The time course of pattern discrimination in the human brain.

In electrophysiological experiments on visual pattern discrimination, decision difficulty was manipulated either via the physical characteristics of the test stimuli, or by changing the instruction given to the observer. Visual stimuli were rectangular matrices each composed of 100 Gabor patches having different orientations. Matrices differed in the number of Gabor patches with vertical, or horizontal, orientation. The observers' task was either to discriminate the dominant orientation or to detect collinear elements in the matrix. Relating task difficulty to performance, in the first experimental paradigm (detection of orientation) we obtained the conventional S-like psychometric function but in the second (detection of collinearity) the psychometric function showed a complicated U-curve. Matching between electrophysiological and psychophysical data and image statistical functions allowed us to establish the relative timing of the cortical processes underlying perception and decision making in relation to textural features. In the first 170ms after stimulus onset coding of the low-level properties of the image takes place. In the time interval 170-400ms, ERP amplitude correlated only with complex image properties, but not with task difficulty. The first effects arising from decision difficulty were observable at 400ms after stimulus onset, and therefore this is probably the earliest electrophysiological signature of the decision making processes, in the given experimental paradigm.

Ageing and spatial reversal learning in humans: findings from a virtual water maze.

Deterioration in spatial memory with normal ageing is well accepted. Animal research has shown spatial reversal learning to be most vulnerable to pathological changes in the brain, but this has never been tested in humans. We studied ninety participants (52% females, 20-80 yrs) in a virtual water maze with a reversal learning procedure. Neuropsychological functioning, mood and personality were assessed to control moderator effects. For data analysis, participants were subdivided post hoc into groups aged 20-24, 25-34, 35-44, 45-64 and 65-80 yrs. Initial spatial learning occurred in all age groups but 65-80-yrs-olds never reached the level of younger participants. When tested for delayed recall of spatial memory, younger people frequented the target area but those over 65 yrs did not. In spatial reversal learning, age groups over 45 yrs were deficient and the 65-80-yrs-olds showed no evidence of reversal. Spatial measures were associated with neuropsychological functioning. Extraversion and measures of depression moderated the age effect on the learning index with older introverted and non-depressed individuals showing better results. Measures of anxiety moderated the age effect on reversal learning with older people having higher anxiety scores showing a preserved reversal learning capability. Results confirmed age to be a major factor in spatial tasks but further showed neuropsychological functioning, psycho-affective determinants and personality traits to be significant predictors of individual differences.

Children's Oncology Group's 2013 blueprint for research: central nervous system tumors.

In the US, approximately 2,500 children are diagnosed annually with brain tumors. Their survival ranges from >90% to <10%. For children with medulloblastoma, the most common malignant brain tumor, 5-year survival ranges from >80% (standard-risk) to 60% (high-risk). For those with high-grade gliomas (HGGs) including diffuse intrinsic pontine gliomas, 5-year survival remains <10%. Sixty-five percent patients with ependymoma are cured after surgery and radiation therapy depending on the degree of resection and histopathology of the tumor. Phase II trials for brain tumors will investigate agents that act on cMET, PDGFRA, or EZH2 in HGG, DIPG, or medulloblastoma, respectively. Phase III trials will explore risk-based therapy stratification guided by molecular and clinical traits of children with medulloblastoma or ependymoma.

GVHD after unrelated cord blood transplant in children: characteristics, severity, risk factors and influence on outcome.

We reviewed our experience in 79 children who had unrelated cord blood transplant (UCBT) between 1996 and 2007 with a major focus on GVHD, comparing both traditional and National Institute of Health (NIH) criteria. The cumulative incidence (CI) of acute GVHD (aGVHD, by day +100) was 0.42 for grade II-IV and 0.22 for grade III-IV. The CI of all aGVHD (NIH, that is, no time limit) at 1 year was 0.45 for grade II-IV and 0.32 for grade III-IV. Infused CD34 cell dose (>1 × 10(5)/kg), pretransplant bacterial infection and nonmalignant disorders were risk factors for grade II-IV aGVHD on univariate analysis. Infused CD34 cell dose remained significant on multivariate analysis. At 1 year, the CI of chronic GVHD (cGVHD) using the Seattle criteria was 0.27, whereas that for cGVHD (NIH) was 0.08. By NIH criteria, the classic form of cGVHD was uncommon (5%) after UCBT. Instead, the acute (71%) and overlap (24%) GVHD variants predominated. Grade II-IV aGVHD was a significant risk factor for cGVHD by both Seattle and NIH criteria. We conclude that GVHD after day +100 after UCBT typically carries features of aGVHD. Moreover, and in marked contrast to adult unrelated donor hematopoietic stem cell transplantation, the GVHD observed in this series did not adversely affect survival.

