Time-frequency characterization of electrocorticographic recordings of epileptic patients using frequency-entropy similarity: a comparison to other bi-variate measures.

Expert evaluation of electrocorticographic (ECoG) recordings forms the linchpin of seizure onset zone localization in the evaluation of epileptic patients for surgical resection. Numerous methods have been developed to analyze these complex recordings, including uni-variate (characterizing single channels), bi-variate (comparing channel pairs) and multivariate measures. Developing reliable algorithms may be helpful in clinical tasks such as localization of epileptogenic zones and seizure anticipation, as well as enabling better understanding of neuronal function and dynamics. Recently we have developed the frequency-entropy (F-E) similarity measure, and have tested its capability in mapping the epileptogenic zones. The F-E similarity measure compares time-frequency characterizations of two recordings. In this study, we examine the method's principles and utility and compare it to previously described bi-variate correspondence measures such as correlation, coherence, mean phase coherence and spectral comparison methods. Specially designed synthetic signals were used for illuminating theoretical differences between the measures. Intracranial recordings of four epileptic patients were then used for the measures' comparative analysis by creating a mean inter-electrode matrix for each of the correspondence measures and comparing the structure of these matrices during the inter-ictal and ictal periods. We found that the F-E similarity measure is able to discover spectral and temporal features in data which are hidden for the other measures and are important for foci localization.

Inferring spatiotemporal network patterns from intracranial EEG data.

OBJECTIVE: The characterization of spatial network dynamics is desirable for a better understanding of seizure physiology. The goal of this work is to develop a computational method for identifying transient spatial patterns from intracranial electroencephalographic (iEEG) data. METHODS: Starting with bivariate synchrony measures, such as phase correlation, a two-step clustering procedure is used to identify statistically significant spatial network patterns, whose temporal evolution can be inferred. We refer to this as the composite synchrony profile (CSP) method. RESULTS: The CSP method was verified with simulated data and evaluated using ictal and interictal recordings from three patients with intractable epilepsy. Application of the CSP method to these clinical iEEG datasets revealed a set of distinct CSPs with topographies consistent with medial temporal/limbic and superior parietal/medial frontal networks thought to be involved in the seizure generation process. CONCLUSIONS: By combining relatively straightforward multivariate signal processing techniques, such as phase synchrony, with clustering and statistical hypothesis testing, the methods we describe may prove useful for network definition and identification. SIGNIFICANCE: The network patterns we observe using the CSP method cannot be inferred from direct visual inspection of the raw time series data, nor are they apparent in voltage-based topographic map sequences.

Estimation of in vivo human brain-to-skull conductivity ratio from simultaneous extra- and intra-cranial electrical potential recordings.

OBJECTIVE: The present study aims to accurately estimate the in vivo brain-to-skull conductivity ratio by means of cortical imaging technique. Simultaneous extra- and intra-cranial potential recordings induced by subdural current stimulation were analyzed to get the estimation. METHODS: The effective brain-to-skull conductivity ratio was estimated in vivo for 5 epilepsy patients. The estimation was performed using multi-channel simultaneously recorded scalp and cortical electrical potentials during subdural electrical stimulation. The cortical imaging technique was used to compute the inverse cortical potential distribution from the scalp recorded potentials using a 3-shell head volume conductor model. The brain-to-skull conductivity ratio, which leads to the most consistent cortical potential estimates with respect to the direct intra-cranial measurements, is considered to be the effective brain-to-skull conductivity ratio. RESULTS: The present estimation provided consistent results in 5 human subjects studied. The in vivo effective brain-to-skull conductivity ratio ranged from 18 to 34 in the 5 epilepsy patients. CONCLUSIONS: The effective brain-to-skull conductivity ratio can be estimated from simultaneous intra- and extra-cranial potential recordings and the averaged value/standard deviation is 25+/-7. SIGNIFICANCE: The present results provide important experimental data on the brain-to-skull conductivity ratio, which is of significance for accurate brain source localization using piece-wise homogeneous head models.

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.

High-resolution EEG: cortical potential imaging of interictal spikes.

