Hyang Woon Lee

Mapping of functional organization in human visual cortex : Electrical cortical stimulation

Objectives: To investigate the pattern of functional organization in the human visual cortex through electrical cortical stimulation. Methods: Electrical cortical stimulation was applied to the occipital cortex and adjacent cortices using subdural grid electrodes in 23 epilepsy patients. Diverse visual responses were recorded. These responses were divided into different categories according to the specific response modalities, such as form, color, and motion. Form visual responses were further subdivided into simple, intermediate, and complex responses. The cortical localization of subdural electrodes was identified using MRI-CT coregistration. The cortical distribution of different visual responses was projected into three-dimensional surface renderings of the brain. The distribution and frequency of subdural electrodes showing different visual responses were quantified by calculating the percentage of the number of electrodes showing one specific type of visual response at the corresponding anatomic region to the total number of electrodes in all brain regions that produced the same response. Results: Simple form responses were obtained mostly at the occipital pole and the inferior occipital gyrus (47.4%) and the striate cortex (42.4%). Intermediate form responses occurred mainly on the peristriate cortex (52.5%) and the lateral occipital (28.0%) and fusiform gyri (19.5%). Complex forms were produced by stimulation of the basal temporo-occipital region (57.6%) and the lateral temporal or lateral temporo-occipital junctional region (42.4%). Color responses occurred on the basal occipital area, mostly at the fusiform (40.0%) and lingual gyri (36.0%). Moving sensations were evoked by stimulation of the basal temporo-occipital (28.4%) and the mesial parieto-occipital or temporo-parieto-occipital junctional regions (23.9%). Conclusions: Different modalities of vision, such as form, color, and moving sensation, appeared to be distributed and organized in different areas of the human visual cortex.

A 6-month longitudinal study of bone mineral density with antiepileptic drug monotherapy.

Antiepileptic drugs (AEDs) can affect bone metabolism, but the exact mechanisms or differences in individual drugs are still unknown. The purpose of this study was to prospectively investigate the alterations in bone mineral density (BMD) and markers of bone metabolism induced by different AEDs in Koreans with epilepsy. Subjects included 33 drug-naïve, newly diagnosed patients with epilepsy aged between 18 and 50. BMD at right calcaneus and various markers for bone metabolism were measured before and after 6months of AED monotherapy including carbamazepine, valproic acid, and lamotrigine. Carbamazepine caused a significant decrease in BMD, which was accompanied by a decrease in the level of vitamin D (25-OHD(3)). BMD and vitamin D were not affected by 6months of valproic acid or lamotrigine therapy. Interestingly, valproic acid and lamotrigine, but not carbamazepine, significantly increased osteocalcin, a marker of bone formation. All AEDs almost doubled the parathyroid hormone level, whereas urinary Pyrilinks, a marker of bone resorption, was not affected by those AEDs. These findings suggest that carbamazepine, a hepatic enzyme-inducing drug, decreases BMD.

Metabolic and Hormonal Disturbances in Women with Epilepsy on Antiepileptic Drug Monotherapy

Summary:  Purpose: Women with epilepsy (WWE) tend to have hormonal and metabolic abnormalities, raising concerns about an increased risk of cardiovascular disorders. This study was performed to determine whether epilepsy itself and/or antiepileptic drug (AED) medication cause metabolic abnormalities.

The effect of topiramate monotherapy on bone mineral density and markers of bone and mineral metabolism in premenopausal women with epilepsy.

Purpose:  To investigate the effect of topiramate on bone mass and metabolism in premenopausal women with epilepsy.

A survey of sleep deprivation patterns and their effects on cognitive functions of residents and interns in Korea

OBJECTIVE To investigate the effects of sleep deprivation on physical health, cognition, and work performance in residents and interns who suffer from chronic sleep deprivation. METHODS Fifty-eight residents and interns were recruited in this study. They completed sleep diary for 2 weeks and questionnaires including health complaints, daytime sleepiness and work performance, and were evaluated with actigraphy. Stroop test, continuous performance test (CPT), trail-making test (TMT) and Korean-California verbal learning test (K-CVLT) were done as neuropsychological evaluations. Subjects were divided into severe sleep deprived (S-SD, average night sleep less than 4 h), mild to moderate deprived (M-SD, 4-6 h), and non-sleep deprived (Non-SD, more than 6 h) groups. RESULTS Forty-one subjects (70.7%) were sleep-deprived. Mean sleep duration was 5.0±1.2 h/night and work duration was 14.9±2.7 h/day. The S-SD group showed higher Epworth Sleepiness Scales than M-SD and Non-SD groups. Severe sleep deprivation was associated with higher level of stress, more frequent attention deficit, and difficulty in learning (P<0.05), but not with decreased neuropsychological test results. CONCLUSION These results suggested that sleep deprivation in residents and interns might affect their health as well as work performance that might influence the quality of patient care, although active compensatory brain mechanisms could be involved to preserve their performance.

