A 12-week exercise programme has a positive effect on everyday executive function in young people with Down syndrome: a pilot non-randomised controlled trial.

BACKGROUND: Exercise has the potential to reduce cognitive decline in people with Down syndrome by maximising their cognitive function. The aim of the study was to determine the effect of regular exercise on cognitive functioning in young people with Down syndrome. METHOD: People with Down syndrome were eligible if aged between 13 and 35 years and enrolled to participate in an exercise programme (called FitSkills). The intervention was a 12-week community-based exercise programme completed with a student mentor. Outcomes were assessed before (week 0) and immediately after (week 13) the intervention. Executive functioning (planning, response inhibition, attention shifting) was assessed using Tower of London, Sustained Attention to Response Task, CANTAB Intra-extra Dimensional Set Shift Test, Cognitive Scale for Down Syndrome, and Behaviour Rating Inventory of Executive Function (BRIEF). Working memory was assessed using the CANTAB Paired Associates Learning task, and information processing speed was assessed using the Motor Screening Task. Outcomes were analysed using ANCOVA with the baseline measure as the covariate. RESULTS: Twenty participants (9 women; mean age 23.6 ± 6.6 years) enrolled. Between-group differences, in favour of the experimental group, were found for the global executive composite score of the BRIEF (mean difference -4.77 units, 95% CI -9.30 to -0.25). There were no between group differences for any other outcome measured. CONCLUSION: Participation in a 12-week exercise programme was effective in improving everyday executive functions in young people with Down syndrome. These preliminary findings need to be confirmed in future randomised controlled trials of community-based exercise with larger sample sizes.

Shared and syndrome-specific adaptive difficulties in preschoolers with Williams syndrome and autism spectrum disorder: a cross-syndrome study.

BACKGROUND: Understanding adaptive functioning profiles in children with Williams syndrome (WS) and autism spectrum disorder (ASD) is critical to inform treatment strategies. However, knowledge in this area is limited and inconclusive. METHOD: The current study aimed to characterise the early adaptive profiles of young children with WS (n = 18; Mage = 47 months) and ASD (n = 26; Mage = 45 months) matched on chronological age and developmental age using the Vineland Scales of Adaptive Behavior, Second Edition. RESULTS: Results suggest that young children with WS and ASD do not differ on their overall level of adaptive functioning but that those with WS show relative strengths in the Socialisation scale compared with children with ASD. No other subscales differed between groups. Within groups, the WS group showed a profile of Communication, Daily Living Skills and Motor < Socialisation, whereas the ASD group did not evidence differences across subscales. CONCLUSIONS: Consideration of the shared and syndrome-specific adaptive profiles provides relevant insight on intervention targets and strategies. Given the shared challenges across the two clinical groups, implications and future directions are discussed.

Preliminary evidence of an effect of cerebellar volume on postural sway in FMR1 premutation males.

Recent evidence suggests that early changes in postural control may be discernible among females with premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene at risk of developing fragile X-associated tremor ataxia syndrome (FXTAS). Cerebellar dysfunction is well described in males and females with FXTAS, yet the interrelationships between cerebellar volume, CGG repeat length, FMR1 messenger RNA (mRNA) levels and changes in postural control remain unknown. This study examined postural sway during standing in a cohort of 22 males with the FMR1 premutation (ages 26-80) and 24 matched controls (ages 26-77). The influence of cerebellar volume, CGG repeat length and FMR1 mRNA levels on postural sway was explored using multiple linear regression. The results provide preliminary evidence that increasing CGG repeat length and decreasing cerebellar volume were associated with greater postural sway among premutation males. The relationship between CGG repeat length and postural sway was mediated by a negative association between CGG repeat size and cerebellar volume. While FMR1 mRNA levels were significantly elevated in the premutation group and correlated with CGG repeat length, FMR1 mRNA levels were not significantly associated with postural sway scores. These findings show for the first time that greater postural sway among males with the FMR1 premutation may reflect CGG repeat-mediated disruption in vulnerable cerebellar circuits implicated in postural control. However, longitudinal studies in larger samples are required to confirm whether the relationships between cerebellar volume, CGG repeat length and postural sway indicate greater risk for neurological decline.