BACKGROUND: It is of clinical importance to localize pathologic brain tissue in epilepsy. Noninvasive localization of cortical areas associated with interictal epileptiform spikes may provide important information to facilitate presurgical planning for intractable epilepsy patients. METHODS: A cortical potential imaging (CPI) technique was used to deconvolve the smeared scalp potentials into the cortical potentials. A 3-spheres inhomogeneous head model was used to approximately represent the head volume conductor. Five pediatric epilepsy patients were studied. The estimated cortical potential distributions of interictal spikes were compared with the subsequent surgical resections of these same patients. RESULTS: The areas of negativity in the reconstructed cortical potentials of interictal spikes in 5 patients were consistent with the areas of surgical resections for these patients. CONCLUSIONS: The CPI technique may become a useful alternative for noninvasive mapping of cortical regions displaying epileptiform activity from scalp electroencephalogram recordings.

Boundary element method-based cortical potential imaging of somatosensory evoked potentials using subjects' magnetic resonance images.

A boundary element method-based cortical potential imaging technique has been developed to directly link the scalp potentials with the cortical potentials with the aid of magnetic resonance images of the subjects. First, computer simulations were conducted to evaluate the new approach in a concentric three-sphere inhomogeneous head model. Second, the corresponding cortical potentials were estimated from the patients' preoperative scalp somatosensory evoked potentials (SEPs) based on the boundary element models constructed from subjects' magnetic resonance images and compared to the postoperative direct cortical potential recordings in the same patients. Simulation results demonstrated that the cortical potentials can be estimated from the scalp potentials using different scalp electrode configurations and are robust against measurement noise. The cortical imaging analysis of the preoperative scalp SEPs recorded from patients using the present approach showed high consistency in spatial pattern with the postoperative direct cortical potential recordings. Quantitative comparison between the estimated and the directly recorded subdural grid potentials resulted in reasonably high correlation coefficients in cases studied. Amplitude difference between the estimated and the recorded potentials was also observed as indexed by the relative error, and the possible underlying reasons are discussed. The present numerical and experimental results validate the boundary element method-based cortical potential imaging approach and demonstrate the feasibility of the new approach in noninvasive high-resolution imaging of brain electric activities from scalp potential measurement and magnetic resonance images.

Reorganization of the hand somatosensory cortex following perinatal unilateral brain injury.

Functional magnetic resonance imaging was used to map the hand somatosensory cortices of nine hemiparetic young adult patients with perinatal unilateral brain injury in the sensorimotor area and five normal subjects. Stimulation of the paretic hand by periodic manual squeezing produced activation in the contralateral hemisphere of three patients and in the ipsilateral hemisphere of three other patients. Paretic hand stimulation produced no activation in either hemisphere of the remaining three patients. Therefore, one-third of the patients demonstrated functional "plasticity" of the brain in the form of inter-hemispheric relocation of the hand somatosensory function. The volume and pattern of activation for both hands was altered for those patients that showed evidence of cortical reorganization to the opposite hemisphere. This differs from the hand motor system, which exhibited inter-hemispheric reorganization in a higher proportion of a related group of hemiparetic subjects.

Electrocorticographic coherence patterns.

The availability of implantable subdural electrode arrays has made systematic studies of electrocorticographic (ECoG) coherence possible. Studies of coherence patterns recorded directly from human cortex are reviewed along with the presentation of original human clinical data, which reveal reliable and characteristic patterns of coherence. A data-driven technique for discriminating between reliable and unreliable coherence and phase values is described and used to reveal the relationship between coherence and cortical anatomy, such as in the region of the central sulcus, where low phase coherence declines and high phase-shifted coherence increases. Analysis of coherence magnitude and phase makes it possible to determine which signals likely arise from the cortical surface, and which arise from the depths of a sulcus. Alterations in coherence patterns caused by tumors or epilepsy are described and may be used to identify normal and pathological functional relationships between distant cortical areas. Some electrophysiologic/pathologic correlations indicate at least two types of epileptic abnormality, implying a sequence in breakdown of epileptic tissue. The relationship between coherence patterns and behavior and cognition is introduced and compared to similar studies of single-unit binding in animals.

