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Biomedical subjects

G A Ojemann

Publications and source records attributed to G A Ojemann.

At least 19 recordsLinked to original sources

Neurons in human temporal cortex active with verbal associative learning.

In neuronal activity recorded from human middle temporal gyrus during learning of associations between word pairs, a population was identified that had greater activity for associations that were learned rapidly during initial encoding compared to those learned slowly or not at all by an individual subject. This population can be separated from other neurons by the combination of inhibition during word reading when no learning is required and excitation during recent memory for words. These neurons are present in both hemispheres, predominately in deeper layers of cortex. During initial encoding, the increased activity appears at presentation of all word pairs but persists for several seconds only for the rapidly learned pairs, likely reflecting rehersal of items being learned. Human associative learning is related to activity of this specific population of "association" neurons, identified here for the first time.

Adult

Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients.

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.

Adult

Human cerebrocortical potentials evoked by stimulation of the dorsal nerve of the penis.

Cortical evoked potentials resulting from stimulation of the dorsal nerve of the penis (DNP) provide a unique opportunity to document the cortical localization of sexual sensory representation in man. The DNP supplies sensory axons to the major portion of the human phallus, including the penile shaft and glans. Animal and human studies indicate that this nerve plays a crucial role in erection and ejaculation. Direct cortical evoked responses to DNP electrical stimulation were recorded in patients undergoing preoperative evaluation for resection of epileptic foci. These studies provided evidence that the primary sensory cortex contains a large area of cortex devoted to the afferent fibers of the DNP and that the sensory field is in a different location than previously described. The location and distribution of this response indicated the need for revision of the traditional concept of the sensory cortical homunculus.

Adult

High-resolution inter-ictal SPET and phased-array MRI in partial epilepsy: an imaging comparison with video/EEG and outcome correlation.

To assess the clinical utility of high-resolution inter-ictal single photon emission tomography (SPET) of regional cerebral perfusion and high-resolution magnetic resonance imaging (MRI) of the brain with a phased-array temporal lobe coil, 35 patients with presumed partial epilepsy were evaluated prospectively by these techniques in addition to prolonged video/electroencephalographic (EEG) monitoring. Twenty of these patients had surgical treatment of partial epilepsy with outcome determinations spanning from 12 months to 3 years at follow-up. There were four categories of imaging findings as compared to scalp/sphenoidal EEG localization. Category I included 12 patients (34% of total) in whom there was complete imaging and EEG concordance. Category II included 4 patients (11%) in whom MRI and EEG were concordant but SPET was divergent or normal. Category III included 13 patients (37%) in whom SPET and EEG were concordant but MRI was divergent or normal. Category IV included 4 patients (11%) in whom neither SPET nor MRI was concordant with EEG. In this study, the relative sensitivities of SPET and MRI for localization of partial epilepsy based on prolonged scalp/sphenoidal video/EEG recordings were 76% and 49%, respectively. We conclude that these neuroimaging techniques (phased-array MRI and inter-ictal cerebral perfusion SPET) are complementary and useful in the pre-operative evaluation of patients with partial epilepsy.

Adolescent

Is partial epilepsy progressive? Ten-year follow-up of EEG and neuropsychological changes in adults with partial seizures.

PURPOSE: This study was undertaken to determine what changes, if any, occur in the electroencephalogram (EEG) and in neuropsychological test findings of adults with medically intractable complex partial epilepsy over a 10-year period. METHODS: We studied 35 adults, with a mean age of 32 years (range, 16-59 years) at time of initial testing. We compared the distribution of epileptiform patterns documented on the initial pair of waking and sleeping EEGs to those observed on another pair obtained 10 years later. During this same 10-year period, we also examined changes in the Wechsler Adult Intelligence Scale (WAIS) and on the tests from the Neuropsychological Battery for Epilepsy. RESULTS: The EEGs of 28 (80%) of patients at the tenth year were identical to those seen initially. Five (14%) of patients demonstrated EEGs after 10 years with either no discharges or only unilateral discharges, where bilateral discharges were seen a decade earlier. Only two (6%) of patients had EEGs at the tenth year that showed bilateral discharges where only unilateral discharges were seen originally. We found no general change in intelligence or neuropsychological functioning after 10 years, although a few subtle losses were noted on several neuropsychological measures. CONCLUSIONS: For most adults with medically intractable complex partial epilepsy, the EEG and neuropsychological test scores remain reasonably stable over a decade.

Adolescent

Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1-[C-11]glucose and FDG: analysis of the FDG lumped constant.