Perception of fragmented images of three-dimensional objects as the observation angle changes.

Recognition thresholds for incomplete two-dimensional images of three-dimensional objects were measured as the observation angle was changed. A new experimental psychophysical method was developed and programmed for this purpose, this being a modification of the Gollin test, which measures perception thresholds of incomplete outline images. After training to a stimulus alphabet, observers' responses were found to be invariant to changes in the observation angles of three-dimensional objects from 15 degrees to 60 degrees. It is suggested that possible algorithms for the formation of models of three-dimensional images in the human visual system do not operate on the basis of simple section, but involve invariance mechanisms.

Analysis of the studies of the perception of fragmented images: global description and perception using local features.

This report presents an analysis of studies of the visual perception of fragmented images. Two approaches to the description of brain functioning during the solution of this task are considered: studies of the perception of the statistical properties of global whole images and studies of the perception of images in terms of local higher-order informative features. These approaches describe two different mechanisms which the human brain may use for recognizing incomplete images. Studies performed using the Gollin test (measurement of recognition thresholds for fragmented outline images during gradual construction of the outline) are given most attention. In solving this task, the visual system extracts the statistical properties of the whole image. Local higher-order informative features are used by the brain as additional sources of information about the image. The role of this source increases on learning a given alphabet of stimuli. In accordance with a matched filtration model, the fragmented images used in the Gollin test are perceived as a whole structure, compared with a reference which is stored in memory and selected using the selective attention mechanism. At the primary filtration step and the matched filtration step, the recognition thresholds of images in the Gollin test reflect the processes of extracting the signal from noise. The Gollin test can be used as a differential tool for the diagnosis of different types of cognitive impairments.

[Incomplete 2-D images perception at viewpoint variation of 3-D objects].

Thresholds of recognition of 3-D objects when viewed as incomplete 2-D images were measured in psychophysical experiments varying perspective of 3-D objects during subject's learning and testing. The new method of measurement of recognition thresholds of the 2-D incomplete images of 3-D objects in Gollin-test has been created. The visual system appears to be capable of extrapolating results that were obtained at the first presentation of object, at one viewing angle to other, subsequent viewing angles. It appears that a template forms immediately after the first presentation of a 2-D projection of that object. This template has "invariance" properties since its use for object identification does not depend on the orientation at which the object is subsequently presented, at least up to an angle of 60 degrees. The algorithm for template formation of 3-D objects in the human visual system needs to be modeled, taking account of the invariance mechanism.

[Analysis of fragmented images perception: local features and global description].

Analysis of experimental investigations of the perception of incomplete images is presented. It illustrates two different approaches to work of the brain mechanisms involved: one approach is based on the perception of whole images and another on local informative features. These approaches describe two different mechanisms, which are possibly used by brain systems for incomplete image recognition. Performance on the Gollin test (measuring recognition thresholds for fragmented line drawings of everyday objects and animals) depends upon recognition based on image informational-statistical characteristics. We suggest that recognition thresholds for Gollin stimuli in part reflect the extraction of signal from noise. The brain uses local informative features as an additional source of information about them. We have suggested that fragmented images in the Gollin-test are perceived as whole structures. This structure is compared with a template in memory which is extracted with the help of selective attention mechanism in accordance with a matched filtration model. The Gollin-test is a tool for differential diagnosis of a various forms of cognitive disorders.

The threshold signal:noise ratio in the perception of fragmented figures.

Perception thresholds were measured for fragmented outline figures (the Gollin test). A new approach to the question of the perception of incomplete images was developed. In this approach, figure fragmentation consisted of masking with multiplicative texture-like noise--this interference was termed "invisible" masking. The first series of studies established that the "similarity" between the amplitude-frequency spectra of test figures and "invisible" masks, expressed as a linear correlation coefficient, had significant effects on the recognition thresholds of these figures. The second series of experiments showed that progressing formation of the figures was accompanied by increases in the correlation between their spatial-frequency characteristics and the corresponding characteristics of the incomplete figure, while the correlation with the "invisible" mask decreased. It is suggested that the ratio of the correlation coefficients, characterizing the "similarity" of the fragmented figure with the intact figure and the "invisible" mask, corresponds to the signal:noise ratio. The psychophysical recognition threshold for figures for naive subjects not familiar with the test image alphabet was reached after the particular level of fragmentation at which this ratio was unity.

