Choice between food and cocaine or fentanyl reinforcers under fixed and variable schedules in female and male rhesus monkeys.

RATIONALE: Illicit drugs may be unpredictable in terms of the time and effort required to obtain them, and this can be modeled with variable- (VR) vs. fixed-ratio (FR) schedules. In a recent experiment (Zamarripa et al. 2023), the potency of cocaine to maintain choice was greatest under a VR (compared with a FR) when food was available under a FR schedule. OBJECTIVES: The goal of the current study was to extend prior choice results with VR vs. FR schedules to a more efficient procedure with cocaine or fentanyl vs. food. Furthermore, the FR schedule of food delivery was manipulated to determine whether increased drug choice under a VR (compared with a FR) schedule depends on the size of the schedule of nondrug reinforcement. METHODS: Adult female (n = 2) and male (n = 4) monkeys chose between cocaine (0-30 µg/kg/injection) or fentanyl (0-1.0 µg/kg/injection) and food (2 pellets/delivery) under a 5-component procedure. In different conditions, food was available under a FR 25, 50, or 100 and cocaine or fentanyl were available under FR or VR 100 schedules. RESULTS: Cocaine's potency to maintain choice was greatest under a VR 100 (compared with FR 100) when food was available under a FR 50 or 100, and fentanyl's potency to maintain choice was generally greatest under a VR 100 (compared with FR 100) when food was available under a FR 25 or 100. However, outcomes between FR and VR schedules with fentanyl were less robust compared with cocaine. CONCLUSION: Variability in the time and effort required to obtain illicit drugs could contribute to excessive allocation of behavior toward drug use at the expense of more predictable nondrug alternatives, supporting treatment or policies aimed at making drug access more predictable through agonist medications or a safe supply. The impact of variable requirements on drug choice may be reduced if nondrug reinforcers are relatively less costly, supporting the use of low-cost reinforcers in behavioral therapies like contingency management.

Neural correlates of unstructured motor behaviors.

OBJECTIVE: We studied the relationship between uninstructed, unstructured movements and neural activity in three epilepsy patients with intracranial electroencephalographic (iEEG) recordings. APPROACH: We used a custom system to continuously record high definition video precisely time-aligned to clinical iEEG data. From these video recordings, movement periods were annotated via semi-automatic tracking based on dense optical flow. MAIN RESULTS: We found that neural signal features (8-32 Hz and 76-100 Hz power) previously identified from task-based experiments are also modulated before and during a variety of movement behaviors. These movement behaviors are coarsely labeled by time period and movement side (e.g. 'Idle' and 'Move', 'Right' and 'Left'); movements within a label can include a wide variety of uninstructed behaviors. A rigorous nested cross-validation framework was used to classify both movement onset and lateralization with statistical significance for all subjects. SIGNIFICANCE: We demonstrate an evaluation framework to study neural activity related to natural movements not evoked by a task, annotated over hours of video. This work further establishes the feasibility to study neural correlates of unstructured behavior through continuous recording in the epilepsy monitoring unit. The insights gained from such studies may advance our understanding of how the brain naturally controls movement, which may inform the development of more robust and generalizable brain-computer interfaces.

Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics.

BACKGROUND: Although they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain. METHOD: We present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects' MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors. RESULTS: The simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted. COMPARISON WITH EXISTING METHODS: Previous models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales. CONCLUSIONS: This multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses.

GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth.

Glioblastoma (GBM) is a deadly primary brain malignancy with extensive intratumoral hypoxia. Hypoxic regions of GBM contain stem-like cells and are associated with tumor growth and angiogenesis. The molecular mechanisms that regulate tumor growth in hypoxic conditions are incompletely understood. Here, we use primary human tumor biospecimens and cultures to identify GPR133 (ADGRD1), an orphan member of the adhesion family of G-protein-coupled receptors, as a critical regulator of the response to hypoxia and tumor growth in GBM. GPR133 is selectively expressed in CD133+ GBM stem cells (GSCs) and within the hypoxic areas of PPN in human biospecimens. GPR133 mRNA is transcriptionally upregulated by hypoxia in hypoxia-inducible factor 1α (Hif1α)-dependent manner. Genetic inhibition of GPR133 with short hairpin RNA reduces the prevalence of CD133+ GSCs, tumor cell proliferation and tumorsphere formation in vitro. Forskolin rescues the GPR133 knockdown phenotype, suggesting that GPR133 signaling is mediated by cAMP. Implantation of GBM cells with short hairpin RNA-mediated knockdown of GPR133 in the mouse brain markedly reduces tumor xenograft formation and increases host survival. Analysis of the TCGA data shows that GPR133 expression levels are inversely correlated with patient survival. These findings indicate that GPR133 is an important mediator of the hypoxic response in GBM and has significant protumorigenic functions. We propose that GPR133 represents a novel molecular target in GBM and possibly other malignancies where hypoxia is fundamental to pathogenesis.

