Passive functional mapping of receptive language areas using electrocorticographic signals.

OBJECTIVE: To validate the use of passive functional mapping using electrocorticographic (ECoG) broadband gamma signals for identifying receptive language cortex. METHODS: We mapped language function in 23 patients using ECoG and using electrical cortical stimulation (ECS) in a subset of 15 subjects. RESULTS: The qualitative comparison between cortical sites identified by ECoG and ECS show a high concordance. A quantitative comparison indicates a high level of sensitivity (95%) and a lower level of specificity (59%). Detailed analysis reveals that 82% of all cortical sites identified by ECoG were within one contact of a site identified by ECS. CONCLUSIONS: These results show that passive functional mapping reliably localizes receptive language areas, and that there is a substantial concordance between the ECoG- and ECS-based methods. They also point to a more refined understanding of the differences between ECoG- and ECS-based mappings. This refined understanding helps to clarify the instances in which the two methods disagree and can explain why neurosurgical practice has established the concept of a "safety margin." SIGNIFICANCE: Passive functional mapping using ECoG signals provides a fast, robust, and reliable method for identifying receptive language areas without many of the risks and limitations associated with ECS.

Real-time detection and discrimination of visual perception using electrocorticographic signals.

OBJECTIVE: Several neuroimaging studies have demonstrated that the ventral temporal cortex contains specialized regions that process visual stimuli. This study investigated the spatial and temporal dynamics of electrocorticographic (ECoG) responses to different types and colors of visual stimulation that were presented to four human participants, and demonstrated a real-time decoder that detects and discriminates responses to untrained natural images. APPROACH: ECoG signals from the participants were recorded while they were shown colored and greyscale versions of seven types of visual stimuli (images of faces, objects, bodies, line drawings, digits, and kanji and hiragana characters), resulting in 14 classes for discrimination (experiment I). Additionally, a real-time system asynchronously classified ECoG responses to faces, kanji and black screens presented via a monitor (experiment II), or to natural scenes (i.e. the face of an experimenter, natural images of faces and kanji, and a mirror) (experiment III). Outcome measures in all experiments included the discrimination performance across types based on broadband γ activity. MAIN RESULTS: Experiment I demonstrated an offline classification accuracy of 72.9% when discriminating among the seven types (without color separation). Further discrimination of grey versus colored images reached an accuracy of 67.1%. Discriminating all colors and types (14 classes) yielded an accuracy of 52.1%. In experiment II and III, the real-time decoder correctly detected 73.7% responses to face, kanji and black computer stimuli and 74.8% responses to presented natural scenes. SIGNIFICANCE: Seven different types and their color information (either grey or color) could be detected and discriminated using broadband γ activity. Discrimination performance maximized for combined spatial-temporal information. The discrimination of stimulus color information provided the first ECoG-based evidence for color-related population-level cortical broadband γ responses in humans. Stimulus categories can be detected by their ECoG responses in real time within 500 ms with respect to stimulus onset.

A method to establish the spatiotemporal evolution of task-related cortical activity from electrocorticographic signals in single trials.

BACKGROUND: Progress in neuroscience depends substantially on the ability to establish the detailed spatial and temporal sequence of neuronal population-level activity across large areas of the brain. Because there is substantial inter-trial variability in neuronal activity, traditional techniques that rely on signal averaging obscure where and when neuronal activity occurs. Thus, up to the present, it has been difficult to examine the detailed progression of neuronal activity across large areas of the brain. NEW METHOD: Here we describe a method for establishing the spatiotemporal evolution of neuronal population-level activity across large brain regions by determining exactly where and when neural activity occurs during a behavioral task in individual trials. We validate the efficacy of the method, examine the effects of its parameterization, and demonstrate its utility by highlighting two sets of results that could not readily be achieved with traditional methods. RESULTS: Our results reveal the precise spatiotemporal evolution of neuronal population activity that unfolds during a sensorimotor task in individual trials, and establishes the relationship between neuronal oscillations and the onset of this activity. CONCLUSIONS: The ability to identify the spatiotemporal evolution of neuronal population activity onsets in single trials gives investigators a powerful new tool with which to study large-scale cortical processes.

Alpha power indexes task-related networks on large and small scales: A multimodal ECoG study in humans and a non-human primate.

