually fatal owing to cranial neuropathies.

Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson's disease.

OBJECT: In recent years, fetal mesencephalic tissue transplant for the treatment of Parkinson's disease (PD) has been demonstrated to hold promise, but potential complications related to growth of allograft tissue have not been well described. This report explores the development and possible causation of a fatal cyst arising from a fetal transplant in the brain. METHODS: The authors report the case of a 52-year-old woman who underwent bilateral putamenal fetal mesencephalic allograft transplant for PD at another hospital. Twenty-three months later she presented to the authors' institution in a coma. Admission computerized tomography and magnetic resonance (MR) studies revealed a contrast-enhancing mural nodule and associated large cyst arising from the left putamen and causing brainstem compression. Despite surgical decompression of the cyst, the patient did not regain consciousness. Biopsy and autopsy specimens were obtained, along with an analysis of the cyst fluid. Genotyping of the nodule and the patient's peripheral lymphocytes by using polymerase chain reaction-based microsatellite analysis was also performed. Biopsy samples and autopsy histopathological studies showed inflammatory cells, hemosiderin-laden macrophages, and astrocytosis. Scattered neurons and multiple rests of choroid plexus were also noted. The cyst had a thin wall and contained liquid that was identical in composition to cerebrospinal fluid (CSF). Genotyping demonstrated the presence of alleles in the nodule DNA that were not present in lymphocytic DNA, indicating that the nodule contained allograft tissue. CONCLUSIONS: The authors hypothesize that the choroid plexus tissue contained in the allograft resulted in CSF production and cyst formation at the transplant site, ultimately leading to the patient's herniation syndrome. The clinical history and large size of the mural nodule indicate slow growth of this allograft site and cyst over time. This case demonstrates that unusual patterns of tissue growth can occur in the brain after fetal tissue transplant and emphasizes the need for long-term monitoring of posttransplant patients by means of MR imaging. Cell sorting should be considered to ensure transplant of pure neuronal and astroglial populations.

Influence of magnetic source imaging for planning intracranial EEG in epilepsy.

BACKGROUND: Magnetic source imaging (MSI) is used routinely in epilepsy presurgical evaluation and in mapping eloquent cortex for surgery. Despite increasing use, the diagnostic yield of MSI is uncertain, with reports varying from 5% to 35%. To add benefit, a diagnostic technique should influence decisions made from other tests, and that influence should yield better outcomes. We report preliminary results of an ongoing, long-term clinical study in epilepsy, where MSI changed surgical decisions. METHODS: We determined whether MSI changed the surgical decision in a prospective, blinded, crossover-controlled, single-treatment, observational case series. Sixty-nine sequential patients diagnosed with partial epilepsy of suspected neocortical origin had video-EEG and imaging. All met criteria for intracranial EEG (ICEEG). At a surgical conference, a decision was made before and after presentation of MSI. Cases where MSI altered the decision were noted. RESULTS: MSI gave nonredundant information in 23 patients (33%). MSI added ICEEG electrodes in 9 (13%) and changed the surgical decision in another 14 (20%). Based on MSI, 16 patients (23%) were scheduled for different ICEEG coverage. Twenty-eight have gone to ICEEG, 29 to resection, and 14 to vagal nerve stimulation, including 17 where MSI changed the decision. Additional electrodes in 4 patients covered the correct: hemisphere in 3, lobe in 3, and sublobar ictal onset zone in 1. MSI avoided contralateral electrodes in 2, who both localized on ICEEG. MSI added information to ICEEG in 1. CONCLUSION: Magnetic source imaging (MSI) provided nonredundant information in 33% of patients. In those who have undergone surgery to date, MSI added useful information that changed treatment in 6 (9%), without increasing complications. MSI has benefited 21% who have gone to surgery.

Dream Bizarreness as the Cognitive Correlate of Altered Neuronal Behavior in REM Sleep.