Understanding the neuropsychiatric phenotype of fragile X-associated tremor ataxia syndrome: a systematic review.

Fragile X-associated tremor ataxia syndrome (FXTAS) is a recently identified X-linked neurodegenerative disorder affecting a proportion of premutation carriers of the Fragile X Mental Retardation 1 (FMR1) gene. Previous research suggests that cognitive and psychiatric features of FXTAS may include primary impairments in executive function and increased vulnerability to mood and anxiety disorders. A number of these reports, however, are based on overlapping cohorts or have produced inconsistent findings. A systematic review was therefore conducted to further elucidate the neuropsychiatric features characteristic of FXTAS. Fourteen papers met inclusion criteria for the review and were considered to represent nine independent FXTAS cohorts. Findings from the review suggest that the neuropsychiatric phenotype of FXTAS is characterised primarily by poorer performance on measures of executive function, working memory, information processing speed, and fine motor control when compared to matched comparison groups. Two studies were identified in which psychiatric symptoms in FXTAS were compared with controls, and these yielded mixed results. Overall the results of this review support previous reports that the neuropsychiatric profile of FXTAS is consistent with a dysexecutive fronto-subcortical syndrome. However, additional controlled studies are required to progress our understanding of FXTAS and how the neuropsychiatric profile relates to underlying pathological mechanisms.

Symbolic sequence learning is associated with cognitive-affective profiles in female FMR1 premutation carriers.

This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)-carriers. A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and intelligence quotient-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers.

Gait adaptation during obstacle crossing reveals impairments in the visual control of locomotion in Williams syndrome.

Recent evidence indicates that individuals with Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, show abnormalities of parietal and cerebellar regions of the brain that may be involved in the visual control of locomotion. Here we examined whether parietal and cerebellar abnormalities contribute to deficits in spatiotemporal characteristics and foot placement variability during obstacle crossing in adults with WS, when compared with an IQ-matched group of adults with Down syndrome (DS) and typically developing adult controls. We used the GAITRite walkway to examine the spatiotemporal characteristics and foot placement variability relative to a small ground-based obstacle in the travel path. We found that adults with WS showed late adjustments to spatiotemporal gait characteristics alongside an exaggerated and more spatially constrained visual guidance of foot positioning in the final steps prior to stepping over the obstacle. In contrast, the adults with DS showed longer step duration and more variable step length and step duration during the crossing and recovery steps after the obstacle, suggestive of cerebellar dysfunction. Although the controls were able to reduce the variability of foot placement across the obstacle crossing trials, both the WS and DS groups did not become more consistent with practice. These findings indicate a less flexible and overly constrained visuomotor system in WS, which is consistent with more widespread and diffuse abnormalities in parietal and cerebellar regions.

The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity?

Friedreich ataxia (FRDA) is the most common of the inherited ataxias. We have suggested that people with FRDA may have impairment in cognitive and/or psychomotor capacity either due to disturbance of projections of the cerebellum to the cortex, direct cortical pathology or perhaps both. To further explore this possibility, we used a movement task incorporating Fitts' Law, a robust description of the relationship between movement time and accuracy in goal-directed aiming movements. By manipulating task difficulty, according to target size and distance, we were able to quantify processes related to motor planning in 10 individuals with FRDA and 10 matched control participants. Compared to control participants, people with FRDA were significantly disadvantaged in terms of movement time to targets with an increasing index of difficulty. Successful completion of this task requires both preplanning of movement and online error detection and correction. The cerebellum and its connections to the frontal cortex via cerebro-ponto-cerebello-thalamo-cerebral loops are fundamental to both processes. These results lend further support to our contention that in FRDA these loops are impaired, reflecting a failure to access prefrontal/anterior regions necessary for effective management of preplanning of movement and online error correction.

Rapid identification of ocular dominance columns in macaques using cytochrome oxidase, Zif268, and dark-field microscopy.