Performing different tasks, such as generating motor movements or processing sensory input, requires the recruitment of specific networks of neuronal populations. Previous studies suggested that power variations in the alpha band (8-12Hz) may implement such recruitment of task-specific populations by increasing cortical excitability in task-related areas while inhibiting population-level cortical activity in task-unrelated areas (Klimesch et al., 2007; Jensen and Mazaheri, 2010). However, the precise temporal and spatial relationships between the modulatory function implemented by alpha oscillations and population-level cortical activity remained undefined. Furthermore, while several studies suggested that alpha power indexes task-related populations across large and spatially separated cortical areas, it was largely unclear whether alpha power also differentially indexes smaller networks of task-related neuronal populations. Here we addressed these questions by investigating the temporal and spatial relationships of electrocorticographic (ECoG) power modulations in the alpha band and in the broadband gamma range (70-170Hz, indexing population-level activity) during auditory and motor tasks in five human subjects and one macaque monkey. In line with previous research, our results confirm that broadband gamma power accurately tracks task-related behavior and that alpha power decreases in task-related areas. More importantly, they demonstrate that alpha power suppression lags population-level activity in auditory areas during the auditory task, but precedes it in motor areas during the motor task. This suppression of alpha power in task-related areas was accompanied by an increase in areas not related to the task. In addition, we show for the first time that these differential modulations of alpha power could be observed not only across widely distributed systems (e.g., motor vs. auditory system), but also within the auditory system. Specifically, alpha power was suppressed in the locations within the auditory system that most robustly responded to particular sound stimuli. Altogether, our results provide experimental evidence for a mechanism that preferentially recruits task-related neuronal populations by increasing cortical excitability in task-related cortical areas and decreasing cortical excitability in task-unrelated areas. This mechanism is implemented by variations in alpha power and is common to humans and the non-human primate under study. These results contribute to an increasingly refined understanding of the mechanisms underlying the selection of the specific neuronal populations required for task execution.

Oscillatory phase modulates the timing of neuronal activations and resulting behavior.

Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior.

recoveriX: a new BCI-based technology for persons with stroke.

Brain-computer interface (BCI) systems have been used primarily to provide communication for persons with severe movement disabilities. This paper presents a new system that extends BCI technology to a new patient group: persons diagnosed with stroke. This system, called recoveriX, is designed to detect changes in motor imagery in real-time to help monitor compliance and provide closed-loop feedback during therapy. We describe recoveriX and present initial results from one patient.

The effects of spatial filtering and artifacts on electrocorticographic signals.

OBJECTIVE: Electrocorticographic (ECoG) signals contain noise that is common to all channels and noise that is specific to individual channels. Most published ECoG studies use common average reference (CAR) spatial filters to remove common noise, but CAR filters may introduce channel-specific noise into other channels. To address this concern, scientists often remove artifactual channels prior to data analysis. However, removing these channels depends on expert-based labeling and may also discard useful data. Thus, the effects of spatial filtering and artifacts on ECoG signals have been largely unknown. This study aims to quantify these effects and thereby address this gap in knowledge. APPROACH: In this study, we address these issues by exploring the effects of application of two types of unsupervised spatial filters and three methods of detecting signal artifacts using a large ECoG data set (20 subjects, four task conditions in each subject). MAIN RESULTS: Our results confirm that spatial filtering improves performance, i.e., it reduces ECoG signal variance that is not related to the task. They also show that removing artifactual channels automatically (using quantitatively defined rejection criteria) or manually (using expert opinion) does not increase the total amount of task-related information, but does avoid potential contamination from one or more noisy channels. Finally, applying a novel 'median average reference' filter does not require the elimination of artifactual channels prior to spatial filtering and still mitigates the influence of channels with channel-specific noise. Thus, it allows the investigator to retain more potentially useful task-related data. SIGNIFICANCE: In summary, our results show that appropriately designed spatial filters that account for both common noise and channel-specific noise greatly improve the quality of ECoG signal analyses, and that artifacts in only a single channel can result in profound and undesired effects on all other channels.

Identifying the Attended Speaker Using Electrocorticographic (ECoG) Signals.

People affected by severe neuro-degenerative diseases (e.g., late-stage amyotrophic lateral sclerosis (ALS) or locked-in syndrome) eventually lose all muscular control. Thus, they cannot use traditional assistive communication devices that depend on muscle control, or brain-computer interfaces (BCIs) that depend on the ability to control gaze. While auditory and tactile BCIs can provide communication to such individuals, their use typically entails an artificial mapping between the stimulus and the communication intent. This makes these BCIs difficult to learn and use. In this study, we investigated the use of selective auditory attention to natural speech as an avenue for BCI communication. In this approach, the user communicates by directing his/her attention to one of two simultaneously presented speakers. We used electrocorticographic (ECoG) signals in the gamma band (70-170 Hz) to infer the identity of attended speaker, thereby removing the need to learn such an artificial mapping. Our results from twelve human subjects show that a single cortical location over superior temporal gyrus or pre-motor cortex is typically sufficient to identify the attended speaker within 10 s and with 77% accuracy (50% accuracy due to chance). These results lay the groundwork for future studies that may determine the real-time performance of BCIs based on selective auditory attention to speech.

