Transforming electrocortical mapping data into standardized common space.

Subdural grid electrodes are implanted routinely for the pre-surgical work up of epilepsy. While different approaches are available, many centers, including ours, visualize electrode locations by co-registering pre-operative 3-D MR images with post-implantation 3-D CT images. This method allows the determination of the electrode positions in relation to the individual patient's anatomy, but does not easily allow comparison across patients. The goal of this study was to develop and validate a method for transforming electrode positions derived from 3-D CT images into standardized space. We analyzed data from twelve patients with subdurally implanted electrodes. Volumetric CT and MRI images were co-registered and then normalized into common stereotactic space. Electrode locations were verified statistically by comparing distances between the anterior commissure and a representative sampling of 8 electrode sites per patient. Results confirm the accuracy of our co-registration method for comparing electrode locations across patients.

How accurate are bedside hearing tests?

The accuracy of five bedside hearing tests was evaluated in 107 consecutive adults, using pure-tone audiometry as the standard reference. Bedside tests had poor sensitivity (< or =0.60), relatively good specificity (> or =0.74), and variable positive predictive value (0.24 to 1.0) for detecting hearing loss. Sensitivity improved when bedside tests were combined with case history. The diagnostic utility of bedside tests routinely administered by neurologists to detect hearing loss in adults requires further study.

Transient unilateral hearing loss induced by electrocortical stimulation.

A 32-year-old patient with seizures experienced decreased right-ear hearing during electrocortical stimulation mapping of the left lateral superior temporal gyrus. Audiometric testing under headphones confirmed a reversible, moderate unilateral hearing loss. Under binaural listening conditions, auditory comprehension was impaired at the same site, whereas word repetition, environmental sound recognition, naming, and spontaneous speech remained intact.

Modeling variability in cortical representations of human complex sound perception.

This study investigated methodological (task, stimulus) and intersubject variability in the cortical representation of auditory processing of complex sounds, including speech. Subjects were adult seizure patients undergoing left hemisphere electrocortical mapping (ECM). We tested auditory discrimination of complex sounds, including frequency-modulated tones and speech syllables (digitized, synthesized) contrasted by phonetic features and lexical status. To measure task effects, auditory comprehension was also tested. Within- and across-patient differences in the distribution of deficits induced by ECM were modeled statistically using the recently developed method of Template Mixture Modeling. Cortical representations of auditory discrimination were smaller, more localized, and less variable across subjects than auditory comprehension. Stimulus effects were observed only for speech-tone contrasts. When tasks and stimuli were held constant, two auditory discrimination centers were identified in the posterior temporal lobe. There was also an interaction between task and intersubject effects, with more intersubject variability in cortical maps of auditory comprehension than auditory discrimination. These results demonstrate the utility of using the statistical modeling approach of Template Mixture Modeling to quantify sources of variability in cortical functional organization.

Electrocorticographic gamma activity during word production in spoken and sign language.

OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.

Human "memories" can be evoked by stimulation of the lateral temporal cortex after ipsilateral medial temporal lobe resection.

A patient with medically intractable seizures and mesial temporal sclerosis underwent a left anterior temporal lobectomy and amygdalohippocampectomy. After 4 months, his seizures recurred and a left temporal, subdural grid of electrodes was placed to localise his seizure focus. Stimulation through the grid evoked four distinct "memories", or experiential phenomena, despite absence of the ipsilateral medial temporal lobe. To our knowledge, this is the first documented case of experiential phenomena evoked by cortical stimulation in the absence of the ipsilateral medial temporal lobe.

Induced electrocorticographic gamma activity during auditory perception. Brazier Award-winning article, 2001.

OBJECTIVE: To define the spatial, temporal, and functional characteristics of induced gamma (>30 Hz) activity during functional activation of the left superior temporal gyrus. METHODS: Electrocorticographic (ECoG) recordings were made in 4 clinical subjects during auditory tone and phoneme discrimination tasks, and event-related changes in the ECoG band power were calculated. The topography and temporal sequence of event-related power changes in different gamma bands were contrasted with those of auditory evoked potentials (AEPs), and with those of event-related power changes in the alpha band (8-12 Hz). RESULTS: Auditory stimuli induced a broadband power augmentation that included 40 Hz, as well as higher (80-100 Hz) gamma frequencies. The topography of gamma augmentation was similar, but not identical, to that of the AEP, and was more focused than that of alpha power suppression. Its temporal onset coincided with the N100, but outlasted it. Phonemes produced greater gamma augmentation than tones, while a similar difference was not observed in the N100. CONCLUSIONS: Auditory perception induces ECoG gamma activity not only at 40 Hz, but also in higher gamma frequencies. This activity appears to be an index of cortical activation that reflects task-specific processing in the human auditory cortex more closely than the AEP or alpha power suppression.