Reexamining treatment of high-grade T1 bladder cancer according to depth of lamina propria invasion: a prospective trial of 200 patients.

BACKGROUND: Management of high-grade T1 (HGT1) bladder cancer represents a major challenge. We studied a treatment strategy according to substaging by depth of lamina propria invasion. METHODS: In this prospective observational cohort study, patients received initial transurethral resection (TUR), mitomycin-C, and BCG. Subjects with shallower lamina propria invasion (HGT1a) were followed without further surgery, whereas subjects with HGT1b received a second TUR. Association of clinical and histological features with outcomes (primary: progression; secondary: recurrence and cancer-specific survival) was assessed using Cox regression. RESULTS: Median age was 71 years; 89.5% were males, with 89 (44.5%) cases T1a and 111 (55.5%) T1b. At median follow-up of 71 months, disease progression was observed in 31 (15.5%) and in univariate analysis, substaging, carcinoma in situ, tumour size, and tumour pattern predicted progression. On multivariate analysis only substaging, associated carcinoma in situ, and tumour size remained significant for progression. CONCLUSIONS: In HGT1 bladder cancer, the strategy of performing a second TUR only in T1b cases results in a global low progression rate of 15.5%. Tumours deeply invading the lamina propria (HGT1b) showed a three-fold increase in risk of progression. Substaging should be routinely evaluated, with HGT1b cases being thoroughly evaluated for cystectomy. Inclusion in the TNM system should also be carefully considered.

Development and validation of a portable platform for deploying decision-support algorithms in prehospital settings.

BACKGROUND: Advanced decision-support capabilities for prehospital trauma care may prove effective at improving patient care. Such functionality would be possible if an analysis platform were connected to a transport vital-signs monitor. In practice, there are technical challenges to implementing such a system. Not only must each individual component be reliable, but, in addition, the connectivity between components must be reliable. OBJECTIVE: We describe the development, validation, and deployment of the Automated Processing of Physiologic Registry for Assessment of Injury Severity (APPRAISE) platform, intended to serve as a test bed to help evaluate the performance of decision-support algorithms in a prehospital environment. METHODS: We describe the hardware selected and the software implemented, and the procedures used for laboratory and field testing. RESULTS: The APPRAISE platform met performance goals in both laboratory testing (using a vital-sign data simulator) and initial field testing. After its field testing, the platform has been in use on Boston MedFlight air ambulances since February of 2010. CONCLUSION: These experiences may prove informative to other technology developers and to healthcare stakeholders seeking to invest in connected electronic systems for prehospital as well as in-hospital use. Our experiences illustrate two sets of important questions: are the individual components reliable (e.g., physical integrity, power, core functionality, and end-user interaction) and is the connectivity between components reliable (e.g., communication protocols and the metadata necessary for data interpretation)? While all potential operational issues cannot be fully anticipated and eliminated during development, thoughtful design and phased testing steps can reduce, if not eliminate, technical surprises.

Relationship between surface area and volume of the mastoid air cell system in adult humans.

INTRODUCTION: The geometry of the adult human mastoid air cell system has not previously been described over a large range of mastoid air cell volumes. METHODS: Twenty subjects with a wide range of mastoid air cell pneumatised areas, as determined by X-ray, underwent computed tomography scanning of the middle ear. Mastoid air cell surface areas and volumes were then reconstructed from serial imaging sections, using Image J software. RESULTS: Mastoid air cell volumes varied from 0.7 to 21.4 ml, and were linearly related to the pneumatised area. Right and left mastoid air cell volumes and surface areas were highly correlated. The mastoid air cell surface area was a linear function of volume. CONCLUSION: The relationship between mastoid air cell surface area and volume is similar over a wide range of volumes. Given that the rate of gas exchange across the mastoid air cell mucosa is related to the mastoid air cell surface area, that rate will thus also be a direct linear function of the mastoid air cell volume.

Cortical abnormalities in epilepsy revealed by local EEG synchrony.