The spleen and splenectomy.

After 1940, the number of splenectomies performed in the United States and elsewhere increased rapidly. Splenectomy for Banti's disease and malaria decreased gradually into disrepute. Removal of the spleen for idiopathic thrombocytopenic purpura, congenital spherocytic anemia and acquired hemolytic anemia became accepted practice. However, debate still continues regarding the proper indications for splenectomy in Gaucher's disease, Felty's syndrome and leukemia.

Iatrogenic splenic injury.

In a previous report from this institution, 21% of splenectomies performed between 1957 and 1967 were for iatrogenic injury to the spleen. In the present study, encompassing the years 1971 to 1987, the frequency of iatrogenic splenic injury was reduced to 9% (134 of 1,557 splenectomies). However, there has been no evidence of a progressive decrease in accidental splenic injury from 1971 to 1987. Although the number of injuries related to operations on the stomach or repair of hiatus hernia have declined somewhat in the past decade, the incidence of splenic injuries secondary to colectomy and nephrectomy has not changed appreciably, and injuries linked to complex operations on the aorta and its branches (19 cases) have increased. No evidence could be found that morbidity was increased if the splenic injury is promptly recognized and managed by splenectomy. However, 13 of these 134 patients required reoperation for control of continued bleeding from unrecognized iatrogenic splenic trauma. Constant awareness of the continued prevalence of this operative complication and the mechanisms by which it is produced should enable surgeons to lessen its frequency and potential sequelae.

Lymphoscintigraphy in melanoma: initial evaluation of a low protein dose monoclonal antibody cocktail.

A low protein dose (73 +/- 10 micrograms total) 131I-labeled monoclonal antibody cocktail made of equal microgram quantities of 225.28S (IgG2a) and 763.24T (IgG1) murine monoclonal antibodies, which bind additively to a high molecular weight antigen of melanoma, was evaluated as a lymphoscintigraphic agent in 17 patients with intermediate to thick (mean Breslow depth, 3.39 +/- 0.64 mm) melanomas or clinical Stage II disease scheduled for nodal dissection. Eleven of the patients were clinically Stage I while 6 were clinically Stage II. 131I antibody cocktail, 258 +/- 10 microCi, was administered s.c. at the site of the primary melanoma or its scar following surgical removal. In eight patients, 63 +/- 8 microCi of 125I nonspecific normal sheep IgG was coadministered s.c. Gamma camera imaging was conducted beginning immediately after and continuing for several days following injection. Surgical resection, weighing, and gamma counting of the draining lymph nodes were undertaken in all patients. On gamma scans, early nodal uptake of antibody was most pronounced and of longest duration in the tumor pathologically positive patients (5 of 7 had visible nodal uptake, 4 of 7 visually stable or rising with time), with the t 1/2 of nodal clearance by gamma scan significantly (P less than 0.05) longer than in the negative patients in whom 4 of 10 showed some, although generally transient (0 of 10 stable or rising), nodal uptake. Scans were not easily interpretable when the injection site was very near the draining nodal group, in part due to the detection of scatter activity from the injection site. In several instances the scan was correct and the clinical examination was incorrect as regards nodal disease. Quantitative analysis of the surgically excised draining nodes showed significantly (P less than 0.001) more 131I anti-melanoma antibody uptake in the 21 tumor-involved nodes [0.01217% injected dose (ID)/node median] than in the 512 tumor-negative nodes (0.00051% ID/node median). Median percentage ID/g of anti-melanoma antibody in tumor-involved nodes was significantly greater (P less than 0.01) than in tumor-negative nodes (0.01984 versus 0.003215% ID/g). 125I-labeled nonspecific antibody did not accumulate significantly more in the tumor-involved nodes on a per node or per g basis in the 283 of 533 nodes studied using the dual-label approach (0.0036 versus 0.00092% ID/g). These data demonstrate that by external imaging and by tissue counting that a radiolabeled anti-melanoma monoclonal antibody cocktail can specifically accumulate to melanoma-involved lymph nodes following s.c. administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Splenectomy for massive splenomegaly.