The optical-geometrical characteristics and thresholds of perception of fragmented outline figures.

Measurements were made of the threshold of recognition of cumulatively forming line figures. The threshold value of the outline, expressed in pixels, depended on the length of the outline of the whole unfragmented figure. Relative threshold values were constant, and for the measures of figure fragments used in the present study, averaged 12.5%. A spatial frequency analysis of the test images was performed. Variation of the amplitude-frequency parameters of the spectra of the images of various figures with threshold fragmentation was minimal as compared with the variation of these parameters in figures with subthreshold or suprathreshold levels of fragmentation.

A study of sequential high dose cyclophosphamide and high dose carboplatin with peripheral stem-cell rescue in resistant or recurrent pediatric brain tumors.

PURPOSE: To determine the maximum tolerated dose (MTD) of carboplatin with autologous hematopoietic stem-cell rescue, in children with poor-prognosis brain tumors. PATIENTS AND METHODS: A previously determined dose of cyclophosphamide with stem-cell rescue was used as a first course. In a second course, carboplatin was given for 3 days with stem-cell rescue to 20 children. The starting dose of carboplatin was 400 mg/m2/day with increments of 75 mg/m2/day in subsequent cohorts. Toxicity and tumor response were recorded. RESULTS: There were two grade IV toxicities at the dose level of 775 mg/m2/day. There were no toxic deaths. Thus, the MTD of carboplatin was 700 mg/m2/day for 3 days. There were six complete responses (33%, 95% confidence interval [CI], 13-59%), two partial responses (11%; 95% CI, 1-35%), four with stable diseases (22%; 95% CI, 6-48%) and six progressed (33%; 95% CI, 13-59%) out of 18 assessable. Seven of the eight responses were in primitive neuroectodermal tumors (PNETs) or Germinomas. One child with a metastatic anaplastic astrocytoma had a CR. The median duration of tumor response was 10 months (range: 1.5-87 months) with two children disease free at 66 and 87 months. Actuarial survival is 21%. Median follow-up of survivors is 35 months (range: 15-87 months). CONCLUSION: The MTD of carboplatin with stem-cell rescue is 700 mg/m2/day for 3 days. Sequential stem-cell supported cyclophosphamide and carboplatin was tolerable in children with brain tumors and produced responses in PNETs and Germinomas.

Intracranial germ cell tumors: a single institution experience and review of the literature.

There is little literature to guide therapy in children and young adults with intracranial germ cell tumors. We present 17 consecutively diagnosed intracranial germ cell tumors at The Children's Hospital, Denver, from 1995 to 2001. Of 17 patients, 3 had considerable delay in diagnosis. Two with suprasellar tumors presented with dementia, blindness and pan-hypopituitarism and another with recurrent subarachnoid hemorrhage. Seven had germinoma, three were metastatic at diagnosis. Ten had non-germinomatous germ cell tumors (NGGCT), 5/10 were alpha feto-protein (AFP) positive only, one beta-human chorionic growth (betaHCG) factor positive only, 3 positive for AFP and betaHCG, and 1 malignant teratoma. Therapy for metastatic patients consisted of chemotherapy followed by craniospinal radiation (CSI). Patients with localized disease received chemotherapy followed by focal radiation. Two patients received chemotherapy only, one because she died of sepsis while receiving chemotherapy and one because of neurologic injury incurred during surgery parents elected for no therapy. Three patients have died, one of tumor recurrence, one from a remote complication of surgery and one of sepsis. Twelve patients are alive without evidence of disease from 10 to 68 months (median 31.5 months). All five children with only AFP positivity, treated with chemotherapy and focal radiation are alive without evidence of disease at 10, 16, 22, 41 and 41 months. Thus, there is little evidence that CSI is necessary in non-metastatic germinomas and AFP positive NGGCTs when combined chemotherapy and radiation therapy is used. However, complications of delayed diagnosis, surgery and chemotherapy are important causes of mortality, with only one patient dying of tumor.

[Signal/noise ratio at the visual recognition threshold of incomplete figures]. / Porogovoe otnoshenie signal/shum pri vospriiatii fragmentirovannykh figur.