Abnormally strong functional linkage between cortical areas has been postulated to play a role in the pathogenesis of partial epilepsy. We explore the possibility that such linkages may be manifest in the interictal EEG apart from epileptiform disturbances or visually evident focal abnormalities. We analyzed samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in nine patients with medically intractable partial epilepsy, measuring interelectrode synchrony using the mean phase coherence algorithm. This analysis revealed areas of elevated local synchrony, or "hypersynchrony" which had persistent spatiotemporal characteristics that were unique to each patient. Measuring local synchrony in a subdural grid results in a map of the cortical surface that provides information not visually apparent on either EEG or structural imaging. We explore the relationship of hypersynchronous areas to the clinical evidence of seizure localization in each case, and speculate that local hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a valuable aid to clinical ICEEG interpretation.

Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus.

Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization.

The nutrient intakes of mothers of low birth weight babies - a comparison of ethnic groups in East London, UK.

The objective of this paper was to compare the nutrient intakes of mothers of different ethnic origins after they had given birth to a low birth weight (LBW) baby (< 2.5 kg). A total of 165 participants from East London, UK completed a prospective 7-day diet diary using household measures, between 8 and 12 weeks post-partum. The data were originally collected as baseline data prior to two separate nutrition intervention studies and were combined and re-interrogated for the purpose of this paper. Folate and iron intakes were low in all ethnic groups compared to the Reference Nutrient Intakes (RNI). Half did not meet the RNI for folate and 88% did not meet the RNI for iron. Nearly a quarter of the group did not achieve the Lower Reference Nutrient Intake (LRNI) for iron. The mean vitamin D and calcium intakes were significantly different between the ethnic groups (P = 0.007, P = 0.001, respectively). African women had the highest vitamin D intakes (4.72 microg d(-1)) and Caucasians and Asians the lowest (2.4 microg d(-1)). Caucasians had the highest calcium intakes (780 mg d(-1)) and Africans the lowest (565 mg d(-1)). Over two-thirds of African, Asian and African-Caribbean women did not meet the RNI for calcium. Thirty-one per cent of Africans did not meet the LRNI for calcium. Our data show a high prevalence of inadequate nutrition among women who deliver LBW babies with differences in nutrient intake between ethnic groups. This information can be used to target specific appropriate dietary advice to ethnic minorities for the prevention or repetition of LBW.

Decrease of sympathetic cardiovascular modulation after temporal lobe epilepsy surgery.

In temporal lobe epilepsy (TLE), there is evidence of ictal and interictal autonomic dysregulation, predominantly with sympathetic overactivity. The effects of TLE surgery on autonomic cardiovascular control and on baroreflex sensitivity (BRS) have not been studied. To evaluate such effects, we monitored heart rate (HR), systolic blood pressure (BP(sys)) and respiration in 18 TLE patients 3-4 months before and after TLE surgery. We used Blackman-Tukey spectral analysis to assess sympathetic and parasympathetic modulation as powers of HR and BP(sys) oscillations in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.5 Hz) bands. BRS was determined as the LF transfer function gain between BP and HR. After surgery, HR, BP(sys), respiration and HF powers remained unchanged, while LF powers of HR (1.57 +/- 1.54 bpm(2)) and BP(sys) (2.19 +/- 1.34 mmHg(2)) and BRS (0.68 +/- 0.31 bpm/mmHg) were smaller than pre-surgical LF powers of HR (3.87 +/- 3.26 bpm(2)) and BP(sys) (4.80 +/- 3.84 mmHg(2)) and BRS (1.12 +/- 0.39 bpm/mmHg; P < 0.05). After TLE surgery, there is a reduction of sympathetic cardiovascular modulation and BRS that might result from decreased influences of interictal epileptogenic discharges on brain areas involved in cardiovascular autonomic control. TLE surgery seems to stabilize the cardiovascular control in epilepsy patients by reducing the risk of sympathetically mediated tachyarrhythmias and excessive bradycardiac counter-regulation, both of which might be relevant for the pathophysiology of sudden unexpected death in epilepsy patients (SUDEP). Thus, TLE surgery might contribute to reducing the risk of SUDEP.

Toxicity and carcinogenicity studies of chlorpromazine hydrochloride and p-cresidine in the p53 heterozygous mouse model.