Strabismus induces an abnormal pattern of alternating light and dark columns of cytochrome oxidase (CO) activity in macaque striate cortex. This pattern may arise because visual perception is suppressed in one eye to avoid diplopia. To test whether CO activity is reduced in the ocular dominance columns of the suppressed eye, we performed monocular enucleation to co-label the ocular dominance columns with Zif268 immunohistochemistry in seven exotropic adult Macaca fascicularis. This approach was unsuccessful, for two reasons. First, Zif268 yielded inconsistent labelling, that was usually greater in the enucleated eye's ocular dominance columns, but was sometimes greater in the intact eye's columns. Therefore, Zif268 was not a reliable method for identifying the ocular dominance columns serving each eye. Second, in three control animals we found that a brief survival period following monocular enucleation (needed for Zif268 levels to change) was long enough to alter CO staining. For example, a survival time of only 3 h was sufficient to induce CO columns, indicating that the activity of this enzyme fluctuates more rapidly than realized previously. Independent of these findings, we have also discovered that acute monocular enucleation produces a vivid pattern of ocular dominance columns visible in unstained or CO-stained sections under dark-field illumination. The ocular dominance columns of the acutely enucleated eye appear dark. This was verified by labelling the ocular dominance columns with [3H]proline. Dark-field illumination of the cortex after acute monocular enucleation offers a new, easy method for identifying the ocular dominance columns in macaques.

Metabolic mapping of suppression scotomas in striate cortex of macaques with experimental strabismus.

Misalignment of the ocular axes induces double vision and rivalry. To prevent these unpleasant sensations, most subjects fixate preferentially with one eye and suppress entirely the deviating eye or else suppress portions of the visual field of either eye. To explore the mechanism of visual suppression, a divergent strabismus (exotropia) was induced in six normal, adult Macaca fascicularis by disinserting the medial rectus muscles. After 4-8 weeks, each animal was chaired to measure its exotropia and to determine its ocular fixation preference. Five of the monkeys developed a clearly dominant eye. It was injected with [(3)H]proline. Alternate sections from flat-mounts of striate cortex were then processed either for autoradiography to label the ocular dominance columns or for cytochrome oxidase (CO) to assess local metabolic activity. Two CO patterns were seen, often in the same cortex. The first consisted of thin dark columns alternating with wide pale columns. This pattern arose from reduced CO activity in the suppressed eye's monocular core zones and both eyes' binocular border strips. The second pattern consisted of thin pale bands from reduced metabolic activity in both eyes' border strips. The thin dark-wide pale CO pattern was more widespread in the three animals with a strong fixation preference. The dark CO columns usually fit in register with the ocular dominance columns of the fixating eye, suggesting that perception was suppressed in the deviating eye. In most animals, however, the correlation switched in peripheral cortex contralateral to the deviating eye, implying local suppression of the fixating eye's temporal retina (beyond 10 degrees), as reported in humans with divergent strabismus. In the two animals with a weak fixation preference, pale border strips were found within the central visual field representation in both hemispheres. This CO pattern was consistent with alternating visual suppression. These experiments provide the first anatomical evidence for changes in cortical metabolism that can be correlated with suppression scotomas in subjects with strabismus.

Monocular core zones and binocular border strips in primate striate cortex revealed by the contrasting effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase activity.