Language lateralisation and early right ear deafness: was Wernicke right?

The effects of early right ear deafness on lateralisation of auditory language functions are not fully known. A 36 year old right handed man, with a history of perinatal right ear deafness and undergoing evaluation for surgical treatment of seizures that began at age 10 years was studied. Language lateralisation testing by intracarotid sodium amobarbital injection showed receptive and expressive language functions to be strongly lateralised to the left hemisphere. Results with intracarotid sodium amobarbital injection further suggested that transmission of auditory input to the patient's left hemisphere was partially dependent on ipsilateral left ear pathways. Cortical language mapping through implanted subdural electrodes localised auditory language functions to traditional left posterior perisylvian language areas. These results suggest that early right ear deafness does not impede left hemisphere lateralisation and localisation of auditory language functions. Moreover, transmission of auditory information to the patient's left hemisphere seems to be accomplished, in part, by recruitment of ipsilateral left ear pathways.

Transcortical sensory aphasia: revisited and revised.

Transcortical sensory aphasia (TSA) is characterized by impaired auditory comprehension with intact repetition and fluent speech. We induced TSA transiently by electrical interference during routine cortical function mapping in six adult seizure patients. For each patient, TSA was associated with multiple posterior cortical sites, including the posterior superior and middle temporal gyri, in classical Wernicke's area. A number of TSA sites were immediately adjacent to sites where Wernicke's aphasia was elicited in the same patients. Phonological decoding of speech sounds was assessed by auditory syllable discrimination and found to be intact at all sites where TSA was induced. At a subset of electrode sites where the pattern of language deficits otherwise resembled TSA, naming and word reading remained intact. Language lateralization testing by intracarotid amobarbital injection showed no evidence of independent right hemisphere language. These results suggest that TSA may result from a one-way disruption between left hemisphere phonology and lexical-semantic processing.

Different generators in human temporal-parasylvian cortex account for subdural laser-evoked potentials, auditory-evoked potentials, and event-related potentials.

In order to localize cortical areas mediating pain we now report subdural cortical potentials evoked by auditory stimulation (auditory-evoked potentials - AEPs) and by cutaneous stimulation with a laser (laser-evoked potentials - LEPs). Stimulation with the laser evokes a pure pain sensation by selective activation of nociceptors. LEPs were maximal over the inferior aspect of the central sulcus and had the same polarity on either side of the sylvian fissure. AEPs were maximal posterior to the LEP maximum and had opposite polarity on opposite sides of the sylvian fissure, consistent with the location of a known generator in the temporal operculum. Auditory P3 (event-related) potentials were maximal over the temporal base. These findings demonstrate that the LEP generator is not in secondary somatosensory cortex on the parietal operculum and is different from the P3 generator.

Making sense out of jargon: a neurolinguistic and computational account of jargon aphasia.

OBJECTIVE: To identify the cognitive and neuroanatomic bases of neologistic jargon aphasia with spared comprehension and production of written words. METHODS: Detailed analysis of performance across experiments of naming, reading, writing, repetition, and word/picture matching by a 68-year-old woman (J.B.N.) served to identify which cognitive mechanisms underlying naming and word comprehension were impaired. J.B.N.'s impairments were then simulated by selectively "lesioning" a computer model of word production that has semantic, word form, and subword phonologic levels of representation (described by Dell in 1986). RESULTS: In comprehension experiments, J.B.N. made far more errors with spoken word input than with written word or picture input (chi-square = 40-59; df = 1; p < 0.0001) despite intact auditory discrimination. In naming experiments (with picture, definition, or tactile input), J.B.N. made far more errors in spoken output relative to written output (chi-square = 14-56; df = 1; p < 0.0001). These selective impairments of spoken word processing were simulated by reducing connection strength between word-level and subword-level phonologic units but maintaining full connection strength between word-level and semantic units in Dell's model. The simulation yielded a distribution of error types that was nearly identical to that of J.B.N., and her CT and MRI scans showed a small subarachnoid hemorrhage in the left sylvian fissure without infarct. Cerebral angiogram showed focal vasospasm in sylvian branches of the left middle cerebral artery. CONCLUSION: Focal left perisylvian dysfunction can result in a highly selective "disconnection" between word-level and subword-level phonologic representations manifest as neologistic jargon aphasia with intact understanding and production of written words.