The carcinogenic potential of chlorpromazine hydrochloride, a psychotropic agent, was assessed in the p53 heterozygous mouse assay. In a 4-week dose range finding study in p53 wild-type mice, doses of 20,40, 60, and 80 mg/kg were poorly tolerated because of mortality secondary to the severe sedative and hypotensive effects of chlorpromazine. Based on 40% mortality at a dose of 20 mg/kg in the dose-range finding study, a high dose of 10 mg/kg was chosen for the 26-week carcinogenicity study in p53 heterozygous mice. Doses of 2.5, 5, and 10 mg/kg chlorpromazine hydrochloride were well tolerated in the 26-week study. The administration of chlorpromazine hydrochloride at dose levels up to and including 10 mg/kg to p53 heterozygous and wild-type mice did not result in a dose-related increase in tumor incidence or in the type of tumors seen in comparison to controls. Findings related to the administration of chlorpromazine in the 26-week study were limited to minimal uterine and ovarian atrophy in p53 wild-type mice dosed with 10 mg/kg chlorpromazine hydrochloride. However, p53 heterozygous mice administered 400 mg/kg p-cresidine, a genotoxic carcinogen commonly used as a positive control for this model, developed urinary bladder tumors. Administration of p-cresidine also resulted in a regenerative anemia, splenic and hepatic hemosiderosis, renal findings, and ovarian and uterine atrophy. This study demonstrated that chlorpromazine hydrochloride, at the doses tolerated, was not carcinogenic in the p53 heterozygous mouse assay.

Late seizure recurrence after multiple subpial transections.

We studied long-term outcome (range, 28-89 months; mean, 56 months) after multiple subpial transections (MSTs) for medically refractory epilepsy. Forty-three (79.6%) of 54 patients had a consistent significant reduction in seizure frequency, and 27 (50%) of the 54 were either entirely seizure free or virtually so. However, 10 (18.6%) patients sustained an increase in seizure frequency several years after surgery, after showing initial postoperative improvement. This suggests that late seizure recurrence is a more important problem in cases in which MST has been performed than for pure resections.

Urinary histamine metabolite elevations during experimental influenza infection.

BACKGROUND: Although histamine is hypothesized to mediate symptoms induced by viral upper respiratory infections, elevations of this mediator have not been observed in nasal lavage fluids recovered from patients with viral upper respiratory infections. OBJECTIVE: The purpose of this study was to use a novel method to determine whether histamine is released during experimental influenza A infection. METHODS: Healthy adults (n = 15) were cloistered and inoculated intranasally with influenza A virus, and monitored for infection and illness. Daily morning void urines were collected and assayed for histamine and its metabolites by gas chromatography-mass spectrometry. Total histamine was calculated for each urine specimen by summing the assayed values of histamine and its metabolites. RESULTS: All subjects were infected and developed illness. ANOVA documented a significant effect of study day (viral infection) on urinary levels of total histamine (P < 0.02). Pairwise analysis showed a significant elevation 2 days after inoculation. CONCLUSIONS: These results provide the first direct evidence that histamine is released in vivo during infection with a virus that causes cold/flu symptoms.

Late seizure recurrence after multiple subpial transections.

We studied long-term outcome (range, 28-89 months; mean, 56 months) after multiple subpial transections (MST) for medically refractory epilepsy. Forty-three (79.6%) of 54 patients had a consistent significant reduction in seizure frequency, and 27 (50%) of the 54 were either entirely seizure free or virtually so. However, 10 (18.5%) patients sustained an increase in seizure frequency several years after surgery, after showing initial postoperative improvement. This suggests that late seizure recurrence is a more important problem in cases in which MST has been performed than for pure resections.

Subfascial implantation of intrathecal baclofen pumps in children: technical note.

OBJECTIVE: Indwelling intrathecal drug delivery systems are becoming increasingly important as a method of neuromodulation within the nervous system. In particular, intrathecal baclofen therapy has shown efficacy and safety in the management of spasticity and dystonia in children. The most common complications leading to explantation of the pumps are skin breakdown and infection at the pump implantation site. The pediatric population poses particular challenges with regard to these complications because appropriate candidates for intrathecal baclofen therapy are often undernourished and thus have a dearth of soft tissue mass to cover a subcutaneously implanted baclofen pump. We report a technique of subfascial implantation that provides greater soft tissue coverage of the pump, thereby reducing the potential for skin breakdown and improving the cosmetic appearance of the implantation site. METHODS: Eighteen consecutively treated children (average age, 8 yr, 7 mo) with spasticity and/or dystonia underwent subfascial implantation of a baclofen pump. These children's mean weight of 42.9 lb is less than the expected weight for a group of children in this age group, ranging from 4 years, 8 months, to 15 years, 7 months. In all patients, the pump was inserted into a pocket surgically constructed between the rectus abdominus and the external oblique muscles and the respective anterior fascial layers. RESULTS: At an average follow-up of 13.7 months, no infection or skin breakdown had occurred at the pump surgical site in any of the 18 patients. CONCLUSION: At this early follow-up, the subfascial implantation technique was associated with a reduced rate of local wound and pump infections and provided optimal cosmetic results as compared with that observed in retrospective cases.

Inter-pregnancy folate and iron status of women in an inner-city population.