We measured recognition thresholds of incomplete figure perception (the Gollin test). This test we regarded as a visual masking problem. Digital image processing permits us to measure the spatial properties and spatial frequency spectrum of the absent part of the image as the mask. Using a noise paradigm, we have measured the signal/noise ratio for Incomplete Figure. Recognition was worse with better spectral "similarity" between the figure and the "invisible" mask. At threshold, the spectrum of the fragmented image was equally similar to that of the "invisible" mask and complete image. We think the recognition thresholds for Gollin stimuli reflect the signal/noise ratio.

[Optical-geometrical parameters and perception threshold of the fragmented contour figures]. / Optiko-geometricheskie kharakteristiki i porogi vospriiatiia fragmentirovannykh konturnykh figur.

The thresholds of recognition of line drawings of common objects were measured using the Gollin-test procedure, in which separate random line fragments are displayed cumulatively up to the point of recognition. It was shown that the mean percentage of contour displayed at threshold recognition for different images was always about 12.5%, despite inter-subject variability between 5% and 25%. The comparative and spatial-frequency analysis of the geometrical parameters of images was carried out for different levels of fragmentation (before threshold, at threshold, and for the complete contour). The magnitude information of the Fourier domain image of figures was characterized by maximum at low and high levels of fragmentation, but at recognition threshold fragmentation it was characterized by minimum variability.

Diffuse, retroperitoneal mesenteric and intrahepatic periportal plexiform neurofibroma in a 5-year-old boy.

We present a case of plexiform neurofibroma involving the retroperitoneum, mesentery, and liver in a 5-year-old boy who underwent evaluation for extent of a palpable left neck mass. The mass had intrathoracic extension with great vessel encasement and extension into the abdomen. Abdominal CT revealed a diffuse low-attenuation non-enhancing mass encasing the retroperitoneal vessels with serpiginous extension into the liver along the portal vein. This spread pattern of plexiform neurofibroma is an unusual manifestation of neurofibromatosis in a young child.

Peripheral placement of apheresis catheters in children: feasibility, safety, and efficacy in the collection of blood stem cells--initial experience.

An 8-F 24-cm-long apheresis catheter was placed in the basilic vein with imaging-guided percutaneous technique in 15 children undergoing leukapheresis for collection of autologous peripheral blood stem cells. There were no immediate or long-term complications. This is a low-morbidity procedure requiring minimal sedation that results in successful collection of peripheral blood stem cells and allows flow rates comparable to those with surgically placed central catheters.

Choroid plexus carcinomas and rhabdoid tumors: phenotypic and genotypic overlap.

Five of six poorly differentiated choroid plexus carcinomas identified at our institution contained cells displaying a rhabdoid phenotype. Immunoperoxidase stains showed focal positivity for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, S100, and vimentin. The MIB-1 proliferative index ranged from 7.0% to 27.1%. All six tumors were p53 positive. Only the one child with Li-Fraumeni syndrome had a p53 germline mutation. Electron microscopy verified choroid plexus differentiation and the co-existence of rhabdoid cells. Of the five studied, four had deletions of chromosome 22 [three with monosomy 22 and one with del(22)(q12)]. Thus, there was a phenotypic and genotypic overlap between choroid plexus carcinomas and rhabdoid tumors.

Rhabdoid glioblastoma.

Rhabdoid phenotypic change has been described in a number of different neoplasms from diverse organ sites. These tumors share common light and electron-microscopic features, display a polyphenotypic immunohistochemical profile and often show cytogenetic abnormalities of chromosome 22. In the central nervous system (CNS), most rhabdoid tumors occur in the posterior fossa of very young children and are associated with a primitive neuroectodermal tumor (PNET) component and are designated atypical teratoid/rhabdoid tumors. Infrequently, other rhabdoid tumors of the CNS have been described, including rhabdoid meningiomas and malignant rhabdoid tumors of uncertain histogenesis. Several examples of conventional gliomas displaying significant areas with rhabdoid morphology were also presented in an abstract by Kepes and Moral [1991], although never published in final manuscript form. We now detail the case of an 18-year-old male with an aggressive, supratentorial CNS rhabdoid tumor that was associated with an epithelioid glioblastoma and apparently arose from areas of low-grade glioma. The rhabdoid tumor component was present in the original tumor but became more predominant with each of 3 successive resections. No areas of PNET were identified. Electron microscopy and immunohistochemistry showed features classic for rhabdoid tumors and cytogenetic studies demonstrated multiple tumor clones with monosomy 22. This case documents progressive rhabdoid transformation of a glioma, expands the spectrum of CNS tumor types that can display a rhabdoid phenotype and highlights the diagnostic and therapeutic challenges with this type of tumor.