In primate striate cortex, geniculocortical afferents in layer IVc terminate in parallel stripes called ocular dominance columns. We propose that this segregation of ocular inputs generates a related but distinct columnar system of monocular core zones alternating with binocular border strips. Evidence for this functional parcellation was obtained by comparing the effects of enucleation, eyelid suture, and retinal laser lesions on cytochrome oxidase (CO) activity in eight macaques. Enucleation produced a high-contrast pattern of dark and light columns in layer IVc, corresponding precisely to the ocular dominance columns, whereas eyelid suture produced a low-contrast pattern of thin dark columns alternating with wide pale columns. [3H]Proline eye injection showed that the thin dark columns corresponded to the core zones of the open eye's ocular dominance columns. The wide pale columns resulted from loss of CO activity in the sutured eye's core zones and within both eyes' border strips. Loss of CO activity within both eyes' border strips suggested that these regions are binocular. To confirm our findings, we compared different CO patterns in the same cortex by making retinal laser lesions in four animals. They produced a CO pattern tantamount to "focal" enucleation, although contrast was low when laser damage was confined to the outer retina. CO levels in cortical scotomas remained severely depressed for months after retinal lesions, even when the other eye was enucleated. This observation provided little anatomical support for the notion of topographic plasticity after visual deafferentation. In a single human subject with macular degeneration, CO revealed a low-contrast pattern of ocular dominance columns, resembling the pattern in monkeys with laser-induced photoreceptor damage.

Effect of early monocular enucleation upon ocular dominance columns and cytochrome oxidase activity in monkey and human visual cortex.

We examined cytochrome oxidase (CO) activity in striate cortex of four macaque monkeys after monocular enucleation at ages 1, 1, 5, and 12 weeks. These animal experiments were performed to guide our interpretation of CO patterns in occipital lobe specimens obtained from two children who died several years after monocular enucleation during infancy for tumor. In the macaques, the ocular dominance columns were labelled by injecting [3H]proline into the remaining eye. After enucleation at age 1 week, ocular dominance columns were eliminated in layer IVc(beta), resulting in a uniform pattern of autoradiographic label and CO staining. However, columns could still be seen in wet, unstained sections and with the Liesegang silver stain. Autoradiographs through layers IVc(alpha) and IVa showed residual, shrunken columns belonging to the missing eye, indicating that enucleation has less drastic effects in these layers. In the two human cases, enucleation at age 1 week also resulted in uniform CO staining in layer IVc. In the macaque after enucleation at age 5 weeks, ocular dominance columns belonging to the missing eye were severely narrowed, but still occupied 20% of layer IVc(beta). CO revealed wide, dark columns alternating with thin, pale columns in layer IVc(beta). The CO pattern and the columns labelled by autoradiography matched perfectly. After enucleation at age 12 weeks, only mild shrinkage of ocular dominance columns occurred. Enucleation at ages 1, 5, and 12 weeks did not alter the pattern of thin-pale-thick-pale stripes in V2. The main findings from this study were that (1) CO histochemistry accurately labels the boundaries of columns in layer IVc(beta) of macaque striate cortex after early monocular enucleation, making it a suitable technique for defining the critical period for plasticity of ocular dominance columns in human striate cortex; (2) enucleation causes more severe shrinkage of ocular dominance columns than eyelid suture; (3) early monocular enucleation obliterates ocular dominance columns in layer IVcbeta, but their pattern remains visible in wet sections and with the Liesegang stain; and (4) enucleation does not affect CO staining in V2.

Pattern of ocular dominance columns and cytochrome oxidase activity in a macaque monkey with naturally occurring anisometropic amblyopia.

Unilateral eyelid suture, a model for amblyopia induced by congenital cataract, produces shrinkage of the deprived eye's ocular dominance columns in the striate cortex. Loss of geniculocortical projections are thought to account for the poor vision in the amblyopic eye. It is uncertain whether ocular dominance columns become shrunken in other forms of amblyopia. We examined the striate cortex in a pigtailed macaque with natural anisometropia discovered at age 5 months. Amblyopia in the left eye was documented at 1 year by behavioral testing. At age 6 years, the left eye was injected with [3H]proline and the striate cortex was processed for autoradiography and cytochrome oxidase (CO). The ocular dominance columns in layer IVc labelled with [3H]proline were normal. CO staining showed a novel pattern of thin dark bands in layer IV. These bands occupied the core zones at the center of the ocular dominance columns. Their appearance resulted from relative loss of CO activity along the borders of the ocular dominance columns, regions specialized for binocular processing. These findings indicate that not all forms of amblyopia are accompanied by shrinkage of ocular dominance columns. The unusual pattern of CO staining in layer IVc reflected a subtle alteration in metabolic activity which may have resulted from impairment of binocular function in anisometropic amblyopia.