Identification of the sensory/motor area and pathologic regions using ECoG coherence.

An electrophysiologic mapping technique which enables identification of the central sulcus and pathologic cortical regions is described. Electrocorticographic recordings of 1 min duration were recorded from 25 patients who were undergoing resection of tumors in the sensory-motor region or being evaluated for temporal lobectomy for epilepsy. Analysis of the patterns of subdural inter-electrode coherence revealed low coherence across the central sulcus for 11/12 cases where its location could be verified with direct cortical stimulation and/or somatosensory evoked potential mapping. Regions of high coherence identified the location of tumors in the sensory-motor region for 10/10 cases. Over the temporal lobe, localized areas of high coherence were evident in 8/9 epilepsy patients, but were not indicative of the location of mesial temporal lobe tumors or inter-ictal spiking, when present. We conclude that analysis of cortical coherence patterns may be helpful for revealing the location of pathologic processes relative to critical cortical areas.

Auditory brain stem response in young and old guinea pigs.

OBJECTIVE: To characterize age-related auditory changes in genetically similar guinea pigs. BACKGROUND: In humans and animals, changes in hearing are known to occur with age. METHODS: Brain stem-evoked responses were measured in genetically similar guinea pigs that ranged 6-36 months in age. Changes in hearing and the input/output function curve were determined. RESULTS: Threshold shift with increase in age was seen. Marked reduction in amplitude of response with increasing age was also demonstrated. No change was seen in latency or interpeak interval. CONCLUSIONS: In genetically similar guinea pigs, age-related changes in threshold occurred. Latency and interpeak intervals remained unchanged. Amplitude of response decreased substantially after 12 months of age to a greater extent than predicted by threshold shifts alone. This phenomenon appears important in understanding the pathophysiology of age-related hearing loss.

Saccular influence on the otolith-spinal reflex and posture during sudden falls of the cat.

HYPOTHESIS: The saccule provides important input for the otolith spinal reflex during sudden falls in the cat. BACKGROUND: Previous studies on cats have identified two distinct components of muscle activity in response to sudden falls: an early otolith-dependent component (OSR) and a later nonlabyrinthine component associated with landing. The presence of an otolith-dependent reflex suggests a discrete role of the otolith organs in the control of posture and locomotion. METHODS: The influence of saccular input on the OSR during sudden falls was studied by simultaneous video and electromyographic (EMG) recordings obtained from saccular-deficient deaf white cats and white cats with normal hearing. RESULTS: A total of 628 sudden falls from five cats (two normal, one unilaterally deaf and two bilaterally deaf) were studied. Normal cats had a total of 337 drops, 276 of which (82%) were acceptable; a unilaterally deaf cat had a total of 79 drops, 56 of which (71%) were acceptable; deaf cats had a total of 212 drops, 177 of which (83%) were acceptable. The earliest of five observed behavioral events was that of forelimb extension which had a mean latency of 98 +/- 32 msec in normal cats and 139 +/- 28 msec in deaf cats (p < 0.0001). The mean latency of early EMG activity in normal cats was 19 +/- 7 msec and in deaf cats was 30 +/- 13 msec (p < 0.0001). The unilaterally deaf cat exhibited behavior and early EMG responses that were similar to those of normal cats. Deaf cats displayed poor body control during landings that improved with experience. CONCLUSIONS: These data demonstrate that the saccule provides important input for the otolith spinal reflex in the cat, and cats that lack both saccules have discernible behavioral and EMG differences in response to sudden falls, when compared with normal cats.

Intra-operative localization of sensorimotor cortex by cortical somatosensory evoked potentials: from analysis of waveforms to dipole source modeling.

