Biomedical subjects

C Kufta

Publications and source records attributed to C Kufta.

At least 19 recordsLinked to original sources

PubMed2004

Visuotopic mapping through a multichannel stimulating implant in primate V1.

We report on our efforts to establish an animal model for the development and testing of a cortical visual prostheses. One-hundred-fifty-two electrodes were implanted in the primary visual cortex of a rhesus monkey. The electrodes were made from iridium with an activated iridium oxide film, which has a large charge capacity for a given surface area, and insulated with parylene-C. One-hundred-fourteen electrodes were functional after implantation. The activity of small (2-3) neuronal clusters was first recorded to map the visually responsive region corresponding to each electrode. The animal was then trained in a memory (delayed) saccade task, first with a visual target, then to a target defined by direct cortical stimulation with coordinates specified by the stimulating electrode's mapped receptive field. The SD of saccade endpoints was approximately 2.5 larger for electrically stimulated versus visual saccades; nevertheless, when trial-to-trial scatter was averaged out, the correlation between saccade end points and receptive field locations was highly significant and approached unity after several months of training. Five electrodes were left unused until the monkey was fully trained; when these were introduced, the receptive field-saccade correlations were high on the first day of use (R = 0.85, P = 0.03 for angle, R = 0.98, P < 0.001 for eccentricity), indicating that the monkey had not learned to perform the task empirically by memorizing reward zones. The results of this experiment suggest the potential for rigorous behavioral testing of cortical visual prostheses in the macaque.

Animals↗

PubMed2000

Postoperative changes in cerebral metabolism in temporal lobe epilepsy.

BACKGROUND: Fludeoxyglucose F 18 positron emission tomography ((18)F-FDG-PET) can detect focal metabolic abnormalities ipsilateral to the seizure focus in 80% of patients with temporal lobe epilepsy (TLE). Regions outside the epileptogenic zone can also be affected. We hypothesized that these remote regions might show altered metabolism, tending to return toward normal values, after surgery. DESIGN: Interictal preoperative and postoperative (18)F-FDG-PET metabolism were compared in patients with refractory TLE. Based on pathological findings, disease was classified in the following 3 groups: mesial temporal sclerosis, mass lesions, and no pathological diagnosis. Quantitative PET data analysis was performed using the region-of-interest template previously described. Global normalization was used to adjust for the effect of antiepileptic medication changes. Data were analyzed by Wilcoxon signed rank test and analysis of variance. SETTING: The Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health. PATIENTS: Twenty-two patients with refractory TLE. RESULTS: Preoperatively, in all groups, cerebral metabolic rate for glucose was decreased ipsilateral to the resection site in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, in all groups, cerebral metabolic rate for glucose increased in ipsilateral inferior frontal area and thalamus. In the mesial temporal sclerosis group, we found a statistically significant increase in the contralateral thalamus. CONCLUSION: Temporal lobe epilepsy is associated with extensive preoperative decreased metabolism in inferior lateral temporal, inferior mesial temporal, and inferior frontal areas and thalamus. Postoperatively, we found increased IF and thalamic metabolism. Seizures may have a reversible effect on brain areas connected with, but remote from, the epileptogenic cortex. Arch Neurol. 2000;57:1447-1452

Adult↗

PubMed1998

Source localization determined by magnetoencephalography and electroencephalography in temporal lobe epilepsy: comparison with electrocorticography: technical case report.

OBJECTIVE AND IMPORTANCE: Source modeling by magnetoencephalography (MEG) and electroencephalography (EEG) may be useful techniques for noninvasive localization of epileptogenic zones for surgery in patients with partial seizures. CLINICAL PRESENTATION: Simultaneous recordings of MEG and EEG, obtained in two patients, were coregistered on each patient's magnetic resonance image for direct comparison of these two methods with intracranial electrocorticography. TECHNIQUE: The average difference between MEG and EEG for localization of the same interictal spikes was approximately 2 cm in one patient and 3.8 cm in the other patient. One patient experienced a complex partial seizure during testing, which permitted comparison between interictal and ictal source localization by both MEG and EEG. The EEG ictal localization differed from the interictal one, whereas the MEG ictal and interictal localizations were more similar. In this patient, the MEG interictal source seemed to localize close to the ictal source, whereas EEG did not. The patients underwent temporal lobectomy after electrocorticography, and the results were compared with the findings of MEG and EEG. Although the results of both techniques agreed with the findings of electrocorticography, in one patient the MEG localization seemed to be more accurate. Both patients experienced good surgical outcomes. CONCLUSION: Both MEG and EEG source localization can add useful and complementary information for epilepsy surgery evaluation. MEG seemed to be more accurate than EEG, especially when comparing interictal versus ictal localization. Further study is needed to evaluate the validity of source localization as useful noninvasive techniques to localize the epileptogenic zone.

