Uri Kramer

Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex

Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40–100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex.

Enhanced Category Tuning Revealed by Intracranial Electroencephalograms in High-Order Human Visual Areas

The functional organization of human sensory cortex was studied by comparing intracranial EEG (iEEG) recordings of local field potentials in neurosurgical patients with functional magnetic resonance imaging (fMRI) obtained in healthy subjects. Using naturalistic movie stimuli, we found a tight correlation between these two measures throughout the human sensory cortex. Importantly, the correlation between the iEEG and fMRI signals was site-specific, exhibiting neuroanatomically specific coupling. In several cortical sites the iEEG activity was confined strictly to one object category. This site selectivity was not limited to faces but included other object categories such as houses and tools. The selectivity of the iEEG signals to images of different object categories was remarkably higher when compared with the selectivity of the corresponding fMRI signals. A plausible interpretation of the fMRI and iEEG results concerns cortical organization in which object categories are organized in a mosaic of narrowly tuned object-selective clusters.

The value of EEG in children with chronic headaches

To establish the usefulness of electroencephalography (EEG) as a diagnostic tool in the evaluation of headaches in children, we retrospectively reviewed the records of all children referred to our outpatient neuropediatric clinic because of recurrent headaches. Of 312 children, 257 (82%) underwent EEG tracings: 143 of the children who had had EEG recordings were diagnosed as migraineurs. In 31 (12%) of the children, the EEG revealed epileptic activity. The highest incidence of epileptic EEG activity was found amongst the children with very brief headaches. In 22 (8.6%) of the children, diffuse or focal slowing was detected. The group with migraine headache had a significantly higher incidence of slowing than the group with other types of headaches. There was no correlation between focal EEG abnormalities and brain radioimaging studies or clinical course. We conclude that despite the high incidence of epileptic abnormalities, the contribution of EEG to diagnosis and treatment in children with chronic headache is minimal, and should not be routinely prescribed in these children.

Clinical Experience With Open-Label Topiramate Use in Infants Younger Than 2 Years of Age

To assess the efficacy, safety, and tolerability of topiramate in infants younger than 24 months of age, we conducted an open-label, multicenter chart review study of infants who received topiramate. Twenty-eight patients were evaluated. All had refractory epilepsy. The mean age of seizure onset was 3.8 months (range 0—10 months). Refractory infantile spasms were the most common epilepsy syndrome. Among infants without infantile spasms, complex partial seizures were the prominent seizure type in eight, followed by simple partial seizures in six. Topiramate was prescribed as add-on therapy in 25 cases and as monotherapy in 3 cases. Seven of the eight infantile spasms cases improved on topiramate therapy, attaining topiramate monotherapy in three infants. Half of the infants with other seizure types responded to topiramate. The average treatment duration among topiramate responders was 11 months. Topiramate was prescribed after a mean of 3.3 antiepilepsy drugs had been used in these infants. In no case was topiramate the first prescribed antiepilepsy drug. Adverse effects occurred only in five patients, leading to topiramate discontinuation in two patients. Topiramate was efficacious and well tolerated in infants younger than 24 months of age with refractory epilepsy. Prospective data are needed to corroborate this observation. (J Child Neurol 2003;18:258—262).

Antagonistic Relationship between Gamma Power and Visual Evoked Potentials Revealed in Human Visual Cortex

Scalp electroencephalography and magnetoencephalography studies have revealed a rapid evoked potential adaptation where one visual stimulus suppresses the event-related potential (ERP) of the second stimulus. Here, we investigated a similar effect revealed in subdural intracranial recordings in humans. Our results show that the suppression of the subdural ERP is not associated with a reduction in the gamma frequency power, considered to reflect the underlying neural activity. Furthermore, the evoked potential suppression (EPS) phenomenon was not reflected in recognition behavior of the patients. Rather, the EPS was tightly linked to the level of gamma activity preceding the event, and this effect was independent of the interstimulus time interval. Analyzing other frequency bands failed to reveal a similar link. Our results thus show a consistent antagonism between subdural ERP and gamma power although both are considered markers for neural activity. We hypothesize that the ERP suppression is due to a desynchronization of neuronal firing resulting from recurrent neural activity in the vicinity of the freshly stimulated neurons and not an attenuation of the overall neural activity.