UNLABELLED: Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2-[18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG relative to glucose from plasma into metabolite pools in the tissue. The proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio of the volumes of distribution of FDG and glucose multiplied by the hexokinase phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc = MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved with tumor. METHODS: We imaged 40 patients with malignant gliomas with 1-[11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated for glioma and contralateral brain regions of interest by an optimization program based on three-compartment, four-rate constant models for the two hexoses. RESULTS: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46 (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus contralateral brain). CONCLUSION: These data strongly suggest that the glioma LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the LC(FDG) of normal brain is higher than previously reported estimates of about 0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism is calculated by the autoradiographic approach with normal brain rate constants and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG) exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of gliomas represent regions where MRGlc, LC(FDG) or their product is higher in glioma than it is in uninvolved brain tissue.

Autoradiography

Reading errors following right hemisphere injection of sodium amobarbital.

The role of the nondominant hemisphere in reading is controversial. We characterized the reading errors made by 64 right-handed adults with complex partial seizures (half with seizure foci on the right and half on the left), after right hemisphere injection of sodium amobarbital. Subjects were presented with 20 six-word sentences and all were found to have speech associated with the left hemisphere only. A variety of reading errors occurred, most of which fell under the syndrome of "neglect dyslexia" including deletions and substitutions of whole words on the left side of a line of text as well as within-word neglect errors. The nature of these errors indicated that they may have been caused by an interaction between a peripheral processing deficit and more centrally located conceptual knowledge of linguistic structure. Other errors could be attributed to a general decrease in attentional mechanisms. Neglect errors at the level of the sentence occurred in the absence of neglect errors at the level of the word although the converse was not true. This suggests that the latter may represent a more severe deficit in the mechanism that causes the former. A double dissociation existed between single word neglect dyslexia errors and "visual" errors, indicating separate processing mechanisms.

Adult

An exploratory comparison of three methods of memory assessment with the intracarotid amobarbital procedure.

This paper has two objectives. The first is to compare three methods of amobarbital memory assessment in 172 adults prior to epilepsy surgery. The three methods are significantly different from one another and there was only a moderate degree of concordance between them; concordance depended upon the method, the side of surgery, and the side of speech. The second objective of the paper is to evaluate the relative abilities of the methods of differentiate, prior to surgery, patients who did and who did not suffer mild to moderate postoperative losses in verbal memory following surgery. To meet this objective a subsample of patients was selected based on the presence or absence of this type of memory loss. Significant differences in the ability of the amobarbital methods to identify the patients at risk for postoperative memory loss were observed, with the method assessing recall memory during drug presence having the best prediction rate.

Adult

Treatment of temporal lobe epilepsy.

Initial management of patients with temporal lobe epilepsy is with antiepileptic drugs, but these control seizures in only half the patients. Patients refractory to drugs should be evaluated for resective surgery. That evaluation requires identification of a focus of onset of seizures, as well as establishing that the focus is in an area of the brain that can be removed with a low risk of new neurologic deficits. Techniques used in that evaluation, including electroencephalography, imaging, recording form intracranial electrodes, use of the intracarotid amobarbitol perfusion test, and the role of specialized studies such as positron emission tomography, are reviewed, along with the correlation of the findings on that evaluation to the control of seizures after surgery. The different surgical techniques for temporal lobe resections are also reviewed, along with the risks of surgery, particularly to recent memory, and the changes in quality of life following surgery.

Anticonvulsants

Outcome following surgery in patients with bitemporal interictal epileptiform patterns.

We reviewed outcome at least 1 year after temporal lobectomy in 44 patients with bitemporal, independent, interictal epileptiform patterns on EEG. All 44 underwent preoperative intracranial monitoring. Twenty-two (50%) were seizure-free, 14 (32%) had at a least 75% reduction in seizures, and eight (18%) had less than a 75% reduction in seizures. We analyzed age of seizure onset, duration of epilepsy, gender, side of operation, history and clinical findings, findings on MRI, results of intracranial EEG-video monitoring, presence or absence of lateralizing neuropsychological deficits, and pathology of resected tissue to identify factors associated with outcome. Three factors emerged as independently associated with a good outcome: concordance of MRI abnormality and side of operation (p = 0.01), history of febrile seizures (p = 0.04), and 100% lateralization of intracranially recorded ictal onsets to the side of operation (p = 0.05). A seizure-free outcome was much more likely to occur if more than one of these factors was present: with at least two factors co-existing, 83% (15/18) of patients were seizure-free, while only 35% (7/20) were seizure-free with a single factor present (p = 0.0009). Of the six patients without any of the three factors, none were seizure-free. We conclude that it is possible to predict reasonably which patients with bitemporal epileptiform abnormalities will have a good outcome after surgery.