Language recovery after left hemispherectomy in children with late-onset seizures.

We investigated the language capabilities of the isolated right hemisphere in 6 children (age, 7-14 years) after left hemidecorticectomy for treatment of Rasmussen's syndrome. Patients were right-handed before surgery and had at least 5 years of normal language development before the onset of seizures. Language testing included speech sound (phoneme) discrimination, single word and phrasal comprehension, repetition, and naming. Within 4 to 16 days after surgery, patients showed improved phoneme discrimination compared with their performance shortly before surgery. Other language functions remained severely impaired until at least 6 months after surgery. By 1 year after surgery, receptive functions were comparable with, or surpassed, patient presurgery performance. Although word repetition was intact by 1 year after surgery, naming remained impaired, and patient speech was limited largely to production of single words. These results suggest that the right hemisphere is innately capable of supporting multiple aspects of phoneme processing. Recovery of higher level receptive and, to a lesser extent, expressive language functions is attributed to plasticity of the right hemisphere, which appears to persist beyond the proposed critical period for language acquisition and lateralization.

Right hemisphere speech perception revealed by amobarbital injection and electrical interference.

OBJECTIVE: To investigate the right hemispheric speech perception capabilities of an adult right-handed patient with seizures. METHODS: Consecutive, unilateral, intracarotid sodium amobarbital injections and left hemispheric electrical interference mapping were used to determine lateralization and localization of speech perception, measured as syllable discrimination. RESULTS: Syllable discrimination remained intact after left and right intracarotid sodium amobarbital injections. Language otherwise strongly lateralized to the left hemisphere. Despite evidence of bilateral speech perception capabilities, electrical interference testing in the left posterior temporal lobe impaired syllable discrimination. CONCLUSIONS: The results suggest a functionally symmetric, parallel system in the adult brain with preferential use of left hemispheric pathways for speech perception.

Intracellular divalent cation homeostasis and developmental competence in the hamster preimplantation embryo.

The intracellular magnesium and calcium ion concentrations of in vivo-developed 2-cell hamster embryos were measured using ratiometric fluorometry. Intracellular magnesium and calcium ion concentrations were found to be 0.369 +/- 0.011 mM and 129.3 +/- 7.5 nM respectively. Culture of 1-cell hamster embryos for 24 hr to the 2-cell stage in control medium containing 0.5 mM magnesium and 2.0 mM calcium resulted in approximately a threefold increase to 343.5 +/- 8.0 nM in intracellular calcium ion concentration, while magnesium ion levels were not altered (0.355 +/- 0.007 mM). Increasing medium magnesium concentrations to 2.0 mM significantly increased intracellular magnesium ion concentrations of cultured 2-cell embryos with a concomitant reduction in intracellular calcium ion concentrations. Furthermore, increasing the medium magnesium concentration to 2.0 mM significantly increased development of 1-cell embryos collected at either 3 or 9 hr post-egg activation to the morula/blastocyst and blastocyst stages. Resultant blastocysts had an increased total cell number and increased development of the inner cell mass. Most important, however, culture with 2.0 mM magnesium increased the fetal potential of cultured 1-cells twofold. Therefore, because highest rates of development were observed in a medium that resulted in reduced intracellular calcium ion concentrations, it appears that altered calcium homeostasis is associated with impaired developmental competence of 1-cell embryos in culture.

Why would you remove half a brain? The outcome of 58 children after hemispherectomy-the Johns Hopkins experience: 1968 to 1996.

PURPOSE: To report the outcomes of the 58 hemispherectomies performed at Johns Hopkins between 1968 and January 1996. METHODS: Charts were reviewed of the 58 hemispherectomies performed at Johns Hopkins Medical Institutions by the Pediatric Epilepsy Group during the years 1968 to 1996. Twenty-seven operations were done for Rasmussen's syndrome, 24 operations for cortical dysplasias/hemimegalencephalies, and 7 for Sturge-Weber syndrome or other congenital vascular problems. Seizure control alone did not seem to adequately describe the outcomes of the procedure. Therefore, a score was constructed that included seizure frequency, motor disability, and intellectual handicap. This burden of illness score better described the child's handicap before and after surgery. RESULTS: Perioperative death occurred in 4 out of 58 children. Of the 54 surviving children, 54% (29/54) are seizure-free, 24% (13/54) have nonhandicapping seizures, and 23% (12/54) have residual seizures that interfere to some extent with function. Reduction in seizures was related to the etiology of the unilateral epilepsy. Eighty-nine percent of children with Rasmussen's, 67% of those with dysplasias, and 67% of the vascular group are seizure-free, or have occasional, nonhandicapping seizures. All operations were considered by the parents and the physicians to have been successful in decreasing the burden of illness. In 44 the procedure was very successful, in 7 it was moderately successful, and in 3 it was minimally successful. Success was related to the etiology, and early surgery was preferable. CONCLUSION: Hemispherectomy can be a valuable procedure for relieving the burden of seizures, the burden of medication, and the general dysfunction in children with severe or progressive unilateral cortical disease. Early hemispherectomy, although increasing the hemiparesis in children with Rasmussen's syndrome, relieves the burden of constant seizures and allows the child to return to a more normal life. In children with dysplasias, early surgery can allow the resumption of more normal development.