Adolescent↗

PubMed1997

Semantic, phonological, and perceptual changes following left and right intracarotid injection (Wada) with a low amytal dosage.

Intracarotid injection of a low dosage of amobarbital (75 mg, 5% solution) was studied in 30 temporal lobectomy candidates while naming achromatic, incongruously, and congruously colored pictorial objects and reading real, nonsense, and embedded words. Semantic errors and phonological alexia followed the left injection, while the right injection induced visuoperceptual errors. When the contralateral hemisphere was anesthetized, the left brain formulated supraordinate categories for words and objects, while the right brain applied concrete labels. The basic language proficiency of patients influenced recovery and outcome; left temporal patients who were interictally anomic performed especially poorly after both injections. Codifying phonological and perceptual changes during the intracarotid amobarbital procedure can improve interpretations about language laterality and organization.

Adult↗

PubMed1997

A direct comparison of PET activation and electrocortical stimulation mapping for language localization.

Mapping eloquent language cortex in presurgical patients typically is accomplished using highly invasive direct cortical stimulation techniques. Functional imaging during language activation using positron emission tomography (PET) is a promising, noninvasive alternative that requires validation. In seven patients undergoing surgical evaluation for intractable epilepsy, we performed both direct cortical stimulation and PET activation mapping of language cortex using identical tasks. MRI, PET, and CT scans were coregistered to directly compare the location of language centers determined by cortical stimulation versus activation PET. We found that cortical regions that showed increased cerebral blood flow during both visual and auditory naming tasks were located in the same regions as subdural electrodes which disrupted language during electrical stimulation. Cortical regions underlying electrodes that did not disrupt language also showed no consistent changes in regional cerebral blood flow during PET activation. Used cautiously, PET activation produces language maps similar to those obtained with direct cortical stimulation, with more complete brain coverage and considerably less invasion.

Adolescent↗

PubMed1995

FDG-PET in children and adolescents with partial seizures: role in epilepsy surgery evaluation.

We used FDG-PET to measure interictal glucose metabolism in 16 children and adolescents (mean age 14.7 years) and complex partial seizures (CPS) (mean seizure onset age 5.0 years). Video-EEG localized the epileptic foci. Glucose metabolism was determined in 14 paired anatomic areas using a standard template. PET hypometabolism was defined as greater than 15% asymmetry. Nine of the 13 (69%) patients with a unilateral EEG focus had regional hypometabolism ipsilateral to the epileptogenic zone. Three subjects had bilateral EEG foci; all had nonfocal PET. MRI (15 patients) concurred with EEG and PET in two, and was normal in seven of nine with focal hypometabolism. One of seven patients with normal PET had a focal MRI abnormality. FDG-PET results are similar to those found in adults, but are present earlier in the natural history of CPS (9.7 vs 22.2 years duration epilepsy) than previously reported. The presence of FDG-PET hypometabolism may be associated with a poor response to drug treatment. PET can identify metabolic abnormalities associated with epileptic foci in children and adolescents and is useful in directing surgical intervention for the control of refractory complex partial epilepsy.

Adolescent↗

PubMed1994

Positron emission tomographic measurement of cerebral blood flow and temporal lobectomy.

We used positron emission tomography (PET) and bolus injection of H2(15O) to measure interictal cerebral blood flow (CBF) in 32 patients who had temporal lobectomy for uncontrolled complex partial seizures. Seizure focus localization was confirmed by ictal video-electroencephalographic (video-EEG) telemetry, and patients who had imaging findings suggesting the presence of a tumor were excluded. PET-CBF studies were interpreted using a standard template by raters blinded to EEG and clinical data, and were not used in surgical planning. After surgery, patients were followed for 32 +/- 18 months. Twenty-six patients were seizure free and 6 had persistent seizures. Mean lateral temporal hypoperfusion was 8 +/- 14% in patients who became seizure free and 9 +/- 6% in patients with persistent seizures. Fourteen patients had at least 15%, and 11 at least 20% hypoperfusion, but were not more likely to be seizure free. Three additional patients had 15 to 20% hypoperfusion in the temporal lobe contralateral to their EEG focus. PET measurement of CBF using bolus H2(15O) should not be used to help select patients for temporal lobectomy.