Adolescent

Absence of bleeding complications in patients undergoing cortical surgery while receiving valproate treatment.

Valproate (VPA) is associated with a variety of idiosyncratic hematological effects including thrombocytopenia, inhibition of platelet aggregation, and fibrinogen depletion. This has led some investigators to recommend discontinuation of VPA therapy prior to elective surgical procedures. However, administration of VPA therapy is not altered prior to surgery at the authors' center and no VPA-associated bleeding complications have been observed. Therefore, a retrospective chart review was conducted to verify the clinical observations in patients who had undergone cortical resection while receiving antiepileptic drugs (AEDs). Baseline, surgical, and postoperative laboratory data were available for a total of 313 patients, 111 of whom were receiving VPA and 202 of whom were receiving AEDs without VPA (control patients). Eighty-seven percent of the patients receiving VPA were also being treated with at least one other AED. The control group was approximately equally divided between monotherapy (55%) and polytherapy (45%) treatments. Platelet counts were significantly lower in the control polytherapy (284 +/- 74 x 10(9)/L) and both VPA groups (279 +/- 113 x 10(9)/L) as compared with the control monotherapy group (314 +/- 85 x 10(9)/L). Baseline fibrinogen levels were significantly lower in the VPA than in the control groups (223 +/- 91 g/dl vs. 278 +/- 95 g/dl). Both pre- and postoperatively, the VPA group had lower red blood cells counts, hematocrit, and hemoglobin levels. There was no significant difference between groups in estimated blood loss during surgery or qualitative wound discharge postsurgery. There was only one case of a bleeding complication, which occurred 14 days postoperatively in a patient receiving carbamazepine monotherapy. The results of this study confirm the clinical observations of an absence of bleeding complications in patients receiving VPA therapy at the time of surgery, despite differences in laboratory parameters.

Adult

Surgical management and seizure outcome in patients with tuberous sclerosis.

The authors report the results obtained in 11 patients with tuberous sclerosis (TS) who underwent cortical resection surgery for medically intractable epilepsy. Patients' ages at time of surgery ranged from 3 to 46 years (mean 19.6 years). Preoperative epileptiform electroencephalographic abnormalities were focal spike wave discharges in six patients (55%), multifocal in four patients (36%), and generalized in one patient (9%). In the multifocal and generalized groups, all patients (45%) were evaluated by means of subdural grid and strip electrode recordings, whereas electrophysiological localization in the remaining patients was derived from ictal and interictal scalp recordings. The seizure foci were found to be extratemporal in six patients (55%) and temporal in five patients (45%). Surgical intervention consisted of craniotomy and seizure foci resection guided by electrocorticographic monitoring and functional mapping in five awake (45%) and six asleep (55%) patients. Neuropathological examination of the resected seizure foci revealed cortical tubers in eight patients and diffuse gliosis in three patients. Follow up ranged from 8 to 127 months (mean 35 months). Six patients (55%) were seizure free, half of whom were not receiving antiepileptic drugs (AEDs); three patients (27%) had a greater than 70% reduction in seizure frequency, although they required AEDs; one patient (9%) had a 50% temporary reduction in seizure frequency during the initial 6-month postoperative period; and one patient (9%) was lost to follow-up study. From this small but adequately followed patient population with TS, the authors conclude that cortical resection of seizure foci tailored to electrocorticographic findings and functional mapping is encouraging for this difficult to manage patient population with medically intractable epilepsy.

Adolescent

Lack of the DNA repair protein O6-methylguanine-DNA methyltransferase in histologically normal brain adjacent to primary human brain tumors.

Exposure to exogenous alkylating agents, particularly N-nitroso compounds, has been associated with increased incidence of primary human brain tumors, while intrinsic risk factors are currently unknown. The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is a major defense against the carcinogenicity of N-nitroso compounds and other alkylators. We report here that in 55% (64/117) of cases, histologically normal brain tissue adjacent to primary human brain tumors lacked detectable MGMT activity [methyl excision repair-defective (Mer-) status]. The incidence of Mer- status in normal brain tissue from brain tumor patients was age-dependent, increasing from 21% in children 0.25-19 years of age to 75% in adults over 50. In contrast, Mer- status was found in 12% (5/43) of normal brain specimens from patients operated for conditions other than primary brain tumors and was not age-dependent. The 4.6-fold elevation in incidence of Mer- status in brain tumor patients is highly significant (chi2 = 24; p < or = 0.001). MGMT activity was independent of age in the lymphocytes of brain tumor patients and was present in lymphocytes from six of nine tumor patients whose normal brain specimen was Mer-. DNA polymerase beta, apurinic/apyrimidinic endonuclease, and lactate dehydrogenase activities were present in all specimens tested, including Mer- specimens from brain tumor patients. Our data are consistent with a model of carcinogenesis in human brain in which epigenetically regulated lack of MGMT is a predisposing factor and alkylation-related mutagenesis is a driving force.

