Age-related declines in neural distinctiveness correlate across brain areas and result from both decreased reliability and increased confusability.

According to the neural dedifferentiation hypothesis, age-related reductions in the distinctiveness of neural representations contribute to sensory, cognitive, and motor declines associated with aging: neural activity associated with different stimulus categories becomes more confusable with age and behavioral performance suffers as a result. Initial studies investigated age-related dedifferentiation in the visual cortex, but subsequent research has revealed declines in other brain regions, suggesting that dedifferentiation may be a general feature of the aging brain. In the present study, we used functional magnetic resonance imaging to investigate age-related dedifferentiation in the visual, auditory, and motor cortices. Participants were 58 young adults and 79 older adults. The similarity of activation patterns across different blocks of the same category was calculated (within-category correlation, a measure of reliability) as was the similarity of activation patterns elicited by different categories (between-category correlations, a measure of confusability). Neural distinctiveness was defined as the difference between the mean within- and between-category similarity. We found age-related reductions in neural distinctiveness in the visual, auditory, and motor cortices, which were driven by both decreases in within-category similarity and increases in between-category similarity. There were significant positive cross-region correlations between neural distinctiveness in different regions. These correlations were driven by within-category similarities, a finding that indicates that declines in the reliability of neural activity appear to occur in tandem across the brain. These findings suggest that the changes in neural distinctiveness that occur in healthy aging result from changes in both the reliability and confusability of patterns of neural activity.

A dissociation between symbolic number knowledge and analogue magnitude information.

Semantic understanding of numbers and related concepts can be dissociated from rote knowledge of arithmetic facts. However, distinctions among different kinds of semantic representations related to numbers have not been fully explored. Working with numbers and arithmetic requires representing semantic information that is both analogue (e.g., the approximate magnitude of a number) and symbolic (e.g., what / means). In this article, the authors describe a patient (MC) who exhibits a dissociation between tasks that require symbolic number knowledge (e.g., knowledge of arithmetic symbols including numbers, knowledge of concepts related to numbers such as rounding) and tasks that require an analogue magnitude representation (e.g., comparing size or frequency). MC is impaired on a variety of tasks that require symbolic number knowledge, but her ability to represent and process analogue magnitude information is intact. Her deficit in symbolic number knowledge extends to a variety of concepts related to numbers (e.g., decimal points, Roman numerals, what a quartet is) but not to any other semantic categories that we have tested. These findings suggest that symbolic number knowledge is a functionally independent component of the number processing system, that it is category specific, and that it is anatomically and functionally distinct from magnitude representations.

Cerebral aging: integration of brain and behavioral models of cognitive function.

There are substantial declines in behavioral measures of cognitive function with age, including decreased function of executive processes and long-term memory. There is also evidence that, with age, there is a decrease in brain volume, particularly in the frontal cortex. When young and older adults perform cognitive tasks that depend heavily on frontal function, neuroimaging evidence indicates that older adults recruit additional brain regions in order to perform the tasks. This additional neural recruitment is termed "dedifferentiation," and can take multiple forms. This recruitment of additional neural tissue with age to perform cognitive tasks was not reflected in the behavioral literature, and suggests that there is more plasticity in the ability to organize brain function than was previously suspected. We review both behavioral and neuroscience perspectives on cognitive aging, and then connect the findings in the two areas. From this integration, we suggest important unresolved questions and directions for future research.

Phakic patients with cystoid macular edema, retinal periphlebitis, and vitreous inflammation.

OBJECTIVE: To characterize a group of phakic patients with idiopathic intermediate uveitis as defined by vitritis, cystoid macular edema, and retinal periphlebitis. DESIGN: Cross-sectional study. PARTICIPANTS: Nineteen phakic patients (35 eyes) with vitreous inflammation, cystoid macular edema, and/or retinal periphlebitis of unknown cause. INTERVENTION: None. MAIN OUTCOME MEASURES: Best-corrected final visual acuities, standardized clinical examinations, photographic and fluorescein angiographic evaluations, and class I and II HLA analysis on all 19 patients. RESULTS: Fifteen of the 19 patients were women. The mean age was 38 years, the mean follow-up was 104 months, and the mean duration of symptoms was 154 months. All 35 affected eyes had significant vitritis; 21 eyes (60%) had cystoid macular edema, 21 eyes (60%) had retinal periphlebitis. The median initial visual acuity was 20/30. The median final visual acuity was 20/20 with 32 (91%) of 35 eyes having 20/40 or better visual acuity at the final visit. No patient developed "snow-banks" or evidence of systemic disease, including multiple sclerosis or sarcoidosis, during the follow-up period. There were no statistically significant HLA associations in these patients compared with controls from another study from Iowa, but the Iowa phakic patients with cystoid macular edema did differ from the Iowa patients with pars-planitis at loci HLA-B8, HLA-B51, and HLA-DR2. CONCLUSIONS: We describe a disease entity of idiopathic intermediate uveitis that affects primarily young to middle-aged women and usually causes bilateral vitritis, cystoid macular edema, and retinal periphlebitis. Most patients retained good vision over a prolonged follow-up period. Multiple sequential examinations and HLA associations suggest that these conditions are distinct from other syndromes of intermediate uveitis, particularly parsplanitis.