Timing of the critical period for plasticity of ocular dominance columns in macaque striate cortex.

Visual deprivation induced by monocular eyelid suture, a laboratory model for congenital cataract, results in shrinkage of ocular dominance columns serving the closed eye. We performed monocular suture in macaques at ages 1, 3, 5, 7, and 12 weeks to define the critical period for plasticity of ocular dominance columns. After a minimum survival of 8 months, complete montages of [3H]proline-labeled columns were reconstructed from flat-mounts of striate cortex in both hemispheres. In any given monkey, visual deprivation induced the columns throughout striate cortex (V1) to retract the same distance from their original borders in layer IVcbeta. After deprivation, the widest columns remained in the foveal representation and along the V1/V2 border, where columns are widest in control animals. The narrowest deprived columns belonged to the ipsilateral eye, especially along the horizontal meridian and in the periphery, where columns are narrowest in control animals. At the earliest age that we tested (1 week), visual deprivation reduced the columns to fragments. These fragments always coincided with a cytochrome oxidase patch, or a short string of patches, in the upper layers. More severe column shrinkage occurred in layer IVcbeta (parvo) than layer IVcalpha (magno). The geniculate input to the patches in layer III (konio) appeared normal after deprivation, despite loss of CO activity. Surprisingly, the blind spot representation of the open eye was shrunken by monocular deprivation, although binocular competition is absent in this region. Our principal finding was that eyelid suture at age 1 week caused the most severe column shrinkage. With suture at later ages, the degree of column shrinkage showed a progressive decline. Deprivation commencing at age 12 weeks caused no column shrinkage. These results imply that primate visual cortex is most vulnerable to deprivation during the first weeks of life. Our experiments should provide further impetus for the treatment of children with congenital cataract at the earliest possible age.

Chronotopic fiber reordering and the distribution of cell adhesion and extracellular matrix molecules in the optic pathway of fetal ferrets.

We have examined the age-related reordering of optic axons as they pass through the chiasmatic region in fetal ferrets. Proportions of young and old optic axons were determined from electron micrographs taken sequentially through the prechiasmatic nerve, chiasm, and tract. This "chronotopic" reordering of axons was shown to emerge gradually, beginning rostral to the fusion of the two optic nerves, but continuing to develop caudal to the chiasmatic midline. Segregation of young from old optic axons was most pronounced within the optic tract. We then compared the emergence of this fiber reorganization to the distribution of cell adhesion and extracellular matrix molecules and to the glial architecture within the pathway. Using immunohistochemistry, the distributions of the cell adhesion molecules L1, NCAM, and TAG-1 and the extracellular matrix molecules laminin-1 and chondroitin sulfate proteoglycans (CSPGs) were determined. Among these, only the distribution of CSPGs was observed to change in a manner that complemented the segregation of young from old optic axons. CSPGs were densest in the deeper parts of the optic tract, coincident with radial glial fibers that turn to course within the region of the oldest optic axons. Both the glial architecture and the CSPG distribution form as a consequence of the invasion of the first optic axons, shown by the developmental sequence of each, and by the fact that these glial and molecular features fail to form in the absence of optic axons. The data suggest a model in which the gradient of CSPGs across the depth of the tract contributes to the formation of the chronotopic fiber reordering by providing a relatively unfavorable environment for subsequent axonal growth. The CSPGs may do so by interfering with adhesion molecules on optic axons that normally promote elongation.

Myelin patterns in V1 and V2 of normal and monocularly enucleated monkeys.