Several groups of authors have recently reported that removal of the massively enlarged spleen (1,500 grams or greater) is associated with a greater morbidity than that encountered in patients with spleens of smaller sizes. In our experience, 46 of 51 patients with massively enlarged spleens had a myeloproliferative disorder (leukemia, lymphoma or agnogenic myeloid metaplasia) and usually had a limited life expectancy. When morbidity in these patients was compared with that in patients with the same diagnosis but spleens of smaller size, no increase in complications or death was found other than a greater operative blood loss in patients with non-Hodgkin's lymphoma. Limitation of operative morbidity in patients with very large spleens depends on careful selection and appropriate operative and perioperative management.

Some factors affecting phencyclidine biotransformation by human liver and placenta.

Samples of human liver and placenta microsomes were analyzed for their in vitro hydroxylation capabilities using phencyclidine, [PCP, 1-(1-phenylcyclohexyl)piperidine] as substrate. Microsomes were prepared from full-term placentas (cesarean deliveries under epidural anesthesia) and from histologically normal liver specimens (staging laparotomies for Hodgkin's disease). Three different hydroxylated PCP metabolites were assayed including 1-(1-phenyl-3-hydroxycyclohexyl)piperidine (3-OH-cyclo-PCP), 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (3-OH-cyclo-PCP), 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (4-OH-cyclo-PCP), and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (4-OH-pip-PCP). The mean amounts of in vitro microsomal hydroxylation of PCP at the three different positions of the PCP ring varied considerably between individual samples of both liver and placenta. The placenta hydroxylated PCP but not as effectively as liver. Evidence for independent hydroxylation of PCP to 3-OH-cyclo-PCP was comparable to 4-OH-cyclo-PCP and 4-OH-pip-PCP. The formation of 3-OH-cyclo-PCP by the liver was enhanced in tobacco smokers. The formation of 4-OH-cyclo-PCP by the liver was negatively correlated with the stage of Hodgkin's disease even though the liver was free of disease in 11 of 12 subjects.

Splenectomy for cytopenias associated with systemic lupus erythematosus.

Splenectomy was performed in 20 patients with refractory cytopenias associated with systemic lupus erythematosus. An immediate and sustained increase in platelet count (greater than 150,000 cells/mm3) was achieved in 12 of 18 patients whose principal indication for operation was thrombocytopenia. Of seven patients with hemolytic anemia, which was linked with thrombocytopenia in five, six had an increase in the hematocrit value of 20 percent or more after operation. The white blood count increased to normal values in three leukopenic patients. We believe that although removal of the spleen is not uniformly successful in correcting cytopenias in patients with systemic lupus erythematosus, splenectomy should be considered in patients refractory to other modalities of treatment.

Splenectomy for thrombocytopenia due to secondary hypersplenism.

The response to splenectomy of patients with thrombocytopenia due to secondary hypersplenism is frequently unpredictable. Our experience indicated that splenectomy is seldom justified for this indication in patients with chronic myelogenous or chronic granulocytic leukemia. Since patients with chronic lymphocytic leukemia, hairy-cell leukemia, and stage IV lymphoma may have a more prolonged life expectancy, removal of the spleen brings about a satisfactory response of thrombocytopenia in some instances. Elevation of platelet counts after splenectomy in patients with agnogenic myeloid metaplasia is most likely to occur in women with the primary form of the disease. In other nonmalignant conditions, splenectomy has resulted in a satisfactory response in the majority of patients.

Splenectomy for idiopathic thrombocytopenic purpura.

Over a period of 20 years, splenectomy has been performed upon 216 patients with idiopathic thrombocytopenic purpura. Splenectomy resulted in an immediate and sustained platelet response in 72 per cent of these patients. An additional 7.4 per cent of the patients had a sustained platelet count of 150,000 per cubic millimeter develop while off all drug therapy within the first postoperative year. Of the remaining patients who failed to meet these criteria, only one died of subsequent thrombocytopenic bleeding and only eight remained on any therapy with steroids or other immunosuppressive agents at last follow-up examination.

Enteric intussusception presenting as a rapidly enlarging mass.

Enteric intussusception is unusual in adults and frequently presents in a confusing manner. A case of jejunojejunal intussusception is presented in which a 15-cm abdominal mass developed in 24 h. The plain film, barium, and ultrasound findings in enteric intussusception are stressed.

Anticoagulant therapy.

This is a brief review of some of the more important aspects of pharmacology and clinical management of anticoagulant therapy for venous thromboembolism. Some controversial aspects of treatment with respect to drug dosage, laboratory monitoring, and intensity and duration of therapy have been discussed. Thromboembolic complications can be reduced by extending the duration of anticoagulant therapy to a minimum period of 4 months after hospital discharge. Longer periods of treatment may be necessary in patients with recurrent deep venous thrombosis or pulmonary embolism. Hemorrhagic complications can be minimized by proper attention to laboratory monitoring and awareness of drug interactions and side effects.