Systemic small noncleaved cell lymphoma presenting as a posterior choroidal mass.

PURPOSE: To describe a patient with intraocular involvement by systemic, small noncleaved cell lymphoma. METHODS: Case report and review of the literature. RESULTS: A patient presented with a diffusely elevated choroidal mass. Systemic evaluation led to the diagnosis of unsuspected disseminated lymphoma. CONCLUSION: Small noncleaved cell lymphoma should be included in the differential diagnosis of a choroidal mass.

The neural development and organization of letter recognition: evidence from functional neuroimaging, computational modeling, and behavioral studies.

Although much of the brain's functional organization is genetically predetermined, it appears that some noninnate functions can come to depend on dedicated and segregated neural tissue. In this paper, we describe a series of experiments that have investigated the neural development and organization of one such noninnate function: letter recognition. Functional neuroimaging demonstrates that letter and digit recognition depend on different neural substrates in some literate adults. How could the processing of two stimulus categories that are distinguished solely by cultural conventions become segregated in the brain? One possibility is that correlation-based learning in the brain leads to a spatial organization in cortex that reflects the temporal and spatial clustering of letters with letters in the environment. Simulations confirm that environmental co-occurrence does indeed lead to spatial localization in a neural network that uses correlation-based learning. Furthermore, behavioral studies confirm one critical prediction of this co-occurrence hypothesis, namely, that subjects exposed to a visual environment in which letters and digits occur together rather than separately (postal workers who process letters and digits together in Canadian postal codes) do indeed show less behavioral evidence for segregated letter and digit processing.

A simple common contexts explanation for the development of abstract letter identities.

Abstract letter identities (ALIs) are an early representation in visual word recognition that are specific to written language. They do not reflect visual or phonological features, but rather encode the identities of letters independent of case, font, sound, and so forth. How could the visual system come to develop such a representation? We propose that because many letters look similar regardless of case, font, and other characteristics, these provide common contexts for visually dissimilar uppercase and lowercase forms of other letters (e.g., e between k and y in key and E in the visually similar context K-Y). Assuming that the distribution of words' relative frequencies is comparable in upper- and lowercase (that just as key is more frequent than pew, KEY is more frequent than PEW), these common contexts will also be similarly distributed in the two cases. We show how this statistical regularity could lead Hebbian learning to produce ALIs in a competitive architecture. We present a self-organizing artificial neural network that illustrates this idea and produces ALIs when presented with the most frequent words from a beginning reading corpus, as well as with artificial input.

Familial internal limiting membrane dystrophy. A new sheen retinal dystrophy.

OBJECTIVE: To describe the clinicopathologic features of a previously unreported retinal dystrophy. METHODS: Fourteen members of a single family were examined. The medical records of 2 additional family members were reviewed. Pathologic examination was performed on 2 eyes of 1 affected patient. RESULTS: Five individuals were identified with a retinal dystrophy characterized by a glistening inner retinal surface throughout the posterior pole. Visual loss occurred in 3 affected patients in later life owing to superficial polycystic retinal edema and retinal folds. Electroretinographic testing revealed a selective diminution of the b wave. Pathologic examination revealed an abnormal internal limiting membrane with schisis cavities in the inner retina. Endothelial cell swelling, pericyte degeneration, and basement membrane thickening were present in retinal capillaries. CONCLUSIONS: A previously unreported sheen retinal dystrophy is described. Pedigree analysis suggests an autosomal dominant mode of inheritance. A primary defect in Müller cells is the suspected, but unproved, cause. No effective treatment for the associated visual loss is known. The term familial internal limiting membrane dystrophy is proposed to describe this condition.

Bilateral visual function after macular hole surgery.

PURPOSE: In this study, the authors apply objective measures of bilateral visual function to investigate the benefits of macular hole surgery to overall visual function. METHODS: Anatomic and visual acuity outcomes were reviewed for patients undergoing primary macular hole surgery at one institution during a 3-year period. Several measures of bilateral visual function were defined to determine the impact of surgery on bilateral visual function. Patient data were analyzed in two separate cohorts based on whether the fellow eye was normal (visual acuity > or = 20/40, fellow eye normal group) or abnormal (visual acuity <20/40, fellow eye abnormal group) at baseline to determine the effect on visual function improvement. RESULTS: The rim of subretinal fluid resolved after surgery in 85% of patients and 82% gained two or more Early Treatment Diabetic Retinopathy Study lines of visual acuity. After surgery, visual acuity in the surgical eye was better than or equal to the fellow eye in 35%, and average visual impairment according to the American Medical Association Guidelines for Disability decreased from 29% to 17%. Among the FEA group, vision in the surgical eye was better than or equal to that of the fellow eye in 70%, and visual impairment was reduced from 52% to 35%. CONCLUSION: Bilateral visual function was improved after macular hole surgery. The improvement rate was markedly better in patients with subnormal vision in the fellow eye.