Brain↗

PubMed1994

Peripheral benzodiazepine receptors and glucose metabolism in human gliomas.

Peripheral benzodiazepine receptors (PBR) are increased in gliomas and augmented glucose metabolism is seen in malignant brain tumors. We investigated the relationship between PBR density (Bmax) and glucose utilization rate (GUR) in 17 patients with cerebral gliomas of different grades. PBR Bmax was assessed by [3H]PK-11195 in vitro binding in surgical specimens and GUR was measured by Positron Emission Tomography with [18F]2-Fluorodeoxyglucose before the surgery. In untreated tumors there was a positive correlation between PBR Bmax and GUR (2r = 0.84). This correlation was not observed in patients who had been treated with radiation and/or chemotherapy prior to surgery (r2 = 0.13). In addition, in untreated patients, the increase in PBR density and GUR appeared to be related to the degree of malignancy.

Adult↗

PubMed1994

Event-related desynchronization and movement-related cortical potentials on the ECoG and EEG.

Event-related desynchronization (ERD) 2.0 sec before and 1.0 sec after movement in the frequency bands of 8-10, 10-12, 12-20 and 20-30 Hz and movement-related cortical potentials (MRCPs) to self-paced movements were studied from subdural recordings over the central region in 3 patients, and from scalp-recorded EEGs in 20 normal volunteers. In direct cortical recordings, the peak ERD response and peak MRCP amplitude to self-paced finger movements were maximal over recording sites in the contralateral hand motor representations. The topography and time of onset of the ERD response to finger and foot movements suggest that the ERD responses in the 8-10 Hz and 10-12 Hz bands are more somatotopically restricted than the responses in the higher frequency bands. The power recovery and subsequent overshoot in the different frequency bands occurred in an orderly fashion with the faster frequencies recovering earlier. The ERD responses on the scalp-recorded EEGs were of lower magnitude and more widely distributed than those occurring on the subdural recordings. Across the population, there was no relation between the magnitude of the ERD response in any of the frequency bands studied and the peak amplitude of the negative slope (pNS') and the frontal peak of the motor potential (fpMP) of the MRCPs. MRCPs and ERD responses originate in similar cortical regions and share some common timing features, but the magnitude and spatial distribution of the two responses appear to be independent of each other, which suggests that the physiological mechanisms governing these two events are different and may represent different aspects of motor cortex activation. Differences in the timing and topographical features of the ERD responses in the various frequency bands also suggest a distinct functional significance for the various spectral components of the electrical activity in the motor cortex.

Adult↗

PubMed1994

Plasticity in the adult human oligodendrocyte lineage.

Preoligodendrocytes have been described in cultures and tissue prints of adult human white matter (Armstrong et al., 1992). To characterize further these precursors of human oligodendrocytes, we have investigated whether they express genes playing a critical role in oligodendrocyte development. In the intact human brain, platelet-derived growth factor receptor alpha (PDGF alpha R) and myelin transcription factor 1 (MyTI) transcripts are expressed in 1-2% of cells of the oligodendrocyte lineage (OL), and clusters of such cells can be found in the periventricular region. Myelin basic protein transcripts containing exon 2 information (exon 2+ MBP), which are characteristic of the premyelinating stage, are detected in 15-20% of OL cells in vivo. When OL cells are separated from human white matter and allowed to regenerate in vitro, a much larger proportion of these cells express developmentally regulated genes, while exon 2- MBP and proteolipid protein (PLP) transcripts characteristic of mature OL cells appear transiently downregulated. Basic fibroblast growth factor (bFGF), even in the presence of PDGF, does not promote DNA synthesis in these cultured OL cells. Yet bFGF induces human oligodendrocytes to regenerate their processes rapidly in vitro and to express O4 antigens as well as exon 2+ MBP, MyTI, and PLP transcripts. While bFGF accelerates early regenerative processes, it also maintains high expression of exon 2+ MBP transcripts in OL cells for up to 2 weeks in vitro. In contrast, high levels of insulin in the absence of bFGF allow accumulation of exon 2- MBP and PLP transcripts in most OL cells at 2-3 weeks in vitro. We propose that the myelinated human brain harbors a small pool of precursors of oligodendrocytes and that growth factor-regulated phenotypic plasticity rather than mitogenic potential accounts for the regeneration of oligodendrocytes in the initial stages of demyelinating diseases such as multiple sclerosis.