Adolescent

Neuronal activity in human right lateral temporal cortex related to visuospatial memory and perception.

Neuronal activity was recorded extracellularly from 22 neurons in the right lateral temporal cortex of 12 patients undergoing awake craniotomy for surgical treatment of epilepsy during tests of visuospatial function. These included: measures of short-term visuospatial memory; face, complex figure and line matching; labeling of facial emotional expressions; and a language task, object naming. Six neurons demonstrated significant changes during one or more of the three 1.3-s epochs following test presentation. All 6 of these neurons demonstrated inhibition during short-term visuospatial memory entry, or retrieval, or both. Four of the neurons also showed significant changes during one or more matching tasks; 8 of 10 of these changes were excitatory. One neuron also demonstrated excitation with labeling of facial emotional expression and another with naming. These data demonstrate in human right lateral temporal cortex a pattern of inhibition of neuronal activity during short-term visuospatial memory that contrasts with excitation during other functions, particularly figure matching.

Adult

Unilateral focal preponderance of interictal epileptiform discharges as a predictor of seizure origin.

OBJECTIVE: To test the hypothesis that seizure origin may be predicted from scalp-recorded electroencephalographic interictal epileptiform patterns that occur exclusively or preponderantly over a single focal region. PATIENTS AND METHODS: Fifty-nine of 98 patients (>=16 years old) with intractable epilepsy who underwent sphenoidal/scalp electroencephalographic video monitoring were identified as having interictal epileptiform discharges preponderantly (>=75% of all discharges) or exclusively over a single unilateral region (basal-temporal, midposterior temporal, frontopolar, superior frontal, central). Ictal recordings in 48 patients could be interpreted as demonstrating focal origins, and the ictal findings were compared with the interictal findings. Eleven patients had uninterpretable ictal recordings or no seizures during monitoring and were not further considered. RESULTS: All seizures arose from the expected region in 39 of the 48 patients (Fisher's exact test, P<.001). Interictal discharges occurred exclusively over a single region in 23 of the 48 patients, and all seizures arose from the expected region in 22 of the 23 patients (P<.001). Seventeen patients among this group of 23 had exclusively unilateral basal-temporal discharges, and all seizures arose from the expected side, with the exception of one seizure that arose from the opposite side in one patient, with her other seizure arising from the expected side (P<.001). All seizures arose from the expected region in three patients who exhibited all interictal discharges arising from a single superior frontal region, in two patients with discharges only over a single midposterior temporal region, and in one patient with exclusively unilateral frontopolar discharges. CONCLUSIONS: Interictal discharges that demonstrate a consistent unilateral focal preponderance over a single region, regardless of location, generally predict seizure origin. If the discharges are exclusive to a single region, there is a greater than 95% probability that all recorded seizures will originate from the expected region.

Adolescent

Cerebral lateralization of neuronal activity during naming, reading and line-matching.

Changes in human right or left temporal cortical neuronal activity during language and visuospatial tasks were investigated during craniotomy under local anesthesia for medically intractable epilepsy in patients known to be left dominant for language based on preoperative intracarotid amobarbital perfusion testing. Extracellular recordings were obtained from 57 neuronal populations (26 from the left hemisphere) in the superior and middle temporal gyri of 34 patients. Frequency of activity was compared during over and silent object naming, word reading and line-matching. Although all recordings were from the cortex not essential for language, statistically significant changes in activity during these tasks were identified in 49% of the populations. Most populations showed significant changes to only one of the tasks, indicating discrete neural networks for reading and naming. Nearby neuronal populations recorded by the same microelectrode usually had different behavioral correlates. There were no significant differences in the proportion of neurons changing activity with language or spatial measures between right (non-dominant) or left (dominant) temporal lobes. Left superior and middle temporal gyrus populations, however, demonstrated significant early reductions in activity during overt or silent naming, while right middle temporal gyrus recordings showed significant early increased activity only during overt naming. Although reading measures elicited more activity from the non-dominant temporal lobe, early reductions in activity were recorded exclusively from the dominant side. Visuospatial tasks evoked changes in neuronal frequency predominantly in the middle temporal gyrus, and during one of these tasks, significant later increases in activity were present bilaterally. Our results indicate that the functional lateralization of cognitive behaviors may depend less on the anatomic location of the associated neuronal activity than on the neurophysiologic characteristics of that activity.

Adult