The human brain can adapt to overcome injury even years after an initial insult. One hypothesis states that early brain injury survivors, by taking advantage of critical periods of high plasticity during childhood, should recover more successfully than those who suffer injury later in life. This hypothesis has been challenged by recent studies showing worse cognitive outcome in individuals with early brain injury, compared with individuals with later brain injury, with working memory particularly affected. We invited individuals who suffered perinatal brain injury (PBI) for an fMRI/diffusion MRI tractography study of working memory and hypothesized that, 30 years after the initial injury, working memory deficits in the PBI group would remain, despite compensatory activation in areas outside the typical working memory network. Furthermore we hypothesized that the amount of functional reorganization would be related to the level of injury to the dorsal cingulum tract, which connects medial frontal and parietal working memory structures. We found that adults who suffered PBI did not significantly differ from controls in working memory performance. They exhibited less activation in classic frontoparietal working memory areas and a relative overactivation of bilateral perisylvian cortex compared with controls. Structurally, the dorsal cingulum volume and hindrance-modulated orientational anisotropy was significantly reduced in the PBI group. Furthermore there was uniquely in the PBI group a significant negative correlation between the volume of this tract and activation in the bilateral perisylvian cortex and a positive correlation between this activation and task performance. This provides the first evidence of compensatory plasticity of the working memory network following PBI.Key words: fMRI; perinatal brain injury; plasticity; spherical deconvolution; tractography; working memory Significance StatementHere we used the example of perinatal brain injury (PBI) associated with very preterm birth to study the brain's ability to adapt to injury sustained early in life. In adulthood, individuals with PBI did not show significant deficits in working memory, but exhibited less activation in typical frontoparietal working memory areas. They also showed a relative overactivation of nontask-specific brain areas (perisylvian cortex) compared with controls, and such activation was negatively correlated with the size of white matter pathways involved in working memory (dorsal cingulum). Furthermore, this "extra" activation was associated with better working memory performance and could represent a novel compensatory mechanism following PBI. Such information could inform the development of neuroscience-based cognitive interventions following PBI.

This study was undertaken to assess whether mild cervical intraepithelial neoplasia (CIN 1) lesions are histologically overdiagnosed and, if so, what the possible reasons are for this. The magnitude of the discrepancy between the histological diagnosis of CIN and corresponding smear results was also investigated. Between January and April 1988, 282 patients were found to have a histological diagnosis of CIN 1. The cervical smear result was negative in 42% of cases, borderline in 14% and in the remaining 44% various grades of CIN were predicted. Review of both cytology smears and histology sections was undertaken to identify reasons for this discrepancy. The results suggest that: (1) there is a tendency among histopathologists to overdiagnose cases of CIN 1, as occurred in 10% of cases in this study: (2) even if strict morphological criteria are followed, there will always be cases where histopathologists are uncertain whether a lesion is CIN 1 or some reactive process--for these cases, 22% in our study, the term borderline is recommended; and (3) cervical smears may give false negative results, as in 35%, 18% and 3% of our cases of CIN 1, CIN 2 and CIN 3 respectively.

Objective To determine whether the cytological detection of persistent cervical intraepithelial neoplasia (CIN) after local ablative treatment is improved by the use of sampling devices other than the Ayre's spatula. Design A randomized controlled study. Setting Lothian Area Colposcopy Clinic. Subjects 856 patients who had received local therapy (CO2 laser or cold coagulation) for CIN II or III between 9 and 30 months earlier. Intervention Each patient had three consecutive cervical smears taken, one with the Ayre's spatula, one with either the Aylesbury, the Rocket or the Multispatula device, and finally one with the Cytobrush. The allocation of which spatula and the order of the first two was randomized. Each patient had a colposcopic examination immediately after the smears were taken. Main outcome measures A comparison of the detection of histologically proven persistent CIN by the Ayre's spatula with the detection of persistent disease by alternative sampling devices. Results Of the 856 patients 130 had histologically proven persistent CIN. Another 98 had suspicious findings on colposcopy but punch biopsies reported as histologically normal. Of the remaining patients with normal colposcopy 130 were randomly selected to form a control group. The cervical smears from these 358 women were reported. Significantly fewer Ayre’ s samples contained endocervical cells than Aylesbury samples (47%vs 59%, difference 12%; 95% CI 3%‐21%; P<0.1), Rocket samples (47%vs 67%; difference 20%, 95% CI; 12%‐32%; P<0.001) or Multispatula samples (47%vs 76%; difference 29%, 95% CI 19–38%; P<0.001). When punch biopsies contained CIN, dyskaryotic cells were seen in 10% of Ayre's samples, 4.3% of Aylesbury samples, 8.3% of Rocket samples, and in no smear taken with the Multispatula. Obtaining a third smear with the Cytobrush did not substantially improve the detection rate of dyskaryosis. Neither the order of use of the spatulas, the form of initial treatment nor the size of the transformation zone had any apparent effect on the cytological detection of persistent CIN. Conclusions We recommend that surveillance of patients who have received local ablative therapy for CIN should be by both cytology and colposcopy, and that cytological samples should be obtained using the Ayre's spatula.

This is a retrospective study carried out to assess the correlation between the cytology and histology of cervical intraepithelial neoplasia in 1325 women. A poor correlation between the cytologic and histologic diagnosis of the various grades of CIN was shown. Forty-one percent of smears with repeated borderline change and 50% of those predicting CIN1 showed a higher grade of CIN on histology. The overall apparent false negative rate of cervical smears for high grade CIN (CIN2 and CIN3) was 19% and for CIN3 alone was only 3%. It is therefore concluded that there is a consistent tendency for cervical cytology to underestimate the severity of histologic lesions and it is therefore important that the clinicians ensure adequate follow-up of patients whose smears show a lesser degree of abnormality.

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