Alterations in white matter microstructures and cognitive dysfunctions in benign childhood epilepsy with centrotemporal spikes

Although benign childhood epilepsy with centrotemporal spikes (BECTS) is known to have good prognosis, patients often manifest neuropsychological impairments. This study aimed to investigate cognitive dysfunctions and their relationship with white matter microstructural changes in BECTS patients.

Short-term variations in response distribution to cortical stimulation

Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change occurring at a given location with stimulation would help predict the distribution of responses elsewhere over the cortex to stimulation at that given location. We did this by studying cortical afterdischarges following electrical stimulation of the cortex in awake humans undergoing evaluations for brain surgery. Response occurrence and location could change within seconds, both nearby to and distant from stimulation sites. Responses might occur at a given location during one trial but not the next. They could occur at electrodes adjacent or not adjacent to those directly stimulated or to other electrodes showing afterdischarges. The likelihood of an afterdischarge at an individual site after stimulation was predicted by spontaneous electroencephalographic activity at that specific site just prior to stimulation, but not by overall cortical activity. When stimulation at a site interrupted motor, sensory or language function, afterdischarges were more likely to occur at other sites where stimulation interrupted similar functions. These results show that widespread dynamic changes in cortical responses can occur in intact cortex within short periods of time, and that the distribution of these responses depends on local brain states and functional brain architecture at the time of stimulation. Similar rapid variations may occur during normal intracortical communication and may underlie changes in the cortical organization of function. Possibly these variations, and the occurrence and distribution of responses to cortical stimulation, could be predicted. If so, interventions such as stimulation might be used to alter spread of epileptogenic activity, accelerate learning or enhance cortical reorganization after brain injury.

Impaired consciousness in epilepsy investigated by a prospective responsiveness in epilepsy scale (RES)

Purpose:  Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery.

Cortical excitability during prolonged antiepileptic drug treatment and drug withdrawal

OBJECTIVE Previous reports characterized the effects of administration of single oral doses of antiepileptic drugs (AED) on cortical excitability. However, AED effects on cortical excitability, and their relationship to plasma blood levels, during chronic drug administration at therapeutic doses are not known. The objective of the study was to determine whether plasma blood levels during chronic administration at therapeutic doses would accurately predict changes in corticomotor excitability. METHODS We used transcranial magnetic stimulation (TMS) to measure cortical excitability during 5 weeks administration of carbamazepine (CBZ) and lamotrigine (LTG), and subsequent AED withdrawal in 20 healthy volunteers. Data were analyzed using ANOVA(RM) and regression analysis. RESULTS Resting motor thresholds (r-MT) increased with increasing total and free CBZ and LTG levels during drug administration, but not drug withdrawal. After acute AED withdrawal, r-MT elevation persisted in most individuals with CBZ despite undetectable plasma levels, compared to a rapid normalization with LTG. In contrast, acute drug withdrawal resulted in a transient decrease in r-MT in 3/10 individuals with CBZ and 2/10 with LTG. CONCLUSIONS Plasma levels provide information on motor cortical function during active treatment phases but not during AED withdrawal. SIGNIFICANCE The transient decrease in r-MT associated with acute AED withdrawal could represent a physiological substrate contributing to AED withdrawal seizures.

Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic connectivity

Objective: The purpose of this study was to investigate functional connectivity (FC) changes in epileptogenic networks in intractable partial epilepsy obtained from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel-based network measure of degree that reflects the number of connections to each voxel. Methods: We measured differences between intrahemispheric- and interhemispheric-ICC (ICCintra−inter) that could reveal localized connectivity abnormalities in epileptogenic zones while more global network changes would be eliminated when subtracting these values. The ICCintra−inter map was compared with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in 29 patients with at least 1 year of postsurgical follow-up. Two independent reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates were compared for various clinical factors. Results: Concordance between the icEEG SOZ and ICCintra−inter map was observed in 72.4% (21/29) of the patients, which was higher in patients with good surgical outcome, especially in those patients with temporal lobe epilepsy (TLE) or lateral temporal seizure localization. Concordance was also better in the extratemporal lobe epilepsy than the TLE group. In 85.7% (18/21) of the cases, the ICCintra−inter values were negative in the SOZ, indicating decreased FC within the epileptic hemisphere relative to between hemispheres. Conclusions: Assessing alterations in FC using fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive presurgical diagnostic tool to improve surgical outcome. In addition, the method reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC may be altered, in the presence of both regional as well as global network abnormalities.