Adolescent↗

PubMed1992

Temporal lobectomy for uncontrolled seizures: the role of positron emission tomography.

We evaluated the role of positron emission tomography (PET) with [18F]deoxyglucose (FDG) (FDG-PET) for planning surgery in 53 patients who had temporal lobectomy for uncontrolled seizures at National Institutes of Health from 1981 to 1990. Investigators blinded to PET data used results of telemetered video-electroencephalographic ictal monitoring and other standard criteria to decide whether subdural electrodes (22 patients, i.e., the "invasive" group) should be implanted or surgery performed. PET scans were analyzed using a standard regional template. Mean lateral but not mesial temporal asymmetry was significantly higher in patients who became seizure free (p < 0.03). Patients with > or = 15% hypometabolism were significantly more likely to be seizure free in the entire study population and the invasive subgroup. Visual identification of hypometabolism was less accurate. When a clear temporal ictal surface electroencephalographic focus was present, FDG-PET provided less additional information. FDG-PET may be particularly valuable if the surface electroencephalographic scan is nonlocalizing. In addition to helping to identify the seizure focus, it may allow limitation of invasive electrode placement to those necessary for functional mapping. When PET is used to identify epileptic foci, quantitative measurements of asymmetry should be made.

Brain↗

PubMed1992

Comparison of PET measurements of cerebral blood flow and glucose metabolism for the localization of human epileptic foci.

We compared the relative sensitivity of two interictal PET techniques, bolus injection of [15O] labeled water for estimation of cerebral blood flow (H2(15)O CBF-PET), and 18F 2-deoxyglucose (18FDG-PET) for cerebral glucose metabolism (CMRglc), and T2-weighted magnetic resonance imaging, in 28 patients with medically intractable complex partial seizures undergoing evaluation for surgery. There were statistically significant associations between lateralization by 18FDG-PET, and MRI, but not H2(15)O CBF-PET, and lateralization of the epileptic focus as defined by scalp-sphenoidal ictal EEG. Fifteen patients had surgery or subdural electrodes. 18FDG-PET was more closely associated with a good outcome than H2(15)O CBF-PET, which, in addition, showed hypoperfusion contralateral to the epileptic temporal lobe in several cases. H2(15)O sensitivity may have been reduced by technical factors, but 18FDG-PET appears to be more specific for localization of epileptic zones.

Adult↗

PubMed1991

Attenuation in detection of somatosensory stimuli by transcranial magnetic stimulation.

Effects of magnetic stimulation (MS) of the scalp and direct cortical electrical stimulation on detection of an electrical stimulus to the index finger (S1) were studied in 7 normal volunteers and a patient with epilepsy. Detection of somatosensory stimuli was attenuated when MS was delivered 200 msec before S1, was blocked when MS was delivered simultaneously to and 20 msec after S1, and was fully recovered when MS was delivered 200 msec after S1. This effect showed topographic specificity, being produced by scalp stimulation of restricted scalp positions contralateral to the finger stimulated, was maximal with low intensities of finger stimulation and high intensities of MS (usually over that required for motor threshold), and could also be produced in the absence of motor evoked responses in a peripheral hand muscle. These results show that a focal cortical stimulus can briefly attenuate detection of somatosensory stimuli before, during, and after cortical arrival of a somatosensory afferent volley. Several different mechanisms probably contribute to this phenomenon.

Adult↗

PubMed1991

Infection of brain microglial cells by human immunodeficiency virus type 1 is CD4 dependent.