Intra-operative localization of sensorimotor cortex is of increasing importance as neurosurgical techniques allow safe and accurate removal of lesions around the central sulcus. Although direct cortical recordings of somatosensory evoked potentials (SEPs) are known to be helpful for cortical localization, source localization models can provide more precise estimates than subjective visual analysis. In addition to intra-operative analysis of waveforms and amplitudes of SEPs to median nerve stimulation in 20 neurosurgical patients, we used a spatiotemporal dipole model to determine the location of the equivalent dipoles consistent with the cortical distribution of the SEPs. The early cortical SEPs were modeled by 2 equivalent dipoles located in the postcentral gyrus. The first dipole was primarily tangentially oriented and explained N20 and P20 peaks. The second dipole was primarily radially oriented and explained P25 activity. We found consistent localization of the first dipole in the postcentral gyrus, which was always located within 8 mm of the central sulcus, with an average distance of 3 mm. This finding provides an objective basis for using the SEP phase reversal method for cortical localization. We conclude that dipole source modeling of the cortical SEPs can be considered as an objective way of localizing the cortical hand sensory area.

Maturation of human visual evoked potentials: 27 weeks conceptional age to 2 years.

Visual evoked potentials to pattern reversal and diffuse flash stimulation were recorded from 520 consecutive pediatric patients and 11 normal infants between the ages of 27 weeks post-conception and 24 months. The latency and peak-to-peak amplitude of the first reproducible positive peak of the binocular pattern visual evoked potential (P100) were measured for five check sizes subtending from 15' to 4 degrees of arc. Three developmental trends were noted: 1) a rapid increase in pattern resolution near term, 2) a subsequent decrease in the latency of P100, and 3) a gradual increase in the amplitude of P100. These three trends reflect the multiplicity of early maturation and are discussed in terms of changes in receptor growth and density, pathway myelination, and cortical synaptivity.

Improved delayed visual reproduction test performance in multiple sclerosis patients receiving interferon beta-1b.

We assessed neuropsychological function longitudinally in 30 MS patients who participated in the pivotal trial of interferon beta-1b (IFN-beta-1b). Nine patients received high-dose IFN-beta-1b (8.0 million units), eight low-dose IFN-beta-1b (1.6 MIU), and 13 placebo. There was significant improvement in Wechsler Memory Scale Visual Reproduction-Delayed Recall scores between years 2 and 4 of the trial in MS subjects receiving high-dose IFN-beta-1b. Motoric performance, MRI lesion area, and depression rating scores did not correlate with this finding. Comparison of MRI at baseline and at years 2 and 4 revealed significant changes over time for the total cohort (p < 0.02). Mean lesion area in the high-dose group did not change over time, whereas the low-dose and placebo groups had increases in total lesion area of 28 and 36%, respectively, at year 4. Expanded disability status scale scores did not change significantly between years 2 and 4 of the trial, nor did they correlate with MRI lesion area at any assessment point. We conclude that high-dose IFN-beta-1b improves delayed visual reproduction test performance in MS patients, a finding unlikely to be explained by practice effects or brain lesion area.

Charles Bonnet syndrome: an early marker for dementia?

OBJECTIVE: To clarify the neuropsychological function in patients with Charles Bonnet Syndrome. DESIGN: Control group comparison study. SETTING: University of Chicago Hospitals. PARTICIPANTS: The neuropsychological function of 15 older adults with presenting complaints of visual hallucinations who met criteria for Charles Bonnet Syndrome (CBS) were compared with 11 demographically matched controls to determine if there was any evidence of functional brain impairment. CBS patients were screened for focal brain lesions and epileptic disturbance via MRI and EEG and also received pattern visual evoked potentials and ophthalmological examinations. MEASUREMENTS: Scores from the Wechsler Adult Intelligence Scale-Revised, Mattis Dementia Rating Scale, Wechsler Memory Scale, and the Auditory Verbal Learning Test were compared. RESULTS: Significant differences were found between the two groups on the neuropsychological measures. Moreover, 14 of 14 subjects had ocular abnormalities and six of eight had abnormal age-corrected pattern visual evoked potentials indicative of dysfunction in the visual system. CONCLUSIONS: The results of the study indicate that patients diagnosed with Charles Bonnet Syndrome evidence neuropsychological changes commonly associated with the early stages of dementia. Therefore, in patients with impaired vision, the appearance of cognitive deficits, albeit subtle, occur with the onset of visual hallucinations. We propose that isolated visual hallucinations in the older adult may be an indication of the early stages of dementia.