Neuroperceptual differences in consonant and vowel discrimination: as revealed by direct cortical electrical interference.

The effects of direct cortical electrical interference on consonant and vowel discrimination were investigated in five patients with implanted subdural electrode arrays. Without electrical interference, patients performance discriminating consonants and vowels was intact. With electrical interference, consonant discrimination was impaired at one electrode site in each patient on the superior temporal gyrus of the lateral left perisylvian cortex. Conversely, vowel and tone discrimination remained relatively intact when tested with electrical interference at the same site. Analysis of patients' consonant discrimination errors revealed that neither differences in acoustic temporal structure nor syllable position fully account for the consonant-vowel perceptual dissociations elicited. Our data suggest that at the cortical level consonant and vowel perception are intrinsically distinct perceptual phenomena. The selective impairment of consonant, but not vowel, discrimination further suggests that consonant and vowel perception are distinguished by differences in relative dependence on the functional--perhaps integrative--resources of the left lateral superior temporal gyrus.

Responses of gametes to the oviductal environment.

Spermatozoa and oocytes are separately formed in highly specialized biological compartments (testes and epididymis, ovarian follicle), then deposited communally in the oviduct in an environment designed to facilitate their final maturation, promote their union, and nurture the resultant zygotes and early embryos. The mammalian oviduct undergoes hormonally-mediated cyclical modifications that climax during the periovulatory period thus ensuring production of the specialized environment required for the gametes. While the number of potential bioeffectors present in the oviduct is immense, there are four classes of modulators that are of particular note for the 'capacitation' or maturation of both the spermatozoa and the eggs or early embryos: beta-amino acids, bicarbonate ion, progesterone, and oviductins. Only the oviductins are unique to the oviduct, while the other three are present either at higher concentrations than in other tissues or arrive within the oviductal milieu coordinately with the gametes. For spermatozoa, beta-amino acids, bicarbonate ion, and progesterone work interactively to promote motility, capacitation, and the acrosome reaction, while oviductins facilitate capacitation and species-specific zona pellucida recognition and adhesion. For embryonic development, progesterone works indirectly by promoting a permissive oviductal environment, bicarbonate ion is required for cleavage, and beta-amino acids, acting as organic osmolytes, membrane stabilizers, and/or antioxidants, are facilitatory. Oviductins adhere to the zona pellucida of the ovulated egg thereby increasing sperm adhesion and speed of sperm penetration. Oviductins in the perivitelline space or endocytosed by the pre-implantation embryo may regulate differentiation during the morula to blastocyst transition. The roles of these mediators and their mechanisms of action for the gametes and early embryos are reviewed and discussed.

Kinematics of trophectoderm projections and locomotion in the peri-implantation hamster blastocyst.

The behavior of golden hamster blastocysts was studied in vitro by continuous time-lapse videomicrography and computer imaging, during and immediately following escape from the zona pellucida. This study revealed numerous small cytoplasmic trophectoderm projections (TEPs) approximately 18 microns long that penetrated the zona pellucida both radically and tangentially and appeared to be actively involved in zona escape in vitro. After escape from their zonae, some blastocysts moved across the culture dish by an endogenous means of locomotion, most likely involving activity of the small TEPs. Several hours after zona escape, embryos expressed large TEPs up to 46 microns long that moved in an undulating manner and showed rapid cycles of extension and retraction; the timing of their appearance suggested that these TEPs are normally involved in attachment to the uterine epithelium. Embryos fixed in utero, during the developmental interval between zona loss and embryo attachment, exhibited large TEPs similar in morphology to those expressed by cultured blastocysts. These observations document for the first time that mammalian blastocysts are capable of endogenous locomotion, confirm TEPs as components of normal blastocyst activity, reveal that there are two kinds of TEPs that differ temporally and morphologically, and extend earlier reports of TEP activity in guinea-pig embryos to the hamster.