A pattern of alternating light and dark columns was observed in wet, unstained sections of macaque striate cortex after monocular enucleation. The columns were clearest in layer IV, but could be detected through the full thickness of the cortex. Subsequent processing for cytochrome oxidase (CO) showed that the light columns in wet sections viewed under darkfield illumination matched the ocular dominance columns serving the enucleated eye. These columns labeled preferentially with an antibody to myelin basic protein, suggesting that greater myelin content accounted for their brighter appearance. However, when sections were counterstained with luxol fast blue, Gallyas and Woelcke myelin techniques, the enucleated eye's columns appeared pale. It is unclear why classical myelin stains and myelin basic protein immunohistochemistry yielded opposite results. Discrepant patterns of myelin distribution were also found in normal animals using different myelin stains. Luxol fast blue showed homogeneous staining in layer IVc of macaque striate cortex, but the Gallyas stain revealed a pattern of thin pale bands alternating with wide dark bands, matching the pattern seen with the Liesegang stain. The CO patches in layers II and III fit in register with the wide dark myelin bands. In layers II and III of striate cortex, the Gallyas and luxol fast blue methods both labeled the CO patches. However, in squirrel monkey V2 the Gallyas stain labeled the pale CO stripes, whereas luxol fast blue labeled the dark CO stripes. These results indicate that pattern of myelin staining in visual cortex can vary according to the choice of technique, and may not reflect the true distribution of myelin. Studies of myeloarchitecture should employ a variety of myelin techniques, including examination of unstained sections, to obtain the most accurate picture of cortical myelin content.

Intrinsic variability of ocular dominance column periodicity in normal macaque monkeys.

Little is known about intrinsic variation from animal to animal in the periodicity of columnar systems within various regions of the mammalian cerebral cortex. To address this issue, complete mosaics of the ocular dominance columns were reconstructed from flat-mounts of the left and right striate cortex (V1) in six normal adult macaques (Macaca fascicularis). To identify the columns, we enucleated the right eye and subsequently processed striate cortex for cytochrome oxidase (CO) activity. Average column areas for the intact eye and the missing eye were nearly equal, confirming that monocular enucleation in adult macaques produces negligible column shrinkage. The contralateral eye's columns occupied more territory than the ipsilateral eye's columns, even in the central visual field representation (0 degree to 8 degrees), where they predominated by 52 to 48%. The column mosaics showed remarkable variation in periodicity. The number of column pairs along the V1/V2 border ranged from 101 sets in one monkey to 154 sets in another. Average column width along the V1/V2 border ranged between 670 and 395 microns, a nearly twofold difference. The widest columns were found in the foveal representation. This high degree of innate variability should be taken into account when considering the effects of various sensory manipulations (e.g., strabismus, anisometropia), which have been reported to alter the periodicity of ocular dominance columns. We found pronounced intrinsic variation in the width and number of ocular dominance columns in a sample of six M. fascicularis, indicating that the number of hypercolumns within a given cortical area can range widely among normal members of the same species.

Anatomical demonstration of ocular dominance columns in striate cortex of the squirrel monkey.

The squirrel monkey is the only primate reported to lack ocular dominance columns. Nothing anomalous about the visual capacity of squirrel monkeys has been found to explain their missing columns, leading to the suggestion that ocular dominance columns might be "an epiphenomenon, not serving any purpose" (Livingstone et al., 1995). Puzzled by the apparent lack of ocular dominance columns in squirrel monkeys, we made eye injections with transneuronal tracers in four normal squirrel monkeys. An irregular mosaic of columns, averaging 225 microns in width, was found throughout striate cortex. They were double-labeled by placing wheat germ agglutinin-horseradish peroxidase into the left eye and [3H]proline into the right eye. The tracers labeled opposite sets of interdigitating columns, proving they represent ocular dominance columns. The columns were much clearer in layer IVc alpha (magno-receiving) than IVc beta (parvo-receiving). In the lateral geniculate body, the parvo laminae showed extensive mixing of ocular inputs, suggesting that increased label spillover contributes to the blurred columns in layer IVc beta. The cytochrome oxidase (CO) patches were organized into distinct rows, but they bore no consistent relationship to the ocular dominance columns. These experiments indicate that ocular dominance columns are less well segregated in squirrel monkeys than macaques, but they are present. This fact is pertinent to a recent study reporting that ocular dominance columns are absent in normal squirrel monkeys, but induced to form by strabismus (Livingstone, 1996).

Pattern of ocular dominance columns in human striate cortex in strabismic amblyopia.