Displaying electrocorticographic findings on gyral anatomy.

Human electrocorticographic findings recorded from subdural arrays of electrodes were topographically mapped directly onto magnetic resonance images of gyral anatomy. With this technique gyri involved in generating somatosensory evoked potentials and epileptic phenomena are easily identified. Regions of the cortex which exhibit local spectral changes associated with cognitive tasks can also be visualized. These composite images of structure and function can provide insight regarding the functional organization of human cortex in relation to gyral anatomy and localized pathologic rhythms.

Locating VEP equivalent dipoles in magnetic resonance images.

Pattern-reversal and diffuse flash visual evoked potentials (VEPs) were obtained from 4 normal adults. A spatiotemporal dipole model was used to determine the location of the hypothetical equivalent dipoles consistent with the scalp distribution of the VEPs. Equivalent dipoles representing ERG and VEP activity were placed within 3-D magnetic resonance images of the brain. Most of the localization error appeared to be due to inadequate sampling of the potential field in frontal and occipital areas by the 10-20 system of electrode placement. Locating electrophysiologic dipoles within magnetic resonance images of brain structure allows evaluation of dipole localization techniques.

Functional magnetic resonance studies of the reorganization of the human hand sensorimotor area after unilateral brain injury in the perinatal period.

Functional magnetic resonance imaging was used to map the hand sensorimotor area of hemiparetic adolescents and young adults who had suffered unilateral brain damage in the perinatal period. Unlike normal subjects, who exhibit cortical activation primarily contralateral to voluntary finger movements, the hemiparetic patients' intact hemispheres were equally activated by contralateral and ipsilateral finger movements. Our findings are consistent with previous clinical observations and animal experiments which suggest that the immature brain is able to reorganize in response to focal injury.

Functional mapping of human motor cortical activation with conventional MR imaging at 1.5 T.

A conventional 1.5-T magnetic resonance (MR) imager was used to detect signal intensity changes on T2*-weighted images of human motor and sensory cortices during performance of hand and tongue movements. Narrow receiver bandwidths were used to improve the signal-to-noise ratio. Protocols consisting of baseline, motor task, rest, and second motor task periods were performed by nine volunteers. Two-dimensional cross correlation was applied to correct in-plane translation and rotation of the head during the imaging session before the control images were subtracted from the task images. Measurements obtained during finger movement tasks indicated a 3%-8% increase in signal intensity near the contralateral central sulcus and smaller ipsilateral signal intensity increases. Bilateral signal intensity increases were also observed during tongue movement studies. A retrospective image registration technique was used to map the signal changes onto conventional anatomic images, which were used to create integrated three-dimensional models of brain structure and function. These integrated images showed that the highest signal intensity due to hand movement was near the putative central sulcus.

The spatial location of EEG electrodes: locating the best-fitting sphere relative to cortical anatomy.

The location of the international 10-20 system electrode positions and 14 fiducial landmarks are described in cartesian coordinates (+/- 1.4 mm average accuracy). Six replications were obtained on 3 separate days from 4 normal subjects, who were compared to each other with a best-fit sphere algorithm. Test-retest reliability depended on the electrode position: the parasagittal electrodes were associated with greater measurement errors (maximum 7 mm) than midline locations. Location variability due to head shape was greatest in the temporal region, averaging 5 mm from the mean. For each subject's electrode locations a best-fitting sphere was determined (79-87 mm radius, 6% average error). A surface-fitting algorithm was used to transfer the electrode locations and best-fitting sphere to MR images of the brain and scalp. The center of the best-fitting sphere coincided with the floor of the third ventricle 5 mm anterior to the posterior commissure. The melding of EEG electrode location information with brain anatomy provides an empirical basis for associating hypothetical equivalent dipole locations with their anatomical substrates.