In the central nervous system of AIDS patients, human immunodeficiency virus (HIV) infects primarily microglia, a cell type of bone marrow origin. Moreover, microglial cells isolated from adult human brain support the replication of macrophage-adapted strains of HIV type 1 (HIV-1) (B.A. Watkins, H.H. Dorn, W.B. Kelly, R.C. Armstrong, B. Potts, F. Michaels, C.V. Kufta, and M. Dubois-Dalcq, Science 249:549-553, 1990). To determine whether the CD4 receptor, which is expressed in brain, mediates the entry of HIV-1 in microglial cells, we analyzed CD4 transcript expression in cultured microglia using highly sensitive polymerase chain reaction detection of cDNAs synthesized from RNA. With this method, CD4 transcripts could be detected in cultured microglia--as well as in various human brain regions and cultured macrophages used as positive controls--along with transcripts for the LDL and Fc receptors which are characteristic of cells of the macrophage lineage. We then attempted to block viral entry into microglial cells using anti-CD4 antibodies or soluble CD4 (sCD4), which recognize binding sites on CD4 and HIV-1 glycoprotein gp120, respectively. Cultures were pretreated with blocking antibodies (Leu-3a, OKT4A) or virus was preincubated with sCD4 prior to infection with HIV-1 strain AD87(M) or BaL. With either viral strain, these treatments resulted in the prevention of infection or significant and dose-dependent reduction in the number of infected cells and in the levels of reverse transcriptase or p24 antigen released in the medium. Thus, brain-derived microglial cells, which are the primary target of HIV-1 infection in the brain, express the CD4 receptor and this receptor is effectively used for viral entry in vitro.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Localization of implanted dipoles by magnetoencephalography.

We attempted to validate the location of sources predicted by magnetoencephalography (MEG) by studying 19 specially designed dipole electrodes implanted in six patients with intractable partial seizures who were undergoing subdural electrode recording. We used a seven-channel magnetometer to measure the magnetic fields produced by passing through the dipoles a 40-microA, 5-msec square-wave pulse followed 40 msec later by a pulse of opposite polarity; 200 pulses were averaged for each magnetometer position. The actual dipole locations were measured from skull radiographs, and we based MEG localization on a spherical head model with the inclusion of volume currents. MEG estimates of the sources were within several centimeters (mean, 1.69 cm) of the measured locations. We conclude that MEG localization was promising.

Electrodes, Implanted↗

PubMed1990

An improved method for localizing electric brain dipoles.

Methods for localizing electrical dipolar sources in the brain differ from one another by the models they use to represent the head, the specific formulas used in the calculation of the scalp potentials, the way that the reference electrode is treated, and by the algorithm employed to find the least-squares fit between the measured and calculated EEG potentials. The model presented here is based on some of the most advanced features found in other models, and on some improvements. The head is represented by a three-layer spherical model. The potential on any point on the scalp due to any source is found by a closed formula, which is not based on matrix rotations. The formulas will accept any surface electrode as the reference electrode. The least-squares procedure is based on optimal dipoles, reducing the number of unknowns in the iterations from six to three. The new method was evaluated by localizing five implanted dipolar sources in human sensorimotor cortex. The distances between the locations of the sources as calculated by the method, and the actual locations were between 0.4 and 2.0 cm. The sensitivity of the method to uncertainties encountered whenever a real head has to be modeled by a three-layer model has also been assessed.

Adult↗

PubMed1990

Pathology of temporal lobe foci: correlation with CT, MRI, and PET.

Twenty-six patients with medically refractory complex partial seizures had temporal lobectomy after evaluation, which included prolonged scalp EEG recordings, positron emission tomography (PET), MRI, and x-ray CT. PET showed a region of focal interictal temporal hypometabolism corresponding to electrographic localization of seizure onset in 21. Five patients had a region of increased MRI signal intensity on the spin echo image in the region of the EEG focus, 2 had an abnormality ipsilateral to but distinct from the EEG focus, and 1 had bilateral findings. CT was abnormal in 3 cases; 2 had tumors. Three patients had low grade tumors (1 with a normal PET). PET can detect metabolic dysfunction associated with mild pathologic changes in epileptic foci, but increased signal intensity on MRI does not necessarily correlate with the degree of pathologic abnormality. Tumors may be less likely when both CT and MRI are normal.

Adolescent↗

PubMed1985

Prediction of survival in glioma patients by means of positron emission tomography.

The aim of this study was to determine whether positron emission tomography (PET) with fluorine-18 (18F)-2-deoxyglucose (FDG) can be used as a prognostic test in patients with high-grade cerebral gliomas, regardless of the treatment given. Forty-five patients with astrocytoma Grade III or IV were included in this analysis. The mean survival time of patients with tumors exhibiting high glucose utilization as determined by PET-FDG was 5 months, whereas patients with gliomas showing lower glucose utilization had a mean survival period of 19 months. It is postulated that PET-FDG scans reflect the biological behavior of high-grade astrocytomas and may be used to predict the survival time of patients harboring such neoplasms.

Adolescent↗