Spatial and Object-Based Attention Modulates Broadband High-Frequency Responses across the Human Visual Cortical Hierarchy

One of the puzzling aspects in the visual attention literature is the discrepancy between electrophysiological and fMRI findings: whereas fMRI studies reveal strong attentional modulation in the earliest visual areas, single-unit and local field potential studies yielded mixed results. In addition, it is not clear to what extent spatial attention effects extend from early to high-order visual areas. Here we addressed these issues using electrocorticography recordings in epileptic patients. The patients performed a task that allowed simultaneous manipulation of both spatial and object-based attention. They were presented with composite stimuli, consisting of a small object (face or house) superimposed on a large one, and in separate blocks, were instructed to attend one of the objects. We found a consistent increase in broadband high-frequency (30–90 Hz) power, but not in visual evoked potentials, associated with spatial attention starting with V1/V2 and continuing throughout the visual hierarchy. The magnitude of the attentional modulation was correlated with the spatial selectivity of each electrode and its distance from the occipital pole. Interestingly, the latency of the attentional modulation showed a significant decrease along the visual hierarchy. In addition, electrodes placed over high-order visual areas (e.g., fusiform gyrus) showed both effects of spatial and object-based attention. Overall, our results help to reconcile previous observations of discrepancy between fMRI and electrophysiology. They also imply that spatial attention effects can be found both in early and high-order visual cortical areas, in parallel with their stimulus tuning properties.

Clinical characteristics of children referred to a child development center for evaluation of speech, language, and communication disorders

Speech, language, and communication disorders are prominent reasons for referrals to a child development center. From 1984 to 1988, 1,090 preschool children were referred to our child development center, which serves the Tel Aviv metropolitan area. Of all referrals, 432 (41%) were primarily due to speech, language, and communication problems. After exclusion of those with IQ < 50 and those with non-language-related disabilities, 323 children remained. The children were classified into different subtypes of developmental language disorders and autistic spectrum disorders. The main developmental language disorder subtypes were combined expressive-receptive (49%) and expressive (44%). Central processing deficits were less common, occurring in 20 (7%) of the children. Parents of children with developmental language disorders had educational levels similar to those of parents of children referred to the child development center for other causes. However, parents of children with infantile autism had higher educational levels than parents of children with developmental language disorder or parents of children referred for other causes (P < .001). Our results reflect the distribution of language and related problems in an unselected population of preschool children referred to a child development center.

Sensitivity and specificity of seizure-onset zone estimation by ictal magnetoencephalography

Purpose:u2002 Ictal video–electroencephalography (EEG) is commonly used to establish ictal onset‐zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure‐onset zone.

Unprovoked seizures and developmental disabilities: clinical characteristics of children referred to a child development center.

Few data are available on the risk of seizures in young children with developmental problems. A retrospective evaluation of 1,946 children 0-5 years of age referred to the Tel Aviv Child Development Center (CDC) between 1981 and 1990 was performed. The study was undertaken to determine the cumulative risk of unprovoked seizures in children referred to a CDC and to assess the risk factors associated with seizures in these children. The center serves the Tel Aviv area for a variety of developmental disabilities. Cumulative risk of seizures and risk factors were assessed using Kaplan-Meier methodology. Unprovoked seizures occurred in 58 patients (3%), including 10 with a single seizure and 48 with two or more seizures. Risk factors for seizures included cerebral palsy (CP) (relative risk [RR] = 28.7), neonatal seizures (RR = 15.2), mental retardation (MR) (RR = 7.8), febrile seizures (RR = 7.7), autism (RR = 3.2), and prematurity (RR = 2.7). The cumulative risk of seizures by age 5 years in children with MR, CP, and MR plus CP was 8%, 47%, and 68%, respectively, compared with 1% in those without MR or CP. On multivariate analysis, CP, MR, prior febrile seizures, and prematurity were associated with an increased risk of seizures. The risk of experiencing unprovoked seizures by age 5 in children with developmental disabilities is 3%, which is fourfold greater than that of the general population. Much of this increased risk is limited to selected subgroups with major disabilities. However, if neither MR nor CP is present, the 1% risk of developing unprovoked seizures by age 5 in children with other developmental problems is not substantially different from that expected in the general population.

Clinical categorization of 312 children with chronic headache

Three hundred and twelve children referred to an outpatient pediatric neurology clinic, with headache that lasted more than 3 months, were retrospectively reviewed. On average, the age of pain onset was 8.4 years. Migraine was diagnosed in 54% of these children and tension-type headache was found in 22% of those with chronic headache. Most children (85%) had common migraine, while classic and complicated migraine was found in only 8.8% and 5.3%, respectively. Brief headaches, lasting from seconds to a few minutes, were found in 5.1% of the children evaluated. In this subgroup, a high rate of epileptic EEG activity was found. Out of 110 children who had undergone computerized tomography, only one was pathological (posterior arachnoid cyst). Our results indicate that chronic and recurrent headache without accompanying neurological symptoms are usually benign and therefore in most cases neuroimaging is not indicated.