Bizarreness is a cognitive feature common to REM sleep dreams, which can be easily measured. Because bizarreness is highly specific to dreaming, we propose that it is most likely brought about by changes in neuronal activity that are specific to REM sleep. At the level of the dream plot, bizarreness can be defined as either discontinuity or incongruity. In addition, the dreamer's thoughts about the plot may be logically deficient. We propose that dream bizarreness is the cognitive concomitant of two kinds of changes in neuronal dynamics during REM sleep. One is the disinhibition of forebrain networks caused by the withdrawal of the modulatory influences of norepinephrine (NE) and serotonin (5HT) in REM sleep, secondary to cessation of firing of locus coeruleus and dorsal raphe neurons. This aminergic demodulation can be mathematically modeled as a shift toward increased error at the outputs from neural networks, and these errors might be represented cognitively as incongruities and/or discontinuities. We also consider the possibility that discontinuities are the cognitive concomitant of sudden bifurcations or "jumps" in the responses of forebrain neuronal networks. These bifurcations are caused by phasic discharge of pontogeniculooccipital (PGO) neurons during REM sleep, providing a source of cholinergic modulation to the forebrain which could evoke unpredictable network responses. When phasic PGO activity stops, the resultant activity in the brain may be wholly unrelated to patterns of activity dominant before such phasic stimulation began. Mathematically such sudden shifts from one pattern of activity to a second, unrelated one is called a bifurcation. We propose that the neuronal bifurcations brought about by PGO activity might be represented cognitively as bizarre discontinuities of dream plot. We regard these proposals as preliminary attempts to model the relationship between dream cognition and REM sleep neurophysiology. This neurophysiological model of dream bizarreness may also prove useful in understanding the contributions of REM sleep to the developmental and experiential plasticity of the cerebral cortex.

Volumetric multishot echo-planar spectroscopic imaging.

Rapid volumetric magnetic resonance spectroscopic imaging (MRSI) is potentially of great relevance to the diagnosis and treatment of focal cerebral diseases such as cancer and epilepsy. A strategy for volumetric multishot echo-planar spectroscopic imaging (MEPSI) is described which allows whole-brain metabolite mapping in approximately 20 min. A multishot trajectory is used in both the spatial and temporal domains which reduces the accumulated phase during each echo train and tolerates conventional Fourier reconstruction without regridding. Also described is a generalized correction for phase discontinuities arising from the multishot acquisition of the time domain, which is independent of the spatial k-space trajectory and is therefore also applicable to multishot spiral MRSI. Whole-brain, lipid-suppressed MEPSI data were acquired from five normal subjects. The mean signal-to-noise ratios (SNRs) (+/-SE) for the n-acetylaspartate (NAA), choline (Cho), and creatine (Cr) maps across all subjects were 21.3 +/- 1.8, 11.7 +/- 0.6, and 9.2 +/- 0.6, respectively, with a computed voxel size of 2.33 ml.

Predicting survival from head trauma 24 hours after injury: a practical method with therapeutic implications.

OBJECTIVE: To develop a method to predict long-term outcome after head injury and determine if outcome can be accurately predicted 24 hours after injury. DESIGN: A retrospective review was performed on a study cohort of 672 head-injured patients admitted in coma (Glascow Coma Scale score < or = 8) who remained comatose for at least 6 hours, survived more than 24 hours, and had 6-month outcome data available. Stepwise logistic regression analysis was used to determine which clinical variables predicted 6-month outcome. Statistically significant clinical predictors were combined into a single examination variable (MPX score), which reflected a rank-ordering of examinations from worst to best, which was then further weighted by patient age. The relation between 6-month outcome and MPX score at admission and 24 hours was plotted and analyzed. MEASUREMENT AND MAIN RESULTS: Age, best motor score, and pupillary reactivity at admission and 24 hours were significant predictors of outcome; extraocular motility was predictive at 24 hours only. Age was the most important independent predictor, followed by best motor score, pupillary reactivity, and extraocular motility. Combining these predictors into MPX score resulted in a set of graphs that reliably predicted long-term outcome. The 24-hour MPX data were better predictors of 6-month outcome and were more specific in predicting negative outcomes than admission data. CONCLUSIONS: The method is simple to use, relying on bedside neurologic examination and a single graph, but appears to predict long-term outcome accurately as early as 24 hours after head injury. If validated on other large series of patients, this method could provide an objective and practical basis for terminating care in patients unlikely to survive a head injury.