The purpose of the present study was to evaluate whether micronutrient supplementation improved the nutritional status of women with poor diets during the inter-pregnancy interval. Fifty-five women who had given birth to a low birth weight baby (<2.5 kg), and who planned to have a further pregnancy, were recruited to a prospective randomised study in East London, UK. Of the fifty-five mothers recruited, forty-four (78 %) met fewer than four of sixteen dietary reference values according to the information provided in a 7 d diet diary, and were categorised as having an 'inadequate' diet. Half of the mothers in the 'inadequate'-diet group were randomly assigned to receive a micronutrient and a single cell oil supplement containing docosahexaenoic acid. All participants received dietary advice based on analysis of their diet diaries, and general lifestyle advice on preparing for pregnancy. Mothers had a blood sample taken at 3 and 9 months post-partum to measure their folate, Fe stores and fatty acid status. Mean serum and erythrocyte folate levels increased significantly between 3 and 9 months post-partum in both the adequate-diet group and the supplemented group. At 9 months post-partum, over half of the unsupplemented, inadequate-diet group remained severely deficient in folate (serum folate <230 nmol/l) and had low serum ferritin levels (<15 microg/l). The high prevalence of inadequate diets in this inner-city population and the low motivation of women to participate in a nutrition programme suggests that consideration should be given to the provision of free folate and Fe supplements to all women in this and similar populations, or at least to women who have delivered a low birth weight baby, who plan further pregnancies.

Effect of intranasal challenge with interleukin-6 on upper airway symptomatology and physiology in allergic and nonallergic patients.

BACKGROUND: Interleukin-6 (IL-6) is a potent regulator of airway inflammation and an important component of biologic homeostasis. Previously, a temporal relationship between the local elaboration of IL-6 and the development of upper airway symptoms and pathophysiologic findings was reported for patients experimentally infected with influenza A virus or rhinovirus. OBJECTIVE: The objective of this study was to determine the provocative effects of direct, intranasal administration of IL-6 on those symptoms, signs, and pathophysiologic findings that accompany viral upper respiratory infection. METHODS: In this double-blind, placebo-controlled, crossover trial, 10 symptomatic allergic, 10 asymptomatic allergic, and 10 nonallergic adult patients were pretreated with intranasal histamine and, after 15 minutes, were challenged with repeated doses of placebo (saline) or with increasing doses (0, 0.01, 0.1, and 1 microg/mL) of recombinant IL-6 at 20-minute intervals, during randomized paired sessions. Symptom scores, sneeze and cough counts, nasal secretion weights, nasal conductance (rhinomanometry), middle ear pressure (tympanometry), Eustachian tube function (sonotubometry), and pulmonary function (spirometry) were evaluated before and after the histamine challenge, after each dose of IL-6 or placebo, and then at 90 minutes and 2, 3, 4, 6, and 24 hours. RESULTS: At the doses used, intranasal challenge with IL-6 was well tolerated. At the 90-minute postchallenge endpoint, a significant effect of challenge substance and group assignment was documented for nasal secretion weight. Paired comparisons showed that the effect was greater for the allergic patients when compared with the nonallergic patients. There were no differences between placebo and IL-6 challenge for any of the other measured parameters. CONCLUSIONS: These results show that local IL-6 at relatively low doses can provoke increased nasal secretions in patients with allergic rhinitis.

Biogenic amines in the human neocortex in patients with neocortical and mesial temporal lobe epilepsy: identification with in situ microvoltammetry.

Biogenic amines in well defined subtypes of human temporal lobe epilepsy (TLE) have not been well characterized. Specimens from five patients with neocortical TLE (NTLE) and nine with mesial TLE (MTLE) were immediately placed in Ringer's lactate; stearate indicator microelectrodes were placed in temporal gray matter, Ag/AgCl reference microelectrodes and auxiliary microelectrodes were placed 3-7 mm contralaterally to the indicator microelectrode. Dopamine (DA), ascorbic acid (AA), norepinephrine (NE) and serotonin (5-HT) were identified by their characteristic oxidative potentials in vitro. Four of five patients with NTLE had NE depletion in temporal neocortex while eight of nine patients with MTLE had high concentrations of NE (chi-square P<0.01). Significant concentrations of DA were present in the temporal lobes of three of five NTLE patients but in only one of the nine MTLE patients (chi-square P<0.05). 5-HT was present in the neocortex of both NTLE and MTLE patients in similar concentrations. AA was found in the neocortex of one NTLE patient. These data support an association between NE depletion and NTLE. The relative NE deficiency along with the consistent presence of DA in NTLE patients suggest an impairment in the catecholamine pathway. The presence of AA, a co-factor in NE synthesis, in the neocortex of one NTLE patient may also be related since AA is a cofactor in NE synthesis.