Brain localization for arbitrary stimulus categories: a simple account based on Hebbian learning.

A central theme of cognitive neuroscience is that different parts of the brain perform different functions. Recent evidence from neuropsychology suggests that even the processing of arbitrary stimulus categories that are defined solely by cultural conventions (e.g., letters versus digits) can become spatially segregated in the cerebral cortex. How could the processing of stimulus categories that are not innate and that have no inherent structural differences become segregated? We propose that the temporal clustering of stimuli from a given category interacts with Hebbian learning to lead to functional localization. Neural network simulations bear out this hypothesis.

Food deprivation during different periods of tadpole (Hyla chrysoscelis) ontogeny affects metamorphic performance differently.

Tadpoles in small, ephemeral pools whose duration and food content are unpredictable can potentially encounter substantial variation in diet composition and availability. We compared the effects of 10 days of food deprivation occurring early, midway and late in ontogeny on the metamorphic size and bioenergetic properties of Hyla chrysoscelis tadpoles. Tadpoles fed throughout ontogeny were controls. Metamorphs from tadpoles starved early and midway in ontogeny had the same snout-vent length and dry mass as controls, but the time to metamorphosis was extended by 8 and 19% respectively. Metamorphs of tadpoles starved late in development attained 85% of the length and 55% of the mass of controls, metamorphosed at the same time as controls, and suffered mortality 15 times greater than other treatments, perhaps because they were near the absolute minimum necessary level of energy reserves. There were no significant differences in percent organic matter, percent tissue water, condition index, and protein or glycogen concentrations between any experimental and control treatments. If food deprivation occurred early in development, the tadpoles caught up to the size of controls, but an extended developmental time would increase the risk of predation or habitat loss. If food reductions occur late in development, perhaps magnified by pond desiccation, tadpoles are stimulated to metamorphose at the same time as controls but at a smaller size. The bioenergetic composition of tadpoles at metamorphosis is unaffected by time of food deprivation.

Modulation of retinoblastoma cell characteristics by hexamethylene bis-acetamide and other differentiating agents in culture.

The undifferentiated Y-79 retinoblastoma cell line can be induced by specific agents to express characteristics of mature retinal cells. In the present study, attached Y-79 cell cultures were treated with hexamethylene bis-acetamide (HMBA) and other differentiating agents and examined for "neuronal" and other properties. Immunocytochemical staining was performed with antibodies against neuron- and retina-specific antigens, [synaptophysin, interphotoreceptor retinoid-binding protein (IRBP), neural cell adhesion molecule (N-CAM), and rod- and cone-specific transducin (TR alpha and TC alpha)] and microtubule-associated protein (MAP-1) and tubulin. Enhanced expression of tubulin was observed with cAMP treatment in FBS media. Expression of N-CAM was observed in all groups. Morphological differentiation was pronounced with HMBA and butyrate treatment, with HMBA inducing increased tubulin expression after 2 weeks of treatment. Expression of TR alpha was minimal under all culture conditions, whereas TC alpha was ubiquitously expressed. This supports the concept that Y-79 retinoblastoma is predominantly of cone neuronal origin and that, surprisingly, immunocytochemical differentiation is not correlated with the marked morphological changes induced by the major differentiating agents used.

Enhancement of infusion-induced brain edema by mediator compounds.

Mediator compounds such as bradykinin, arachidonic acid, and LT are released in the brain in conditions causing cerebral swelling. The potential of these compounds to enhance this process was studied in the infusion-induced model of brain edema. Cats subjected to chloralose anesthesia were infused with 400 microliters of artificial CSF into the right and left frontal white matter within 2.5 hr. CSF infused into the left hemisphere contained either bradykinin (40 microM), arachidonic acid (3 mM), LTB4 (15 microM), or LTC4 (16 microM), respectively. Evans blue was administered as blood-brain barrier indicator. Water content of gray and white matter was microgravimetrically determined in serial coronal brain slices. Infusion of CSF only led to an increase in water content from 69 to between 75% and 79%. Addition of bradykinin effectively enhanced the infusion edema but did not open the barrier to Evans blue. Arachidonic acid even more effectively led to an increase in water content and opened the barrier to Evans blue, in addition. Infusion of LT (LTB4, as well as LTC4) was not found to increase further the infusion edema and did not open the blood-brain barrier to Evans blue. It is concluded that the infusion edema model is suitable for studying the edema-enhancing potential of mediator compounds. Marked enhancement of vasogenic brain edema by bradykinin or arachidonic acid again demonstrates a pathophysiological function of these compounds as mediators of secondary brain damage, although LT are unlikely to be specifically involved in vasogenic edema formation.