Previous experiments in animals have shown that early unilateral eyelid suture, a model of amblyopia induced by cataract, causes shrinkage of ocular dominance columns serving the deprived eye in the striate cortex. It is unknown whether the ocular dominance columns are affected in amblyopia produced by strabismus. We examined specimens of striate cortex obtained postmortem from a 79-year-old woman with a history of amblyopia in her left eye (20/800) since age 2 from accommodative esotropia. Four years prior to her death, she suffered an ischemic infarct of the left optic disc. This injury to the left optic disc made it possible to label the ocular dominance columns using cytochrome oxidase histochemistry. The pattern of ocular dominance columns was reconstructed throughout most of the right striate cortex. No shrinkage of columns was found. In the left cortex only half the column mosaic was labelled, because the patient had some residual vision in the temporal retina of her left eye. The columns within the labelled portion of the overall mosaic appeared normal. These findings indicate that shrinkage of ocular dominance columns does not occur in humans with amblyopia caused by accommodative esotropia. The ocular dominance columns are probably no longer susceptible to shrinkage at the age when most children with this condition begin to develop amblyopia.

An adult-like pattern of ocular dominance columns in striate cortex of newborn monkeys prior to visual experience.

In macaque monkeys, the geniculocortical afferents serving each eye segregate in layer IVc of striate cortex during early life into a pattern of alternating inputs called ocular dominance columns. It has been disputed whether visual experience is necessary for the formation of ocular dominance columns. To settle this issue, fetal monkeys were delivered prematurely by Caesarean section at embryonic day 157 (E157), 8 d before the end of normal gestation. To avoid light exposure, the Caesarean section and all subsequent feedings and procedures were done in absolute darkness, using infrared night-vision goggles. Tritiated proline was injected into the right eye 1 d after delivery (E158). One week later at postnatal age 0 (P0), the equivalent of a full-term pregnancy (E165/P0), alternate sections of unfolded and flattened visual cortex were prepared for autoradiography or cytochrome oxidase (CO). All three newborns studied at E165/P0 had well segregated ocular dominance columns organized into the characteristic mosaic present in adults. In the upper layers, a mature pattern of CO patches (also known as blobs or puffs) was visible, aligned with the ocular dominance columns in layer IVc. Every other row of patches in layers II, III was labeled by [3H]proline. In V2, a distinct system of alternating thick-pale-thin-pale CO stripes was present. These findings indicate that stimulation of the retina by light is not necessary for the development of columnar systems in the visual cortex. Ocular dominance columns, patches, and V2 stripes all are well formed before visual experience. Even the thalamic input to the patches in the upper layers of striate cortex is segregated by eye in newborns.

Glial domains and axonal reordering in the chiasmatic region of the developing ferret.

This study has examined the developing glial architecture of the optic pathway and has related this to the changing organization of the constituent axons. Immunocytochemistry was used to reveal the distribution of glial profiles, and DiI was used to label either radial glial profiles or optic axons. Electron microscopy was used to determine the distribution of glial profiles, axons, growth cones, and wrists at different locations along the pathway. Three different glial boundaries were defined: Two of these are revealed as changes in the distribution of vimentin-immunoreactive profiles occurring in the prechiasmatic optic nerve and at the threshold of the optic tract, respectively, and one by the presence of glial fibrillary acidic protein (GFAP)-immunoreactive profiles at the chiasmatic midline. The latter, midline boundary may be related to the segregation of nasal from temporal optic axons. The boundary at the threshold of the optic tract coincides with the segregation of dorsal from ventral optic axons that emerges at this location in the pathway. The segregation of old from young optic axons is shown to occur only gradually along the pathway. Glial profiles are most frequent in the deeper parts of the tract, coursing parallel to the optic axons and orthogonal to their usual radial axis. These are suggested to arise from later-growing radial glial fibers that are diverted to grow amongst the older optic axons. Those glial profiles may subsequently impede axonal invasion, thus creating the chronotopic reordering by forcing the later-arriving axons to accumulate superficially.